Franca Moschiano

Melatonin versus Placebo in the Prophylaxis of Cluster Headache: A Double-Blind Pilot Study with Parallel Groups

A fall in nocturnal plasma melatonin occurs in patients with cluster headache, suggesting that melatonin may play a role in the promotion of attacks. During a cluster period, we administered melatonin to 20 cluster headache patients (2 primary chronic, 18 episodic) in a double-blind placebo-controlled study of oral melatonin 10 mg (n=10) or placebo (n=10) for 14 days taken in a single evening dose. Headache frequency was significantly reduced (ANOVA, p<0.03) and there were strong trends towards reduced analgesic consumption (ANOVA, p<0.06) in the treatment group. Five of the 10 treated patients were responders whose attack frequency declined 3-5 days after treatment, and they experienced no further attacks until melatonin was discontinued. The chronic cluster patients did not respond. No patient in the placebo group responded. There were no side effects in either group. Although the response rate is low, melatonin may be suitable for cluster headache prophylaxis in some patients, particularly those who cannot tolerate other drugs.

Verapamil in the prophylaxis of episodic cluster headache: A double-blind study versus placebo

Article abstract The authors performed a double-blind, double-dummy study to compare the efficacy of verapamil with placebo in the prophylaxis of episodic cluster headache. After 5 days’ run-in, 15 patients received verapamil (120 mg tid) and 15 received placebo (tid) for 14 days. The authors found a significant reduction in attack frequency and abortive agents consumption in the verapamil group. Side effects were mild. These findings provide objective evidence for the effectiveness of verapamil in episodic cluster headache prophylaxis.

Twenty-Four-Hour Melatonin and Cortisol Plasma Levels in Relation to Timing of Cluster Headache

The cyclic recurrence of cluster periods and the regular timing of headache occurrence in cluster headache (CH) induced us to study the circadian secretion of melatonin and cortisol in 12 patients with episodic CH, during a cluster period, and compare them with 7 age- and sex-matched healthy controls. Blood was sampled every 2, h for 24 h. All subjects were confined to a dark room from 22.00 to 08.00. Plasma melatonin levels were significantly reduced in CH patients (repeated measures ANOVA p < 0.03; mesor p < 0.02), and the cortisol mesor was significantly increased (p < 0.03). Amplitudes and acrophases did not differ between the groups. Individual cosinor analysis showed that 4/12 (33.3%) CH patients had no significant melatonin rhythm, and that 5/11 (45.5%) had no cortisol rhythm. Group analysis of cosinor revealed significant rhythmicity of melatonin and cortisol secretion in both groups. In controls, the timing of melatonin and cortisol acrophase significantly correlated with each other, indicating that the biorhythm controllers for the secretion of these hormones were synchronized. Such correlation was not found in the CH patients; mesor, amplitude and acrophase of melatonin and cortisol did not correlate with duration of illness, duration of headache in course, or time since last headache attack.

Genetic abnormalities of the protein C system: shared risk factors in young adults with migraine with aura and with ischemic stroke?

Migraine, particularly migraine with aura (MA), may be a risk factor for ischemic stroke (IS). The reasons for this association are unknown. We investigated the presence of genetic abnormalities of the protein C system in 83 MA patients, 31 IS patients, and 124 healthy controls, all aged under 45 years. We found an increased frequency of activated protein C resistance due to Arg506Gln factor V mutation, and of protein S deficiency in both disorders, with figures higher than those reported in the general population and significantly different from those found in controls. These prothrombotic genetic abnormalities may be shared risk factors in IS and MA, and may play a role in increasing the risk of cerebrovascular disease in migraineurs.

Naratriptan in the short-term prophylaxis of pure menstrual migraine.

Menstrual migraines are particularly difficult-totreat. Few studies on the use of triptans in short-term prophylaxis of menstrually related migraine have been recently conducted, but evidences of triptans’ efficacy in the specific case of pure menstrual migraine (PMM) are lacking.The aim of this study is to explore the efficacy and tolerability of naratriptan as short-term prophylaxis of pure menstrual migraine (PMM) attacks. A multi-centre, open, non comparative, pilot six-month study was conducted in women, aged 18 years or older, with regular menstrual cycles and with a history of migraine without aura exclusively associated to the perimenstrual period. After an observation period of three months, patients took for three consecutive menstrual cycles oral naratriptan 1 mg twice daily, starting two days before the expected onset of menstruation and continuing for six days. Ninety-eight women with a history of PMM were screened for study participation, and 61 entered the study. Fifty-nine comprised the intent-to-treat population. The mean number of PMM attacks decreased from 3.5±1.4 in the 3-month observation period to 1.6±1.3 in the 3-month treatment with naratriptan. The pecentage of responders (subjects who recorded a decrease—equal or more than 50%—in the mean number of attacks) was 61.4%. A tendency towards a decrease in headache severity and in the presence of associated symptoms was observed during treatment. At least one adverse event during the treatment period was reported by 19 patients (31.1%). No serious adverse events occurred. Naratriptan may be an effective and safe treatment option in the short-prophylaxis of PMM.

