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HISTORY AND FINDINGS A 69-year-old woman reported marked restriction of voluntary movements of the hands in the preceding 6 months. She had also experienced loss of motivation, memory and concentration. Her skin was pale yellow, and scratches on her skin indicated marked pruritus. INVESTIGATIONS Neurological examination revealed decreased vibratory sense in both legs. Haemoglobin concentration was 8.3 g/dl, mean corpuscular volume 114 fl, vitamin B12 level < 100 ng/l, folic acid level normal. Antibody titre against parietal cells was increased, vitamin B12 resorption diminished. Gastroscopy revealed small raised lesions, made up of hyperplastic cells which stained with chromogranin, indicating a diagnosis of microcarcinoid of the gastric mucosa. TREATMENT AND COURSE On administration of cobalamine (1,000 micrograms i.m. daily for 2 weeks, twice weekly for 6 weeks, then once per week for the last 7 months) the blood picture returned to normal, but the microcarcinoids, the psychological symptoms and the apraxia of the hands were unchanged.

Patients with obstructive sleep apnoea syndrome (OSAS) have an increased car accident rate. Investigations on accident frequency are based on case history, insurance reports and driving simulator studies. The present study combines neuropsychological testing of different attention aspects engaged in driving a car and driving simulation to evaluate a suitable instrument for assessing therapeutic effects of continuous positive airway pressure (CPAP). Driving simulator investigation and neuropsychological testing of alertness, vigilance and divided attention were performed in 31 patients with polysomnographically confirmed OSAS (apnoea-hypopnoea index 24.8+/-21.5.h(-1)) before, and 2 and 42 days after initiation of CPAP. Divided attention and alertness improved significantly during CPAP, whereas vigilance remained unchanged. However, accident frequency (OSAS before therapy: 2.7+/-2.0; 2 days after CPAP: 1.5+/-1.4; 42 days after CPAP: 0.9+/-1.3) and frequency of concentration faults (OSAS before therapy: 12.4+/-5.1; 2 days after CPAP: 6.5+/-3.9; 42 days after CPAP: 4.9+/-3.3) decreased in the simulated driving situation after 2 and 42 days of therapy. There was no relation between accident frequency, concentration faults and daytime sleepiness, as measured by the Epworth Sleepiness Scale, and polysomnographic or neuropsychological findings, respectively. In conclusion, the present results suggest that driving simulation is a possible benchmark parameter of driving performance in obstructive sleep apnoea syndrome patients.

Daytime sleepiness is a leading symptom of various diseases, and is an important cause of accidents at the workplace and on the road. For the evaluation of accident frequency, the medical history, neurophysiological and neuropsychological tests, and driving simulator performance are applied. The present paper describes these different methods, and assesses their value in predicting accidents. In the last resort, no single test suffices to evaluate the accident risk of patients suffering from daytime sleepiness--rather, a combination of the methods described is needed, in particular when an expert opinion on a patient's ability to drive is required. To date, no controlled studies have been done to compare the predictive value of the methods considered herein. Our results suggest that the nearness of driving simulation to reality makes it a suitable additional test method, in particular for the monitoring of results under treatment.

Der seltenen adulten Polyglukosankorperkrankheit (APBD) liegen autosomal-rezessiv vererbte Defekte des Glykogen-Branching-Enzyms zugrunde. Die Erkrankung wird meist zwischen dem 40. und 60. Lebensjahr klinisch manifest und verlauft langsam progredient. Pathologisch-anatomisch konnen charakteristische globulare Ablagerungen (Polyglukosankorper, PGK) in Biopsaten von Haut, Muskulatur und peripheren Nerven sowie im Zentralnervensystem nachgewiesen werden. Diese bestehen biochemisch aus verzweigungsarmen Glykogenmolekulen mit pathologisch langen einzelnen Polysaccharidketten. Wir berichten uber die Sektionsbefunde einer 50 Jahre alt gewordenen Patientin, die klinisch an typischen neurologischen Ausfallen wie spastischen Lahmungen, Blaseninkontinenz, Sensibilitatsstorungen und kognitiven Einschrankungen bis hin zur Demenz litt. Sie verstarb unerwartet an einem akuten Herztod. Erst durch die Autopsie konnte eine bereits fortgeschrittene Kardiomyopathie mit reichlich scholligen Polyglukosankorpern in den Herzmuskelfasern als Todesursache nachgewiesen werden. Diese Fallbeobachtung zeigt, dass bei der adulten Polyglukosankorperkrankheit neben den bekannten Speicherphanomenen in Nervensystem und Muskulatur auch die Moglichkeit einer Herzbeteiligung zu berucksichtigen ist.

