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Background Asymptomatic carotid artery stenosis (ACS) has a low risk of stroke. To achieve an advantage over noninterventional best medical treatment (BMT), carotid endarterectomy (CEA) or carotid artery stenting (CAS) must be performed with the lowest possible risk of stroke. Therefore, an analysis of risk-elevating factors is essential. Grade of ipsilateral and contralateral stenosis as well as plaque morphology are known risk factors in ACS. Methods The randomized, controlled, multicenter SPACE-2 trial had to be stopped prematurely after recruiting 513 patients. 203 patients were randomized to CEA, 197 to CAS, and 113 to BMT. Within one year, risk factors such as grade of stenosis and plaque morphology were analyzed. Results Grade of contralateral stenosis (GCS) was higher in patients with any stroke (50%ECST vs. 20%ECST; p=0.012). Echolucent plaque morphology was associated with any stroke on the day of intervention (OR 5.23; p=0.041). In the periprocedural period, any stroke was correlated with GCS in the CEA group (70%ECST vs. 20%ECST; p=0.026) and with echolucent plaque morphology in the CAS group (6% vs. 1%; p=0.048). In multivariate analysis, occlusion of the contralateral carotid artery (CCO) was associated with risk of any stroke (OR 7.00; p=0.006), without heterogeneity between CEA and CAS. Conclusion In patients with asymptomatic carotid artery stenosis, GCS, CCO, as well as echolucent plaque morphology were associated with a higher risk of cerebrovascular events. The risk of stroke in the periprocedural period was increased by GCS in CEA and by echolucent plaque in CAS. Due to small sample size, results must be interpreted carefully.

A variety of associated movements have been described in patients with pyramidal tract lesions. We report three patients in whom involuntary stretching of an otherwise plegic arm could be observed during yawning. These patients had radiologically verified lesions at different levels of the pyramidal tract. As yawning and stretching are an automatic behavioural pattern in animals, it is likely that stretches during yawning in man are also an automatic motor pattern, usually inhibited in the presence of an intact corticospinal tract. The physiological function of yawning is unclear at present. Yawning might be the somatomotor manifestation of a particular emotional state characterized by boredom and fatigue. Our observation that movements of an otherwise plegic arm occur in patients with pyramidal tract lesions supports therefore the concept of an emotional motor system which has an independent input to motoneurones in the brain stem and the spinal cord.

Entzundliche Erkrankungen des Gastrointestinaltrakts konnen mit neurologischen Symptomen assoziiert sein. In seltenen Fallen gehen diese der gastrointestinalen Manifestation uber Jahre voraus, weshalb die Kenntnis der Symptome auch fur Neurologen relevant ist. Die einheimische Sprue, durch Unvertraglichkeit auf das Getreideprotein Gluten charakterisiert, geht neurologischerseits mit einer auch neuroradiologisch fassbaren zerebellaren Atrophie mit entsprechender zerebellarer Symptomatik einher. Durch eine konsequente glutenfreie Diat sind gastroenterologische Symptomatik und haufig auch die Ataxie behandelbar. Die neurologische Symptomatik des M. Whipple, einer durch ein grampositives Bakterium verursachten gastrointestinalen Infektion, ist sehr variabel. Kognitive Einbussen, supranukleare Okulomotorikstorungen, Bewegungsstorungen und Symptome der hypothalamischen Dysfunktion sind die haufigsten Symptome dieser seltenen Erkrankung. Die Diagnosesicherung erfolgt uber den Erregernachweis mittels PCR im Liquor. Bei M. Crohn und Colitis ulcerosa treten neurologische Symptome in etwa gleicher Haufigkeit auf. Neben verschiedenen Formen von Polyneuropathien kann es bei Patienten mit chronisch-entzundlichen Darmerkrankungen zu vaskular vermittelten ZNS-Manifestationen kommen, wobei sowohl embolisch bedingte Schlaganfalle und Sinusvenenthrombosen als auch zerebrale Vaskulitiden beobachtet werden.

Elementary geometric imagery seen in the visual aura of migraine can be experienced as incorporated into the content of a dream which precedes the awakening with a migraine headache. Furthermore, recurrent dreams featuring complex visual imagery, often terrifying nightmares, can occur as migraine aura symptoms. The said phenomena are illustrated by two original case reports and discussed against the background of a review of the literature.