Homocysteine plasma levels in patients with migraine with aura

We investigated homocysteine plasma levels in 136 MA sufferers and in 117 sex-and age-matched controls. Mean homocysteine plasma levels — as well as the proportion of subjects with hyperhomocysteinaemia — were significantly higher in patients with MA than in healthy controls. Hyperhomocysteinaemia may be a link between MA and ischaemic stroke.

Headache and anxiety–depressive disorder comorbidity: the HADAS study

Psychiatric comorbidity (prevalence and types) was tested in a naturalistic sample of adult patients with pure migraine without aura, and in two control groups of patients, one experiencing pure tension-type headache and the other combined migraine and tension-type headaches. The study population included 374 patients (158, 110 and 106) from nine Italian secondary and tertiary centres. Psychiatric comorbidity was recorded through structured interview and also screened with the Mini International Neuropsychiatry Interview (MINI). Only anxiety and depression were investigated. Psychiatric disorders were reported by 49 patients (14.6%; 10.9% of patients with migraine, 12.8% of those with tension-type headache and 21.4% of those with combined migraine and tension-type headaches). The MINI interview detected a depressive episode in 59.9% of patients with migraine, 68.3% of patients with tension-type headache and 69.6% of patients with combined migraine and tension-type headaches. Depression subtypes were significantly different across groups (p=0.03). Anxiety (mostly generalised) was reported by 18.4% of patients with migraine, 19.3% of patients with tension-type headache, and 18.4% of patients with combined migraine and tension-type headaches. The values for panic disturbance were 12.7, 5.5 and 14.2, and those for obsessive–compulsive disorders were 2.3, 1.1 and 9.4% (p=0.009). Based on these results, psychopathology of primary headache can be a reflection of the burden of the disease rather than a hallmark of a specific headache category.

Possible Identification of Cervicogenic Headache Among Patients With Migraine: An Analysis of 374 Headaches

According to Sjaastad, the pain in cervicogenic headache, a form not recognized by the IHS, is long lasting and always side‐locked unilateral. The frequency of side‐locked unilateral pain (defined here as no change in side from onset) and other characteristics of cervicogenic headache were investigated in 300 outpatients using information collected on standard forms in structured interviews. Three hundred seventy‐four headaches diagnosed according to IHS criteria were identified. Three hundred forty‐eight of these headaches were long‐lasting (duration of more than 4 hours); migraine (65%) followed by tension‐type headache (25%) were the commonest forms. Side‐locked unilaterality was present in 29% (101 of 348), and occurred most frequently in migrainous disorders not fulfilling the criteria (25 of 56, 44.6%). This group differed significantly from the other migraine conditions for longer pain duration (P<0.02) and less frequent nausea, vomiting, photophobia, phonophobia (P<0.0001), and aggravation by physical activity (P<0.02). With these characteristics, this group resembled cervicogenic headache. However, in none of these patients was pain triggered by head or neck movements, and the frequency of head or neck trauma did not differ from other headaches. A more precise definition of clinical criteria for cervicogenic headache vs migraine is, therefore, required.

Coagulation abnormalities in migraine and ischaemic cerebrovascular disease: a link between migraine and ischaemic stroke?

Abstract.Migraine, particularly migraine with aura, is a risk factor for ischaemic stroke. The mechanisms underlying this association are obscure. One hypothesis is that shared risk factors may be the cause of this association. Over the last decade, studies have suggested an association between migraine and genetic abnormalities in coagulation factors which play an important role in stroke pathogenesis. Although the results of studies on various prothrombotic conditions are conflicting, findings suggest a higher frequency of some genetic abnormalities in migraine with aura patients. Thus, persistent hypercoagulability may explain the tendency for these patients to develop thromboembolic cerebrovascular events, especially when they are exposed to additional procoagulant stresses. Further studies on larger samples are required to test this hypothesis.

Electromyographic biofeedback-assisted relaxation training in juvenile episodic tension-type headache: clinical outcome at three-year follow-up.

Although tension-type headaches are more common than migraine in children and adolescents, the limited studies that have been conducted with juveniles have focused chiefly on migraine treatment and its course. This report describes the clinical benefits for an electromyographic biofeedback-assisted relaxation treatment program for a group of children and adolescents experiencing episodic tension-type headache and examines whether the clinical presentation changed for headaches that remained. Of the 54 consecutive juveniles who began treatment, 38 completed and were available to participate in the 3-year follow-up. Headaches improved measurably immediately following treatment, with further gains being evident through 3 years. The few headaches that did occur at 3 years were nearly identical symptom-for-symptom to those that were experienced prior to treatment. This report suggests that behavioural treatment is a viable and durable intervention for juvenile episodic tension-type headache, but more definitive claims cannot be made due to the uncontrolled nature of the study. Further investigation is warranted.