Required readings for Cranial Nerve module by Prof. Carrick

Anatomy of the Cranial Nerves by Laine & Smoker

Understanding the Brain Stem, by Daniels, et al

Both from Neuroimaging Clinics of North America, Vol 8, No 1, February 1998

 

These are the references utilized by Prof Carrick in preparing his lecture on Cranial nerves.

Bibliography

 

1. Abele, M.; Burk, K.; Andres, F.; Topka, H.; Laccone, F.; Bosch, S.;

Brice, A.; Cancel, G.; Dichgans, J.; Klockgether, T. Autosomal

dominant cerebellar ataxia type I. Nerve conduction and evoked

potential studies in families with SCA1, SCA2 and SCA3.

Brain. 1997 Dec; 120( Pt 12): 2141-8; ISSN: 0006-8950.

ENGLAND. Forty-one patients suffering from autosomal

dominant cerebellar ataxia type I (ADCA-I) were subjected to

a genotype-phenotype correlation analysis using molecular

genetic assignment to the spinocerebellar ataxia type 1, 2 or 3

(SCA1, -2 or -3) genetic locus, clinical examination and nerve

conduction as well as evoked potential studies. Pyramidal

tract signs, pale discs, and dysphagia were more frequent in

SCA1 compared with SCA2 and SCA3 patients, while double

vision occurred less frequently. Visual evoked potentials and

motor evoked potentials following transcranial magnetic

stimulation were abnormal in almost all SCA1 patients, but

only in a minority of SCA2 and SCA3 patients. In contrast,

somatosensory evoked potentials were delayed or absent in the

majority of patients with no significant differences between

the mutations. Abnormalities of brainstem auditory evoked

potentials were found in about half of the patients

irrespective of the underlying mutation. In addition, reduced

sensory nerve action potentials, suggesting sensory axonal

neuropathy were found in all three mutations. These findings

provide electrophysiological evidence that pyramidal and

visual pathways are differentially affected in SCA1, SCA2 and

SCA3 patients.

2. Acri, J. B.; Wong, G.; Lyon, T.; Witkin, J. M.; Basile, A. S.

Localization and pharmacological characterization of pigeon

diazepam-insensitive GABAA receptors. Neuroscience. 1997

Mar; 77(2): 371-8; ISSN: 0306-4522.

UNITED-STATES. Transduction mechanisms associated with

ligand binding at diazepam-insensitive subtypes of GABAA

receptors remain largely unknown, but unique behavioral

effects of ligands binding at these sites have been reported in

pigeons. The present study further evaluated the

pharmacological characteristics of diazepam-insensitive

GABAA receptors in pigeon brain, using [3H]Ro 15-4513.

Autoradiography detected diazepam-insensitive

benzodiazepine sites on GABAA receptors in a number of brain

regions, with the highest densities present in the olfactory

bulb, hippocampus, thalamic nuclei and cerebellar granule cell

layers, with densities of approximately 10-20% of total

benzodiazepine receptor binding. Saturation analysis revealed

significant densities (approximately 10% of total

benzodiazepine receptor binding) of extracerebellar diazepam-

insensitive benzodiazepine receptors in optic lobe,

hippocampus, and brainstem compared to 27% in cerebellum.

As reported for mammalian diazepam-sensitive

benzodiazepine receptors, GABA (50 microM) generally

increased the affinities of agonists and partial agonists, had

little effect on the affinities of antagonists, and decreased

the affinity of an inverse agonist for pigeon cerebellar

diazepam-sensitive benzodiazepine receptors. GABA

modulation of ligand binding to diazepam-insensitive

benzodiazepine receptors was less than that observed for

diazepam-sensitive sites, and no positive modulation was

observed. These results demonstrate the presence of

cerebellar and extracerebellar diazepam-insensitive

benzodiazepine receptors in pigeon brain, with distribution

patterns and pharmacology similar to those reported in

mammals. The comparable central localization and

pharmacological properties of drugs at diazepam-sensitive and

-insensitive benzodiazepine receptors in pigeons and rats

attests to the evolutionary conservation of GABAA systems..

0; 0; 0; 0; 0; 0; 439-14-5; 56-12-2; 91917-65-6.

3. Adle Biassette, H.; Chetritt, J.; Bergemer Fouquet, A. M.; Wechsler,

J.; Mussini, J. M.; Gray, F. Pathology of the central nervous

system in Chester-Erdheim disease: report of three cases. J-

Neuropathol-Exp-Neurol. 1997 Nov; 56(11): 1207-16; ISSN:

0022-3069.

UNITED-STATES. Chester-Erdheim disease is a rare form of

non-Langerhans cell histiocytosis consisting of disseminated

xanthogranulomatous infiltration and fibrosis that primarily

involves the bones, visceral organs and systemic fatty spaces.

Involvement of the central nervous system is variable, and

neuropathological features have seldom been documented. We

report the neuropathological findings in 3 autopsy cases. One

patient had radiological and pathological bone changes

characteristic of Chester-Erdheim disease. Neuropathology

revealed multiple characteristic xanthogranulomas

disseminated in the cerebral hemispheres, hypothalamus,

cerebellum, and brainstem. The second patient presented first

with cutaneous lesions characteristic of Langerhans cell

histiocytosis. She subsequently developed bone abnormalities

suggestive of Chester-Erdheim disease, which was confirmed

by autopsy, raising the possibility of a common spectrum of

histiocytosis including both diseases. Gross examination of

the brain was normal, however, microscopy showed

infiltration of the brain by characteristic non-Langerhans cell

xanthogranulomas. The third patient presented with systemic

features characteristic of Chester-Erdheim disease.

Neurological signs included gait disturbance, seizures and

confusion. Examination of the brain did not show any

histiocytic infiltration, but did show changes suggestive of

Hallervorden-Spatz syndrome. Association of Chester-Erdheim

disease and Hallervorden-Spatz syndrome has not been

previously reported. The relationship between both conditions

is unclear.

4. Aiba, I.; Hashizume, Y.; Yoshida, M.; Okuda, S.; Murakami, N.;

Ujihira, N. Relationship between brainstem MRI and

pathological findings in progressive supranuclear palsy--study

in autopsy cases. J-Neurol-Sci. 1997 Nov 25; 152(2): 210-7;

ISSN: 0022-510X.

NETHERLANDS. The relationship between the features of MRI in

brainstem and pathological findings was investigated in eight

autopsy cases with progressive supranuclear palsy (PSP).

Features of T1-weighted images at midbrain level were

atrophy of tegmentum and tectum, and dilatation of aqueduct.

Histologically, these findings were consistent with atrophy of

periaqueductal gray matter, quadrigeminal plate, and

tegmentum. In these lesions, we detected neuronal loss,

decrease in density of myelinated fibers, gliosis, rarefaction

of tissues, and tau-positive structures such as neurofibrillary

tangles (NFTs), glial fibrillary tangles (GFTs) and neuropil

threads. At pons level, atrophy of tegmentum, atrophy of

pontine base, and dilatation of prepontine cistern were found.

Tau-positive structures were observed not only in tegmentum

but also in pontine base. The density of the tau-positive

structure was closely related to the severity of atrophy.

Features of T2-weighted images were high intensity in the

periaqueductal lesion and tegmentum in pons. In these lesions,

severe histological findings were detected. The MRI features

in brainstem were closely related to the histological findings

as PSP.

5. Amagai, S. Time coding in the midbrain of mormyrid electric fish.

II. Stimulus selectivity in the nucleus exterolateralis pars

posterior. J-Comp-Physiol-A. 1998 Feb; 182(2): 131-43; ISSN:

0340-7594.

GERMANY. The anterior and posterior exterolateral nuclei (ELa

and ELp) of the mormyrid midbrain are thought to play a

critical role in the temporal analysis of the electric discharge

waveforms of other individuals. The peripheral

electroreceptors receiving electric organ discharges (EODs) of

other fish project through the brainstem to ELa via a rapid

conducting pathway. EODs, composed of brief, but stereotyped

waveforms are encoded as a temporal pattern of spikes. From

previous work, we know that phase locking is precise in ELa.

Here it is shown that evoked potentials recorded from ELp

show a similar high degree of phase locking, although the

evoked potentials last much longer. Single-unit recordings in

ELp reveal two distinct populations of neurons in ELp: type I

cells are responsive to voltage step functions, and not tuned

for stimulus duration; type II cells are tuned to a specific

range of stimulus durations. Type II cells are less responsive

than type I cells, tend to respond with bursts of action

potentials rather than with single spikes, have a longer

latency, show weaker time locking to stimuli, and are more

sensitive to stimulus polarity and amplitude. The stimulus

selectivity of type II cells may arise from convergence of type

I cell inputs. Despite the loss of rapid conduction between ELa

and ELp, analysis of temporal features of waveforms evidently

continues in ELp, perhaps through a system of labeled lines.. 0;

124-87-8.

6. Amodio, P.; Marchetti, P.; Del Piccolo, F.; Beghi, A.; Comacchio, F.;

Carraro, P.; Campo, G.; Baruzzo, L.; Marchiori, C.; Gatta, A. The

effect of flumazenil on subclinical psychometric or

neurophysiological alterations in cirrhotic patients: a double-

blind placebo-controlled study. Clin-Physiol. 1997 Sep; 17(5):

533-9; ISSN: 0144-5979.

ENGLAND. It is not yet clear if benzodiazepine receptor

ligands, implicated in the pathophysiology of hepatic coma,

also have a role in subclinical cognitive or neurophysiological

alterations in cirrhotic patients. Therefore, we carried out a

double-blind, placebo-controlled study to evaluate the

effectiveness of flumazenil, a benzodiazepine antagonist, on

brainstem auditory evoked responses and on the number

connection test in cirrhotic patients with subclinical

neurophysiological or cognitive alterations. Thirteen cirrhotic

subjects with subclinical neurophysiological or cognitive

alterations were studied. A total of 3 mg of flumazenil or

saline was infused intravenously. Before and after the

infusion, the number connection test was administered and

brainstem auditory evoked responses recorded. After 72 h,

patients were crossed over. Flumazenil did not influence

brainstem auditory evoked responses or the number connection

test. A screening test for benzodiazepines was negative in all

subjects. We conclude that benzodiazepine receptor ligands

have a negligible role, if any, in the pathophysiology of

subclinical neurophysiological or cognitive alterations of

cirrhotic patients.. 0; 0; 78755-81-4.

7. Anderson, C. W.; Nishikawa, K. C. The functional anatomy and

evolution of hypoglossal afferents in the leopard frog, Rana

pipiens. Brain-Res. 1997 Oct 17; 771(2): 285-91; ISSN: 0006-

8993.

NETHERLANDS. Previously, we suggested that afferents are

present in the hypoglossal nerve of the leopard frog, Rana

pipiens. The basis for this was behavioral data obtained after

transection of the hypoglossal nerve. These afferents

coordinate the timing of tongue protraction with mouth

opening during feeding. The goal of the present study was to

define anatomically these hypoglossal afferents in Rana

pipiens. Retrograde tracing was performed using horseradish

peroxidase, fluorescent dextran amines and neurobiotin. Data

show that the cell bodies of hypoglossal afferents are located

in the dorsal root ganglion of the third spinal nerve and enter

the brainstem through its dorsal root. The afferents ascend in

the dorsomedial funiculus and move laterally after they pass

the obex. They project in the granular layer of the cerebellum

and the medial reticular formation. The cervical afferents that

travel in this pathway are known to carry proprioceptive and

cutaneous sensory information. We hypothesize that the

presence of afferents in the hypoglossal nerve is a derived

characteristic of anurans, which has resulted from the re-

routing of afferent fibers from the third spinal nerve into the

hypoglossal nerve. The appearance of hypoglossal afferents

coincides with the morphological acquisition of a highly

protrusible tongue.. EC 1.11.1.-.

8. Anderson, C. W.; Nishikawa, K. C. The functional anatomy and

evolution of hypoglossal afferents in the leopard frog, Rana

pipiens. Brain-Res. 1997 Oct 17; 771(2): 285-91; ISSN: 0006-

8993.

NETHERLANDS. Previously, we suggested that afferents are

present in the hypoglossal nerve of the leopard frog, Rana

pipiens. The basis for this was behavioral data obtained after

transection of the hypoglossal nerve. These afferents

coordinate the timing of tongue protraction with mouth

opening during feeding. The goal of the present study was to

define anatomically these hypoglossal afferents in Rana

pipiens. Retrograde tracing was performed using horseradish

peroxidase, fluorescent dextran amines and neurobiotin. Data

show that the cell bodies of hypoglossal afferents are located

in the dorsal root ganglion of the third spinal nerve and enter

the brainstem through its dorsal root. The afferents ascend in

the dorsomedial funiculus and move laterally after they pass

the obex. They project in the granular layer of the cerebellum

and the medial reticular formation. The cervical afferents that

travel in this pathway are known to carry proprioceptive and

cutaneous sensory information. We hypothesize that the

presence of afferents in the hypoglossal nerve is a derived

characteristic of anurans, which has resulted from the re-

routing of afferent fibers from the third spinal nerve into the

hypoglossal nerve. The appearance of hypoglossal afferents

coincides with the morphological acquisition of a highly

protrusible tongue.. EC 1.11.1.-.

9. Aouda, A.; Hayashi, F.; Fukuda, Y.; Masuda, Y. An in vitro

brainstem-heart preparation of the neonatal rat with intact

right vagus nerve. Jpn-J-Physiol. 1997 Oct; 47(5): 443-8; ISSN:

0021-521X.

JAPAN. An in vitro brainstem preparation of the neonatal rat

with intact right vagal (X) innervation of the right atrium, and

intact medullary roots of the left X and glossopharyngeal (IX)

nerves for stimulation was developed. The preparation was

continuously superfused with artificial CSF at 25 degrees C.

The electrical activity of the right atrium was recorded to

determine the heart rate. Applications of atropine or

propranolol to the superfusate did not alter the heart rate.

Electrical stimulation (0.5 ms pulse, 20 Hz) of the left IX and X

afferents elicited a reduction in the heart rate from 70.3 +/-

13.2 to 50.6 +/- 13.2 beats/min (mean +/- SD, p < 0.05), which

was abolished after division of the right X or application of

atropine to the superfusing solution. A similar reflex

bradycardia was seen in a preparation with intact left vagal-

right atrium innervation during right IX and X afferent

stimulation. Cervical spinal cord transection affected neither

the baseline heart rate nor the magnitude of the reflex

bradycardia. Longitudinal sectioning of the medulla oblongata

in the mid-line down to the level of the posterior inferior

cerebellar artery abolished the heart rate response. After

bilateral cervical vagotomies, electrical stimulation (0.5 ms

pulse, 20 Hz, up to 100 microA) of the ventrolateral medulla

oblongata, lateral funiculus at C2 or intermediate nucleus of

the spinal cord at Th1-4 did not affect the heart rate. These

results indicate that the functions in the lower brainstem are

preserved in this preparation, at least in regard to the

generation of reflex bradycardia. The results also suggest that

the laterality of cardiac vagal innervation and sympathetic

innervation will develop during the postnatal period. This

preparation may be useful for the study of the central neuronal

network controlling the heart rate.. 0; 0; 51-55-8; 525-66-6.

10. Arslan, E.; Turrini, M.; Lupi, G.; Genovese, E.; Orzan, E. Hearing

threshold assessment with auditory brainstem response (ABR)

and ElectroCochleoGraphy (ECochG) in uncooperative children.

Scand-Audiol-Suppl. 1997; 46: 32-7; ISSN: 0107-8593.

DENMARK. Two-hundred-and-sixty uncooperative children (442

ears) performed auditory brainstem response (ABR) and

Electrocochleography (ECochG) in the same diagnostic session

under general anaesthesia, and the results obtained with the

two different methods were compared. A difference > or = 20

dB between the two methods was found in 134 ears (30.3%).

The presence of middle ear effusion and symptoms of a

possible central nervous system pathology were considered in

order to verify the evidence of a correlation between the

difference in ABR-ECochG results and these clinical

parameters. The presence of middle ear effusion was not

significantly correlated with differences > or = 20 dB (p =

0.1347). On the contrary, the presence of symptoms indicative

of a possible central nervous system (CNS) involvement was

significantly correlated with differences > or = 20 dB (p =

0.0000). ABR has to be considered the first choice in hearing

assessment strategy, either for screening or diagnosis.

However, the diagnosis of hearing loss only on the basis of the

presence or absence of wave V requires some care in case of

suspected central auditory pathway lesions. In these cases,

ECochG may be the only reliable diagnostic tool for hearing

assessment in uncooperative subjects.

11. Arvanitogiannis, A.; Flores, C.; Shizgal, P. Fos-like

immunoreactivity in the caudal diencephalon and brainstem

following lateral hypothalamic self-stimulation. Behav-Brain-

Res. 1997 Nov; 88(2): 275-9; ISSN: 0166-4328.

NETHERLANDS. Fos immunohistochemistry was used to stain

neurons in the caudal diencephalon, midbrain and hindbrain

driven by rewarding stimulation of the lateral hypothalamus

(LH). Increases in Fos-like immunoreactivity were most

pronounced ipsilateral to the site of stimulation and tended to

be confined within discrete structures such as the posterior

LH, arcuate nucleus, ventral tegmental area (VTA), central

gray, dorsal raphe, pedunculopontine area (PPTg), parabrachial

nucleus, and locus coeruleus. At least two of these structures,

the VTA and PPTg, have been implicated in medial forebrain

bundle self-stimulation.. 0.

12. Austin, A. R.; Pawson, L.; Meek, S.; Webster, S. Abnormalities of

heart rate and rhythm in bovine spongiform encephalopathy.

Vet-Rec. 1997 Oct 4; 141(14): 352-7; ISSN: 0042-4900.

ENGLAND. Heart rates of healthy cows and cows suspected of

having bovine spongiform encephalopathy were measured by

auscultation and by a portable cardiac monitor. Bradycardia

was demonstrated in suspect cases which were confirmed

histopathologically. Disturbances in cardiac rhythm were also

evident in some cases. Healthy cows deprived of food exhibited

bradycardia. The administration of pharmacological doses of

atropine indicated that bradycardia in BSE was mediated by

increased vagal influence, suggesting that the cardioinhibitory

reflexes in the caudal brainstem were functionally altered by

the disease.. 0; 51-55-8.

13. Austin, M. C.; Rhodes, J. L.; Lewis, D. A. Differential distribution

of corticotropin-releasing hormone immunoreactive axons in

monoaminergic nuclei of the human brainstem.

Neuropsychopharmacology. 1997 Nov; 17(5): 326-41; ISSN:

0893-133X.

UNITED-STATES. Corticotropin-releasing hormone (CRH) has

been implicated in a variety of physiological and behavioral

responses to stress, as well as in the pathophysiology of

certain psychiatric disorders. Although studies in rodents

support a neuromodulatory influence of CRH on monoamine

neurotransmission in a number of brain regions, little

information in available to support a similar role for CRH in

the human brain. The present study used immunocytochemistry

to characterize the anatomical organization of CRH-

immunoreactive axons in the human brainstem. Substantial

regional differences in the density and distribution of CRH-

immunoreactive axons were found in the dopamine-,

noradrenaline- and serotonin-containing cell body regions of

the human brainstem. Dense networks of CRH-immunoreactive

axons were found in the medial subnuclei of the ventral

mesencephalon and in the dorsolateral region of the locus

coeruleus. Moderate densities of CRH-positive fibers were

located in the median and dorsal raphe, whereas lower

numbers of CRH-labeled axons appeared in the substantia nigra

pars compacta. In addition, differences in CRH innervation

density were observed within each region. For example, the

dorsal tier of the substantia nigra contained a greater density

of CRH-labeled axons than the ventral tier. In all monoamine-

containing nuclei, CRH-labeled axons exhibited numerous

beaded varicosities and fine intervaricose segments. The

differential distribution of CRH-containing axons across these

human brainstem nuclei suggests that the influence of CRH on

monoamine function may be neurotransmitter-specific.. 50-

67-9; 51-61-6; 9015-71-8.

14. Baguley, D. M.; Beynon, G. J.; Grey, P. L.; Hardy, D. G.; Moffat, D. A.

Audio-vestibular findings in meningioma of the cerebello-

pontine angle: a retrospective review. J-Laryngol-Otol. 1997

Nov; 111(11): 1022-6; ISSN: 0022-2151.

ENGLAND. The aim of this study was the determination of the

incidence of symptoms of audio-vestibular dysfunction and of

abnormalities on audio-vestibular testing in patients found to

have a unilateral meningioma of the cerebello-pontine angle

(CPA). The case notes of 25 patients diagnosed with unilateral,

sporadic and histologically proven CPA meningioma were

retrospectively reviewed. The age range of this series was 31-

71 years, with a mean age of 50 years. Two patients were

male (eight per cent) and 23 were female (92 per cent). The

mean length of history was 44.7 months. The distribution of

tumour size was skewed toward larger tumours, with 15 cases

(60 per cent) having tumours with a maximum diameter

greater than 3.5 cm on imaging. Pure tone audiometry was

normal in five cases (20 per cent), and no patients exhibited

the high frequency sensorineural hearing loss that is

characteristic of vestibular schwannoma. Speech audiometry

was normal in 50 per cent of cases. Caloric testing was

abnormal in 77 per cent of the 18 cases tested, whilst

auditory brainstem responses (ABR) were abnormal in 100 per

cent of the 18 cases who had sufficient hearing for this test

to be possible. The presence of normal audiometry in patients

with a proven CPA lesion indicates that, if in a protocol for

investigation, asymmetry of hearing is mandatory then some

pathology will be missed. Any suspicion of a CPA lesion

warrants investigation even in the absence of hearing loss. The

investigation of choice for the identification of CPA lesions

has become magnetic resonance imaging (MRI). If this

technique is not available then this study indicates that ABR

is a suitable and sensitive investigation. It should be borne in

mind however that the data in this study has been derived from

a series of predominantly large tumours, and the sensitivity of

ABR to smaller CPA meningiomata may fall, as is the case for

vestibular schwannoma.

15. Bakchine, S.; Crassard, I.; Seilhan, D. Anosognosia for hemiplegia

after a brainstem haematoma: a pathological case [letter]. J-

Neurol-Neurosurg-Psychiatry. 1997 Nov; 63(5): 686-7; ISSN:

0022-3050.

ENGLAND.

16. Ballanyi, K.; Lalley, P. M.; Hoch, B.; Richter, D. W. cAMP-dependent

reversal of opioid- and prostaglandin-mediated depression of

the isolated respiratory network in newborn rats. J-Physiol-

Lond. 1997 Oct 1; 504( Pt 1): 127-34; ISSN: 0022-3751.

ENGLAND. 1. Membrane potential (Vm) and resistance (Rm) of

ventral respiratory group (VRG) neurons were measured in the

isolated brainstem-spinal cord from newborn rats during bath

application of the opioid receptor agonists fentanyl or [D-

Ala2, D-Leu5]-enkephalin (Ala-Leu-Enk) and of the

prostaglandin E1 (PGE1). 2. PGE1 (0.1-3 microM) and fentanyl

or Ala-Leu-Enk (1-50 microM) produced depression and, at

higher doses, block of inspiratory nerve activity and

respiration-related postsynaptic potentials. This apnoea was

associated with hyperpolarization and Rm fall in 25% of

thirty-two VRG neurons tested, whereas resting Vm and Rm

were not changed in the other cells. 3. The selective mu- and

delta-receptor blockers naloxonazine (10-20 microM) and

naltrindole (50-100 microM) antagonized the effects of 5

microM fentanyl and 50 microM Ala-Leu-Enk, respectively. 4.

Opioid- and PGE1-evoked respiratory depression was reversed

upon elevation of endogenous cAMP levels by stimulating

adenylyl cyclase with 100 microM forskolin, activating

dopamine D1 receptors with 50-100 microM 6-chloro-7,8-

dihydroxy-3-allyl-1-phenyl-2, 3,4,5-tetrahydro-1H-3-

benzazepine (6-chloro-APB) or preventing cAMP breakdown

with 50-100 microM isobutylmethylxanthine. 5. The results

indicate that opioid- or prostaglandin-induced respiratory

depression is due to a fall in cAMP levels in cells responsible

for generation of rhythm or providing a tonic drive to the

respiratory network. 6. We suggest that elevation of cAMP

levels is an effective antidote in neonates against such forms

of respiratory depression.. 0; 0; 0; 0; 0; 0; 28822-58-4; 60-

92-4; 745-65-3.

17. Bardoul, M.; Drian, M. J.; Konig, N. AMPA/kainate receptors

modulate the survival in vitro of embryonic brainstem cells.

Int-J-Dev-Neurosci. 1997 Oct; 15(6): 695-701; ISSN: 0736-

5748.

ENGLAND. This study aimed at analyzing the involvement of

(RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic

acid/kainate (AMPA/kainate) receptors in the survival of

cultured rat embryonic brainstem cells, dissociated on

embryonic day 14. The cell number was estimated after

pharmacological manipulation of the receptors by exposure to

agonists or antagonists. The developmental stage at the

moment of drug application was critical for cell survival. We

observed after 8 days in vitro a much stronger decrease in the

number of gamma-enolase-positive cells when the cultures

were treated for 3 days with the antagonist 6,7-

dinitroquinoxaline-2,3-dione (DNQX) starting on the day of

plating than when DNQX was added after 5 days in vitro.

Conversely, exposure to the agonists (RS)-2-amino-3-(3-

hydroxy-5-tri-fluoromethyl-4-isoxazolyl)-propion ic acid (T-

AMPA) or kainate for 3 days significantly reduced cell survival

only when the treatment was initiated after 5 days in vitro.

Survival of S-100-positive cells was not affected after

exposure to either agonists or antagonists. Neither agonist nor

antagonist treatment modified cell proliferation, as assessed

by 5-bromo-2'-deoxyuridine (BrdU) staining, suggesting that

the decrease in the number of gamma-enolase-positive cells is

essentially due to cell death. If some of the processes we

observed in vitro correspond to analogous events in vivo, then

exposure to excitatory amino acid receptor agonists or

antagonists at critical stages of embryogenesis may alter the

development of the central nervous system.. EC 4.2.1.11; 0; 0;

0; 0; 0; 59-14-3.

18. Barrett, T. G.; Bundey, S. E. Wolfram (DIDMOAD) syndrome. J-Med-

Genet. 1997 Oct; 34(10): 838-41; ISSN: 0022-2593.

ENGLAND. Wolfram syndrome (MIM 222300) is the association

of juvenile onset diabetes mellitus and optic atrophy, also

known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus,

Optic Atrophy, and Deafness). Patients present with diabetes

mellitus followed by optic atrophy in the first decade, cranial

diabetes insipidus and sensorineural deafness in the second

decade, dilated renal outflow tracts early in the third decade,

and multiple neurological abnormalities early in the fourth

decade. Other abnormalities include primary gonadal atrophy.

Death occurs prematurely, often from respiratory failure

associated with brainstem atrophy. Most patients eventually

develop all complications of this progressive,

neurodegenerative disorder. The pathogenesis is unknown, but

the prevalence is 1 in 770000 in the UK and inheritance is

autosomal recessive. A Wolfram gene has recently been

mapped to chromosome 4p16.1, but there is evidence for locus

heterogeneity, and it is still possible that a minority of

patients may harbour a mitochondrial genome deletion. The

best available diagnostic criteria are juvenile onset diabetes

mellitus and optic atrophy, but there is a wide differential

diagnosis which includes other causes of neurodegeneration.

19. Basar, R.; Sargon, M. F.; Tekdemir, Y.; Elhan, A. The marginal

mandibular branch of the facial nerve. Surg-Radiol-Anat. 1997;

19(5): 311-4; ISSN: 0930-1038.

GERMANY. The peripheral, extraparotid course and localisation

of the marginal mandibular branch of the facial n. is described,

with variations, based on the dissection of 40 cadaver half

heads. Its anatomical relationships with the ramus of

mandible and facial a. are studied and morphometric features

are reported. Knowledge of the accurate course and

relationship of the marginal mandibular branch should help to

protect this nerve from surgical injury.

20. Bayliss, D. A.; Viana, F.; Talley, E. M.; Berger, A. J.

Neuromodulation of hypoglossal motoneurons: cellular and

developmental mechanisms. Respir-Physiol. 1997 Nov; 110(2-

3): 139-50; ISSN: 0034-5687.

NETHERLANDS. Hypoglossal motoneurons (HMs) in the caudal

brainstem have a respiratory-related activity pattern and

contribute to control of upper airway resistance. In this

review, we focus primarily on signalling mechanisms utilized

by neurotransmitters to enhance HM excitability. In particular,

we consider: (1) the membrane depolarization induced by a

number of different putative transmitters [thyrotropin-

releasing hormone (TRH), serotonin (5-HT), norepinephrine

(NE)]; and (2) the inhibition of a calcium-dependent spike after

hyperpolarization (AHP) by 5-HT and its effect on firing

behavior. Potential functional consequences on HM behavior of

these different neurotransmitter effects is discussed. In

addition, we describe postnatal changes in transmitter effects

and suggest potential cellular mechanisms to explain those

developmental changes. Most of the data discussed are derived

from in vitro electrophysiological recordings performed in

preparations from neonatal and adult rats.

21. Becker, T.; Becker, G.; Seufert, J.; Hofmann, E.; Lange, K. W.;

Naumann, M.; Lindner, A.; Reichmann, H.; Riederer, P.; Beckmann,

H.; Reiners, K. Parkinson's disease and depression: evidence for

an alteration of the basal limbic system detected by

transcranial sonography. J-Neurol-Neurosurg-Psychiatry. 1997

Nov; 63(5): 590-6; ISSN: 0022-3050.

ENGLAND. OBJECTIVES: Depression is a frequent symptom in

Parkinson's disease. Compelling evidence suggests a role of

the brainstem in the control of mood and cognition. In patients

with unipolar depression transcranial sonography (TS) studies

have shown structural alteration of the mesencephalic

brainstem raphe which could suggest an involvement of the

basal limbic system in the pathogenesis of primary mood

disorders. The objective of the present study was to evaluate

whether a similar alteration could be found in depressed

patients with Parkinson's disease using TS. METHODS: Thirty

patients with Parkinson's disease and 30 age and sex adjusted

controls were examined by TS. Raphe echogenicity was rated

semiquantitatively. The severity of motor symptoms and

depression was rated using standard research instruments.

RESULTS: Raphe echogenicity was significantly reduced in

depressed patients with Parkinson's disease compared with

nondepressed patients with Parkinson's disease and control

subjects. Raphe echogenicity correlated negatively with

degree of motor impairment, and differences in raphe echo

between depressed and non-depressed patients with

Parkinson's disease were upheld when motor impairment was

controlled for. CONCLUSION: These preliminary findings

suggest that, as in unipolar depression, a morphological

alteration of the brainstem raphe might be involved in the

pathogenesis of depression in Parkinson's disease. This raphe

alteration may reflect involvement in the basal limbic system

in the pathogenesis of secondary depression. This concept is in

line with current knowledge on the pathogenesis of both

depression in Parkinson's disease and primary depressive

disorders.

22. Bereiter, D. A.; Bereiter, D. F.; Tonnessen, B. H.; Maclean, D. B.

Selective blockade of substance P or neurokinin A receptors

reduces the expression of c-fos in trigeminal subnucleus

caudalis after corneal stimulation in the rat. Neuroscience.

1998 Mar; 83(2): 525-34; ISSN: 0306-4522.

UNITED-STATES. Stimulation of the cornea activates neurons

in two distinct regions of the spinal trigeminal nucleus: at the

transition between trigeminal subnucleus interpolaris and

subnucleus caudalis and at the transition between trigeminal

subnucleus caudalis and the upper cervical spinal cord as

estimated by expression of the immediate early gene, c-fos. To

determine if receptors for substance P or neurokinin A,

neurokinin 1 and neurokinin 2 receptors, respectively,

contribute to the production of Fos-positive neurons in these

brainstem regions, receptor-selective antagonists were given

intracerebroventricularly 15 min prior to stimulation of the

cornea in anesthetized rats. The number of Fos-positive

neurons produced in superficial laminae at the trigeminal

subnucleus caudalis/cervical cord transition by application of

the selective small fiber excitant, mustard oil, to the corneal

surface was reduced by the neurokinin 1 receptor antagonist,

CP99,994 (5-100 nmol, i.c.v.) and the neurokinin 2 receptor

antagonist, MEN10,376 (0.01-1.0 nmol, i.c.v.). Combined

pretreatment with CP99,994 and the competitive N-methyl-D-

aspartate receptor antagonist, CPP, caused a greater reduction

in c-fos expression at the subnucleus caudalis/cervical cord

transition than after either drug alone suggesting interaction

between receptors for glutamate and substance P. Tachykinin

receptor antagonists did not reduce the number of Fos-positive

neurons produced at the subnucleus interpolaris/subnucleus

caudalis transition. The elevation in plasma concentration of

adrenocorticotropin, but not the increases in arterial pressure

or heart rate, evoked by corneal stimulation was prevented by

pretreatment with CP99,994 or MEN10,376 at doses lower

than those needed to reduce c-fos expression. The results

indicate that receptors for substance P and neurokinin A

contribute to the transmission of sensory input from corneal

nociceptors to brainstem neurons in trigeminal subnucleus

caudalis and to increased activity of the hypothalamo-

pituitary axis that accompanies acute stimulation of the

cornea.. 0; 0; 0; 0; 0; 0; 135306-85-3; 136982-36-0; 404-86-

4; 86933-74-6; 9002-60-2.

23. Bernstein Goral, H.; Diener, P. S.; Bregman, B. S. Regenerating and

sprouting axons differ in their requirements for growth after

injury. Exp-Neurol. 1997 Nov; 148(1): 51-72; ISSN: 0014-4886.

UNITED-STATES. After spinal cord injury at birth, axotomized

brainstem-spinal and corticospinal neurons are capable of

permanent regenerative axonal growth into and through a fetal

spinal cord transplant placed into the site of either a spinal

cord hemisection or transection. In contrast, if fetal tissue

which is not a normal target of the axotomized neurons

(embryonic hippocampus or cortex) is placed into a neonatal

spinal cord hemisection, brainstem-spinal serotonergic axons

transiently innervate the transplant, but subsequently

withdraw. The first set of experiments was designed to test

the hypothesis that after spinal cord transection, serotonergic

axons would cross the nontarget transplant, reach normal

spinal cord targets caudal to the transection, and gain access

to requisite target-derived cues, permitting permanent

maintenance. Surprisingly, after a complete spinal cord

transection, brainstem-spinal axons failed to grow into an

inappropriate target even transiently. These observations

suggest that the transient axonal ingrowth into nontarget

transplants may represent lesion-induced axonal sprouting by

contralateral uninjured axons. We have used double-labeling

with fluorescent dyes, to test directly whether axonal

sprouting of neurons which maintain collaterals to uninjured

spinal cord targets (1) provide the transient ingrowth of

brainstem-spinal axons into a nontarget transplant and (2)

contribute to permanent ingrowth into target-specific

transplants. Uninjured red nucleus, raphe nucleus, and locus

coeruleus neurons extend axons into the nontarget transplant

while maintaining collaterals to the host spinal cord caudal to

the transplant. The lesion-induced sprouting by uninjured

axons was also observed with a target-specific transplant.

Taken together, these studies suggest that sprouting and

regenerating axons may differ in their requirements for

growth after injury.. 0; 50-67-9.

24. Berrebi, A. S.; Spirou, G. A. PEP-19 immunoreactivity in the

cochlear nucleus and superior olive of the cat. Neuroscience.

1998 Mar; 83(2): 535-54; ISSN: 0306-4522.

UNITED-STATES. We applied antiserum to PEP-19, a

presumptive calcium-binding polypeptide, to the auditory

brainstem of cats to determine whether this antiserum would

selectively reveal cochlear nucleus neurons and their

projections. We report that the entire populations of ventral

cochlear nucleus bushy and multipolar cells, but not octopus

cells, express this peptide in their somata and dendrites.

Presumed axons of spherical bushy cells located dorsally and

thicker globular bushy cell fibers located ventrally in the

trapezoid body are immunostained, as are thin fibers presumed

to represent the axons of multipolar cells. Large calyceal

endings in the medial nucleus of the trapezoid body are densely

immunoreactive as are smaller punctate profiles that outline

immunonegative neuronal profiles in the medial and lateral

superior olives. These features of immunolabeling indicate

that PEP-19 is expressed in all neuronal compartments. Within

the entire superior olivary complex, relatively few neurons are

immunolabeled, and the vast majority of these are found in the

periolivary nuclei. There are many more immunostained

neurons in lateral than in medial periolivary cell groups, but

their combined numbers are dwarfed by the numbers of

immunolabeled cells in the ventral cochlear nucleus. The

borders of the principal nuclei and some of the periolivary cell

groups are well defined by the distribution of PEP-19-

immunoreactive fibers and puncta. Since ventral cochlear

nucleus bushy cells comprise the predominant input to

principal nuclei of the superior olive, and the entire bushy cell

population is immunolabeled by PEP-19 antiserum, the

numbers and distribution of their inputs can be quantified. In

this study we report that immunoreactive puncta apposed to

the cell bodies and proximal dendrites of neurons in the medial

superior olive occur at a density of 20/100 microns2.

Moreover, we demonstrate by pre-embedding immunoelectron

microscopy that the PEP-19-immunoreactive punctate profiles

observed in the medial superior olive by light microscopy

represent presynaptic terminal boutons that contain round

synaptic vesicles and form asymmetric synaptic junctions,

features traditionally associated with excitatory synapses.

Thus, this antiserum represents a useful tool for investigating

the distribution of ventral cochlear nucleus fibers and

synaptic terminals within their target nuclei in the superior

olive.. 0; 106494-08-0.

25. Berridge, C. W.; Stratford, T. L.; Foote, S. L.; Kelley, A. E.

Distribution of dopamine beta-hydroxylase-like

immunoreactive fibers within the shell subregion of the

nucleus accumbens. Synapse. 1997 Nov; 27(3): 230-41; ISSN:

0887-4476.

UNITED-STATES. The nucleus accumbens (Acb) can be divided

into distinct subfields, delineated on the basis of

histochemical markers as well as by afferent and efferent

projection patterns. The shell subregion has reciprocal

relationships with a variety of limbic areas and brainstem

autonomic structures, and has been suggested to participate in

motivation-related processes, including reward, stress, and

arousal. The locus coeruleus (LC)-noradrenergic system has

similarly been implicated in the modulation of behavioral

state and stress-related processes, and previous studies have

demonstrated reciprocal projections between the locus

coeruleus and Acb shell. To better understand the anatomical

substrate through which LC could influence activity within

Acb shell, immunohistochemical methods were used to

visualize the extent and the distribution of noradrenergic

axons within this structure. Coronal sections of rat brain were

processed to visualize immunoreactivity for the

norepinephrine synthetic enzyme dopamine beta-hydroxylase

(DBH), a specific marker for noradrenergic processes. In some

cases, alternate sections were processed for

immunohistochemical localization of substance P, in order to

delineate core, shell, and pallidal compartments. Moderate-to-

dense DBH-like immunoreactivity (DBHir) was found in

approximately the caudal half of the shell subregion,

particularly in caudalmost (septal pole) and ventral zones. The

innervation of the septal pole was contiguous with a dense

innervation of the bed nucleus of the stria terminalis. Few

immunoreactive fibers were observed in the caudate-putamen,

Acb core, or rostral Acb shell. Many DBHir fibers within the

shell region were highly arborized with numerous varicosities,

features indicative of terminal fields. These observations

suggest noradrenergic systems might modulate certain

processes associated with stress, behavioral state, or

reinforcement via actions within the Acb shell.. EC 1.14.17.1;

33507-63-0; 51-41-2.

26. Bice, T. N.; Beal, J. A. Quantitative and neurogenic analysis of

neurons with supraspinal projections in the superficial dorsal

horn of the rat lumbar spinal cord. J-Comp-Neurol. 1997 Dec 1;

388(4): 565-74; ISSN: 0021-9967.

UNITED-STATES. Dual retrograde axonal tracers, Fluoro-Gold

(FG) and true blue (TB), were used in conjunction with

[3H]thymidine autoradiography to determine the number and

neurogenic pattern of neurons with supraspinal projections in

the superficial dorsal horn (SDH), i.e., laminae I and II, in

spinal segment L1 of the rat. FG was injected into rostral

brain centers (dorsal thalamus and midbrain), and TB was

injected into the caudal brainstem (medulla) in young adult

rats previously administered [3H]thymidine in utero. Following

stereological correction, each dorsal horn had an average of

1.22 neurons in lamina I and 0.24 neurons in lamina II that had

supraspinal projections per 10-microm transverse section. In

the SDH, 52% of the neurons with supraspinal projections were

found to project to rostral brain centers alone, 3.0% only to

the caudal brainstem, and 45% to both areas. There was no

significant difference in the percentage distribution of each of

the three groups of neurons between lamina I and lamina II.

Cell counts in the present study, in conjunction with previous

observations in the literature, suggest that the majority of

supraspinal projection neurons in the SDH fall into two groups:

1) spinomesencephalic neurons with collaterals to the medulla

and 2) spinothalamic neurons with collaterals to the midbrain.

The neurogenesis of supraspinal projection neurons in the SDH

proceeded along an axon-length gradient, whereby neurons

with the longest axons, those with projections to rostral brain

centers, completed neurogenesis prior to neurons with shorter

axons, those with projections only to the caudal brainstem.

The generation of all SDH neurons with supraspinal projections

was completed on embryonic day 14 (E14), 2 days prior to the

completion of neurogenesis for SDH neurons with intraspinal

projections.

27. Bodie, D.; Bennett Clarke, C. A.; Davis, K.; Postelwaite, J. P.;

Chiaia, N. L.; Rhoades, R. W. Organization, development, and

effects of infraorbital nerve transection on galanin binding

sites in the trigeminal brainstem complex. Somatosens-Mot-

Res. 1997; 14(3): 168-80; ISSN: 0899-0220.

ENGLAND. Previous experiments from this laboratory have

indicated that transection of the infraorbital nerve (ION, the

trigeminal [V] branch that supplies the mystacial vibrissae

follicles) at birth and in adulthood has markedly different

effects on galanin immunoreactivity in the V brainstem

complex. Adult nerve transection increases galanin

immunoreactivity in the superficial layers of V subnucleus

caudalis (SpC) only, while neonatal nerve transection results

in increased galanin expression in vibrissae-related primary

afferents throughout the V brainstem complex. The present

study describes the distribution of binding sites for this

peptide in the mature and developing V ganglion and brainstem

complex and determines the effects of neonatal and adult ION

damage and the associated changes in galanin levels upon their

distribution and density. Galanin binding sites are densely

distributed in all V brainstem subnuclei and are particularly

dense in V subnucleus interpolaris and the superficial layers

of SpC. They are present at birth (P-0) and their distribution is

similar to that in adult animals. Transection of the ION in

adulthood and examination of brainstem 7 days later indicated

marked reductions in the density of galanin binding sites in

the V brainstem complex. With the exception of the superficial

laminae of SpC, the same reduction in density remained

apparent in rats that survived > 45 days after nerve cuts.

Transection of the ION on P-0 resulted in no change in the

density of galanin binding sites in the brainstem after either 7

or > 60 days survival. These results indicate that densely

distributed galanin binding sites are present in the V

brainstem complex of both neonatal and adult rats, that they

are located in regions not innervated by galanin-positive

axons, and that their density is not significantly influenced by

large lesion-induced changes in the primary afferent content

of their natural ligand.. 0; 0.

28. Bogucki, J.; Gielecki, J.; Czernicki, Z. The anatomical aspects of a

surgical approach through the floor of the fourth ventricle.

Acta-Neurochir-Wien. 1997; 139(11): 1014-9; ISSN: 0001-

6268.

AUSTRIA. In 1993 Kyoshima et al. introduced safe entry zones

in the region of the 4th ventricle floor: infrafacial triangle and

suprafacial triangle. Is it possible to demarcate these zones

precisely in every case intra-operatively? A postmortem study

of 40 brainstems of patients who had died of non-brain

disease was performed to evaluate the degree of individual

morphological and morphometrical variability of the 4th

ventricle floor. The purpose of this study was to find constant

landmarks and distances within the rhomboid fossa region

which would help a neurosurgeon to determine safe approach

zones through the 4th ventricle floor to brainstem lesions.

Several anatomical landmarks-median sulcus, obex, vestibular

area, vagal triangle, hypoglossal triangle-were found to be

sufficiently visible in all examined brainstems. However, the

facial colliculus which is a border structure between the

infrafacial and suprafacial safe approach zone was poorly

visible in about 37% of the analyzed material. The striae

medullares were not found to be good orientation structures as

they were not visible in 30% of the material and exhibited

individual variability of a high degree in relation to their

number and arrangement. In the morphometrical study analyzed

measurements were taken by utilizing the digital image

analyzer MULTISCAN. Based on the results obtained the authors

suggest new borders of the infrafacial safe approach zone and

morphometrical directions to determine the suprafacial safe

approach zone in cases when the facial colliculus is not

clearly visible or invisible intra-operatively.

29. Bonaventure, P.; Voorn, P.; Luyten, W. H.; Jurzak, M.; Schotte, A.;

Leysen, J. E. Detailed mapping of serotonin 5-HT1B and 5-HT1D

receptor messenger RNA and ligand binding sites in guinea-pig

brain and trigeminal ganglion: clues for function. Neuroscience.

