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A spongiform leucoencephalopathy sometimes develops as a result of inhaling illicit heroin as well as due to carbon monoxide-intoxication. Clinically psychiatric symptoms precede a neurological deterioration. Some patients die. After a brief description of several epidemiological and historical-cultural aspects regarding the smoking of opiates, the typical neuroradiological signs such as hypodensity of the white matter in CCT and signal alterations in MRT, and neuropathological sequelae such as intramyelinic vacuolisation are listed. Pathophysiologically an edema of the white matter in the beginning is suspected. Second, a dysfunction of the mitochondria is addressed relying on the particular metabolism of the oligodendrocytes. Since smoking of heroin is an increasingly preferred way of application in all continents and therapeutic options are still lacking, the need of further explanation of the underlying processes is stressed.

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In myasthenia gravis (MG), humoral and cellular immune mechanisms are involved in the autoimmune pathogenesis. In this study, we investigated the role of the CD45 molecule in MG, having recently reported an association in multiple sclerosis. CD45, a protein-tyrosine phophatase receptor type C (PTPRC), is essential for both thymic selection and peripheral activation of T and B cells. Our aims were to determine (a) the prevalence of a functional mutation in the CD45 gene (exon 4 77C --> G; prevalence analysis), and (b) the distribution of memory (CD45RO+) and naive (CD45RA+) T cells in the peripheral blood (subset analysis). T cells from 78 patients with generalised MG were stained with monoclonal antibodies against CD45RO, CD45RA, CD4 and CD8 and quantified by four-colour flow cytometry. The control panel for the prevalence analysis (a) consisted of 303 healthy individuals. (b) From those, 67 age- and sex-matched probands were randomly selected as controls for the subset analysis. Patients were stratified according to their MG onset age, thymic pathology and immunosuppressive treatment. Statistical analysis was performed by Fisher's exact test, asymptotic chi2 test, the two-sided Mann-Whitney test and Spearman's correlation coefficient. As a result, the 77C --> G mutation in exon 4 of the CD45 gene was found in 1 of 78 patients versus none of the 303 controls. Thus, no association was detected with this single nucleotide polymorphism in MG patients overall. Surprisingly, however, ratios of CD45RO+ to CD45RA+ T cells were lower among CD8+ T cells from patients with late-onset MG (P = 0.023). Thymoma patients also showed a similar trend among CD4+ and CD8+ T-cells, as expected. These differences were not related to immunosuppressive drug treatment or thymectomy (in the 67 informative patients). Since there is no other evidence for increased thymopoiesis in late-onset MG, we propose an altered subset balance in the circulation.

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Over a period of 12 months, all persons among the 10.4 million inhabitants of the state of Baden-Württemberg were included in the study who had suffered severe brain damage and were treated in special early rehab units, comprising 147 beds for adults and 43 for children. With 830 patients admitted, the incidence of severe brain damage was 7.98/100.000 in adults and 1.11/100.000 in children. 50 to 70 year old patients were over-represented, those older than 70 years were underrepresented due to geriatric rehab facilities for the latter. Male patients dominated, while female were somewhat younger. 54% of the patients were admitted from the hospital which had performed primary care, with an average stay of 67 days. Average early rehab duration was 53 days (arithmetic average; median 40 days, some patients required up to one year). 32.8% of the patients had suffered traumatic brain damage (ICD 851, 852, 854) and 40.9% non-traumatic brain affection (ICD 430, 431, 433-438, 310, 348), including 12.2% CVA (ICD 433-438), 8.5% subarachnoid and 12.3% intracerebral hemorrhage. Severity as indexed by the early rehab Barthel index improved from an initial average of -119 to -34 at discharge. 80% of the patients showed an overall improvement (71% of them by up to 200 points and 46% by up to 100 points).

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We report on eight patients with stiff-man syndrome (SMS) or its "plus" variant, progressive encephalomyelopathy with rigidity and myoclonus (PERM) receiving intrathecal baclofen via pump. In six of the patients, follow-ups continued for approximately 2.5 to 6.5 years after pump implantation. Intrathecal baclofen was an effective last-resort alternative for patients who responded poorly to or did not tolerate oral antispasticity medications. General mobility increased, and spasms and rigidity were reduced; however, no complete remissions were observed either before or after pump implantation. PERM patients showed more severe and rapid progression of symptoms and more attacks of autonomic dysregulation than SMS patients. They also required higher doses and more rapid dosage increases. Complications of intrathecal baclofen therapy included spasm-induced rupture of the catheter, catheter dislocation causing radicular symptoms, and pump malfunction resulting in inaccurate dosage administration. Patients suffered fewer side effects with intrathecal baclofen than with oral medication, but overdose resulted in a transient, comalike state in one patient and sudden dosage reduction due to pump failure was fatal in another.

