Clinical-biochemical correlates of migraine attacks in rizatriptan responders and non-responders

The present study was aimed at verifying the clinical characteristics of a typical attack in 20 migraine patients, 10 responders and 10 non-responders to rizatriptan, and at investigating any differences in the levels of neuropeptides of the trigeminovascular or parasympathetic systems [calcitonin gene-related peptide (CGRP), neurokinin A (NKA) and vasoactive intestinal peptide (VIP) measured by radioimmunoassay methods in external jugular blood] between responders and non-responders. In all responders to rizatriptan, pain was unilateral, severe, and pulsating, and in five of them at least one sign suggestive of parasympathetic system activation was recorded. Five patients who were non-responders to rizatriptan referred bilateral and non-pulsating pain, even though severe in most of them. CGRP and NKA levels measured before rizatriptan administration were significantly higher in responders than in non-responders (P < 0.0001 and P < 0.002, respectively). In the five patients with autonomic signs among rizatriptan responders, detectable VIP levels were found at baseline. One hour after rizatriptan administration, a decrease in CGRP and NKA levels was evident in the external jugular venous blood of rizatriptan responders, and this corresponded to a significant pain relief and alleviation of accompanying symptoms. VIP levels were also significantly reduced at the same time in the five patients with autonomic signs. After rizatriptan administration, CGRP and NKA levels in non-responder patients showed less significant variations at all time points after rizatriptan administration compared with rizatriptan responders. The present study, although carried out on a limited number of patients, supports recent clinical evidence of increased trigeminal activation associated with a better triptan response in migraine patients accompanied by parasympathetic activation in a subgroup of patients with autonomic signs. In contrast, the poor response seems to be correlated with a lesser degree of trigeminal activation, lower variations of trigeminal neuropeptides after triptan administration, and no evidence of parasympathetic activation at baseline.     

An open-label pilot study on the efficacy and tolerability of levetiracetam in the prophylaxis of migraine

Abstract A preliminary, open label study was conducted on 20 patients with migraine without aura and with high headache frequency to assess the efficacy and tolerability of the new antiepileptic drug levetiracetam. Patients were treated with levetiracetam for three months. The drug was started at a dose of 500 mg and slowly increased within 10 days to the target dose of 2000 mg/day. After 3 months of treatment, 11 (57.9%) of 19 patients who completed the study had a reduction of at least 50% in headache frequency. The intensity of migraine attacks was significantly reduced as was the use of symptomatic drugs. A 3-month carry-over effect was found in about two-thirds of the 11 patients reporting a positive treatment response. Levetiracetam was well tolerated and no patient discontinued the drug due to side effects. This preliminary study supports the potential role of levetiracetam as a new preventive treatment for migraine without aura. The promising results obtained should be confirmed by further research with a double-blind controlled design.     

Botulinum toxin type A in prophylactic treatment of migraine headaches: a preliminary study

Abstract The purpose of this study was to determine the safety and efficacy of botulinum toxin type A (BOTOX; Allergan, Irvine, USA) in migraine prophylaxis. We performed a double-blind, randomized, 90-day placebo-controlled study that enrolled 30 adult migraineurs. Patients received 50 units botulinum toxin type A (n=15) or placebo (n=15). Outcome measures were monthly frequency and duration of migraine attacks and the number of severe attacks. Botulinum toxin type A produced significantly greater reductions in the frequency of migraine attacks of any severity at Day 90 (-3.14 vs. -0.53; p<0.05) and in the frequency of severe migraine attacks at Days 60 (-1.4 vs. -0.54; p<0.05) and 90 (-1.8 vs. -0.20; p<0.02). One patient in the botulinum toxin type A group experienced mild, transient frontalis muscle weakness lasting approximately 30 days. Botulinum toxin type A injections were well tolerated and provided effective migraine prophylaxis in these patients.     