Patients with obstructive sleep apnea syndrome (OSAS) have an accident rate between two and seven times higher than normals. Investigations on accident frequency are based on case history, insurancy reports, and driving simulator investigations. The present controlled study was planned to test whether an increased accident risk could be demonstrated in patients with OSAS before and on CPAP (continuous positive airway pressure)-therapy using the driving simulator C.A.R. Driving simulator performance was investigated in 31 patients with polysomnographically confirmed OSAS (apnea-hypopnea-index 24.8 +/- 21.5/h) before, 2 and 42 days after initiation of CPAP and was compared to 10 healthy controls in whom OSAS was excluded by polysomnography. Driving simulator performance was significantly worse in OSAS as compared to normals especially in terms of accident frequency (OSAS: 2.7 +/- 2.0, controls: 1.3 +/- 1.5, p < 0.05) and concentration faults (OSAS: 12.4 +/- 5.1, controls: 7.1 +/- 3.2, p < 0.01). On CPAP accident frequency (OSAS before therapy: 12.4 +/- 5.1, 2 days CPAP: 1.5 +/- 1.4, p < 0.01; 42 days CPAP: 0.9 +/- 1.3, p < 0.001) and frequency of concentration faults (OSAS before therapy: 12.4 +/- 5.1, 2 days CPAP: 6.5 +/- 3.9, p < 0.001; 42 days CPAP: 4.9 +/- 3.3, p < 0.001) could be lowered significantly both in the short and medium term of therapy. The driving simulator C.A.R. is an adequate tool for the evaluation of an increased accident risk in OSAS-patients and demonstrates the efficiency of CPAP-therapy.

A 45-year-old woman developed meningoencephalitis owing to an infection with Brucella abortus. The probable source of infection was contaminated ewe's milk cheese. Treatment with cefotaxim and doxycycline led to regression of the clinical symptoms and serological findings.

Autopsy of a 50-year-old woman with adult polyglucosan body disease and missense mutations (Arg515His, Arg524Gln) in the glycogen branching enzyme gene (GBE) revealed accumulation of polyglucosan bodies in the heart, brain, and nerve. GBE activity was decreased in the morphologically affected tissues but was normal in unaffected tissues. GBE mRNA transcripts were similar in all tissues and in controls, which confirms the lack of tissue-specific GBE isoforms.

The prevalence of clinical and electrophysiological signs of peripheral nerve disease was evaluated in 151 patients with chronic obstructive pulmonary disease. Patients with concomitant disorders affecting the peripheral nervous system were excluded. Thirty patients had clinical signs of a mild sensorimotor and distal neuropathy and 13 additional patients had only electrophysiological abnormalities. The rate and the severity of the neuropathy correlated with the severity of chronic hypoxaemia. Three out of 20 patients with mild hypoxaemia (PaO2 less than 15 mm Hg below normal) had polyneuropathy as compared with 15 out of 36 with severe hypoxaemia (PaO2 more than 30 mm Hg below normal (rates different at the 10% level)). PaO2 and age were the only variables discriminating between patients with and without peripheral neuropathy.

Patients with obstructive sleep apnoea syndrome (OSAS) have an increased car accident rate. Investigations on accident frequency are based on case history, insurance reports and driving simulator studies. The present study combines neuropsychological testing of different attention aspects engaged in driving a car and driving simulation to evaluate a suitable instrument for assessing therapeutic effects of continuous positive airway pressure (CPAP). Driving simulator investigation and neuropsychological testing of alertness, vigilance and divided attention were performed in 31 patients with polysomnographically confirmed OSAS (apnoea-hypopnoea index 24.8+/-21.5.h(-1)) before, and 2 and 42 days after initiation of CPAP. Divided attention and alertness improved significantly during CPAP, whereas vigilance remained unchanged. However, accident frequency (OSAS before therapy: 2.7+/-2.0; 2 days after CPAP: 1.5+/-1.4; 42 days after CPAP: 0.9+/-1.3) and frequency of concentration faults (OSAS before therapy: 12.4+/-5.1; 2 days after CPAP: 6.5+/-3.9; 42 days after CPAP: 4.9+/-3.3) decreased in the simulated driving situation after 2 and 42 days of therapy. There was no relation between accident frequency, concentration faults and daytime sleepiness, as measured by the Epworth Sleepiness Scale, and polysomnographic or neuropsychological findings, respectively. In conclusion, the present results suggest that driving simulation is a possible benchmark parameter of driving performance in obstructive sleep apnoea syndrome patients.

What are the clinical findings in patients with chronic complex regional pain syndrome (CRPS)?Bedside examination was performed in 40 patients with CRPS and a mean illness duration of 43 months. To evaluate motor and autonomic disturbances, rating scales were developed and applied. Quantitative sensory testing (QST) was conducted in 24 patients.Clinical examination revealed sensory abnormalities in 93% of patients examined (in 56% limited to the affected limb, in 7% in the upper quadrant of the body, in 30% hemisensory impairment of the ipsilateral body side), and 60% of the patients suffered from mechanical allodynia in the affected limb. Patients with generalized sensory impairment had a significantly longer illness duration, pain intensity and significantly higher frequency of mechanical allodynia/hyperalgesia than patients with sensory deficits limited to the limb affected. In patients with generalized sensory abnormalities, QST revealed significant changes of cold, warm and touch thresholds on the ipsilateral compared to the contralateral body side. Mild/moderate motor abnormalities could be demonstrated in 45% of patients, tremor (50%), impaired joint movements, 45%, and 40% of patients revealed autonomic disturbances.In chronic CRPS, among clinical symptoms and signs, pain and sensory impairment play a major role. Mechanical allodynia reveals the highest level of subjective disability among all symptoms. With respect to hemisensory impairment, functional disturbances of central pain processing in the nucleus ventralis posterior of the thalamus are postulated.