1998 Jan; 82(2): 469-84; ISSN: 0306-4522.

UNITED-STATES. The similar pharmacology of the 5-HT1B and

5-HT1D receptors, and the lack of selective compounds

sufficiently distinguishing between the two receptor

subtypes, have hampered functional studies on these receptors.

In order to provide clues for differential functional roles of

the two subtypes, we performed a parallel localization study

throughout the guinea-pig brain and the trigeminal ganglia by

means of quantitative in situ hybridization histochemistry

(using [35S]-labelled riboprobes probes for receptor

messenger RNA) and receptor autoradiography (using a new

radioligand [3H]alniditan). The anatomical patterns of 5-HT1B

and 5-HT1D receptor messenger RNA were quite different.

While 5-HT1B receptor messenger RNA was abundant

throughout the brain (with highest levels in the striatum,

nucleus accumbens, olfactory tubercle, cortex, hypothalamus,

hippocampal formation, amygdala, thalamus, dorsal raphe and

cerebellum), 5-HT1D receptor messenger RNA exhibited a more

restricted pattern; it was found mainly in the olfactory

tubercle, entorhinal cortex, dorsal raphe, cerebellum,

mesencephalic trigeminal nucleus and in the trigeminal

ganglion. The density of 5-HT(1B/1D) binding sites (combined)

obtained with [3H]alniditan autoradiography was high in the

substantia nigra, superior colliculus and globus pallidus,

whereas lower levels were detected in the caudate-putamen,

hypothalamus, hippocampal formation, amygdala, thalamus and

central gray. This distribution pattern was indistinguishable

from specific 5-HT1B receptor labelling in the presence of

ketanserin under conditions to occlude 5-HT1D receptor

labelling; hence the latter were below detection level.

Relationships between the regional distributions of the

receptor messenger RNAs and binding sites and particular

neuroanatomical pathways are discussed with respect to

possible functional roles of the 5-HT1B and 5-HT1D receptors..

0; 0; 0; 0.

30. Borday, V.; Fortin, G.; Champagnat, J. Early ontogeny of rhythm

generation and control of breathing. Respir-Physiol. 1997 Nov;

110(2-3): 245-9; ISSN: 0034-5687.

NETHERLANDS. The ability of central networks to produce

rhythmic motor behaviours linked to the respiratory function,

is a remarkably conserved property of the brainstem reticular

formation in vertebrates. Conserved cellular and molecular

mechanisms also underlie the early embryonic development of

the brainstem, leading to a segmented rhombencephalon in all

vertebrates. We have proposed that the neural network that

controls breathing after birth, derives from a primordial

rhythmic network first active in the segmented hindbrain of

the embryo. Observations on transgenic mice support this

hypothesis: homozygous inactivation of Krox-20, a gene

governing segmentation, leads to a lower-than-normal

respiratory frequency (fR), despite fetal maturation of the

respiratory network and functional compensatory control after

birth.

31. Bottai, D.; Dunn, R. J.; Ellis, W.; Maler, L. N-methyl-D-aspartate

receptor 1 mRNA distribution in the central nervous system of

the weakly electric fish Apteronotus leptorhynchus. J-Comp-

Neurol. 1997 Dec 8; 389(1): 65-80; ISSN: 0021-9967.

UNITED-STATES. We have isolated a partial cDNA for the N-

methyl-D-aspartate (NMDA) receptor 1 (NMDAR1) subunit from

an Apteronotus leptorhynchus brain cDNA library. The A.

leptorhynchus cDNA fragment, which corresponds to

nucleotides 135-903 within the 5' region of the rat NR1 mRNA,

encodes 252 amino acids that are >80% identical to the

homologous segments of the rat, human, and duck NR1 proteins.

RNAse protection assays revealed that the A. leptorhynchus

NR1 mRNA was highly enriched in the forebrain and

hypothalamus, with lesser amounts in the brainstem, and very

low levels in the cerebellum. In situ hybridization also

demonstrated that neurons in the pallial forebrain were highly

enriched in NR1 transcripts. High levels of NR1 mRNA were

found in pyramidal cells within the optic tectum and

octavolateral regions. Pyramidal cells of the electrosensory

lateral line lobe had the highest levels of expression, and the

NR1 mRNA was found to be selectively enriched in their apical

dendrites.. 0; 0; 9007-49-2.

32. Braune, S.; Hetzel, A.; Prasse, A.; Dohms, K.; Guschlbauer, B.;

Lucking, C. H. Stimulation of sympathetic activity by carbon

dioxide in patients with autonomic failure compared to normal

subjects. Clin-Auton-Res. 1997 Dec; 7(6): 327-32; ISSN: 0959-

9851.

ENGLAND. In vivo studies selectively assessing preganglionic

and central autonomic nervous system activity in patients

with autonomic failure have so far been limited to testing

pituitary function. In animal experiments carbon dioxide (CO2)

selectively stimulates central sympathetic nuclei in the

ventrolateral medulla and preganglionic sympathetic neurons

in the cervical trunk. This central stimulation seems to

overrule less pronounced peripheral vasodilatatory effects.

This study addressed the question of whether hypercapnea is a

suitable challenge procedure to test preganglionic and central

autonomic activity in healthy subjects and in patients with

autonomic failure of preganglionic and central origin. Seven

patients with multiple system atrophy (MSA) and 30 age-

matched healthy volunteers underwent a protocol including a

Valsalva manoeuvre (VM) under normo- and hypercapnic

conditions and exposure to hypercapnea under supine resting

conditions. Blood pressure (BP), heart rate (HR) and end-tidal

CO2 partial pressure were measured continuously and non-

invasively. In normal controls hypercapnea induced

significantly higher BP values in phases II, IIe, III and IV of

the VM compared to the normocapnic VM and a significant

increase in BP during steady-state supine exposure compared

to normocapnic baseline. HR increased significantly only after

40 s of steady-state hypercapnea during the latter challenge.

In patients with MSA and autonomic failure, in whom a

predominantly preganglionic lesion of the autonomic nervous

system is established, no significant effects of hypercapnea

on the cardiovascular parameters were found. Although this

non-invasive challenge procedure cannot differentiate between

pre- and postganglionic autonomic failure, exposure to

hypercapnea enables the investigation of efferent autonomic

activity to vasoconstrictors generated from autonomic centres

in the brainstem and cervical trunk.. 124-38-9.

33. Bredow, S.; Guha Thakurta, N.; Taishi, P.; Obal, F. Jr; Krueger, J. M.

Diurnal variations of tumor necrosis factor alpha mRNA and

alpha-tubulin mRNA in rat brain. Neuroimmunomodulation.

1997 Mar; 4(2): 84-90; ISSN: 1021-7401.

SWITZERLAND. The experiments described herein were

designed to determine whether tumor necrosis factor alpha

(TNF-alpha) displays a diurnal variation in various areas of the

normal rat brain. TNF-alpha mRNA transcripts were detected

by reverse-transcriptase polymerase chain reaction. To

monitor diurnal changes in TNF-alpha and alpha-tubulin

expression, rats were sacrificed every 4 h for 24 h starting 1

h after light onset; relative mRNA levels were determined for

the cerebellum, cortex, hippocampus, hypothalamus and

brainstem. TNF-alpha mRNA was higher during the light than in

the dark phase in the hypothalamus and hippocampus. alpha-

Tubulin mRNA exhibited a similar diurnal variation in the

hypothalamus, hippocampus and cortex. In contrast, beta-actin

mRNA was lower during the light phase than the dark phase in

the hippocampus and cortex. The observed diurnal variations in

TNF-alpha mRNA are consistent with the hypothesis that TNF

has a physiological role in the brain.. 0; 0; 0.

34. Bregman, B. S.; McAtee, M.; Dai, H. N.; Kuhn, P. L. Neurotrophic

factors increase axonal growth after spinal cord injury and

transplantation in the adult rat. Exp-Neurol. 1997 Dec; 148(2):

475-94; ISSN: 0014-4886.

UNITED-STATES. The capacity of CNS neurons for axonal

regrowth after injury decreases as the age of the animal at

time of injury increases. After spinal cord lesions at birth,

there is extensive regenerative growth into and beyond a

transplant of fetal spinal cord tissue placed at the injury site.

After injury in the adult, however, although host corticospinal

and brainstem-spinal axons project into the transplant, their

distribution is restricted to within 200 micron of the

host/transplant border. The aim of this study was to

determine if the administration of neurotrophic factors could

increase the capacity of mature CNS neurons for regrowth

after injury. Spinal cord hemisection lesions were made at

cervical or thoracic levels in adult rats. Transplants of E14

fetal spinal cord tissue were placed into the lesion site. The

following neurotrophic factors were administered at the site

of injury and transplantation: brain-derived neurotrophic

factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4),

ciliary-derived neurotrophic factor (CNTF), or vehicle alone.

After 1-2 months survival, neuroanatomical tracing and

immunocytochemical methods were used to examine the

growth of host axons within the transplants. The neurotrophin

administration led to increases in the extent of serotonergic,

noradrenergic, and corticospinal axonal ingrowth within the

transplants. The influence of the administration of the

neurotrophins on the growth of injured CNS axons was not a

generalized effect of growth factors per se, since the

administration of CNTF had no effect on the growth of any of

the descending CNS axons tested. These results indicate that

in addition to influencing the survival of developing CNS and

PNS neurons, neurotrophic factors are able to exert a

neurotropic influence on injured mature CNS neurons by

increasing their axonal growth within a transplant. Copyright

1997 Academic Press.. 0; 0; 0; 0; 0; 0; 143551-63-7; 50-67-

9.

35. Breitman, D. R.; Lee, S. S. Blunted responsiveness of the neuronal

activation marker Fos in brainstem cardiovascular nuclei of

cirrhotic rats. Hepatology. 1997 Dec; 26(6): 1380-5; ISSN:

0270-9139.

UNITED-STATES. Cardiovascular function in cirrhosis is

deranged, with indirect evidence of abnormal central

cardiovascular regulation. We aimed to elucidate the role of

brainstem cardiovascular nuclei in hemodynamic regulation by

examining the protein product, Fos, of the immediate-early

gene c-fos, in cirrhotic rats. Cirrhosis was induced by chronic

bile duct ligation (BDL) of 25-days duration, while controls

underwent a sham operation. To examine the effects of

jaundice per se in the absence of cirrhosis, a third group of 5-

day BDL rats was also studied. All rats were anesthetized with

pentobarbital, and catheters were inserted to measure

baseline blood pressure and heart rate. Separate groups were

then subjected to volume manipulation by a hypotensive

hemorrhage or isotonic saline infusion, or no challenge. Ninety

minutes after the volume manipulation, the animals were

killed and the medulla sectioned and stained for Fos by

immunohistochemisty. The nucleus tractus solitarius (NTS) of

the sham-operated unchallenged rats showed scant Fos

immunoreactivity (27.8 +/- 3.3 cells), but both hemorrhage and

volume infusion significantly increased Fos staining (86.0 +/-

3.7 and 95.2 +/- 8.5, respectively). In contrast, the

unchallenged cirrhotic rats showed markedly increased Fos in

the NTS (154.6 +/- 27.0), but neither hemorrhage nor volume

infusion significantly changed the amount of Fos staining. Fos

staining in the ventrolateral medulla (VLM) followed a similar

pattern with low staining in the unchallenged sham rats and

increased staining in the other groups, but no differences

between the unchallenged and the volume-manipulated

cirrhotic groups. The 5-day BDL jaundiced rats showed no

baseline increase in Fos staining, nor any significant increase

after hemorrhage. These results showing baseline activation

of central neuronal regions responsible for blood pressure

homeostasis, but completely blunted responsiveness in

cirrhotic rats, confirm a central origin of disordered

cardiovascular regulation. The presence of jaundice may also

contribute to the central cardiovascular hyporesponsiveness..

0.

36. Brodsky, M. C.; Fray, K. J. Brainstem hypoplasia in the Wildervanck

(cervico-oculo-acoustic) syndrome [letter]. Arch-Ophthalmol.

1998 Mar; 116(3): 383-5; ISSN: 0003-9950.

UNITED-STATES.

37. Brooks, P. J.; Kleopoulos, S. P.; Funabashi, T.; Mobbs, C. V.; Pfaff, D.

W. Widespread expression and estrogen regulation of PPEIA-3'

nuclear RNA in the rat brain. Proc-Natl-Acad-Sci-U-S-A. 1997

Dec 9; 94(25): 14037-41; ISSN: 0027-8424.

UNITED-STATES. We previously identified a novel nuclear RNA

species derived from the preproenkephalin (PPE) gene. This

transcript, which we have named PPEIA-3' RNA, hybridizes

with probes directed at a region of PPE intron A downstream

of an alternative germ-cell transcription start site, but does

not contain PPE protein coding sequences. We now report that

estrogen treatment of ovariectomized rats increases the

expression of conventional PPE heteronuclear RNA, and also

induces the expression of PPEIA-3' RNA, apparently in separate

cell populations within the ventromedial nucleus of the

hypothalamus. Further, we show that cells expressing PPEIA-3'

are found in several neuronal groups in the rat forebrain and

brainstem, with a distinct topographical distribution. High

densities of PPEIA-3' containing cells are found in the

reticular thalamic nucleus, the basal forebrain, the vestibular

complex, the deep cerebellar nuclei, and the trapezoid body, a

pattern that parallels the distribution of atypical nuclear

RNAs described by other groups. These results suggest that

this diverse neuronal population shares a common set of

nuclear factors responsible for the expression and retention of

this atypical RNA transcript. The implication of these results

for cell-specific gene transcription and regulation in the brain

and the possible relationship of PPEIA-3' RNA and other

atypical nuclear RNAs is discussed.. 0; 0; 0; 50-28-2; 63231-

63-0; 93443-35-7; 983-30-2.

38. Bucher, S. F.; Dieterich, M.; Seelos, K. C.; Brandt, T. Sensorimotor

cerebral activation during optokinetic nystagmus. A functional

MRI study. Neurology. 1997 Nov; 49(5): 1370-7; ISSN: 0028-

3878.

UNITED-STATES. Self-motion or object motion can elicit

optokinetic nystagmus (OKN), which is an integral part of

dynamic spatial orientation. We used functional MR imaging

during horizontal OKN to study cerebral activation patterns in

sensory and ocular motor areas in 10 subjects. We found

activation bilaterally in the primary visual cortex, the

motion-sensitive areas in the occipitotemporal cortex (the

middle temporal and medial superior temporal areas), and in

areas known to control several types of saccades such as the

precentral and posterior median frontal gyrus, the posterior

parietal cortex, and the medial part of the superior frontal

gyrus (frontal, parietal, and supplementary eye fields).

Additionally, we observed cortical activation in the anterior

and posterior parts of the insula and in the prefrontal cortex.

Bilateral activation of subcortical structures such as the

putamen, globus pallidus, caudate nucleus, and the thalamus

traced the efferent pathways of OKN down to the brainstem.

Functional MRI during OKN revealed a complex cerebral

network of sensorimotor cortical and subcortical activation.

39. Burkard, R.; Palmer, A. R. Responses of chopper units in the

ventral cochlear nucleus of the anaesthetised guinea pig to

clicks-in-noise and click trains. Hear-Res. 1997 Aug; 110(1-

2): 234-50; ISSN: 0378-5955.

NETHERLANDS. Auditory brainstem responses (ABRs) have been

measured with clicks, clicks masked by noise, click trains and

pseudorandom maximum length sequences (MLS) of clicks. To

investigate the neuronal populations contributing to the ABR

under these stimulation conditions, we measured the

extracellular responses of ventral cochlear nucleus (VCN)

units in the urethane-anaesthetised guinea pig. We studied 23

chopper, 7 primary-like and 7 onset units. This report focuses

on the responses from chopper units. The probability of

discharge for chopper units increased with increasing click

level reaching nearly 100% in many units, over a range of about

20-30 dB. Following each response to a click there was a 5-10

ms suppression of the spontaneous or noise evoked activity. As

the level of the noise was increased over a range of 20-30 dB,

the response to the clicks gradually decreased leading to a

complete abolition of the click response at high noise levels.

In a few units, low level noise produced a facilitation of the

response to single clicks. In response to constant level equally

spaced click trains, discharge probability increased with

increasing minimum pulse interval (MPI), approaching 100% for

MPIs of 4-8 ms in some units. The recovery afforded by the

gaps in the MLS train often resulted in higher discharge

probability for MLS than click trains with the same MPI, while

response probabilities for MLS and click trains were similar

when compared at equivalent average click rates. At short

MPIs (0.5 and 1.0 ms), peri stimulus time histograms in

response to click trains resembled those to best frequency

(BF) tones and noisebursts, with chopping peaks unrelated to

unit BF. VCN units show highly synchronised and reliable

responses to click trains, MLS trains and clicks masked by

noise. The decrease in discharge rate and increase in latency

of chopper units with decreasing click level, increasing click

rate and increasing masker level parallel the peak amplitude

and latency changes observed in the auditory brainstem

response.

40. Calore, E. E.; Cavaliere, M. J.; Calore, N. M. Cerebral amebiasis in

the acquired immunodeficiency syndrome. Acta-Neurol-Belg.

1997 Dec; 97(4): 248-50; ISSN: 0300-9009.

BELGIUM. Rare cases of cerebral amebiasis have been

described in AIDS patients. We report the case of a 46 year-old

homosexual man with AIDS who developed an intermittent

amnesia and a right palpebral ptosis. The cerebrospinal fluid

contained 169 cells (75% lymphocytes). The patient died five

days after hospitalization. Necropsy revealed thrombosis of

small vessels of the periventricular regions as well as

necrosis and hemorrhage of the periventricular tissue,

cerebellum and brainstem. The inflammatory process was

scarce and composed mainly of CD-68 positive macrophages. In

these regions as well as in meninges there were many

trophozoites of ameba of the Acanthamoeba group. Although

cerebral amebiasis is rare even in AIDS, the clinician should

be attentive to this diagnosis in patients with an insidious

encephalitis and cerebral cognitive abnormalities, with or

without focal motor signs.

41. Camuscu, H.; Dujovny, M.; Abd, el Bary T.; Beristain, X.; Vinas, F. C.

Microanatomy of the perforators of the anterior

communicating artery complex. Neurol-Res. 1997 Dec; 19(6):

577-87; ISSN: 0161-6412.

ENGLAND. We describe the microanatomy of the perforating

arteries arising from the anterior communicating artery

complex (5 mm distal of the anterior cerebral artery, the

anterior communicating artery, and 5 mm proximal of the

distal anterior cerebral artery). Thirteen unfixed human brains

were used in this study. The origin and number of perforators

are described, as is the site of brain penetration, and results

are correlated with previous studies. The hemodynamics of

blood flow in relation to the formation of an anterior

communicating artery aneurysm and different surgical

approaches are mentioned. The neuropsychological outcome

after aneurysm clipping with regards to the pattern of blood

supply from the anterior cerebral artery complex is also

discussed.

42. Cendes, F.; Andermann, F.; Dubeau, F.; Matthews, P. M.; Arnold, D. L.

Normalization of neuronal metabolic dysfunction after surgery

for temporal lobe epilepsy. Evidence from proton MR

spectroscopic imaging. Neurology. 1997 Dec; 49(6): 1525-33;

ISSN: 0028-3878.

UNITED-STATES. Surgery is a safe and effective treatment for

patients with temporal lobe epilepsy (TLE) who do not respond

adequately to anticonvulsant medication and in whom the

seizure generator can be identified and safely removed. Proton

MR spectroscopic imaging (MRSI) can image and quantify

neuronal damage in patients with TLE based on reduced signals

from N-acetylaspartate (NAA), a compound localized

exclusively in neurons. We performed proton MRSI in patients

with TLE before and after surgical treatment to determine

whether NAA or other resonance intensities changed in the

temporal lobes of patients with TLE after surgery, and

whether these changes correlated with surgical outcome. N-

acetylaspartate resonance intensity relative to creatine

(NAA/Cr) was abnormally low preoperatively in at least one

temporal lobe in all 14 patients examined. It was low

ipsilaterally in the patients who became seizure free and

bilaterally in those who did not. Postoperatively, it increased

to the normal range on the side of surgery in all patients who

became seizure free. In the one patient who became seizure

free and who had low NAA/Cr in both temporal lobes before

surgery, NAA/Cr values in the contralateral, unoperated

temporal lobe also increased to the normal range. In contrast,

NAA relative intensity ratios did not change in those patients

who continued to have seizures after surgery. The creatine

resonance intensity (Cr) in the temporal lobes was high,

relative to the brainstem, in seven patients preoperatively.

After surgery, the Cr remained high in two patients, both of

whom continued to have seizures. We conclude that NAA (and

Cr) abnormalities in TLE do not result solely from neuronal

loss and gliosis but can be reversible after postsurgical

control of seizures. This implies that the NAA and Cr

abnormalities in patients with TLE, at least in part, are

dynamic markers of both local and remote physiologic

dysfunction associated with ongoing seizures.. 0; 56-84-8;

57-00-1; 62-49-7; 997-55-7.

43. Chauhan, S.; Kochar, D. K.; Solanki, B. S.; Kumawat, B. L. Brainstem

auditory evoked potentials (BAEPs) and somatosensory evoked

potentials (SEPs) in enteric encephalopathy (EE).

Electromyogr-Clin-Neurophysiol. 1997 Oct; 37(7): 423-9; ISSN:

0301-150X.

BELGIUM. BAEPs and SEPs were studied in 25 patients of

enteric encephalopathy in acute phase and the results were

compared with 25 healthy control persons. In the study the

important observations of BAEPs were delayed peak latency of

wave III, wave V and delayed ILP I-V, and of SEPs was

prolonged peak latency of N20. The electrophysiological

evidence suggests metabolic cause for the coma and the SEP

changes were similar to those observed in cerebral malaria

reported earlier in this laboratory.

44. Cheng, J. D.; Espinosa, de los Monteros A; de Vellis, J. Glial- and

fat-specific expression of the rat glycerol phosphate

dehydrogenase-luciferase fusion gene in transgenic mice. J-

Neurosci-Res. 1997 Oct 15; 50(2): 300-11; ISSN: 0360-4012.

UNITED-STATES. Glycerol phosphate dehydrogenase (GPDH) is a

metabolic enzyme that catalyzes the conversion of

dihydroxyacetone phosphate to glycerol-3-phosphate. It

provides phospholipid precursors for lipid biosynthesis and

energy metabolism. In the brain, GPDH enzymatic activity,

protein, mRNA are exclusively associated with

oligodendroglial and Bergmann glial cells. Expression of GPDH

in the brain increases dramatically during the active period of

myelination, and is regulated by extracellular signals. In an

effort to understand the mechanism that confers glial-

specific expression of GPDH, we have examined the role of the

5' flanking sequence of the rat GPDH gene in conferring cell-

specific expression of reporter gene in transgenic mice.

Luciferase reporter constructs containing either the full-

length GPDH 5' flanking region (p4.3), or a distally truncated

version (p2.6), were injected into mouse zygotes. Three

independent lines of transgenic mice containing the p4.3, and

seven lines of mice containing the p2.6 constructs, were

analyzed. Luciferase enzyme activity was detectable only in

brain and fat, not in other GPDH-positive organs such as liver,

muscle, and kidney. Both the full-length and the distally

deleted transgenes were expressed similarly in these two

organs, indicating that the distal portion of the 5' flanking

region was not required for brain- and fat-specific expression.

Immunocytochemical analyses revealed that luciferase

immunoreactivity colocalized with glial fibrillary acidic

protein (GFAP)-positive Bergmann glia in the cerebellum, and

myelin basic protein (MBP)-positive oligodendroglia in the

cerebral cortex and the brainstem. Results here suggest that

the rat GPDH 5' flanking region directs glial-specific

expression of GPDH transcription in the brain, and provide a

good model for analyses of changes in glial metabolism in

response to extracellular perturbations in vivo.. EC 1.1.-; EC

1.13.12.-.

45. Chu, N. S.; Yang, S. S.; Liaw, Y. F. Evoked potentials in liver

diseases. J-Gastroenterol-Hepatol. 1997 Oct; 12(9-10): S288-

93; ISSN: 0815-9319.

AUSTRALIA. Evoked potentials are objective and quantitative

methods capable of evaluating functions of both peripheral and

central nervous systems (PNS and CNS). During the past 8

years, we have been using somatosensory, brainstem auditory,

and pattern-reversal visual evoked potentials (SEP, BAEP, VEP)

to study hepatic encephalopathy (HE) as well as functional

status of the PNS and CNS in various liver diseases including

viral hepatitis B, alcoholic liver disease and Wilson's disease

(WD). In HE irrespective of its etiologies, there is a sequential

prolongation and eventual disappearance of cortical

components of the median nerve evoked SEP while there is no

change in BAEP, suggesting that HE is primarily due to a

disturbance in cerebral cortical function and that median SEP

may be used for early detection of HE and for monitoring its

clinical course. In addition, absence of the N20-P25

component, or presence of only the N20 component of the wave

complex in fulminant hepatic failure is associated with high

mortality, whereas presence of late cortical components in HE

is usually associated with reversibility of clinical course.

Central conduction time (CCT) of the BAEP is prolonged in

patients with WD, alcoholic liver disease and liver cirrhosis

due to hepatitis B. Furthermore, BAEP abnormality is most

severe in WD, followed by alcoholic liver disease, and finally

hepatitis B. Peripheral nerve conduction as determined by the

N9 latency of SEP is slowed in alcoholic liver disease and liver

cirrhosis of chronic hepatitis B, but normal in WD. Our studies,

therefore, suggest that evoked potentials may be useful in the

evaluation of both CNS and PNS functions in various liver

diseases and also in the diagnosis and monitoring of HE.

46. Clark, J. L.; Moushegian, G.; Rupert, A. L. Interaural time effects on

the frequency-following response. J-Am-Acad-Audiol. 1997

Oct; 8(5): 308-13; ISSN: 1050-0545.

CANADA. Frequency-following responses (FFRs) were recorded

to evaluate differences between monaural and binaural

waveforms and waveforms evoked by stimuli with interaural

time disparities. Eight normal-hearing adult females served as

subjects. The stimuli were monaural and binaural 450-Hz

tonebursts at 65 and 60 dB SL and interaural time differences

of 0 and 660 microseconds, respectively. Normalized

amplitudes and periodicities of FFR waveforms within and

between subjects were compared. The results showed

asymmetric FFR to the various stimuli used in this study.

Binaural FFR waveforms were greater than monaural but

smaller than summed monaural FFRs. Binaural FFR amplitudes

evoked by a zero time difference were greater than amplitudes

evoked by a 660-microseconds difference. Additionally, tight

phase-locked periodicities were evoked in the FFR monaurally

and binaurally. The averaged FFR periodicity to all stimulus

conditions from all subjects was 2.29 msec, differing only 6.8

microseconds from the period of the 450-Hz stimulus. In

contrast, monaural and binaural neurons in the lower brain

stem typically exhibit much less synchroneities to low-

frequency tones than the FFR. These data provide evidence that

the FFR is not simply a sum of neuronal action potentials. The

findings suggest instead the presence of brainstem neuronal

networks. Such putative neuronal ensembles apparently

maintain a closer correspondence to the period of a low-

frequency sound, whether monaural or binaural, than the

discharge patterns of single neurons.

47. Colletti, V.; Fiorino, F. G.; Carner, M.; Tonoli, G. Mechanisms of

auditory impairment during acoustic neuroma surgery.

Otolaryngol-Head-Neck-Surg. 1997 Dec; 117(6): 596-605;

ISSN: 0194-5998.

UNITED-STATES. Hearing loss during removal of acoustic

neuroma (AN) may be due to labyrinthine and/or neural and/or

vascular damage. Surgical maneuvers relating to perioperative

and postoperative hearing may give rise to mechanisms of

auditory impairment. Recording action potentials from the

intracranial portion of the cochlear nerve (CN) has proven

particularly useful for identifying the mechanisms of

iatrogenic auditory injury. In this paper intraoperative and

postoperative auditory impairments are investigated in

relation to surgical steps in a group of 47 subjects with AN

(size ranging from 5 to 25 mm) undergoing removal by a

retrosigmoid-transmeatal approach. Drilling of the internal

auditory canal (IAC), removal of the AN from the IAC fundus,

coagulation close to the CN, lateral to medial tumor traction,

separation of the CN from the facial nerve, and stretching of

the CN have proven to be the most critical surgical steps in

hearing preservation. On the other hand, maneuvers such as

intracapsular tumor removal, vestibular neurectomy, suction

close to the AN, and closure of the IAC defect did not correlate

with changes in auditory potentials. Predisposing factors to

postoperative hearing deterioration were IAC enlargement

greater than 3 mm, IAC tumor size greater than 7 mm,

extracanalar tumor size greater than 20 mm, labyrinth medial

to the IAC fundus, severe involvement of the CN in the IAC,

preoperative abnormal auditory brainstem responses, and

normal vestibular reflectivity. Age and preoperative hearing

did not prove to be statistically related to postoperative

hearing. The variations in morphology and latency of CNAPs are

discussed in relation to the mechanisms of iatrogenic injury.

48. Colon, G. P.; Quint, D. J.; Dickinson, L. D.; Brunberg, J. A.; Jamerson,

K. A.; Hoff, J. T.; Ross, D. A. Magnetic resonance evaluation of

ventrolateral medullary compression in essential

hypertension. J-Neurosurg. 1998 Feb; 88(2): 226-31; ISSN:

0022-3085.

UNITED-STATES. OBJECT: The authors designed a blinded

prospective study comparing patients with essential

hypertension to patients without hypertension in which

magnetic resonance (MR) imaging was used to evaluate the role

of lateral medullary compression by adjacent vascular

structures as a cause of neurogenic hypertension. METHODS:

Patients with documented essential hypertension were

recruited to undergo thin-slice axial brainstem MR imaging

evaluation. Nonhypertensive (control) patients scheduled to

undergo MR imaging for other reasons also underwent thin-

slice MR imaging to form a basis for comparison. Magnetic

resonance images obtained in patients from the hypertensive

(30 patients) and the control (45 patients) groups were then

compared by four independent reviewers (two

neuroradiologists and two neurosurgeons) who were blinded to

the patients' diagnosis and hypertensive status. Images were

reviewed with regard to left versus right vertebral artery

(VA) dominance, compression of the medulla on the left and/or

right side, and brainstem rotation. Medullary compression was

graded as either vessel contact without associated brainstem

deformity or vessel contact with associated brainstem

deformity. CONCLUSIONS: There was a tendency toward left VA

dominance in the hypertensive group compared with the

control group, although a significant difference was shown by

only one of the four reviewers. There were no differences in

brainstem compression or rotation between the hypertensive

and nonhypertensive groups. These results are contrary to

those of recently published studies in which MR imaging

and/or MR angiography revealed lateral brainstem vascular

compression in hypertensive patients but not in

nonhypertensive (control) patients. Reasons for this

discrepancy are discussed. On the basis of their own

experience and that of others, the authors believe that

neurogenic hypertension does exist. However, thin-slice MR

imaging may not be a reliable method for detecting

neurovascularly induced essential hypertension and the

prevalence of neurovascular compression as the source of

hypertension may be overestimated when using current

imaging techniques.

49. Comi, G. Evoked potentials in diabetes mellitus. Clin-Neurosci.

1997; 4(6): 374-9; ISSN: 1065-6766.

UNITED-STATES. Abnormalities of central afferent and

efferent pathways have been revealed by evoked potential

studies in diabetic patients. Central conduction time is only

slightly prolonged; in afferent pathways the primary sensory

neuron is more affected than in the subsequent stages,

probably as an expression of a central-peripheral distal

axonopathy. Central nervous system abnormalities are more

frequent in patients with peripheral neuropathy, but evoked

potential can be abnormal even in patients without neuropathy.

Brainstem auditory evoked potential (BAEP), somatosensory

evoked potentials (SEPs) and visual evoked potentials (VEPs)

can be affected together, but isolated abnormalities are more

frequently observed. Diffuse neuropathological changes have

been found in the optic nerves, periventricular regions,

brainstem and spinal cord in postmortem pathological studies.

Similar changes have been found in animals with experimental

diabetes. The pathophysiology of central nervous system (CNS)

abnormalities is uncertain, many causes are probably active in

including neural damage: chronic hyperglycemia, hypoglycemic

episodes, angiopathy, blood-brain barrier dysfunction and

others, still unknown.

50. Cone Wesson, B.; Ramirez, G. M. Hearing sensitivity in newborns

estimated from ABRs to bone-conducted sounds. J-Am-Acad-

Audiol. 1997 Oct; 8(5): 299-307; ISSN: 1050-0545.

CANADA. This study focused on the problem of estimating

hearing sensitivity in newborns from auditory brainstem

responses (ABRs) evoked by clicks and 500 Hz and 4000 Hz

tonebursts presented by a bone-conduction (BC) oscillator. The

effects of acoustic energy transmitted to the ear canal,

gender, and ear differences were also investigated. ABR

thresholds for BC stimuli were 56, 52, and 53 dB (re 1 microN)

or -5, -14, and 0 dB nHL (re adult psychophysical threshold)

for click and 500 Hz and 4000 Hz tonebursts, respectively. For

newborns, ear canal SPLs generated by the BC stimuli were as

much as 21 dB greater than those in adults. Gender-related

threshold differences were significant, with female infants

having lower thresholds than males; however, ear differences

were not. The findings of this study can be used to set

appropriate BC stimulus levels for screening or assessment of

newborns.

51. Coplin, W. M.; Kim, D. K.; Kliot, M.; Bird, T. D. Mutism in an adult

following hypertensive cerebellar hemorrhage: nosological

discussion and illustrative case. Brain-Lang. 1997 Oct 1;

59(3): 473-93; ISSN: 0093-934X.

UNITED-STATES. Mutism after cerebellar injury has been

associated with tumors, hemorrhage, and surgery of midline

cerebellar structures. Literature review identified 54 cases,

primarily in children after surgical splitting of the inferior

vermis. We present a 47-year-old who developed transient

mutism after cerebellar hemorrhage. This represents the first

report of transient mutism in an adult with neither tumor nor

brainstem infarction and documents the importance of

cerebellar structures for initiation and production of speech in

adulthood. This case further differs from those previous

because of the long mute period and the subsequent return of

continued ataxic and dysarthric speech.

52. Couldwell, W. T.; Zhang, W.; Allen, R.; Arce, D.; Stillerman, C. B.

Cerebellar contusion associated with type I Chiari

malformation following supratentorial head trauma: case

report. Neurol-Res. 1998 Jan; 20(1): 93-6; ISSN: 0161-6412.

ENGLAND. Acute presentation of Type I Chiari malformation in

children is distinctly rare. An 11 year old male suffered a

trauma to the right temporal-parietal region in a tobogganing

accident resulting in an open depressed skull fracture.

Radiographic evaluation included a Computed Tomographic scan

which also demonstrated a significant cerebellar contusion

and the presence of subarachnoid hemorrhage in the region of

craniovertebral junction. Magnetic Resonance imaging revealed

an underlying Type I Chiari malformation. Somatosensory

evoked responses shortly following the injury demonstrated

slowing of conduction across the lower brainstem. The open

depressed fracture was debrided and elevated. Subsequent

observation resulted in slow improvement in neurological

function. A followup somatosensory evoked potential study

performed 21 days following the accident showed

improvement in conduction across the craniovertebral

junction. The tonsillar ectopia associated with Type I Chiari

malformation may predispose to cerebellar, upper spinal and

brainstem injury following supratentorial trauma.

53. Counter, S. A.; Buchanan, L. H.; Ortega, F.; Laurell, G. Normal

auditory brainstem and cochlear function in extreme pediatric

plumbism. J-Neurol-Sci. 1997 Nov 6; 152(1): 85-92; ISSN:

0022-510X.

NETHERLANDS. Lead (Pb) intoxication in children has been

associated with encephalopathy, sensory and cognitive

impairments. We investigated the prevalence and neuro-

sensory effects of Pb exposure in children living in Andean

villages of Ecuador with high Pb contamination from discarded

automobile batteries used in the local ceramics glazing

industry. Venous blood samples were collected from 107

children in the Pb glazing area and from 39 children living in a

geographically distant area with no known Pb contamination

and measured for blood lead (PbB) levels. Auditory brainstem

responses (ABR) and audiological/otological tests were

conducted on children in the Pb-Glazing Group. The median PbB

level for children in the Pb-Glazing Group was 40.0 microg per

dl (range: 6.2-128.2 microg per dl) and for the non Pb-Glazing

Group 6.0 microg per dl (1.9-18.0 microg per dl). The

differences in PbB levels for children in the study and control

areas were statistically significant (t-test, P<0.0001). ABR

tests on the Pb-Glazing Group indicated normal wave latencies

and neural transmission times, and no statistical correlation

between PbB level and interpeak latencies. Audiological tests

showed normal cochlear function and no statistical relation

between auditory thresholds and PbB level. Contrary to

prevailing assumptions, elevated PbB levels in children do not

invariably impair auditory brainstem neural transmission or

sensory-neural cochlear function, both of which have been

implicated as significant contributors to the

neurodevelopmental disabilities associated with childhood

plumbism.. 7439-92-1.

54. Crary, M. A.; Baldwin, B. O. Surface electromyographic

characteristics of swallowing in dysphagia secondary to

brainstem stroke. Dysphagia. 1997 Sep; 12(4): 180-7; ISSN:

0179-051X.

UNITED-STATES. Surface electromyography (SEMG) provides an

noninvasive avenue for evaluating swallowing physiology. This

report describes SEMG characteristics associated with

swallow attempts in 6 dysphagic patients who had suffered

brainstem stroke compared with 6 age and gender-matched

controls. Results indicated that patients with dysphagia

secondary to brainstem stroke differed in both amplitude and

timing aspects of swallowing attempts from asymptomatic

controls. Specifically, the results indicated that during

swallow attempts, dysphagic patients produced more muscle

activity over a shorter duration and with less coordination

than controls. Potential physiological mechanisms of these

results are discussed.

55. Cwik, V. A.; Hanstock, C. C.; Allen, P. S.; Martin, W. R. Estimation

of brainstem neuronal loss in amyotrophic lateral sclerosis

with in vivo proton magnetic resonance spectroscopy.

Neurology. 1998 Jan; 50(1): 72-7; ISSN: 0028-3878.

UNITED-STATES. In vivo proton magnetic resonance

spectroscopy (MRS) may be used to quantify brainstem

neuronal degeneration in ALS because of the neuronal

localization of N-acetylaspartate and N-

acetylaspartylglutamate, together termed NA, which are

estimated with this technique. We measured the ratio of NA to

creatine/phosphocreatine (NA/Cr) with proton MRS at 3.0 tesla

(T) in a 4.3-cm3 volume in the pons and upper medulla of 12

ALS patients and 17 age-matched control subjects. Brainstem

NA/Cr was reduced in ALS versus control subjects (mean +/-

SD: 1.57 +/- 0.20 versus 1.95 +/- 0.14; p < 0.0001). Patients

with severe spasticity or prominent bulbar weakness had the

lowest NA/Cr ratios; those with predominantly lower motor

neuron limb weakness had near-normal ratios. We conclude

that proton MRS may quantify region-specific neuronal

dysfunction in ALS.. 0.

56. Daniels, D. L.; Mark, L. P.; Ulmer, J.; Maas, E. F.; Borne, J. A.;

Calderwood, G. W. Understanding the brain stem. Neuroimaging-

Clin-N-Am. 1998 Feb; 8(1): 55-68; ISSN: 1052-5149.

UNITED-STATES. This article highlights features of brain

anatomy that are important to know in interpreting magnetic

resonance images. This article concentrates on the names of

some brain stem structures, the three-dimensional appearance

of six important tracts, and the location of cranial nerve

nuclei.

57. Darlington, D. N.; Tehrani, M. J. Blood flow, vascular resistance,

and blood volume after hemorrhage in conscious

adrenalectomized rat. J-Appl-Physiol. 1997 Nov; 83(5): 1648-

53; ISSN: 8750-7587.

UNITED-STATES. Hemorrhage leads to cardiovascular collapse

and death in adrenal-insufficient animals. To determine

whether the cardiovascular collapse is due to vasodilation

and/or failure to restore blood volume, we used radiolabeled

microspheres and 125I-labeled albumin to measure blood flow

and blood volume in conscious adrenalectomized (ADX) rats

after 15 ml.kg-1.3 min-1 hemorrhage. In ADX rats, hemorrhage

led to a greater fall than in sham rats in blood flow in the

stomach, small intestines, cecum, colon, spleen, hepatic portal

vein, kidney, testis, lung, thymus, bone, fat, forebrain,

cerebellum, and brainstem. The greater fall in blood flow was

caused by an increase in vascular resistance in these organs

except brain and hepatic artery. Sham rats maintained or

increased brain and hepatic artery blood flow after

hemorrhage whereas flow decreased and remained depressed in

ADX rats. ADX rats failed to restore blood volume, whereas

sham rats completely restored blood flow by 2 h. We conclude

that cardiovascular collapse in ADX rats does not result from

vasodilatation but may result from a failure to restore blood

volume. The failure to restore blood volume and the low blood

flow to organs, especially brain and liver, may contribute to

mortality in ADX rats after hemorrhage.

58. Dassesse, D.; Hemmens, B.; Cuvelier, L.; Resibois, A. GTP-

cyclohydrolase-I like immunoreactivity in rat brain. Brain-Res.

1997 Nov 28; 777(1-2): 187-201; ISSN: 0006-8993.

NETHERLANDS. GTPCH-I immunoreactive structures in the rat

brain were studied using a polyclonal antibody raised in the

chick. General mapping was made using the avidin-biotin-

peroxidase technique and compared with the distribution of

tyrosine hydroxylase and serotonin immunoreactivities. Double

immunofluorescence was performed in order to establish real

intracellular colocalization. GTPCH-I immunoreactivity was

generally found to be low. Immunostained neurons were

present in all the serotonin cell groups. In catecholaminergic

neurons, although tyrosine hydroxylase immunoreactivity was

always very high, GTPCH-I immunoreactivity was extremely

variable, from relatively strong (substantia nigra, ventral

tegmental area) to low (locus coeruleus, caudal part of the

hypothalamus), extremely low (rostral hypothalamus, ventral

brainstem) or almost absent (dorsal brainstem, some

hypothalamic nuclei). When feasible, double immunolabeling

revealed that all the serotonin cells and most of the tyrosine

hydroxylase cells were also expressing GTPCH-I. Our results

argue in favor of a regulation of tyrosine hydroxylase activity

by the intracellular synthesis of BH4.. EC 1.14.16.2; EC

3.5.4.16; 0; 17528-72-2; 22150-76-1; 50-67-9; 51-41-2.

59. Davies, A. M. Studies of neurotrophin biology in the developing

trigeminal system. J-Anat. 1997 Nov; 191( Pt 4): 483-91;

ISSN: 0021-8782.

ENGLAND. The accessibility of the primary sensory neurons of

the trigeminal system at stages throughout their development

in avian and mammalian embryos and the ease with which

these neurons can be studied in vivo has facilitated

investigation of several fundamental aspects of neurotrophin

biology. Studies of the timing and sequence of action of

neurotrophins and the expression of neurotrophins and their

receptors in this well characterised neuronal system have led

to a detailed understanding of the functions of neurotrophins

in neuronal development. The concepts of neurotrophin

independent survival, neurotrophin switching and neurotrophin

cooperativity have largely arisen from work on the trigeminal

system. Moreover, in vitro studies of trigeminal neurons

provided some of the first evidence that the neurotrophin

requirements of sensory neurons are related to sensory

modality. The developing trigeminal system has been studied

most extensively in mice and chickens, each of which has

particular advantages for understanding different aspects of

neurotrophin biology. In this review, I will outline these

advantages and describe some of the main findings that have

arisen from this work.. 0; 0.

60. Davis, M.; Walker, D. L.; Lee, Y. Amygdala and bed nucleus of the

stria terminalis: differential roles in fear and anxiety

measured with the acoustic startle reflex. Philos-Trans-R-

Soc-Lond-B-Biol-Sci. 1997 Nov 29; 352(1362): 1675-87; ISSN:

0962-8436.

ENGLAND. Neural stimuli associated with traumatic events

can readily become conditioned so as to reinstate the memory

of the original trauma. These conditioned fear responses can

last a lifetime and may be especially resistant to extinction. A

large amount of data from many different laboratories

indicate that the amygdala plays a crucial role in conditioned

fear. The amygdala receives information from all sensory

modalities and projects to a variety of hypothalamic and

brainstem target areas known to be critically involved in

specific signs that are used to define fear and anxiety.

Electrical stimulation of the amygdala elicits a pattern of

behaviours that mimic natural or conditioned states of fear.

Lesions of the amygdala block innate or conditioned fear and

local infusion of drugs into the amygdala have anxiolytic

effects in several behavioural tests. Excitatory amino acid

receptors in the amygdala are critical for the acquisition,

expression and extinction of conditioned fear.

61. Davison, J. S.; Reynolds, K. A. Activation of brainstem neurons by

duodenal stimuli as revealed by fos protein immunochemistry:

evidence for a role of CCK. Proc-West-Pharmacol-Soc. 1997;

40: 101-2; ISSN: 0083-8969.

UNITED-STATES. 0; 0; 0; 9011-97-6.