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It has been suggested that antibodies against non-acetylcholine receptor proteins of striated muscle are markers of the presence of a thymic epithelial tumor in patients with myasthenia gravis (MG). These antibodies may be measured using an immunofluorescence assay against striated muscle (anti-STR) or an ELISA with a recombinant 30-kd titin fragment (anti-MGT30). To directly compare anti-STR with anti-MGT30, we examined the sera of 276 consecutive patients with known or suspected MG. Definite diagnoses and thymic histology, if available, were correlated with the antibody assays. Of the 276 patients, 164 had MG. Thymic histology was obtained in 44 patients: 18 had lymphofollicular hyperplasia, 13 thymic epithelial tumors, 8 atrophy, and 5 were normal. When compared with anti-STR, anti-MGT30 showed a sensitivity of 69% (STR 77%), specificity of 100% (STR 56%, p = 0.026), negative predictive value of 82% (STR 77%), and positive predictive value of 100% (STR 56%, p = 0.003) for the identification of a thymic epithelial tumor versus thymic hyperplasia. We conclude that the anti-MGT30 ELISA is better than the anti-STR immunofluorescence assay for the diagnosis of paraneoplastic MG.

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We report on a woman patient who since 1976 has suffered eight episodes of a meningoencephalitis with features of limbic encephalitis. The duration of the individual episodes has varied from 3 weeks to 2 months. Each time recovery has always been complete. Despite numerous cultural and serological examinations of blood and cerebral spinal fluid (CSF), no infectious agent has been detected. The etiology and entity of this illness are still unclear. To our knowledge such a clinical course has never been reported.

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In a retrospective review 78 compartmental syndromes, treated between 1980 and 1988, were analyzed. The mean follow-up was 42 months. 43 patients (53%) suffered an traffic accident. Direct trauma forces predominated (66 patients). The functional results after crush injuries had been worser than after contusion injuries or direct trauma forces. The functional results depended from the posttraumatic interval of decompression. The later the fasciotomy the worser the functional results had been. A wide fascial decompression is necessary. Two cases of rebound compartmental syndromes after unilateral fasciotomy reveal the skin as an important limiting factor in severe cases of compartmental syndrome.

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1. To assess the contribution of tubular secretion to the renal excretion of pyridostigmine, and its modification by other cationic drugs, six volunteers were given single oral doses of 60-mg pyridostigmine bromide with and without co-administration of ranitidine or pirenzepine. Renal clearances were determined by h.p.l.c. analysis of pyridostigmine and enzymic measurement of endogenous creatinine in plasma and urine. 2. In patients with myasthenia receiving continuous pyridostigmine therapy, renal clearance values were obtained in the same manner with and without ranitidine (10 patients) or pirenzepine (nine patients) co-medication. 3. Pyridostigmine was not bound to plasma proteins. Its renal clearance averaged 6.65 ml/min per kg (350% of the creatinine clearance) in all subjects, 74% being due to net tubular secretion. 4. Mean values for pyridostigmine renal clearance and for clearance by secretion were decreased in the presence of pirenzepine, but plasma concentrations were not affected significantly. Ranitidine caused a small non-significant decrease of the pyridostigmine clearance in patients. 5. Pyridostigmine had a higher elimination (2 h-1) than the absorption rate constant (0.23 h-1) when administered orally as a non-retarded preparation. 6. The renal clearance of creatinine was slightly increased by pyridostigmine in volunteers and slightly decreased by pirenzepine in the total group of subjects.

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In 18 patients with generalised myasthenia treated with oral pyridostigmine, muscular strength, decrement of neuromuscular transmission in the trapezius muscle on repetitive accessory nerve stimulation, and pyridostigmine plasma level were measured repeatedly during 1-3 dosing intervals. Significant correlations between pyridostigmine concentrations and functional parameters were present in three out of 11 cases in which plasma levels changed by at least 25 ng/ml during the investigational period and peak levels did not exceed 100 ng/ml. Several other observations indicated that pyridostigmine at levels above 100 ng/ml may impair neuromuscular function.

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The third case of adult-onset rod disease (nemaline myopathy) with abundant myofibrillar as well as intranuclear rods is described. The 61-year-old woman suffered from progressive weakness of proximal extremities and of the neck, mimicking polymyositis. Muscle biopsy revealed a striking myopathic pattern, with intranuclear rods occurring in 31% of the fibres. On light and electron microscopy and by immunohistochemical study, the rods differed from myofibrillar rods. The absence of alpha-actinin in intranuclear rods suggests an enhanced readiness of actin filaments to bind to diverse proteins, instead of overproduction of alpha-actinin as the pathogenetic basis of the rod formation.