A review of perinatal acute pain: treating perinatal pain to reduce adult chronic pain

Changes in neural connections and activity after an acute insult are hypothesised to contribute to chronic pain syndromes in mature experimental animals and humans. Over the last decade, studies have suggested that exposure to repeated painful procedures during the early perinatal period results in profound changes in sensitivity of nociceptive pathways. Both animal and human studies show that early pain experiences increase pain responses beyond the period of infancy. These data suggest a need to increase implementation of guidelines for minimising pain exposures during infancy. In addition, an experimental perinatal pain model may provide a unique opportunity to study the effects on the nervous system of both painful insults and pre–emptive analgesia.     

LY293558, a novel AMPA/GluR5 antagonist, is efficacious and well-tolerated in acute migraine

Glutamatergic hyperactivity is implicated migraine pathogenesis. Also, LY293558, an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate (KA) receptor antagonist, is effective in preclinical models of migraine. We therefore tested LY293558 in acute migraine. We conducted a randomized, triple-blind, parallel-group, double-dummy, multicentre trial of 1.2 mg/kg intravenous (IV) LY293558, 6 mg subcutaneous (SC) sumatriptan, or placebo in the treatment of acute migraine. The primary efficacy variable was the headache response rate, i.e. headache score improvement from moderate/severe at baseline to mild/none at 2 h. Of 45 enrolled patients, 44 patients (20M:24F; mean age +/- SD = 40 +/- 9 years) completed the study. Response rates were 69% for LY293558 (P = 0.017 vs. placebo), 86% for sumatriptan (P < 0.01 vs. placebo) and 25% for placebo. LY293558 and sumatriptan were superior to placebo (P < 0.01 for all comparisons) on all other measures of improvement in pain and migraine associated symptoms. Fifteen percent of patients who took LY293558 reported adverse events (AEs) (n = 2; one mild, one severe). Fifty-three percent of patients who took sumatriptan (n = 8; seven mild, one moderate) and 31% of those who received placebo reported AEs (n = 5; four mild, one severe). The efficacy and safety results of LY293558 in this small migraine proof of concept trial, together with supportive preclinical data, provide evidence for a potential role of nonvasoactive AMPA/KA antagonists in treating migraine. Larger trials are needed to further test the hypothesis.     

Slow cortical potentials in migraine families

Amplitude and habituation of event-related potentials are abnormal in migraine. We investigated 43 migraine and 41 healthy families to evaluate the influences of age, sex and familial contribution on the variance of amplitude and habituation of the contingent negative variation (CNV). Analysis of individual differences in relation to the CNV habituation was performed. The study demonstrated that habituation of the early CNV component characterizes migraine considerably better than the CNV amplitudes. Habituation, however, is strongly influenced by age. Migraine adults and children generally showed reduced habituation. Surprisingly, more than 30% of the healthy adults demonstrated a marked loss of habituation. The reduced CNV habituation represented a high sensitivity but low specificity to migraine, especially in children. CNV amplitude and habituation parameters revealed a considerable familial contribution associated with migraine. No familial influence on either morphology or habituation of the CNV in healthy families or between healthy members of migraine families was observed. The low specificity and familial transmission of CNV parameters in members of migraine families suggest that increased amplitudes and reduced habituation of CNV do not constitute a primary risk factor for migraine, but rather represent a predisposition. Genetic components probably affect variation of the CNV amplitude and habituation.     

Distribution of intranasal C-zolmitriptan assessed by positron emission tomography

