Prospective analysis of factors related to migraine attacks: the PAMINA study.

Migraine is related to numerous factors such as hormones, stress or nutrition, but information about their actual importance is limited. Therefore, we analysed prospectively a wide spectrum of factors related to headache in migraineurs. We examined 327 migraineurs recruited via newspapers who kept a comprehensive diary for 3 months. Statistical analysis comprising 28 325 patient days and 116 dichotomous variables was based on the interval between two successive headache attacks. We calculated univariate Cox regression analyses and included covariables with a P-value of <0.05 in two stepwise multivariate Cox regression analyses, the first accounting for a correlation of the event times within a subject, the second stratified by the number of headache-free intervals. We performed similar analyses for the occurrence of migraine attacks and for the persistence of headache and migraine. Menstruation had the most prominent effect, increasing the hazard of occurrence or persistence of headache and migraine by up to 96%. All other factors changed the hazard by <35%. The two days before menstruation and muscle tension in the neck, psychic tension, tiredness, noise and odours on days before headache onset increased the hazard of headache or migraine, whereas days off, a divorced marriage, relaxation after stress, and consumption of beer decreased the hazard. In addition, three meteorological factors increased and two others decreased the hazard. In conclusion, menstruation is most important in increasing the risk of occurrence and persistence of headache and migraine. Other factors increase the risk less markedly or decrease the risk.

Facial pain in a neurological tertiary care centre--evaluation of the International Classification of Headache Disorders.

The aim of this study was to examine the diagnostic spectrum of facial pain and to evaluate the clinical features relevant to the differential diagnosis in a neurological tertiary care centre. This is the first investigation comparing the first with the second edition of the International Classification of Headache Disorders (ICHD-I, ICHD-II) in consecutively referred patients comprising a broad spectrum of disorders without restricting the inclusion to certain diagnoses. Studying 97 consecutive patients referred for facial pain, we found trigeminal neuralgia or other types of cranial neuralgia in 38% and 39% according to ICHD-I and ICHD-II, respectively; persistent idiopathic facial pain was diagnosed in 27% and 21%, respectively. The proportion of patients who could not be classified was 24% in ICHD-I and 29% in ICHD-II. Six per cent of the patients had cluster headache or chronic paroxysmal hemicrania, the remaining 5% had various other disorders. The agreement between ICHD-I and ICHD-II was very good to perfect. In ICHD-II, sensitivity and specificity were similar to ICHD-I, the specificity and negative predictive value were imrpoved in single features of trigeminal neuralgia, but were widely unchanged in persistent idiopathic facial pain. The number of patients who could not be classified was larger in ICHD-II than in ICHD-I. Modifying the diagnostic criteria for different types of facial pain, in particular changes in the criteria of persistent idiopathic facial pain, might be helpful in reducing the number of patients with unclassifiable facial pain.

Clinical features of migraine: a cross-sectional study in patients aged three to sixty-nine.

We investigated 260 consecutive patients classified as migraine cases aged 3-69 at two tertiary headache centres, one for children and adolescents and the other for adults to evaluate the relationship between age and clinical features of migraine cross-sectionally. We only included subjects with definite migraine without or with aura and we excluded subjects with coexisting tension-type headache, medication overuse and/or other clinically relevant disorders. The percentage of males decreased markedly from childhood to adulthood and this affected the evaluation of age-related changes in male patients, as only large differences reached the level of statistical significance. In females, the headache duration and the prevalence of unilateral, pulsating pain, photophobia and phonophobia increased, whereas the prevalence of aggravation by physical activity decreased with age. In conclusion, this cross-sectional, clinic-based study on a strictly defined sample of 260 consecutive patients with definite migraine covering a wide range of age from the very young to the old suggests marked age-related differences of the clinical features of migraine in females and failed to demonstrate similar differences in males due to the small number of adult male migraineurs.

Sequential MRI in a case of Creutzfeldt-Jakob disease.

A 48-year-old man suddenly developed clinically and electroencephalographically nonspecific dementia. On MRI sequences, only diffusion-weighted images (DWI) of the cortex were unequivocally pathological. Obvious atrophy and basal ganglia signal changes appeared only 9 months after the onset. Brain biopsy confirmed Creutzfeldt-Jakob disease (CJD). In rapidly progressive dementia, we recommend DWI for early diagnosis of CJD.

Are there predictive factors for long-term outcome after withdrawal in drug-induced chronic daily headache?