62. de Lecea, L.; Kilduff, T. S.; Peyron, C.; Gao, X.; Foye, P. E.;

Danielson, P. E.; Fukuhara, C.; Battenberg, E. L.; Gautvik, V. T.;

Bartlett, FS 2nd; Frankel, W. N.; van, den Pol AN; Bloom, F. E.;

Gautvik, K. M.; Sutcliffe, J. G. The hypocretins: hypothalamus-

specific peptides with neuroexcitatory activity. Proc-Natl-

Acad-Sci-U-S-A. 1998 Jan 6; 95(1): 322-7; ISSN: 0027-8424.

UNITED-STATES. We describe a hypothalamus-specific mRNA

that encodes preprohypocretin, the putative precursor of a pair

of peptides that share substantial amino acid identities with

the gut hormone secretin. The hypocretin (Hcrt) protein

products are restricted to neuronal cell bodies of the dorsal

and lateral hypothalamic areas. The fibers of these neurons are

widespread throughout the posterior hypothalamus and project

to multiple targets in other areas, including brainstem and

thalamus. Hcrt immunoreactivity is associated with large

granular vesicles at synapses. One of the Hcrt peptides was

excitatory when applied to cultured, synaptically coupled

hypothalamic neurons, but not hippocampal neurons. These

observations suggest that the hypocretins function within the

CNS as neurotransmitters.. 0; 0; 0; 0; 1393-25-5.

63. Debus, J.; Hug, E. B.; Liebsch, N. J.; O'Farrel, D.; Finkelstein, D.;

Efird, J.; Munzenrider, J. E. Brainstem tolerance to conformal

radiotherapy of skull base tumors. Int-J-Radiat-Oncol-Biol-

Phys. 1997 Dec 1; 39(5): 967-75; ISSN: 0360-3016.

UNITED-STATES. PURPOSE: The aim of this study was to

analyze the long-term incidence of brainstem toxicity in

patients treated for skull base tumors with high dose

conformal radiotherapy. METHODS AND MATERIALS: Between

1974 and 1995, 367 patients with chordomas (n = 195) and

chondrosarcomas (n = 172) of the base of skull have been

treated with combined megavoltage photon and 160 MeV proton

radiotherapy. Following 3D treatment planning with

delineation of target volumes and critical nontarget

structures dose distributions and dose-volume histograms

were calculated. Radiotherapy was given an 1.8 Gy or CGE

(=Cobalt Gray Equivalent) dose per fraction, with prescribed

target doses ranging from 63 CGE to 79.2 CGE (mean = 67.8

CGE). Doses to the brainstem surface were limited to < or = 64

CGE and to the brainstem center to < or = 53 CGE. RESULTS:

Follow-up time ranged from 6 months to 21.4 years (mean =

42.5 months). Brainstem toxicity was observed in 17 of 367

patients attributable to treatment, resulting in death of three

patients. Actuarial rates of 5 and 10-year high-grade toxicity-

free survival were 94 and 88%, respectively. Increased risk of

brainstem toxicity was significantly associated with

maximum dose to brainstem, volume of brainstem receiving >

or = 50 CGE, > or = 55 CGE, and > or = 60 CGE, number of

surgical procedures, and prevalence of diabetes or high blood

pressure. Multivariate analysis identified three independent

factors as important prognosticators: number of surgical

procedures (p < 0.001), volume of the brainstem receiving 60

CGE (p < 0.001), and prevalence of diabetes (p < 0.01).

CONCLUSIONS: Tolerance of brainstem to fractionated

radiotherapy appears to be a steep function of tissue volume

included in high dose regions rather than the maximum dose of

brainstem alone. In addition, presence of predisposing factors

as well as extent of surgical manipulation can significantly

lower brainstem tolerance in the individual patient.

64. Delalande, I.; Thomas, D.; Forzy, G.; Hautecoeur, P.; Gallois, P.

[Diagnostic importance of middle latency auditory evoked

potentials (MLAEP) in multiple sclerosis]. Interet diagnostique

des potentiels evoques auditifs de latence moyenne (PEALM)

dans la sclerose en plaques. Neurophysiol-Clin. 1997 Sep;

27(4): 293-9; ISSN: 0987-7053.

NETHERLANDS. This study was aimed at assessing the interest

of middle latency auditory evoked potentials (MLAEP)

recordings in multiple sclerosis (MS). Brainstem auditory

evoked potentials (BAEP) and MLAEP were recorded in 40

control subjects and 65 patients who had MS according to

Poser's criteria. Na and Pa latencies were significantly

delayed in the MS group. These abnormalities were detected in

60% of the patients. In 26% of the cases with normal BAEP,

abnormalities of MLAEP were present. In 71% of the patients

abnormalities of both BAEP and MLAEP were observed. These

results suggest the ability of MLAEP recordings to detect

lesions of the auditory pathways rostral to the pons and show

the value of their combined recordings in MS patients.

65. Denavit Saubie, M.; Champagnat, J.; Fortin, G. Maturation of

brainstem respiratory neuronal networks. Pediatr-Pulmonol-

Suppl. 1997; 16: 216-7; ISSN: 1054-187X.

UNITED-STATES.

66. Dequardo, J. R.; Tomori, O.; Brunberg, J. A.; Tandon, R. Does

neuroanatomy predict ECT response? Prog-

Neuropsychopharmacol-Biol-Psychiatry. 1997 Nov; 21(8):

1339-52; ISSN: 0278-5846.

ENGLAND. 1. Structural neuropathologic abnormalities have

been associated with severe psychiatric illnesses, including

bipolar disorder, major depressive disorder, and schizophrenia.

In the latter, ventricular enlargement has been variably

associated with symptom severity and poor treatment

response. In patients with severe depressive disorders, the

relationship between cortical and subcortical pathology and

ventricle enlargement, symptom severity, and response to

treatment is far from clear. 2. The present study investigated

the relationship between structural CNS pathology, symptom

severity and treatment response in patients undergoing ECT. It

was hypothesized that patients with greater neuroanatomic

abnormalities would demonstrate greater initial symptom

severity and poorer response to ECT. 3. The subjects were 57

patients with unipolar or bipolar depression admitted for ECT

treatment. Symptom severity was quantified using the

Hamilton Depression Rating Scale (HRSD) at baseline and post-

ECT. 4. Lateral and third ventricle-brain ratio (LVBR, 3VBR)

were determined from CT scans and cortical atrophy was rated

by a faculty neuroradiologist. 5. Contrary to our first

hypothesis, structural pathology was not associated with

baseline symptom severity. In terms of treatment response,

the number of treatments required to achieve benefit was

correlated with larger 3VBR; CT variables were not related to

total post-treatment or change in HRSD score. Third ventricle

enlargement may be an index of generalized pathology or

regional brainstem abnormalities that influence ECT response

rate by limiting individual seizure efficacy or neurochemical

responsiveness, thereby necessitating a greater number of ECT

treatments, without significant impact on overall response.

67. Desole, M. S.; Esposito, G.; Migheli, R.; Sircana, S.; Delogu, M. R.;

Fresu, L.; Miele, M.; de Natale, G.; Miele, E. Glutathione

deficiency potentiates manganese toxicity in rat striatum and

brainstem and in PC12 cells. Pharmacol-Res. 1997 Oct; 36(4):

285-92; ISSN: 1043-6618.

ENGLAND. Levels of dopamine (DA), dihydroxyphenylacetic acid

(DOPAC), homovanillic acid (HVA), noradrenaline (NA),

glutathione (GSH), ascorbic acid (AA), dehydroascorbic acid

(DHAA) and uric acid (UA) were determined in the striatum

and/or in the brainstem of 3-month-old male Wistar rats after

subchronic oral exposure to MnCl2 (20 mg kg-1 daily) alone or

associated to buthionine (S,R)sulphoximine-ethyl ester (BSO-

E), an inhibitor of GSH synthesis. The NA, DA, DOPAC, GSH and

glutathione disulphide (GSSG) concentrations were also

determined in PC12 cells incubated with Mn alone or

associated with either BSO-E or AA. When PC12 cells were

incubated with AA, cellular AA and DHAA concentrations were

also determined. It was found that BSO-E: (a) decreased GSH

levels in the striatum and in the brainstem; (b) potentiated the

Mn-induced increase in AA oxidation and uric acid formation in

both brain regions; and (c) potentiated the Mn-induced DA and

NA depletion in the brainstem. Moreover, the changes in

striatal DA metabolism induced by the BSO-E association with

Mn (decrease in DA, DOPAC and HVA levels and in the DOPAC +

HVA/DA ratio) are consistent with the hypothesis of a loss of

dopaminergic neurons. In PC12 cells, BSO-E decreased GSH and

GSSG levels and potentiated the Mn-induced decrease-in DA

and NA concentrations. On the contrary, AA antagonised the

Mn-induced DA and NA depletion. AA antagonised also the Mn-

and MN+ BSO-induced decrease in PC12 cells viability. In

conclusion, the impairment of neuronal antioxidant system

activity plays a permissive role in the oxidative stress-

mediated Mn neurotoxicity.. 0; 0; 131202-22-7; 1982-67-8;

50-81-7; 51-61-6; 70-18-8; 7773-01-5.

68. Diamant, N. E. Neuromuscular mechanisms of primary peristalsis.

Am-J-Med. 1997 Nov 24; 103(5A): 40S-43S; ISSN: 0002-9343.

UNITED-STATES. Primary peristalsis of the esophagus is

initiated by the act of swallowing. Control of the orderly

contraction must take into account coordination of the

activity in the esophageal body with the sphincters at either

end, integration of activity between the striated and smooth

muscle portions of the esophagus, and the central and

peripheral neural and muscular control mechanisms present.

Peristalsis in the striated section is directed by sequential

vagal excitation arising in a brainstem "Central Program

Generator." Peristalsis in the smooth muscle section involves

the interaction of central and peripheral neural mechanisms

and probably the interaction between these neural mechanisms

and smooth muscle properties. Coordination of activity

between the striated and smooth muscle portions has similar

multifaceted neural and mechanical components. In the smooth

muscle, 2 main neural mechanisms, a cholinergic excitatory

one and a nonadrenergic, noncholinergic (NANC) inhibitory one

interact together and with central and local influences to

regulate the amplitude, velocity, and direction of propagation

of the peristaltic contraction.

69. Diener, H. C.; Gendolla, A.; Juptner, M.; Kaube, H.; Limmroth, V.

Emerging treatments in headache. Eur-Neurol. 1997; 38(3):

167-74; ISSN: 0014-3022.

SWITZERLAND. Recent PET studies performed in humans during

migraine attacks revealed a 'spreading depression-like'

oligemia in the occipital cortex during the aura phase and a

region of increased blood flow in the brainstem during the

headache phase. Animal models were established to test new

migraine drugs. A number of 5-HT agonists, the so-called

'triptans', will be available in future besides sumatriptan to

treat acute migraine attacks. Migraine prophylaxis is still

hampered by the fact that we do not understand the action of

drugs used for this purpose and do not have an animal model.

Nevertheless, new substances were introduced recently into

the prophylaxis of migraine.. 0; 0; 0.

70. Diener, P. S.; Bregman, B. S. Fetal spinal cord transplants support

growth of supraspinal and segmental projections after

cervical spinal cord hemisection in the neonatal rat. J-

Neurosci. 1998 Jan 15; 18(2): 779-93; ISSN: 0270-6474.

UNITED-STATES. Cervical spinal cord injury at birth

permanently disrupts forelimb function in goal-directed

reaching. Transplants of fetal spinal cord tissue permit the

development of skilled forelimb use and associated postural

adjustments (, companion article). The aim of this study was

to determine whether transplants of fetal spinal cord tissue

support the remodeling of supraspinal and segmental pathways

that may underlie recovery of postural reflexes and forelimb

movements. Although brainstem-spinal and segmental

projections to the cervical spinal cord are present at birth,

skilled forelimb reaching has not yet developed. Three-day-old

rats received a cervical spinal cord overhemisection with or

without transplantation of fetal spinal cord tissue (embryonic

day 14); unoperated pups served as normal controls.

Neuroanatomical tracing techniques were used to examine the

organization of CNS pathways that may influence target-

directed reaching. In animals with hemisections only,

corticospinal, brainstem-spinal, and dorsal root projections

within the spinal cord were decreased in number and extent. In

contrast, animals receiving hemisections plus transplants

exhibited growth of these projections throughout the

transplant and over long distances within the host spinal cord

caudal to the transplant. Raphespinal axons were apposed to

numerous propriospinal neurons in control and transplant

animals; these associations were greatly reduced in the

lesion-only animals. These observations suggest that after

neonatal cervical spinal cord injury, embryonic transplants

support axonal growth of CNS pathways and specifically

supraspinal input to propriospinal neurons. We suggest that

after neonatal spinal injury in the rat, the transplant-

mediated reestablishment of supraspinal input to spinal

circuitry is the mechanism underlying the development of

target-directed reaching and associated postural adjustments.

71. Duan, M. L.; Canlon, B. Differences in forward masking after a

temporary and a permanent noise-induced hearing loss. Audiol-

Neurootol. 1996 Nov; 1(6): 328-38; ISSN: 1420-3030.

SWITZERLAND. The forward masking curve of the auditory

brainstem response (ABR) at selected frequencies together

with the quantification of hair cell loss through the analysis

of cochlear surface morphology was studied in guinea pigs

before and after acoustic trauma resulting in either a

temporary or a permanent threshold shift. In the presence of a

noise-induced temporary threshold shift, the slope of the

forward masking curve was not significantly different from

the pre-exposure curve. In contrast, during the acute phase of

the permanent threshold shift, the slope of the forward

masking curve was significantly reduced compared to the pre-

exposure value. After a recovery period of 2 weeks, the slope

of the forward masking curve from the permanently damaged

group returned to nearly normal values despite a persisting

ABR threshold shift and significant loss of outer hair cells.

The potential for analyzing the slope of the forward masking

curve in order to distinguish between the acute phase of a

permanent threshold shift and a temporary threshold shift is

discussed.

72. Duan, M. L.; Canlon, B. Forward masking is dependent on inner hair

cell activity. Audiol-Neurootol. 1996 Nov; 1(6): 320-7; ISSN:

1420-3030.

SWITZERLAND. The goal of this study was to test the

hypothesis that the inner hair cell complex (inner hair cell and

dendritic contacts) is solely responsible for generating the

slope of the forward masking curve. To test this hypothesis

two experiments were performed. The first was to measure

forward masking from the Bronx waltzing mouse, a mutant

possessing an inner hair cell defect. The Bronx waltzing mouse

demonstrated an approximately 60-dB auditory brainstem

response (ABR) threshold shift compared to CBA/CBA mice at

8 and 12 kHz. The slope of the forward masking curve was

significantly reduced compared to the control group,

particularly at the early delay times between 0 and 4 ms. The

second model employed kainic acid to affect the dendrites

beneath the inner hair cell. After the intracochlear infusion of

kainic acid, there was an approximately 47-dB ABR threshold

shift at 4 and 8 kHz compared to pre-infusion thresholds. The

slope of the forward masking curve from the kainic-acid group

was significantly reduced compared to the artificial-

perilymph group. Primarily the early delay times were

affected by kainic acid (0-4 ms). Morphological analysis

showed that there was extensive swelling of the afferent

nerve radial dendrites under the inner hair cells. The results

from the present study, as well as the preceding article,

suggest that the analysis of the slope of the forward masking

curve may be used for the detection of inner hair cell or radial

dendrite damage, independent of outer hair cell damage. The

present finding could provide a useful means of employing a

clinical test for determining the function of the inner hair cell

complex using a non-invasive measure of auditory function.

73. Duan, M. L.; Canlon, B. Outer hair cell activity is not required for

the generation of the forward masking curve. Audiol-Neurootol.

1996 Nov; 1(6): 309-19; ISSN: 1420-3030.

SWITZERLAND. Forward masking of the auditory brainstem

response (ABR) was achieved by increasing the time interval

from 0 to 12 ms between the masker offset and the probe

onset. The forward masking response demonstrated a near

linear function with an approximate 3.0-dB increase in

masking threshold for every millisecond interval increase in

the control guinea pig. The slope of the masking curve at

selected frequencies together with the quantification of hair

cell loss through the analysis of cochlear surface morphology

was studied before and after chemical insult. The

intracochlear infusion of sodium salicylate caused an

approximately 45-dB threshold shift of the ABR whereas the

slope of the forward masking curve was not significantly

different from the control values at the tested frequencies (1,

4, and 8 kHz). Systemic kanamycin administration (400 mg/kg

body weight for 9 consecutive days) caused a permanent ABR

threshold shift of 43-63 dB at 1, 4, and 8 kHz. The slope of the

forward masking curve was not significantly different at 1

kHz despite significant outer hair cell loss. The slope of the

forward masking curve at 4 and 8 kHz showed significant

reductions at the time intervals between 0 and 4 ms. Analysis

of the kanamycin-treated cochleae revealed not only

significant outer hair cell loss throughout the cochlea but

significant inner hair cell and inner pillar cell loss in the

basal end of the cochlea. The results suggest that the outer

hair cells are not needed for maintaining a normal forward

masking curve, whereas the slope of the forward masking

curve is sensitive to alterations induced to either the inner

hair cells or the inner pillar cells.. 54-21-7; 59-01-8.

74. Dubayle, D.; Viala, D. Effects of CO2 and pH on the spinal

respiratory rhythm generator in vitro. Brain-Res-Bull. 1998;

45(1): 83-7; ISSN: 0361-9230.

UNITED-STATES. In vitro brainstem spinal cord preparations

isolated from newborn rats were used to separately test the

effects of modifications of FCO2 and pH of artificial

cerebrospinal fluid on the frequency and amplitude of spinal

respiratory activity recorded from C2-C8 ventral roots.

Different substances such as L-glutamic acid (3 x 10[-3] M),

N-methyl-D-aspartic acid (5 x 5 x 10[-6] M), amphetamine (6

mg/100 ml), 5-hydroxytryptophane (10[-3] M), or modified K+

(10[-3] M) were tested for their capacity to elicit stable

changes in spinal respiratory activity over a long time period

(more than 30 min) and with high frequency of occurrence, i.e.,

in at least 50% of the cases. None of the above drugs were

found to be suitable for the investigation of the

chemosensitivity of the spinal respiratory generator (sRG)

because they were only able to maintain spinal respiratory

activity for around 15 min. Given these data, the previously

used procedure of activation through initial deep diethyl ether

anaesthesia of newborn rats was employed [3] to test the

chemosensitivity of the sRG because this treatment resulted

in the maintenance of spinal respiratory activity with a

regular pattern for 30 min, even if it occurred in only 25% of

the preparations. After an increase in FCO2 from 5 to 7% (at

constant pH 7.4), a significant (p < 0.05) enhancement of the

mean frequency was observed on spinal respiratory bursting in

both brainstem spinal cord and isolated spinal cord

preparations. The changes in burst amplitude, however, were

quite variable from one experiment to the other. At constant

FCO2 (5%), a decrease in pH from 7.4 to 7.2 enhanced spinal

respiratory frequency on brainstem spinal cord or isolated

spinal cord preparations, while an increase in pH from 7.4 to

7.6 decreased it. Under these pH conditions, we did not observe

any reproducible variations in spinal burst amplitude. From

these results, we conclude that this spinal generator is

chemosensitive to both CO2 and [H+], suggesting that it

belongs to the respiratory system. Our data provide evidence

for the existence of spinal CO2 and/or H+ chemoreceptors..

124-38-9; 300-62-9; 56-69-9; 56-86-0; 6384-92-5; 7440-

09-7.

75. Ebraheim, N. A.; Lu, J.; Skie, M.; Heck, B. E.; Yeasting, R. A.

Vulnerability of the recurrent laryngeal nerve in the anterior

approach to the lower cervical spine. Spine. 1997 Nov 15;

22(22): 2664-7; ISSN: 0362-2436.

UNITED-STATES. STUDY DESIGN: To perform anatomic

dissections and measurements of the recurrent laryngeal nerve

between the inferior thyroid artery and superior border of the

clavicle (mid-portion) on both sides. OBJECTIVES: To

determine quantitatively the differences in course and

location between the recurrent laryngeal nerves on both sides

and to relate this to the vulnerability of the recurrent

laryngeal nerve during an anterior approach to the lower

cervical spine. SUMMARY OF BACKGROUND DATA: The

midportion of the recurrent laryngeal nerve is usually

encountered in the anterior approach to the lower cervical

spine, especially on the right side. No quantitative regional

anatomy describing the course and location of the mid-portion

of the recurrent laryngeal nerve is available in the literature.

METHODS: Fifteen adult cadavers were used for dissections of

the recurrent laryngeal nerve. The length of the recurrent

laryngeal nerve between the superior border of the clavicle

and the inferior thyroid artery, and the angle of the recurrent

laryngeal nerve with respect to sagittal plane, were measured

bilaterally. In addition, six cross-sections at C7 were obtained

to determine the linear distances between esophagotracheal

groove and the recurrent laryngeal nerve. RESULTS: The

recurrent laryngeal nerve on the right runs in a superior and

medial direction, with an angle of 25.0 degrees +/- 4.7 degrees

relative to sagittal plane, compared with 4.7 degrees +/- 3.7

degrees on the left. The length of the recurrent laryngeal nerve

between the superior border of the clavicle and the inferior

thyroid artery is 23.0 +/- 4.4 mm on the left, and 22.8 +/- 4.3

mm on the right. The recurrent laryngeal nerve lies deep

within the esophagotracheal groove on the left, but 6.5 +/- 1.2

mm anterior and 7.3 +/- 0.8 mm lateral to the

esophagotracheal groove on the right. CONCLUSIONS: The

recurrent laryngeal nerve on the right side is highly vulnerable

to injury if ligature of the inferior thyroid vessels is not

performed as laterally as possible or if retraction of the

midline structures along with the recurrent laryngeal nerve is

not performed intermittently. Avoiding injury to the recurrent

laryngeal nerve, especially on the right side, is a major

consideration during an anterior approach to lower cervical

spine.

76. Eckhardt Henn, A.; Steinhorst, N.; Krauthauser, H.; Thomalske, C.;

Tettenborn, B.; Hoffmann, S. O.; Hopf, H. C. [Illness-specific

control issues in patients with vertigo as the main symptom].

Krankheitsspezifische Kontrolluberzeugungen bei Patienten

mit der Leitsymptomatik Schwindel. Psychother-Psychosom-

Med-Psychol. 1997 Nov; 47(11): 403-9; ISSN: 0173-7937.

GERMANY. The study explored the relationship between health

locus of control and anxiety in 90 patients with the chief

complaint of dizziness/vertigo. The patients were subjected

to a neurological examination, including standardised history,

physical examination, electronystagmography with caloric

testing and posturography, auditory and visually brainstem-

evoked responses, masseter reflex, vertebrobasiliar

transcranial Doppler, optional: cranial imaging (CCT/MRI),

cardial diagnostic, and a psychiatric-psychodynamic

examination (including psychometric tests: STAI-G X2, KKG,

SBA-S). The whole group of patients (psychogenic and organic

dizziness) had a specific pattern of health locus of control:

"double health external" (Type IV-Wallston and Wallston 1982).

Patients with psychogenic dizziness showed a higher score of

external locus of control (chance) compared with the patients

with organic dizziness. High anxiety scores were accompanied

by high scores of external locus of control (powerful others

and chance) above all in the patients with psychogenic

dizziness. Implications for therapy are discussed.

77. Elkind, M. S.; Mohr, J. P. Cerebellar hemorrhage. New-Horiz. 1997

Nov; 5(4): 352-8; ISSN: 1063-7389.

UNITED-STATES. Cerebellar hemorrhage may present with a

spectrum of clinical manifestations, from a benign course

with little to no neurologic deficit to a rapidly fatal course

with hydrocephalus and brainstem compression. In patients

with clinical deterioration, ventricular drainage and surgical

evacuation of clot may be life-saving. Several retrospective

studies have attempted to define radiographic indicators of

the need for surgery with moderate success. A rational

approach to the management of the patient with cerebellar

hemorrhage is presented.

78. Ellis, C. M.; Simmons, A.; Lemmens, G.; Williams, S. C.; Parkes, J. D.

Proton spectroscopy in the narcoleptic syndrome. Is there

evidence of a brainstem lesion? Neurology. 1998 Feb; 50(2

Suppl 1): S23-6; ISSN: 0028-3878.

UNITED-STATES. There is controversy regarding the

relationship of structural or biochemical brainstem lesions to

"idiopathic" narcolepsy. Most cases of the narcoleptic

syndrome are considered to be idiopathic because no structural

lesion is detectable, although some cases of secondary

narcolepsy are known to be associated with no structural

brainstem lesions. Using proton spectroscopy, we determined

levels of ventral pontine metabolite pools in 12 normal

subjects and 12 subjects with idiopathic narcolepsy. REM

sleep is generated in ventral pontine areas. Proton

spectroscopy was used to study levels of N-acetyl aspartate

(NAA) as a marker of cell mass, creatine and phosphocreatine

(Cr + PCr), and choline (Cho). The intensity of the peaks, as

determined by the area under the peak (AUP), was measured.

The AUP correlates with the quantity of chemical present. In

this study, the ratios of NAA to Cr + PCr were similar in

normal subjects and in narcoleptic subjects with idiopathic

narcolepsy. No differences in measured metabolic ratio were

observed in subjects who slept during the scan procedure

compared with those who remained awake. Subjects with

"symptomatic" narcolepsy accompanied by an obvious

structural brain lesion were not studied. Proton spectroscopy

of the brain initiates a new kind of neurochemistry, allowing

the noninvasive study of metabolic pools in the living human

brain without the use of any kind of tracer or radioactive

molecule. In this study, there was no evidence of cell loss in

the ventral pontine areas of subjects with the narcoleptic

syndrome.. 56-84-8; 57-00-1; 67-07-2; 997-55-7.

79. Erisir, A.; Van Horn, S. C.; Sherman, S. M. Distribution of synapses

in the lateral geniculate nucleus of the cat: differences

between laminae A and A1 and between relay cells and

interneurons. J-Comp-Neurol. 1998 Jan 12; 390(2): 247-55;

ISSN: 0021-9967.

UNITED-STATES. Laminae A and A1 of the lateral geniculate

nucleus in the cat are generally considered to be a structurally

and functionally matched pair of inputs from two eyes,

although there are subtle light microscopic and physiological

differences. The present study aims to display ultrastructural

differences between these two laminae based on electron

microscopic observances on the connectivity patterns of their

afferents onto two main cell types: relay cells, and

interneurons present in this nucleus. In a design of population

measurement from randomized sample areas in laminae A and

A1 from six brains, all synaptic contacts made by three

terminal types of the geniculate nucleus were identified, and a

number of relative distribution properties were analyzed.

When the A-laminae were considered as a homogeneous

structure, the distribution of the three terminal types on

geniculate cells was similar to previously reported results,

confirming the validity of the sampling strategies used; RLP

(retinal) terminals provided one-fifth of all synapses, whereas

RD (from cortex and brainstem) and F (inhibitory) types

constituted one-half and one-third, respectively. The relay

cells alone received a similar composition of afferents.

However, interneurons alone received approximately equal

amounts of synapses from the three sources. Similar analyses

comparing the distributions in lamina A and A1 revealed that

RD and F terminals, but not RLP terminals, innervate these two

laminae differently; more RD and fewer F terminals were

found in lamina A1. This difference was also present in the

distribution of terminals on relay cells alone, but not on

interneurons. These results suggest that (1) retinal terminals

form a significantly larger fraction of the input to

interneurons than to relay cells; correspondingly, cortex and

brainstem provide a smaller fraction of all inputs to

interneurons than to relay cells; and (2) laminae A and A1 are

not strictly equivalent projection sites of the two retinae. The

results are discussed in relation to the Y-cell subpopulation in

lamina A1 that is involved in corticotectal, as well as

corticogeniculate circuits, as opposed to Y-cells of lamina A

that are involved in only the latter.

80. Espinosa, de los Monteros A; Zhao, P.; Huang, C.; Pan, T.; Chang, R.;

Nazarian, R.; Espejo, D.; de Vellis, J. Transplantation of CG4

oligodendrocyte progenitor cells in the myelin-deficient rat

brain results in myelination of axons and enhanced

oligodendroglial markers. J-Neurosci-Res. 1997 Dec 1; 50(5):

872-87; ISSN: 0360-4012.

UNITED-STATES. Transplantation of oligodendrocyte (Ol)

progenitor cells into the central nervous system is a

promising approach for the treatment of myelin disorders. This

approach requires providing adequate numbers of healthy cells

with myelinating potential. We recently showed the successful

transplantation of Ol progenitors into the myelin-deficient

(md) rat brain. In the present work, CG4 cells, a cell line with

properties of Ol progenitors, were labeled with fast blue and

grafted into P3-P5 pups born to carrier mothers. Examination

of host brains 2 weeks posttransplant indicated that CG4 cells

display a much more extensive migration capacity than their

wild-type counterparts. These cells synthesized myelin

components. In addition, ultrastructural analysis showed

myelin formation along axons of md hosts in various brain

regions, including corpus callosum, cerebellum, and brainstem.

Furthermore, in situ hybridization studies performed on

sagittal sections revealed extensive expression of

transferrin-mRNA within the md host parenchyma. The high

survival and functional features displayed by CG4 cells after

transplantation, together with their striking wide distribution

within the host parenchyma, as assessed by the presence of

myelinated fibers in mutant hosts, emphasizes the importance

of using highly motile and proliferative Ol progenitor cells.

Strategies to improve the condition and life span of md rat

pups are currently under investigation.. 0; 0; 11096-37-0.

81. Facchetti, D.; Mai, R.; Micheli, A.; Marciano, N.; Capra, R.;

Gasparotti, R.; Poloni, M. Motor evoked potentials and disability

in secondary progressive multiple sclerosis. Can-J-Neurol-Sci.

1997 Nov; 24(4): 332-7; ISSN: 0317-1671.

CANADA. BACKGROUND: To investigate the mechanisms

underlying disability in multiple sclerosis (MS), 40 patients

with the relapsing-remitting form of the disease and 13

patients with secondary progressive MS underwent multimodal

evoked potential (EP), motor evoked potential (MEP), and spinal

motor conduction time evaluation. Clinical disability was

evaluated by the expanded disability status scale (EDSS) and

functional system scales. In secondary progressive MS

patients, magnetic resonance imaging (MRI) was used to obtain

a semiquantitATive estimate of the total lesion load of the

brain. RESULTS: Spinal motor conduction time was

significantly longer in secondary progressive MS patients than

controls (p < 0.001) and relapsing-remitting MS patients (p <

0.05), but did not differ between relapsing-remitting patients

and controls. Spinal motor conduction times also correlated

directly with EDSS scores (p < 0.001) and pyramidal functional

system scores (p < 0.001). Brain lesion load (4960.3 +/-

3719.0 mm2) and the total number of lesions (67.7 +/- 37.0) in

secondary progressive MS did not correlate with disability

scores. For the following EPs, the frequencies of abnormalities

were significantly higher in secondary progressive MS patients

than relapsing-remitting patients: visual evoked potentials (p

< 0.05), somatosensory evoked potentials and upper limb motor

evoked potentials (p < 0.01), and brainstem auditory evoked

potentials, lower limb somatosensory evoked potentials and

lower limb motor evoked potentials (p < 0.001). CONCLUSIONS:

These findings suggest that disability in secondary

progressive MS patients is mainly due to progressive

involvement of corticospinal tract in the spinal cord.

82. Fenton, G. W. The postconcussional syndrome reappraised. Clin-

Electroencephalogr. 1996 Oct; 27(4): 174-82; ISSN: 0009-

9155.

UNITED-STATES. Despite the apparently benign nature of mild

head injury, reflected by the short post-traumatic amnesia

duration, relative absence of CNS signs and brief hospital stay,

a significant number of patients report persistent

symptomatology over the weeks or months afterwards. Largely

subjective in nature, such symptom clusters are termed the

postconcussion syndrome. The discrepancy between the

predominantly subjective complaints and negative examination

findings has generated uncertainty and debate about the

respective causation roles of organic and psychogenic factors.

Over the past 30 years evidence for organic brain changes has

accumulated through studies of cerebral circulation,

neuropsychological deficits, evoked potential recordings and

neuroimaging. This paper reviews data from two UK

prospective studies of the evolution and course of

postconcussional symptomatology using parallel psychosocial,

neuropsychiatric, quantitative EEG and brainstem auditory

evoked potential recordings. Changes in theta power occurred

early with resolution within 10 days. Prolonged brainstem

evoked response I-V intervals were seen in between 27% and

46% of patients. Symptom chronicity noted in a minority of

people (13%) was associated with a high prevalence of

brainstem dysfunction, while the degree of QEEG recovery

appeared to relate to the intensity of early symptom reaction

to the trauma. Levels of perceived stress at the time of the

injury or afterwards were not related to symptom formation,

but chronic social difficulties were a feature of the 21% of

patients who initially improved but had a late exacerbation of

symptoms between 6 weeks and 6 months after the trauma.

83. Frank, M. G.; Page, J.; Heller, H. C. The effects of REM sleep-

inhibiting drugs in neonatal rats: evidence for a distinction

between neonatal active sleep and REM sleep. Brain-Res. 1997

Dec 5; 778(1): 64-72; ISSN: 0006-8993.

NETHERLANDS. Neonatal active sleep (AS) has been considered

to be homologous and continuous with rapid-eye-movement

(REM) sleep in adult animals. We have recently proposed an

alternative view that AS is an undifferentiated sleep state

distinct from REM sleep. To test these opposing views on the

relationship of AS and REM sleep, neonatal rats (P11, P14 and

P20) were systemically injected with compounds that inhibit

REM sleep in adults. Zimelidine (ZMI) and desipramine (DMI) are

monoamine uptake inhibitors which increase synaptic

concentrations of serotonin and norepinephrine, respectively.

Serotonin and norepinephrine inhibit brainstem cholinergic

neurons important in REM sleep generation. Atropine (ATR) is a

muscarinic receptor antagonist that blocks the post-synaptic

effects of cholinergic projections. Only DMI (5 mg/kg)

suppressed AS at P11. ZMI (6 mg/kg) and ATR (6 mg/kg) did not

suppress AS until P14. These data suggest that serotonergic

and cholinergic regulation of AS are absent before P14. The

fact that AS in P11 rats is not affected by cholinergic

antagonists supports the hypothesis that AS and REM sleep

represent different sleep states.. 0; 0; 0; 50-47-5; 51-55-8;

56775-88-3.

84. Fujimoto, Y.; Isozaki, E.; Ootake, T.; Matsubara, S.; Hirai, S.

[Hallucination in opsoclonus-polymyoclonus syndrome]. Rinsho-

Shinkeigaku. 1997 Sep; 37(9): 806-9; ISSN: 0009-918X.

JAPAN. Here we report 2 cases of opsoclonus-polymyoclonus

syndrome (OPS) associated with viral encephalitis. They had

sleep disturbance, and visual hallucination. Case 1 had

auditory hallucination in addition, and case 2 had dreamlike

behavior. Those hallucination, which were colorful and vivid,

usually appeared at the bed time. Their hallucinations were

similar to peduncular hallucinations and you may also call

hypnagogic hallucinations, which are often seen in patients

with narcolepsy. Dreamlike behavior is observed during REM

sleep in patients with brainstem damage or sometimes in the

healthy elderly people. The presence of sleep disturbance,

hypnagogic hallucination, and dreamlike behavior suggests that

there may be some relationship between OPS and REM sleep.

Considering that REM sleep is suppressed by serotonergic

projection of the dorsal raphe nucleus in addition to several

reports about brainstem lesion with serotonergic

abnormalities in this disorder, we considered that dysfunction

of serotonergic neurons of the dorsal raphe nucleus might be

related in the development of OPS.. 50-67-9.

85. Fukazawa, T.; Moriwaka, F.; Hamada, K.; Hamada, T.; Tashiro, K.

Facial palsy in multiple sclerosis. J-Neurol. 1997 Oct;

244(10): 631-3; ISSN: 0340-5354.

GERMANY. Facial palsy occurred in 21 (19.6%) of 107 Japanese

patients with multiple sclerosis (MS) during a mean follow-up

period of 4.3 years. We observed residual signs of facial palsy

in five other patients in whom acute onset was confirmed

from medical records. Facial palsy began on average 7.6 years

after the onset of MS but in five patients (4.7%) was the first

symptom of MS, preceding the next MS symptom by 0.5-3 years.

Facial palsy was usually associated with other brainstem

signs, while two patients showed only facial palsy 1 and 3

years after the onset of MS. Twenty-one (84.0%) of the 25

patients who underwent brain magnetic resonance imaging

(MRI) showed brainstem lesions in the pontine tegmentum

ipsilateral to the facial palsy. However, the two patients

without other symptoms or signs had no apparent causal lesion

on MRI, which suggests difficulty in differentiating idiopathic

Bell's palsy from MS- associated facial palsy by MRI, although

it has an excellent capacity to detect causal lesions of facial

palsy associated with MS.

86. Funakoshi, K.; Kadota, T.; Atobe, Y.; Goris, R. C.; Kishida, R. NADPH-

diaphorase activity in the vagal afferent pathway of the

dogfish, Triakis scyllia. Neurosci-Lett. 1997 Nov 21; 237(2-3):

129-32; ISSN: 0304-3940.

IRELAND. Nicotinamide adenine dinucleotide phosphate

(NADPH)-diaphorase activity was examined in the cranial

sensory ganglia and brainstem of the banded dogfish, Triakis

scyllia. Positive neurons were found in the vagal sensory

ganglion projecting to the coelomic organs, but not in those

projecting to the gills or the lateral line organs. Nerve

terminals in the vagal lobe were also positive. No positive

neurons were found in the glossopharyngeal, facial, or

trigeminal sensory ganglia. These results suggest that use of

nitric oxide in the vagal sensory transmission from the

coelomic organs may have been maintained in the evolutionary

process from fish to mammals.. EC 1.14.13.39; EC 1.6.99.1.

87. Futamura, N.; Matsumura, R.; Murata, K.; Suzumura, A.; Takayanagi,

T. [An apparently sporadic case with spinocerebellar ataxia

type 1 (SCA1)]. Rinsho-Shinkeigaku. 1997 Aug; 37(8): 708-10;

ISSN: 0009-918X.

JAPAN. We reported a sporadic case with late onset SCA1.

There was no family history of neurological diseases. His

parents had been healthy until they died at the age of 77 and

89 years, respectively. The patient noticed gait disturbance at

age of 60. Thereafter, he gradually developed cerebellar

ataxia, hyporeflexia, mild atrophy of the facial and limb

muscles and moderate deep sensory disturbance. MRI of the

brain showed moderate atrophy of the cerebellum and

brainstem. Sequencing analysis of SCA1 gene demonstrated

that the patient had an expanded allele with 40 CAG repeats

and no CAT interruption. Consequently, he was diagnosed as

having SCA1. These results suggest the possibility that among

apparently sporadic cases with cerebellar ataxia, there are

some cases of SCA1 with mild CAG repeat expansion.. 0.

88. Gamkrelidze, G.; Giaume, C.; Peusner, K. D. The differential

expression of low-threshold sustained potassium current

contributes to the distinct firing patterns in embryonic

central vestibular neurons. J-Neurosci. 1998 Feb 15; 18(4):

1449-64; ISSN: 0270-6474.

UNITED-STATES. The principal cells of the chick tangential

nucleus are second-order sensory neurons that participate in

the three-neuron vestibulo-ocular and vestibulocollic reflexes.

In postnatal animals, second-order vestibular neurons fire

repetitively on depolarization. Previous studies have shown

that, although this is an important feature for normal reflex

function, it is only acquired gradually during embryonic

development. Whereas at 13 embryonic days (E13) the principal

cells accommodate after firing a single spike, at E16 a few

principal cells repetitively can fire multiple action potentials

on depolarization. Finally, in the hatchling, the vast majority

of principal cells is capable of nonaccommodating firing on

depolarization. As a first step in understanding the

mechanisms underlying developmental change in excitability

of these second-order vestibular neurons, we analyzed the

outward potassium currents and their role in accommodation,

using brainstem slices at E16. The principal cells exhibited

transient and sustained potassium currents, with both of these

containing calcium-dependent components. Further, both high-

and low-threshold sustained potassium currents have been

distinguished. The low-threshold dendrotoxin-sensitive

sustained potassium current (IDS) is associated with principal

cells that accommodate and is not expressed in those that fire

repetitively. Finally, blocking of IDS transforms

accommodating cells into neurons capable of firing trains of

action potentials on depolarization. These findings indicate

that suppression of IDS during development is sufficient to

transform accommodating principal cells into

nonaccommodating firing neurons and suggests that

developmental regulation of this current is necessary for the

establishment of normal vestibular function.. 7440-09-7;

7440-70-2.

89. Gao, K.; Mason, P. Somatodendritic and axonal anatomy of

intracellularly labeled serotonergic neurons in the rat medulla.

J-Comp-Neurol. 1997 Dec 15; 389(2): 309-28; ISSN: 0021-

9967.

UNITED-STATES. A knowledge of the anatomy of medullary

serotonergic cells is critical to understanding local and

brainstem circuits in which these cells participate.

Serotonergic neurons (n = 16) were identified, as previously

described (Mason [1997] J. Neurophysiol. 77:1087-1098) by

their slow and steady background discharge in halothane

anesthetized rats. Neurons were then intracellularly labeled

with Neurobiotin and visualized with 3,3'diaminobenzidine. The

validity of the physiological identification of serotonergic

cells was confirmed by processing two neurons that were

physiologically characterized as serotonergic for serotonin

immunoreactivity; both tested cells contained immunoreactive

serotonin. The dendrites and axon of each labeled cell were

reconstructed by using a three-dimensional computerized

system. Somata were small or medium in size and had

fusiform, triangular, or multipolar shapes. The dendritic arbor

was constricted with most dendrites extending for less than

500 microm from the soma. All labeled axons projected

caudally and travelled in the ventrolateral medulla, either

dorsal or ventral to the lateral reticular nucleus. Most cells

had collaterals and/or dense axonal swellings in the nucleus

reticularis gigantocellularis, nucleus reticularis

magnocellularis, raphe magnus, and the ventrolateral medulla.

Non-local collaterals and swellings were also observed in the

nucleus reticularis gigantocellularis and in the ventrolateral

medulla at all medullary levels. The results demonstrate that

1) the dendrites of serotonergic cells are restricted to raphe

magnus and the ventral part of nucleus reticularis

magnocellularis; and 2) serotonergic cells project to

medullary nuclei that contain bulbospinal cells which project

to dorsal, intermediate, and ventral horns. Serotonergic cell

projections to brainstem sites may mediate the integration of

sensory, autonomic, and motor modulation at the brainstem

level.. 50-67-9.

90. Garcia Silva, M. T.; Ribes, A.; Campos, Y.; Garavaglia, B.; Arenas, J.

Syndrome of encephalopathy, petechiae, and ethylmalonic

aciduria. Pediatr-Neurol. 1997 Sep; 17(2): 165-70; ISSN: 0887-

8994.

UNITED-STATES. We report a boy 20 months of age with

encephalopathy, petechiae, and ethylmalonic aciduria (EPEMA).

Other clinical features were severe hypotonia, orthostatic

acrocyanosis, and chronic diarrhea. Magnetic resonance

imaging (MRI) of the brain demonstrated bilateral lesions in

the lenticular and caudate nuclei, periaqueductal region,

subcortical areas, white matter, and brainstem. Short and

medium chain Acyl-CoA dehydrogenase and cytochrome c

oxidase (COX) activities in fibroblasts were normal. Muscle

histochemistry disclosed diffuse COX deficiency, and

respiratory chain activities in muscle disclosed severe COX

deficiency. Twelve other patients with similar clinical

features have been reported. Muscle COX activity, studied only

in four, demonstrated a clear-cut defect.. EC 1.9.3.1; 0; 0;

601-75-2.

91. Gass, A.; Filippi, M.; Rodegher, M. E.; Schwartz, A.; Comi, G.;

Hennerici, M. G. Characteristics of chronic MS lesions in the

cerebrum, brainstem, spinal cord, and optic nerve on T1-

weighted MRI. Neurology. 1998 Feb; 50(2): 548-50; ISSN: 0028-

3878.

UNITED-STATES. We analyzed the prevalence of severely

hypointense lesions on T1-weighted MRI in the brainstem,

spinal cord, and optic nerve from 65 patients with MS. About

half of 1,274 supratentorial lesions were classified as

severely hypointense. Severe hypointensity was not seen in the

optic nerve and spinal cord, and in only one of 168 chronic

brainstem lesions. Tissue destruction in the brainstem, spinal

cord, and optic nerve of MS patients does not usually result in

severely hypointense lesions.

92. Genovese, R. F.; Newman, D. B.; Li, Q.; Peggins, J. O.; Brewer, T. G.

Dose-dependent brainstem neuropathology following repeated

arteether administration in rats. Brain-Res-Bull. 1998; 45(2):

199-202; ISSN: 0361-9230.

UNITED-STATES. Histopathological effects of the artemisinin

antimalarial, beta-arteether, were evaluated in rats.

Arteether (3.125-12.5 mg/kg/day, IM, in sesame oil) was

administered for 7 consecutive days. Seven days following the

last injection, histological evaluation of the brainstem was

performed. Rats treated with 12.5 mg/kg showed significant

neuropathology, including chromatolysis, in the nucleus

trapezoideus and nucleus superior olive. To a lesser extent,

neuropathology was present in the nucleus ruber. Mild

neuropathology was also detected in other brainstem regions

examined. Although no statistically significant neuropathology

was found for the groups treated with 6.25 mg/kg/day and

3.125 mg/kg/day, substantial neuropathology was observed in

a single rat in each of these treatment conditions. These

results confirm and extend previous studies demonstrating

brainstem neurotoxicity from artemisinin antimalarials.