Do comorbid psychological disorders, dysfunctional pain processing, and psychosocial pain coping occur with complex regional pain syndrome (CRPS) and is a connection between clinical and psychological manifestations apparent?In addition to securing information on case histories and performing clinical neurological examinations of chronic CRPS patients, the structured clinical interview (SCID), pain perception scale, and the Kiel Pain Inventory were employed.The structured clinical interview revealed evidence of a depressive episode in 65% of CRPS patients. Pain perception is similar to neuropathic pain syndromes and patient history revealed a slightly increased frequency of anxiety and affective disorders. Depressive syndrome occurred significantly more often in right-sided CRPS; otherwise, there were no significant correlations between medical history, clinical examination, and frequency of psychological disorders. However, CRPS patients with allodynia manifest clinical signs of special psychological distress.In chronic CRPS depressive syndrome frequently develops and psychological treatment can be recommended.

Besides painful ophthalmoplegia, patients suffering from Tolosa-Hunt syndrome often present increasing loss of visual perception. The impairment of the optic nerve leads to a delay of the VEP (visual evoked potentials) responses. Using the method of magnetic resonance imaging (MRI), some patients present unspecific alterations in the vicinity of the optic nerve. However, both methods (VEP and MRI) are unsuitable to assess the effect of an impaired optic nerve function on neuronal processing in the visual cortex. We report one patient suffering from Tolosa-Hunt syndrome affecting the optic nerve. We used fMRI (functional magnetic resonance imaging) to show how this impairment of the optic nerve alters cortical processing of visual information. The activity of the unaffected visual cortex was bilaterally reduced when compared to healthy volunteers but greater that obtained from patients suffering from bilateral occipital infarction. Our results offer new opportunities to assess the efficiency of therapy in patients with increasing loss of visual perception due to the Tolosa-Hunt syndrome. Further studies are necessary to investigate, whether fMRI also provides the possibility to assess the efficiency of drug therapy on optic nerve function.

Patients suffering from multiple sclerosis often complain of fatigue and sleepiness. Patients often cannot distinguish between these symptoms. Daytime sleepiness, attention and concentration deficits affect life quality severely. Usually symptoms of MS are characterized by the Expanded Disability Status Scale (EDSS). In new studies the MSFC proves to be a more sensitive method especially estimating the cognitive deficits.31 RRMS patients (18 women, 13 men, mean age 35.6 +/- 8.3 years) and 19 healthy controls (9 men, 1 woman, age: 55.1 +/- 7.8 years) were assessed by: 1) morning and evening protocols of the German Sleep Society, 2) Epworth Sleepiness Scale (ESS), 3) Extended Disability Status Scale (EDSS), 4) MS Functional Composite (MSFC) based on arm function, ambulation and cognition (paced auditory serial addition test, PASAT), 5) Fatigue Severity Scale (FSS).The EDSS-Score ranged from 1.0 to 6.5 (2.8 +/- 1.4). Mean Z-Score of MSFC was -0.19 +/- 0.63. Most deficits could be shown in the PASAT. Total sleep time correlated with recovery capacity of sleep (r = 0.42, P0.05). The ESS-Score was 6.1 +/- 2.9 (1 - 14). FSS-Score was raised with intraindividual variability (4,33 +/- 1.62, 1.4 - 7). The EDSS failed to correlate with the ESS- or FSS-Score. FSS correlated significantly with arm function (r = 0.465) und ambulation (r = 0.436) in the MSFC (P0.05).MS-Patients are often not able to distinguish between fatigue and sleepiness. By using different scales judging sleepiness and fatigue significant differences could be evaluated. Fatigue is mainly linked to motoric deficits scored by the MSFC. Therefore medication with stimulants seems not to be useful in fatigue therapy.

The aim of our study was to determine the role of N-methyl-d-aspartate (NMDA)-mediated mechanisms in cortical excitability changes after limb amputation, and their possible relationship to phantom pain.Sixteen upper limb amputees who were suffering from chronic phantom pain received the NMDA-antagonist memantine or placebo for 3 weeks. Intracortical inhibition (ICI) and intracortical facilitation (ICF) were determined at baseline and on day 21 using transcranial magnetic stimulation. Simultaneously, phantom pain intensity was assessed.Memantine reduced ICF and enhanced ICI to roughly the same extent as seen in healthy subjects in a previous study. These changes were not correlated to the reduction of phantom pain.We therefore conclude that NMDA-mediated mechanisms influence changes of ICI and ICF occurring after limb amputation. However, our results suggest that these cortical excitability changes and phantom pain are independent of each other.

Coenesthesias can be defined as disorders of body perception or body hallucinations, projected in different parts of the body. Patients complain of intractable pain or dysesthesia. These symptoms are reported even from organs where we usually have no perception. Coenesthesia must be regarded as a symptom that can be observed in various psychiatric diseases, e.g., schizophrenia. However, in rare cases coenesthesias can be documented in neurological diseases, e.g., intracranial tumors or infections. Therefore, accurate assessment of possible differential diagnoses is important. In late stages, coenesthesias can easily be recognized because of their "bizarre" character. In early stages, however, patients often complain of intractable, unlocalizable burning pain. They frequently undergo operations because of their great suffering. The drug treatment of first choice is neuroleptics, but the results are unpredictable.The case studies of three patients are presented and discussed (patient 1 with coenaesthetic schizophrenia, patient 2 with coenesthesia in the course of a delusional (paranoid) disorder; patient 3 with coenesthesia caused by carcinomatous meningitis).