BackgroundTranscranial magnetic stimulation of the motor cortex may not only elicit excitatory responses in hand muscles contralateral to the stimulated hemisphere, but may also suppress tonic voluntary electromyogram activity in muscles ipsilateral to the stimulation. This inhibition is mediated between the motor cortices via the corpus callosum.AimsTo investigate motor excitability and interhemispheric (transcallosal) connections in patients with schizophrenia.MethodTranscallosal inhibition and motor conduction parameters were investigated in ten patients with schizophrenia and in ten age- and gender-matched healthy subjects.ResultsTranscallosal conduction time (TCT) and duration of the inhibition were significantly longer in patients with schizophrenia (mean (s.d.)): TCT, 12.4 (2.9) ms in normal subjects and 15.3 (2.6) ms in patients (P=0.03); mean duration, 34.1 (4.9) ms in normal subjects and 51.9 (16.8) ms in patients (P=0.01).ConclusionsMagnetic motor conduction parameters are unaltered in schizophrenia, but transcallosal inhibition is significantly delayed and prolonged. This may indicate abnormal function of the corpus callosum in these patients.

Spontaneous intracranial hypotension is a rare cause of chronic postural headache. We report the case of a 58-year-old woman with a 1.5 year history of chronic headache in upright position, nausea and vomiting. Neurological examination was normal. The Gd-enhanced MRI of the brain showed an abnormal meningeal enhancement over the cerebral convexity. The CSF was normal. Opening pressure during lumbar puncture was 6 cm H2O in the lateral recumbent position. No evidence of underlying systemic, infectious or neoplastic diseases could be detected. The headache was alleviated under theophylline therapy. Spontaneous intracranial hypotension should be considered in the differential diagnosis of chronic postural headache. MRI revealing meningeal enhancement and low opening pressure in lumbar puncture are important findings for the diagnosis of spontaneous intracranial hypotension.

Clinical and experimental data have indicated an up-regulation of amyloid precursor protein (APP) after various types of CNS injury. In the present study the cellular source of lesion-induced APP has been investigated in a neurotoxic CNS model. Quinolinic acid injection into the striatum results in neuronal degeneration, while glial cells survive. APP immunoreactivity was detected in glial cells starting at postoperative day 3 and persisted until day 21, the last time point studied. Double immunocytochemistry identified the majority of APP-immunoreactive cells as glial fibrillary acidic protein-immunoreactive astrocytes. There was no evidence of amyloid fibril deposition during this time. It is concluded that following excitotoxic neuronal degneration APP is mainly produced by reactive astrocytes in the lesioned area.

1. In order to establish the afferent source responsible for the M1 and M2 stretch reflex components of the voluntarily activated human triceps surae muscle, mechanical reflex testing was applied before and during ischaemic blockade of the lower limb. This procedure is known to affect large, fast conducting afferent fibres earliest, specifically Ia afferents arising from muscle spindle afferents. 2. It was found that both the M1 and M2 components were eliminated at the same time, at a point when the P40 peak in the somatosensory evoked potential, produced from stimulation of fast conducting peripheral afferents, was also abolished. This evidence indicates that both reflex components are mediated by information carried by muscle spindle Ia afferents. 3. The M1 component was selectively increased in the early stages of ischaemia. The M2 response did not increase during this period, but showed a tendency to reduce in amplitude. This effect may arise as the result of increased recruitment of motor units in the M1 component reducing the number of units available for activation in the M2 response. 4. These results do not support the view that the M2 reflex component of the triceps surae muscle is mediated by secondary afferent information, but indicate, rather, that both the M1 and M2 components are mediated by Ia afferent information acting on spinal pathways.

Intrastriatal injection of quinolinic acid (QA) in the rat leads to several structural and biochemical events which resemble neuropathological changes seen in the striatum of Huntington's disease patients. In the present experiment the accompanying microglial response in striatal projection areas following QA injection was studied immunocytochemically using monoclonal macrophage/microglial markers. After injection of 240 nmol of QA a marked microglial reaction was observed in the entire striatum, whereas injection of the same amount of solvent resulted only in a local microglial reaction around the injection site. Activated microglia were also found in the globus pallidus (GP), the entopeduncular nucleus (EP), the substantia nigra (SN), and the ventroanterior/ventrolateral, the ventromedial, and, in some rats, the reticular thalamic nucleus. The remote microglial reaction started in the first-order projection areas at Day 1 (GP) or Day 3 (EP, SN) and was found in the second-order projection areas (thalamic nuclei) by Day 5. Areas projecting to the striatum such as the amygdala and intralaminar thalamic nuclei remained free of activated microglia. It is concluded that a microglial response in striatal projection areas accompanies excitotoxic striatal injury. Anterograde degeneration of striatal projection neurons can explain the microglial activation in first-order projection areas but other mechanisms such as neuronal hyperexcitation following removal of inhibitory striatal input must be responsible for the rapid transsynaptic microglial activation seen in the thalamus.

