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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.

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.

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.

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.

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.

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.

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.

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 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.

Twenty-three patients (10 men, 13 women; age: from 23 to 81 years, mean 52 years) with Bell's palsy were investigated by magneto-electrical stimulation in order to evaluate the usefulness of this method for prognostication. At each examination the facial nerve was electrically stimulated, and an orbicularis-oculi-reflex was elicited. Follow-up investigations were possible in 13 patients. All patients showed pathological long- and short-latency responses at the first examination. The blink reflex examination revealed a pathological result in all cases. The responses to electrical stimulation were pathological only in 35%. The follow-up examinations revealed that the analysis of the short-latency response did not give a prognostic information. In contrast, maintained elicitation of the long-latency response pointed to a favourable prognosis. In follow-up investigations, the increase of amplitude and the decrease of latency of the long-latency response correlated with a complete recovery, while the decrease of amplitude and the increase of latency correlated with a partial recovery. The improvement of the responses in magnetic stimulation preceded the clinical improvement. By using magnetic stimulation, an early registration and evaluation of the course of Bell's palsy are possible.

Patients with trigeminal neuralgia are usually investigated by elicitation of the orbicularis oculi reflex and trigeminal evoked potentials. These neurophysiological methods do not allow direct judgement of the trigeminal nerve. By transcranial magnetic stimulation, however, non-invasive investigation of the efferent part of the trigeminal nerve is possible. 10 patients (4 men, 6 women, aged from 43 to 73 years) with trigeminal neuralgia affecting the second or third division were examined. In all patients bilateral long-latency responses after stimulation of the tractus corticonuclearis and short-latency responses after stimulation of the proximal part of the trigeminal nerve were registered. 8 patients showed normal short- and long-latency responses, while in one other patient the long-latency responses were delayed on both sides. The remaining patient revealed a significant difference of amplitude compared to the contralateral long-latency response. This patient had a pontine lesion as shown by blink reflex and a pathological trigeminal evoked potential. In both these latter patients multiple sclerosis was diagnosed. Use of transcranial magnetic stimulation may thus prove helpful in the differential diagnosis of neurological disorders presenting with trigeminal neuralgia.

During 1988 to 1992 18 patients with spondylodiscitis and neurological deficits were treated in our clinic. Tuberculous spondylodiscitis was diagnosed in 4 patients and 14 suffered from non specific spondylodiscitis. The mean age was 59 years (range 25-77). 16 (89%) of the patients had risk factors like diabetes mellitus, genitourinary tract infection, respiratory tract infection, rheumatism, intervertebral disc operation and old spine fracture. MR-tomography revealed the most valuable diagnostic method. 14 patients with progressive spinal cord compression, and root lesions because of gross vertebral damage and epidural abscess underwent operative removal of the focus with intercorporal spondylodesis. Postoperative neurological examination revealed improvement in 7 and no changes in the other 7 patients. In 4 patients with non specific spondylodicitis and radicular deficits conservative treatment was performed and spontaneous interbody fusion without persisting neurological complaints occurred.

5 patients (3 men, 2 women, aged from 28 to 51 years) with unilateral facial palsy after surgery of a cerebellopontine angle tumour have been investigated by transcranial magnetic stimulation. The purpose was to evaluate the prognostic aspects of this method, which was compared with the electrical stimulation of the facial nerve and the elicitation of an orbicularis-oculi reflex. The components of the blink reflex were absent in all cases. In 3 patients electrical stimulation was possible (compound muscle action potentials were delayed). With transcranial magnetic stimulation ipsilateral short-latency and contralateral long-latency responses (stimulation of the cortex) were elicited and registered from the M. mentalis as well as 3 times from the M. orbicularis oculi. The short-latency response revealed no prognostic aspects. Despite the missing response, a recovery was possible. Long-latency responses could be evoked in all patients. The extent of delay in latency was strongly correlated with clinical improvement of the paresis. Interestingly, this correlation could also be observed in the single rami of the facial nerve when two muscles were investigated in a patient. Transcranial magnetic stimulation is an important improvement in electrophysiological diagnosis of perioperative lesion of facial nerve to prove continuity of the nerve and to evaluate the clinical course.

By means of transcranial magnetic stimulation bilateral compound muscle action potentials of long latency and ipsilateral potentials of short latency can be obtained in muscles supplied by cranial nerves. In this study motor evoked potentials were recorded from the mentalis muscle of 14 patients with traumatic brain lesions. These results were compared with clinical and radiological as well as other neurophysiological examinations. In spite of the absence of paralysis in muscles supplied by the facial nerve, 9 patients showed pathological long-latency responses, which correlated with the localisation of the paralysis of the limbs. In contrast to this, the degree of pathological latencies of motor evoked potentials did not correspond with the degree of paresis in different patients. A prediction concerning the clinical outcome could not be made by the results of motor evoked potentials. The clinical data showed a poor correlation with the structural brain lesions seen in the CT-scan and the results of EEG, BAEP and orbicularis oculi reflex examination. In conclusion, transcranial magnetic stimulation of cranial nerves proved to be a sensitive method for the evaluation of degree and localization of motor deficits following traumatic brain lesion and seems to be superior to the other examinations compared.

