Is familial hemiplegic migraine a hereditary form of basilar migraine?

We studied aura symptoms in 83 patients from 6 unrelated families suffering from familial hemiplegic migraine. Fifty-five of the patients reported symptoms that allowed us to categorize them as basilar migraine (BM) patients, in accordance with the International Headache Society (IHS) criteria. In a control group of 33 patients suffering from migraine with aura and 33 patients suffering from migraine without aura, 9 patients complained of vertigo, and only one patient of diplopia during one of her attacks. None of these control patients fulfilled the IHS criteria for BM We suggest that familial hemiplegic migraine and BM may share certain pathophysiologic mechanisms, which may consist of a (genetically determined) disturbance of basilar artery blood flow.     

Investigation of neuromuscular transmission in some rare types of migraine

The aim of this study was to delineate any dysfunction of neuromuscular transmission (NMT) by single-fibre electromyography (SFEMG) in some rare types of migraine. Recent studies have shown subclinical dysfunction of NMT in migraine with aura and cluster headache by using SFEMG, whereas another recent study has shown NMT to be normal in familial hemiplegic migraine (FHM) with CACNA1A mutations. Thirty patients with rare primary headache syndromes [18 with sporadic hemiplegic migraine (SHM), six with FHM and six with basilar-type migraine (BM)] and 15 healthy control subjects without any headache complaints underwent nerve conduction studies, EMG and SFEMG during voluntary contraction of the extensor digitorum communis muscle. Ten to 20 different potential pairs were recorded and individual jitter values calculated. The results obtained from patient groups were compared with those from the normal subjects. Of 600 individual jitter values of the patients, 27 (4.5%) were abnormally high, whereas only 3/205 (1.5%) jitter values from normal subjects were abnormal. Abnormal NMT was found in 4/30 (13.3%) patients (three SHM and one BM), but in none of the control subjects. Only in SHM patients was the number of individual abnormal jitter values slightly but significantly different from normal controls. The present study demonstrates that subclinical NMT abnormality is slightly present in only SHM and BM patients, but not in FHM patients.     

Migraine Mimics

The symptoms of migraine are non‐specific and can be present in many other primary and secondary headache disorders, which are reviewed. Even experienced headache specialists may be challenged at times when diagnosing what appears to be first or worst, new type, migraine status, and chronic migraine.     

Retinal migraine reappraised

Retinal migraine is usually characterized by attacks of fully reversible monocular visual loss associated with migraine headache. Herein we summarize the clinical features and prognosis of 46 patients (six new cases and 40 from the literature) with retinal migraine based upon the International Classification of Headache Disorders-2 (ICHD-2) criteria. In our review, retinal migraine is most common in women in the second to third decade of life. Contrary to ICHD-2 criteria, most have a history of migraine with aura. In the typical attack monocular visual features consist of partial or complete visual loss lasting <1 h, ipsilateral to the headache. Nearly half of reported cases with recurrent transient monocular visual loss subsequently experienced permanent monocular visual loss. Although the ICHD-2 diagnostic criteria for retinal migraine require reversible visual loss, our findings suggest that irreversible visual loss is part of the retinal migraine spectrum, perhaps representing an ocular form of migrainous infarction. Based on this observation, the authors recommend migraine prophylactic treatment in an attempt to prevent permanent visual loss, even if attacks are infrequent. We also propose a revision to the ICHD-2 diagnostic criteria for retinal migraine.     

Imaging abnormalities in sporadic hemiplegic migraine on conventional MRI, diffusion and perfusion MRI and MRS

Prolonged hemiparetic migraine aura can cause diagnostic confusion and be mistaken for ischaemic stroke occurring during the course of a migraine--'migrainous infarction'. We report a case of prolonged hemiparesis occurring during the course of a migraine attack. Though initially confused with migrainous infarction, we suggest with sequential magnetic resonance imaging, magnetic resonance angiography, diffusion, perfusion images and magnetic resonance spectroscopy that the hemiplegia was not of vascular origin and that the patient had sporadic hemiplegic migraine. We hypothesize that the mechanisms of sporadic hemiplegic migraine probably lie at a cellular level, similiar to familial hemiplegic migraine.     

Rational combination therapy in refractory migraine

Refractory migraine (RM) headaches pose important treatment challenges to the patients who live with them and the clinicians who try to treat them. Defined based on the lack of response to acute, preventive, and nonpharmacologic treatment, RM is often treated with a combination of treatments. Although combination therapy for RM has not been systematically studied in randomized trials, clinical experience suggests that a rational approach to RM treatment, utilizing a combination of treatments, may be effective where monotherapy has failed. In this article we briefly identify patient populations appropriate for more aggressive migraine prevention with combination therapy. We then discuss modifiable risk factors and comorbidities in migraine and then focus on the use of rational combination therapy, as well as the duration migraine preventatives should be considered for use. Future research is needed to evaluate the full potential of rational combination treatment as a strategy for treating and ultimately preventing RM.     

Triptans in the treatment of basilar migraine and migraine with prolonged aura

OBJECTIVE: To report on the use of triptans in migraine with prominent neurologic symptoms. BACKGROUND: As stated in their package inserts, the triptans are contraindicated in patients with basilar or familial hemiplegic migraine, and physicians are reluctant to prescribe these drugs to other patients with prominent or prolonged aura. METHODS: We evaluated 13 patients with basilar migraine, familial hemiplegic migraine, or migraine with prominent or prolonged aura who had received triptans. RESULTS: Excellent; no adverse events. CONCLUSION: The contraindication of triptans in basilar migraine should be reconsidered. Similarly, prominent or prolonged aura may not represent a reasonable contraindication to triptan therapy.     

