E. Hokkanen

Ergotamine Abuse: Results of Ergotamine Discontinuation, with Special Reference to the Plasma Concentrations

Twenty-three patients suffering from continuous headache linked with habitual daily use of ergotamine tartrate were studied. Their headaches were classified clinically, and possible side effects of ergotamine medication, plasma levels of ergotamine, and occurrence of withdrawal symptoms after discontinuation of drug abuse were recorded. Seventeen of the patients were clinically diagnosed as suffering from “ergotamine headache”, and seven of them complained of coldness in the extremities. Plasma ergotamine levels were measured by using a radioimmunoassay. In almost half of the patients the 1 h plasma levels after the daily dose were below the detection limit of the procedure (0.12 ng/ml). The duration and severity of the withdrawal symptoms did not correlate with the doses and plasma levels of ergotamine. In only 4 of the 21 patients who were followed up for 3 to 6 months did headache symptoms not improve after ergotamine withdrawal. The results indicate that even small (0.5-1.0 mg/day) doses of ergotamine tartrate taken regularly may cause continuous headache symptoms and withdrawal symptoms after discontinuation.

Systemic availability of ergotamine tartrate after oral, rectal and intramuscular administration.

SummaryPlasma ergotamine levels were measured in 33 volunteers (subgroups 11, 12 and 10) after a single dose of ergotamine administered by various routes. Ergotamine tartrate was given in doses normally used in the treatment of acute migraine — 2.0 mg orally, 2.0 mg combined with 100 mg caffeine rectally and 0.5 mg i. m. Plasma ergotamine concentrations were determined by radioimmunoassay. The highest and longest lasting levels were found after i. m. administration, the peak concentration being 1.94±0.34 (SEM) ng/ml at 1/2 h. The corresponding maximum concentrations after oral and rectal administration were 0.36±0.08 ng/ml at 2 h and 0.42±0.09 ng/ml at 1 h. In most of the subjects the plasma ergotamine level began to rise again at 24 to 48 h. The cause of the elevation is not known but it might favour possible accumulation of the drug. Absorption from suppositories was at least as good as after oral administration and the former route may therefore be advantageous for migraine patients in whom nausea and vomiting during an attack may prevent efficient oral medication.

Efficacy of Nimodipine in the Prophylaxis of Migraine

The efficacy of nimodipine in the prophylaxis of migraine was assessed in a double-blind, placebo-controlled, cross-over study carried out on 33 patients, 20 of whom suffered from classic and 13 from common migraine. Four patients dropped out, but not as a result of the side effects of the drug. The duration of drug treatment was 8 weeks. The dosage used was 30 mg four times daily. Nimodipine proved to be better than placebo, the number of migraine attacks and severity of headache showing a significant reduction. The drug was well tolerated and no marked side effects were noted. The results suggest that nimodipine is a useful new prophylactic drug for migraine, but further studies are needed before its final value can be evaluated.

Systemic availability of ergotamine tartrate after three successive doses and during continuous medication.

SummaryPlasma ergotamine concentrations were determined by radioimmunoassay in 10 healthy subjects after a 2 mg oral dose of ergotamine, administered at 24 h intervals on three consecutive days. After the first dose the mean peak plasma level of 0.35±0.05 (SEM) ng/ml was found 1–2 h after administration. In the samples obtained 2 h after the second and third doses, plasma ergotamine levels did not exceed the first peak value. On the other hand, after the third and last dose the plasma ergotamine began to rise slowly, reaching maximum of 0.70± 0.10 ng/ml on the 6th day after administration. This supports the concept of accumulation of the drug or of immunoreactive metabolites. CSF ergotamine was determined in 4 patients, who underwent lumbar puncture for other diagnostic purposes, 1 to 2 h after the 2 mg oral dose. A concentration of 0.40± 0.03 ng/ml was observed. In seven out of 18 migraine patients who were taking ergotamine preparations daily (mean 11.7 mg/week), ergotamine could not be detected in plasma 1 h after administration of the dose. In the remaining migraine patients, the pattern of plasma ergotamine after both the daily and the test doses was similar to that of the 10 healthy subjects. The results in volunteers and migraine patients suggest notable variation in bioavailability of the drug. It seems that in most subjects there is accumulation or tissue redistribution of ergotamine or its immunoreactive metabolites, although in a significant number of migraine patients who use the drug daily, ergotamine does not appear to be biologically available.