Nine healthy volunteers aged 18-28 years were recruited into this open, single-centre, two-phase trial. In phase 1, two volunteers received a single dose of 11C-zolmitriptan 2.5 mg administered as a nasal spray and then underwent positron emission tomography (PET) scanning to determine the most appropriate times for scanning in phase 2. In phase 2, six volunteers received two doses and an additional volunteer one dose of 11C-zolmitriptan 2.5 mg intranasally. Volunteers underwent PET scanning over sectors covering one of the nasopharynx, lungs or abdomen, for up to 1.5 h postdose. The brain was also scanned and plasma zolmitriptan levels were measured. Almost 100% of the administered dose was detected in the nasopharynx immediately after dosing. This declined thereafter to about 50% at 20 min and to 35% at 80 min after dosing. Radioactivity appeared slowly in the upper abdomen, with 25% of given radioactivity detected at 20 min and persisting until 80 min after dosing. Minimal radioactivity was detected in the lungs. Radioactivity was detectable within brain tissue suggesting central penetration of zolmitriptan. Zolmitriptan in plasma had approached its maximum concentration by 15 min postdose. The data indicate initial absorption across the nasal mucosa contributing to an early systemic availability. 11C-Zolmitriptan administered intranasally was well tolerated.     

Classification and clinical features of headache patients: an outpatient clinic study from China

This study aimed to analyze and classify the clinical features of headache in neurological outpatients. A cross-sectional study was conducted consecutively from March to May 2010 for headache among general neurological outpatients attending the First Affiliated Hospital of Chongqing Medical University. Personal interviews were carried out and a questionnaire was used to collect medical records. Diagnosis of headache was according to the International classification of headache disorders, 2nd edition (ICHD-II). Headache patients accounted for 19.5% of the general neurology clinic outpatients. A total of 843 (50.1%) patients were defined as having primary headache, 454 (27%) secondary headache, and 386 (23%) headache not otherwise specified (headache NOS). For primary headache, 401 (23.8%) had migraine, 399 (23.7%) tension-type headache (TTH), 8 (0.5%) cluster headache and 35 (2.1%) other headache types. Overall, migraine patients suffered (1) more severe headache intensity, (2) longer than 6 years of headache history and (3) more common analgesic medications use than TTH ones (p < 0.001).TTH patients had more frequent episodes of headaches than migraine patients, and typically headache frequency exceeded 15 days/month (p < 0.001); 22.8% of primary headache patients were defined as chronic daily headache. Almost 20% of outpatient visits to the general neurology department were of headache patients, predominantly primary headache of migraine and TTH. In outpatient headaches, more attention should be given to headache intensity and duration of headache history for migraine patients, while more attention to headache frequency should be given for the TTH ones.     

The prevalence of migraine in women aged 40-74 years: a population-based study

The objective of this study was to investigate the age-dependence of the prevalence and characteristics of migraine headache and migraine visual aura. A neurologist interviewed 728 women attending a mammography screening programme. International Headache Society (IHS) criteria were used. The lifetime prevalence of migraine headache was 31.5% and the 1-year prevalence 18.0%. The magnitude of the decline of the prevalence of active (one or more attacks in the previous year) migraine headache was estimated to 50% per decade. The prevalence of active migraine visual aura was 3.8%. This did not vary by age. Except for the pain intensity and the presence of nausea, other characteristics and concomitant symptoms did not change with age. Active migraine headache and migraine visual aura in middle-aged and older women are common and modified differently by age. We suggest that the decline of prevalence of active migraine headache with age is caused by a decrease in pain intensity.     

Association between blood pressure measures and recurrent headache in adolescents: cross-sectional data from the HUNT-Youth study

The relationship between blood pressure and headache in youth has not been explored and the objective of the present study was to provide data on this association in an adolescent population. Cross-sectional data from a large population-based survey, the Young-HUNT study, on 5,847 adolescents were used to evaluate the association between blood pressure (systolic, diastolic, mean arterial and pulse pressure) and recurrent headache, including migraine and tension-type headache. Increasing pulse pressure was inversely related to recurrent headache prevalence, and both tension-type headache and migraine. For systolic blood pressure such an inverse relationship was present for recurrent headache and tension-type headache prevalence. For migraine, the results were not significant, although there was a tendency in the same direction (p = 0.05). High-pulse pressure has previously been found to be inversely related to the prevalence of migraine and tension-type headache in an adult population. This inverse relationship has now been demonstrated to be present among adolescents also, supporting the results from a previous study in adults, that blood pressure regulation may be linked to the pathophysiology of headache.