Sprouting of dorsal root axons has been suggested to occur in the mature cat spinal cord caudal to a hemisection at a low thoracic level sparing the dorsal columns. The lesion interrupts supraspinal descending projections, while leaving ascending collaterals of dorsal root axons intact. This hypothesis was re-evaluated by comparing the light and electron microscopic immunoreactivity of B-50 (GAP-43) on both sides of the postulated target regions for sprouting, the intermediate gray and the dorsal horn. The neural-specific phosphoprotein B-50 is involved in regenerative and developmental axonal outgrowth and synaptic plasticity. The light microscopic distribution pattern and density of B-50 immunostaining, measured by quantitative densitometry, were bilaterally symmetrical in all segments below the hemisection 3.5, 8, 14, 21, and 56 days postoperatively, as they were in the intact animal. Ultrastructurally, growth cone-like profiles were not detectable during putative periods of sprouting in regions of interest. After removal of degenerated axon terminals, vacated postsynaptic places appeared to be covered by astrocytic processes. These results indicate that, under the present experimental conditions, sprouting of primary afferents in adult cats is unlikely to be involved in functional plasticity after removal of descending pathways. © 1993 Wiley-Liss, Inc.

The nucleus of Onuf in the sacral spinal cord contains motoneurons that innervate the pelvic floor muscles and possess somatic and autonomic characteristics. We show in this study that in the intact adult cat, the immunocytochemical labelling of the nervous tissue-specific growth-associated protein, B-50 (GAP-43), which persists in Onuf's nucleus, differs markedly from that in the remaining ‘purely somatic’ motor nuclei of the sacral spinal cord. At the light microscopic level, an intense B-50 (GAP-43) immunoreactivity (B-50-IR) in the neuropil of Onuf's nucleus contrasts with a faint staining in the other spinal motor nuclei. Ultrastructurally, B-50-IR is found in Onuf's nucleus within some unmyelinated small diameter nerve fibres and numerous axon terminals on dendritic and somatic surfaces. Conversely, in all other motor nuclei only a few of these structures are stained. No other cellular profiles show B-50-IR in the tissue examined. According to the proposed functions of B-50 (GAP-43), its persistence in mature spinal axon terminals may indicate a latent capability of functional and structural remodeling, as well as an involvement in long-term enhancement in synaptic transmission. If so, these properties would be considerably more pronounce in Onuf's nucleus as compared to purely somatic motor nuclei.

Both somatosensory evoked potentials (SEP) and striatal glucose consumption (rCMRGlc) measured by positron emission tomography (PET) have been reported to be abnormal early in the course of Huntington's disease (HD). To compare their diagnostic value, SEP and rCMRGlc were measured in a group of 18 first degree off-spring of HD families: 6 had manifest HD with chorea and the remaining 12 individuals were chorea-free subjects at risk for HD. In five patients with manifest disease, both SEP and striatal rCMRGlc were significantly abnormal, defined in SEP as having either a bilaterally absent frontal N30 amplitude or a reduction of the parietal N20/P25 amplitude below 1 microV on at least one side; in PET as exhibiting a reduction of the cerebellar ratio (CR) of both caudate and lentiform rCMRGlc below the 99% confidence limits of these variables determined in 20 normal volunteers. The remaining patient with manifest HD had questionably abnormal SEP and significantly reduced indices of striatal rCMRGlc. The five persons at risk for HD who had normal SEP also had normal striatal rCMRGlc; those three at-risk patients with abnormal SEP also had a reduction of the CR of both caudate and lentiform rCMRGlc. Of the remaining four individuals at risk for HD who had questionably abnormal SEP, three had CR values of striatal rCMRGlc in the normal range and one a reduction of the CR of lentiform rCMRGlc. In at-risk patients, the SEP diagnosis correlated significantly with caudate (r = -0.8; p < 0.002) and lentiform (r = -0.76; p < 0.005) rCMRGlc. These data indicate a parallel deterioration of SEP and striatal rCMRGlc early in the course of HD even before the development of chorea.