Daytime sleepiness is a leading symptom of various diseases, and is an important cause of accidents at the workplace and on the road. For the evaluation of accident frequency, the medical history, neurophysiological and neuropsychological tests, and driving simulator performance are applied. The present paper describes these different methods, and assesses their value in predicting accidents. In the last resort, no single test suffices to evaluate the accident risk of patients suffering from daytime sleepiness--rather, a combination of the methods described is needed, in particular when an expert opinion on a patient's ability to drive is required. To date, no controlled studies have been done to compare the predictive value of the methods considered herein. Our results suggest that the nearness of driving simulation to reality makes it a suitable additional test method, in particular for the monitoring of results under treatment.

Varicella zoster virus (VZV) causes varicella (chickenpox), remains dormant in dorsal root and cranial nerve ganglia and can be reactivated as a consequence of declining VZV-specific cellular immunity leading to herpes zoster (shingles). Patients older than 50 years of age affected by herpes zoster may suffer a significant decrease of quality of life. These patients and immunocompromised individuals are at increased risks for severe complications, involving the eye, the peripheral and the central nervous system (prolonged pain, postherpetic neuralgia). Such complications occur with and without cutaneous symptoms. The German Dermatology Society (DDG) has released guidelines in order to guarantee updated management to anyone affected by herpes zoster. Diagnosis is primarily clinical. The gold standard of laboratory diagnosis comprises PCR and direct identification of VZV in cell cultures. Detection of IgM- and IgA-anti VZV antibodies may be helpful in immunocompromised patients. Therapy has become very effective in the last years. Systemic antiviral therapy is able to shorten the healing process of acute herpes zoster, to prevent or to alleviate pain and other acute and chronic complications, particularly, when given within 48 h to a maximum of 72 h after onset of the rash. Systemic antiviral therapy is urgently indicated in patients beyond the age of 50 years and in patients at any age with herpes zoster in the head and neck area, especially in patients with zoster ophthalmicus. Further urgent indications are severe herpes zoster on the trunk and on the extremities, herpes zoster in immunosuppressed patients and in patients with severe atopic dermatitis and severe ekzema. Only relative indications for antiviral therapy exist in patients younger than 50 years with zoster on the trunk and on the extremities. In Germany acyclovir, valacyclovir, famciclovir and brivudin are approved for the systemic antiviral treatment of herpes zoster. These compounds are all well tolerated by the patients and do not differ with regard to efficacy and safety. Brivudin has a markedly higher anti-VZV potency than oral acyclovir, valacyclovir and famciclovir and thus offers a simpler dosing regimen. It must be given only once daily during 7 days in comparison to three and five times dosing per day of valacyclovir, famciclovir and acyclovir, respectively. Brivudin is an antiviral agent with no nephrotoxic properties, which is an advantage when compared to acyclovir. The most important aim of therapy of herpes zoster is to achieve painlessness. Appropriately dosed analgesics in combination with a neuroactive agent (i.e. amitriptylin) are very helpful when given together with antiviral therapy. The additive therapy with corticosteroids may shorten the degree and duration of acute zoster pain, but has no essential effect on the development of postherpetic neuralgia, which is a very difficult condition to treat. Thus early presentation to a pain therapist is recommended in specific cases.

Adult polyglucosan body disease (APBD) is a rare genetic disorder, inherited in an autosomal recessive mode. The disease is caused by mutations of the gene coding for the glycogen-branching enzyme, which is essential for branching of polyglucose chains in the normal glycogen molecule. The age of clinical manifestation of the disease mostly is between 40 and 60 years and its course is slowly progressive. Characteristic globular deposits (polyglucosan bodies, PGB) can be detected in biopsies of skin and skeletal muscle as well as in the peripheral and central nervous system. Biochemically, PGBs consist of poorly branched glycogen molecules with abnormally long polysaccharide chains. We report the case of a 50-year-old female patient with APBD who suffered from neurological symptoms such as spastic tetraparesis, urinary incontinence, hypesthesia and dementia. She died unexpectedly of cardiac failure. At autopsy a severe cardiomyopathy with abundant PGBs in the heart muscle fibres could be proven as the cause of death. This observation shows that in addition to the known deposition of PGBs in nervous system and skeletal muscle, an involvement of the heart has to be considered in APBD as well.

The Multiple Sclerosis Functional Composite (MSFC) comprises quantitative functional measures of leg, hand/arm and cognitive function. We examined the responsiveness of the MSFC compared with the Expanded Disability Status Scale (EDSS) during treatment of relapses in patients with multiple sclerosis (MS).27 patients received 1000 mg intravenous methylprednisolone (i.v.-MP) for 5 days, followed by oral methylprednisolone for 14 days. The MSFC and the EDSS-score were assessed on day 0, before the first corticosteroid treatment, on day 5, after the last course of i.v. MP, and on day 20 after the treatment was finished. Before the first administration of the MSFC, patients were trained for the paced auditory addition test (PASAT) performing three test trials. In order to analyse practice effects, 10 MS patients without an acute exacerbation were tested three times under the same conditions as the treated group.The median EDSS-score was 2.5 in both groups. On day 5 it remained unchanged in all treated patients, on day 20 a decrease of 0.5 EDSS point occurred in five patients, and in two patients an improvement with a decrease of more than 0.5 point was observed. There was no statistically significant difference between the EDSS-scores on day 0, 5 and 20. The mean MSFC-score in the treated group was -0.14 +/- 0.63 on day 0, 0.17 +/- 0.66 on day 5, and 0.42 +/- 0.59 on day 20. On the last study day, 26 patients improved compared with day 0. The differences between the MSFC-scores at the three points of time were statistically significant for the treated group (P0.001), but not for the control group.During and after treatment of relapses in patients with MS, the MSFC appears to be more sensitive in detecting changes in function than the EDSS.