OBJECTIVES: To investigate prognostic factors for long-term outcome of patients after inpatient withdrawal because of drug-induced chronic daily headache. PROCEDURES: Fifty-five patients (36 females) were re-examined by means of a standardized interview after inpatient withdrawal. The mean observation period was 9.28 +/- 2.85 years (mean +/- SD; median 8.58; range 5.00-13.50). RESULTS: Five years after withdrawal, one-third of the patients (34.6%) had an overall favourable outcome, one-third (32.7%) had no recurrent drug overuse and reported a clear-cut improvement of headache, and one-third (32.7%) developed recurrent drug overuse. Most relapses occurred within 2 years, and a small percentage within 5 years. No predictors for long-term outcome after inpatient withdrawal were found. CONCLUSIONS: All patients with drug-induced chronic daily headache should be considered as good candidates for inpatient withdrawal, and no patient should be excluded from that therapy.

A dose-defining study of sumatriptan suppositories in the acute treatment of migraine.

In this dose-ranging, randomised, multinational, multicentre, double-blind, placebo-controlled, parallel group study, 431 patients treated a single migraine attack with study medication: sumatriptan suppository 6 mg, 12.5 mg, 25 mg, 50 mg, 100 mg, or placebo. Patients were treated in the clinic with a single dose in suppository form. All doses of sumatriptan, except 6 mg, were significantly better than placebo (p < 0.004) and achieved similar rates of headache relief within two hours of dosing. The highest response rate was in the 25 mg group (72%) compared with placebo (37%) (p < 0.001). Fewer patients required rescue medication in the active groups (1% 100 mg to 13% 6 mg) compared with placebo (17%), and more patients were able to work and function normally two hours after dosing (41%, 100 mg; 20%, placebo). The overall incidence of adverse events was similar in the placebo, 6 mg and 12.5 mg groups (14-17%) but higher in the 25 mg, 50 mg and 100 mg groups (25%, 32% and 29% respectively). Analysis of plasma sumatriptan levels indicated rapid rectal absorption for all doses (median tmax = 1.0 hr). It is concluded that sumatriptan, in doses above 6 mg, is an effective and well tolerated treatment for acute migraine. From this study doses of 12.5 mg and 25 mg sumatriptan were identified as having the best efficacy/safety profile and were evaluated further.

Cardiac effects of sumatriptan: findings of Holter monitoring and review of the literature.

The aim of this study was to elucidate possible electrocardiographic effects of sumatriptan in a selected group of patients with severe headache requiring in-patient treatment. The patients (n = 21) were treated with sumatriptan in addition to various other compounds and were asked to record any symptoms following the administration of sumatriptan. In addition, Holter monitoring was performed in all subjects. In agreement with other studies, the adverse events reported by the patients were not related to ECG changes and, vice versa, ECG changes were not accompanied by clinical symptoms. The Holter findings before and after administration of sumatriptan were significantly different in three patients, i.e. recurrent episodes of ST depression and increase in extrasystoles. These changes occurred within a period of 1.45 to 18 hours and were not reproducible when Holter monitoring was repeated without sumatriptan. Even though the findings might be explained by spontaneous variability of Holter monitoring or other factors, this study does not definitely discount the possibility that sumatriptan may cause ST segment changes and increase pre-existing extrasystoles. Controlled studies are required to clarify this issue.

Long-term outcome of patients with headache and drug abuse after inpatient withdrawal: five-year follow-up.

Thirty-eight patients with "chronic daily" headache and ergotamine and/or analgesics abuse according to the criteria proposed by the International Headache Society were re-investigated 5 years after inpatient drug withdrawal. At the end of the observation period, 19 patients (50.0%) had their headaches on only 8 days per month or less, 18 patients (47.4%) were free of symptoms or had only mild headaches. A close correlation was found between the frequency of headache and the duration of drug abuse, as well as between the intensity of headache and the number of tablets taken per month. Frequency and intensity of headache had changed within the first 2 years after withdrawal, but remained stable afterwards. Fifteen patients (39.5%) reported on recurrent drug abuse. Patients with migraine showed a tendency towards a better prognosis compared to patients with tension-type headache or with combined migraine and tension-type headache. The results of this study highlight the long-term efficacy of inpatient drug withdrawal in patients with headache and ergotamine and/or analgesics abuse.

Magnesium in the prophylaxis of migraine--a double-blind placebo-controlled study.

The migraine prophylactic effect of 10 mmol magnesium twice-daily has been evaluated in a multicentre, prospective, randomized, double-blind, placebo-controlled study. Patients with two to six migraine attacks per month without aura, and history of migraine of at least 2 years, were included. A 4-week baseline period without medication was followed by 12 weeks of treatment with magnesium or placebo. The primary efficacy end-point was a reduction of at least 50% in intensity or duration of migraine attacks in hours at the end of the 12 weeks of treatment compared to baseline. With a calculated total sample size of 150 patients, an interim analysis was planned after completing treatment of at least 60 patients, which in fact was performed with 69 patients (64F, 5M), aged 18-64 years. Of these, 35 had received magnesium and 34 placebo. The number of responders was 10 in each group (28.6% under magnesium and 29.4% under placebo). As determined in the study protocol, this was a major reason to discontinue the trial. With regard to the number of migraine days or migraine attacks there was no benefit with magnesium compared to placebo. There were no centre-specific differences, and the final assessments of treatment efficacy by the doctor and patient were largely equivocal. With respect to tolerability and safety, 45.7% of patients in the magnesium group reported primarily mild adverse events like soft stool and diarrhoea in contrast to 23.5% in the placebo group.