Furthermore, these results suggest that, in rats, brainstem

auditory pathways may be particularly vulnerable. Early

detection of arteether neuropathology may, therefore, require

examination of auditory functions.. 0; 0; 109716-83-8.

93. Geschwind, D. H.; Perlman, S.; Figueroa, K. P.; Karrim, J.; Baloh, R.

W.; Pulst, S. M. Spinocerebellar ataxia type 6. Frequency of the

mutation and genotype-phenotype correlations [see comments].

Neurology. 1997 Nov; 49(5): 1247-51; ISSN: 0028-3878.

Note: Comment in: Neurology 1997 Nov;49(5):1196-9.

UNITED-STATES. Spinocerebellar ataxia type 6 (SCA6) is the

most recently identified mutation causing autosomal-

dominant cerebellar ataxia without retinal degeneration

(ADCA). The SCA6 mutation is allelic with episodic ataxia type

2 (EA-2), but the two differ clinically because of the presence

of progressive, rather than episodic, ataxia in SCA6. SCA6

accounts for 12% of families with ADCA in an ethnically

heterogeneous population of patients. Clinical examination,

quantitative eye movement testing, and imaging data show

that the brainstem is normal in most patients with SCA6,

especially within the first 10 years of symptoms. Most

patients show progressive ataxia from the onset, but several

patients show an episodic course resembling EA-2. Thus, SCA6

mutations not only account for patients with ADCA I and ADCA

III phenotypes but also for some patients presenting with

episodic features that are typical for EA-2. Interestingly, a

compound heterozygote for the SCA6 expansion manifested an

earlier onset and more rapid course than family members with

the same larger expanded allele.

94. Gestreau, C.; Bianchi, A. L.; Grelot, L. Differential brainstem Fos-

like immunoreactivity after laryngeal-induced coughing and

its reduction by codeine. J-Neurosci. 1997 Dec 1; 17(23):

9340-52; ISSN: 0270-6474.

UNITED-STATES. We used the expression of the immediate-

early gene c-fos, a marker of neuronal activation, to localize

brainstem neuronal populations functionally related to fictive

cough (FC). In decerebrate, paralyzed, and ventilated cats, the

level of Fos-like immunoreactivity (FLI) was examined in five

groups of animals: (1) controls, sham-operated unstimulated

animals; (2) coughing cats, including both animals in which FC

was elicited by unilateral electrical stimulation of the

superior laryngeal nerve (SLN) and (3) those in which FC was

elicited by bilateral SLN stimulation; (4) stimulated-treated

cats, in which bilateral SLN stimulation was applied after

selective blockade of FC by codeine; and (5) codeine controls,

sham-operated unstimulated cats subjected to administration

of codeine. Fifteen brainstem structures were compared for

numbers of labeled cells. Because codeine selectively blocks

FC, brainstem nuclei activated specifically during FC were

identified as regions showing increased FLI after FC and

significant reductions in FLI after FC suppression by codeine

in stimulated-treated cats. In coughing animals, we observed a

selective immunoreactivity in the interstitial and

ventrolateral subdivisions of the nucleus of the tractus

solitarius, the medial part of the lateral tegmental field, the

internal division of the lateral reticular nucleus, the nucleus

retroambiguus, the para-ambigual region, the retrofacial

nucleus, and the medial parabrachial nucleus. FLI in all these

nuclei was significantly reduced in stimulated-treated cats.

Our results are consistent with the involvement of neurons

overlapping the main brainstem respiratory-related regions as

well as the lateral tegmental field and the lateral reticular

nucleus in the neural processing of laryngeal-induced FC.. 0; 0;

0; 76-57-3.

95. Ghezzi, A.; Filippi, M.; Falini, A.; Zaffaroni, M. Cerebral

involvement in celiac disease: a serial MRI study in a patient

with brainstem and cerebellar symptoms. Neurology. 1997 Nov;

49(5): 1447-50; ISSN: 0028-3878.

UNITED-STATES. A patient with celiac disease and relapsing-

progressive symptoms suggesting brainstem and cerebellar

involvement underwent serial MRIs. The first examination

revealed multiple enhancing and nonenhancing lesions.

Thereafter, a large enhancing cerebellar lesion appeared,

followed by severe cerebellar atrophy. The presence of

structural neuronal damage was confirmed by proton MR

spectroscopy and magnetization transfer imaging. MRI results

and CSF findings suggested that neurologic complications were

more likely due to an inflammatory process.

96. Giugni, E.; Pozzilli, C.; Bastianello, S.; Gasperini, C.; Paolillo, A.;

Koudriavtseva, T.; Frontoni, M.; Farina, D.; Bozzao, L. MRI

measures and their relations with clinical disability in

relapsing-remitting and secondary progressive multiple

sclerosis. Mult-Scler. 1997 Aug; 3(4): 221-5; ISSN: 1352-

4585.

ENGLAND. To further evaluate the relationship between

clinical disability and Magnetic Resonance Imaging (MRI)

lesion burden, we examined 85 patients with clinically

definite multiple sclerosis (54 relapsing-remitting and 31

secondary progressive). This cross-sectional study reports on

the correlations between total and infratentorial lesion

volume on both T1 and T2 weighted images, and overall

physical disability measured by Expanded Disability Status

Scale, ambulation index and individual functional systems.

Assessment of the hypointense lesion load on T1 weighted

images rather than the hyperintense lesion load on T2

weighted images at brain MRI was shown to be useful for

differentiating relapsing-remitting from secondary

progressive Multiple Sclerosis. A weak relationship between

disability and total lesion volume on both T1 and T2 weighted

images was found in relapsing-remitting Multiple Sclerosis. In

secondary progressive Multiple Sclerosis, infratentorial lesion

volume on T2 weighted images represents the only marker of

disability. Finally, the presence of cerebellar, brainstem and

mental impairment was significantly associated to a greater

total lesion volume on MRI, while no relationship was found

with other functional systems.

97. Gnadt, J. W.; Lu, S. M.; Breznen, B.; Basso, M. A.; Henriquez, V. M.;

Evinger, C. Influence of the superior colliculus on the primate

blink reflex. Exp-Brain-Res. 1997 Oct; 116(3): 389-98; ISSN:

0014-4819.

GERMANY. In this study we used microstimulation to

investigate the influence of the superior colliculus on the

trigeminal blink reflex. We report that stimulation in the

intermediate to deep layers of the tectum produced inhibition

of reflex blinks at a latency of approximately 26 ms. We

considered the hypothesis that the blink inhibition was

mediated via the omnipause neurons (OPNs) of the eye

movement control system in the brainstem. Our results show

that the least effective sites for suppression were in the

rostral colliculus. This is inconsistent with the prediction

that OPNs should be maximally recruited from the rostral

tectum near the "fixation zone." From these points and other

considerations, we conclude that the reflex blink suppression

from the superior colliculus is not directly mediated by the

OPNs or the saccadic eye movement circuits.

98. Gozal, D.; Torres, J. E. Maturation of anoxia-induced gasping in the

rat: potential role for N-methyl-D-aspartate glutamate

receptors. Pediatr-Res. 1997 Dec; 42(6): 872-7; ISSN: 0031-

3998.

UNITED-STATES. After anoxia-induced apnea, gasping remains

the last operative mechanism for survival. In developing rats,

the gasping response to anoxia exhibits triphasic

characteristics. Because anoxia is associated with enhanced

release of glutamate, we hypothesized that N-methyl-D-

aspartate (NMDA) glutamate receptors may underlie

components of the gasping response. Rat pups aged 2 d (n = 50),

5 d (n = 43), 10 d (n = 42), and 15 d (n = 45) underwent anoxic

challenges with 100% N2 in a whole body plethysmograph, 30

min after intraperitoneal administration of MK801 [(+)-5-

methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine

hydrogen maleate; dizocilpine] (3 mg/kg), a noncompetitive

NMDA glutamate receptor channel antagonist, or normal saline.

In control pups, after primary apnea onset, a triphasic gasping

pattern was apparent at all postnatal ages and included two

distinct types of gasps (I and II). In 2- and 5-d MK801-treated

animals, phase 1 and type I gasps were absent, leading to

marked prolongations of the gasp latency and phase 2, the

latter displaying type II gasps only. In addition, phase 3

duration was also prolonged with increased type II gasp

frequencies. In contrast, in some 10-d-old (40%) and in all 15-

d-old MK801-treated pups, although overall gasping duration

was prolonged, the triphasic gasping pattern seen in matched

controls was also present. We conclude that NMDA glutamate

receptors mediate particular phasic components of the gasping

response during early postnatal life but not at later stages of

development. We speculate that developmental changes occur

in both function and expression of NMDA and other

neurotransmitters within brainstem regions underlying the

neural substrate for gasp generation.. 0; 0; 77086-22-7.

99. Grundemar, L.; Ny, L. Several neuropeptide Y receptors modulate

cyclic AMP production in the rat brainstem. Proc-West-

Pharmacol-Soc. 1997; 40: 21-3; ISSN: 0083-8969.

UNITED-STATES. 0; 0; 60-92-4.

100. Guest, J. D.; Rao, A.; Olson, L.; Bunge, M. B.; Bunge, R. P. The ability

of human Schwann cell grafts to promote regeneration in the

transected nude rat spinal cord. Exp-Neurol. 1997 Dec; 148(2):

502-22; ISSN: 0014-4886.

UNITED-STATES. Advances in the purification and expansion of

Schwann cells (SCs) from adult human peripheral nerve,

together with biomaterials development, have made the

construction of unique grafts with defined properties possible.

We have utilized PAN/PVC guidance channels to form solid

human SC grafts which can be transplanted either with or

without the channel. We studied the ability of grafts placed

with and without channels to support regeneration and to

influence functional recovery; characteristics of the graft and

host/graft interface were also compared. The T9-T10 spinal

cord of nude rats was resected and a graft was placed across

the gap; methylprednisolone was delivered acutely to decrease

secondary injury. Channels minimized the immigration of

connective tissue into grafts but contributed to some necrotic

tissue loss, especially in the distal spinal cord. Grafts without

channels contained more myelinated axons (x = 2129 +/- 785)

vs (x = 1442 +/- 514) and were larger in cross-sectional area

( x = 1.53 +/- 0.24 mm2) vs (x = 0.95 +/- 0.86 mm2). The

interfaces formed between the host spinal cord and the grafts

placed without channels were highly interdigitated and

resembled CNS-PNS transition zones; chondroitin sulfate

proteoglycans was deposited there. Whereas several neuronal

populations including propriospinal, sensory, motoneuronal,

and brainstem neurons regenerated into human SC grafts, only

propriospinal and sensory neurons were observed to reenter

the host spinal cord. Using combinations of anterograde and

retrograde tracers, we observed regeneration of propriospinal

neurons up to 2.6 mm beyond grafts. We estimate that 1% of

the fibers that enter grafts reenter the host spinal cord by 45

days after grafting. Following retrograde tracing from the

distal spinal cord, more labeled neurons were unexpectedly

found in the region of the dextran amine anterograde tracer

injection site where a marked inflammatory reaction had

occurred. Animals with bridging grafts obtained modestly

higher scores during open field [(x = 8.2 +/- 0.35) vs (x = 6.8

+/- 0.42), P = 0.02] and inclined plane testing (x = 38.6 +/- 0.

542) vs (x = 36.3 +/- 0.53), P = 0.006] than animals with

similar grafts in distally capped channels. In summary, this

study showed that in the nude rat given methylprednisolone in

combination with human SC grafts, some regenerative growth

occurred beyond the graft and a modest improvement in

function was observed. Copyright 1997 Academic Press.

101. Guilleminault, C.; Heinzer, R.; Mignot, E.; Black, J. Investigations

into the neurologic basis of narcolepsy. Neurology. 1998 Feb;

50(2 Suppl 1): S8-15; ISSN: 0028-3878.

UNITED-STATES. The understanding of narcolepsy has been

enhanced by neurophysiologic investigations in humans and by

pharmacologic and biochemical studies using the canine model

of narcolepsy. Repetitive microsleeps have a more deleterious

effect on performance than several short complete naps during

the day. Under normal living conditions, the nocturnal sleep of

narcoleptic patients is disrupted, and the spectral analysis of

central EEG leads shows less delta power density per epoch

than it does in age-matched controls, who have an absence or

decrease of the usual decay in delta power across the night.

Cataplexy is associated with a drop in H-reflex, even during

partial cataplectic attacks. Monitoring of heart rate and intra-

arterial blood pressure during cataplexy in humans shows a

decrease in heart rate and an increase in blood pressure with

onset of cataplexy, but the change in heart rate is secondary to

the change in blood pressure. Investigations of narcoleptic

Doberman pinschers have implicated several

neurotransmitters in the brainstem and amygdala. In vivo

dialysis and in situ injections of carbachol indicate that the

pontine reticular formation is not the only muscarinic

cholinergic region involved, but data support the existence of a

multisynaptic descending pathway involved in the muscle

atonia of cataplexy. Carbachol injections into the basal

forebrain induce status cataplecticus. Experimental findings

suggest a hypersensitivity of the overall muscarinic

cholinergic system and that this hypersensitive cholinergic

system is linked to the limbic system. An increase in the

postsynaptic D2 dopaminergic receptor is observed in the

amygdala of narcoleptic dogs compared with controls, with

impairment of dopamine release. The associated findings

suggest that an abnormal cholinergic-dopaminergic interaction

could underlie the pathophysiology of narcolepsy.

102. Guo, Y.; Yao, D. [The application of otoacoustic emissions in

paediatric hearing screening]. Chung-Kuo-I-Hsueh-Ko-Hsueh-

Yuan-Hsueh-Pao. 1996 Aug; 18(4): 284-7; ISSN: 1000-503X.

CHINA. We conducted auditory test of 132 high risk infants by

using both otoacoustic emissions (OAE) and auditory brainstem

response (ABR) screening. The result showed that the passing

rate was 88.3% (233/264 ears) for OAE and 92% (243/264

ears) for ABR. The sensitivity and specificity of OAE in

comparison to ABR were 90.5% (19/21 ears) and 95% (230/243

ears) respectively. The mean test time was 3 min for OAE and

30 min for ABR. We therefore conclude that OAE is a highly

sensitive, reliable and convenient method to be used for

paediatric hearing screening.

103. Gustafsson, B.; Oland, L.; Davison, J. S. Relationship between

nitric oxide synthase activity, vasopressin and oxytocin in the

brainstem and hypothalamus of the ferret. Proc-West-

Pharmacol-Soc. 1997; 40: 103-4; ISSN: 0083-8969.

UNITED-STATES. EC 1.14.13.39; 0; 50-56-6.

104. Habler, H. J.; Boczek Funcke, A.; Michaelis, M.; Janig, W. Responses

of distinct types of sympathetic neuron to stimulation of the

superior laryngeal nerve in the cat. J-Auton-Nerv-Syst. 1997

Sep 10; 66(1-2): 97-104; ISSN: 0165-1838.

NETHERLANDS. Stimulation of afferents in the superior

laryngeal nerve (SLN) leads to apnea and evokes reflexes in

sympathetic neurons. It is not clear whether these reflexes

are secondary to changes in the brainstem respiratory network

or due directly to the afferent input on neurons belonging to

central sympathetic pathways. To clarify this question, single

thoracic preganglionic sympathetic neurons projecting into the

cervical sympathetic trunk (CST) were classified as described

previously and then tested for their responses to electrical

stimulation of the superior laryngeal nerve (SLN) in

chloralose-anesthetized, paralysed and artificially ventilated

cats. SLN stimulation was performed with intensities

sufficient to suppress central inspiratory activity detected by

phrenic and recurrent laryngeal nerve recordings. Sympathetic

neurons were tested under different levels of respiratory

drive. Thirteen group I (putative muscle vasoconstrictor)

neurons were mostly activated by SLN stimulation when

respiratory drive was low, but depressed when it was high;

this was due to the change in inspiration-related activity. Ten

of eleven group II (putative cutaneous vasoconstrictor)

neurons were depressed during SLN stimulation. This inhibition

was independent of central respiratory drive. Inhibition also

occurred in those neurons which predominantly discharged

during postinspiration. Eight group III neurons which showed a

discharge confined to inspiration were inhibited but mostly

not silenced by SLN stimulation. Group IV (functionally

unclassified) neurons either showed no response (n = 5) or

were slightly inhibited (n = 2). The responses of group I

neurons, but not the responses of group II and group III

neurons, showed a significant positive correlation with those

of systemic blood pressure. The observed responses

corroborate the classification made previously. The results

also demonstrate that the responses of sympathetic neurons to

SLN stimulation are not merely due to the respiratory

modulation of their activity, but rather consist of two

components, one occurring independently of and the other

secondary to, the changes in respiration.

105. Hamlyn, P. J. Neurovascular relationships in the posterior cranial

fossa, with special reference to trigeminal neuralgia. 2.

Neurovascular compression of the trigeminal nerve in

cadaveric controls and patients with trigeminal neuralgia:

quantification and influence of method. Clin-Anat. 1997; 10(6):

380-8; ISSN: 0897-3806.

UNITED-STATES. The theory of neurovascular compression has

been tested by comparing the neurovascular relationships of

the trigeminal nerve in a series of operative observations in

patients affected by trigeminal neuralgia with those of a

control series of cadavers matched for age, sex and side, in

which operative conditions were simulated during

simultaneous arterial and venous injection--filling to

physiological pressures, as described in Part 1 of this article.

A rigorous system of classification of neurovascular relations

is defined. In 46 patients with trigeminal neuralgia, 91% had a

vessel in contact with the trigeminal nerve adjacent to the

brain stem and in all but one a groove was created. Multiple

vessels were found in 17% and in two both the root entry zone

and lateral portions of the nerve were compressed. However, in

35 randomly selected fresh cadavers, not known to have

suffered neurological disease, 14% had neurovascular contact

and a further 26% had vessels "near" to the nerve. No vessel

was associated with a groove and no multiple vessels, or sites

of contact, were encountered. The difference between the

control cadavers and the operative findings in patients related

to an increase in the number of arteries. Injection-filling of

the cadaveric vessels doubled the numbers of vessels in

contact with, and near to the nerve. The technique used and

system of classification applied showed an association

between arterial contact and trigeminal neuralgia. The

technique may provide a suitable method for the testing of the

neurovascular compression theory in other conditions.

106. Hansen, L. A. The Lewy body variant of Alzheimer disease. J-

Neural-Transm-Suppl. 1997; 51: 83-93; ISSN: 0303-6995.

AUSTRIA. The Lewy body variant of Alzheimer disease (LBV)

occupies a messy middle ground between Alzheimer disease

(AD) on the one hand, and pure Lewy body diseases (Parkinson's

disease or diffuse Lewy body disease), on the other. In addition

to brainstem and neocortical Lewy bodies, LBV brains have

enough neocortical neuritic plaques to meet diagnostic

criteria for AD. However, neurofibrillary pathology in LBV is

modest, since tangle densities in LBV are typically

intermediate between AD and age-matched controls or pure

Lewy body disease brains. Apolipoprotein E-4 is

overrepresented in LBV, as it is in AD but is not in PD or

diffuse Lewy body disease (DLBD). Neurologically, LBV patients

often display sufficient parkinsonian signs to separate them

from AD, but these findings are usually too subtle to warrant

clinical diagnoses of Parkinson's disease (PD).

Neuropsychological deficits in LBV include a subcortical

dementia pattern similar to DLBD, and more severe global

cognitive impairment reminiscent of AD.. 0; 0.

107. Hartmann, R.; Shepherd, R. K.; Heid, S.; Klinke, R. Response of the

primary auditory cortex to electrical stimulation of the

auditory nerve in the congenitally deaf white cat. Hear-Res.

1997 Oct; 112(1-2): 115-33; ISSN: 0378-5955.

NETHERLANDS. Neural activity plays an important role in the

development and maintenance of sensory pathways. However,

while there is considerable experience using cochlear implants

in both congenitally deaf adults and children, little is known

of the effects of a hearing loss on the development of the

auditory cortex. In the present study, cortical evoked

potentials, field potentials, and multi- and single-unit

activity evoked by electrical stimulation of the auditory nerve

were used to study the functional organisation of the auditory

cortex in the adult congenitally deaf white cat. The absence of

click-evoked auditory brainstem responses during the first

weeks of life demonstrated that these animals had no auditory

experience. Under barbiturate anaesthesia, cortical potentials

could be recorded from the contralateral auditory cortex in

response to bipolar electrical stimulation of the cochlea in

spite of total auditory deprivation. Threshold, morphology and

latency of the evoked potentials varied with the location of

the recording electrode, with response latency varying from

10 to 20 ms. There was evidence of threshold shifts with site

of the cochlear stimulation in accordance with the known

cochleotopic organisation of AI. Thresholds also varied with

the configuration of the stimulating electrodes in accordance

with changes previously observed in normal hearing animals.

Single-unit recordings exhibited properties similar to the

evoked potentials. Increasing stimulus intensity resulted in an

increase in spike rate and a decrease in latency to a minimum

of approximately 8 ms, consistent with latencies recorded in

AI of previously normal animals (Raggio and Schreiner, 1994).

Single-unit thresholds also varied with the configuration of

the stimulating electrodes. Strongly driven responses were

followed by a suppression of spontaneous activity. Even at

saturation intensities the degree of synchronisation was less

than observed when recording from auditory brainstem nuclei.

Taken together, in these auditory deprived animals basic

response properties of the auditory cortex of the congenitally

deaf white cat appear similar to those reported in normal

hearing animals in response to electrical stimulation of the

auditory nerve. In addition, it seems that the auditory cortex

retains at least some rudimentary level of cochleotopic

organisation.

108. Hashimoto, M.; Ohtsuka, K. Bilateral internal ophthalmoplegia as a

feature of oculomotor fascicular syndrome disclosed by

magnetic resonance imaging. Am-J-Ophthalmol. 1998 Jan;

125(1): 121-3; ISSN: 0002-9394.

UNITED-STATES. PURPOSE: To describe the magnetic resonance

imaging features of bilateral internal ophthalmoplegia as an

oculomotor fascicular syndrome. METHODS: A 55-year-old man

was initially examined with bilateral photophobia. Neuro-

ophthalmologic examinations disclosed preganglionic bilateral

internal ophthalmoplegia. Magnetic resonance imaging of the

brainstem was performed. RESULT: Magnetic resonance imaging

disclosed high-intensity areas on T2-weighted images along

medial portions of the bilateral oculomotor fascicles in the

mesencephalon. CONCLUSION: These findings suggest that

mesencephalic lesions may selectively cause bilateral internal

ophthalmoplegia as a partial oculomotor fascicular syndrome.

109. Haslett, R. S.; Batterbury, M.; Cuypers, M.; Cooper, R. L. Inter-

observer agreement in clinical optic disc measurement using a

modified 60 D lens. Eye. 1997; 11( Pt 5): 692-7; ISSN: 0950-

222X.

ENGLAND. PURPOSE: To assess the inter-observer agreement of

the measurement of optic disc dimensions by two observers

using a modified 60 dioptre (D) fundus examination lens.

METHOD: The vertical disc and cup diameters of 29 eyes were

measured by two independent observers using a 60 D lens

modified by incorporation of a 0.1 millimetre scale graticule.

The vertical cup/disc ratio was calculated. Inter-observer

agreement was assessed by calculation of the inter-observer

differences and by the weighted kappa statistic. RESULTS: The

two observers showed good agreement for the measurement of

disc diameter (mean difference -0.04; range -0.04, 0.2) and for

cup diameter (mean difference -0.03; range 0.3, 0.2). Closer

agreement for the vertical cup/disc ratio was achieved (mean

kappa 0.96; 95% confidence limits 0.90, 1.0). The 95%

confidence limit for the mean inter-observer difference in

cup/disc ratio was 0.11, suggesting that a change of > 0.1 in

the assessment of the cup/disc ratio by this technique is

significant at the 5% level. CONCLUSION: High inter-observer

agreement of optic disc measurement can be achieved with

this technique. The method has the potential to improve the

clinical evaluation of the optic disc and the precision and

accuracy of the clinical measurement of other fundal

structures.

110. Hata, R.; Matsumoto, M.; Matsuyama, T.; Yamamoto, K.; Hatakeyama,

T.; Kubo, T.; Mikoshiba, K.; Sakaki, S.; Sugita, M.; Yanagihara, T.

Brainstem auditory evoked potentials during brainstem

ischemia and reperfusion in gerbils. Neuroscience. 1998 Mar;

83(1): 201-13; ISSN: 0306-4522.

UNITED-STATES. To evaluate the reversibility of neural

function in the brainstem following ischemia, we investigated

the effect of transient brainstem ischemia on the brainstem

auditory evoked potential in gerbils. Brainstem ischemia was

produced by bilateral extracranial occlusion of vertebral

arteries. Local cerebral blood flow was measured by

quantitative autoradiography after 5 min of ischemia and was

reduced to less than 3 ml/100 g per min in the pons and lower

midbrain, indicating severe and reproducible brainstem

ischemia. During brainstem ischemia, brainstem auditory

evoked potential waveforms disappeared completely. After a

brief ischemic insult (5 min), all four brainstem auditory

evoked potential components recovered to normal. After longer

ischemic insults (10-30 min), brainstem auditory evoked

potential components never recovered to normal. Microtubule-

associated protein 2 immunoreactivity revealed differential

vulnerability of the acoustic relay nuclei in the brainstem.

Neurons in the lateral lemniscus were most vulnerable,

followed in order by neurons in the trapezoid body, the

superior olive and the cochlear nucleus. We also demonstrated

a close relationship between the reversibility of ischemia-

induced changes on brainstem auditory evoked potential and

ischemic lesions of these relay nuclei. These data may be

useful for evaluating the therapeutic window of thrombolytic

therapy during acute vertebrobasilar occlusion.. 0.

111. Hayashi, M.; Maruki, K.; Maruki, K. [A case of multiple pterygium

syndrome (Escobar) with horseshoe kidney]. No-To-Hattatsu.

1998 Jan; 30(1): 61-4; ISSN: 0029-0831.

JAPAN. We report a 25-year-old male with multiple pterygium

syndrome (Escobar) complicated with a horseshoe kidney. He

had clinical characteristics of Escobar syndrome, including

palpebral ptosis, auricular anomalies, pterygia with

contracture of the elbow and knee joints, syndactyly and

polydactyly of the feet, and growth failure. Renal scintigraphy

and abdominal MRI and CT demonstrated a horseshoe kidney,

which was thought to be an incidental association. He had no

auditory brainstem response, but he could respond to sounds of

low-frequency and the voices of familiar persons. Neither

brain MRI and CT nor SPECT demonstrated any abnormalities.

Further neurophysiological and neuroradiological studies are

necessary to elucidate neurological deficits in this syndrome.

112. He, L.; Sarrafizadeh, R.; Houk, J. C. Three-dimensional

reconstruction of the rubrocerebellar premotor network of the

turtle. Neuroimage. 1995 Mar; 2(1): 21-33; ISSN: 1053-8119.

UNITED-STATES. Neuroanatomical studies have demonstrated

that the organization of the reptilian rubrocerebellar limb

premotor network is similar to that of mammals. This network

is composed of prominent recurrent connections among the red

nucleus, lateral cerebellar nucleus and lateral reticular

nucleus. In this paper the rubrocerebellar system of the turtle

was three-dimensionally reconstructed to permit detailed

examination of its anatomical organization. Each nucleus and

its major efferent pathway was imaged and reconstructed

from separate anatomical cases. Section images were used to

draw tissue boundaries, mark cell positions and locate axonal

trajectories. For each nucleus, drawings of section images

containing labeled cells were stacked in the rostrocaudal

direction using anatomical landmarks, and a graphic model of

the surface was constructed using the method of triangulation.

An ellipsoid of equal concentration was computed for each

nucleus to ascertain their three-dimensional boundaries and

location within the brainstem. To examine the entire

rubrocerebellar network, a template of the turtle brainstem

and cerebellum was constructed. The component nuclei of the

rubrocerebellar network and their axonal projections were

then spatially warped onto the template reconstruction on a

section by section basis. The final three-dimensional

reconstruction of the turtle rubrocerebellar limb premotor

network could be rotated in space, allowing proper

visualization of the anatomical details of this system.

Furthermore, we were able to mathematically section through

the reconstruction to obtain brainstem slices with differing

orientations and thickness.

113. Heid, S.; Jahn Siebert, T. K.; Klinke, R.; Hartmann, R.; Langner, G.

Afferent projection patterns in the auditory brainstem in

normal and congenitally deaf white cats. Hear-Res. 1997 Aug;

110(1-2): 191-9; ISSN: 0378-5955.

NETHERLANDS. Cochlear implantation in congenitally deaf

children is developing to a successful medical tool. Little is

known, however, on morphology and pathophysiology of the

central auditory system in these auditory deprived children.

One form of congenital hearing loss, that seen in the deaf

white cat, was investigated to see if there are differences in

the afferent pathways from the cochlear nuclei to the inferior

colliculus. The retrogradely transported fluorescent tracer

diamidino yellow (DY) was injected into different parts of the

central nucleus of the inferior colliculus (ICC) of normal cats

and deaf white cats. It was found that the main afferent

projection patterns in deaf white cats were unchanged in spite

of congenital auditory deprivation; minor differences were

seen.. 0; 0; 88746-72-9.

114. Heils, A.; Wichems, C.; Mossner, R.; Petri, S.; Glatz, K.; Bengel, D.;

Murphy, D. L.; Lesch, K. P. Functional characterization of the

murine serotonin transporter gene promoter in serotonergic

raphe neurons. J-Neurochem. 1998 Mar; 70(3): 932-9; ISSN:

0022-3042.

UNITED-STATES. We have isolated and characterized the 5'-

flanking regulatory region of the murine serotonin 5-HT

transporter (5-HTT) gene. A TATA-like motif and several

potential binding sites for transcription factors, including two

AP1, several AP2 and AP4 binding sites, CCAAT and GC boxes

(SP1 binding sites), a nuclear factor-kappaB, and a cyclic AMP

response element-like motif, are present in the 5'-flanking

region. A approximately 2.2-kb fragment (-2,143 to +51 with

respect to the transcription start site), which had been fused

to the luciferase reporter gene and transiently expressed in a

5-HTT-expressing cell line and in serotonergic raphe neurons

derived from embryonic rat brainstem, displayed both

constitutive and inducible promoter activity. Functional

promoter mapping revealed two clusters of activating

elements from bp -82 to -527 and bp -1,001 to -1,937. A

cell/neuron-selective silencer element(s) is contained

between bp -294 and -527. Our findings suggest that (1) the

murine 5-HTT gene promoter is active in serotonergic raphe

neurons but significantly repressed in neuronal cells from

frontal cortex that do not express 5-HTT, (2) the information

contained within approximately 0.5 kb of the 5'-flanking

sequence is sufficient to confer its cell-selective expression,

(3) the promoter responds to cyclic AMP- and protein kinase C-

dependent induction, and (4) the expression of the 5-HTT is

regulated by a combination of positive and negative cis-acting

elements operating through a basal promoter unit defined by a

TATA-like motif. Fusion of the 5-HTT gene promoter unit to a

gene of choice may aid its cell-selective expression in

transgenic strategies.. EC 2.7.1.-; EC 4.2.1.11; 0; 0; 0; 0; 0;

16561-29-8; 50-67-9; 60-92-4; 66428-89-5.

115. Helbling, D.; Boutellier, U.; Spengler, C. M. Modulation of the

ventilatory increase at the onset of exercise in humans.

Respir-Physiol. 1997 Sep; 109(3): 219-29; ISSN: 0034-5687.

NETHERLANDS. The fast initial increase in ventilation at the

start of exercise is generally assumed to be of reflex origin

(exercising limbs) and/or caused by a 'feedforward' mechanism

increasing breathing via brainstem respiratory centres or

cortical areas controlling respiratory muscles. We wanted to

test whether this ventilatory increase is in part a learned

response which can be modified. Eleven subjects did two 20

min low-intensity arm-cranking exercise bouts on eight

different days. Seven subjects were assigned to the

experimental group which performed exercise paired with an

1.5 L external dead space. Before and after their eight exercise

'training'-days, these subjects did the same exercise without

dead space. At the beginning of the first post-training

exercise test (without dead space), the ventilatory increase at

the start of exercise (sum of the first four breaths) was

significantly increased (31.1 +/- 4.1 L . min-1) compared to

the pre-training test session (24.4 +/- 3.9 L . min-1). No

significant change was observed in the control group. We

conclude that part of the ventilatory increase at the start of

exercise can be modulated and might possibly be a learned

response.. 124-38-9; 7782-44-7.

116. Herbison, A. E. Noradrenergic regulation of cyclic GnRH secretion.

Rev-Reprod. 1997 Jan; 2(1): 1-6; ISSN: 1359-6004.

ENGLAND. The GnRH cells represent the final output neurones

of an integrated neuronal network used by the brain to

generate pulsatile LH secretion from the pituitary gland.

Changes in LH secretion profile throughout the ovarian cycle,

including the preovulatory LH surge, result principally from

alterations in the output of this GnRH network and it has been

a key goal of many neurobiologists to elucidate the

components and nature of this network. This review documents

recent progress in understanding the role of noradrenaline

within the GnRH network and highlights and explains its

'enabling' or permissive characteristics. Network behaviour

analysis suggests that noradrenaline should be considered as a

permissive agent promoting high output states of the GnRH

network. On the basis of recent molecular and neuroanatomical

data, it is proposed that oestrogen influences brainstem

noradrenergic neurones specifically within the nucleus tractus

solitarius to facilitate synaptic transmission within the GnRH

network. In this manner, noradrenaline is likely to play a role

in bringing about the increased GnRH messenger RNA

expression and secretion necessary for ovulation.. 0; 33515-

09-2; 51-41-2; 9002-67-9.

117. Hermanson, O.; Blomqvist, A. Differential expression of the AP-

1/CRE-binding proteins FOS and CREB in preproenkephalin

mRNA-expressing neurons of the rat parabrachial nucleus after

nociceptive stimulation. Brain-Res-Mol-Brain-Res. 1997 Nov;

51(1-2): 188-96; ISSN: 0169-328X.

NETHERLANDS. Several subgroups in the brainstem

parabrachial nucleus (PB), which is a major target for

nociresponsive neurons in the medullary and spinal dorsal

horn, contain large numbers of preproenkephalin (ppENK)

mRNA-expressing neurons. To elucidate how noxious stimuli

may regulate ppENK transcription in these neurons, we have in

the present study investigated whether immunoreactivity for

the transcription factors FOS and phosphorylated CREB

(pCREB), respectively, is displayed in the ppENK mRNA-

expressing neurons after peripheral nociceptive stimulation.

Rats received injection of formalin into one hindpaw, and were

killed 30-80 min later. With a combination of

immunohistochemistry and in situ hybridization, we found that

only a small number of ppENK mRNA-expressing neurons in PB

displayed FOS-immunoreactivity after nociceptive

stimulation. In contrast, large numbers of ppENK mRNA-

expressing neurons displayed pCREB-like immunoreactivity

after nociceptive stimulation. Most of the ppENK mRNA/pCREB-

expressing neurons were found in the Kolliker-Fuse and

internal lateral subnuclei, but many double-labeled cells were

also seen in the ventral lateral and central lateral subnuclei.

In addition, a cluster of ppENK mRNA/pCREB-expressing

neurons was found in the medial part of the medial

parabrachial nucleus. Our findings suggest that CREB rather

than FOS regulates nociceptive-related second messenger

activation of ppENK transcription in parabrachial neurons.. 0;

0; 0; 0; 0; 0; 50-00-0; 93443-35-7.

118. Hidaka, T. [Scanning and transmission electron microscopic

observations of the inner ear of hamsters with

hyperlipidemia]. Nippon-Jibiinkoka-Gakkai-Kaiho. 1997 Sep;

100(9): 900-8; ISSN: 0030-6622.

JAPAN. The relationship between hyperlipoproteinemia and

sensorineural hearing loss has been studied by means of guinea

pig models with hypercholesterolemia. However, these

observations of the inner ear using guinea pig models have

been limited to a short time. By using a golden hamster model

with hypercholes terolemia, I was able to observe the inner

ear for a long time. Two-month-old hamsters were fed a

hyperlipid diet consisting of standard chow supplemented with

3% cholesterol and 15% cattle fat for 30, 60, 90, 120, and over

150 days. Six-month-old hamsters were fed the hyperlipid diet

for 30 days. Then the animals were examined for auditory

dysfunction and morphological changes in the cochlea.

Biochemical findings in the serum showed

hyperlipoproteinemia, especially hypercholesterolemia.

Regarding auditory dysfunction, the threshold change in the

auditory brainstem response (ABR) was mild. Scanning and

transmission electron microscopic revealed many protrusions

toward the endolymphatic space on the surface of the marginal

cells of the stria vascularis. Vascular degeneration of the

marginal cells and intermediate cells of the stria vascularis

was also observed. In addition, protrusions containing a

lysozome structure consisting of outer piller cells were

observed on the organ of Corti. These results with

experimental hamsters fed a hyperlipid diet indicate that such

a diet may induce functional changes in the cochlea such as

auditory dysfunction with the occurrence in

hypercholesterolemia.

119. Higashida, R. T.; Smith, W.; Gress, D.; Urwin, R.; Dowd, C. F.;

Balousek, P. A.; Halbach, V. V. Intravascular stent and

endovascular coil placement for a ruptured fusiform aneurysm

of the basilar artery. Case report and review of the literature.

J-Neurosurg. 1997 Dec; 87(6): 944-9; ISSN: 0022-3085.

UNITED-STATES. The authors demonstrate the technical

feasibility of using intravascular stents in conjunction with

electrolytically detachable coils (Guglielmi detachable coils

[GDCs]) for treatment of fusiform, broad-based, acutely

ruptured intracranial aneurysms and review the literature on

endovascular approaches to ruptured aneurysms and cerebral

stent placement. A 77-year-old man presented with an acute

subarachnoid hemorrhage of the posterior fossa. A fusiform

aneurysm with a broad-based neck measuring 12 mm and

involving the distal vertebral artery (VA) and proximal third of

the basilar artery (BA) was demonstrated on cerebral

angiography. The aneurysm was judged to be inoperable. Six

days later a repeated hemorrhage occurred. A 15-mm-long

intravascular stent was placed across the base of the

aneurysm in the BA and expanded to 4 mm to act as a bridging

scaffold to create a neck. A microcatheter was then guided

through the interstices of the stent into the body and dome of

the aneurysm, and GDCs were deposited for occlusion. The

arteriogram obtained after stent placement demonstrated

occlusion of the main dome and body of the aneurysm. The coils

were stably positioned and held in place by the stent across

the distal VA and BA fusiform aneurysm. Excellent blood flow

to the distal BA and posterior cerebral artery was maintained

through the stent. There were no new brainstem ischemic

events attributable to the procedure. No rebleeding from the

aneurysm had occurred by the 10.5-month follow-up

evaluation, and the patient has experienced significant

neurological improvement. Certain types of intracranial

fusiform aneurysms may now be treated by combining

intravascular stent and GDC placement for aneurysm occlusion

via an endovascular approach. This is the first known clinical

application of this novel approach in a ruptured cerebral

aneurysm.

120. Hoebel, B. G. Neuroscience and appetitive behavior research: 25

years. Appetite. 1997 Oct; 29(2): 119-33; ISSN: 0195-6663.

ENGLAND. Neuroscience techniques have made major

contributions to the understanding of appetitive behavior.

Highlights in six areas are summarized to illustrate progress

during the 25 years of the Columbia Appetitive Behavior

Seminar: (1) discovery of angiotensin and aldosterone in the

control of thirst and salt appetite; (2) electrophysiological

decoding of chemoreceptive information in the brain; (3) a new

foundation in the hypothalamus built on peptides, such as

neuropeptide Y and galanin, interacting with monoamines and

steroids in the control of appetite for macronutrients; (4)

discovery of numerous peptides that mediate and integrate

satiety, such as cholecystokinin, insulin, leptin and

enterostatin, and other systems that suppress eating during

illness; (5) better understanding of appetite suppressant

drugs, and (6) exploration of a circuit that translates

hypothalamic signals into behavioral action through

connections to brainstem reflex arcs and forebrain

instrumental response systems.Copyright 1997 Academic

Press Limited.. 0.

121. Hommet, C. D.; De Toffol, B.; Cottier, J. P.; Autret, A. Bilateral

olivary hypertrophy and palatal myoclonus. Surg-Neurol. 1998

Feb; 49(2): 215-6; ISSN: 0090-3019.

UNITED-STATES. We report on a case of palatal myoclonus

associated with olivary hypertrophy on magnetic resonance

imaging (MRI) in a 63-year-old man. This rare radiological

finding must be differentiated from a brainstem tumor.

122. Hone, S. W.; Commins, D. J.; Rames, P.; Chen, J. M.; Rowed, D.;

McLean, A.; Nedzelski, J. M. Prognostic factors in

intraoperative facial nerve monitoring for acoustic neuroma.

J-Otolaryngol. 1997 Dec; 26(6): 374-8; ISSN: 0381-6605.

CANADA. OBJECTIVES: To determine the predictive value of

intraoperative threshold stimulus for facial nerve outcome and

the prevalence and prognostic value of persistent trains of

activity and frequent spontaneous or mechanically induced

contractions during acoustic neuroma surgery. STUDY DESIGN:

Prospective recording and subsequent review of facial nerve

activity. SETTING: Tertiary referral centre. PATIENTS AND

METHODS: Consecutive patients undergoing acoustic neuroma

surgery. Intraoperative facial nerve activity was digitised and

stored on a personal computer for future analysis. Operative

events were flagged. Recordings were available in 27 patients.

MAIN OUTCOME MEASURES: Frequent mechanically induced

contractions (< 20), prolonged trains of facial nerve activity

(total time > 199 seconds), and facial nerve brainstem

stimulus threshold were correlated with facial nerve outcome.

RESULTS: A brainstem stimulus threshold > 0.1 mA was

significantly associated with intermediate or poor facial

nerve function (House-Brackmann grade > 2) on the sixth

postoperative day, at 1 month and 6 months. Patients with

normal or near-normal facial function on the first day and a

threshold of > 0.1 mA were significantly more likely to

develop a delayed facial nerve palsy. Frequent contractions

were noted in 74% of patients and persistent train activity in

59%. Neither was predictive of facial nerve outcome.

CONCLUSIONS: An elevated brainstem threshold is helpful in

predicting delayed facial nerve palsy and suboptimal facial

nerve outcome. Persistent train activity and frequent

contractions, do not have major prognostic significance.

123. Howland, R. H. Sleep-onset rapid eye movement periods in

neuropsychiatric disorders: implications for the

pathophysiology of psychosis. J-Nerv-Ment-Dis. 1997 Dec;

185(12): 730-8; ISSN: 0022-3018.

UNITED-STATES. This paper reviews the literature describing

the occurrence of sleep-onset rapid eye movement periods in

narcolepsy, schizophrenia, psychotic depression, and delirium

tremens; the association of narcolepsy with psychotic

disorders; the neuropathology of the brainstem in narcolepsy

and schizophrenia; and other behavioral disorders resulting

from probable brainstem pathology. These findings suggest

that some forms of psychosis are a manifestation of

pathophysiological changes in the brainstem. Some

implications of this hypothesis for the treatment of psychoses

are discussed. Future research should investigate psychoses

and the psychobiological correlates of such biological markers

as sleep-onset rapid eye movement periods across diagnostic

categories.. 0.

124. Hsu, H. L.; Hsiao, P. H.; Hou, J. W.; Tsai, W. Y.; Wang, T. R. Partial

DiGeorge anomaly associated with 10p deletion. J-Formos-

Med-Assoc. 1997 Dec; 96(12): 996-9; ISSN: 0929-6646.

TAIWAN. We report a girl with partial DiGeorge anomaly

associated with a distal chromosome 10p deletion. The initial

manifestation was hypocalcemia convulsion at the age of 14

days. The patient was small for her gestational age and

showed symptoms of poor feeding and inspiratory stridor.

Facial dysmorphisms included a cupped ear, hypertelorism

downslanted and short palpebral fissures frontal bossing,

anteverted nostrils, a flat nasal bridge, and micrognathia.

Developmental delay was also noted. Hypoplasia of the thymus

was detected by ultrasound examination, but results of

immunologic studies were all normal at 6 weeks of age. The

echocardiogram, brain ultrasound, electroencephalogram, and

magnetic resonance images of the brain were normal, but

brainstem auditory evoked potentials showed bilateral

sensorineural hearing loss. Chromosomal analysis showed 16,

XX, del(10)(p12.3); the parents had normal karyotypes. After

treatment with vitamin D, calcium gluconate, and magnesium

sulfate, the patient's serum calcium and magnesium levels

were within normal limits. She was discharged and received

regular follow-up at our clinic for physical therapy and to

ensure adequate supply of divalent cations. Complex partial

seizure was noted at the age of 1 year and was controlled with

carbamazepine. To our knowledge, this is the first Taiwanese

reported to have partial DiGeorge anomaly associated with 10p

deletion. We recommend that standard karyotyping should be

performed in children suspected to have this anomaly.