Patients with obstructive sleep apnea syndrome (OSAS) have an accident rate between two and seven times higher than normals. Investigations on accident frequency are based on case history, insurancy reports, and driving simulator investigations. The present controlled study was planned to test whether an increased accident risk could be demonstrated in patients with OSAS before and on CPAP (continuous positive airway pressure)-therapy using the driving simulator C.A.R. Driving simulator performance was investigated in 31 patients with polysomnographically confirmed OSAS (apnea-hypopnea-index 24.8 +/- 21.5/h) before, 2 and 42 days after initiation of CPAP and was compared to 10 healthy controls in whom OSAS was excluded by polysomnography. Driving simulator performance was significantly worse in OSAS as compared to normals especially in terms of accident frequency (OSAS: 2.7 +/- 2.0, controls: 1.3 +/- 1.5, p0.05) and concentration faults (OSAS: 12.4 +/- 5.1, controls: 7.1 +/- 3.2, p0.01). On CPAP accident frequency (OSAS before therapy: 12.4 +/- 5.1, 2 days CPAP: 1.5 +/- 1.4, p0.01; 42 days CPAP: 0.9 +/- 1.3, p0.001) and frequency of concentration faults (OSAS before therapy: 12.4 +/- 5.1, 2 days CPAP: 6.5 +/- 3.9, p0.001; 42 days CPAP: 4.9 +/- 3.3, p0.001) could be lowered significantly both in the short and medium term of therapy. The driving simulator C.A.R. is an adequate tool for the evaluation of an increased accident risk in OSAS-patients and demonstrates the efficiency of CPAP-therapy.

beta-chemokines were recently demonstrated in active MS-lesions. We tested whether MCP-1 and RANTES can also be detected in CSF and serum of patients with MS and whether release is associated with inflammatory disease activity.CSF and serum from 34 patients with newly diagnosed relapsing-remitting MS (RR-MS), 17 patients with viral meningitis (VM) and 19 patients with non-inflammatory neurological diseases (NIND) were investigated by ELISA. RR-MS patients underwent lumbar puncture and Gd-enhanced MRI examinations within 2 days.MCP-1 was strong intrathecally released in all patients. Compared to NIND CSF-levels were increased in VM (P0.001) and were decreased in RR-MS (P0.05). RANTES was only detected in serum in all patients. Levels were higher in VM and RR-MS compared to NIND (P0.05). A total of 14/34 RR-MS patients exhibited active Gd-enhancing lesions on MRI. They had lower MCP-1 levels in CSF (P0.001) and serum (P0.05) and higher serum levels of RANTES (P0.05) as compared to patients without active lesions.MCP-1 and RANTES are differentially released during acute attacks of RR-MS, which might reflect different immunregulatory roles of these beta-chemokines in RR-MS.

We report on a 36-year-old man who developed an inflammatory polyradiculoneuropathy similar to Guillain-Barré syndrome 9 days after hepatitis B vaccination. Extensive immunotherapy including immunoglobulins, steroids, plasmapheresis, cyclophosphamide and methotrexate did not stop the progressive course of the disease and the patient died 4 months later due to multiorgan failure with septic shock symptoms and adult respiratory distress syndrome (ARDS).The neuropathological investigation showed severe axonal loss with mild demyelination of peripheral nerves and mononuclear cell infiltrates, predominantly T-lymphocytes, in nerve roots and spinal ganglia. In addition, there were unusual, perivascular and parenchymal lymphocytic cell infiltrates in the grey matter, especially the anterior horns of the spinal cord. The temporal relationship to hepatitis B vaccination, the strong increase of HBs-antibodies within 3 weeks after vaccination, and the presumptive immune mediated pathology of this disorder suggest a possible etiologic link with hepatitis B vaccine.

Mutations in the sarcoglycan (SG) genes cause a subset of limb-girdle muscular dystrophies (LGMD). We report a Spanish patient with progressive LGMD exhibiting an almost isolated loss of gamma-SG and a homozygous Delta521-T mutation in the gamma-SG gene. These results suggest that isolated loss of gamma-SG might remain undetected using only the alpha-SG antibody in routine muscle biopsy studies. Both alpha- and gamma-SG antibodies should be used in the diagnostic detection of patients with LGMD.

The aim of our study was to measure the effects of the glutamate antagonist riluzole on different parameters of motor excitability, using transcranial magnetic stimulation (TMS) during 7 days of riluzole administration, and to correlate these effects with riluzole plasma levels. Nine healthy volunteers received a dose of 100 mg riluzole from day 1 to 7 of the study period. Electrophysiological examinations were performed on day 1 before and 2 h, 5 h and 8 h after riluzole administration, on day 2, day 3 and day 5 before riluzole administration, and on day 8. Plasma samples were taken simultaneously. The excitability of the motor cortex, supraspinal and spinal motor pathways was tested by studying intracortical facilitation and inhibition, the cortical silent period and motor threshold after TMS, as well as the peripheral silent period and F-wave amplitudes after electrical peripheral nerve stimulation. We found a significant reduction of intracortical facilitation, which correlated significantly with riluzole plasma levels. To a lesser extent, intracortical inhibition was enhanced on day 1, motor threshold was increased on day 8 and F-wave amplitudes were reduced. These changes did not correlate with riluzole plasma levels. We conclude that the main effect of riluzole in vivo is a reduction of intracortical facilitation, which is closely related to the drug's level in the plasma. The most probable mechanism involves an effect on glutamatergic synaptic transmission.

