Sodium valproate in Huntington's disease.

The authors assessed the effect of sodium valproate, which is thought to elevate brain gamma-aminobutyric acid (GABA) levels, in the treatment of Huntington's disease by an objective ultrasound method in three patients with Huntington's disease. Despite plasma levels ranging from 47.0 to 140.8 microgram/ml (mean, 104.7), sodium valproate had no beneficial effect on involuntary movements. The authors stress the importance of activation to achieve a standard level of arousal in the assessment of involuntary movements.

Proximal motor neuropathy, dermato-endocrine syndrome, and IgG kappa paraproteinemia.

The association of monoclonal paraproteinemia, neuropathy, and dermato-endocrine disturbances is well recognized in Japan, and it also occurs in white patients. Neuropathy in such patients is classically distal and sensorimotor, and the paraprotein almost always contains lambda light chains. A 58-year-old white man presented with severe progressive proximal motor neuropathy, dermato-endocrine changes, and an IgG kappa paraprotein. Over a 2 1/2-year period, treatment with melphalan and prednisolone produced improvement in the neuropathy and resolution of dermato-endocrine features with a corresponding decline in the serum paraprotein concentration. Subsequent reappearance of the paraprotein, despite treatment, was associated with clinical relapse.

Cell-mediated immunity to measles virus in multiple sclerosis: correlation with disability.

The blastogenic transformation of lymphocytes on exposure to antigen was used to investigate cell-mediated immune responses to viruses implicated in the pathogenesis of multiple sclerosis. In 12 patients with "early" multiple sclerosis, lymphocyte reactivity to measles virus, parainfluenza virus, and vaccinia virus did not differ significantly from reactivity in a healthy control group. However, there was a significant inverse correlation between the lymphocyte blastogenic response to measles and vaccinia viruses and the predetermined degree of disability from multiple sclerosis. A deficient cellular response to measles virus, and possibly to other common viruses, is therefore probably a consequence of the disease itself, and not a causal factor.

Improvement in multiple sclerosis during prolonged induced hypothermia.

Moderate hypothermia (33 degrees C) was induced for 7 and 3 days, respectively, in two patients with multiple sclerosis. In both patients, striking improvement of clinical signs persisted throughout the period of cooling, indicating the potential for sustained reversal of the neurologic deficit. Hypothermia may aid management of severe acute exacerbations of multiple sclerosis.

Urinary excretion of methylarginine in human disease.

Methylated amino acids are excreted in urine upon degradation of some tissue proteins. The urinary excretion ratios of NG,N'G-dimethylarginine (syn-DMA) and NG,NG-dimethylarginine (unsym-DMA) were studied in healthy adults and in patients with various diseases. The normal ratio of sym- to unsym-DMA in urine was 0.98 and ranged from 0.71 to 1.33; ratios were not significantly different in multiple sclerosis, cerebrovascular accident, cancer, and systemic lupus erythematosus. However, patients with liver, disease, including chronic active hepatitis, were found on average to have a significantly altered ratio of 0.79, range 0.49-1.30, owing to an increase in the excretion of unsym-DMA. Hence measurements of the urinary excretion of dimethylarginine could become a useful aid in assessing recovery of liver cells in patients with chronic liver disease.

Cancer and teratogenesis: infrequent occurrence after medical use of immunosuppressive drugs.

This study examines long term "medical" immunosuppression with azathioprine or cyclophosphamide for immunopathic disease in relation to cancer and foetal malformation. The experience represent an aggregate of 241 years of treatment and 508 patient-years of follow-up in 133 non-transplant patients. For azathioprine the mean duration of treatment was 1-9 years and the mean duration of observation was 3-8 years, and for cyclophosphamide, the mean durations of treatment and observation were 0-7 and 4-6 years. A sample of 70 patients was shown by in vivo tests to have significantly suppressed cell-mediated immunity. In the period of review there were observed two cancers, both squamous cell carcinomas of skin, two benign neoplasms and six keratoses; after the period of review, three further cancers were recorded, one being in a subject with a known previous cancer. Nine pregnancies with azathioprine yielded no foetal malformations.

Binding properties of radiolabeled basic protein of myelin: reassessment in relation to diagnostic immunoassays.

The binding of radioiodinated basic protein of myelin ([125I]BPM) to a sheep lymphocyte cell pellet, sheep erythrocytes, and cell-free tubes used in the assay was investigated as a possible diagnostic procedure in multiple sclerosis. [125I]BPM apparently bound to 5 x 10(6) sheep lymphocytes incrementally with no plateau, up to 300 ng, and also to sheep erythrocytes; when cells were transferred to fresh tubes, over 90% of the radioactivity remained on the original tube, regardless of the tube surface. Various substances, including BPM and unrelated basic proteins, competitively inhibited the binding of basic protein of myelin to sheep cells and assay tubes. Binding was inhibited by sera from patients with multiple sclerosis, but equally so by normal sera. The large capacity of BPM to bind nonspecifically could limit its use in the above type of binding assay and would need to be allowed for in conventional radioimmunoassays.

A 'profile' of immune responsiveness in multiple sclerosis.

An 'immunological profile' of various indices of B-cell function and T-cell function was developed for the 'early' case of multiple sclerosis (MS). This was compared against two groups of controls comprising age and sex-matched healthy subjects, and patients with other disabling neurological diseases (CNS controls) who were matched for age, sex, and type and duration of disability. Some indices of humoral immune responsiveness, such as the induced primary response to monomeric flagellin and the 'resting' levels of antibody to measles and rubella viruses, showed significant augmentation. Cellular immune deficits were attributed to an illness effect per se because (a) cell-mediated immunity was depressed, but only when compared with that of healthy subjects and not when compared with that of the CNS controls, and (b) transformation responses of lymphocytes to viral antigens were inversely related to disability status. The abnormalities in humoral immune responses demonstrable in this study do not provide an explanation for this disease; if there is a relevant 'immunological fault', the nature of this needs to be sought from within the neuraxis rather than from the systemic circulation.

Experience with continuous ambulatory EEG monitoring.

The value of continuous ambulatory EEG monitoring in the management of patients with seizures was assessed. Eighty-seven patients were studied over a two-year period, and 198 recordings were made. In six patients data from the monitor record changed management significantly by suggesting a diagnosis other than that made clinically and by routine EEG. In a further 33 patients data strongly supporting the clinical diagnoses were obtained. In 47 patients no positive diagnostic data were obtained, and in one patient the data could not be reconciled with the clinical picture. The ambulatory EEG was particularly useful for detecting nocturnal fits, such as tonic seizures, and for differentiating genuine seizures from pseudoseizures. Limitations of the instrument include the presence of only four channels and some distortion and degradation of the EEG signal. In spite of these problems, the instrument was found to be a valuable aid in the evaluation of patients with seizures.