Objective: To characterize the phenotype of hereditary rippling muscle disease (RMD) and to report the results of genetic linkage studies.Background: RMD is a rare autosomal-dominant inherited muscle disorder. Individuals complain of muscle stiffness, exercise-induced muscle pain, and cramp-like sensations. The characteristic feature of RMD is increased mechanical muscle irritability, which is electrically silent in electromyographic examinations.Methods: Forty-six individuals from two unrelated German kindreds with RMD were examined. Linkage analysis to the RMD locus on chromosome 1q41-q43 was performed.Results: In kindred A, 15 individuals from four generations, and in kindred B, four individuals from three generations had clinical features of RMD. The most consistent clinical findings were percussion-induced rapid muscle contractions (PIRCs) and muscle mounding, which were present in all 19 affected individuals. Only 12 individuals exhibited muscle rippling, indicating that rippling is not always present in RMD. Twelve of 19 individuals had muscle-related complaints, primarily exertional cramps and stiffness. The mean age at the onset of complaints was 22 years (range, 5 to 54 years). Seven of 19 individuals showed only mechanical-induced muscle irritability but did not have muscular symptoms. Genetic analysis excluded linkage to the RMD locus on chromosome 1q4 in both kindreds.Conclusions: The phenotype of RMD is variable but generalized PIRCs are the most obvious and reliable clinical feature of RMD. Diagnostic criteria of RMD should include generalized PIRCs in addition to muscle mounding, rippling, and creatine kinase elevation.

The electrically and optically elicited orbicularis oculi reflex (OOR) and facial nerve latency were investigated in eight patients from three families. Each had autosomal dominant peroneal muscular atrophy. In a family with the dominantly inherited hypertrophic type markedly delayed latencies of the early reflex component of the OOR were found while the facial nerve had remained unaffected. These findings were interpreted as an indicator for supraorbital nerve involvement. In the other two investigated families of hypertrophic and neuronal type, a prolonged facial nerve latency was demonstrable. In these cases the latency of the optically evoked blink reflex was also delayed, while the latency of the early reflex component of the OOR was within normal limits or only slightly delayed. It is assumed that the different degree of cranial nerve involvement in these families is the expression of their genetically determined peculiarities.

In a double-blind controlled trial of 194 patients with clinically definite active multiple sclerosis, 98 were randomized to treatment with cyclosporine (CyA, 5 mg/kg/day), and 96 to treatment with azathioprine (Aza, 2.5 mg/kg/day). Eighty-five patients in the CyA group and 82 in the Aza group completed a treatment period of 24 to 32 months in accordance with the study protocol. No significant differences could be detected between the two treatment groups at the end of the trial. Assessment was done by serial quantitative neurological examinations and Kurtzke's Expanded Disability Status Scale. Frequency of relapse and patient self-evaluation also failed to show significant differences. Overall deterioration observed in both groups during the trial was only minor. The incidence of side effects in the CyA group was more than two times that in the Aza group. We conclude that CyA as a single agent cannot be the drug of final choice in long-term immunosuppressive treatment of relapsing-remitting and relapsing-progressive multiple sclerosis.

Thyronine (T4), triiodothyronine (T3), and reverse-triiodothyronine (rT3) levels were evaluated in cerebrospinal fluid (CSF) and in serum of 12 patients with definite amyotrophic lateral sclerosis (ALS) by specific radioimmunoassays. Circulating microsomal and thyroglobulin antibodies were also evaluated. In all patients serum levels of T4, T3 and rT3 were within normal limits. In CSF, the rT3 levels were significantly elevated to 0.118 micrograms/l (mean), the T4 levels were not significantly elevated, and the T3 levels were below the detection limit of 0.03 micrograms/l. A correlation between the elevated rT3 levels in CSF and the severity or type of ALS could not be demonstrated by this study. The antithyroid antibodies (thyroglobulin antibodies, microsomal antibodies) showed normal titres and did not suggest disturbances of thyroid autoimmunity in the patients with ALS.