Die Begutachtung von MS–Patienten bringt Schwierigkeiten mit sich, die im Wesen der Erkrankung liegen: Es gibt noch keine Klarheit hinsichtlich der Atiologie und Pathogenese. Ein eindeutig definierbarer Krankheitsbeginn ist bei der MS nicht festzustellen und er stimmt sicher nicht mit dem Zeitpunkt der Diagnosestellung nach den Poser–Kriterien uberein. Es kann nicht, wie nach Unfallverletzungen, ein weitgehend abgeschlos-senes Krankheitsbild beurteilt werden, sondern es muss stets mit einer Dynamik der Erkrankung und einer fliesenden Veranderung des Krankheitsbildes gerechnet werden. Es fehlen zuverlassige pradiktive Parameter im Hinblick auf den Verlauf und die Prognose, sodass die an uns gutachterlich am haufigsten gestell-ten Fragen nach der Zusammenhangsfrage mit krankheitsauslosenden oder -verschlimmernden Faktoren, Minderung der Erwerbsfahigkeit (MdE) und Grad der Behinderung (GdB), Erwerbs– und Berufsfahigkeit, Rehabilitation sowie Kraftfahreignung nicht mit Sicherheit und abschliesend beantwortet werden konnen.

Hemifacial spasm (HFS) presents a frequent movement disorder. It is thought to have an organic origin. It therefore has to be distinguished from other facial involuntary movements, especially psychogenic tics, because the therapeutic approach differs. The present study opted to evaluate the diagnostic value of the postexcitatory inhibition (pI) after transcranial magnetic stimulation (TMS). After stimulating the contralateral hemisphere with the conventional flat coil and recording from the mentalis muscle, in 10 healthy controls and 10 patients postexcitatory inhibition was determined. PI showed no side to side difference in healthy controls (96.9 + 12.7 ms right, 87.9 +/- 10.8 ms left side, interhemispheric difference 6.4 +/- 3.8 ms). In 8 patients with hemifacial spasm, the duration of pI on the non-affected side did not differ from the healthy controls (87.9+/-43.5 ms). During spasm, pI on the affected side shortened increasingly until no inhibition could be induced. Afterwards the spasm pI was prolonged significantly (up to 140 ms longer than opposite side) before returning to normal values. Two patients presented no side differences of pI during the "spasm". An emotional conflict situation could be evaluated, supporting the diagnosis of somatoform disorder. As postexcitatory inhibition is mainly due to cerebral mechanisms, the electrophysiological results of the study pointed to a cortical influence on the hemifacial spasm. TMS seems to be an electrophysiological tool which allows a differentiation between organic and psychogenic spasm and enables a different therapeutic approach.

In the pathogenesis of Guillain-Barré syndrome (GBS) a dysregulation of cytokines is supposed. The protein concentration and mRNA expression of TNFalpha and TGFbeta1 were investigated in cerebrospinal fluid (CSF) and blood in 10 patients with GBS. TNFalpha-mRNA was increased at the beginning of the disease and demonstrated a decline during the time course (P = 0.001). The level of TNFalpha protein was elevated in only a few patients. TGFbeta1-mRNA (P = 0.001) and the active TGFbeta1 protein (P0.05) increased during the course of GBS, and the level of total TGFbeta1 protein was temporarily elevated (P = 0.005). A low ratio of TNFalpha-/TGFbeta-mRNA expression correlated to a good clinical course (P0.05). The results indicate an association of TNFalpha with disease activity. TGFbeta1 seems to terminate and limit the inflammatory reactions and to promote the healing course of GBS. In addition the investigations show that in GBS immunoregulatory mechanisms also take place in the CSF compartment itself and that CSF cells are involved in the production of pro-inflammatory as well as immunosuppressive cytokines.

In the cytoplasm of Schwann cells of a sural nerve biopsy from a 21-year-old female patient with chronic neuropathy we noted numerous unique, usually double membrane-bound, osmiophilic, granular or globular inclusions, approximately 30-600 microm in diameter. Some of these membrane-bound vesicular or tubular structures contained less dense or no osmiophilic inclusions. Morphometry revealed a reduction of the myelin area per endoneural area to approximately 13% (normal value: 20- 30%) and of the density of myelinated nerve fibers to 5,412/mm(2) (normal value at this age: 6,000-9,000/mm(2)). Large myelinated nerve fibers were predominantly reduced in number, and no myelinated nerve fibers with diameters larger than 4.5 microm were seen. Numerous, usually small onion bulb formations indicated a predominantly demyelinating type of neuropathy. This is to the best of our knowledge the first case of a chronic demyelinating neuropathy in which this kind of presumably pathognostic deposits in the cytoplasm of Schwann cells was detected.

