European Multicenter Trial of Nimodipine in the Prophylaxis of Classic Migraine (Migraine With Aura)

SYNOPSIS
This double-blind, randomized study of the Nimodipine 40 mg t.i.d. vs placebo in the prophylaxis of classic migraine (migraine with aura) included 89 patients. Required migraine frequency was 2–8 migraine days/4 weeks and at least two of the attacks within the last 6 months had to be with aura. The study was carried out at 11 European centers. After a 4 week run-in period, patients were randomly allocated to nimodipine or placebo for 12 weeks (parallel groups). There were 7 dropouts, 3 on Nimodipine, and 4 on placebo. A gradual and verymarked improvement was seen both with Nimodipine and placebo amounting to between 60 and 90 per cent during the last 4 weeks. Statistical analysis on all included patients (intention to treat) revealed no difference between Nimodipine and placebo for migraine days or migraine index. In patients "valid for analysis of efficacy" there were also no significant difference. Due to a very marked placebo effect and use of the parallel groups design, the present trial is relatively weak despite a fairly large sample size. It cannot rule out the possibility of an important effect of Nimodipine in classic migraine with a high degree of certainty.     

Transcranial Doppler (TCD) After Nitroglycerin in Migraine Without Aura

Nitroglycerin, a vasodilating agent, was administered sublingually in migraine without aura patients and in healthy volunteers. Systolic, diastolic and time-mean flow velocity and pulsatility index, were measured by transcranial Doppler sonography in the major intracranial arteries before and after nitroglycerin administration. Following nitroglycerin administration, a significant decrease in systolic and time-mean velocity and pulsatility index was observed in migraine patients, whereas in control subjects only time-mean velocity decreased significantly. Based on those findings we hypothesize a more marked responsiveness to nitroglycerin in migraine patients as compared to healthy subjects.     

Sanomigran for Migraine Prophylaxis; Controlled Multicenter Trial in General Practice

SYNOPSIS
Pizotifen, a tricyclic antiserotonin agent and inhibitor of certain other biogenic amines, was effective in reducing the severity and frequency of migraine attacks, producing complete remission in some cases, in a double-blind placebo controlled trial in 36 patients. Serious side effects were not reported during the trial period.     

Nimodipine versus Flunarizine in Common Migraine: A Controlled Pilot Trial

SYNOPSIS
The effects of Nimodipine and Flunarizine, both calcium-antagonist drugs, in the prevention of common migraine were investigated in a double-blind randomized parallel study. Five patients of the 30 included in the study dropped out because of adverse reactions. Two were treated with Nimodipine and three with Flunarizine. Our results suggest a similar efficacy for both drugs, although Nimodipine seems to have a shorter latency of effect. Nimodipine is a useful new agent for common migraine prevention.     

Cerebrovascular Reactivity in Migraine With and Without Aura

Abnormal cerebrovascular regulation has been implicated in the pathogenesis of migraine. Our aim in this study was to evaluate cerebrovascular reactivity to different stimulations in migraine with and without aura. Using bilateral transcranial Doppler, the changes of flow velocity during hypercapnia and mental and motor activity were measured in the middle cerebral adages of 15 controls and 30 patients with migraine with aura (n=l5) or without aura (n=15) in an attack-free period. Vascular response to all tests was similar in controls and patients. In patients with unilateral headache, no side-to-side difference was found. These findings suggest that no alteration of cerebrovascular reactivity exists outside attacks in migraine with and without aura. Further studies with transcranial Doppler considering all intracranial vessels and the comparison with other techniques of flow investigation with better regional resolution are needed to confirm these data.     

Autonomic Nervous System Function in Migraine Without Aura

Autonomic nervous system functions were studied in 13 females with migraine without aura during headache-free intervals, using physiological, pharmacological and biochemical methods. Heart-rate in the resting condition and blood pressure rises in the cold-face and isometric handgrip tests were higher than in controls. Normal cardiovascular responses to the Valsalva manoeuvre and to noradrenaline infusion suggest that the baroreflex arc is intact. Normal heart rate responses to the Valsalva manoeuvre, to the cold-face test and to deep breathing confirmed a normal cardiac parasympathetic function. Clonidine infusion showed a sedative and depressor effect and an inhibition of plasma NA similar to those occurring in controls, suggesting a normal central sympathetic tone. As a whole, the physiological, pharmacological and biochemical tests were consistent with a non-specific sympathetic hyperactivity, but do not confirm any impairment of the autonomic control of the cardiovascular system in migraine patients in headache-free intervals.     

Is Nimodipine Useful in Migraine Prophylaxis? Further Considerations

Nimodipine is one of the most discussed calcium antagonists used in cerebrovascular diseases and, recently, in migraine prophylaxis. Its specificity in preventing cerebral arterial constriction has been invoked to explain nimodipine's efficacy in migraine. The discovery of neuronal receptors specific for dihydropyridines, however, favours a mechanism of action for nimodipine that is not exclusively vascular. This is in accordance with a view of migraine pathogenesis which implicates a primary neuronal event as the basis of the vascular changes observed in migraine patients.     