The habituation of the electrically (stimulation of the supraorbital nerve) elicited orbicularis oculi reflex (OOR) was investigated in 51 healthy volunteers (average age: 39 years). Ten reflex responses were registered from the left and right side including eyes open, eyes closed, and during task performance. The stimulus frequency was 1/s. The data were transmitted to an LAB 8e computer and statistically treated. The influence of stimulus frequency on habituation was examined separately. The following parameters of habituation as devised by Thompson and Spencer were demonstrable: dishabituation, habituation of dishabituation, spontaneous recovery, and influence of stimulus intensity. The analysis of habituation during task performance with the Kruskal-Wallis test revealed a statistically significant decrease of habituation. The early reflex component (R1) amplitudes increased during the 1/s stimulation. This effect was also statistically significant. The increase in R1 amplitude during 1/s stimulation was interpreted as "facilitation".

Familial occurrence of Meralgia paresthetica is uncommon. Only few familial case studies have been reported up to now. The author presents a family with Meralgia in four generations, suggesting a distinctly autosomal dominant trait.

According to the clinical classification of amyotrophic lateral sclerosis by Hemmer its "hemiplegic type" is described from two observations in 37 personal cases. The peculiar difficulties of differential diagnosis especially with the hemiplegic type of multiple sclerosis in two further cases are discussed in detail. Four cases of "Mills' syndrome" are compared. "Mills' syndrome" has been assumed to be a slowly progressive, unilateral ascending or descending variant of amyotrophic lateral sclerosis. A study of Mills' original papers and evaluation of personal observations leads to a more critical assessment. In Mills' original cases, widely different entities such as multiple sclerosis, syphilis, and parkinsonism are included besides amyotrophic lateral sclerosis. In the light of the investigations presented here, Mills' syndrome seems to be merely an obsolete clinical term.

Meningopolyradiculitis (Garin-Bujadoux syndrome, Bannwarth syndrome) is the second stage of Lyme disease, a tick-borne Borrelia infection. Almost 60% of these patients develop an acute peripheral facial paresis. The disease can be differentiated from Bell's palsy only by finding the specific Borrelia antibodies in serum and CSF. Other cranial nerve lesions can be found besides facial paresis. The follow-up of seven Borrelia-infected patients is described: one showed bilateral, the others unilateral, facial paresis. High dosage of penicillin or tetracycline for 10-14 days is the appropriate therapy. The prognosis of facial paresis in tick-borne Borrelia infection is considered to be good. All our patients showed complete recovery of motor nerve function.

The electrically, by stimulation of the supraorbital nerve elicited blink reflex has been used as a diagnostic procedure in various neurological diseases. For avoiding false positive or negative interpretations of measurements, methodology and statistical treatment of normal values is of basic importance. This paper summarizes the results of investigations in 51 healthy volunteers and presents a detailed statistical treatment. New findings are presented concerning the reflex parameters under different stimulus conditions. Some characteristic features of habituation, known from animal experiments, could be demonstrated for the first time at the human orbicularis oculi reflex.

The optically evoked orbicularis oculi-reflex (OOR) was investigated in 50 healthy volunteers by monocular and binocular stimulation, including eyes open and eyes closed. Latency, amplitude, and duration correlated considerably with the stimulus intensity. There was no significant correlation to the diameter of the pupil, provided that a constant supramaximal stimulus intensity was used. A statistically significant difference of the reflex parameters between males and females could not be demonstrated. In 12% of the healthy volunteers the optic orbicularis oculi-reflex could not be evoked. The mean age of these subjects was 53 years, and distinctly higher than the mean age of the whole collective (32,6 years). A slight, statistically not significant increase of latency and duration was found with increasing age. The optically evoked OOR even habituated rapidly during aperiodic stimulation. To prevent habituation interstimulus intervals of 30 s were necessary. During the 1 Hz-stimulation habituation was already observed at the third reflex response. The amplitudes decreased, and the latencies increased with increasing distance of the flash light. Measurable differences were observed even with distance changes of 10 cm. There was no significant influence of eye-closing on latency, amplitude and duration of the optic orbicularis oculi-reflex. The orbicularis oculi-reflex following a bright flash of light with a latency about 50 ms was differentiated from an eyelid-closure following a low flash intensity with a latency between 80 and 90 ms.

Alteration of the early component of the blink reflex (delayed latency or abolished reflex) is considered to be relatively specific for pontine lesions (multiple sclerosis, vacular lesions of the brain-stem, neoplasms, syringes); provided, the trigeminal and facial nerve are unaffected. In comatose patients the electrically, by stimulation of the supraorbital nerve elicited blink reflex was super-imposed (50 or 100 responses) with the LAB 8/e-computer (off-line). It was found that the R1 component was abolished even in cases with supratentorial lesions and secondary brain-stem alterations, while no specific pontine lesions were demonstrated by neuropathological examination. Therefore it is suggested that delayed or abolished blink reflexes in coma due to supratentorial mass lesions are not concluslive for pontine lesions: they rather may reflect an unspecific secondary brain-stem alteration. Recording of the EEG reveals that in some cases the extinction of the early blink reflex precedes corresponding EEG alterations; this may be a matter of prognostic value.

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.