Since its initial description by Mollaret in 1944, the etiology of the chronic aseptic meningitis has remained unknown. This rare disease may cause diagnostic problems if bacterial or viral causes are suspected. A different form of aseptic meningitis may be seen following a variety of drug treatments, especially with non-steroidal anti-rheumatic drugs: In many reports since 1978, meningitic attacks following administration of ibuprofen have been reported. We describe two cases of Mollaret-Meningitis with certain specialities: one case shows clear encephalitic involvement with aphasia in all six attacks. In the other case, five meningitic attacks appeared spontaneously, while two were drug-induced: the first attack was seen after a lumbar myelography with lopamidol and one attack appeared two hours after oral administration of 400 mg ibuprofen. It is suggested that Mollaret-Meningitis is a special form of a drug-induced allergic reaction, the provoking agent of which remains unknown.

Developmental venous anomalies (DVA) are congenital aberrations in the cerebral venous system reflecting failure of normal embryogenesis. They are considered the most common intracranial vascular malformation. Although they are generally regarded as benign entities, their clinical significance remains controversial--case reports do exist considering DVA to be the origin of thrombosis, cerebral ischemia, and hemorrhage. We report a 26-year-old patient suffering from thrombosis of a DVA.

Idiopathic trigeminal neuralgia is almost always associated with pathological nerve/vessel contact. Symptomatic forms of trigeminal neuralgia include cases of multiple sclerosis, infratentorial tumours and postherpetic neuralgia. Vascular malformations causing neuralgia have rarely been reported. We present the case of a 55-year old woman, who suffered from facial pain and ptosis on her left side. Repeated neurological examinations as well as repeated magnetic resonance imaging did not lead to a definite diagnosis or therapy. The pain suddenly stopped three weeks before admission and only a slight left sided facial hypaesthesia persisted. Reevaluating the older MRI we found a small signal alteration of 2 mm in the caudal part of the left trigeminal nucleus. A new MRI showed a subacute haemorrhage into a small brainstem cavernoma, which must have caused the pain and later on the hypaesthesia. Small vascular malformations are a rare cause of neuropathic facial pain.

A variety of associated movements have been described in patients with pyramidal tract lesions. We report three patients in whom involuntary stretching of an otherwise plegic arm could be observed during yawning. These patients had radiologically verified lesions at different levels of the pyramidal tract. As yawning and stretching are an automatic behavioural pattern in animals, it is likely that stretches during yawning in man are also an automatic motor pattern, usually inhibited in the presence of an intact corticospinal tract. The physiological function of yawning is unclear at present. Yawning might be the somatomotor manifestation of a particular emotional state characterized by boredom and fatigue. Our observation that movements of an otherwise plegic arm occur in patients with pyramidal tract lesions supports therefore the concept of an emotional motor system which has an independent input to motoneurones in the brain stem and the spinal cord.

In previous studies the later parts of the electrically evoked R2 blink reflex has been found to be more susceptible to the inhibitory effects of repetitive stimulation and prepulses. Consequently, it has been suggested that the R2 reflex may be composed of distinct subcomponents. However, as of yet, no study revealed electromyographical evidence for this hypothesis, probably due to a putative temporal overlap that makes it difficult to clearly separate distinct R2 subcomponents. In the present study we investigated the electrically evoked blink reflex in 26 healthy volunteers by using the paradigm of self-stimulation, which has been found to inhibit the R2 and may thus help to differentiate putative R2 subcomponents. In most of the participants self-stimulation resulted in inhibition of the reflex involving predominantly later sections of R2. In addition, in three subjects it was possible to clearly separate distinct R2 subcomponents. These findings suggest that the electrically elicited R2 blink reflex--like the acoustic blink response--consists of superimposed distinct subcomponents. Based on their differential modulation evoked by habituation, pre-stimulation and self-elicitation it is hypothesized that the early portions of the R2 represent the electrically evoked blink reflex, whereas the later sections belong to the generalized startle reaction in man. However, due to their temporal overlap a differentiation might not be possible in conventional recordings.

Some inflammatory diseases of the gastrointestinal system are associated with neurological symptoms which, in rare cases, may precede the onset of the gastrointestinal manifestation of the disease. Celiac sprue is characterized by an intolerance to the wheat protein gluten. The typical neurological manifestation of celiac sprue is cerebellar ataxia. The ataxia as well as the gastrointestinal symptoms can be treated with a strictly gluten-free diet. The neurological symptoms of Whipple's disease, a disorder caused by gram-positive bacilli, are variable. Typical symptoms of cerebral Whipple's disease include dementia, ophthalmoplegia, movement disorders, and signs of hypothalamic dysfunction. Nowadays, the diagnosis of cerebral Whipple's disease is made by PCR detection of the bacilli in the CSF. Crohn's disease and ulcerative colitis are associated with neurological symptoms to a similar proportion. Various forms of polyneuropathies have been observed. The CNS manifestations of inflammatory bowel diseases include thromboembolic stroke, cerebral venous thrombosis, and cerebral vasculitis.