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A 43-year-old female with adrenoleukodystrophy (ALD) is described, who developed spastic tetraparesis, suffered grand mal seizures, and became stuporous and demented during the last 5 years of her life. Computed tomography revealed symmetrical hypodense lesions in the peritrigonal regions. Adrenal insufficiency was not evident except for skin pigmentation. The ultrastructure of a rectal biopsy specimen showed inclusions with lamellae and interspersed clefts in macrophages of the submucosal layer. At autopsy, the adrenals were found to contain large foam cells filled with similar inclusions. The brain cortex and the spinal cord were histologically normal. However, cerebral white matter exhibited widespread demyelination which spared only the arcuate fibres. In regions of less severe demyelination scattered inflammatory cells were seen. On electron microscopy, aggregates of typical paired leaflets with distinct intermediate lines were demonstrated in perivascular macrophages. Histochemical study showed these cells to contain free as well as esterified cholesterol. Gas chromatographic analysis of very long chain fatty acids (VLFA) from the demyelinated cerebral white matter showed a marked increase of C26:0 fatty acid in cholesterol esters and above-normal values for C24:0 and C24:1 in gangliosides. It is suggested that the condition was a heterozygote form of X-linked ALD. Patients with neurodegenerative symptoms with or without adrenal insufficiency can easily be screened for X-linked ALD by VLFA analysis in blood or cultured fibroblasts.

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The case of a 42-year-old man is reported, who on four occasions developed a hypokalaemic periodic paralysis after an intramuscular injection of "Ambene". The detailed examination of this patient shows, that it is the primary, autosomal dominant inherited form of hypokalaemic periodic paralysis, and not the secondary form, which is caused by a renal or gastrointestinal loss of potassium. Clinical and electrophysiological, as well as histopathological and electron microscopic findings are presented, showing the typical vacuolar myopathy with submicroscopic tubular structures. In the literature there is evidence for an increased sensitivity of the muscle membrane to insulin with an increased potassium-shift inside the cell in hypokalaemic periodic paralysis. "Ambene" is a combination, which contains amongst other substances dexamethasone and the local anaesthetic drug lidocain. In the present case the paresis was possibly caused by a combined effect of dexamethasone with a consequent hyperglycaemia and lidocain with a change in the excitability of the muscle membrane. The pathophysiological mechanism of hypokalaemic periodic paralysis is discussed in terms of the release by the combination of these two drugs. It has not previously been reported that "Ambene" can provoke a hypokalaemic periodic paralysis. This is a severe side effect because of the resulting cardiac and respiratory problems.

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Correlation studies on patients with myasthenia gravis are reported in which clinical assessment of fatigue and neurophysiological findings are compared to blood levels of pyridostigmine. Measurements using a high-pressure liquid chromatography method (HPLC), give reproducible results. The levels of pyridostigmine in the serum or plasma of healthy controls and of patients show no essential differences. Components of coffee, tea, chocolate and cigarettes can markedly disturb the chromatography by adding additional peaks, so that interpretation becomes difficult or impossible. Blood levels can be measured approximately one hour after oral intake of 60 mg pyridostigmine. Concentrations rise for two to four hours and then decline exponentially. The half-life of pyridostigmine was between 156 and 210 minutes. Despite identical oral dosages, the concentration differed intraindividually and interindividually among patients. While the blood level does not reach its maximum value for 1-1 1/2 to 3 hours, the maximum clinical and neurophysiological effect of pyridostigmine appears 30-60 minutes after ingestion. Variable distribution of cholinesterase inhibitors over the different compartments (blood, synaptic region) is assumed to cause this temporal lag. If the total amount of pyridostigmine is divided into 4-5 doses, the concentration profiles over the course of a day are relatively stable. There is no significant correlation between the variations in blood level throughout one day, and changes in myasthenic symptomatology. Effects of pyridostigmine can be measured at levels as low as 5 ng/ml; at levels above 40 ng/ml further improvement can be detected only rarely. Blood levels were lower if corticosteroids were administered simultaneously; azathioprine had no influence on blood levels. Blood levels assays allow better differentiation of cholinergic and myasthenic crises and the identification of disturbed absorption and interactions with other medications.