We describe a 46 year old patient with adult polyglucosan body disease (APBD). She presented clinically with late onset pyramidal tetraparesis, sensory motor polyneuropathy and micturition difficulties. Magnetic resonance imaging of the brain revealed extensive leucencephalopathy and diffuse atrophy. The diagnosis based on the demonstration of polyglucosan bodies in the sural nerve biopsy. In search of a possible metabolic defect, we evaluated glycogen metabolism in this patient and her clinically unaffected daughters. Branching enzyme activity in the patients leukocytes was between 20-30% of the lower limit of normal range, whereas their children displayed values of 80%, suggesting a possible autosomal recessive mode of transmission. Branching enzyme deficiency in APBD with predominantly attack of the central and peripheral nervous system was so far described in 3 Jewish patients.

The mechanisms by which IFNbeta-1b acts in the treatment of multiple sclerosis (MS) patients are not completely known. We investigated the influence of IFNbeta-1b on the mRNA-expression of the immunosuppressive cytokine TGFbeta-1 and the proinflammatory mediator TNFalpha in an in vitro model by the method of non-radioactive in situ hybridization. Peripheral blood lymphocytes (PBL) were isolated from eight patients with relapsing remitting form of MS during remission and from six healthy controls. They were stimulated with IFNbeta-1b in different concentrations for 24 h. In both groups a statistically significant dose-dependent increase of TGFbeta-1-mRNA and decrease of TNFalpha-mRNA was demonstrable in the cultured stimulated blood lymphocytes compared to unstimulated cells. Stimulations with lipopolysaccharide (LPS) led to an increase of both cytokine-mRNAs in the lymphocytes. These data suggest specific and dose-dependent effects of IFNbeta-1b and hint at immunomodulatory properties of this drug to regulate the cytokine dysbalance in MS. This might be one mechanism by which IFNbeta-1b mediates its beneficial effects on the course of the disease.

The term "frontal lobe syndrome" comprises a variety of different clinical syndromes produced by focal lesions involving the prefrontal cortex. However, similar syndromes can be observed after lesions involving subcortical structures connected with the prefrontal cortex in neuronal networks. With respect to the different clinical pictures and underlying brain lesions, prefrontal lobe dysfunction may be divided into a disorganized type, caused by lesion of the dorsolateral prefrontal lobe and its connections, a disinhibited type that can be observed following lesions of the orbitofrontal cortex, and an apathetic type following lesions affecting the functional balance between the cingulum and the supplementary motor area. As intracerebral lesions are rarely limited to the brain regions described, in the majority of patients various degrees of behavioural dysfunction can be observed. The case reports of four patients illustrating the three major prefrontal syndromes following severe head injury (n = 2) or cerebrovascular disease (n = 2) are presented and diagnostic implications as well as possible treatment strategies are discussed.

Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disease affecting 1 in 20,000 males either as cerebral ALD in childhood or as adrenomyeloneuropathy (AMN) in adulthood. Recently, the ALD gene has been identified by positional cloning. We report three males patients with AMN and a fourth patient with juvenile ALD. Biochemical studies showed elevated plasma concentration of saturated very-long-chain fatty acids. Genomic DNA of the patients was analysed for possible sequence variations in the ALD gene by PCR amplification and single strand conformation polymorphism analysis. Three missense mutations (Ser515Phe, Glu267Lys and Arg401Trp) and a 9-bp deletion were detected predicting, respectively, the replacement and absence of amino acids in the deduced amino acid sequence of the ALD protein. In the patients' families, detection of the respective mutations allows the identification of carriers of ALD/AMN. Mutational screening in ALD families is of practical importance in improving genetic counseling.

Possible changes in the organization of the cortex in patients with facial palsy, serving as a model of peripheral motor deefferentation, were investigated by using transcranial magnetic stimulation (TMS) and positron emission tomography (PET). With TMS, the size of the area producing muscle-evoked potentials (MEPs) of the abductor pollicis brevis muscle, the sum of MEP amplitudes within this area, and the volume over the mapping area were compared between both hemispheres in 8 patients. With PET, increases in regional cerebral blood flow, measured with the standard H2(15)O2 bolus injection technique, were compared between 6 patients and 6 healthy volunteers during sequential finger opposition. Patients moved the hand ipsilateral to the facial palsy, the control subjects the right hand. Of 9 patients in total, 5 participated in both experiments. With both methods, an enlargement of the hand field contralateral to the facial palsy was found, extending in a lateral direction, into the site of the presumed face area. The PET data showed that the enlargement of the hand field in the somatosensory cortex (SMC) is part of a widespread cortical reorganization, including the ipsilateral SMC and bilateral secondary motor and sensory areas. We report for the first time, using two different noninvasive methods, that peripheral, mere motor deefferentation is a sufficient stimulus for reorganizational changes in the healthy adult human cortex.