Cheyne-Stokes respiration is characterized by recurrent phases of central apneas during sleep alternating with a crescendo-decrescendo hyperventilation. This abnormal respiratory pattern is often observed in patients with severe congestive heart failure and associated with fragmentation of sleep, excessive daytime sleepiness, and a relatively high mortality. Increased peripheral and central chemosensitivity, prolonged circulation time, and reduced blood gas buffering capacity are the major factors contributing to the pathology. However, the exact pathophysiologic mechanisms are not clear yet. Respiratory stimulants, oxygen and continuous or bilevel positive airway pressure (CPAP or BiPAP) might reduce the severity of Cheyne-Stokes respiration but have little effect on daytime sleepiness and cardiac function. There is only limited data supporting the assumption that intensive heart failure therapy has an effect on Cheyne-Stokes respiration.A 55-year-old male patient with dilative cardiomyopathy (NYHA IV) suffered excessive daytime sleepiness (Epworth Sleepiness Scale: 24 points). The patient was a heavy snorer with a normal body mass index. Treatment was initiated including ACE-inhibitors, beta-receptor blockers, diuretics and digoxin. The patient underwent sleep analysis with a Somno-Check system which demonstrated Cheyne-Stokes breathing (Respiratory Disturbance Index RDI: 40/h, lowest desaturation 76%) and body position dependent snoring. Oxygen therapy (21/min) had no effect on daytime sleepiness. Due to the cardiac condition, the patient was accepted for heart transplantation. Three weeks after transplantation sleep analysis was repeated and demonstrated a lack of evidence for periodic breathing (RDI 1/h, no desaturations below 90%), while snoring remained unchanged. Daytime sleepiness improved significantly (Epworth Sleepiness Scale: 6 points). Three weeks after normalizing left ventricular function a complete recovery from severe Cheyne-Stokes respiration was observed.Adequate therapy of the underlying cause of Cheyne-Stokes breathing such as end-stage congestive heart failure might sufficiently abolish any breathing abnormalities.

To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) in patients with narcolepsy.Using rTMS, three patients with narcolepsy and cataplexy were investigated with and without their anticataplectic medication. rTMS of the motor cortex was performed at an intensity of 110% of resting motor threshold, a frequency of 20 Hz, and a duration of 2s. EMG activity was recorded for both the right and left first dorsal interosseous muscle (FDI). Eight healthy controls were also investigated under the same conditions.The study was carried out in the sleep laboratory of the Neurology Department (University of Aachen).One female and two male patients with narcolepsy/cataplexy.N/A.In three narcoleptic patients, after three days of not taking their usual anticataplectic medication, rTMS of the motorcortex induced an interruption of voluntary EMG activity in the FDI. EMG reduction lasted from 0.6 to 3.5s and was more pronounced in the hand contralateral to the stimulated hemisphere. This result was not observed in these patients when taking their regular medication nor in the normal controls. Stimulation of other cortical areas, as well as stimulation of the peripheral nervous system, did not induce muscle weakness episodes.We postulate that rTMS of the descending voluntary motor pathway triggers muscle atonia similar to cataplexy by indirectly activating the mechanisms responsible for the generation of muscle atonia during REM sleep and cataplexy. We conclude that rTMS, in the future, might prove to be a useful addition to the diagnostic repertoire for narcolepsy.

Background: A routine infectious disease service was established in January 1998 in order to optimize the antibiotic usage and prescription pattern of a neurologic intensive care unit (NICU). Methods: Treatment guidelines for the most prevalent infections wer implemented and individual antibiotic regimes were discussed at the bedside with infectious disease experts. Results: This interdisciplinary cooperation reduced the total number of antibiotics prescribed by 38.1%, from 7,789 in 1997 to 4,822 in 1998, without comprimising patient outcomes (mortality rate: 22/313 patients in 1997 vs 32/328 patients in 1998). Total patient days (2,254 days vs 2,296 days) and average length of stay in the NICU (7.2 days vs 7.0 days) were comparable. Antimicrobial expenditure decreased by 44.8% (71,680 Euros in 1997 vs 39,567 Euros in 1998). Taking into account the costs for the infectious disease service (approximately 8,000 Euros in 1998), a total saving of 24,113 Euros was made. The dramatic reduction in antibiotic usage (mainly of carbapenems) resulted in a statistically significant decreased isolation of Stenotrophomonas maltophilia (p < 0.05), Enterobacter cloacae (p < 0.05), multiresistant Pseudomonas aeruginosa (p < 0.05) and Candida spp. (p < 0.05), without any change in the infection control guidelines. Conclusion: These data show that an infectious disease service can optimize and reduce antibiotic usage. This results in a decrease in the occurrence of multiresistant gram-negative pathogens and Candida spp. in intensive care units, and, at the same time, saves costs.