Visual Cortex Excitability in Migraine With and Without Aura

OBJECTIVES: Previous research using transcranial magnetic stimulation has produced equivocal findings concerning thresholds for the generation of visual phosphenes in migraine with aura. These studies were methodologically varied and did not systematically address cortical excitability in migraine without aura. We therefore studied magnetophosphene thresholds in both migraine with aura and migraine without aura compared with headache-free controls. METHODS: Sixteen subjects with migraine with aura and 12 subjects with migraine without aura were studied and compared with 16 sex- and age-matched controls. Using a standardized transcranial magnetic stimulation protocol of the occipital cortex, we assessed the threshold stimulation intensity at which subjects just perceived phosphenes via a method of alternating course and fine-tuning of stimulator output. RESULTS: There were no significant differences across groups in the proportion of subjects seeing phosphenes. However, the mean threshold at which phosphenes were reported was significantly lower in both migraine groups (migraine with aura=47%, migraine without aura=46%) than in controls (66%). Moreover, there was no significant correlation between individual phosphene threshold and the time interval to the closest migraine attack. CONCLUSION: Our findings confirm that the occipital cortex is hyperexcitable in the migraine interictum, both in migraine with and without aura.     

偏头痛先兆的发病机理

近年来,越来越多的研究结果显示,皮质扩布性抑制可能是偏头痛先兆的病理生理学基础。笔者对偏头痛先兆与皮质扩布性抑制之间的关系进行综述。     

Migraine Stroke: A Possible Complication of Both Migraine With and Without Aura

We describe four migraine patients who developed an ischemic stroke during their typical migraine attacks.
Cerebral infarction as a possible complication of migraine without aura is discussed.
We propose a review of the migraine stroke definition of the International Headache Society.     

Lipid Composition of Platelets in Patients Suffering From Migraine Without Aura

Patients with migraine have a platelet hyper-aggregability. As this alteration could be the consequence of an abnormal lipid composition of platelet membranes, we studied the phospholipid specimens and the cholesterol/phospholipid ratio in platelets of seven patients suffering from migraine. The holesterol/phospholipid ratio was 0.7 ± 0.1 (normal 0.6 ± 0.1, molar ratio). The proportion of five main platelet phospholipids components including phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, phosphatidylserine, and phosphatidylinositol, were also normal. These data suggest that platelet hyperactivity in patients with migraine is not due to an altered lipid content of these cells.     

A Placebo-Controlled Crossover Trial of Nimodipine in Pediatric Migraine

An 8-month, double-blind, placebo-controlled crossover trial was carried out on the use of nimodipine in migraine prophylaxis in 37 patients aged 7 to 18 years old. After a 4-week medication-free run-in period, 19 subjects (Group 1) received a placebo while 18 (Group 2) received nimodipine (10-20 mg t.i.d., according to body weight), for 12 weeks. After a 4-week wash-out period, the groups switched therapy for a further 12 weeks. 30 patients completed the trial and the number of dropouts was comparable in the 2 groups. The only side-effect during nimodipine treatment was mild abdominal discomfort (3 cases). The treatments were evaluated on the basis of frequency and duration of attacks. There was a significant reduction in both parameters during the first period of treatment. During the second period of treatment, nimodipine proved to have a significantly greater effect than the placebo with regard to frequency, whereas the response was similar with the placebo as regards duration of attacks. The latter parameter shows a significant decrease during the treatment periods, regardless of type of therapy.     

The Frontotemporal Region Plays a Role in the Genesis of Migraine Without Aura

We have compared the migraine-inducing effect of nitroglycerin ointment applied to the frontotemporal region of the head, which is innervated by the ophthalmic and maxillary divisions of the trigeminal nerve, with that of nitroglycerin applied to the chin (innervated by the mandibular division), the posterolateral region of the neck (innervated by the second and third cervical roots), the lateral surface of the proximal third of the forearm (innervated by the sixth cervical root), and the medial surface of the upper-arm region (second dorsal root). One hundred patients suffering from migraine without aura were randomly divided into five equal groups. Each group received an application of 5 mg nitroglycerin in 2% ointment on a preselected body area for 2 hours. Frontotemporal nitroglycerin induced a significantly greater number of early onset migraine attacks with respect to the arm and forearm regions. In all cases, nitroglycerin applied to the frontotemporal region resulted in subsequent migraine, whereas there was a significant number of negative trials with nitroglycerin applied to the neck, arm, and forearm vs the frontotemporal area. It, therefore, appears that the trigeminal nerve endings in the affected frontotemporal region are particularly sensitive to the migraine-inducing effect of the nitrate. This suggests a peripheral neurogenic hypothesis of migraine genesis.     

Flunarizine in Migraine Prophylaxis: An Indian Trial

Flunarizine, a calcium channel blocker is considered useful in migraine prophylaxis. We report the first Indian trial with this drug. Fifteen patients with migraine were studied in a 6 months double-blind, placebo-controlled crossover trial. Flunarizine was superior to placebo in reducing the severity and duration of the individual attacks though there was no statistically significant effect on frequency of migraine attacks. The side effects most frequently caused by flunarizine were weight gain and daytime sleepiness.     

Clonazepam (Rivotril) in Migraine Prophylaxis

SYNOPSIS
A double-blind cross-over study with clonazepam (Rivotril) 0.5 mg b.i.d. versus placebo was carried out in 38 migraine patients. After a pre–test period of 4 weeks, Rivotril 1 mg per day and placebo were given during a 4 week period each, in a randomized fashion; thereafter Rivotril 2 mg per day was given for 4 weeks in a semi-blind fashion.
With regard to headache days, the results for both I and 2 mg Rivotril differed significantly (p<0.05) from the pre–test status, whereas with regard to the headache index, only the result for 2 mg differed significantly from pre-test results. When the placebo results (and not the pre–test results) were used, no significant difference was found with either 1 or 2 mg Rivotril.
More than half the patients complained of some drowsiness on Rivotril medication, particularly in the initial phase. Eighteen patients continued with Rivotril medication on a long–term basis in an open trial with some beneficial effect and less side–effects.