Cyclandelate in the prophylaxis of migraine: a randomized, parallel, double-blind study in comparison with placebo and propranolol. The Study group.

Cyclandelate inhibits calcium-induced contraction of vascular smooth muscle cells, platelet aggregation induced by thrombin, platelet-activating-factor and adenosine, and also suppresses a provoked 5HT release from platelets. This pharmacological profile suggests that cyclandelate may have a potential prophylactic effect in migraine. To test this hypothesis, a double-blind multicentre study was performed in 214 patients to investigate the efficacy and tolerability of cyclandelate compared to placebo and propranolol. After a 4-week baseline period, eligible patients (randomization 3:2:3) were treated for 12 weeks with daily doses of 1.200 mg cyclandelate (n = 81), placebo (n = 55) or 120 mg propranolol (n = 78). The number of migraine attacks (> or = 50% responders) and the migraine duration/month were compared based on the difference between baseline and the last 4 weeks of prophylactic treatment. The percentage of patients with a reduction in migraine attacks of > or = 50% treated with cyclandelate (37.0%) or propranolol (42.3%) was not significantly superior to placebo (30.9%; p > 0.025). The mean duration of migraine in hours (h) per month decreased in both active treatment groups (cyclandelate: 36.8 h, p = 0.046; propranolol: 34.4 h, p = 0.039) compared to placebo (13.7 h) without reaching statistical significance (alpha/2 = 0.025). The clinical efficacy of cyclandelate and propranolol was comparable. Adverse experiences were reported by 13 patients (16.0%) treated with cyclandelate, by 5 patients (9.1%) treated with placebo and by 19 patients (24.4%) treated with propranolol. These were drug-related in 7.1% (n = 6) of patients treated with cyclandelate and in 9% (n = 7) of patients treated with propranolol. In summary, cyclandelate has a comparable efficacy to that of propranolol, an established drug of first choice in the prophylaxis of migraine. Both drugs were better than placebo, but not significantly so. Both active treatments were well tolerated.

[Sumatriptan--side effects and problems in routine clinical practice]. / Sumatriptan--Nebenwirkungen und Probleme beim Einsatz im klinischen Alltag.

AIM: The study tried to investigate the efficacy, adverse events and possible risk factors of sumatriptan in daily clinical practice. PATIENTS AND METHODS: 72 outdoor patients, who had treated their headaches at least once with sumatriptan, partly prescribed to them by outdoor physicians, were asked about their experiences with the drug. According to the criteria of the International Headache Society (1988) 55 patients were suffering from migraine, 11 from cluster headache and 6 from tension-type headache. RESULTS: Migraine and cluster patients rated the drug as effective as described in literature. Adverse events were reported by 69% of the patients which was more frequent than in most clinic studies described. Adverse events were usually not serious and transient. They were reported significantly more often by migraine patients than by patients with cluster headache and might not all be correlated to the therapy of sumatriptan. CONCLUSION: Sumatriptan has shown to be effective in the treatment of an acute migraine- and cluster-headache. The risk as to severe adverse events, especially cardial adverse events, exists if contraindications for sumatriptan are not considered. Sumatriptan should therefore only be prescribed to carefully diagnosed migraine and cluster headache patients. It should, however, not be given to patients suffering from drug abuse, because they might just change over to sumatriptan.

D2 receptor blockade by flunarizine and cinnarizine explains extrapyramidal side effects. A SPECT study.

Twenty-six patients under treatment with the calcium channel blockers flunarizine (Fz) or cinnarizine (Cz) were examined-with single-photon emission computed tomography using [123I]iodobenzamide as a ligand. The striatal dopamine D2 receptor-binding potential was determined and found to be reduced by 14 to 63% (39.5 +/- 15.0%; p < 0.0001) in patients compared with age-matched control values. This reduction was larger in 12 patients with extrapyramidal symptoms and was only slowly reversible after discontinuation of treatment. Patients treated for > 6 months had significantly larger reductions than patients treated for a shorter period. Parkinsonian symptoms were only seen in patients older than 50 years. Our findings prove a neuroleptic-like action of Fz and Cz, which seems to be the major reason for their extrapyramidal side effects. Older age and long-term treatment are predisposing factors for these effects.

Improvement of decreased critical flicker frequency (CFF) in headache patients with drug abuse after successful withdrawal.

