Studies to assess if pizotifen prophylaxis improves migraine beyond the benefit offered by acute sumatriptan therapy alone.

Two multi-centre studies-one double-blind, placebo-controlled (study 1) and one open (study 2)-were set up to assess if pizotifen prophylaxis improved migraine beyond the benefit offered by acute sumatriptan therapy alone. Eighty-eight patients completed the blinded study and 63 patients completed the open study. Both studies were of crossover design with patients undertaking a 4 week run-in period prior to a 12-week treatment period. Following a 4-week washout period patients commenced a second 12-week treatment period on the alternative treatment regimen. All breakthrough attacks were treated with 100 mg oral sumatriptan with an optional 2 doses available to treat any recurrence within 24 h of taking dose 1. Pizotifen was built up to a final daily dose of 1.5 mg over a 2-week period and patients remained on this dose for a further 10 weeks. Patients in the blinded study were given matching placebo tablets for one of the two treatment periods. The efficacy of sumatriptan was not affected by pizotifen. The median of the monthly attack rate experienced by patients was slightly lower whilst patients were on pizotifen and sumatriptan than while on placebo prophylaxis and sumatriptan or sumatriptan alone; study 1, 3.5 vs 3.9 attacks per month (p = 0.008); study 2, 2.9 vs. 3.2 attacks per month (p = 0.23). Also, while on pizotifen and sumatriptan more patients had a greater proportion of their time in the study migraine-free. From the results of these studies it does not appear that pizotifen reduces migraine severity; regardless of the treatment regimen the initial headache severity of most attacks was moderate. Weight gains experienced by patients while on pizotifen and sumatriptan were greater than the weight gains experienced while on placebo prophylaxis and sumatriptan or sumatriptan alone (period 1); study 1, 2.6 vs. 1.0 kg (p = 0.002); study 2, 1.6 vs. -0.8 kg (p < 0.0001). The combination of pizotifen and sumatriptan did not result in any additional adverse events other than those usually seen with each medication alone. In these studies, where the average number of migraine attacks was around 4 per month, the benefits conferred by pizotifen were at the expense of the adverse events associated with the drug, particularly weight gain. Therefore the clinical benefit of treatment with pizotifen for patients who have less than 4 attacks per month should be carefully reviewed as acute treatment with sumatriptan may be the most appropriate treatment. Pizotifen may be better reserved for those patients who have 4 of more attacks per month.

Neurological paraneoplastic syndromes in patients with small cell lung cancer. A prospective survey of 150 patients.

One hundred and fifty patients presenting with small cell lung cancer (SCLC) to chest physicians, were assessed neurologically. Neuromuscular or autonomic deficits were common and occurred in up to 44% of cases. Weakness, dry mouth, and weight loss were not mutually independent and may represent the syndrome formerly described as carcinomatous neuromyopathy. By contrast, undoubted paraneoplastic syndromes were much less commonly detected. Two patients had the Lambert-Eaton myasthenic syndrome (LEMS) and one had subacute sensory neuropathy (SSN). In these patients, neurological symptoms antedated other manifestations of cancer, by between six and 17 months. The 95% confidence interval for the prevalence of LEMS or SSN among SCLC patients was 0-4%, consistent with the results of previous retrospective or smaller studies: summing these, the overall prevalence of LEMS among SCLC patients is close to 3%, which implies about 250 new cases per annum in England and Wales. If LEMS and SSN are the least uncommon neurological paraneoplastic syndromes in SCLC patients, this may reflect the accessibility of motor nerve terminals and dorsal root ganglia to cross-reactive anti-tumour cell antibodies.

Adrenoleukodystrophy: heterogeneity in two brothers.

A man with hypoadrenalism died from a rapidly progressive pseudobulbar palsy, due to adult onset adrenoleukodystrophy. This diagnosis suggested that his brother, with a longstanding spastic paraparesis, suffered from adrenomyeloneuropathy. Both cases were confirmed biochemically. The heterogeneity of expression of this x-linked disorder is described, with the consequent difficulty in diagnosis and nomenclature.