P. T. G. Davies

RED WINE AS A CAUSE OF MIGRAINE

Patients with migraine who believed that red wine but not alcohol in general had a headache-provoking effect on them were challenged either with red wine or with a vodka and diluent mixture of equivalent alcohol content, both consumed cold out of dark bottles to disguise colour and flavour. The red wine, which had a negligible tyramine content, provoked a typical migraine attack in 9 of 11 such patients, whereas none of the 8 challenged with vodka had an attack. Neither red wine nor vodka provoked such episodes in other migrainous subjects or controls. These findings show that red wine contains a migraine-provoking agent that is neither alcohol nor tyramine.

Chocolate is a Migraine-Provoking Agent

Patients with migraine who believed that chocolate could provoke their attacks were challenged with either chocolate or a closely matching placebo. In a double-blind parallel group study, chocolate ingestion was followed by a typical migraine episode in 5 out of 12 patients, while none of the 8 patients challenged with placebo had an attack (p = 0.051). The median time to the onset of the attack was 22 h. This brief study provides some objective evidence that chocolate is able to provoke a migraine attack in certain patients who believe themselves sensitive to it.

Some clinical comparisons between common and classical migraine: a questionnaire‐based study

In a questionnaire-based study we compared the clinical features of migraine with aura (classical migraine) and migraine without aura (common migraine) in 354 and 397 patients, respectively, attending The Princess Margaret Migraine Clinic. Other than those related to the aura, no significant differences were seen in any clinical features of the attack (e.g. frequency or duration of attacks, time of day at onset, location of headache at onset, severity of headache, or nausea and vomiting). Common migraine attacks were significantly more likely to occur at weekends (p = 0.002). Dietary triggers tended to be more troublesome in classical migraineurs while pregnancy and the menstrual cycle affected both migraine types equally. Classical migraine patients were twice as likely to have a history of hypertension (p < 0.05) and showed a slightly but not significantly greater tendency to depression. Family histories of migraine were similar in each migraine type. We conclude that classical and common migraine are fundamentally similar in their clinical characteristics and that the occurrence of focal neurological symptoms during a migraine attack has little influence on the rest of the attack.

Kinetics of platelet 5-hydroxytryptamine uptake in headache patients

Platelet 5-hydroxytryptamine (5-HT) uptake was measured in asymptomatic headache patients attending a specialist migraine clinic, and in hospital staff who did not suffer from regular or severe headache. Current levels of anxiety and depression were assessed in all subjects using the Hospital Anxiety and Depression (HAD) scale and their possible influence on the uptake kinetics taken into account during the analysis of results. The Michaelis-Menten constant (K m ) was significantly raised in common migraine and tension headache compared with controls (p < 0.001 and p < 0.01, respectively), but not in classical migraine or cluster headache. The increase remained significant after adjusting for differences in age, sex, presence of anxiety or depression (HAD sub-scale score 3 8), drug intake during the week before testing, time elapsed since last attack and time of assay (am or pm). No differences were observed between patients and controls in the maximal rate of uptake (V max) or platelet count, and previous reports of a reduction in V max in patients experiencing attack within 5 days prior to testing could not be confirmed. The cause and significance of an increased K m are not clear, but plasma factors acting as competitive inhibitors for the uptake site or an alteration in the configuration of the uptake site are possible explanations. If confirmed, the shared biochemical abnormality may suggest that common migraine and tension headache have a common pathogenesis.

Platelet [3H]imipramine binding in migraine and tension headache in relation to depression.

Platelet [3H]imipramine binding was measured in 40 migrainous (7 classical and 33 common) and 17 tension headache patients and in 28 normal controls. A significant reduction in Bmax was found in migraine compared with controls (p less than 0.05) but not in tension headache. In migraine, there was no significant relationship between Bmax and depression or anxiety score on the self-rating Hospital Anxiety and Depression (HAD) Scale, suggesting that the reduction in Bmax is a concomitant of migraine itself rather than a manifestation of associated depression. Preliminary evaluation using the Schedule of Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) tended to confirm this conclusion.

Hepatic cytochrome P450 ‐mediated oxidation function in migraine

Hepatic cytochrome P450-dependent oxidation is deficient in 5% to 10% of the Caucasian population. A similar percentage seems to suffer from migraine. The hypothesis was tested that an oxidation deficiency possibly relevant to potential dietary triggers plays a role in the pathogenesis of migraine. In 37 migraine sufferers and 26 controls age- and sex-matched to 26 of these patients, debrisoquine hydroxylation following an oral dose of 10 mg was employed as a marker of oxidation status, determined by calculating the metabolic ratio (MR): urinary debrisoquine/urinary 4–hydroxydebrisoquine. MR was similarly distributed in migraineurs and controls. Three subjects in each group were poor metabolizers (MR ± 30, versus normal range, 0.1–12). MR in patients did not depend on type of migraine (common versus classic), attack frequency, the presence of trigger factors, smoking or a history of adverse reactions or sensitivity to medicines.

Urinary output of endogenous monoamine oxidase inhibitor and isatin during acute migraine attacks

Urinary output of endogenous monoamine oxidase (MAO) inhibitory activity, was significantly raised in serial samples collected across a migraine attack compared with collections during attack-free periods and in healthy controls, which did not differ from each other. There was a highly significant correlation in output between isatin, a major fraction of the MAO inhibitory activity, and output of the MAO inhibitory activity itself. However, although there was a tendency towards increased isatin excretion during migraine attacks, it failed to reach statistical significance.

Differential Changes in Receptor‐Mediated Transduction in Migraine and Cluster Headache: Studies on Polymorphonuclear Leucocytes

SYNOPSIS

Cerebral hemisphere function and migraine

An hypothesis that migraine is the experience of a protective vascular response to cerebral information overload has been explored to a limited extent by examining the association between laterality of the attack and verbal and spatial performances under standard symptom-free conditions. The study was restricted to individuals with unilateral symptoms always presenting on the same side. It emerged that those with classical migraine do not always have prodromata referable to the same side as the pain. Indeed, in the present study, prodromata were almost exclusively referable to the left (dominant) cerebral hemisphere. A subgroup of those with speech disturbances as a feature of the prodromal symptoms was also found to have relatively impaired language abilities on routine testing. It is this finding that lends some support to the hypothesis. The findings also invite the refining proposition that information overload, as defined in the hypothesis, is almost always borne by the dominant (verbal) hemisphere in our species. Such overload might concurrently or sequentially also overtax a suggested limited right hemisphere language capacity, in terms of the hypothesis, accounting for the right-sided pain sometimes presenting in these cases. Otherwise, pain appears to be predominantly left-sided or midline. Perhaps the frequency of this particular syndrome is an indictment of the limitations of language as a basis for communication, as well as reflecting the possibility that most of our stressful transactions and their cerebral processing use a verbal substrate. The results also reveal the need for agreement on rules for classification of laterality in migraine.

Nimodipine, a Calcium Entry Blocker, Platelets, and Migraine

Any theory of migraine pathogenesis must account for, or predict, the mechanism of action of drugs used effectively in prophylactic treatment. The platelet theory of migraine pathogenesis proposes that such drugs act by inhibiting platelet aggregation and/or the release reaction, or by interfering with the pharmacological activity of the release products [1], notably 5-HT. The importance of the platelet as a prime mover in the migrainous process is now doubted [2,3]. To some extent the efficacy of the major prophylactic drugs, pizotifen and methysergide, can be explained within the platelet theory of migraine, but our work has shown that this theory cannot accommodate the actions of beta-blockers on platelet activity measured ex vivo [2].