A placebo-controlled trial of isoprinosine in patients with multiple sclerosis.

Isoprinosine was used under double-blind, randomised, and placebo-controlled conditions in 52 patients with relapsing/remitting or progressive multiple sclerosis. All patients received pulsed treatment with methylprednisolone. There was no significant effect of treatment on clinical disability or the accumulation of MRI abnormalities, after correction of results for multiple comparisons. It is concluded that isoprinosine is not effective therapy for multiple sclerosis.

Quantitative magnetic resonance imaging in multiple sclerosis: the effect of high dose intravenous methylprednisolone.

Magnetic resonance imaging was performed on 50 patients with clinically definite or probable multiple sclerosis before and 15 days after starting treatment with intravenous methylprednisolone (0.5 g daily for 5 days). Scans were abnormal in 49 patients. New lesions had appeared on the second scan in nine individuals and in seven a single pre-existing lesion appeared to have become smaller but in no case were lesions seen to disappear. Two patients showed both reduction in the size of an abnormal area and development of a single new lesion indicating that corticosteroids do not appear rapidly to alter the process underlying plaque formation. Measurements of relaxation times were performed in 12 randomly selected patients. All showed elevated values in normal appearing white matter but not cortex before treatment compared with 18 healthy controls. After treatment a significant decrease of T1 and T2 was observed in cortex, and of T1 alone in normal appearing white matter. No significant change could be detected within lesions, a finding attributed to the wide range of relaxation values observed at these sites before treatment. Since brain water content is increased in normal appearing white matter of multiple sclerosis patients, and is significantly reduced by high-dose methylprednisolone, resolution of oedema may contribute to the rapid spontaneous or corticosteroid induced symptomatic recovery that characterises the disease in its early stages.

A comparison of the acute effect of single doses of vigabatrin and sodium valproate on photosensitivity in epileptic patients.

The acute effect of oral administration of a single dose of vigabatrin, a new antiepileptic drug which acts by irreversible enzyme-activated inhibition of the brain enzyme, GABA-aminotransferase, on the photoconvulsive response in patients with photosensitive epilepsy, was compared with that of the established antiepileptic drug, sodium valproate. Both drugs significantly suppressed the photoconvulsive response in 3 out of 6 subjects. This result was interpreted as further evidence of vigabatrin's potential value in the future treatment of patients with epilepsy.

A double-blind controlled trial of high dose methylprednisolone in patients with multiple sclerosis: 2. Laboratory results.

Laboratory measurements were compared in paired samples from 50 patients included in a double-blind placebo controlled trial of methylprednisolone in the treatment of multiple sclerosis. Cerebrospinal fluid total cell count, IgG and C9 indices, and percentage of peripheral blood OKT8 positive cells were abnormal at entry and returned closer to the normal range after active than placebo treatment, but the differences were not statistically significant. The percentage of peripheral blood OKT4 positive cells was normal at entry as was the amplitude of visual evoked potentials, whereas their latency was prolonged; these measurements were each uninfluenced by methylprednisolone. Corticosteroids might act merely by influencing oedema, but the laboratory results suggest that methylprednisolone affects immunological events which underly rapid onset and recovery of symptoms in patients with multiple sclerosis; additional forms of treatment are needed to maintain these clinical and immunological effects.

A double-blind controlled trial of high dose methylprednisolone in patients with multiple sclerosis: 1. Clinical effects.

A randomised double-blind, placebo-controlled trial of high-dose, pulsed intravenous methylprednisolone was carried out in 50 individuals with multiple sclerosis; 22 patients were in acute relapse and 28 had chronic progressive disease. After a baseline assessment using the Kurtzke functional and expanded disability status scales each patient was randomly allocated to intravenous treatment with methylprednisolone (500 mg) or a saline placebo administered as a single daily dose for 5 days. Clinical assessments were repeated at 1 and 4 weeks after starting treatment. The results from all 50 patients showed a highly significant effect in favour of methylprednisolone treatment (p less than 0.001). In patients with relapse, there was a significant decrease in clinical disability scores at 1 and 4 weeks in the methylprednisolone treated group compared with controls (p less than 0.05 for each comparison). In the chronic progressive group, disability scores at 4 weeks only were significantly lower after treatment with methylprednisolone (p less than 0.01), mainly attributable to improvement in pyramidal function.

A clinical trial of single dose rectal and oral administration of diazepam for the prevention of serial seizures in adult epileptic patients.

The clinical anticonvulsant efficacy of single dose rectal and oral administration of diazepam 20 mg was examined in two double-blind placebo-controlled trials in adult epileptic patients. All subjects suffered from drug resistant epilepsy and frequently experienced serial seizures. Diazepam was administered rectally as a new experimental suppository formulation immediately after a seizure and was highly effective in preventing recurrent fits within a 24 h observation period (p less than 0.001). Pharmacokinetic studies revealed a wide range of serum diazepam concentrations 60 min after administration of the suppository (mean serum diazepam level 190 +/- 73 (SD ng/ml). In a similar study oral administration of diazepam 20 mg significantly reduced the incidence of serial seizures compared with a placebo (p less than 0.01) and the mean 60 min serum diazepam level was 273 +/- 190 (SD) ng/ml.

Acute cervical cord injuries in patients with epilepsy.

Seven cases with acute cervical cord lesions associated with a fit and fall, were found in approximately 500 patients with epilepsy over a period of 7 years. In all patients the epilepsy was refractory to drug therapy and six suffered tonic fits which resulted in falls and frequent head injuries. Notable radiological changes were found in the cervical spine; there was ankylosis in five, hyperostosis in four and the minimum sagittal diameter of the bony canal was less than 11mm in three cases. The findings indicate that repetitive trauma may be a factor in producing bony changes in the cervical spine which put the patient at risk of cervical cord injury, especially when the spinal canal is developmentally narrow.