125. Huang, C. R.; Chang, W. N.; Lui, C. C.; Wu, H. S.; Liou, C. W.

Neuroimages of Japanese encephalitis: report of three

patients. Chung-Hua-I-Hsueh-Tsa-Chih-Taipei. 1997 Aug;

60(2): 105-8; ISSN: 0578-1337.

TAIWAN. The cranial computed tomography (CT) and magnetic

resonance image (MRI) studies of three Japanese encephalitis

(JE) patients, 24 to 37 years of age, are reported. The initial

findings of CT study were limited but initial MRI studies

revealed multiple lesions involving the brainstem, basal

ganglia and bilateral thalami. Follow-up MRI studies showed

small residual lesions only. The result shows that MRI can

delineate and detect brain lesions better than CT in patients in

the acute stage of JE. The locations of lesions in MRI study are

noteworthy and have a good correlation with pathologic

anatomic distribution. Therefore, MRI study is helpful in early

diagnosis of JE.

126. Huang, C. C.; Chu, N. S. Acute dystonia with thalamic and

brainstem lesions after initial penicillamine treatment in

Wilson's disease. Eur-Neurol. 1998; 39(1): 32-7; ISSN: 0014-

3022.

SWITZERLAND. Dystonia is a common manifestation in

Wilson's disease (WD). The striatum, especially the putamen,

has been considered to be responsible for dystonia. We

reported 3 patients who developed acute generalized dystonia

and akinetic rigid syndrome following an initial therapy with

d-penicillamine 125-500 mg daily. Brain MRI revealed lesions

in the thalamus and the brainstem, particularly the

tegmentum, and the basis pontis in addition to the basal

ganglion lesions. After the episode, 1 patient continued to

receive d-penicillamine therapy and 2 changed to zinc sulfate

treatment. The generalized dystonia improved in the following

3 months and 3 years respectively in 2 patients. Follow-up

brain MRI of these 2 patients revealed that the lesions in the

thalamus and brainstem disappeared or resolved almost

completely. From these data, acute generalized dystonia with

brainstem and thalamic lesions may occur in WD patients after

an initial d-penicillamine therapy. Furthermore, the dystonia

may resolve following the disappearance of the brainstem and

thalamic lesions.. 52-67-5.

127. Huang, X.; Gerhardt, K. J.; Abrams, R. M.; Antonelli, P. J. Temporary

threshold shifts induced by low-pass and high-pass filtered

noises in fetal sheep in utero. Hear-Res. 1997 Nov; 113(1-2):

173-81; ISSN: 0378-5955.

NETHERLANDS. Auditory brainstem responses (ABRs) were

obtained from nine late gestational age fetal sheep in utero

before and after a 16-h exposure to low-pass (cut-off

frequency 1.0 kHz) and high-pass (cut-off frequency 1.0 kHz)

noises (approximately 120 dB sound pressure level, recorded in

air). Bone-conduction ABRs were elicited by broadband clicks

and 0.5, 1.0 and 2.0 kHz tone bursts. Following low-pass noise

exposure, ABR thresholds and wave IV latencies increased

significantly for 0.5 and 1.0 kHz tone bursts. The high-pass

noise exposure produced significant shifts in ABR thresholds

and wave IV latencies only for the 1.0 kHz tone bursts. These

findings confirm previous reports of low-frequency sound

transmission into the fetal inner ear.

128. Hultcrantz, M.; Spangberg, M. L. Pathology of the cochlea following

a spontaneous mutation in DBA/2 mice. Acta-Otolaryngol-

Stockh. 1997 Sep; 117(5): 689-95; ISSN: 0001-6489.

NORWAY. The DBA/2 strain of mice usually presents with

noise-induced epileptic seizures and hearing disorders. After a

spontaneous mutation a strain with early hearing loss and

circling behaviour was produced. This strain presents with

clinical symptoms found in diseases connected to inner ear

disorders. These animals do not suffer from periodical

disorders, however, but have functional disturbances

continuously and can therefore serve as an animal model for

diseases originating from both parts of the inner ear. The

genetic inheritance appears to be autosomal recessive.

Offspring showed circling behaviour and severe pathology in

the vestibular part of the inner ear. In the present study

pathology of the cochlear part of the inner ear was visualized

using conventional microscopical techniques. The content of

actin and fodrin was labelled immunohistochemically, and

hearing was assessed with auditory brainstem recordings.

After 1 month the animals showed deterioration of the

cochlear part of the inner ear. At 6 months no organ of Corti

remained and the animals were deaf. Transmission and

scanning electron microscopy revealed severe apical hair cell

changes. The content of alpha-actinin and fodrin in the DBA/2

mouse was already fainter than that in age-matched CBA

control mice at the age of 1 month. Labelling of antibodies

against fodrin increased in the supporting cells of the older

animals, probably owing to the replacement of hair cells.. 0;

0; 0; 0; 0.

129. Iglesias Osma, C.; Gomez Sanchez, J. C.; Suquia Mugica, B.; Querol

Prieto, R.; de Portugal, Alvarez J. [Paget's disease of bone and

basilar impression associated with an Arnold-Chiari type-1

malformation]. Enfermedad osea de Paget e impresion basilar

asociadas a malformacion de Arnold-Chiari tipo I. An-Med-

Interna. 1997 Oct; 14(10): 519-22; ISSN: 0212-7199.

SPAIN. The patient, a 78-year-old female with history of

headache and progressive gait disturbance for almost one year,

was admitted to our department because of dysphagia and

dysphonia since three months before. Neurological examination

revealed nystagmus, cerebellar ataxia, deafness, and vesical

incontinence. No cerebral injuries were detected by computed

tomography (CT) scan, although Paget's. Disease of Bone (PDB)

was suggested, confirmed by biochemical and scintigraphic

studies. The plain skull X-ray showed platybasia. As all the

disarrangements were not explained by PDB complications

alone, nuclear magnetic resonance imaging (MRI) was

performed which demonstrated an Arnold-Chiari malformation

(ACM) type I, with mild tonsillar herniation and anterior

compression of the brainstem due to basilar impression,

without syringomyelia. The association of PDB and ACM is a

peculiarity seldom reported. The surgical approach was

rejected, but the severity of symptoms and osteitis deformans

biochemical activity needed a treatment; it was orientated to

modify bone turnover using etidronate, a bisphosphonate,

which induced clinical improvement and a decrease in serum

alkaline phosphatase as well as in other bone resorption

markers, without side effects. The good status and

biochemical remission have been maintained a year later..

7414-83-7.

130. Illing, R. B.; Forster, C. R.; Horvath, M. Evaluating the plasticity

potential of the auditory brain stem nucleus in the rat. Am-J-

Otol. 1997 Nov; 18(6 Suppl): S52-3; ISSN: 0192-9763.

UNITED-STATES. OBJECTIVE: To study the adaptation of the

auditory brainstem to auditory loss. STUDY DESIGN: Growth-

associated protein 43 (GAP-43) immunoreactivity was studied

in in rats whose cochleas had been removed. RESULTS AND

DISCUSSION: Neurons in the lateral superior olive were found

to synthesize GAP-43 in a pattern that paralleled the changes

in GAP-43 immunoreactivity in the cochlear nucleus after

cochlear ablation. These findings suggest that new patterns of

synaptic communication can be established after damage to

the cochlea.

131. Inagi, K.; Schultz, E.; Ford, C. N. An anatomic study of the rat

larynx: establishing the rat model for neuromuscular function.

Otolaryngol-Head-Neck-Surg. 1998 Jan; 118(1): 74-81; ISSN:

0194-5998.

UNITED-STATES. The gross and microscopic anatomy of the rat

larynx was studied with particular attention to myology and

neuromuscular structures to further validate it as a model to

evaluate morphologic and functional changes induced by

botulinum injection. A laryngeal alar cartilage (LAIC), alar

cricoarytenoid (ACA) muscle, and a superior cricoarytenoid

muscle (SCA) were identified as anatomic structures not

previously described. Two portions (medial and lateral) of the

thyroarytenoid muscle (TA) were distinguished. The function

of the ACA was suggested to be similar to the aryepiglottis

muscle in humans and the function of the SCA was suggested

to be similar to the human interarytenoid muscle. The

predominant pattern of motor endplate (MEP) distribution in

rat laryngeal muscles (posterior cricoarytenoid, lateral

cricoarytenoid, cricothyroid, and SCA) was to have MEPs

concentrated mostly at the midbelly of muscle where they

were distributed throughout the cross-sectional area of the

midbelly. The TA and ACA differed from this pattern. The

lateral TA had MEPs concentrated at the anterior third of its

belly and those of the medial TA were located at the midbelly.

Motor endplates in the ACA were located mostly at the

posterior portion of muscle. Muscle fiber-typing showed subtle

differences between the intrinsic laryngeal muscles. Fast

fibers were predominant in the rat laryngeal muscles. This

study supports the expanded use of rats in studies of laryngeal

neuromuscular function and disease in humans.. 0.

132. Ito, K.; Ishikawa, Y.; Skinner, R. D.; Mrak, R. E.; Morrison Bogorad,

M.; Mukawa, J.; Griffin, W. S. Lesioning of the inferior olive

using a ventral surgical approach. Characterization of

temporal and spatial astrocytic responses at the lesion site

and in cerebellum. Mol-Chem-Neuropathol. 1997 Aug; 31(3):

245-64; ISSN: 1044-7393.

UNITED-STATES. Activated astrocytes, intrinsic components

of both local and remote (axonal target regions) central

nervous system injury responses, are now recognized as active

metabolic and regulatory mediators in many neurological

disorders. To further define these responses, we devised a new

ventral surgical approach to unilaterally lesion the inferior

olivary nuclear complex, which has a single predominant

remote target, the cerebellum. Activated astrocyte number,

volume, and density, as well as the total volume of brainstem

involved in the astrocytic response, all peaked at postlesion

day (pld) 4, returning toward, but not to, unoperated control

values at pld 24 (p < 0.05). In contrast, the peak astrocyte

response in the cerebellum was delayed, being greatest at pld

6 (p < 0.05 compared to control or pld 2). These responses were

associated with increases in overexpression of S100 beta, an

astrocyte-derived neurite growth factor, and with an increase

in cerebellar steady-state levels of a neuronal injury response

protein, the beta-amyloid precursor protein (beta-APP). This

is similar to correlated increases in these two proteins that

are found in epilepsy and Alzheimer disease. Our studies

defining remote astrocytic and neuronal responses may be

important for understanding glial-neuronal mechanisms

underlying the spread of neuropathological changes in

conditions such as Alzheimer disease.. 0; 0; 0.

133. Itoh, M.; Fueki, N.; Kurata, K.; Hayashi, M.; Morimatsu, Y.; Satoh, J.

[Localized lesions on MRI in the globus pallidus, subthalamic

nuclei and hippocampus in patients with severe intellectual

and motor disabilities]. No-To-Hattatsu. 1997 Nov; 29(6): 449-

54; ISSN: 0029-0831.

JAPAN. We examined the clinical picture of eight patients

with severe intellectual and motor disabilities, who had

experienced prolonged and severe neonatal jaundice, and

showed localized lesions in the globus pallidus, subthalamic

nuclei and hippocampus on MRI. All patients had athetoid

tetraplegia, and five patients showed disturbed ocular

movements and seven showed dysphagia. Five patients could

communicate with others or utter words, and all showed

mental retardation. Auditory brainstem responses were

abnormal in seven, and the percentage of REM sleep on all-

night polysomnography was reduced in three. Neither CT nor

T1-weighted MR images could detect any changes in the

pallidum or subthalamic nuclei, while T2-weighted MR images

disclosed bilateral high signals in the pallidum, especially in

the internal segment, in all patients. Five of the 7 patients, in

whom coronal T2-weighted MR imagings were obtained,

showed high signals in the subthalamic nuclei. The

hippocampus showed atrophy and/or T2-prolongation in seven

patients. In one autopsy case, these MRI changes were

concordant with pathological lesions. In patients with athetoid

cerebral palsy, brainstem dysfunctions, and abnormal ABR,

localization of MRI lesions to the pallidum and subthalamic

nuclei is evidence for neonatal bilirubin encephalopathy.

134. Javed, A.; Van, De Kar LD; Gray, T. S. p-Chlorophenylalanine and

fluoxetine inhibit D-fenfluramine-induced Fos expression in

the paraventricular nucleus, cingulate cortex and frontal

cortex but not in other forebrain and brainstem regions. Brain-

Res. 1997 Nov 7; 774(1-2): 94-105; ISSN: 0006-8993.

NETHERLANDS. D-Fenfluramine, a putative serotonin releaser

and reuptake inhibitor, is commonly prescribed for the

treatment of obesity. Brain sites activated by D-fenfluramine

have been mapped via the expression of the immediate early

gene Fos. However, it is not clear that serotonin release in the

brain mediates the effects of D-fenfluramine on Fos

expression. The present study determined whether D-

fenfluramine induces the expression of Fos in the brain

through the release of serotonin. Rats were pretreated either

with the serotonin depleting drug p-chlorophenylalanine

(PCPA) or with the serotonin reuptake inhibitor fluoxetine.

Both drugs inhibited D-fenfluramine-induced Fos expression in

the cingulate cortex, frontal cortex, and the parvocellular

subdivision of the paraventricular nucleus of the

hypothalamus. Neither drug reduced D-fenfluramine-induced

Fos responses in several other brain areas, including the

caudate-putamen, amygdala, and brainstem regions such as the

lateral parabrachial nucleus and nucleus of the solitary tract.

These results indicate regional specificity of mechanisms

mediating D-fenfluramine-induced Fos expression. It is likely

that D-fenfluramine-induced Fos expression at various sites in

the brain is mediated via a combination of serotonin release

and other, as yet unidentified, neurotransmitters.. 0; 0; 0; 0;

458-24-2; 54910-89-3; 7424-00-2.

135. Jing, X.; Li, R.; Meng, Z. [The progress of morphological research on

the parabrachial nucleus]. Chen-Tzu-Yen-Chiu. 1996; 21(3): 4-

8; ISSN: 1000-0607.

CHINA. In this paper, the progress of morphological research

on the PBN, the cytoarchitecture of the PBN, and the fiber

connections between the PBN and the spinal, the brainstem,

the forebrain and the other nucleus were summarized. Its

function in the relationship between the meridian and the

internal organ was also assumed.

136. Johansson, J.; Forsgren, L.; Sandgren, O.; Brice, A.; Holmgren, G.;

Holmberg, M. Expanded CAG repeats in Swedish spinocerebellar

ataxia type 7 (SCA7) patients: effect of CAG repeat length on

the clinical manifestation. Hum-Mol-Genet. 1998 Feb; 7(2):

171-6; ISSN: 0964-6906.

ENGLAND. Spinocerebellar ataxia 7 (SCA7) is a

neurodegenerative disorder characterized by degeneration of

the cerebellum, brainstem and retina. The gene responsible for

SCA7, located on chromosome 3p, recently was cloned and

shown to contain a CAG repeat in the coding region of the gene,

that is expanded in SCA7 patients of French origin. We

examined the SCA7 repeat region in four Swedish SCA7

families as well as in 57 healthy controls. All Swedish SCA7

patients exhibited expanded CAG repeats with a strong

negative correlation between repeat size and age of onset. The

repeat length in SCA7 patients ranged from 40 to >200

repeats. The largest expansion was observed in a juvenile case

with an age of onset of 3 months, and represents the longest

polyglutamine stretch ever reported. In patients with 59

repeats or more, visual impairment was the most common

initial symptom observed, while ataxia predominates in

patients with <59 repeats. Two of the Swedish SCA7 families

analysed in this study were shown to be related

genealogically. The other two SCA7 families could not be

traced back to a common ancestor. All four families shared the

same allele on the disease chromosome at a locus closely

linked to SCA7, suggesting the possibility of a founder effect

in the Swedish population.

137. Johnson, D. E.; Seidler, F. J.; Slotkin, T. A. Early biochemical

detection of delayed neurotoxicity resulting from

developmental exposure to chloropyrifos. Brain-Res-Bull.

1998; 45(2): 143-7; ISSN: 0361-9230.

UNITED-STATES. Developing animals are more sensitive than

adults to the delayed neurotoxicity caused by chlorpyrifos

exposure. In developing rat brain, chlorpyrifos doses that

cause no discernible systemic toxicity and only a minor degree

of cholinesterase inhibition, nevertheless evoke alterations in

cell function and number that appear after several days' delay.

In the current study, neonatal rats were exposed to subtoxic

doses of chlorpyrifos (no weight loss or mortality) on either

postnatal days 1-4, or postnatal days 11-14, and the effects

on cellular RNA levels were determined in two brain regions

that are targeted for delayed neurotoxicity-the brainstem and

forebrain. In both regions, chlorpyrifos exposure evoked

significant alterations in RNA concentration and content,

variables that are ordinarily very tightly controlled in the

developing brain. The effects on RNA appeared well before the

deficits in cell function and number and showed a regional

selectivity similar to that of subsequent, delayed

neurotoxicity. Deficits in RNA were more prominent in the

brainstem, an early-developing brain region, than in the

forebrain, which develops later. These results suggest that

chlorpyrifos can elicit delayed developmental neurotoxicity by

targeting the pivotal macromolecules that control cell

differentiation in a critical postmitotic period. The lower

threshold for these cellular effects compared to that for

systemic toxicity indicates that the developing brain is a

selective target for chlorpyrifos, effects that should be

considered in assessing safety thresholds.. 0; 2921-88-2;

63231-63-0.

138. Johnson, K. R.; Erway, L. C.; Cook, S. A.; Willott, J. F.; Zheng, Q. Y. A

major gene affecting age-related hearing loss in C57BL/6J

mice. Hear-Res. 1997 Dec; 114(1-2): 83-92; ISSN: 0378-5955.

NETHERLANDS. A major gene responsible for age-related

hearing loss (AHL) in C57BL/6J mice was mapped by analyses

of a (C57BL/6J x CAST/Ei) x C57BL/6J backcross. AHL, as

measured by elevated auditory-evoked brainstem response

(ABR) thresholds, segregated among backcross mice as

expected for a recessive, primarily single-gene trait. Both

qualitative and quantitative linkage analyses gave the same

genetic map position for the AHL gene (Ahl on chromosome 10,

near D10Mit5. Marker assisted selection was then used to

produce congenic lines of C57BL/6J that contain different

CAST-derived segments of chromosome 10. ABR test results

and cochlear histopathology of aged progenitors of these

congenic lines are presented. Ahl is the first gene causing

late-onset, non-syndromic hearing loss that has been reported

in the mouse.

139. Kaga, K.; Iwasaki, S.; Tamura, A.; Suzuki, J.; Haebara, H. Temporal

bone pathology of acoustic neuroma correlating with presence

of electrocochleography and absence of auditory brainstem

response. J-Laryngol-Otol. 1997 Oct; 111(10): 967-72; ISSN:

0022-2151.

ENGLAND. The temporal bone pathology of a 74-year-old

female affected by vestibular schwannoma was compared with

findings of auditory brainstem response and

electrocochleography. At age 71, she complained of hearing

loss in the left ear in which pure tone audiometry revealed

threshold elevation in the middle- and high-frequency range.

Temporal bone CT scanning revealed a medium-sized

cerebellopontine angle tumour in the left ear. ABR showed no

response in the left ear, but the electrocochleography showed

clear compound action potentials. Three years later, at age 74,

she died of metastatic lung cancer and sepsis. The left

temporal bone pathology consisted primarily of a large

vestibular schwannoma occupying the internal auditory

meatus. The organ of Corti was well preserved in each turn. In

the modiolus, the numbers of spiral ganglion cells and cochlear

nerve fibres in each turn were decreased. These histological

findings suggest that clear compound action potentials were

recorded from the distal portion of the cochlear nerve in spite

of the presence of the vestibular schwannoma, but ABR could

not be detected because of the blockade of the proximal

portion of the cochlear nerve by the vestibular schwannoma.

140. Kee, C.; Koo, H.; Ji, Y.; Kim, S. Effect of optic disc size or age on

evaluation of optic disc variables. Br-J-Ophthalmol. 1997 Dec;

81(12): 1046-9; ISSN: 0007-1161.

ENGLAND. AIMS/BACKGROUND: It has been reported that the

number of optic nerve fibres decrease with age, and the

cup/disc (C/D) ratio increases as the optic disc size increases.

Consequently, the normal value of the optic disc variables

measured by an optic disc analyser may change according to

the optic disc size or age. The effect of individual variations

in optic disc size or age on interpretation of optic disc

variables was investigated. METHODS: Topographic optic disc

variables of 104 normal Asian adults of both sexes aged 40 to

68 were measured using a confocal scanning laser

ophthalmoscope (TopSS, Laser Diagnostic Technologies, Inc).

Fourteen variables were evaluated according to the optic disc

size or age. Statistical analysis was done by regression

analysis. RESULTS: With an increase in optic disc size, the

increase in cup shape, effective area, 1/2 depth area, C/D

ratio, neuroretinal rim area, volume above, volume below, and

1/2 depth volume were statistically significant (p < 0.05).

However, contour variation, mean contour depth, average

depth, maximum depth, average slope, and maximum slope

were not affected (p > 0.1). Age did not have any significant

influence on optic disc variables (p > 0.1). CONCLUSION: Optic

disc size, but not age, should be considered in the

interpretation of optic disc variables.

141. Kehrli, P.; Ali, M. M.; Maillot, C.; Fortman, J.; Misra, M.; Dujovny, M.

Comparative microanatomy of the lateral wall of the

'cavernous sinus' in humans and the olive baboon. Neurol-Res.

1997 Dec; 19(6): 571-6; ISSN: 0161-6412.

ENGLAND. Despite many studies of the 'cavernous sinus'

lateral wall, the anatomy of this area remains controversial.

We performed a comparative microanatomical and

histoarchitectural study in 14 humans and in 10 nonhuman

primates (Papio cynocephalus anubis). Venous channels and

cranial nerves were embedded in the 'interperiosteodural

space'. The dura propria of the lateral wall could be removed

without entering the venous compartment. The oculomotor and

trochlear nerves were accompanied by an arachnoidal and dural

sheath. The oculomotor nerve sheath stopped under the

anterior clinoid process in baboons. The trigeminal ganglion

was covered posteriorly with an arachnoid membrane and

adhered firmly to the dura propria on lateral and anterior

sections. The three branches of the trigeminal nerve had no

arachnoid covering, except for arachnoid granulations in

humans. In baboons, the oculomotor and trochlear nerves were

thicker than in humans, while the ophthalmic nerve was

thinner. The abducens nerve belonged to the lateral wall of the

sinus in baboons and had no arachnoidal sheath except in the

first millimeters of Dorello's canal. After leaving their

arachnoidal and dural sheath, the intracavernous cranial

nerves acquired a typical peripheral sheath. The venous

channels in both species were true dural sinuses. Willis cords

and adipose tissue were identified.

142. Kelley, M. S.; Lurie, D. I.; Rubel, E. W. Rapid regulation of

cytoskeletal proteins and their mRNAs following afferent

deprivation in the avian cochlear nucleus. J-Comp-Neurol.

1997 Dec 22; 389(3): 469-83; ISSN: 0021-9967.

UNITED-STATES. During development, removal of neuronal

input can lead to profound changes in postsynaptic cells,

including atrophy and cell death. In the chicken brainstem

cochlear nucleus, the nucleus magnocellularis (NM),

deprivation of auditory input via unilateral cochlea removal or

silencing the eighth nerve with tetrodotoxin leads to a loss of

25-30% of the neurons and the atrophy of surviving neurons.

One intracellular component that may be involved in both cell

atrophy and cell death is the cytoskeleton. The degradation of

the cytoskeleton following deafferentation could potentially

lead to either atrophy or death of NM neurons. However, little

is known regarding the role of neuronal input on the

cytoskeletal structure of NM neurons and whether changes in

the cytoskeleton are responsible for cell death following

deafferentation. The present study examined whether changes

in the cytoskeleton of NM neurons occurred following cochlea

removal. Several components of the cytoskeleton were

analyzed following unilateral afferent deprivation. Levels of

immunostaining for tubulin, actin, and microtubule-associated

protein 2 (MAP-2), and levels of beta-tubulin and beta-actin

mRNAs were assessed in NM neurons following cochlea

removal. Our results revealed that afferent deprivation results

in a rapid decrease in immunostaining for all three

cytoskeletal proteins examined. These decreases were

observed as early as 3 hours after cochlea removal and

persisted for up to 4 days. In addition, these changes occurred

in all deafferented NM neurons at the early time points,

indicating that both dying and surviving NM neurons undergo a

similar change in their cytoskeletons. In contrast to the

decreases in immunostaining, levels of beta-tubulin and beta-

actin mRNAs were not noticeably altered by deafferentation.

Our findings indicate that the cytoskeleton is altered or

degraded following deafferentation but that this process is

not regulated at the transcriptional level.. 0; 0; 0; 1672-46-4.

143. Kikuchi, M.; Tagawa, Y.; Iwamoto, H.; Hoshino, H.; Yuki, N.

Bickerstaff's brainstem encephalitis associated with IgG anti-

GQ1b antibody subsequent to Mycoplasma pneumoniae

infection: favorable response to immunoadsorption therapy. J-

Child-Neurol. 1997 Sep; 12(6): 403-5; ISSN: 0883-0738.

UNITED-STATES. 0; 0; 0.

144. King, A. J.; Jiang, Z. D.; Moore, D. R. Auditory brainstem

projections to the ferret superior colliculus: anatomical

contribution to the neural coding of sound azimuth. J-Comp-

Neurol. 1998 Jan 19; 390(3): 342-65; ISSN: 0021-9967.

UNITED-STATES. The mammalian superior colliculus (SC)

contains a neural map of auditory space. It is not known

whether this topographic representation emerges at the level

of the SC or is relayed there from other auditory areas. We

have used retrograde labelling techniques in ferrets to

examine the sources and pattern of innervation from auditory

brainstem nuclei. After multiple injections of wheat germ

agglutinin conjugated to horseradish peroxidase (WGA-HRP)

into the SC, the heaviest concentrations of labelled cells were

found in the nucleus of the brachium (BIN) and external nucleus

of the inferior colliculus, with much weaker labelling in the

nucleus sagulum, dorsal, intermediate and ventral nuclei of the

lateral lemniscus, paralemniscal regions, and periolivary

nuclei. The projections were predominantly ipsilateral,

although labelled cells were found on both sides of the

brainstem. Single injections of WGA-HRP or discrete

injections of red and green latex microspheres revealed that

the caudal and lateral regions of the SC receive the heaviest

projections, although the majority of the retrogradely labelled

neurons in the contralateral BIN project to rostral SC. On the

ipsilateral side, neurons in rostral and caudal regions of the

BIN were labelled primarily by the tracer injected into rostral

and caudal regions of the SC, respectively. However, no clear

segregation was apparent in the BIN after injections into the

medial and lateral regions or in any of the other nuclei after

either injection paradigm. These data suggest that converging

inputs from several auditory brainstem nuclei contribute to

the construction of the auditory space map in the SC, although

information about sound azimuth may be conveyed to this

nucleus via a spatially ordered projection from the ipsilateral

BIN.. 0.

145. Knappertz, V. A.; Tegeler, C. H.; Hardin, S. J.; McKinney, W. M. Vagus

nerve imaging with ultrasound: anatomic and in vivo validation.

Otolaryngol-Head-Neck-Surg. 1998 Jan; 118(1): 82-5; ISSN:

0194-5998.

UNITED-STATES. To provide the anatomic basis and

demonstrate the reproducibility of ultrasound studies for the

identification of the vagus nerve within its course in the

carotid sheath in the neck, cadaveric and in vivo imaging

studies were conducted. On transverse B-mode images of the

neck, there is a centrally hypoechoic and peripherally

hyperechoic structure between the common carotid artery and

the jugular vein inside the carotid sheath. This structure was

also identified in a fresh, nonpreserved cadaver and was

marked with a hypodermic needle by means of a transdermal

approach. Neck dissection was performed leaving the carotid

sheath intact. B-mode imaging yielded detailed anatomic

information about the structures in the carotid sheath. Further

dissection showed the vagus nerve as the target of the needle.

One hundred consecutive transverse carotid scans were

reviewed, and the characteristic echo patterns of the vagus

nerve were identified in 97 instances. A distinct and

reproducible, round, hypoechoic structure was defined

adjacent to the common carotid artery and jugular vein as the

vagus nerve. On the basis of this study, a new, noninvasive, and

highly reproducible method to locate the vagus nerve in the

carotid sheath is introduced. This may lead to further clinical

application such as presurgical localization or ultrasound-

guided needle studies. Stimulation of the vagus nerve has been

proposed for seizure therapy. The diagnosis of vagus nerve

tumors may be improved.

146. Kochanek, K.; Skarzynski, H.; Cwynar, B.; Wrobel, B. [The auditory

brainstem response recordings in small children at night].

Badania sluchowych potencjalow wywolanych pnia mozgu u

malych dzieci w porze wieczorno-nocnej. Otolaryngol-Pol.

1997; 51(2): 223-7; ISSN: 0030-6657.

POLAND. Authors compare two methods of hearing assessment

using ABR recordings in children at the age of 1 to 6 years.

Following are the applied methods: 1) ABR recording in natural

sleep at night and 2) ABR recording in pharmacologically

induced sleep. Advantages and disadvantages of the methods

are presented and parameters such as: time of examination,

number of averages, number of artefacts and percentage of

successful recordings have been evaluated.

147. Koide, R.; Onodera, O.; Ikeuchi, T.; Kondo, R.; Tanaka, H.; Tokiguchi,

S.; Tomoda, A.; Miike, T.; Isa, F.; Beppu, H.; Shimizu, N.;

Watanabe, Y.; Horikawa, Y.; Shimohata, T.; Hirota, K.; Ishikawa,

A.; Tsuji, S. Atrophy of the cerebellum and brainstem in

dentatorubral pallidoluysian atrophy. Influence of CAG repeat

size on MRI findings. Neurology. 1997 Dec; 49(6): 1605-12;

ISSN: 0028-3878.

UNITED-STATES. To elucidate how the size of the expanded

CAG repeat of the gene for dentatorubral pallidoluysian

atrophy (DRPLA) and other factors affect the atrophy of the

brainstem and cerebellum, and the appearance of high-

intensity signals on T2-weighted MRI of the cerebral white

matter of patients with DRPLA, we quantitatively analyzed the

MRI findings of 26 patients with DRPLA, the diagnosis of

which was confirmed by molecular analysis of the DRPLA gene.

When we classified the patients into two groups based on the

size of the expanded CAG repeat of the DRPLA gene (group 1,

number of CAG repeat units > or = 66; group 2, number of CAG

repeat units < or = 65), we found strong inverse correlations

between the age at MRI and the areas of midsagittal structures

of the cerebellum and brainstem in group 1 but not in group 2.

Multiple regression analysis, however, revealed that both the

patient's age at MRI and the size of the expanded CAG repeat

correlated with the areas of midsagittal structures.

Involvement of the cerebral white matter as detected on T2-

weighted images was observed more frequently in patients

belonging to group 2 than in group 1 patients. Furthermore it

was demonstrated that high-intensity signals can be detected

on T2-weighted images of the cerebral white matter of

patients with a largely expanded CAG repeat (group 1) in their

thirties. These results suggest that patient age as well as the

size of the expanded CAG repeat are related to the degree of

atrophy of the brainstem and cerebellum, and the white matter

changes in patients with DRPLA.. 0; 0.

148. Koos, W. T.; Day, J. D.; Matula, C.; Levy, D. I. Neurotopographic

considerations in the microsurgical treatment of small

acoustic neurinomas. J-Neurosurg. 1998 Mar; 88(3): 506-12;

ISSN: 0022-3085.

UNITED-STATES. OBJECT: The authors studied the

relationships between tumor size, location, and topographic

position relative to the intact facial nerve bundles in acoustic

neurinomas to determine the influence of these factors on

hearing preservation postoperatively. Consistent topographic

relationships were found. METHODS: Four hundred fifty-two

patients with acoustic neurinoma treated via a retrosigmoid

approach were analyzed with respect to hearing preservation

and facial nerve function. One hundred fifteen tumors were

identified as small and were categorized as Grades I and II.

Patients with Grade I tumors, that is, purely intracanalicular

lesions, all had good hearing preoperatively, defined by a less

than 50-dB pure tone average and 50% speech discrimination

score. All 14 Grade I tumors were removed, resulting in

preservation of the patient's hearing by these criteria. There

were no particular topographic anatomical relationships

associated with these tumors that affected hearing

preservation. Grade II tumors, defined as those protruding into

the cerebellopontine angle without contacting the brainstem,

were found in 101 patients and were divided by size into two

grades: IIA (< 1 cm) and IIB (1-1.8 cm). In 90 patients with

Grade IIA tumors, 72 (89%) of 81 who had preserved hearing

preoperatively maintained it postoperatively, and in the 11

patients with Grade IIB tumors, six of whom had good hearing

preoperatively, four (67%) had preserved hearing

postoperatively. Six morphological types were identified based

on their neurotopographic relationships to the elements of the

vestibulocochlear nerve. CONCLUSIONS: Hearing preservation

postsurgery by tumor type was as follows: 1A, 92%; 1B, 88%;

1C, 100%; 2A, 83%; 2B, 92%; and 3, 57%. Combined, this

represents a hearing preservation rate of 87% after surgical

treatment of Grade II acoustic neurinomas. Full nerve function

was maintained in 88% of patients with anatomically

preserved facial nerves in both Grade I and II tumors. The

remaining 12% of patients retained partial function of the

facial nerve. Two patients in the series lost anatomical

integrity of the nerve due to surgery.

149. Korpelainen, J. T.; Sotaniemi, K. A.; Huikuri, H. V.; Myllyla, V. V.

Circadian rhythm of heart rate variability is reversibly

abolished in ischemic stroke. Stroke. 1997 Nov; 28(11): 2150-

4; ISSN: 0039-2499.

UNITED-STATES. BACKGROUND AND PURPOSE: Acute brain

infarction significantly decreases heart rate variability as a

result of cardiovascular autonomic dysregulation. However,

information regarding circadian rhythms of heart rate and

heart rate variability is limited. METHODS: In this prospective

study, we analyzed 24-hour circadian rhythm of heart rate and

the time and frequency domain measures of heart rate

variability in 24 patients with hemispheric brain infarction, 8

patients with medullary brainstem infarction, and 32 age- and

sex-matched healthy control subjects. ECG data were obtained

from the patients in the acute phase and at 6 months after the

infarction. RESULTS: In the acute phase of stroke, all the

components of heart rate variability, ie, standard deviation of

RR intervals, total power, high-frequency power, low-

frequency power, and very-low-frequency power, were similar

at night (from midnight to 6 AM) and during the day (from 9 AM

to 9 PM), indicating that the circadian oscillation of heart rate

variability had been abolished. At 6 months after brain

infarction, the circadian rhythm had returned and, as in the

control subjects, the values at night were significantly higher

than those in the daytime. The values in hemispheric and in

brainstem infarction did not differ significantly from each

other. CONCLUSIONS: These results suggest that circadian

fluctuation of heart rate variability is reversibly abolished in

the acute phase of ischemic stroke and that it returns during

the subsequent 6 months. The loss of the relative vagal

nocturnal dominance may contribute to the incidence of

cardiac arrhythmias and other cardiovascular complications

after acute stroke.

150. Krowicki, Z. K.; Nathan, N. A.; Hornby, P. J. Cyclooxygenase

inhibition in the dorsal vagal complex of the rat evokes

increases in gastric motor function. J-Physiol-Paris. 1997

May; 91(3-5): 209-13; ISSN: 0928-4257.

FRANCE. To characterize the involvement of brainstem

cyclooxygenase (COX) in the vagal control of gastric motor

function, tolmetin, a reversible COX inhibitor, was applied to

the surface of the dorsal medulla oblongata or microinjected

into the dorsal vagal complex (DVC) in alpha-chloralose

anesthetized rats, while intragastric pressure and contractile

activity of the pyloric circular and greater curvature

longitudinal muscle were monitored. Tolmetin, applied to the

surface of the medulla oblongata, increased intragastric

pressure and stimulated contractile activity of gastric smooth

muscle. Comparable gastric motor effects were observed after

microinjection of tolmetin into the DVC. All the effects of

tolmetin were abolished by bilateral vagotomy at the

midcervical level. These results demonstrate for the first

time that COX inhibition evokes vagally-mediated gastric

motor effects in the DVC of the rat and support a role for COX

products in gastrointestinal regulation.. 0; 26171-23-3.

151. Kulik, A.; Matesz, C. Projections from the nucleus isthmi to the

visual and auditory centres in the frog, Rana esculenta. J-

Hirnforsch. 1997; 38(3): 299-307; ISSN: 0021-8359.

GERMANY. The lectin Phaseolus vulgaris leucoagglutinin was

injected into the nucleus isthmi (NI) in order to study its

anterograde and retrograde projections in the frog. The

following areas of termination could be discerned in the

brainstem: (1) Each of the five subnuclei of the torus

semicircularis (TOS) received fibres from the NI. The

projection was the most extensive on the three main subnuclei

which disclosed also retrogradely labelled neurones on the

side of injections. The subependymal subnuclei contained the

least number of labelled fibres. (2) Both hemispheres of the

optic tectum (TO) were supplied by fibres from the NI. Labelled

fibres were more numerous on the side of injections, and

preterminal and terminal fibres covered columnar-like areas

in layers 8 and 9. Several retrogradely labelled neurones were

found in layer 6. Relatively few labelled fibres were seen on

the contralateral side. They formed patch-like areas of

termination in layer 9. (3) The anterodorsal (AD) and

anteroventral (AV) nuclei were reciprocally inter-connected

with the NI. The fibre connections were less extensive on the

contralateral side. In the rhombencephalon (4) the cochlear

nucleus (CN) and (5) the superior olive (SO) were also

reciprocally connected with the NI on both sides, but with

much weaker projection on the side contralateral to

injections. (6) Only a weak anterograde labelling was observed

in the contralateral NI and in the ipsilateral reticular

formation.. 0; 0.

152. Kumar, V.; Tandon, O. P. Neurotoxic effects of rubber factory

environment. An auditory evoked potential study.

Electromyogr-Clin-Neurophysiol. 1997 Nov; 37(8): 469-73;

ISSN: 0301-150X.

BELGIUM. The effects of rubber factory environment on

functional integrity of auditory pathway have been studied in

forty rubber factory workers using Brainstem Auditory Evoked

Potentials (BAEPs) technique to detect early subclinical

impairments. Results indicate that 47 percent of the workers

showed abnormalities in prolongations of either peak latencies

or interpeak latencies when compared with age and sex

matched control subjects not exposed to rubber factory

environment. The percent distribution of abnormalities (ears

affected) were in the order of extrusion and calendering (75%)

> vulcanising (41.66%) > mixing (28.57%) > loading and dispatch

(23.07%) > tubing (18.75%) sections of the factory. This

incidence of abnormalities may be attributed to solvents being

used in these units of rubber factory. These findings suggest

that rubber factory environment does affect auditory pathway

in the brainstem.. 0; 0; 9006-04-6.

153. Kungel, M.; Friauf, E. Physiology and pharmacology of native

glycine receptors in developing rat auditory brainstem

neurons. Brain-Res-Dev-Brain-Res. 1997 Sep 20; 102(2): 157-

65; ISSN: 0165-3806.

NETHERLANDS. Glycinergic neurotransmission is mediated via

inhibitory glycine receptors (GlyRs) which are heterogeneous

during development. Electrophysiological studies performed on

recombinant GlyRs have identified different pharmacological

properties and attributed them to differences in their subunit

composition. Here, we report on age-related changes in the

response properties of native GlyRs in the mammalian brain.

Whole-cell patch-clamp recordings were obtained from

neurons of the medial nucleus of the trapezoid body (MNTB), a

major relay station in the mammalian auditory brainstem.

Experiments were performed in acute medullary slices of rats

between postnatal day (P) 1 and P15, a period during which

synapse maturation occurs. Glycine-induced currents were

present throughout the period under investigation and

displayed age-related modifications in their amplitude,

kinetic characteristics, and sensitivity to drugs. Current

amplitudes and GlyR desensitization behavior increased with

age. The alpha 1 subunit-specific GlyR antagonist

cyanotriphenylborate (CTB) was barely effective in reducing

glycine-induced currents during the first few postnatal days,

yet a significant increase of the inhibitory effect occurred

after the first postnatal week. This finding indicates that

alpha 1 subunit-containing GlyRs become expressed only

postnatally in the MNTB. Picrotoxin, which most effectively

blocks recombinant alpha 2-homooligomers, reduced glycine-

induced currents in neonatal MNTB neurons, suggesting that

alpha 2-homooligomers may form native GlyR isoforms. Our

results show that the physiology and pharmacology of GlyRs in

the auditory brainstem underlie age-related changes which are

most probably produced through a replacement of "neonatal"

alpha 2 subunits with "adult" alpha 1 subunits.. 0; 0; 124-87-

8; 14568-16-2.

154. Laine, F. J.; Smoker, W. R. Anatomy of the cranial nerves.

Neuroimaging-Clin-N-Am. 1998 Feb; 8(1): 69-100; ISSN: 1052-

5149.

UNITED-STATES. The anatomy of cranial nerves I and III

through XII are presented. Each nerve is diagrammatically

illustrated from its nuclear or its sensory origin and

correlated with magnetic resonance and computed tomography

images. The important identifying anatomical landmarks are

demonstrated along the course of each nerve. Peripheral motor

and sensory components are also discussed.

155. Lalwani, A. K.; Linthicum, F. H.; Wilcox, E. R.; Moore, J. K.; Walters,

F. C.; San Agustin, T. B.; Mislinski, J.; Miller, M. R.; Sinninger, Y.;

Attaie, A.; Luxford, W. M. A five-generation family with late-

onset progressive hereditary hearing impairment due to

cochleosaccular degeneration. Audiol-Neurootol. 1997 May;

2(3): 139-54; ISSN: 1420-3030.

SWITZERLAND. Cochleosaccular dysplasia or degeneration

(Scheibe degeneration) is considered the most common cause

of profound congenital hearing impairment, and accounts for

approximately 70% of cases 2 with hereditary deafness. A

five-generation family with hereditary hearing impairment

associated with cochleosaccular degeneration has recently

been identified. The diagnosis of classical Scheibe

degeneration was based on histopathological findings in the

temporal bones of the proband, a 61-year-old profoundly deaf

male. Auditory structures in the brainstem of the proband

were also studied. Twenty-two members of the family were

contacted for surveys and blood samples. Of these, 6 males and

2 females have hearing impairment. Complete audiological

evaluation was done on 12 family members, and prior

audiologic records of the proband and affected family members

were available for study. Affected family members suffer a

mild bilateral high-frequency hearing loss during childhood

and adolescence, and progress to moderate-to-profound

deafness in the second and third decades of life. The family is

suitable for linkage analysis and does not map to previously

reported loci harboring autosomal dominant, nonsyndromic

hereditary hearing impairment genes. The genetic study of this

family will be helpful in identifying the genes which, when

mutated, result in Scheibe degeneration.

156. Lambert, P. R. Evaluation of the dizzy patient. Compr-Ther. 1997

Nov; 23(11): 719-23; ISSN: 0098-8243.

UNITED-STATES. This discussion has focused primarily on the

history and physical examination of the patient with dizziness

which, in fact, are the two most important elements in the

evaluation process. To perform the examination expeditiously

and completely, a broad differential diagnosis of dizziness

must be kept in mind. The clinician should also keep in mind

two basic objectives: first, to identify serious pathology (e.g.,

central nervous system lesion, brainstem ischemia, cardiac

arrhythmia); and second, to recognize diseases that can be

specifically treated, such as an endocrine abnormality, middle

ear infection, Meniere's disease, or a drug reaction.

Reassurance and/or vestibular rehabilitation are the

mainstays of therapy for the patients not falling into the

above two categories.

157. Lamm, K.; Arnold, W. Noise-induced cochlear hypoxia is intensity

dependent, correlates with hearing loss and precedes reduction

of cochlear blood flow. Audiol-Neurootol. 1996 May; 1(3): 148-

60; ISSN: 1420-3030.

SWITZERLAND. Anesthetized and artificially ventilated guinea

pigs were exposed to broad-band noise of 95, 101, 106 or 115

dB SPL for 30 min and studied for 180 min after cessation of

noise. The partial pressure of oxygen (pO2) in the perilymph,

the cochlear blood flow (CoBF) and auditory-evoked potentials

were continuously recorded. Arterial blood pressure,

electrocardiogram, inspiratory and expiratory gas levels,

arterial blood gas levels and acid-base status were kept

stable to exclude influences of these parameters on cochlear

parameters. Exposure to 95 dB SPL did not affect

perilymphatic pO2 or CoBF. Cochlear microphonics (CMs) were

reduced, but compound action potentials of the auditory nerve

(CAPs) and auditory brainstem potentials (ABRs) increased

after exposure to this low-level noise. Perilymphatic pO2

decreased during exposure to 101 dB SPL and then further

decreased during the subsequent 60 min after cessation of the

noise. CoBF did not change significantly during and 30 min

after noise but then paralleled the decline of perilymphatic

pO2. However, both parameters showed a clear indication of

recovery in the second and third hours after noise. At 101 dB

SPL, CMs were again reduced immediately, CAPs were

unaltered and ABRs again increased. Exposure to 106 and to

115 dB SPL resulted in a decrease in both perilymphatic pO2

and CoBF; this decrease began during the exposure but became

progressively worse after the noise. Hearing loss was

observed immediately with exposure and showed no signs of

further deterioration after cessation. The observed time

courses of changes are important. They reveal that hearing

loss and cochlear hypoxia precede reduction in CoBF due to

noise exposure. The potential mechanisms underlying these

effects are discussed.. 7782-44-7.