Elementary geometric imagery seen in the visual aura of migraine can be experienced as incorporated into the content of a dream which precedes the awakening with a migraine headache. Furthermore, recurrent dreams featuring complex visual imagery, often terrifying nightmares, can occur as migraine aura symptoms. The said phenomena are illustrated by two original case reports and discussed against the background of a review of the literature.

Spontaneous intracranial hypotension is a rare cause of chronic postural headache. We report the case of a 58-year-old woman with a 1.5 year history of chronic headache in upright position, nausea and vomiting. Neurological examination was normal. The Gd-enhanced MRI of the brain showed an abnormal meningeal enhancement over the cerebral convexity. The CSF was normal. Opening pressure during lumbar puncture was 6 cm H2O in the lateral recumbent position. No evidence of underlying systemic, infectious or neoplastic diseases could be detected. The headache was alleviated under theophylline therapy. Spontaneous intracranial hypotension should be considered in the differential diagnosis of chronic postural headache. MRI revealing meningeal enhancement and low opening pressure in lumbar puncture are important findings for the diagnosis of spontaneous intracranial hypotension.

Stereotaxic intrastriatal injection of the naturally occurring N-methyl-D-aspartate (NMDA) agonist quinolinic acid (QA) serves as a valuable in vivo model to study excitotoxic cell damage in the central nervous system (CNS). Although morphological changes such as neuronal loss, glial activation and remote reactions following QA injection have been described in some detail, much less is known about the molecular mechanisms mediating the accompanying glial response. Cytokines are known to play a crucial role in almost all kinds of CNS alterations. We now demonstrate that IL-6, a multifunctional glycoprotein which belongs to the family of neurokines, is expressed endogenously in the rat striatum following QA injection. Using Northern blot analysis, a massive but transient upregulation of IL-6 mRNA could be detected. This started 3 h after QA injection, reached a maximum at 6 h and disappeared within 24 h. That activated microglia are the most likely cellular source of the observed corresponding IL-6 protein expression could be concluded by comparing the immunocytochemical pattern of IL-6 expression and microglial activation. Interestingly, astrocytes initially downregulate their expression of glial fibrillary acidic protein (GFAP) in the excitotoxically injured striatum, but show a delayed increase in GFAP immunoreactivity starting in the periphery of the striatum, subsequently expanding to the core. The early transient IL-6 expression may play an important role in initiating the delayed astrocytic response following excitotoxic cell injury.

A 46-year old patient is reported presenting with somatosensory focal seizures of either arm as the only manifestation of an otherwise clinically inapparent sarcoidosis. MRI showed signs of a granulomatous leptomeningeal affection. Histological examination of a meningeal biopsy proved the diagnosis of sarcoidosis by demonstrating noncaseating granulomas. There was no other clinical manifestation of sarcoidosis. Chest X-ray was normal and the serum level of angiotensin-converting-enzyme was only slightly elevated. The CD4/CD8 ratio in the bronchoalveolar lavage cell population, however, was clearly abnormal, supporting the role of this diagnostic tool in the diagnosis of sarcoidosis.

Home ventilation has developed as a sufficient and safe method in many neurological diseases afflicting respiratory functions. To achieve an overview of the situation of these patients in Germany, a questionnaire was distributed by the manufacturer of the most commonly used ventilator in Germany. The patients were asked to send the form back, even anonymous, to the Department of Neurology, RWTH Aachen. 65 of 110 questionnaires were answered, most of patients with muscle dystrophy's (n = 14), Polio (n = 14) and spinal cord injuries (n = 11). Home ventilation in ALS was performed in 3 cases only. The majority of patients (n = 30) was aged between 20 and 49 years, but here were also 5 children younger than 10 years. Most patients were ventilated not more than 4 years, but there were also 5 patients ventilated for over 20 years, all of them Polio-patients. 70% of all lived at home with their relatives, who take care for them. Nevertheless, 13 were full- or part-time working.