This study was designed to examine the immunogenetic background predisposing to multiple sclerosis (MS). Three hundred fifty-eight clinically well-characterized MS patients from Germany were investigated and compared to 395 healthy control subjects. Each individual was genotyped for 22 polymorphic markers located within or close to immunorelevant candidate genes including HLA-DRB1*, T-cell receptor (TCR), cell interaction molecules, cytokines, and cytokine receptor genes. Altogether, approximately 17,000 genetic analyses were performed. Patients were grouped according to the course of MS-relapsing-remitting or chronic progressive. Most of the genetic markers were not associated with increased risk or their exact contribution was not clear (e.g., tumor necrosis factor). The relative risks for HLA-DRB1*15+ and DRB1*03+ individuals were 3.64 and 1.42, respectively. In both groups of patients, certain TCRB gene polymorphisms were risk factors. In DRB1*03+ individuals the relative risk was increased (22) when a specific TCRBV6S3 allele was also inherited. Furthermore, distinct linkage disequilibria of TCRBV6S1/TCRBV6S3 elements in patients and control subjects strongly suggested an additional risk factor in the TCRBV region for DRB1*15+ individuals. These findings are discussed with respect to the pathogenesis and rational approaches to the therapy of MS.

A 69-year-old woman reported marked restriction of voluntary movements of the hands in the preceding 6 months. She had also experienced loss of motivation, memory and concentration. Her skin was pale yellow, and scratches on her skin indicated marked pruritus.Neurological examination revealed decreased vibratory sense in both legs. Haemoglobin concentration was 8.3 g/dl, mean corpuscular volume 114 fl, vitamin B12 level100 ng/l, folic acid level normal. Antibody titre against parietal cells was increased, vitamin B12 resorption diminished. Gastroscopy revealed small raised lesions, made up of hyperplastic cells which stained with chromogranin, indicating a diagnosis of microcarcinoid of the gastric mucosa.On administration of cobalamine (1,000 micrograms i.m. daily for 2 weeks, twice weekly for 6 weeks, then once per week for the last 7 months) the blood picture returned to normal, but the microcarcinoids, the psychological symptoms and the apraxia of the hands were unchanged.

The aim of the present study was to examine the value of the sympathetic skin response (SSR) in the diagnosis of reflex sympathetic dystrophy (RSD).SSR was recorded in 20 normal subjects and in 24 patients with predominantly chronic RSD. In 3 patients with RSD, additional recordings of the SSR were performed before and several times after administration of local anaesthetics via a plexus catheter on the diseased side. SSR was recorded with standard EMG apparatus. Disc electrodes were positioned on the middle of the volar and dorsal surfaces of the hands and feet. Electrical stimuli were applied to the middle of the forehead at irregular intervals longer than 60 s.In normal subjects inter- and intraindividually different monophasic, biphasic and triphasic potentials without difference in the waveform between sides were recorded. SSR abnormalities were found in 15 patients with RSD and correlated with the severity of the disease. In patients with slight dystrophy SSR was predominantly normal, while in most of those with intermediate dystrophy differences in the SSR waveform between sides were observed. In the presence of severe dystrophy SSR amplitude was predominantly decreased on the affected side. Following the administration of local anaesthetics via a plexus catheter, the differences in SSR waveform became smaller in patients with initial distinct side difference of the waveform. However, differences in SSR amplitudes or latencies between sides were not affected.Side differences in SSR waveform could be due to a mild, reversible unilateral sudomotor dysfunction, whereas differences in SSR amplitude or latency indicate more serious damage to sudomotor activity, possibly due to dysfunction of autonomic fibres. In patients with slight dystrophy sweat secretion is predominantly normal, while in severe dystrophy more serious damage to the sweat secretory system can be observed. SSR provides useful information on sudomotor dysfunction in patients with RSD. However, as there is no consensus on the clinical criteria for diagnosis of RSD, it is also not possible to determine the diagnostic value of SSR in the diagnosis of RSD.

A 36 year old male patient with adrenomyeloneuropathy (AMN) developed progressive spastic paraparesis and sensory ataxia from the age of 18. Biochemical studies showed increased plasma concentrations of saturated very long chain fatty acids (VLCFAs), subclinical evidence of adrenal insufficiency, and primary hypogonadism. Three female family members had increased plasma concentrations of VLCFAs, suggesting carrier status of adrenoleukodystrophy (ALD). Molecular genetic analysis detected a missense point mutation (C1930T) in exon 6 within the ALD gene, which predicts substitution of an amino acid (Ser515Phe) that is conserved between the deduced amino acid sequence of the peroxisomal membrane protein PMP70 and ALD protein. Detection of this point mutation allows diagnosis of ALD or AMN, identification of heterozygotes, and prenatal diagnosis of ALD.

Cytologic cerebrospinal fluid abnormalities that most distinctly point to the diagnosis of Lyme meningoradiculitis are pronounced mononuclear pleocytosis composed mainly of T lymphocytes, large amounts of plasma cells and IgM-positive B cells. In this study, repeat examinations revealed decreasing cell numbers and almost normal cell counts 100-130 days after the onset. B cells persisted over the whole observation period in five of six patients and were not related to any clinical symptoms or signs indicative of persistent meningitis or central nervous system involvement. The CD4/CD8 ratio of the helper/inducer and suppressor/cytotoxic lymphocyte subsets declined in all the patients after antibiotic treatment. It might be useful as a marker of the disease activity.

Die kaudalen Hirnnerven sind die Nn. glossopharyngeus, vagus, accessorius und hypoglossus. Sie sind Kiemenbogennerven, d.h. sie innervieren in der Wand des Kopfdarmes Koperabschnitte visceraler Herkunft, nur der N. hypoglossus ist aus zwei oder drei Spinalnerven geformt, deren sensible Wurzelanteile zuruckgebildet sind: Er wird zum motorischen Zungennerv.