158. Lan, J.; Jiang, D. H. Excessive iron accumulation in the brain: a

possible potential risk of neurodegeneration in Parkinson's

disease. J-Neural-Transm. 1997; 104(6-7): 649-60; ISSN:

0300-9564.

AUSTRIA. In this study a chronic cerebral iron-loaded model

was established by feeding mice with high iron diet. Data

indicated that brain iron concentrations were significantly

increased in iron-fed mice compared with those of controls. A

significant increase in oxidized glutathione (GSSG), decrease

in total glutathione (oxidized and reduced glutathione, GSSG +

GSH), and therefore increase in the GSSG/(GSSG + GSH) ratios

were observed in iron-loaded mice. Hydroxyl radical (.OH)

levels in striatum and brainstem were also significantly

increased. Excessive iron alone did not change either dopamine

(DA) or lipid peroxidation (LPO) concentrations in striatum.

However, a single injection of 1-methyl-4-phenyl-1,2,3,6-

tetrahydropyridine (MPTP, 30 mg/kg, i.p.) into the iron-loaded

mice caused a great enhancement in all these biochemical

abnormalities. These findings suggest that iron does induce

oxidative stress, but not severely injury neurons per sc.

Excessive iron accumulation in the brain, however, is a

potential risk for neuronal damage, which may promote by

triggering factor(s). This supports the hypothesis that

excessive cerebral iron may contribute to the aetiology of

Parkinson's disease (PD).. 0; 27025-41-8; 28289-54-5; 3352-

57-6; 70-18-8; 7439-89-6.

159. Lasky, R. E. Rate and adaptation effects on the auditory evoked

brainstem response in human newborns and adults. Hear-Res.

1997 Sep; 111(1-2): 165-76; ISSN: 0378-5955.

NETHERLANDS. Auditory evoked brainstem response (ABR)

latencies increased and amplitudes decreased with increasing

stimulus repetition rate for human newborns and adults. The

wave V latency increases were larger for newborns than

adults. The wave V amplitude decreases were smaller for

newborns than adults. These differences could not be explained

by developmental differences in frequency responsivity. The

transition from the unadapted to the fully adapted response

was less rapid in newborns than adults at short (= 10 ms)

inter stimulus intervals (ISIs). At longer ISIs (= 20 ms) there

were no developmental differences in the transition to the

fully adapted response. The newborn transition occurred in a

two stage process. The rapid initial stage observed in adults

and newborns was complete by about 40 ms. A second slower

stage was observed only in newborns although it has been

observed in adults in other studies (Weatherby and Hecox,

1982; Lightfoot, 1991; Lasky et al., 1996). These effects were

replicated at different stimulus intensities. After the

termination of stimulation the return to the wave V unadapted

response took nearly 500 ms in newborns. Neither the newborn

nor the adult data can be explained by forward masking of one

click on the next click. These results indicate human

developmental differences in adaptation to repetitive auditory

stimulation at the level of the brainstem.

160. Launey, T.; Eustache, I.; Ferrand, N.; Gueritaud, J. P. Synaptic

inputs on rat brainstem motoneurones in organotypic slice

culture. Neuroreport. 1997 Oct 20; 8(15): 3287-91; ISSN:

0959-4965.

ENGLAND. To study the formation of target specific afferents

on brain stem motoneurones of the rat, we used an organotypic

co-culture of embryonic rat (E18) brain stem explants

containing the facial or hypoglossal motor nuclei together

with a tongue explant. The brain stem explants also contained

known dorsal premotor structures such as lateral reticular

nuclei and vestibular or spinal trigeminal nuclei. In cultures

maintained in vitro for over 3 weeks, silver impregnation

studies identified neurones in the dorsal sensory structures

with axons arborizing within the motor nucleus. A double

fluorescent labelling procedure demonstrated that axons

originating from dorsal sensory regions come in close contact

with identified motoneurones. Electrical stimulation of

neurones in the dorsal regions induced monosynaptic and

polysynaptic EPSPs and spikes in identified motoneurones

together with muscle contraction. This work demonstrates

that premotor structures in slice cultures develop organotypic

functional synaptic connections with embryonic brain stem

motoneurones.. 0.

161. Laurie, D. J.; Bartke, I.; Schoepfer, R.; Naujoks, K.; Seeburg, P. H.

Regional, developmental and interspecies expression of the

four NMDAR2 subunits, examined using monoclonal antibodies.

Brain-Res-Mol-Brain-Res. 1997 Nov; 51(1-2): 23-32; ISSN:

0169-328X.

NETHERLANDS. Mouse monoclonal antibodies were raised

against bacterially expressed protein sequences of the NR2A,

NR2B, NR2C and NR2D subunits of the rat NMDA receptor. From

immunoblots of rat brain proteins, the apparent molecular

weights of these subunits were 165, 170, 135 and 145 kDa,

respectively. Proteins of similar masses were observed on

immunoblots of specifically transfected HEK293 cells.

Deglycosylation with endoglycosidase F reduced the mass of

each endogenous NR2 subunit by approximately 10 kDa. In

distribution studies, NR2A-immunoreactive protein (IRP) was

located throughout the adult rat brain, NR2B-IRP was

primarily in the forebrain, NR2C-IRP was predominantly in the

cerebellum and NR2D-IRP was mainly found in the thalamus,

midbrain and brainstem. Whereas NR2A- and NR2C-IRPs

increased during rat brain post-natal development, NR2B- and

NR2D-IRPs were abundant at birth and declined with age,

especially in cerebellum. NR2-IRPs of mouse, rabbit, frog and

human brain were of sizes similar to those of the

corresponding rat subunits and were similarly distributed. In

summary, NR2 subunits are large glycoproteins whose specific

expression profiles in the brain are developmentally and

regionally regulated and which are similarly expressed in a

variety of species.. 0; 0; 0.

162. Le, K. T.; Villeneuve, P.; Ramjaun, A. R.; McPherson, P. S.; Beaudet,

A.; Seguela, P. Sensory presynaptic and widespread

somatodendritic immunolocalization of central ionotropic P2X

ATP receptors. Neuroscience. 1998 Mar; 83(1): 177-90; ISSN:

0306-4522.

UNITED-STATES. Recent evidence suggests that extracellular

ATP plays a neurotransmitter role in the central nervous

system. Its fast ionotropic effects are exerted through a

family of P2X ATP-gated channels expressed in brain and

spinal cord. To determine the physiological significance of

central ATP receptors, we have investigated the localization

of a major neuronal P2X receptor at the cellular and

subcellular levels using affinity-purified antibodies directed

against the C-terminal domain of P2X4 subunit. Subunit-

specific anti-P2X4 antibodies detected a single band of 57,000

+/- 3000 mol. wt in transfected HEK-293 cells and in

homogenates from adult rat brain. The strongest expression of

central P2X receptors was observed in the olfactory bulb,

lateral septum, cerebellum and spinal cord. P2X4

immunoreactivity was also evident in widespread areas

including the cerebral cortex, hippocampus, thalamus and

brainstem. In all regions examined, P2X receptors were

associated with perikarya and dendrites where they were

concentrated at the level of afferent synaptic junctions,

confirming a direct involvement of postsynaptic ATP-gated

channels in fast excitatory purinergic transmission. Moreover,

P2X4-containing purinoceptors were localized in axon

terminals in the olfactory bulb and in the substantia

gelatinosa of nucleus caudalis of the medulla and dorsal horn

of the spinal cord, demonstrating an important selective

presynaptic role of ATP in the modulation of neurotransmitter

release in central sensory systems.. 0; 0; 56-65-5.

163. Leighton, S. E.; Kay, R.; Leung, S. F.; Woo, J. K.; Van Hasselt, C. A.

Auditory brainstem responses after radiotherapy for

nasopharyngeal carcinoma. Clin-Otolaryngol. 1997 Aug; 22(4):

350-4; ISSN: 0307-7772.

ENGLAND. The effect of irradiation for nasopharyngeal

carcinoma on auditory brainstem responses and hearing was

investigated in 19 otologically normal patients undergoing

standard fractionated megavoltage radiotherapy. Auditory

brainstem responses and pure tone audiometry were performed

before radiotherapy, and at 3 and 12 months after completion

of radiotherapy. There were no significant changes in the wave

I-III and III-V interpeak intervals, or in sensorineural hearing

thresholds (bone conduction at 4 kHz and average of bone

conduction at 0.5, 1, 2 and 4 kHz), after radiotherapy. In

contrast to previous studies, we found no evoked potential

evidence of subclinical brainstem damage arising from

irradiation for nasopharyngeal carcinoma.

164. Lenkei, Z.; Palkovits, M.; Corvol, P.; Llorens Cortes, C. Expression

of angiotensin type-1 (AT1) and type-2 (AT2) receptor mRNAs

in the adult rat brain: a functional neuroanatomical review.

Front-Neuroendocrinol. 1997 Oct; 18(4): 383-439; ISSN: 0091-

3022.

UNITED-STATES. The discovery that all components of the

renin-angiotensin system (RAS) are present in the central

nervous system led investigators to postulate the existence of

a local brain RAS. Supporting this, angiotensin immunoreactive

neurons have been visualized in the brain. Two major pathways

were described: a forebrain pathway which connects

circumventricular organs to the median preoptic nucleus,

paraventricular nucleus, and supraoptic nucleus, and a second

pathway connecting the hypothalamus to the medulla

oblongata. Blood-brain barrier deficient circumventricular

organs are rich in angiotensin II receptors. By activating these

receptors, circulating angiotensin II may act on central

cardiovascular centers via angiotensinergic neurons, providing

a link between peripheral and central angiotensin II systems.

Among the effector peptides of the brain RAS, angiotensin II

and angiotensin III have the same affinity for the two

pharmacologically well-defined receptors: type 1 (AT1) and

type 2 (AT2). When injected in the brain, these peptides

increase blood pressure, water intake, and anterior and

posterior pituitary hormone release and may modify memory

and learning. The cloning of AT1 and AT2 receptor cDNAs has

revealed that these receptors belong to the seven

transmembrane domain receptor family. In rodents, two AT1

receptor subtypes, AT1A and AT1B, have been isolated. Using

specific riboprobes for in situ hybridization histochemistry,

recent studies mapped the distribution of AT1A, AT1B, and

AT2 receptor mRNAs in the adult rat and found a predominant

expression of AT1A and AT2 mRNA in the brain and of AT1B in

the pituitary. Very limited overlap was found between the

brain expression of AT1A and AT2 mRNAs. In several

functional entities of the brain, such as the preoptic region,

the hypothalamus, the olivocerebellary system, and the

brainstem baroreflex arc, the colocalization of receptor mRNA,

binding sites, and angiotensin immunoreactive nerve terminals

suggests local synthesis and expression of angiotensin II

receptors. In other areas, such as the bed nucleus of the stria

terminalis, the median eminence, or certain parts of the

nucleus of the solitary tract, angiotensin II receptors are

likely of extrinsic origin. The neuronal expression of AT1A and

AT2 receptors was demonstrated in the subfornical organ, the

hypothalamus, and the lateral septum. By using double label in

situ hybridization, AT1A receptor expression was localized in

corticotropin releasing hormone but not in vasopressin

containing neurons in the hypothalamus. The information is

discussed together with functional data concerning the role of

brain angiotensins, in an attempt to provide a better

understanding of the physiological and functional roles of each

receptor subtype.. 0; 0; 11128-99-7; 9041-90-1.

165. Leon, S. FE; Arimura, K.; Osame, M. Multiple sclerosis and HTLV-I

associated myelopathy/tropical spastic paraparesis are two

distinct clinical entities. Mult-Scler. 1996 Sep; 2(2): 88-90;

ISSN: 1352-4585.

ENGLAND. Multiple sclerosis (MS) and HTLV-I associated

myelopathy/tropical spastic paraparesis (HAM/TSP) can

overlap in their clinical features and thereby cause

difficulties for clinicians in relation to diagnosis and therapy.

However, epidemiological biochemical, immunological,

virological and radiological studies point to a number of

significant differences. Recent comparative

neurophysiological data, including blink reflex studies,

obtained in these disorders, is briefly reviewed here and

provides additional evidence of difference. The abnormal blink

reflex in patients with MS consist of prolonged latencies and

absences of R1 and R2 responses and are mainly due to

demyelinating lesions around the pans. In contrast, in HAM/TSP

the blink reflex abnormalities frequently include an unusual

early response, R1k, which is probably a consequence of

interneuronal hyperexcitability around the brainstem. Thus

these findings provide further support for our contention that

HAM/TSP and multiple sclerosis are distinctly different both

as clinical entities and in their underlying pathomechanisms.

166. Lesinski, A.; Littmann, X.; Battmer, R. D.; Lenarz, T. Comparison of

preoperative electrostimulation data using an ear-canal

electrode and a promontory needle electrode. Am-J-Otol. 1997

Nov; 18(6 Suppl): S88-9; ISSN: 0192-9763.

UNITED-STATES. OBJECTIVE: To compare the electrical

stimulation results of the ear-canal electrode with those of a

promontory needle. PATIENTS AND METHODS: In thirty-three

adult patients, the ear-canal electrode test was compared

with the needle electrode promontory test with respect to

sound perception, rhythm detection, frequency, and disturbing

side effects. RESULTS: The ear-canal electrode test, in

comparison with the needle electrode promontory test,

resulted in vibrotactile sensation in addition to auditory

sensation in some patients, less auditory fatigue, higher

threshold levels, and lower discomfort levels. CONCLUSION:

Reliable assessment of deafness in children requires, in

addition to electrical stimulation, determination of the

electrical evoked auditory brainstem response with the

patient under anesthesia.

167. Lesperance, M. M.; Grundfast, K. M.; Rosenbaum, K. N. Otologic

manifestations of Wolf-Hirschhorn syndrome. Arch-

Otolaryngol-Head-Neck-Surg. 1998 Feb; 124(2): 193-6; ISSN:

0886-4470.

UNITED-STATES. OBJECTIVE: To determine if

haploinsufficiency for chromosome 4p16.3 in Wolf-Hirschhorn

syndrome (WHS) is associated with cochlear hearing loss.

DESIGN: Case series. SETTING: Tertiary care center. PATIENTS:

Six patients with WHS were identified through a database and

charts were retrospectively reviewed. MAIN OUTCOME

MEASURES: Presence of sensorineural hearing loss as assessed

by brainstem auditory evoked response. RESULTS: One of the 6

patients had sensorineural hearing loss. Three of the 6

patients had chronic otitis media with effusion and underwent

bilateral tympanostomy tube placement; 2 of these 3 had cleft

lip and palate, and 1 had a bifid uvula. One of the 6 patients

had spontaneous nystagmus. Five of the 6 patients had

preauricular and/or auricular abnormalities. CONCLUSIONS:

More than 25 genes for nonsyndromic hereditary hearing

impairment have been mapped. One of these genes, DFNA6, was

identified through linkage analysis of a family with dominant,

progressive, low-frequency sensorineural hearing loss. DFNA6

maps to chromosome 4p16.3, a region that is partially deleted

in patients with WHS. In our series, we identified the second

patient with WHS in the literature with bilateral

sensorineural hearing loss. The incidence and type of otologic

findings are consistent with those reported in the literature.

Analysis of patients with chromosomal rearrangements

represents one strategy toward identifying candidate genes

for genetic hearing impairment.

168. Li, H.; Mizuno, N. Single neurons in the spinal trigeminal and

dorsal column nuclei project to both the cochlear nucleus and

the inferior colliculus by way of axon collaterals: a

fluorescent retrograde double-labeling study in the rat.

Neurosci-Res. 1997 Oct; 29(2): 135-42; ISSN: 0168-0102.

IRELAND. A number of single neurons in the spinal trigeminal

nucleus (STN) and the dorsal column nucleus (DCN) were found

to project simultaneously to the cochlear nucleus (CoN) and

the external cortex of the inferior colliculus (ICe) by way of

axon collaterals. Each rat was injected with Fluoro-Gold (FG)

into CoN on one side and with tetramethylrhodamine-dextran

amine (TMR-DA) into ICe on the side ipsilateral or

contralateral to the FG injection. In these rats, a number of

neuronal cell bodies in DCN and the interpolar and caudal

subnuclei of STN were double-labeled retrogradely with both

FG and TMR-DA, mainly on the side ipsilateral to the FG

injection into CoN. These neurons in STN and DCN might

mediate somatosensory inputs simultaneously to the two

lower brainstem nuclei, CoN and ICe, which constitute the

relays of the auditory pathway.. 0; 0; 0; 82785-14-6; 9004-

54-0.

169. Liao, J.; Lai, H.; Lu, D. [Applied anatomical study of the lingual

nerve]. Chung-Hua-Kou-Chiang-Hsueh-Tsa-Chih. 1996 Mar;

31(2): 101-3; ISSN: 1002-0098.

CHINA. The lingual nerve and its adjacent structures were

observed and measured on 32 adult cadavours. Its length was

69.7 mm and it was divided, bounded by the internal pterygoid

muscle, into three segments and the length and diameter of

them were respectively measured. According to its

relationship with the lingual nerve, the submandibular

ganglion can be classified into fusion type (being 46.9%) and

free type (being 53.1%), and its superoinferior and

transeversal diameters were separately measured to be 2.7

and 2.9 mm. The lingual nerve and its lingual branches were

closely related to submandibular duct and there were two

intersects. The relation and clinical significance of the third

segment of lingual nerve and its neighbor structures were

studied.

170. Lin, C. M.; Hsu, J. C.; Wu, R. S.; Wu, K. C.; Yu, C. L.; Wu, H. F.; Tan, P.

P. Evoked facial nerve EMG and brainstem auditory evoked

potential monitoring in cerebellopontine angle tumor

resection. Acta-Anaesthesiol-Sin. 1997 Sep; 35(3): 141-7.

TAIWAN. BACKGROUND: The preservation of normal nerve

function or identification of nerve route is critical in some

surgeries of cerebellopontine angle tumors. Over the last 5

years, intraoperative facial nerve electromyogram (EMG) and

brainstem auditory evoked potential (BAEP) were applied for

evaluation of facial nerve integrity and brainstem function in

patients while undergoing resection of cerebellopontine angle

(CPA) tumor. This report represents the retrospective analysis

of our results. METHODS: The inhalational anesthesia with 1-

1.5% isoflurane in pure O2 was used. Muscle relaxation was

maintained with continuous infusion of atracurium. The degree

of muscle relaxation was aimed at a T4/T1 ratio of train-of-

four response more than 20% of the adductus pollicis upon

ulnar nerve stimulation at the wrist. In 236 patients suffering

from CPA tumor without facial palsy, the EMG of the mentalis

muscle ipisilateral to the tumor was obtained through

stimulation of the facial nerve. The stimulation was applied

with a nerve finder, which delivered an electrical stimulation

of a single 2 mamp direct current. The EMG finding was

compared with the clinical result. In 198 patients, BAEP was

used to monitor the brainstem function during tumor resection.

In case of intact hearing the BAEP was taken ipsilateral to the

operation side and in case with total hearing loss

contralateral BAEP to operation side was used. For BAEP

stimulation, 90 db click sound stimulation with frequency of

11.26 Hz was applied to both ears. BAEP signals were obtained

and recorded at the mastoid region of either side in reference

to the vertex. The EMG and BAEP signals were recorded and

saved to an evoked potential monitor. RESULTS: In facial nerve

EMG monitoring, there were two false positive and no false

negative tests. Except for the two false positive tests, the

postoperative clinical results in the other cases were

compatible with the intraoperative facial nerve EMG findings.

In BAEP monitoring, there were twenty-eight positive tests.

CONCLUSIONS: The low incidence of false negative test

suggests that facial nerve EMG is valuable in detection of

facial nerve function in CPA tumor resection. Intraoperative

BAEP abnormality is possibly useful in identifying

postoperative brainstem dysfunction.

171. Lin, H. H.; Wu, S. Y.; Lai, C. C.; Dun, N. J. GABA- and glycine-

mediated inhibitory postsynaptic potentials in neonatal rat

rostral ventrolateral medulla neurons in vitro. Neuroscience.

1998 Jan; 82(2): 429-42; ISSN: 0306-4522.

UNITED-STATES. Whole-cell patch recordings were made from

rostral ventrolateral medulla neurons of two in vitro

preparations: (i) brainstem spinal cords of two- to five-day-

old rats, and (ii) coronal brainstem slices of eight- to 12-day-

old rats, and the inhibitory synaptic activities in these

neurons have been studied. In brainstem spinal cord

preparations, Lucifer Yellow was diffused into the recording

neurons at the end of experiments. Medullary neurons were

characterized as: (i) spinally projecting by the appearance of

an antidromic spike following electrical stimulation of the

spinal tract between T2 and T3 segments, and (ii) adrenergic

by the detection of phenylethanolamine-N-methyltransferase

immunoreactivity in Lucifer Yellow-filled neurons. Of the 13

spinally projecting and phenylethanolamine-N-

methyltransferase-positive medullary neurons, focal

stimulation elicited in the presence of glutamate receptor

antagonists an inhibitory postsynaptic potential in nine

neurons. Inhibitory synaptic potentials were reversibly

eliminated by the GABA(A) receptor antagonist bicuculline

(10-20 microM) in six of nine neurons, by the glycine receptor

antagonist strychnine (0.1-1 microM) in two and by a

combination of bicuculline and strychnine in one neuron. In

brainstem slice preparations, focal stimulation elicited three

types of synaptic potential: (i) an excitatory postsynaptic

potential, (ii) an inhibitory postsynaptic potential and (iii) a

biphasic synaptic potential consisting of an excitatory

synaptic potential followed by an inhibitory synaptic

potential. Inhibitory synaptic potentials had a reversal

potential between -70 and -80 mV, reversed their polarity in a

low (6.7 mM) Cl- Krebs' solution, and suppressed or blocked by

either bicuculline or strychnine or both. Elimination of

inhibitory synaptic potentials unmasked in some cells an

excitatory synaptic potential or enhanced the excitatory

synaptic potential component in medullary neurons with a

biphasic response, indicating a marked convergence of

excitatory and inhibitory inputs onto a single neuron. A

population of medullary neurons appeared to be pacemaker

neurons whereby they discharged spontaneously. When

discharges were suppressed by membrane hyperpolarization,

focal stimulation elicited inhibitory synaptic potentials in

8/23 neurons tested. Our results suggest that inhibitory

synaptic potentials in medullary neurons are mediated by

either GABA and/or glycine which open primarily Cl- channels.

The prevalence of inhibitory synaptic potentials in medullary

neurons indicates an essential role of inhibitory transmission

in controlling the input and output ratio of these neurons.. 0;

0; 485-49-4; 56-12-2; 56-40-6; 57-24-9.

172. Linker, S. P.; Ruckenstein, M. J.; Acker, J.; Gardner, G. An accurate,

cost-effective approach for diagnosing retrocochlear lesions

utilizing the T2-weighted, fast-spin echo magnetic resonance

imaging scan. Laryngoscope. 1997 Nov; 107(11 Pt 1): 1525-9;

ISSN: 0023-852X.

UNITED-STATES. Recent data indicate that the auditory

brainstem response (ABR) fails to identify a significant

number of retrocochlear lesions. Although the magnetic

resonance imaging (MRI) scan with paramagnetic enhancement

is highly accurate at detecting these lesions, it is time

consuming and expensive. We report on our prospective

evaluation of a cohort of 155 patients who underwent T2-

weighted, fast-spin echo MRI scans designed to screen for

retrocochlear lesions. This imaging technique is rapidly

performed and provides superb visualization of the relevant

anatomic structures at a global cost of $475. Four tumors

were identified with this technique. Cost analysis indicates

that supplanting ABR with this limited MRI may well represent

a cost-effective approach for evaluating patients with

suspected retrocochlear lesions.

173. Liss, A. G.; Wiberg, M. Loss of primary afferent nerve terminals in

the brainstem after peripheral nerve transection: an

anatomical study in monkeys. Anat-Embryol-Berl. 1997 Oct;

196(4): 279-89; ISSN: 0340-2061.

GERMANY. In order to investigate the changes in the

somatosensory organization that occur after a peripheral

nerve injury, a purely sensory nerve (radial nerve - superficial

branch) was divided in adult monkeys (Macaca fascicularis).

The nerve ends were immediately rejoined by an epineural

suturing technique. After 6-21 months the nerve investigated

was exposed to an intra-axonal nerve tracer (horseradish

peroxidase conjugate) in order to label the primary afferent

terminals within the cuneate nucleus of the brainstem. The

non-transected nerve on the contralateral side was similarly

exposed and served as a control. Terminal labelling was seen

throughout the cuneate nucleus, mainly in the middle of its

rostro-caudal extension, and in this part it showed a patchy

appearance superimposed on cell clusters within the pars

rotunda. This pattern of distribution was seen both on the

experimental and control sides. On the experimental side there

was an obvious loss of terminal labelling within the terminal

field as estimated using an image-analysing system: Compared

with the contralateral side the median loss (peroxidase

activity) was 83% and between 6 and 21 months only minor

restoration of the terminal intensity was observed. These

results in the primate confirm earlier results in the cat that

transection and microsurgical repair of a sensory nerve causes

a considerable loss of neurons capable of intraaxonal

transport.. EC 1.11.1.-.

174. Liu, J.; Merlie, J. P.; Todd, R. D.; O'Malley, K. L. Identification of

cell type-specific promoter elements associated with the rat

tyrosine hydroxylase gene using transgenic founder analysis.

Brain-Res-Mol-Brain-Res. 1997 Oct 15; 50(1-2): 33-42; ISSN:

0169-328X.

NETHERLANDS. Transcriptional regulatory elements capable of

directing transgene expression to individual cells are powerful

tools for manipulating a given CNS circuit. Delineating these

elements via traditional transgenic analysis is both costly and

labor intensive. Here we have used the rat tyrosine

hydroxylase (TH) promoter as a model to describe and validate

the use of founder animals for systematic promoter studies.

No significant differences were found when data obtained from

founder animals expressing a 6.0 kb TH promoter directing

LacZ were compared with animals derived from an analogous

transgenic line. Subsequent studies with founder animals

expressing beta-galactosidase directed by various lengths of

rat TH promoter revealed different patterns of expression.

Specifically, a locus coeruleus regulatory domain was

localized between 3.4 and 6.0 kb of the rat TH promoter, a

hypothalamic regulatory domain between 2.5 and 3.4 kb and a

brainstem regulatory domain between 0.8 and 6.0 kb. At least

one element of a midbrain specific regulatory domain was

within 2.5 kb of the transcriptional start site. Olfactory bulb

specific elements however appeared to reside outside of the

sequences tested. Specific patterns of ectopic gene expression

were also observed suggesting the presence of negative

regulatory elements. Thus, TH appears to be regulated in a

complex modular fashion by both positive and negative

regulatory elements. Taken together, this study demonstrates

the feasibility and reliability of founder analysis for promoter

studies of genes expressed in complex spatial and temporal

patterns.. EC 1.14.16.2; 51-61-6.

175. Liu, M.; Wu, J.; Wang, W. [Immunohistochemical study on morphine

in human tissues from opiate associated death]. Hua-Hsi-I-Ko-

Ta-Hsueh-Hsueh-Pao. 1996 Jun; 27(2): 151-4; ISSN: 0257-

7712.

CHINA. The morphine distribution in human tissues was

studied by immunohistochemical method. Four cases of opiate

associated death were examined. Morphine was demonstrated

not only in some neuronal cytoplasma of cerebral cortex,

hippocampus, basal ganglia thalamus, brainstem, and

cerebellum, but also found in some nervous fibers and some

capillary walls in the central nervous system. Besides, it was

also found in the capsule and mesenchyma of heart, liver,

spleen, lung, kidney, adrenal gland, pancreas, thymus,

thyroidea and testis. Morphine was not seen in the parenchyma

of these organs. It was suggested that the postmortem

redistribution was not in the central nervous system, but in

other organs. We considered that immunohistochemical

staining of morphine is useful in the diagnosis of death from

opiate addiction.. 57-27-2.

176. Liu, X.; McPhee, G.; Seldon, H. L.; Clark, G. M. Histological and

physiological effects of the central auditory prosthesis:

surface versus penetrating electrodes. Hear-Res. 1997 Dec;

114(1-2): 264-74; ISSN: 0378-5955.

NETHERLANDS. To rehabilitate profoundly deaf patients who

are not suitable for cochlear implants, central auditory

prostheses have been implanted. To compare two possible

electrode configurations - penetrating and surface ones -

electrical stimulation of the cochlear nucleus with both types

of arrays was tested on guinea pigs and cats.

Electrophysiological, autoradiographic and histological

measures were used to study effects of the central auditory

prostheses on the auditory pathway. The results showed that a

successful electrically evoked auditory brainstem response

could be recorded with both surface and penetrating electrodes

in cats and guinea pigs. In guinea pigs the penetrating

electrodes had advantages over surface arrays in the sense of

lower thresholds and wider dynamic ranges. In cats

penetrating electrodes showed lower thresholds than surface

ones. In cats and guinea pigs stimulated with either surface or

penetrating electrodes, evoked 2-deoxyglucose (2-DG) label

was found in the auditory pathway from the cochlear nucleus

to the inferior colliculus. No non-auditory tissues were found

with evoked 2-DG label. Histological results showed that in

subdivisions of the guinea pig cochlear nucleus stimulated

with penetrating electrodes the neurone density was

decreased, and the mean soma area was increased compared

with the control side. In the cat, penetrating electrodes were

associated only with increased mean soma area in parts of the

stimulated cochlear nucleus. These results suggest that the

physiological advantages of penetrating electrodes over

surface ones were achieved with some trade-off in safety,

especially in the guinea pig.. 154-17-6.

177. Lossos, A.; Schlesinger, I.; Okon, E.; Abramsky, O.; Bargal, R.;

Vanier, M. T.; Zeigler, M. Adult-onset Niemann-Pick type C

disease. Clinical, biochemical, and genetic study. Arch-Neurol.

1997 Dec; 54(12): 1536-41; ISSN: 0003-9942.

UNITED-STATES. BACKGROUND: Niemann-Pick type C disease is

an autosomal recessive neurometabolic disorder of unknown

origin mapped to chromosome 18q11-12 in most of the studied

families. In contrast to the sphingomyelin lipidoses, in

Niemann-Pick type C disease, fibroblasts are impaired in

intracellular homeostatic responses to exogenous low-density

lipoprotein (LDL) cholesterol. Biochemical heterogeneity of the

disorder in relation to abnormal LDL processing is associated

with various clinical presentations, but adult-onset Niemann-

Pick type C disease is rare and has not been comprehensively

characterized. OBJECTIVE: To describe clinical, biochemical,

and genetic features of adult-onset Niemann-Pick type C

disease in 3 siblings. DESIGN AND SETTING: Case series in a

tertiary care center. PATIENTS: The 3 siblings manifested a

variable combination of vertical supranuclear

ophthalmoplegia, ataxia, and splenomegaly. Brain magnetic

resonance imaging showed cerebellar atrophy; brainstem

auditory evoked responses were unobtainable, and bone marrow

examination disclosed typical foam cells. The patients were

20, 26, and 28 years old and belonged to a sibship of 13 born of

consanguineous healthy parents. METHODS: Esterification of

exogenous LDL cholesterol in cultured skin fibroblasts and

filipin staining for free intracellular cholesterol. Polymerase

chain reaction-based DNA linkage study using AC

microsatellite markers D18S40, D18S44, D18S480, and

D18S66. RESULTS: Fibroblasts of the 3 patients showed a 23%

to 58% block in the induced cholesterol esterification after 4

1/2 hours and a mild to moderate accumulation of free

cholesterol. DNA study demonstrated linkage to the major

18q11-12 Niemann-Pick type C locus and identified unaffected

carriers. CONCLUSIONS: These results confirm the diagnosis of

the least biochemically affected Niemann-Pick type C

phenotype in this family with adult-onset disease and support

a correlation between the mild laboratory and clinical findings

in this age group.. 0; 9007-49-2.

178. Lozza, A.; Pepin, J. L.; Rapisarda, G.; Moglia, A.; Delwaide, P. J.

Functional changes of brainstem reflexes in Parkinson's

disease. Conditioning of the blink reflex R2 component by

paired and index finger stimulation. J-Neural-Transm. 1997;

104(6-7): 679-87; ISSN: 0300-9564.

AUSTRIA. Recovery curves of the R2 component of the blink

reflex have been studied in 10 control subjects and 13

parkinsonian patients both after ipsilateral paired stimulation

of the supraorbital nerve and after index finger stimulation. In

control subjects, both types of conditioning induced a

comparable marked inhibition lasting more than 600 ms. In

parkinsonian patients, inhibition was reduced after both

conditionings. However, differences appeared in the magnitude

of the changes: after paired stimulation, it was less

significant (ANOVA and post-hoc Duncan's test: p = 0.04) than

after index finger stimulation (p = 0.002). In that latter

situation, the more marked reduction in inhibition is

interpreted, in the light of current physiologic knowledge, by

hypoactivity of the Nucleus Reticularis Giganto Cellularis

(NRGC) which would make less efficient inhibitory

interneurones in the trigemino-facial pathway. The results are

thus compatible with the suggestion that NRGC is made

indirectly less active in Parkinson's disease.

179. Lu, W.; Zhang, M.; Neuman, R. S.; Bieger, D. Fictive oesophageal

peristalsis evoked by activation of muscarinic acetylcholine

receptors in rat nucleus tractus solitarii. Neurogastroenterol-

Motil. 1997 Dec; 9(4): 247-56; ISSN: 1350-1925.

ENGLAND. The aim of the present study was to determine if

muscarinic acetylcholine receptor-mediated peristaltic

rhythmogenesis in the rat oesophagus is a central motor

program that can be generated without peripheral sensory

support. In anaesthetized male Sprague-Dawley rats, pressure-

ejection of glutamate (10-20 pmol) and muscarine (5-10 pmol)

in the sub-nucleus centralis of the nucleus tractus solitarii

(NTSC) evoked monophasic pressure waves and rhythmic

oesophageal peristalsis, respectively, but did not change mean

arterial blood pressure or respiration. Application of

muscarine (50-100 pmol) to the NTS extraventricular surface

evoked rhythmic multi-unit burst discharges in the compact

formation of the nucleus ambiguus (AMBC) that led to

oesophageal peristalsis in a phase-locked manner. Evoked

rhythmic AMBC activity persisted during neuromuscular

blockade with curare, although the peak frequency of

individual bursts was decreased. In a brainstem slice

preparation, intracellular and whole cell patch recordings

from AMBC neurones during focal stimulation of the NTSC

region with muscarine revealed rhythmic depolarizing waves

that showed a pattern similar to that of rhythmic oesophageal

peristalsis. The present findings support the concept that

medullary circuits comprising premotor neurones of the NTSC

are intrinsically capable of generating rhythmic

oesophagomotor output, but are subject to a powerful

modulation by peripheral sensory feedback.. 0; 300-54-9; 56-

86-0; 57-95-4; 7447-40-7.

180. Luckman, S. M. Comparison of the expression of c-fos, nur77 and

egr1 mRNAs in rat hypothalamic magnocellular neurons and

their putative afferent projection neurons: cell- and stimulus-

specific induction. Eur-J-Neurosci. 1997 Nov; 9(11): 2443-51;

ISSN: 0953-816X.

ENGLAND. Hypothalamic magnocellular neurons and their

afferent inputs provide a model system in which to study the

regulation of inducible transcription factors in the brain in

vivo. Osmotic stimulation of rats produced by graded infusions

of saline at different tonicities was found to lead to the

induction of c-fos, nur77 and egr1 mRNAs in magnocellular

neurons, as well as in putative afferent neurons, including

those in structures of the forebrain (subfornical organ, median

preoptic nucleus and organum vasculosum of the lamina

terminalis). The results presented suggest that stronger levels

of osmotic stimulation recruit additional afferents from the

forebrain and brainstem that can act on magnocellular neurons

via alternative receptors. A single systemic injection of the

peptide cholecystokinin produced robust induction of c-fos and

nur77 mRNAs in afferent neurons of the brainstem nucleus

tractus solitarii and in magnocellular neurons. Despite the

fact that these two neuronal populations are clearly

electrically active, egr1 was not induced by this stimulus,

providing examples of cell- and stimulus-specificity of its

expression. This study re-emphasizes that the induction of

transcription factors is largely dependent on the nature of the

afferent input and does not correlate necessarily to the

electrical activity of the neuron.. 0; 0; 0; 0; 0; 0; 0; 121479-

42-3; 9011-97-6.

181. Luscher, B.; Hauselmann, R.; Leitgeb, S.; Rulicke, T.; Fritschy, J. M.

Neuronal subtype-specific expression directed by the GABA(A)

receptor delta subunit gene promoter/upstream region in

transgenic mice and in cultured cells. Brain-Res-Mol-Brain-

Res. 1997 Nov; 51(1-2): 197-211; ISSN: 0169-328X.

NETHERLANDS. The promoter of the GABA(A) receptor delta

subunit gene was analyzed in transgenic mice and in cultured

cells to study sequences involved in neuronal subtype-specific

gene expression. A 6.4-kb genomic fragment faithfully

directed neuron-specific transcription of a lacZ reporter gene

in the central nervous system. The transgene expression

pattern in the cerebral cortex, hippocampal formation,

thalamus, and brainstem was consistent with the regional and

neuronal subtype-specific expression of the endogenous delta

subunit protein in both developing and mature brain. In the

cerebellum, however, the transgene was ectopically expressed

in Purkinje cells and silent in granule cells, where the

endogenous delta subunit is abundantly expressed. These mice

provide a useful tool for investigating activity-dependent

regulation of GABA(A) receptor expression under physiological

and pathological conditions. Transfection studies using

primary cortical neurons and astroglial cells revealed that the

delta subunit gene promoter was selectively active in neurons

even when truncated to a 267-bp core fragment. In conclusion,

the delta subunit gene promoter/upstream region contains the

information for neuronal subtype-specific expression in the

entire brain except in the cerebellum and is selectively active

in primary cortical neurons in vitro.. 0; 0.

182. Maeoka, Y.; Yamamoto, T.; Ohtani, K.; Takeshita, K. Pontine

hypoplasia in a child with sensorineural deafness. Brain-Dev.

1997 Sep; 19(6): 436-9; ISSN: 0387-7604.

NETHERLANDS. A 2-year-old girl with bilateral sensorineural

deafness showed pontine hypoplasia as well as a bulging

contour of the pontine tegmentum on magnetic resonance

imaging (MRI). There were no bilateral responses of brainstem

auditory-evoked potentials (BAEPs). The absent late

components of blink reflex (BR) indicated brainstem

dysfunction. Chromosomal abnormalities and

neurodegenerative or neurometabolic disorders, which might

have been the cause of the pontine hypoplasia, were ruled out.

The authors describe a rare case with pontine hypoplasia

combined with sensorineural deafness and absent blink reflex

and suggest that the brainstem in this child may become

involved in the early gestation period.

183. Maier, S. E.; Chen, W. J.; Miller, J. A.; West, J. R. Fetal alcohol

exposure and temporal vulnerability regional differences in

alcohol-induced microencephaly as a function of the timing of

binge-like alcohol exposure during rat brain development.

Alcohol-Clin-Exp-Res. 1997 Nov; 21(8): 1418-28; ISSN: 0145-

6008.

UNITED-STATES. In humans, microcephaly (small head for body

size) is a common feature of fetal alcohol syndrome. An

analogous measure, termed microencephaly (small brain for

body size), can be used for evaluating the detrimental effects

of the differential timing of alcohol exposure on brain

development in animal model systems. Timed-pregnant rats

were exposed to binge-like alcohol during either the first 10

days (first trimester equivalent) or second 10 days of

gestation (second trimester equivalent), or the combination of

first and second trimesters equivalent for prenatal

treatments. Offspring from some of the animals exposed to

alcohol during the combined first and second trimesters

equivalent were raised artificially from postnatal day (P) 4

through P9 (part of the third trimester equivalent), and also

received binge-like alcohol during this period, producing

animals that were exposed to alcohol during all three

trimesters equivalent. Offspring from untreated dams were

also raised artificially and received alcohol only from P4 to

P9, thus creating animals that were exposed to alcohol only

during part of the third trimester equivalent. All pups were

perfused on P10. Appropriate controls (nutritional and

normally reared) were used for every alcohol treatment

combination. Peak blood alcohol concentrations were not

different among the treatment groups for a given sampling

time. Significant somatic growth deficits occurred in

offspring exposed to alcohol for the equivalent of all three

trimesters, compared with offspring exposed to alcohol during

other periods. Brain growth in offspring also was significantly

affected by the timing of alcohol exposure. The whole brain,

forebrain, and cerebellum to body weight ratios of pups

exposed to alcohol during the third trimester had more

significant brain growth deficits than pups in groups exposed

to alcohol during other times of brain development. Although

alcohol exposure during the third trimester had a significant

detrimental impact on overall brain growth, significant

differences in temporal vulnerability were also found for the

brainstem to body weight ratios. Offspring of dams exposed to

alcohol during the first trimester had the same magnitude of

deficit as those exposed to alcohol during the third trimester,

and those two groups were significantly deficient compared

with the groups exposed to alcohol at other times, suggesting

some differential vulnerability of this region to alcohol-

induced injury at different times of development. This study is

the first thorough examination of microencephaly and gross

regional vulnerability of the developing brain as related to

temporal factors of alcohol exposure in an animal model

system, and the results support and expand on the findings of

the available clinical literature. Furthermore, our results

substantiate claims that the cessation of alcohol before the

third trimester can lessen the severity of some alcohol-

related birth deficits.. 64-17-5.

184. Maloney, S. R.; Bastings, E. P.; Blair, D.; Quinlevan, L.; Good, D. C.

The course of cortico-hypoglossal projections in the human

brainstem: functional testing using transcranial magnetic

stimulation [letter]. Brain. 1997 Oct; 120( Pt 10): 1910-1;

discussion 1911-4; ISSN: 0006-8950.

ENGLAND.

185. Manfredi, M.; Beltramello, A.; Bongiovanni, L. G.; Polo, A.; Pistoia,

L.; Rizzuto, N. Eclamptic encephalopathy: imaging and

pathogenetic considerations. Acta-Neurol-Scand. 1997 Nov;

96(5): 277-82; ISSN: 0001-6314.

DENMARK. Eclampsia is a rare condition peculiar to pregnant

and puerperal women, characterized by clinical pre-eclampsia

(hypertension, proteinuria, edema) and generalized seizures.

Three cases of eclamptic encephalopathy are reported: CT and

MRI demonstrated transient abnormalities in the cortical and

subcortical regions of the posterior areas of the brain -

namely, parieto-occipital lobes - associated with occasional

involvement of basal ganglia and/or brainstem. Pathogenesis

is still unclear. Strict similarity with the pathological

findings characterizing hypertensive encephalopathy suggests

that a focal impairment in cerebral autoregulation may be the

cause of vasodilation and fluid extravasation leading to

hydrostatic edema; selective involvement of posterior areas

could be explained by their lesser degree of adrenergic

innervation supporting circulatory autoregulation mechanisms.

186. Manley, N. R.; Capecchi, M. R. Hox group 3 paralogous genes act

synergistically in the formation of somitic and neural crest-

derived structures. Dev-Biol. 1997 Dec 15; 192(2): 274-88;

ISSN: 0012-1606.

UNITED-STATES. Hox genes encode transcription factors that

are used to regionalize the mammalian embryo. Analysis of

mice carrying targeted mutations in individual and multiple

Hox genes is beginning to reveal a complex network of

interactions among these closely related genes which is

responsible for directing the formation of spatially restricted

tissues and structures. In this report we present an analysis

of the genetic interactions between all members of the third

paralogous group, Hoxa3, Hoxb3, and Hoxd3. Previous analysis

has shown that although mice homozygous for loss-of-function

mutations in either Hoxa3 or Hoxd3 have no defects in common,

mice mutant for both genes demonstrate that these two genes

strongly interact in a dosage-dependent manner. To complete

the analysis of this paralogous gene family, mice with a

targeted disruption of the Hoxb3 gene were generated.

Homozygous mutants have minor defects at low penetrance in

the formation of both the cervical vertebrae and the IXth

cranial nerve. Analysis and comparison of all double-mutant

combinations demonstrate that all three members of this

paralogous group interact synergistically to affect the

development of both neuronal and mesenchymal neural crest-

derived structures, as well as somitic mesoderm-derived

structures. Surprisingly, with respect to the formation of the

cervical vertebrae, mice doubly mutant for Hoxa3 and Hoxd3 or

Hoxb3 and Hoxd3 show an indistinguishable defect, loss of the

entire atlas. This suggests that the identity of the specific

Hox genes that are functional in a given region may not be as

critical as the total number of Hox genes operating in that

region.. 0; 0; 0; 0.

187. Manquillo, A.; Martinez Mena, J.; Quintana, P.; Paradinas, F.; Saez,

J.; Revilla, C.; Galan, J. M. [Neurophysiological aspects of

Proteus syndrome]. Aspectos neurofisiologicos en el sindrome

de Proteus. Rev-Neurol. 1997 Oct; 25(146): 1572-4; ISSN:

0210-0010.