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Comparative pyridostigmine kinetics in plasma were measured in 10 healthy subjects given 4 mg iv and 60 mg oral pyridostigmine bromide. As determined from the AUC ratio, oral availability was 11.5% to 18.9% (means = 14.3%). Mean t 1/2 of the plasma level decline after oral dosing was 200 minutes, twice as long as the terminal elimination t1/2 after intravenous infusion (97 minutes). Thus absorption may proceed at a slower rate than elimination. Comparison of intraindividual data revealed strict dependence of the AUC on the infused dose (2, 4, and 8 mg) in one subject and variability in AUC up to a factor of two when two subjects took oral pyridostigmine three times. Patients with myasthenia who were receiving continuous therapy with oral pyridostigmine had AUC values per unit dose corresponding to those in healthy subjects. Storage stability of pyridostigmine in plasma required acidification of samples and storage at -75 degrees C. When native plasma was kept at -20 degrees C, there was appreciable loss of pyridostigmine within 1 to 2 months, the extent of which depended on the initial concentration.

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Eighteen patients with exclusively ocular symptoms of myasthenia were thymectomised. Suspected thymoma, resistance to pyridostigmine therapy or relapse following immunosuppressive therapy were taken as indications for surgery. The mean preoperative observation period before operation was 40 months, and after operation was 26 months. There was no operative or postoperative morbidity or mortality. Histological thymic abnormalities were found in all patients (in one case, thymoma; in four, persistent thymus; in 13, thymic hyperplasia). The histological abnormalities were identical to those found in generalised myasthenia. This included the distribution of T-cell subtypes as identified by use of monoclonal antibodies. The severity of ocular symptoms was rated using a score developed for this purpose. The score progressively declined after surgery to an average of 70% of its initial amount in 80% of patients. Full remission occurred in three cases. No patient developed generalized myasthenia. Antibody titres against acetylcholine receptors if elevated preoperatively also dropped following surgery, with one exception. Clear criteria for the expected therapeutic success of thymectomy could not be identified. Based on our results, and on the assumed significance of the thymus gland for pathogenesis, thymectomy should be considered in patients with pure ocular symptoms.

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A new rating scheme (score) is presented for ocular symptomatology in myasthenia gravis. The score (0-10) combines separate ratings upper eyelid weakness (ptosis) and paralysis of the outer ocular muscles (double vision). It is relatively insensitive to subjective influences and to the rater's experience. It yields replicable values which are especially important for longitudinal studies, for testing new therapeutic strategies and for their statistical validation.

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In a 46-year-old female patient with malignant thymoma and concomitant myasthenia gravis relapse with gravitational metastases occurred 6 1/2 years after the first operation. Metastases could be removed surgically only partially and were subsequently irradiated with 50 Gy. After 3 1/2 years renewed metastatic growth occurred. Until then the concomitant myasthenia had been stable during treatment with pyridostigmine and azathioprin and intermittent prednisone; acetylcholine receptor antibody titres had remained largely stable. Combined cytostatic treatment with vincristine, cyclophosphamide, prednisone and doxorubicin or cisplatin led to regression of metastases during the observation period of 1 1/2 years and at the same time to stabilisation of the myasthenia. Acetylcholine receptor antibody titres decreased and this was roughly paralleled by clinical improvement. Whereas there is no obvious correlation of antibodies against acetylcholine-receptor protein and tendency of tumour growth there is good agreement with the course of the accompanying myasthenia.

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Repetitive nerve stimulation (5/second) was done at the median nerve at the wrist and at the accessory nerve just behind the sternocleidomastoid muscle before and 20 seconds to 5 minutes after tetanic nerve stimulation (1 minute). Since the degree of the neuromuscular block depends on the body temperature these investigations were done successively at skin temperatures of 32 degrees C and 36 degrees C. A comparison of the results obtained revealed the highest rate of pathologic decrement with posttetanic accessory nerve stimulation (32 degrees C = 77%, 36 degrees C = 87%), whereas with posttetanic median nerve stimulation pathological results were obtained in a significantly lower proportion (32 degrees C = 50%, 36 degrees C = 60%). The advantages of the stimulation of the accessory nerve for the detection of partial neuromuscular block are: 1. The superficially located accessory nerve allows for supramaximal stimulation with rather low stimulus intensities (6-20 mA). 2. Since the accessory nerve is mainly a motor nerve, the stimulation is less painful than the stimulation of a mixed nerve. 3. Stimulation of a proximal nerve is more sensitive for detecting a defect in neuromuscular transmission than stimulation of a distal nerve. 4. There is no risk of a pneumothorax and of a traumatic nerve lesion as there is with stimulation of the brachial plexus by needle electrodes.

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