A considerable proportion of headache patients fulfill the criteria of "drug abuse" (definition according to the International Headache Society [IHS] criteria). These patients exhibit markedly reduced vigilance and continuous performance, as shown by the results of critical flicker frequency (CFF) analysis. The present study deals with the question whether this impairment of vigilance and continuous performance is reversible. Forty-eight headache patients with drug abuse were investigated three times by means of CFF analysis: immediately before (A), immediately after (B), and 3 weeks after having finished (C) inpatient drug withdrawal. Immediately after withdrawal, a significant decrease of headache intensity was observed. The CFF values, however, remained unchanged at a depressed level, probably due to withdrawal medication and the initial sedative side effects of thymoleptic agents (given as prophylaxis). Three weeks after withdrawal, however, the CFF values were significantly improved, and were now within a range not far from the normal values known from a healthy general population. Thus, even after many years of drug abuse, headache patients have a good chance to improve their vigilance and continuous performance and to reach normal or close to normal levels.

MMPI and critical flicker frequency (CFF) analysis in headache patients with and without drug abuse.

Sixty-three headache patients (migraine: n = 28; tension-type headache: n = 35) who fulfilled the IHS criteria of 'drug abuse' were investigated by means of the Minnesota Multiphasic Personality Inventory (MMPI) and the Critical Flicker Frequency (CFF) analysis. The results were compared to those of 63 headache patients without drug abuse (matched-pair case-control study). With respect to the MMPI results, no statistically significant differences between patients with drug abuse and patients without drug abuse were found. However, patients with drug abuse showed significantly decreased CFF values compared to patients without drug abuse. This was true both for patients with migraine and for patients with tension-type headache. Thus, CFF analysis may serve as a useful method to differentiate between headache patients with drug abuse and those without drug abuse.

[Drug therapy of migraine--a review of the literature]. / Die medikamentöse Therapie der Migräne--ein Literaturüberblick.

The medical treatment of migraine has two objective points: therapy for treating symptoms of an acute attack and prophylactic therapy for reducing frequency and severity of migraine attacks. A number of different therapeutic approaches for a symptomatic and a prophylactic therapy exists. The following article tries to give a survey of possible treatment strategies of migraine published within the last three years.

Oculomotor abnormalities in Dyssynergia cerebellaris myoclonica.

In 1921 Ramsay-Hunt first described the syndrome of dyssynergia cerebellaris myoclonica (DCM), characterized by the clinical triad of action myoclonus, progressive ataxia and epilepsy with cognitive impairment, subsequently also referred to as the "Ramsay-Hunt syndrome". The cause of the symptoms of this rare degenerative syndrome (incidence: 500,000) is the impairment of a regulatory mechanism between nucleus dentatus, nucleus ruber and the bulbar olive. We present two sisters, aged 29 and 30 years, who were investigated for oculomotor abnormalities. The patients were diagnosed as having DCM according to clinical symptomatology, which was confirmed by neurophysiological and radiological findings. In both cases saccadic velocity was markedly reduced, whereas saccadic latency showed a significant increase. In addition, smooth pursuit eye-movements were abnormal and presented reduced gain. These findings suggest that pontine areas and the vestibulocerebellum also seem to be affected in DCM.

Dopamine D2 receptor blockade and antimigraine action of flunarizine.

We studied in vivo the influence of flunarizine on dopamine D2 receptors and investigated whether dopamine D2 receptor blockade is involved in its antimigraine action. Eleven migraine patients, treated with flunarizine, 10 mg per day, underwent single photon emission computer tomography (SPECT) using [123I] labeled iodobenzamide, a ligand with high affinity and high specificity for D2 receptors. There was a reduction of the dopamine D2 receptor binding potential in all patients compared to age-matched controls. The efficacy of flunarizine in migraine prophylaxis failed to correlate with the degree of the dopamine D2 receptor blockade. The antimigraine action of flunarizine may not involve antidopaminergic mechanisms.

Use and abuse of analgesics in tension-type headache.

Eighty patients suffering from tension-type headache for an average of 21 years were asked to report on all drugs they had ever taken (type, dosage, duration of intake, efficacy) or were taking currently. The patients had consumed on average 6.3 different drugs. The cumulative doses of derivatives of para-aminophenol, pyrazolone, and salicylic acid in some cases reached a maximum of several kilograms. Most drugs were classified by the patients as "moderately effective". The rating "very effective" was assigned primarily to barbiturates; however, barbiturates are no longer used as components of compound analgesic drugs in Austria. At the time of investigation, patients consumed 2.5 (mean) different drugs, primarily as compound preparations. Seventeen patients (21%) showed signs of possible analgesics- or ergotamine-induced headache and were therefore advised to undergo withdrawal therapy. Our results show that patients with tension-type headache are at considerable risk of becoming drug-dependent and of acquiring analgesics-induced headache.