Recent neuropathological studies have indicated that the degenerative process in patients with early Huntington’s disease is restricted to a subpopulation of caudate neurons projecting to the internal pallidal segments (Albin et al., 1990). In more advanced cases of Huntington’s disease degenerative changes are found in other parts of the basal ganglia as well as in cortical and thalamic areas (for review Richardson, 1990). The question what causes the progression of the neuropathology has not yet been answered. Does the hitherto unknown pathogenetic mechanism affect these extrastriatal areas at a later timepoint or do transneuronal degenerative processes play a role here?

Sprouting of dorsal root axons has been suggested to occur in the mature cat spinal cord caudal to a hemisection at a low thoracic level sparing the dorsal columns. The lesion interrupts supraspinal descending projections, while leaving ascending collaterals of dorsal root axons intact. This hypothesis was re-evaluated by comparing the light and electron microscopic immunoreactivity of B-50 (GAP-43) on both sides of the postulated target regions for sprouting, the intermediate gray and the dorsal horn. The neural-specific phosphoprotein B-50 is involved in regenerative and developmental axonal outgrowth and synaptic plasticity. The light microscopic distribution pattern and density of B-50 immunostaining, measured by quantitative densitometry, were bilaterally symmetrical in all segments below the hemisection 3.5, 8, 14, 21, and 56 days postoperatively, as they were in the intact animal. Ultrastructurally, growth cone-like profiles were not detectable during putative periods of sprouting in regions of interest. After removal of degenerated axon terminals, vacated postsynaptic places appeared to be covered by astrocytic processes. These results indicate that, under the present experimental conditions, sprouting of primary afferents in adult cats is unlikely to be involved in functional plasticity after removal of descending pathways.

The distribution of the neural-specific growth associated protein B-50 (GAP-43), which persists in the mature spinal cord and dorsal root ganglia, has been studied by light and electron microscopic immunohistochemistry in the cat. Throughout the spinal cord, B-50 immunoreactivity was seen confined to the neuropil, whereas neuronal cell bodies were unreactive. The most conspicuous immunostaining was observed in the dorsal horn, where it gradually decreased from superficial laminae (I–II) toward more ventral laminae (III–V), and in the central portion of the intermediate gray (mainly lamina X). In these regions, the labelling was localized within unmyelinated, small diameter nerve fibres and axon terminals. In the rest of the intermediate zone (laminae VI–VIII), B-50 immunoreactivity was virtually absent. The intermediolateral nucleus in the thoracic and cranial lumbar cord showed a circumscribed intense B-50 immunoreactivity brought about by the labelling of many axon terminals on preganglionic sympathetic neurons. In motor nuclei of the ventral horn (lamina IX), low levels of B-50 immunoreactivity were present in a few axon terminals on dendritic and somal profiles of motoneurons. In dorsal root ganglia, B-50 immunoreactivity was mainly localized in the cell bodies of small and medium-sized sensory neurons. The selective distribution of persisting B-50 immunoreactivity in the mature cat throughout sensory, motor, and autonomie areas of the spinal cord and in dorsal root ganglia suggests that B-50-positive systems retain in adult life the capacity for structural and functional plasticity.

Transection of the rat facial nerve leads to an intrinsic microglial reaction in the facial nucleus. In the present study, we have examined immunocytochemically the expression of cell adhesion molecules during this process. Resting microglia constitutively expressed the LFA-1 alpha and beta chain (CD11a and CD18) in the white matter, rather than in the intact, control facial nucleus. From 24 h after facial nerve transection onward, activated microglia showed an increased expression of LFA-1 alpha and beta. The immunoreactivity reached its peak around day 7 following axotomy, i.e. at a time when activated microglia are found in a close perineuronal position. In contrast, the expression of the principal ligand of LFA-1, i.e. ICAM-1, remained unchanged following axotomy; the immunoreactivity being constitutively found on cerebral blood vessels. Increased LFA-1 expression thus appears to be a general marker for microglial activation and might further be involved in the rearrangement of the microglial cytoskeleton upon activation of this cell.

A fast route for transmission of deep and cutaneous afferent information to the frontal cortex is well established in non-human primates. Whether the incoming cortical information gives rise to early frontal somatosensory evoked potentials (SEPs) in humans is still a matter of contention. We attempted to solve this question by investigating the topography of SEP generators evoked by median nerve stimulation in 30 healthy subjects and in 30 patients suffering from Huntington's disease, who are known to have reduced SEP amplitudes. Using an earlobe reference, SEPs were recorded with an array of either five surface electrodes over the contralateral parietal cortex or 32 electrodes distributed over the whole scalp. In normal subjects analysis of frontal potentials revealed an early positive (P22) and negative (N30) component which could not be explained by generators located in the parietal cortex. Apart from the reduction of parietal components (N20, P25) frontal P22 and N30 were diminished or absent in Huntington's disease patients. Frontal potentials were even reduced in those patients who had parietal SEP amplitudes within the range of normal subjects. These frontal changes are similar to those reported in other basal ganglia disorders. Basal ganglia dysfunction might therefore be associated with changes of frontal SEP components.