SPAIN. INTRODUCTION: The Proteus Syndrome was defined in

1983 by Wiedeman. However, the first case mentioned in the

literature was that of Joseph Merrick, the Elephant Man,

presented by Sir Frederick Treves in 1884. It is a rare

pathological condition. Its multiple clinical features include;

partial gigantism of hands and/or feet, pigmented nevi,

hemihypertrophy of the body, tumors, skeletal anomalies,

growth disorders and visceral anomalies. Hereditary

transmission has not been clearly defined. Diagnosis and

treatment require the participation of experts from several

medical and surgical specialties. CLINICAL CASE: We present a

case sent to our hospital for the surgical correction of cranio-

facial malformations. Epileptic crises post-operatively

indicated the need for neurological and neuro-physiological

study. This was done by means of conventional electro-

encephalography: brainstem, somato-sensorial and visual

auditory evoked potentials, together with imaging techniques

which showed the structural and functional asymmetry of the

central nervous system at both cerebral and brainstem levels.

CONCLUSIONS: Few neuro-physiological studies are included in

the literature we reviewed for this paper. Therefore we do not

know whether the functional anomalies of the central nervous

system which we describe should be considered to be part of

the syndrome.

188. Maria, B. L.; Drane, W. B.; Quisling, R. J.; Hoang, K. B. Correlation

between gadolinium-diethylenetriaminepentaacetic acid

contrast enhancement and thallium-201 chloride uptake in

pediatric brainstem glioma. J-Child-Neurol. 1997 Sep; 12(6):

341-8; ISSN: 0883-0738.

UNITED-STATES. We previously showed that thallium-201

(201Tl) chloride is accumulated in over 75% of brain tumors,

including brainstem gliomas. The imaging of 201Tl with single

photon emission computed tomography (SPECT) may require an

abnormal increase in permeability of tumor vessels to allow

penetration of the blood-brain barrier. To test this hypothesis,

we evaluated the correlation between gadolinium enhancement

and the degree of 201Tl uptake on SPECT and the contributions

of either gadolinium enhancement or 201Tl uptake to the

prognosis in children with brainstem gliomas. Forty-two sets

of paired SPECT scans and magnetic resonance imaging (MRI)

scans were obtained longitudinally in 13 cases. Altogether, 31

of 42 pairs (74%) of scans showed concordance between the

presence of gadolinium enhancement and 201Tl uptake. There

were no cases that demonstrated 201Tl uptake but lacked

gadolinium enhancement. The results indicate that 201Tl

SPECT is of value primarily when brainstem tumors have

vessels that are demonstrably permeable to gadolinium, prior

to or as a result of radiotherapy.. 0; 0; 80529-93-7.

189. Marson, L. Identification of central nervous system neurons that

innervate the bladder body, bladder base, or external urethral

sphincter of female rats: a transneuronal tracing study using

pseudorabies virus. J-Comp-Neurol. 1997 Dec 29; 389(4): 584-

602; ISSN: 0021-9967.

UNITED-STATES. Transneuronal tracing techniques were used

to identify the putative spinal and brainstem neurons involved

in continence and voiding in the female rat. Pseudorabies

virus, Bartha's K strain, was injected into either the external

urethral sphincter, the bladder base, or the bladder body. After

3-5 days, the rats were perfused with fixative, and virus-

labelled cells were identified by using immunohistochemistry.

External urethral sphincter (EUS) injections resulted in

labelling of pudendal motoneurons in the dorsolateral nucleus

of L6. Putative spinal interneurons were found in the medial

cord from T13 to S1 and in the lateral gray of T13-L2 and L5-

S1. After both bladder base and bladder body injections, the

majority of pseudorabies virus-labelled cells were found in

the lateral gray and medial cord of L6-S1. A number of those

found in the intermediolateral cell column resembled the

parasympathetic preganglionic neurons; the remaining neurons

in the lateral and medial gray were presumed to be

interneurons. Very few pseudorabies virus-labelled cells were

found rostral to T10. In the brainstem, transneuronally

labelled cells were found in the parapyramidal medullary

reticular formation, Barrington's nucleus, raphe magnus, raphe

pallidus, subcoeruleus pars alpha, locus coeruleus, the A5

noradrenergic cell group, and ventromedial periaqueductal gray

after all injection sites. Pseudorabies virus-labelled cells

were also seen in the forebrain following the longest survival

times; areas consistently labelled included the lateral

hypothalamus, the parvocellular region of the paraventricular

nucleus, and the medial preoptic area. These studies indicate

that there is a substantial overlap of central nervous system

neurons that innervate the EUS and the bladder in the female.

190. Martin, G. R. Pre-clinical pharmacology of zolmitriptan (Zomig;

formerly 311C90), a centrally and peripherally acting

5HT1B/1D agonist for migraine. Cephalalgia. 1997 Oct; 17

Suppl 18: 4-14; ISSN: 0333-1024.

NORWAY. Zolmitriptan (Zomig; formerly 311C90) is a novel 5-

hydroxytryptamine (5HT)1B/1D receptor agonist with proven

efficacy in the acute treatment of migraine with or without

preceding aura. The drug differs from presently available

members of this drug class in that it combines 5HT1B/1D

receptor partial agonist activity with robust oral

pharmacokinetics and an ability to inhibit trigeminovascular

activation centrally as well as peripherally in preclinical

studies. Consistent with its selectivity for 5HT1B/1D

receptors, zolmitriptan produces constriction of various

isolated blood vessels, most notably cranial arteries. In

anaesthetized animals, these vascular effects manifest as a

selective constriction of cranial arterio-venous anastomoses

resulting in a redistribution of carotid arterial blood flow.

This effect is produced without significant effects on heart

rate, blood pressure or blood flow to the brain, heart or lungs.

Zolmitriptan also inhibits trigeminal-evoked increases in

cerebral blood flow in anaesthetized cats and blocks

trigeminal-evoked plasma protein extravasation in the dura of

guinea-pigs. These actions are consistent with a pre-

junctional inhibition of neuropeptide release from

perivascular afferents of the trigeminal nerve, as confirmed

by independent studies showing that zolmitriptan blocks

elevations of calcitonin-gene-related peptide in jugular

venous blood during electrical stimulation of the trigeminal

ganglion. In all of these effects, zolmitriptan is three to four

times more potent than sumatriptan, but produces the same

maximum response. Zolmitriptan crosses the intact blood-

brain barrier to inhibit trigeminovascular activation in the

brainstem. This was shown initially by the ability of the drug

to block a brainstem reflex provoking vasoactive intestinal

peptide release from the VIIth cranial (facial) nerve during

trigeminal stimulation. Subsequent ex vivo autoradiography

confirmed that intravenously injected [3H]zolmitriptan labels

a discrete population of cells in the trigeminal nucleus

caudalis (TNC) and nucleus tractus solitarius. Direct evidence

for a central neuromodulatory effect of zolmitriptan was

provided by electrophysiological experiments which clearly

demonstrated that the drug inhibits the excitability of cells in

the TNC after systemic administration. This novel pre-clinical

profile not only distinguishes zolmitriptan from sumatriptan,

but raises intriguing questions about the clinical relevance of

a dual action. Studies to date show that zolmitriptan indeed

modulates cranial sensory processing in humans, yet central

side-effects are no different from sumatriptan. This property

may account for the remarkable consistency in clinical

efficacy observed in clinical trials.. 0; 0; 139264-17-8.

191. Martin Schild, S.; Zadina, J. E.; Gerall, A. A.; Vigh, S.; Kastin, A. J.

Localization of endomorphin-2-like immunoreactivity in the

rat medulla and spinal cord. Peptides. 1997; 18(10): 1641-9;

ISSN: 0196-9781.

UNITED-STATES. Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and

endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) are endogenous ligands

that have greater affinity and selectivity for the mu-opiate

receptor than any other known mammalian peptide. A

polyclonal antiserum, screened for specificity to

endomorphin-2 by immunodot-blot assay and preabsorption

controls, was used for localization of this peptide.

Immunocytochemistry performed on the brainstem, spinal

cord, and sensory ganglia of rats by the avidin-biotin-

peroxidase method revealed a continuous dense aggregation of

endomorphin-2-like immunoreactive varicose fibers in the

superficial laminae of the dorsal horn of the medulla and

spinal cord. Immunoreactive fibers were detected in the dorsal

root as well as within the dorsal root ganglia. The results

suggest that endomorphin-2 is synthesized in primary sensory

neurons in ganglia, transported to the superficial dorsal horn,

and released near neurons expressing mu receptors. Its

distribution appears to represent a functional unit likely to be

associated with modulation of nociceptive stimuli.. 0; 0; 0; 0;

0.

192. Mascalchi, M.; Tosetti, M.; Plasmati, R.; Bianchi, M. C.; Tessa, C.;

Salvi, F.; Frontali, M.; Valzania, F.; Bartolozzi, C.; Tassinari, C.

A. Proton magnetic resonance spectroscopy in an Italian family

with spinocerebellar ataxia type 1. Ann-Neurol. 1998 Feb;

43(2): 244-52; ISSN: 0364-5134.

UNITED-STATES. Linkage and DNA analysis, magnetic

resonance (MR) imaging, and single-voxel proton MR

spectroscopy were obtained in 10 members of an Italian

kindred with spinocerebellar ataxia type 1 (SCA1). The size of

the basis pontis, cerebellar hemispheres, middle cerebellar

peduncles, and medulla oblongata were decreased in 4

members carrying the SCA1 gene, compared with 6 unaffected

subjects. Diffuse signal changes in the pons and cerebellum

were observed only in the carrier with the longest disease

duration and greatest disability. The N-

acetylaspartate/creatine ratio and the choline/creatine ratio

in the basis pontis were markedly decreased in 2 symptomatic

SCA1 carriers and moderately decreased in 2 asymptomatic

SCA1 carriers, compared with the unaffected family members

and a control group of 10 healthy volunteers. Minor decreases

in the N-acetylaspartate/creatine ratio and the normal

choline/creatine ratio were observed in the cerebellar

hemisphere of the SCA1 carriers. Reduction of the N-

acetylaspartate/creatine ratio, demonstrated by MR

spectroscopy in the pons, is likely to reflect a loss of neuronal

viability and might represent a biochemical marker of SCA1

more sensitive than brainstem and cerebellum atrophy and

signal changes shown by MR imaging.. 56-84-8; 57-00-1; 62-

49-7; 6917-35-7; 9007-49-2; 997-55-7.

193. Maschka, D. A.; Bauman, N. M.; McCray, PB Jr; Hoffman, H. T.;

Karnell, M. P.; Smith, R. J. A classification scheme for

paradoxical vocal cord motion. Laryngoscope. 1997 Nov; 107(11

Pt 1): 1429-35; ISSN: 0023-852X.

UNITED-STATES. Paradoxical vocal cord motion (PVCM) is

characterized by the inappropriate adduction of the true vocal

cords during inspiration. Multiple causes have been proposed

for this group of disorders, which share the common finding of

mobile vocal cords that adduct inappropriately during

inspiration and cause stridor by approximation. Management of

this group of disorders has been complicated by the lack of a

classification scheme to include all types of PVCM. We propose

that PVCM be classified according to its underlying etiology

and recognize the following causes of the disorder: 1.

brainstem compression; 2. cortical or upper motor neuron

injury; 3. nuclear or lower motor neuron injury; 4. movement

disorder; 5. gastroesophageal reflux; 6. factitious or

malingering disorder; 7. somatization/conversion disorder.

Case reports are presented to illustrate the characteristic

features and diagnostic evaluation used in assessing patients

with PVCM. Management varies depending on the cause of PVCM

and entails speech therapy, pharmacologic therapy, behavioral

modification, and/or surgical intervention. Recognition of the

multiple causes of PVCM allows otolaryngologists to

formulate well-directed diagnostic evaluation and treatment.

194. Mason, C. A.; Sretavan, D. W. Glia, neurons, and axon pathfinding

during optic chiasm development. Curr-Opin-Neurobiol. 1997

Oct; 7(5): 647-53; ISSN: 0959-4388.

ENGLAND. The importance of vision in the behavior of animals,

from invertebrates to primates, has led to a good deal of

interest in how projection neurons in the retina make specific

connections with targets in the brain. Recent research has

focused on the cellular interactions occurring between retinal

ganglion cell (RGC) axons and specific glial and neuronal

populations in the embryonic brain during formation of the

mouse optic chiasm. These interactions appear to be involved

both in determining the position of the optic chiasm on the

ventral diencephalon (presumptive hypothalamus) and in

ipsilateral and contralateral RGC axon pathfinding,

development events fundamental to binocular vision in the

adult animal.

195. Mason, J. A.; Herrmann, K. R. Universal infant hearing screening by

automated auditory brainstem response measurement.

Pediatrics. 1998 Feb; 101(2): 221-8; ISSN: 0031-4005.

UNITED-STATES. BACKGROUND: Our purpose was to identify

infants with a bilateral, permanent, handicapping hearing loss

and to provide them with amplification before age 6 months.

METHODOLOGY: The study population consisted of 10,372

infants born during a 5-year period. Universal hearing

screening by automated auditory brainstem response was done

in the nursery. Infants who failed the screening test were

followed up diagnostically. Infants who were not tested in the

nursery were followed up as outpatients. Hearing aids were

recommended for those infants who had bilateral hearing loss.

RESULTS: Successful screening in the nursery was achieved for

96% of infants. The failure rate was 4%. The incidence of

bilateral loss requiring amplification was 1.4/1000. The

false-positive rate was 3.5% after the initial screening and

.2% when a two-stage screening procedure was used. The

incidence of congenital bilateral hearing loss in the well

population was 1/1000, and in the neonatal intensive care unit

population, 5/1000. The cost of screening was $17 per infant,

and the cost to identify each true bilateral hearing loss was

$17,750. Amplification was recommended for 15 infants; well

infants who used hearing aids before age 6 months achieved

age-appropriate speech and language development.

CONCLUSIONS: Mild, moderate, and severe bilateral, persistent

hearing loss can be identified in the nursery by automated

auditory brainstem response measurement to provide

amplification before age 6 months and thus optimize speech

and language development.

196. Matsumoto, K.; Tada, E.; Tamesa, N.; Tomita, S.; Ohmoto, T.

Stereotactic brachytherapy for a cystic metastatic brain

tumor in the midbrain. Case report. J-Neurosurg. 1998 Jan;

88(1): 141-4; ISSN: 0022-3085.

UNITED-STATES. The authors report a rare case of a cystic

metastasis in the midbrain that was successfully treated by

brachytherapy following stereotactic biopsy and aspiration of

the intratumoral cyst. Stereotactic aspiration of cystic

lesions can lead to clinical improvement and brachytherapy

prevents cyst recurrence. A 46-year-old man was referred to

the authors' institution with a 2-month history of a left

hemisensory disturbance and a 1-month history of progressive

hemiparesis. Magnetic resonance (MR) imaging revealed a ring-

enhancing cystic mass in the midbrain. On the basis of this

imaging study, a differential diagnosis that included

brainstem abscess, glioma, and metastatic tumor was made.

Magnetic resonance imaging-guided stereotactic biopsy and

aspiration of the intratumoral cyst were performed, yielding 5

ml of yellowish-white fluid. Histological examination provided

a diagnosis of adenocarcinoma. During the surgery, a catheter

through which brachytherapy would be delivered was inserted

at a predetermined target. The patient's left hemiparesis and

sensory disturbance were markedly improved and

brachytherapy was begun 2 days postoperatively. Three

radioactive isotopes composed of iridium-192 were implanted

to irradiate the tumor tissue. The total dose at the tumor

periphery was 30 Gy, which was administered over 100 hours.

External-beam radiotherapy (20 Gy) was added after

completion of the brachytherapy. At discharge from the

hospital, the patient was alert and all his neurological

symptoms had resolved. Follow-up MR imaging revealed

stabilization of the cyst and no recurrence of the tumor. The

patient is alive and well 18 months following the

brachytherapy. This case suggests that brachytherapy can

delay cyst recurrence, suppress tumor growth, and prolong

survival in patients with cystic brainstem metastasis.. 0.

197. Matsuyama, K.; Drew, T. Organization of the projections from the

pericruciate cortex to the pontomedullary brainstem of the

cat: a study using the anterograde tracer Phaseolus vulgaris-

leucoagglutinin. J-Comp-Neurol. 1997 Dec 29; 389(4): 617-41;

ISSN: 0021-9967.

UNITED-STATES. The anterograde tracer Phaseolus vulgaris-

leucoagglutinin (PHA-L) was used to study the distribution and

density of the projections that originate from four identified

subdivisions of the pericruciate cortex (namely, the forelimb

and hind limb representations of area 4, area 6a beta, and area

6a gamma) and that terminate in the pontomedullary brainstem

in the cat. Injections of PHA-L in all areas of the pericruciate

cortex labelled numerous fibers and their terminal swellings

in the brainstem. The major target regions of all four cortical

areas were the pontine nuclei and the pontomedullary reticular

formation (PMRF). Injections into both the forelimb and hind

limb representations of area 4 and into area 6a beta resulted

in a dense pattern of terminal labelling in restricted regions

of the medial and lateral parts of the ipsilateral pontine

nuclei. The labelling following the area 6a beta injection was

spatially distinct from that seen following the area 4

injections. Injections into the forelimb representation of area

4 as well as into area 6a beta and 6a gamma resulted in the

labelling of numerous terminal swellings bilaterally in the

PMRF; in contrast, there were few labelled terminal swellings

in the PMRF following injections into the hind limb

representation of area 4. Terminal swellings on individual

corticoreticular fibers were far less densely aggregated than

those in the pontine nuclei. The dense pattern of innervation to

restricted regions of the pontine nuclei supports previous

suggestions that the corticopontine projections retain a high

degree of topographical specificity that could be used in the

control of discrete voluntary movements. In contrast, the more

diffuse pattern of the projections to the PMRF may facilitate

the selection and activation of the complex postural patterns

that accompany voluntary movement.. 0; 0.

198. McAllen, R. M.; Malpas, S. C. Sympathetic burst activity:

characteristics and significance. Clin-Exp-Pharmacol-Physiol.

1997 Nov; 24(11): 791-9; ISSN: 0305-1870.

AUSTRALIA. 1. The activity recorded from mammalian

sympathetic nerves comes in bursts, which result from large

numbers of fibres firing synchronously. 2. Human sympathetic

nerve activity behaves similarly to that in animals, although

burst rates may be lower. 3. Vasomotor, cardiac and sudomotor

nerve fibres all fire in bursts. Whether other sympathetic

pathways do so is unknown. 4. Sympathetic activity is

intrinsically 'bursty' but not intrinsically regular. 5. Bursting

is a population phenomenon, not usually evident in the firing of

individual neurons. 6. Bursts in post-ganglionic nerves are

driven by synchronously firing preganglionic neurons. 7. The

origin of bursts remains controversial. Preganglionic neuron

properties are likely to be important in at least shaping

bursts. 8. Burst amplitude, which reflects the number of fibres

firing together, and burst probability are controlled

independently. 9. Baroreceptors affect burst probability over a

wide range, but have less effect on mean burst amplitude. How

they affect burst timing within the cardiac cycle is discussed.

10. Burst probability is determined 'downstream' of the rostral

ventrolateral medulla, implicating either the spinal cord or

recurrent brainstem connections in burst generation. 11.

Neuroeffector responses are too slow to follow individual

bursts. However, bursting will promote spatial facilitation at

both ganglionic and effector levels, which may increase the

dynamic range of neural control.

199. McGregor, H. P.; Westcott, K.; Walker, D. W. The effect of prenatal

exposure to carbon monoxide on breathing and growth of the

newborn guinea pig. Pediatr-Res. 1998 Jan; 43(1): 126-31;

ISSN: 0031-3998.

UNITED-STATES. In utero hypoxia may affect the development

of the brain and result in altered respiratory responses

postnatally. Using a barometric plethysmograph, we examined

the effects of exposing pregnant guinea pigs to 200 ppm

carbon monoxide (CO) for 10 h/d from d 23-25 of gestation

until term (approximately 68 d) on the ventilatory responses

of their 4-5-d-old neonates at rest, and during progressive

asphyxia and steady state hypercapnia. Exposure to this

concentration of CO produced significantly higher levels of

carboxyhemoglobin (COHb) in maternal (8.53 +/- 0.6% versus

0.25 +/- 0.1%) and fetal blood (13.0 +/- 0.4% versus 1.6 +/-

0.1%) from CO-treated animals when compared with controls.

Hematocrit was significantly higher in the CO-treated

neonates (46.3 +/- 1.0% versus 41.3 +/- 0.9%) at 5-6 d of age,

although no difference existed between the groups for COHb at

this time. There was no difference between the groups for

length of gestation, litter size, or birth weight, but CO-

treated neonates were significantly smaller at 4 d of age

(102.4 +/- 3.7 g) compared with controls (132.0 +/- 5.0 g). At

4-5 d of age there was no difference between the groups for

either tidal volume (VT), respiratory frequency (f), or minute

ventilation (VE) at rest, but during steady state hypercapnia (4

and 6% CO2) the CO-treated neonates had a significantly

greater VT and VE (but not f) than did controls. During

progressive asphyxia, CO-treated animals had a significantly

greater VT than did controls from 1-8% CO2. There was a

significant fall in f at 1 and 3% CO2 in CO-treated animals;

however, this effect did not persist, resulting in a

significantly increased VE from 3 to 8% CO2. The inspiratory

flow rate (VT/expiratory time) was significantly increased in

the CO-treated neonates during progressive asphyxia; this

occurred in the absence of a difference in inspiratory time

between the groups. These results indicate that prenatal

exposure to CO increases CO2 sensitivity in 4-5-d-old guinea

pigs. This may be due to developmental alterations in the areas

of the brainstem responsible for respiratory control.. 630-08-

0.

200. McLachlan, R. S. Vagus nerve stimulation for intractable epilepsy:

a review. J-Clin-Neurophysiol. 1997 Sep; 14(5): 358-68; ISSN:

0736-0258.

UNITED-STATES. Electrical stimulation of the vagus nerve in

the neck by using a programmable stimulator similar to a

cardiac pacemaker is being explored as a treatment for

epilepsy. There is sound rationale based on studies of animal

seizure models for pursuing this treatment modality, and early

clinical trials provide support for efficacy in patients with

intractable epilepsy at least equivalent to that of some of the

new antiepileptic drugs. Safety and tolerability have been

demonstrated in >800 patients worldwide since the first

implant in 1988. Most of these had partial seizures for which

resective epilepsy surgery was not feasible or had failed, but

efficacy of vagal stimulation appears to be the same for both

partial and generalized epilepsy. Specific selection criteria

for this procedure have yet to be established, and further

studies are warranted to determine whether vagal stimulation

becomes an accepted procedure for epilepsy management.

201. Megerian, C. A.; Burkard, R. F.; Ravicz, M. E. A method for

determining interaural attenuation in animal models of

asymmetric hearing loss. Audiol-Neurootol. 1996 Jul; 1(4):

214-9; ISSN: 1420-3030.

SWITZERLAND. Asymmetric or unilateral sensorineural hearing

loss is an important hall-mark of various forms of

sensorineural hearing loss. Animal research regarding the

etiology and mechanism of these disorders often requires

hearing estimates in each ear of experimental animals.

Monaural auditory testing of animals with experimentally

induced unilateral hearing loss therefore requires prior

knowledge of interaural attenuation (IAA) to facilitate

contralateral masking. The purpose of this study is to describe

a method of determining frequency-specific IAA data and to

present relevant information obtained in the rats--a

frequently used animal in studies of acquired sensorineural

hearing loss. A custom-made sound source was designed to

accomplish threshold determination at important frequencies

in the dynamic range of rats. Six male Long-Evans rats were

surgically monauralized by ablation/obliteration of the

cochlea. Auditory brainstem response (ABR) thresholds were

determined for ipsilateral and contralateral presentations of

2-kHz, 10-kHz, and 40-kHz toneburst. IAA was calculated by

subtracting the frequency-specific ABR threshold obtained

from the normal ear from that obtained following tone

presentation to the 'dead' ear, and was found to average 65.0

+/- 10.5 dB at 2 kHz, 45.0 +/- 8.4 dB at 10 kHz, and 47 +/-

15.1 dB at 40 kHz (+/- standard deviation). Using data obtained

from the animal demonstrating the smallest IAA, masking is

not needed until a threshold asymmetry of 50 dB at 2 kHz and

30 dB at 10 and 40 kHz is observed. In order to obtain bilateral

auditory threshold information in any animal model of

asymmetric hearing loss, data regarding IAA are needed in

order to know when to apply contralateral masking and

therefore avoid crossover stimulation of the non-test ear. The

protocol presented herein provides guidelines for use in any

animal model of sensorineural hearing loss which may

demonstrate unilateral or asymmetric deficits.

202. Melzer, P.; Smith, C. B. Plasticity of cerebral metabolic whisker

maps in adult mice after whisker follicle removal--II.

Modifications in the subcortical somatosensory system.

Neuroscience. 1998 Mar; 83(1): 43-61; ISSN: 0306-4522.

UNITED-STATES. The follicles of whiskers C1-3 were removed

from the left side of the snout of adult mice. Adjacent

whiskers B1-3 and D1-3 were stimulated while local rates of

glucose utilization were measured with the [14C]2-

deoxyglucose method two, four, eight, 64, 160 and

approximately 250 days after follicle removal. Local

metabolic activity in the trigeminal sensory brainstem and

somatosensory thalamus was compared with that of

unoperated mice with the same stimulation and of mice with

the same lesion that had all whiskers clipped. Actual rates of

glucose utilization were measured in brainstem subnuclei

caudalis and interpolaris whereas metabolic activation was

only assessable by colour-coded imaging in brainstem nucleus

principalis and in the thalamic ventrobasal complex. Whisker

stimulation activated the somatotopically appropriate loci in

brainstem and thalamus. In addition, the territory deprived by

follicle removal was metabolically activated in subnuclei

caudalis and interpolaris at all time intervals examined. The

activation was statistically significant in subnucleus

interpolaris at two days, indicating that the metabolic

representations of whiskers neighbouring the lesion rapidly

expanded into the deprived territory. Nucleus principalis

showed a broad metabolic activation at two and four days that

was absent at the longer time intervals examined. Instead, at

approximately 250 days the metabolic representations of the

whiskers adjacent to the lesion were enlarged into the

deprived territory as in the subnuclei. Since metabolic whisker

representation in the ventrobasal complex appeared to have

changed in the same fashion, follicle removal apparently

resulted in congruent modifications of the whisker map in the

three nuclei of termination as well as in the thalamic relay at

the longest time interval examined. Since metabolic

responsiveness of the deprived barrels in barrel cortex of the

same animals increased statistically significantly only

several months after follicle removal, the novel neural

responses in the brainstem were not effectively transmitted

to barrel cortex immediately and the slowly evolving cortical

modifications are more likely to be associated with regrowth

of the connectivity of primary neurons. By contrast, unmasking

of hitherto suppressed inputs may underlie the early expansion

of metabolic whisker representation in the brainstem.. EC

1.9.3.1; 50-99-7.

203. Middleton, M. L.; Wilson, K. M.; Keith, R. W. Central auditory

evaluation of patients with spasmodic dysphonia. Ear-Nose-

Throat-J. 1997 Oct; 76(10): 710-5; ISSN: 0145-5613.

UNITED-STATES. Spasmodic dysphonia is a focal laryngeal

dystonia characterized by inappropriate contractions of the

intrinsic laryngeal musculature. The prevalence of associated

neurological findings has led to detailed investigation of the

central nervous system. Previous research revealed latency

abnormalities in patients' auditory brainstem responses. The

present study further investigated central auditory findings in

patients with spasmodic dysphonia, including brainstem and

cortical function. Fourteen normal-hearing patients with

spasmodic dysphonia were tested using the auditory brainstem

response (ABR) and SCAN-A test of central auditory

processing. The ABR estimated brainstem transmission time

and evaluated auditory pathway integrity at a high stimulus

rate. SCAN-A assessed the auditory cerebral cortex.

Implications of these findings are discussed. We found no ABR

abnormalities in subjects with spasmodic dysphonia. Positive

SCAN-A findings were negligible. The ABR findings contradict

previous reports.. 0; 0.

204. Milsom, W. K.; Harris, M. B.; Reid, S. G. Do descending influences

alternate to produce episodic breathing? Respir-Physiol. 1997

Nov; 110(2-3): 307-17; ISSN: 0034-5687.

NETHERLANDS. This study examines the episodic breathing

patterns of three disparate groups of vertebrates. In an in

vitro bullfrog brainstem-spinal cord preparation, episodic

breathing was replaced by uniformly spaced breaths following

transection caudal to the optic chiasma. The same effect was

produced in hibernating squirrels by inhalation of mild

anesthesia. Preliminary data suggest that a similar conversion

is also produced in hibernating squirrels by vagotomy, in

conjunction with blockade of central NMDA-type glutamate

receptors. In all cases, even though overall breathing

frequency increased, due to elimination of periods of apnea,

instantaneous breathing frequency slowed. Seals breathe

episodically in sleep and when these animals awaken after the

start of a breathing episode, breathing also immediately

slows. The data presented here are consistent with the

suggestion that in all vertebrates, higher centres can modulate

the central rhythm generator for breathing, in both a positive

and a negative fashion. During episodic breathing, in the

species studied here, these modulating influences alternate in

a fashion that produces periods of apnea alternating with

periods of relatively high frequency ventilation.

205. Morley, B. J. The embryonic and post-natal expression of the

nicotinic receptor alpha 3-subunit in rat lower brainstem.

Brain-Res-Mol-Brain-Res. 1997 Sep; 48(2): 407-12; ISSN:

0169-328X.

NETHERLANDS. The mRNA expression of the alpha 3 nicotinic

acetylcholine receptor subunit in the rat lower brainstem is

more widespread in the embryo and at birth than in the mature

brain, but the major cell groups expressing alpha 3 are

generally the same, with two exceptions. The transcript for

the alpha 3-subunit is transiently expressed in the ventral

cochlear nucleus (VCN). Expression was very high in the

embryonic and early post-natal VCN, but was significantly

decreased in the VCN late in the post-natal period (about post-

natal day 15). Conversely, alpha 3 mRNA was not expressed in

the motor trigeminal nucleus until about PN3.. 0; 0.

206. Motte, J. E.; da Silva, Fernandes MJ; Marescaux, C.; Nehlig, A.

Effects of pentylenetetrazol-induced status epilepticus on c-

Fos and HSP72 immunoreactivity in the immature rat brain.

Brain-Res-Mol-Brain-Res. 1997 Oct 15; 50(1-2): 79-84; ISSN:

0169-328X.

NETHERLANDS. Pentylenetetrazol (PTZ)-induced status

epilepticus (SE) leads to acute and long-term metabolic

decreases in specific brain regions of rats at 10 (P10) or 21

days after birth (P21). These decreases are not related to

apparent neuronal damage. Therefore, to better understand the

neuronal activation and stress response to PTZ in immature

rats, we mapped the expression of c-Fos and of the 72 kDa

heat-shock protein (HSP72) in the same model of severe SE

induced by the repetitive i.p. injections of subconvulsive doses

of PTZ. Rats were sacrificed either at 2 or 24 h after the onset

of SE in order to reveal c-Fos immunoreactivity, and at 24 and

72 h for HSP72 expression. Hematoxylin-eosin staining was

performed at 24, 72 and 144 h after SE. The expression of c-

Fos at 2 h after SE was more marked at P21 than at P10 and

was prominent at both ages in the hippocampal dentate gyrus,

cerebral cortex and amygdala. Some immunoreactivity was

also present in the hypothalamus, thalamus and a few

brainstem and cerebellar regions at both ages. There was a

good relation between the regions expressing c-Fos and those

exhibiting acute metabolic decreases at P21. Conversely, PTZ

seizures did not lead to any expression of c-Fos at 24 h after

SE or of HSP72 at 24 or 72 h at any age. Cell density was not

affected by PTZ-induced SE at any age and at any time. These

results suggest that c-Fos is a useful marker of neuronal

activation induced by severe and prolonged seizures in the

immature brain. The lack of HSP72 and of late c-Fos

expression likely reflect the absence of neuronal damage in

this model of PTZ-induced SE in the immature rat.. 0; 0; 0; 0;

0; 54-95-5.

207. Muellbacher, W.; Mamoli, B. The course of cortico-hypoglossal

projections in the human brainstem: functional testing using

transcranial magnetic stimulation [letter]. Brain. 1997 Oct;

120( Pt 10): 1909-10; discussion 1911-4; ISSN: 0006-8950.

ENGLAND.

208. Munoz Farjas, E. [Neurophysiological studies of headaches].

Estudios neurofisiologicos en cefaleas. Rev-Neurol. 1997 Oct;

25(146): 1611-6; ISSN: 0210-0010.

SPAIN. INTRODUCTION AND OBJECTIVE: The diagnosis of

headache is based on the clinical criteria suggested by the IHS

in 1988. The neurophysiological examinations often used in the

study of headache may support the clinical diagnosis and give

information as to the prognosis. The objective of this paper is

to review the neurophysiological examinations most often

used in the clinical and pathological investigation of headache.

DEVELOPMENT: As shown by recent studies, the EEG is of little

value in the routine evaluation of a patient with headache.

However, it may be useful as an exploratory test for

underlying pathology in atypical headache or when intra-

cranial pathology is suspected. Evoked potentials, when used

to study migraine, show absence of Habituation (or

Potentiation) in migraine patients. This finding may represent

abnormality in the processing of information at a cortical

level in these patients. There is a tendency to unify the theory

of neurone hypoxia and the absence of Habituation in Migraine

as a single hypothesis of pathogenesis. Negative Contingent

Variation has proved to be clinically useful to optimize

treatment in Migraine. The electromyogram and Muscle

Reflexes have been used in the study of Tension Type

Headaches, ES2 changes, showing brainstem antinociceptive

reflexes support the participation of a central factor in the

origin of chronic Tension Headache. CONCLUSION:

Neurophysiological tests may be useful in investigation of the

pathology of headache since they permit a functional study of

many neurone paths and the action of drugs on the central

nervous system.

209. Munro, K. J.; Paul, B.; Cox, C. L. Normative auditory brainstem

response data for bone conduction in the dog. J-Small-Anim-

Pract. 1997 Aug; 38(8): 353-6; ISSN: 0022-4510.

ENGLAND. Auditory brainstem response (ABR) is a valuable

tool for the diagnosis of hearing disorders in dogs, but is

hampered by the lack of published normative data. The aim of

the present study was to obtain normative data for bone

conduction, without masking, under clearly defined conditions.

Subjects comprised 20 Dalmatians and 20 Jack Russell

terriers. Two methods were investigated: holding the bone

vibrator against the head by hand or by applying a 500 g

weight. The results revealed no difference in hearing threshold

between the two breeds or for the two methods of applying the

bone vibrator to the head. The mean hearing threshold was

close to 0 decibels re normal hearing level (dB nHL), which is

the biological norm for humans. Hence, bone conduction

thresholds can be used for confirmation of conductive hearing

impairment in the dog, in the same way as in humans.

210. Munro, K. J.; Shiu, J. N.; Cox, C. L. The effect of head size on the

auditory brainstem response for two breeds of dog. Br-J-

Audiol. 1997 Oct; 31(5): 309-14; ISSN: 0300-5364.

ENGLAND. Many studies have shown that the auditory

brainstem response (ABR) is influenced by the sex of the

subject. The explanation offered most often for this sex

difference is the smaller head size and brain dimensions in the

female. Since breeds of dog have different head sizes, this

makes them useful subjects to test the hypothesis that ABR

latency covaries with head size. Subjects comprised 20

Dalmatians and 20 Jack Russell terriers. The maximum width

of the head was 123 +/- 8 mm in the Dalmatian and 88 +/- 5

mm in the Jack Russell. An auditory brainstem response was

carried out using a click stimulus at 75 dB nHL. The latency of

wave V and the I-V interval was longer (0.3 and 0.17 ms

respectively) in the Dalmatian, although the correlation of

these measurements with head size (which ranged from -0.2 to

+0.3) was not statistically significant. These findings do not

support the theory that differences in ABR latency are due to

differences in head size per se. Correlation of latency with

body temperature and with age was also weak and not

statistically significant.

211. Murata, K.; Araki, S.; Yokoyama, K.; Okumura, T.; Ishimatsu, S.;

Takasu, N.; White, R. F. Asymptomatic sequelae to acute sarin

poisoning in the central and autonomic nervous system 6

months after the Tokyo subway attack. J-Neurol. 1997 Oct;

244(10): 601-6; ISSN: 0340-5354.

GERMANY. Six to eight months after the Tokyo subway attack

in March 1995, the neurophysiological effects of acute sarin

poisoning were investigated in 18 passengers exposed to sarin

(sarin cases) in the subways to ascertain the focal or

functional brain deficits induced by sarin. The event-related

and visual evoked potentials (P300 and VEP), brainstem

auditory evoked potential, and electrocardiographic R-R

interval variability (CVRR), together with the score on the

posttraumatic stress disorder (PTSD) checklist, were

measured in the sarin cases and the same number of control

subjects matched for sex and age. None of the sarin cases had

any obvious clinical abnormalities at the time of testing. The

P300 and VEP (P100) latencies in the sarin cases were

significantly prolonged compared with the matched controls.

In the sarin cases, the CVRR was significantly related to

serum cholinesterase (ChE) levels determined immediately

after exposure; the PTSD score was not significantly

associated with any neurophysiological data despite the high

PTSD score in the sarin cases. These findings suggest that

asymptomatic sequelae to sarin exposure, rather than PTSD,

persist in the higher and visual nervous systems beyond the

turnover period of ChE; sarin may have neurotoxic actions in

addition to the inhibitory action on brain ChE.. 107-44-8.

212. Nagata, K.; Nikaido, Y.; Yuasa, T.; Fujimoto, K.; Kim, Y. J.; Inoue, M.

Germinoma causing wallerian degeneration. Case report and

review of the literature. J-Neurosurg. 1998 Jan; 88(1): 126-8;

ISSN: 0022-3085.

UNITED-STATES. Germinomas occurring in the thalamus and

basal ganglia sometimes cause atrophy of the cerebral

hemisphere on the affected side. The authors present the case

of a 12-year-old girl with a germinoma that developed in the

basal frontal lobe and cerebral basal ganglia. Magnetic

resonance imaging showed atrophy not only of the cerebrum

but also of the brainstem. A T2-weighted image revealed an

area of high intensity that proved to be wallerian degeneration

extending from the corona radiata and internal capsule to the

brainstem. The authors suggest that this pathological change

may be involved in the development of the symptoms and

hemiatrophy associated with germinomas in this region of the

brain.

213. Neubauer, J. A. Mechanisms of apnea. Curr-Opin-Pulm-Med. 1995

Nov; 1(6): 491-7; ISSN: 1078-1641.

UNITED-STATES. Instabilities in breathing pattern are a

common feature of sleep, giving rise to a variety of syndromes

that vary in the magnitude of respiratory disturbance but that

all lead to frequent arousals and sleep fragmentation. Although

these syndromes vary in intensity of respiratory disturbance,

the underlying mechanism of each is determined to a large

extent on the neural processes that promote periodicities in

net respiratory output. This review focuses on recent

publications that have evaluated central brainstem processes

for their involvement in the initiation and resolution of an

apneic episode. In particular, this review focuses on several

neural processes that can play an important role in promoting

respiratory instability. These include spontaneous oscillations

within the respiratory network, instability in the chemical

control system due to increased gain in the feedback

controller, differences in the controller gains of the upper

airway and pump muscle effectors, state-dependent

instabilities, and loss of stabilizing processes (eg,

poststimulus potentiation.).

214. Nielsen, S. E.; Olsen, S. O. Validation of play-conditioned

audiometry in a clinical setting. Scand-Audiol. 1997; 26(3):

187-91; ISSN: 0105-0397.

DENMARK. The aim of the present study was to investigate at

what ages children were able to participate in play-

conditioned audiometry in a clinical setting. Data concerning

age and gender for 294 children (182 boys and 112 girls) were

continuously recorded with details regarding audiometric

method and number of successfully determined thresholds.

Some children were tested more than once, resulting in a total

of 449 examinations. The results are compared with those of

other studies in which visual reinforced audiometry (VRA),

condition-orientation reflex audiometry (COR) and play-

conditioned audiometry are used, and show that in a clinical

setting it is possible to determine at least one threshold in

more than 35% of children tested at ages above 16 months. At

2 years of age, about 50% of the children are able to establish

thresholds at least at three frequencies and from 3 years of

age nearly 75% of the children could establish 6 thresholds or

more. It is concluded that VRA, COR and play-conditioned

audiometry should be considered along with objective hearing

tests like brainstem audiometry (ABR) or measurement of

otoacoustic emissions (OAE) when assessing hearing in infants

and small children.

215. Niemi Junkola, U.; Shehab, S.; Redgrave, P. Anticonvulsant and

behavioural effects of bicuculline injected into the

mesencephalic locomoter region of rats. Brain-Res. 1997 Dec

19; 778(2): 401-4; ISSN: 0006-8993.

NETHERLANDS. Previous microinjection mapping studies in the

mesencephalon established a significant association between

the induction of locomotor activation and the suppression of

tonic seizures in the electroshock model of epilepsy. The

purpose of the present study was to see if this relationship

also applies in an area of the brainstem commonly known as

the mesencephalic locomotor region (MLR). The principal

findings were the following. (i) Activation of extensive areas

of the dorsal midbrain and tegmentum, including the MLR, by

unilateral injections of the GABA antagonist bicuculline

induced leg movements and suppressed the tonic component of

electroshock-induced seizures. (ii) A highly significant

correlation was observed between these two variables. (iii) In

some cases, however, the induction of phasic leg movements

was neither sufficient nor necessary for tonic seizure

suppression. It is possible, therefore, that injection-elicited

changes in tonic aspects of limb control may be more directly

related to the suppression of tonic motor seizures in the

electroshock model of epilepsy.. 0; 0; 485-49-4.

216. Nofzinger, E. A.; Mintun, M. A.; Wiseman, M.; Kupfer, D. J.; Moore, R.

Y. Forebrain activation in REM sleep: an FDG PET study. Brain-

Res. 1997 Oct 3; 770(1-2): 192-201; ISSN: 0006-8993.

NETHERLANDS. Rapid eye movement (REM) sleep is a behavioral

state characterized by cerebral cortical activation with

dreaming as an associated behavior. The brainstem

mechanisms involved in the generation of REM sleep are well-

known, but the forebrain mechanisms that might distinguish it

from waking are not well understood. We report here a

positron emission tomography (PET) study of regional cerebral

glucose utilization in the human forebrain during REM sleep in

comparison to waking in six healthy adult females using the

18F-deoxyglucose method. In REM sleep, there is relative

activation, shown by increased glucose utilization, in

phylogenetically old limbic and paralimbic regions which

include the lateral hypothalamic area, amygdaloid complex,

septal-ventral striatal areas, and infralimbic, prelimbic,

orbitofrontal, cingulate, entorhinal and insular cortices. The

largest area of activation is a bilateral, confluent paramedian

zone which extends from the septal area into ventral striatum,

infralimbic, prelimbic, orbitofrontal and anterior cingulate

cortex. There are only small and scattered areas of apparent

deactivation. These data suggest that an important function of

REM sleep is the integration of neocortical function with basal

forebrain-hypothalamic motivational and reward mechanisms.

This is in accordance with views that alterations in REM sleep

in psychiatric disorders, such as depression, may reflect

dysregulation in limbic and paralimbic structures.. 0; 154-17-

6; 50-99-7.

217. Oates, P.; Stapells, D. R. Frequency specificity of the human

auditory brainstem and middle latency responses to brief

tones. II. Derived response analyses. J-Acoust-Soc-Am. 1997

Dec; 102(6): 3609-19; ISSN: 0001-4966.

UNITED-STATES. This study investigated the frequency

specificity of the auditory brainstem (ABR) and middle latency

(MLR) responses to 500- and 2000-Hz brief tones using

narrow-band derived response analyses of the responses

recorded in high-pass masking noise [Oates and Stapells, J.

Acoust. Soc. Am. 102, 3597-3608 (1997)]. Stimuli were

linear- and exact-Blackman-gated tones presented at 80 dB

ppe SPI. Cochlear contributions to ABR wave V-V' and MLR

wave Na-Pa were assessed by response amplitude profiles as a

function of derived band center frequency. The largest

amplitudes of waves V and Na-Pa occurred in the 500- and

707-Hz derived bands in response to the exact-Blackman- and

linear-gated 500-Hz tones. The peak in the response amplitude

profiles for wave V to both 2000-Hz stimuli was seen in the

2000-Hz derived band. For wave Na-Pa, the maxima in the

amplitude profiles occurred in the 2000- and 1410-Hz derived

bands for the exact-Blackman- and linear-gated tones. Smaller

cochlear contributions to the ABR/MLR were also present at

0.5-1 octave above and below the nominal stimulus

frequencies. The ABR/MLR to 500- and 2000-Hz 80 dB ppe SPL

tones thus shows good frequency specificity, with no

significant differences in the frequency specificity of: (1) ABR

versus MLR; (2) these evoked potentials to 500-versus 2000-

Hz tones; and (3) responses to exact-Blackman- versus linear-

gated tones.

218. Oates, P.; Stapells, D. R. Frequency specificity of the human

auditory brainstem and middle latency responses to brief

tones. I. High-pass noise masking. J-Acoust-Soc-Am. 1997

Dec; 102(6): 3597-608; ISSN: 0001-4966.