Plasma High-Density Lipoprotein Cholesterol in Epileptics Treated with Various Anticonvulsants

Plasma high-density lipoprotein (HDL) cholesterol in 97 epileptics on long-term anticonvulsant therapy was investigated. Therapy with phenytoin alone or in combination with carbamazepine or phenobarbital was associated with elevated plasma HDL cholesterol levels as compared with controls. HDL cholesterol in patients treated with carbamazepine did not diverge from control values. Patients treated with phenytoin and phenobarbital in combination showed higher HDL cholesterol levels than those treated with phenytoin alone. There was an inverse correlation between the HDL cholesterol and serum triglyceride levels. The results demonstrate that high plasma HDL cholesterol might be associated with therapy involving some anticonvulsants known to be potent enzyme inducers. This suggests that the elevation of HDL cholesterol during therapy is probably related to the drug-caused enzyme induction phenomenon.

Serial measurements of quantitative EEG and cerebral blood flow and circulation time after brain infarction

The quantitative EEG (QEEG), regional cerebral blood flow (rCBF) and circulation time of 17 patients were examined semisimultaneously thrice during the first 3 months after a cerebral supratentorial infarction. The EEG was quantified according to normalized slope descriptor technique in nine patients and by means of a combined period and amplitude analysis in eight patients. Intravenously injected isotopes 133Xenon and 99TcmO4 were used for blood flow and circulation time measurements. The QEEG‐values improved during the whole follow‐up period. Cerebral blood flow stayed low for all 3 months and did not alter during this period, while initially prolonged circulation time to some extent improved within 2 weeks remaining, however, prolonged even thereafter. A tendency for a positive correlation between QEEG and rCBF values in the infarcted hemisphere could be seen.

Tolfenamic acid and ergotamine abuse.

SYNOPSIS

Juvenile amyotrophic lateral sclerosis. A report of two cases in a single family.

This paper presents two juvenile cases of familial amyotrophic lateral sclerosis. They are the first and fourth child in a family with seven children from the eastern part of Finland. All seven children, as well as the parents, were examined by our group. In the first case the disease showed a rather mild course, while in the second a noticeable progression was observed even during a period of 10 months. The patients come from a rural area with a stable population and low immigration, which may favor an enrichment of certain genes and therefore support the possible hereditary basis for the disease.

Efficacy of Nimodipine in Comparison with Pizotifen in the Prophylaxis of Migraine

The efficacy of nimodipine in comparison with that of pizotifen was assessed in the prophylaxis of migraine in a double-blind cross-over study, in which a double-dummy technique was also utilized. The study was carried out on 43 migraine patients, of whom 15 had classic and 28 had common migraine. A 4-week run-in placebo period preceded the drug treatments, the drug treatments lasted 12 weeks, and there was a washout placebo period of 4 weeks between nimodipine and pizotifen treatments. The dosages used were 40 mg three times daily for nimodipine and 0.5 mg three times daily for pizotifen. Both nimodipine and pizotifen proved to be better than placebo, the number of migraine attacks showing a significant reduction. There was no difference between nimodipine. and pizotifen in antimigrainous efficacy, but there were fewer side effects during the nimodipine period. The results suggest that nimodipine is an effective drug for the prophylaxis of migraine, with few side effects and therapeutic efficacy equal to that of pizotifen.

Urinary Excretion and Cerebrospinal Fluid Concentration of Cyclic Adenosine-3’,5’-monophosphate in Various Neurological Diseases

Cerebrospinal fluid (CSF) concentration and urinary excretion of cyclic adenosine-3’,5’-monophosphate (cAMP) were measured by a radioimmunoassay method from 84 and 47 neurological patients, respective