Both somatosensory evoked potentials (SEP) and striatal glucose consumption (rCMRGlc) measured by positron emission tomography (PET) have been reported to be abnormal early in the course of Huntington's disease (HD). To compare their diagnostic value, SEP and rCMRGlc were measured in a group of 18 first degree off-spring of HD families: 6 had manifest HD with chorea and the remaining 12 individuals were chorea-free subjects at risk for HD. In five patients with manifest disease, both SEP and striatal rCMRGlc were significantly abnormal, defined in SEP as having either a bilaterally absent frontal N30 amplitude or a reduction of the parietal N20/P25 amplitude below 1 microV on at least one side; in PET as exhibiting a reduction of the cerebellar ratio (CR) of both caudate and lentiform rCMRGlc below the 99% confidence limits of these variables determined in 20 normal volunteers. The remaining patient with manifest HD had questionably abnormal SEP and significantly reduced indices of striatal rCMRGlc. The five persons at risk for HD who had normal SEP also had normal striatal rCMRGlc; those three at-risk patients with abnormal SEP also had a reduction of the CR of both caudate and lentiform rCMRGlc. Of the remaining four individuals at risk for HD who had questionably abnormal SEP, three had CR values of striatal rCMRGlc in the normal range and one a reduction of the CR of lentiform rCMRGlc. In at-risk patients, the SEP diagnosis correlated significantly with caudate (r = -0.8; p0.002) and lentiform (r = -0.76; p0.005) rCMRGlc. These data indicate a parallel deterioration of SEP and striatal rCMRGlc early in the course of HD even before the development of chorea.

Transforming growth factor-beta 1 (TGF-beta 1) and interleukin-1 beta mRNA expression were studied in rat brains after 30 min of global ischemia by in situ hybridization. Ischemia was produced by four-vessel occlusion followed by different recirculation times ranging between 15 min and 7 days. TGF-beta 1 mRNA could first be detected 3 days after ischemia in the hippocampus, in layers II/III of cortex, in the striatum and in parts of the ventral thalamus. At 7 days after recirculation a prominent increase in TGF-beta 1 mRNA was observed in the CA1 sector of the hippocampus. Induction of interleukin-1 beta mRNA, however, was less marked and limited to the rostral striatum 3 and 7 days after ischemia. TGF-beta 1 expression 7 days after ischemia correlated well with the histological localization of regions where neuronal degeneration and subsequent astrocytic and microglial activation had occurred. In adjacent brain sections, the distribution of TGF-beta 1 mRNA after 7 days closely resembled that of the immunostaining pattern of activated microglia, indicating that at this time point TGF-beta 1 mRNA was mainly produced by microglial cells. The late induction of TGF-beta 1 mRNA after ischemia points to an involvement in the persistent glial response rather than the initial glial activation. The differential pattern of interleukin-1 beta mRNA induction indicates regional variations of cytokine production after ischemic brain lesions.

Intrastriatal injection of quinolinic acid (QA) in rats provides an animal model that mimics some of the neuropathological and neurochemical alterations observed in the striatum of patients with Huntington's disease (HD). One of the very early neurophysiological signs in HD is a diminution of amplitude of early somatosensory evoked potentials (SEPs) recorded over the parietal cortex. The present study investigated whether the QA model exhibits similar neurophysiological abnormalities. Two weeks after unilateral intrastriatal injection of QA (240 nmol) or of the solvent, early SEPs were recorded with chronically implanted electrodes from the somatosensory cortex or from the ventrobasal nucleus of the thalamus of lightly pentobarbital-anesthetized rats, in response to single-shock electrical stimulation of the contralateral forepaw. Whereas intrastriatal injection of solvent did not influence SEPs, the striatal QA lesion significantly reduced the amplitude of early cortical SEPs by about 40% without affecting the latency. SEPs recorded from the ventrobasal nucleus were unchanged after QA lesion. Histological examination and glial fibrillary acid protein staining after intrastriatal injection of QA revealed no evidence for damage in the somatosensory system. It is concluded that (1) the QA animal model of HD mimics some of the SEP abnormalities of patients, and (2) a striatal lesion modulates somatosensory transmission to the cortex in rats.