UNITED-STATES. This study investigated the frequency

specificity of the auditory brainstem (ABR) and middle latency

(MLR) responses to 500- and 2000-Hz brief tones using high-

pass noise masking. Stimuli were linear- (2-1-2 cycles) and

exact-Blackman- (5 cycles) gated tones presented at 80 dB

peak-to-peak equivalent (ppe) SPL. Cochlear contributions to

ABR wave V-V' and MLR wave Na-Pa were assessed by the

effects of high-pass noise masking on response amplitudes and

latencies. The high-pass noise results demonstrate that the

ABR and the MLR to the 80 dB ppe SPL brief tones show good

frequency and place specificity. Changes in ABR or MLR

amplitude and latency with high-pass noise masking did not

occur as the masker cutoff was decreased from 2 to 3 octaves

above the stimulus nominal frequency until it was within one-

half octave of this frequency, below which amplitudes rapidly

decreased (500- and 2000-Hz tones) and latencies increased

(500-Hz tones). No significant differences existed in the

frequency specificity of the ABR versus MLR, or in these

evoked potentials to exact-Blackman- versus linear-gated

tones.

219. Obonai, T.; Yasuhara, M.; Nakamura, T.; Takashima, S.

Catecholamine neurons alteration in the brainstem of sudden

infant death syndrome victims. Pediatrics. 1998 Feb; 101(2):

285-8; ISSN: 0031-4005.

UNITED-STATES. BACKGROUND: Sudden infant death syndrome

(SIDS) is a leading cause of postneonatal infant death. The

pathogenesis of sudden death is still unknown, but an

abnormality in the central nervous regulation of breathing

during sleep has been suggested. OBJECTIVE: The aim of study

is to confirm the brainstem disorder of SIDS victims. In order

to do this, it is necessary to investigate the alterations of

brain neurotransmitter systems thought to be involved in

respiratory control. DESIGN: Neuropathologic study performed

on the brainstem of SIDS victims. SUBJECT/METHODS: The

disorders of catecholaminergic systems in 22 SIDS victims

were examined on the substantia nigra in the midbrain, locus

coeruleus in the pons, vagal nuclei, and area reticularis

superficialis ventrolateralis with the immunohistochemical

method. Immunoperoxidase staining was performed with the

antityrosine hydroxylase (TH) and the glial fibrillary acidic

protein antibodies. Immunoreactivity was compared with 13

age-matched control infants. For statistical analysis, the chi

2 test and the Student's t test were performed. RESULTS: The

main finding was diminished TH immunoreactivity in the vagal

nuclei and area reticularis superficialis ventrolateralis of

SIDS victims, suggesting that adrenaline and noradrenaline

neurons are altered in SIDS. In addition, this decrease in TH

was closely correlated with brainstem gliosis. CONCLUSION:

These catecholaminergic changes may be caused by chronic

hypoxia or ischemia, and also may underlie alterations in

respiratory and cardiovascular control in sleep.. EC 1.14.16.2;

0; 0; 0.

220. Obrist, M. K.; Wenstrup, J. J. Hearing and hunting in red bats

(Lasiurus borealis, Vespertilionidae): audiogram and ear

properties. J-Exp-Biol. 1998 Jan; 201( Pt 1): 143-54; ISSN:

0022-0949.

ENGLAND. We examined aspects of hearing in the red bat

(Lasiurus borealis) related to its use of biosonar. Evoked

potential audiograms, obtained from volume-conducted

auditory brainstem responses, were obtained in two bats, and

the sound pressure transformation of the pinna was measured

in three specimens. Field-recorded echolocation signals were

analysed for comparison. The fundamental sonar search calls

sweep from 45 to 30 kHz (peak energy at 35 kHz), approach-

phase calls sweep from 65 to 35 kHz (peak 40 kHz) and

terminal calls sweep from 70 to 30 kHz (peak 45 kHz). The

most sensitive region of the audiogram extended from 10 kHz

to 45-55 kHz, with maximum sensitivity as low as 20 dB SPL

occurring between 25 and 30 kHz. A relative threshold

minimum occurred between 40 and 50 kHz. With increasing

frequency, the acoustic axis of the pinna moves upwards and

medially. The sound pressure transformation was noteworthy

near 40-45 kHz; the acoustic axis was closest to the midline,

the -3 dB acceptance angles showed local minima, and the

pinna gain and interaural intensity difference were maximal.

These results are related to the known echolocation and

foraging behavior of this species and match the spectral

components of approach- and final-phase calls. We conclude

that co-evolution with hearing prey has put a higher selective

pressure on optimizing localization and tracking of prey than

on improving detection performance.

221. Ohtsuka, K.; Hashimoto, M.; Nakamura, Y. Bilateral trochlear nerve

palsy with arachnoid cyst of the quadrigeminal cistern. Am-J-

Ophthalmol. 1998 Feb; 125(2): 268-70; ISSN: 0002-9394.

UNITED-STATES. PURPOSE: To report bilateral trochlear nerve

palsy and its magnetic resonance imaging characteristics in a

patient with an arachnoid cyst of the quadrigeminal cistern.

METHOD: We performed magnetic resonance imaging of the

brainstem of a 54-year-old man who had bilateral trochlear

nerve palsy and mild truncal ataxia. RESULTS: Magnetic

resonance imaging disclosed an arachnoid cyst of the

quadrigeminal cistern with enlargement of the lateral, third,

and fourth ventricles. The tectum of the midbrain and the

ambient and interpeduncular cisterns were markedly

compressed by the arachnoid cyst. CONCLUSION: These findings

suggest that the bilateral trochlear nerve palsy in this patient

was caused by the arachnoid cyst of the quadrigeminal cistern.

222. Okabe, S.; Mackiewicz, M.; Kubin, L. Serotonin receptor mRNA

expression in the hypoglossal motor nucleus. Respir-Physiol.

1997 Nov; 110(2-3): 151-60; ISSN: 0034-5687.

NETHERLANDS. Brainstem serotonin (5-HT)-containing cells

are remarkable for their widespread axonal projections and

having their highest activity during wakefulness and lowest

during rapid eye movement sleep. One important site of action

of 5-HT is on upper airway motoneurons. However, which of

the 14 known 5-HT receptors mediate the effects is uncertain.

We used the reverse transcriptase/polymerase chain reaction

to detect mRNA for six distinct 5-HT receptors (1A, 1B, 2A,

2C, 3 and 7) in 50 nl micro-punches collected from the

hypoglossal (XII) motor nucleus and, for comparison, from the

viscerosensory nucleus of the solitary tract (NTS) in adult

rats. The relative abundance of the distinct mRNAs was

characterized by the minimal number of amplification cycles

(25-40) necessary to detect a given mRNA. In the XII nucleus,

mRNA for type 1B, 2A and 2C receptors was detectable after

29-31 cycles, detection of type 3 and 7 receptor mRNA

required 33-35 cycles; and type 1A receptor mRNA was not

detected. In the NTS, detection of mRNA for type 1B, 2C and 7

receptors required 31-33 cycles; type 1A receptor mRNA

required 39 cycles; and type 2A receptor mRNA was not

detected. The data from the XII nucleus demonstrate that not

only the previously recognized type 1B, 2A and 2C receptors,

but also type 3 and 7 receptors have the potential to mediate

serotonergic effects in XII motoneurons.. 0; 0.

223. Okada, Y.; Kawai, A.; Muckenhoff, K.; Scheid, P. Role of the pons in

hypoxic respiratory depression in the neonatal rat. Respir-

Physiol. 1998 Jan; 111(1): 55-63; ISSN: 0034-5687.

NETHERLANDS. The main purpose of this study was to evaluate

the role of the pons in hypoxic respiratory depression (HRD) of

the neonatal rat. Experiments were conducted using the

isolated brainstem-spinal cord preparation of the neonatal rat

(1-3 days old). The brainstem was transected at various

levels. We found that ablation of the diencephalon decreased

respiratory frequency (fR), and conversely, that ablation of the

midbrain or pons increased fR. In the preparation with the pons

intact (without the midbrain), hypoxia (superfusate PO2 = 56

mmHg) caused strong depression of respiratory activity, which

was characterized by a steady decrease in fR and in integrated

inspiratory burst amplitude (integral of Phr). In the

preparation with the intact ventral pons (without midbrain and

dorsal pons) we observed similar, though weaker, HRD. When

the entire pons was ablated, integral of Phr was little

depressed by hypoxia and thus, HRD was further attenuated. We

conclude that the pons contributes importantly to the

induction of hypoxic respiratory depression in the neonatal rat.

Both the ventral and dorsal portions of the pons are involved in

the control of hypoxic respiratory depression. In addition, we

show that the respiratory modulatory functions of the

diencephalon (facilitating) and midbrain (inhibitory) are

already expressed at the time of birth.

224. O'Neill, W. E.; Zettel, M. L.; Whittemore, K. R.; Frisina, R. D.

Calbindin D-28k immunoreactivity in the medial nucleus of the

trapezoid body declines with age in C57BL/6, but not CBA/CaJ,

mice. Hear-Res. 1997 Oct; 112(1-2): 158-66; ISSN: 0378-5955.

NETHERLANDS. This study compared calbindin D-28k

immunoreactivity in the medial nucleus of the trapezoid body

(MNTB) in young (3-4 month old) and old (24-26 month old)

CBA/CaJ mice, and young (3-4 month old), middle-aged (6.5-

8.5 month old), and old (24-29 month old) C57BL/6 mice.

C57BL/6 mice exhibit progressively more severe peripheral

(sensorineural) hearing loss between 4 and 12 months of age,

whereas CBA/CaJ mice show little change in peripheral

sensitivity until very late in life. We obtained auditory

brainstem response audiograms on all subject mice. Old CBA

mice were selected for study whose audiograms matched those

of young CBA and C57 controls. Middle-aged C57 mice showed

elevated thresholds indicative of peripheral degeneration.

Brain sections were reacted with anti-calbindin D-28k (CB).

Staining patterns in Nissl and anti-CB material were

characterized and cells were counted. We found no significant

change in the number of CB+ cells or the total number of cells

in the MNTB of old CBA mice compared to young controls.

However, the mean number of CB+ cells decreased by 11% in

middle-aged, and by 14.8% in old C57 mice. Since the decline in

C57 mice was significant by 6.5-8.5 months of age, the

decrease could be the consequence of a loss of input from the

cochlear nucleus where cell numbers are known to decline by

this age in this strain. The total number of neurons in MNTB

assessed from Nissl material showed a more modest 7.1%

decline with age in C57 mice, implying that the greater loss of

CB immunoreactive cells with age cannot be completely

attributed to a reduction in the total number of cells.. 0; 0.

225. Onimaru, H.; Arata, A.; Homma, I. Neuronal mechanisms of

respiratory rhythm generation: an approach using in vitro

preparation. Jpn-J-Physiol. 1997 Oct; 47(5): 385-403; ISSN:

0021-521X.

JAPAN. The respiratory network in the ventrolateral medulla

of the brainstem-spinal cord preparation from newborn rat

involves pre-inspiratory (Pre-I) neurons, three types of

inspiratory (Insp I, II, III) neurons and two types of expiratory

(Exp-i, Exp-p-i) neurons as major subtypes, which were

classified according to patterns of postsynaptic potentials.

The neuronal respiratory-related membrane potential

fluctuations of these cells indicate at least four

distinguishable phases of the in vitro respiratory cycle: pre-

inspiratory, inspiratory, post-inspiratory (E1), and late-

expiratory (E2). A current hypothesis for the central pattern

generator of respiration proposed by our group is that Pre-I

neurons in the rostral ventrolateral medulla, with intrinsic

burster properties, produce the primary respiration rhythm.

This rhythm triggers an inspiratory pattern generator

composed of Insp neurons in the rostral and caudal

ventrolateral medulla. Respiratory neurons possess several

types of ionic channels which are involved in the generation of

rhythm and burst pattern. Particularly, P-type Ca2+ channels

and TTX-sensitive persistent Na+ channels are postulated to

contribute to the intrinsic burst generation of Pre-I neurons.

N-type Ca2+ channels may be involved in the maintenance and

termination of inspiratory burst activity via the activation of

Ca2(+)-dependent K+ channels. Respiratory neuron networks in

this preparation were compared with those of different in

vitro preparations, like rhythmic slices or perfused

brainstems and of adult mammals in vivo. Many types of

synaptic connections among respiratory neurons in adult

mammals were also found in the (rostral) ventrolateral

medulla of a brainstem-spinal cord preparation from newborn

rat. The characteristics of the inspiratory burst pattern and

inspiratory off switch mechanisms in newborn rat

preparations might be explained by insufficient inhibitory (or

excitatory) synaptic inputs to the inspiratory pattern

generator due to an immature neuron network and/or

deafferentiation.. 0.

226. Onofrj, M.; Thomas, A.; Paci, C.; Scesi, M.; Tombari, R. Event

related potentials recorded in patients with locked-in

syndrome. J-Neurol-Neurosurg-Psychiatry. 1997 Dec; 63(6):

759-64; ISSN: 0022-3050.

ENGLAND. OBJECTIVE: To determine the possibility of

recording "cognitive" event related potentials (ERPs) in

locked-in patients and therefore to determine whether ERPs

can have a role in differential diagnosis of coma. METHODS:

ERPs to classic auditory or visual "odd ball paradigms" were

recorded three to four days, seven to eight days, and 30 to 60

days after admission to the intensive care unit, in four

patients affected by basilar artery thromboembolism resulting

in locked-in syndrome. Two patients (one 32 year old man, one

31 year old woman) could move the eyes laterally and

vertically spontaneously and on command. One patient (a 39

year old man) had a "one and half syndrome", one patient (a 40

year old woman) could only elevate the left eyelid and eye.

Results were compared with data from 30 age matched

controls. In the last recording session a letter recognition

paradigm was applied, in which ERPs were produced by the

identification of letters forming a word. Results were

compared with five age matched controls. Brainstem lesions

extending to the pontomesencephalic junction were found on

MRI and CT. RESULTS: ERPs to the oddball paradigms were

recorded in three patients in the first recording session, in all

patients in the second recording session. Latency, amplitude,

and topographic distribution of ERP components were inside

normal limits. With the letter recognition paradigm the

patients could emit a P3 component to correspond with target

letters, with the same margin of error as controls.

CONCLUSION: It is possible to record ERPs in patients with

locked-in syndrome shortly after the acute ischaemic lesion,

and therefore to assess objectively cognitive activities.

Furthermore the letter recognition paradigm could be

implemented to facilitate linguistic communication with

patients with locked-in syndrome.

227. Pamantung, T. F.; Leroy, J. P.; Mabin, D.; Le Mevel, J. C. Role of

dorsal vagal motor nucleus in angiotensin II-mediated

tachycardia in the conscious trout Oncorhynchus mykiss.

Brain-Res. 1997 Oct 24; 772(1-2): 167-75; ISSN: 0006-8993.

NETHERLANDS. Responses of heart rate (HR) and mean arterial

blood pressure (MABP) were examined following

microinjection of angiotensin II ([Asn1,Val5]AI) within the

dorsal vagal motor nucleus (DVN) of the conscious trout's

brainstem. AII (15-125 fmol) preferentially and significantly

increased HR in a dose-dependent manner, but the rise in MABP

was not dose-dependent and was only significant (P < 0.05)

after injection of AII at a dose of 62.5 fmol. The

cardiovascular action of AII was site-specific, since

administrations of the peptide at a dose of 62.5 fmol, but

outside the boundaries of the DVN, were devoid of any effect

on HR or MABP. All the responses to DVN injections of AII were

totally prevented by DVN injection of 1 nmol of losartan, a

mammalian non-peptide AII subtype 1 (AT1) receptor

antagonist. The ability of DVN injection of AII to induce a

tachycardic response was negatively correlated to HR basal

values. In conclusion, these results indicate that, at

femtomolar doses, AII exerts a central neurocardioregulatory

role, involving a localized receptor closely related to the

mammalian AT1 receptor subtype within the DVN of the trout..

11128-99-7; 114798-26-4.

228. Panigrahy, A.; Filiano, J. J.; Sleeper, L. A.; Mandell, F.; Valdes

Dapena, M.; Krous, H. F.; Rava, L. A.; White, W. F.; Kinney, H. C.

Decreased kainate receptor binding in the arcuate nucleus of

the sudden infant death syndrome. J-Neuropathol-Exp-Neurol.

1997 Nov; 56(11): 1253-61; ISSN: 0022-3069.

UNITED-STATES. The human arcuate nucleus is postulated to

be homologous to ventral medullary surface cells in animals

that participate in ventilatory and blood pressure responses to

hypercarbia and asphyxia. Recently, we reported a significant

decrease in muscarinic cholinergic receptor binding in the

arcuate nucleus in victims of the sudden infant death

syndrome compared with control patients that died of acute

causes. To test the specificity of the deficit to muscarinic

cholinergic binding, we examined kainate binding in the

arcuate nucleus in the same database. We assessed 3H-kainate

binding to kainate receptors with tissue receptor

autoradiography in 17 brainstem nuclei. Analysis of covariance

was used to examine differences in binding by diagnosis,

adjusted for postconceptional age (the covariate). Cases were

classified as SIDS, 47; acute control, 15; and chronic group

with oxygenation disorder, 17. (Acute controls are infants who

died suddenly and unexpectedly and in whom a complete

autopsy established a cause of death). The arcuate nucleus was

the only region in which there was a significant difference in

the age-adjusted mean kainate binding between the SIDS group

(37+/-2 fmol/mg tissue) and both the acute controls (77+/-4

fmol/mg tissue) (p < 0.0001) and the chronic group (69+/-4

fmol/mg tissue) (p < 0.0001). There was a positive correlation

between the density of muscarinic cholinergic and kainate

binding in the SIDS cases only (R = 0.460; p = 0.003). The

neurotransmitter deficit in the arcuate nucleus in SIDS

victims involves more than one receptor type relevant to

carbon dioxide and blood pressure responses at the ventral

medullary surface.. 0; 487-79-6.

229. Panigrahy, A.; Sleeper, L. A.; Assmann, S.; Rava, L. A.; White, W. F.;

Kinney, H. C. Developmental changes in heterogeneous patterns

of neurotransmitter receptor binding in the human

interpeduncular nucleus. J-Comp-Neurol. 1998 Jan 19; 390(3):

322-32; ISSN: 0021-9967.

UNITED-STATES. The interpeduncular nucleus (IPN) exhibits

many complex features, including multiple subnuclei,

widespread projections with the forebrain and brainstem, and

neurotransmitter heterogeneity. Despite the putative

importance of this nucleus, very little is known about its

neurochemical development in the human. The human IPN is

cytoarchitectonically simple, unlike the rat IPN, which

displays considerable heterogeneity. In the following study,

we hypothesized that the developing human IPN is

neurochemically heterogeneous despite its cytological

simplicity. The chemoarchitecture in this study was defined by

neurotransmitter receptor binding patterns by using

quantitative tissue autoradiography for the muscarinic,

nicotinic, serotoninergic, opioid, and kainate receptors. We

examined neurotransmitter receptor binding in the developing

human IPN in a total of 15 cases. The midbrains of five

midgestational fetuses (19-26 gestational weeks) and six

infants (38-74 postconceptional weeks) were examined. The

midbrain of one child (4 years) and three adults (20-68 years)

were analyzed as indices of maturity. At all ages examined,

high muscarinic binding was localized to the lateral

subdivision of the IPN, high serotoninergic binding was

localized to the dorsal IPN, and high opioid receptor binding

was localized to the medial IPN. The developmental profile

was unique for each radioligand. We report a heterogenous

distribution of neurotransmitter receptor binding in the

developing human IPN, which supports a complex role for it in

human brain function.. 0; 0; 0; 0; 0; 465-65-6; 487-79-6; 50-

37-3; 54-11-5; 6581-06-2.

230. Panzica, G. C.; Garzino, A. Anatomically specific colocalization of

NADPH-diaphorase and choline acetyltransferase in the quail

brainstem. Neurosci-Lett. 1997 Aug 15; 231(3): 151-4; ISSN:

0304-3940.

IRELAND. On the basis of previous studies demonstrating a

wide colocalization of NADPH-diaphorase (ND) and choline

acetyltransferase (ChAT) in mammalian and reptilian

brainstem, ND histochemistry and ChAT immunocytochemistry

have been combined to study the distribution of both markers

in the mesopontine region of an avian species, the Japanese

quail (Coturnix japonica). Co-existence of the two

neurochemical markers is present only in part of the system,

namely, in the nucleus tegmentalis pedunculo-pontinus, in the

nucleus tegmentalis latero-dorsalis, in the nucleus

mesencephalicus profundus, and in the nucleus reticularis

paragigantocellularis. The degree of colocalization varies in

these regions from about 50 to 95% of the ChAT population.

However, several other nuclei in the same region display only

one of the two markers. These results confirm that even if the

general distribution of the ND-positive neurons is largely

comparable in vertebrates, there exists species-specific

differences in the extension of the system and in the degree of

colocalization with other neurochemical markers.. EC 1.6.99.1;

EC 2.3.1.6.

231. Parham, K. Distortion product otoacoustic emissions in the

C57BL/6J mouse model of age-related hearing loss. Hear-Res.

1997 Oct; 112(1-2): 216-34; ISSN: 0378-5955.

NETHERLANDS. One of the earliest histopathological changes

associated with age-related hearing loss appears to be the

disruption of outer hair cells (OHCs). To evaluate age-related

changes in OHC function, distortion product otoacoustic

emissions (DPOAEs) were recorded in the young and aging

C57BL/6J mouse. Starting in young adulthood, the C57 mouse

displays age-related elevation of auditory brainstem response

thresholds, beginning in the high frequencies and progressing

toward lower frequencies. The 2f1-f2 DPOAEs of mice between

2 and 20 months of age were examined for f2s between 8 and

16 kHz. In this octave region, the features of 2f1-f2 DPOAEs in

the 2-month-old C57 mouse were comparable to those

described for non-murine rodents in the literature in terms of

optimum f2/f1 ratio, optimum primary level difference,

input/output (I/O) function features and microstructure. It

was determined that f2/f1 = 1.2 and L1-L2 = 20 dB were

optimal stimulus parameters for investigation of the effects

of age on C57 DPOAEs. Age-related changes in DPOAE I/O

functions consisted of a right shift (i.e. increased DPOAE

detection thresholds), disappearance of 'notches' and

shallowing of the slopes after 8 months of age. As DPOAE I/O

functions continued to shift to the right and DPOAE levels

decreased with age, the appearance of I/O functions became

complex to include regions of steep or shallow slopes and

plateaus. The present results suggest that the age-related

elevation of auditory thresholds in the C57 mice is associated

with substantial progressive changes in OHC function.

232. Parkis, M. A.; Berger, A. J. Clonidine reduces hyperpolarization-

activated inward current (Ih) in rat hypoglossal motoneurons.

Brain-Res. 1997 Sep 19; 769(1): 108-18; ISSN: 0006-8993.

NETHERLANDS. We used intracellular recording techniques to

investigate the actions of clonidine on hypoglossal

motoneurons (HMs) in rat brainstem slices. Clonidine (10-100

microM) produced a small (2-6 mV), dose-dependent

hyperpolarization in HMs, accompanied by an increase in peak

input resistance (RN). It also slowed the time course of the

depolarizing 'sag' of the voltage response to constant

hyperpolarizing current steps. These effects were mimicked by

the alpha2-adrenoceptor (alpha2-AR) agonist guanabenz, but

not by the Ih-imidazoline receptor agonists moxonidine or

rilmenidine. Recorded in single-electrode voltage clamp mode,

clonidine decreased input conductance of HMs and reduced the

amplitude of a hyperpolarization-activated inward current

(Ih). Clonidine's effect on Ih was three-fold: it shifted the

half-activation voltage (V1/2) in the hyperpolarizing direction

(by 4.4 +/- 0.7 mV at a dose of 10 microM), decreased the

maximal current (by approximately 20%), and slowed the time

course of Ih activation at all voltage steps. At the most

hyperpolarized potential steps, clonidine slowed activation of

Ih dramatically, yielding a striking increase in the activation

time constant. The alpha2-AR antagonists yohimbine and

idazoxan reduced clonidine's effect on V1/2 and on the Ih

activation time course, but neither blocked clonidine's

reduction of the maximal current, nor its strong slowing of Ih

activation at the most hyperpolarized steps. We were unable to

mimic or occlude clonidine's actions with the adenylate

cyclase inhibitor SQ 22536 nor with the non-specific protein

kinase inhibitor H-7. We conclude that clonidine

hyperpolarizes HMs via a reduction of the amount of Ih that is

active at rest, and that the response is mediated in part by

alpha2-ARs. Some effects of clonidine on these neurons do not

appear to be receptor-mediated, and may be due to physical

block by clonidine of Ih channels.. EC 2.7.1.37; EC 4.6.1.1; 0; 0;

0; 17318-31-9; 4205-90-7; 73-24-5; 84477-87-2.

233. Parsadanian, A. S.; Cheng, Y.; Keller Peck, C. R.; Holtzman, D. M.;

Snider, W. D. Bcl-xL is an antiapoptotic regulator for postnatal

CNS neurons. J-Neurosci. 1998 Feb 1; 18(3): 1009-19; ISSN:

0270-6474.

UNITED-STATES. Bcl-xL is a death-inhibiting member of the

Bcl-2/Ced9 family of proteins which either promote or inhibit

apoptosis. Gene targeting has revealed that Bcl-xL is required

for neuronal survival during brain development; however, Bcl-

xL knock-out mice do not survive past embryonic day 13.5,

precluding an analysis of Bcl-xL function at later stages of

development. Bcl-xL expression is maintained at a high level

postnatally in the CNS, suggesting that it may also regulate

neuron survival in the postnatal period. To explore functions of

Bcl-xL related to neuron survival in postnatal life, we

generated transgenic mice overexpressing human Bcl-xL under

the control of a pan-neuronal promoter. A line that showed

strong overexpression in brainstem and a line that showed

overexpression in hippocampus and cortex were chosen for

analysis. We asked whether overexpression of Bcl-xL

influences neuronal survival in the postnatal period by

studying two injury paradigms that result in massive neuronal

apoptosis. In the standard neonatal facial axotomy paradigm,

Bcl-xL overexpression had substantial effects, with survival

of 65% of the motor neurons 7 d after axotomy, as opposed to

only 15% in nontransgenic littermates. To investigate whether

Bcl-xL regulates survival of CNS neurons in the forebrain, we

used a hypoxia-ischemia paradigm in neonatal mice. We show

here that hypoxia-ischemia leads to substantial apoptosis in

the hippocampus and cortex of wild-type neonatal mice.

Furthermore, we show that overexpression of Bcl-xL is

neuroprotective in this paradigm. We conclude that levels of

Bcl-xL in postnatal neurons may be a critical determinant of

their susceptibility to apoptosis.. 0; 0.

234. Pasman, J. W.; Rotteveel, J. J.; Maassen, B.; de Graaf, R.; Visco, Y.

Diagnostic and predictive value of auditory evoked responses

in preterm infants: II. Auditory evoked responses. Pediatr-Res.

1997 Nov; 42(5): 670-7; ISSN: 0031-3998.

UNITED-STATES. In this study, the diagnostic and predictive

value of brainstem, middle latency, and cortical auditory

evoked responses (BMC-AERs) obtained in the neonatal period

in 81 preterm infants was assessed in relation to

neurodevelopmental outcome. The preterm infants were

neonatally classified according to risk category and

gestational age. The BMC-AERs were analyzed with respect to

detectability, latencies, and amplitudes as well as derived

latency and amplitude measures. At 5 y of age the

neurodevelopmental outcome was assessed from neurologic

and neuropsychologic evaluations. The results showed that

BMC-AER differences mainly correlated with risk category

(low risk/high risk) and to some extent with degree of

prematurity. In view of these findings the degree of

prematurity and the effect of risk category have to be taken

into account, when BMC-AERs are applied in the preterm period

to predict neurodevelopmental outcome. In this study the BMC-

AERs for infants with abnormal neurodevelopmental outcome

were scarcely distinguishable from the BMC-AERs for infants

with normal neurodevelopmental outcome. Thus far, this and

previous reports have indicated that BMC-AERs in preterm

infants are useful in maturational studies and with infants

showing symptoms related to lesions or dysfunction of the

peripheral and/or central auditory system. For predicting

neurodevelopmental outcome in preterm infants, BMC-AERs are

of limited clinical value.

235. Pasman, J. W.; Rotteveel, J. J.; Maassen, B.; de Graaf, R.; Visco, Y.

Diagnostic and predictive value of auditory evoked responses

in preterm infants: I. Patient characteristics and long-term

neurodevelopmental outcome. Pediatr-Res. 1997 Nov; 42(5):

665-9; ISSN: 0031-3998.

UNITED-STATES. The diagnostic and predictive value of

brainstem, middle latency, and cortical auditory evoked

responses, obtained in the neonatal period, in 81 preterm

infants was assessed in relation to neurodevelopmental

outcome. Eighteen healthy term infants served as a control

group. In this report the patient characteristics and

neurodevelopmental outcome are presented. The preterm

infants were neonatally classified according to risk category

and gestational age. At 5 y of age the neurodevelopmental

outcome was assessed based on neurologic and

neuropsychologic evaluations. The neuropsychologic test

results showed the highest IQ scores in term infants,

intermediate IQ scores in low risk preterm infants, and lowest

IQ scores in high risk preterm infants. The intermediate IQ

scores in the low risk preterm group were due to significantly

lower test scores in a small subgroup of low risk preterm

infants. In a post hoc analysis 12 low risk preterm infants

with an unfavorable outcome could be identified. The

neuropsychologic test results of the remaining low risk

infants showed no clear differences compared with the term

infants. The results suggest that the unfavorable outcome of

the low risk preterm group as a whole is due to moderate to

severe impairment of the few, rather than slight impairment

of the majority.

236. Passani, L. A.; Vonsattel, J. P.; Coyle, J. T. Distribution of N-

acetylaspartylglutamate immunoreactivity in human brain and

its alteration in neurodegenerative disease. Brain-Res. 1997

Oct 24; 772(1-2): 9-22; ISSN: 0006-8993.

NETHERLANDS. The dipeptide N-acetylaspartylglutamate

(NAAG) may be involved in the process of glutamatergic

signaling by both acting at glutamate receptors and as a

glutamate protransmitter. In the present study we determined

the cellular localization and distribution of NAAG-like

immunoreactivity (NAAG-LI) in normal human brain and in

neurodegenerative disorders to ascertain the degree of NAAG's

colocalization to putative glutamatergic pathways.

Immunohistochemistry with an antibody against NAAG was

performed on control, Huntington's disease (HD) and

Alzheimer's disease (AD) human autopsy and biopsy brain

sections from the cerebral cortex, hippocampus, amygdala,

neostriatum, brainstem and spinal cord. In normal human brain,

NAAG-LI was widespread localized to putative glutamatergic

pyramidal neurons of the cerebral cortex and hippocampus.

Punctate NAAG-LI was present in areas known to receive

neuronal glutamatergic input, such as layer IV of the cerebral

cortex, striatal neuropil, and the outer portion of the

molecular layer of the hippocampal dentate gyrus. In the two

pathologic brain regions examined, the HD neostriatum and the

AD temporal cortex, we observed a widespread loss of NAAG-

LI neurons. In addition NAAG-LI reactive microglia surrounding

plaques were seen in AD temporal cortex but not in the HD

striatum. Our results suggest that NAAG is substantially

localized to putative glutamatergic pathways in human brain

and that NAAG-LI neurons are vulnerable to the

neurodegenerative process in HD and AD.. 0; 0; 3106-85-2.

237. Pau, K. Y.; Ma, Y. J.; Yu, J. H.; Yang, S. P.; Airhart, N.; Spies, H. G.

Topographic comparison of the expression of norepinephrine

transporter, tyrosine hydroxylase and neuropeptide Y mRNA in

association with dopamine beta-hydroxylase neurons in the

rabbit brainstem. Brain-Res-Mol-Brain-Res. 1997 Sep; 48(2):

367-81; ISSN: 0169-328X.

NETHERLANDS. In mammalian species, ovulation occurs

following a massive release of hypothalamic gonadotropin-

releasing hormone (GnRH). Several chemicals, including

norepinephrine (NE) and neuropeptide Y (NPY), are responsible

for the initiation and/or magnitude and duration of this pre-

ovulatory GnRH surge. In the central nervous system, NE neural

cell bodies are located in the brainstem; some are co-localized

with NPY neurons and/or co-express the NE transporter (NET)

gene which dictates NET protein production. The activity of

NET at NE terminals is critical for synaptic NE function. In the

rabbit, coitus induces a hypothalamic NE release which

precedes the GnRH surge. We hypothesize that the coital

stimulus is transmitted to the brainstem and transformed and

integrated into GnRH-stimulating signals via NE, NET and/or

NPY. However, very little is known about the distribution of

cells expressing NET, NPY and tyrosine hydroxylase (TH, the

rate-limiting enzyme of NE synthesis) in this species.

Therefore, we utilized the sensitive in situ hybridization

technique to identify the presence of these messages in

conjunction with the location of NE cells, the latter being

marked by dopamine beta-hydroxylase (DBH), the specific

enzyme for NE synthesis. Three non-mated New Zealand White

does were perfused with 4% paraformaldehyde and their

brainstems were sectioned at 20-micron thick between 2 mm

caudal to the obex and the rostral pons. Serial sections were

immunohistochemically stained for DBH and hybridized with

rabbit-specific TH and NET cRNAs and a human NPY probe. The

data suggest that several DBH-positive areas in the medulla

expressed one or more messages, i.e. the lateral tegmentum

(A1) and the nucleus of the solitary tract (A2) expressed all

three mRNAs, the area postrema (AP) contained NET and TH

mRNAs but not NPY cells. In the pons, the locus coeruleus (LC),

subnucleus of coeruleus (LCs) and lateral tegmental nuclei

(A5) expressed NET and TH mRNAs but contained little or no

NPY message. The distribution patterns of TH and NET appeared

to be similar in the LC, LCs, A2 and AP.. EC 1.14.16.2; EC

1.14.17.1; 0; 0; 0; 136253-20-8; 51-41-2.

238. Penkowa, M.; Hidalgo, J.; Moos, T. Increased astrocytic expression

of metallothioneins I + II in brainstem of adult rats treated

with 6-aminonicotinamide. Brain-Res. 1997 Nov 7; 774(1-2):

256-9; ISSN: 0006-8993.

NETHERLANDS. The cerebral distribution of metallothioneins I

and II (MT-I + II) was studied in adult rats subjected to i.p.

injection with the gliotoxin 6-aminonicotinamide (6-AN). Grey

matter regions of the brainstem heralded numerous OX-42-

positive macrophages and microglia, indicating that 6-AN

primarily caused damage to this part of the brain. In the grey

matter regions infiltrated with OX-42-positive cells,

astrocytes identified by anti-GFAP and MT-I + II antibodies

were almost absent. By contrast, in the peripheral zone of the

lesioned regions numerous reactive GFAP- and MT-I + II-

positive astrocytes were observed. The blood-brain barrier

(BBB) to serum albumin was compromised in the entire

brainstem. The astrocytic expression of MT-I + II could reflect

the brains needs to scavenge metal ions released from either

damaged cells or plasma proteins entering the brain due to the

injured BBB, as well as it could reflect the potential

antioxidant function of MT-I + II.. 0; 0; 329-89-5; 9038-94-2.

239. Perez, N. M.; Benedito, M. A. Activities of monoamine oxidase

(MAO) A and B in discrete regions of rat brain after rapid eye

movement (REM) sleep deprivation. Pharmacol-Biochem-Behav.

1997 Oct; 58(2): 605-8; ISSN: 0091-3057.

UNITED-STATES. Rapid eye movement (REM) sleep deprivation

increases monoaminergic (noradrenergic and serotonergic)

turnover and their metabolites in whole brain of rats. This

increase in metabolites may indicate increased activity of the

enzymes responsible for the inactivation of monoamines. To

test this hypothesis, we assayed the activity of

monoamineoxidases (MAOs) A and B in hippocampus,

hypothalamus, brainstem and its divisions pons and medulla

oblongata in rats deprived of REM sleep for 96 h. REM sleep

deprivation was carried out by the flower-pot technique. A

control group remained in their home cages. MAO A was

assayed by using [14C]-5-hydroxytryptamine as the substrate

(50 microM final concentration) and MAO B by using [14C]-

beta-phenylethylamine (2 microM final concentration). The

enzymes were assayed in the mitochondrial fraction.The

results obtained showed that a significant decrease in the

activity of MAO A was obtained in the brainstem and an

increase in medulla oblongata and no statistical differences in

the activity of MAO B in brainstem, pons and medulla oblongata

and MAO A in pons; there were also no differences in the

activities of both MAO A and B in hippocampus and

hypothalamus. Although our results confirmed previous data

regarding changes in MAO A activity in brainstem and medulla

oblongata, they did not confirm our hypothesis that the

increase in monamine turnover and metabolites in the brain

would be the result of increased MAO activity.. EC 1.4.3.4.

240. Perl, E.; Shufman, E.; Vas, A.; Luger, S.; Steiner, J. E. Taste- and

odor-reactivity in heroin addicts. Isr-J-Psychiatry-Relat-Sci.

1997; 34(4): 290-9; ISSN: 0333-7308.

ISRAEL. Opiates in general, and heroin in particular, are known

to induce compulsive drug-seeking and drug-taking behavior.

Addiction is accompanied by psychobiological processes which

may distort perception of sensory stimuli. Gustatory and

olfactory stimuli are hedonically polarized and therefore most

appropriate for the assessment of the organism's reactivity to

"useful" and "harmful" chemosensory events. Previous studies

revealed that psychophysical self-estimates and reflectory

facial expressions mirror with comparable reliability the

hedonics of the perceived taste and odor sensations. In the

present study both cognitive verbal and reflectory facial

expressions of a group of: a) heroin addicts were recorded and

compared to those of a group of b) detoxified former addicts

and to c) a group of matching controls. Results show that all

three groups differentiate between pleasant, indifferent and

aversive tastes and odors. Active addicts estimated sweet

taste and savory smells as being somewhat more pleasant, and

bitter and sour tastes and a putrid odor as less unpleasant

than did the other two groups. The reflectory facial displays of

addicts were less expressive and discriminative than those of

the two other groups. Taste- and odor-induced facial displays

are known to be controlled primarily by the brainstem. The

findings indicate that heroin-addiction affects brain-

mechanisms, which mirror taste- and odor-hedonics.

Modulation of the phylogenetically ancient, sensory-motor

coordinations was found to be of a different pattern than that

of the cortically-controlled cognitive reactions.

241. Personett, D.; Sugaya, K.; Hammond, D.; Robbins, M.; McKinney, M.

Use of capillary electrophoresis with laser-induced

fluorescence detection to assess messenger ribonucleic acid

molecules amplified by the polymerase chain reaction:

applications in the cloning of cells. Electrophoresis. 1997 Sep;

18(10): 1750-9; ISSN: 0173-0835.

GERMANY. Progressive and selective degeneration of specific

classes of neurons occurs in the Alzheimer's disease (AD)

brain. Differential vulnerability in this disease is evident even

within supopulations that synthesize and release acetylcholine

as a transmitter; i.e., basal forebrain cholinergic neurons

degenerate but other classes of cholinergic neurons are

relatively preserved. The basis for this selective vulnerability

is unknown. Studies of differential neuronal vulnerability in

AD would be facilitated if cell lines expressing

neurotransmitter-specific phenotypes could be cloned from

the brain. Capillary electrophoresis (CE) with laser-induced

fluorescence (LIF) has been shown to be a sensitive method of

detection and quantitation of the DNA products of the

polymerase chain reaction (PCR). CE/LIF was combined with

the PCR to detect phenotypic messenger RNA (mRNA)

molecules, converted to cDNA using reverse transcriptase

(RT), in cultures of virally immortalized brainstem progenitor

cells produced during establishment of a cloning strategy.

RT/PCR methods were developed for detection of the mRNAs

for choline acetyltransferase (ChAT), the neuronal,

constitutive isoform of nitric oxide synthase (c-NOS), and the

growth-associated protein GAP-43, three genes known to be

expressed in central cholinergic neurons. A "nondestructive"

method of screening cultured cells for their expression of c-

NOS was established using depolarization with medium

containing 50 mM potassium ion. These approaches were first

validated using cultured SN56 (cholinergic) and N1E-115 (c-

NOS-positive) neuroblastoma cells, and with primary

brainstem cultures. For the cloning of novel cell lines,

progenitor cells were isolated from the embryonic day 13

fetal brainstem and were immortalized by transfection with a

retroviral vector that confers a temperature-sensitive SV-40

transforming activity and neomycin resistance. Cell colonies

surviving in G418-containing media were isolated and cloned

by dilution. Clonal cultures were expanded by growth at 33

degrees C, differentiated by switching to a low-serum medium

and growth at 39 degrees C, and screened for depolarization-

induced accumulation of nitrite in the medium. The subset of

putative c-NOS-positive clones (about 4%) were then screened

for their expression of mRNAs using RT/PCR in combination

with CE/LIF. This screening protocol proved to be powerful in

the rapid isolation and phenotypic characterization of

immortalized progenitor cells cloned from embryonic rat

brainstem.. EC 1.14.13.39; EC 2.3.1.6; 0; 0.

242. Pierrefiche, O.; Bischoff, A. M.; Richter, D. W.; Spyer, K. M. Hypoxic

response of hypoglossal motoneurones in the in vivo cat. J-

Physiol-Lond. 1997 Dec 15; 505( Pt 3): 785-95; ISSN: 0022-

3751.

ENGLAND. 1. In current and voltage clamp, the effects of

hypoxia were studied on resting and synaptic properties of

hypoglossal motoneurones in barbiturate-anaesthetized adult

cats. 2. Twenty-nine hypoglossal motoneurones with a mean

membrane potential of -55 mV responded rapidly to acute

hypoxia with a persistent membrane depolarization of about

+17 mV. This depolarization correlated with the development

of a persistent inward current of 0.3 nA at holding potentials

close to resting membrane potential. 3. Superior laryngeal

nerve (SLN) stimulation-evoked EPSPs were reduced in

amplitude by, on average, 46% while IPSP amplitude was

reduced by 31% SLN stimulation-evoked EPSCs were reduced by

50-70%. 4. Extracellular application of adenosine (10 mM)

hyperpolarized hypoglossal motoneurones by, on average, 5.6

mV, from a control value of -62 mV. SLN stimulation-evoked

EPSPs decreased by 18% and IPSPs decreased by 46% during

adenosine application. 5. Extracellular application of the KATP

channel blocker glibenclamide led to a blockade of a persistent

outward current and a significant increase of SLN stimulation-

evoked EPSCs. 6. We conclude that hypoglossal motoneurones

have a very low tolerance to hypoxia. They appear to be under

metabolic stress even in normoxia and their capacity to

activate protective potassium currents is limited when

compared with other brainstem neurones. This may help to

explain the rapid disturbance of hypoglossal function during

energy depletion.. 0; 56-65-5; 58-61-7.

243. Pintor, J.; Puche, J. A.; Gualix, J.; Hoyle, C. H.; Miras Portugal, M. T.

Diadenosine polyphosphates evoke Ca2+ transients in guinea-

pig brain via receptors distinct from those for ATP. J-Physiol-

Lond. 1997 Oct 15; 504( Pt 2): 327-35; ISSN: 0022-3751.

ENGLAND. 1. The ability of diadenosine polyphosphates, namely

P1,P2-di(adenosine) pyrophosphate (Ap2A), P1,P3-

di(adenosine) triphosphate (Ap3A), P1,P4-di(adenosine)

tetraphosphate (Ap4A), P1,P5-di(adenosine) pentaphosphate

(Ap5A) and P1,P6-di(adenosine) hexaphosphate (Ap6A) to evoke

Ca2+ signals in synaptosomes prepared from three different

regions of the guinea-pig brain was examined. 2. In

synaptosomal preparations from the paleocortex (cortex),

diencephalon/brainstem (midbrain) and cerebellum all the

dinucleotides evoked Ca2+ signals that were concentration

dependent over the range 1-300 microM. ATP and its synthetic

analogues, alpha,beta-methylene ATP, 2-methylthio ATP and

adenosine 5'-O-(2-thio)diphosphate (all 100 microM) also

evoked Ca2+ signals in these preparations. 3. In the midbrain

and cerebellum preparations, responses to ATP and its

analogues were attenuated or abolished by the P2 receptor

antagonist suramin (100 microM) but responses to the

dinucleotides were not. Also, desensitization by a dinucleotide

blocked responses to dinucleotides but not mononucleotides,

and desensitization by a mononucleotide blocked responses to

mononucleotides but not dinucleotides. 4. In cortical

preparations, suramin (100 microM) blocked responses to both

classes of nucleotides. Furthermore, there was mutual cross-

desensitization between the mono- and dinucleotides. 5. The

adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-

dipropylxanthine, did not affect responses evoked by the

dinucleotides, nor did the pyrimidine UTP. 6. It is concluded

that there are specific dinucleotide receptors, activated by

diadenosine polyphosphates, but not ATP or UTP, on synaptic

terminals in guinea-pig diencephalon/ brainstem and

cerebellum. These receptors bear a similarity to the

dinucleotide receptor (P4 receptor) in rat brain. In guinea-pig

cerebral cortex synaptosomes, diadenosine polyphosphates

appear to act via the same receptor as ATP.. 0; 0; 0; 0;