Acute migraine medications and evolution from episodic to chronic migraine: a longitudinal population-based study

Background.— Though symptomatic medication overuse is believed to play a major role in progression from episodic to chronic or transformed migraine (TM), population‐based longitudinal data on these agents are limited. Objectives.— To assess the role of specific classes of acute medications in the development of TM in episodic migraine (EM) sufferers after adjusting for other risk factors for headache progression. Methods.— As a part of the American Migraine Prevalence and Prevention study (AMPP), we initially surveyed a population sample of 120,000 individuals to identify a sample of migraineurs to be followed annually over 5 years. Using logistic and linear regression, we modeled the probability of transition from EM in 2005 to TM in 2006 in relation to medication use status at baseline. Adjustments were made for gender, headache frequency and severity, and prevention medication use. Results.— Of 8219 individuals with EM in 2005, 209 (2.5%) had developed TM by 2006. Baseline headache frequency was a risk factor for TM. Using acetaminophen user as the reference group, individuals who used medications containing barbiturates (OR = 2.06, 95%CI = 1.3‐3.1) or opiates (OR = 1.98, 95%CI = 1.4‐2.2) were at increased risk of TM. A dose–response relationship was found for use of barbiturates. Use of triptans (OR = 1.25, 95%CI = 0.9‐1.7) at baseline was not associated with prospective risk of TM. Overall, NSAIDs (OR = 0.85, 95%CI = 0.63‐1.17) were not associated with TM. Indeed, NSAIDs were protective against transition to TM at low to moderate monthly headache days, but were associated with increased risk of transition to TM at high levels of monthly headache days. Conclusion.— EM sufferers develop TM at the rate of 2.5% per year. Any use of barbiturates and opiates was associated with increased risk of TM after adjusting for covariates, while triptans were not. NSAIDs were protective or inducers depending on the headache frequency.     

Characteristics of Menstrual vs Nonmenstrual Migraine: A Post Hoc,Within‐Woman Analysis of the Usual‐Care Phase of a Nonrandomized Menstrual Migraine Clinical Trial

Objective.— To compare, using a within‐woman analysis, the severity, duration, and relapse of menstrual vs nonmenstrual episodes of migraine during treatment with usual migraine therapy. Background.— Studies comparing the clinical characteristics of menstrual and nonmenstrual migraine attacks have yielded conflicting results, contributing to disagreement regarding whether menstrual migraine attacks are clinically more problematic than nonmenstrual migraine attacks. Methods.— Post hoc within‐woman analysis of the usual‐care phase (month 1) of a 2‐month, multicenter, prospective, open‐label study at 21 US medical practices (predominantly primary care). Participants were women ≥18 years of age with regular predictable menstrual cycles (28 ± 4 days) who self‐reported a ≥1‐year history of migraine attacks occurring between days ?2 and +3 (menses onset = day +1) and ≥8 such attacks within the previous 12 cycles. Migraine treatment episodes were categorized as menstrual (occurring on days ?2 to +3 of menses) or nonmenstrual (occurring on days +4 to ?3 of menses). Pain severity, functional impairment, duration, relapse in 24 hours, and use of rescue medication were compared. Sources of variability (within‐ or between‐patient) were determined using mathematical modeling. The http://www.clinicaltrial.gov code for trial is NCT00904098. Results.— Women (n = 153; intent to treat) reported 212 menstrual (59.2%) and 146 nonmenstrual (40.8%) migraine treatment episodes. Compared with nonmenstrual treatment episodes, menstrual episodes were more likely to cause impairment (unadjusted odds ratio, 1.65, 95% CI, 1.05‐2.60; P = .03), were longer (unadjusted hazard ratio 1.68; 95% CI, 1.31‐2.16; P < .001), and were more likely to relapse within 24 hours (unadjusted odds ratio, 2.66; 95% CI, 1.25‐5.68; P = .01). Within‐patient effects accounted for only 18‐33% of the total variance in these outcomes. Conclusions.— Post hoc, within‐woman analysis of migraine treatment episodes categorized based on International Headache Society criteria showed that menstrual treatment episodes were more impairing, longer lasting, and more likely to relapse than nonmenstrual treatment episodes in this selected population of women with frequent menstrual migraine. The current analysis indicates that most of the variability in these outcomes is due to differences between headache types and not within‐patient differences for a given type of headache, suggesting that menstrual episodes are potentially treatable. These findings underscore the differences between menstrual and nonmenstrual episodes of migraine and the need to offer effective migraine treatment to women. (Headache 2010;50:528‐538)     

Sumatriptan is effective in the treatment of menstrual migraine: a review of prospective studies and retrospective analyses

Menstrual migraine may be debilitating, long-lasting, and refractory to treatment. Because the efficacy and tolerability of abortive and prophylactic treatment options for menstrual migraine have generally not been evaluated in controlled clinical trials, treatment choices are often made on the basis of personal experience and anecdotal reports. This article reviews evidence from retrospective analyses and prospective studies showing that sumatriptan injection and tablets are effective and well tolerated in menstrual migraine. (1) Sumatriptan injection 6 mg was as effective in the treatment of menstrual migraine attacks as it was for nonmenstrual attacks in a retrospective analysis of data from two randomized, double-blind, placebo-controlled, parallel-group trials (n = 1104). In the menstrual migraine group, 80% of women treated with sumatriptan injection 6 mg compared with 19% of placebo-treated patients reported headache relief 1 h postdose (p < 0.001). (2) Sumatriptan injection 6 mg was effective in the acute treatment of menstrual migraine attacks in a prospective, double-blind, placebo-controlled, parallel-group, two-attack study (n = 226). Across the two attacks, 70-71% of patients treating menstrual migraine attacks with sumatriptan injection 6 mg compared with 22-24% of placebo-treated patients reported headache relief 1 h postdose (p < 0.001). (3) Sumatriptan tablets 100 mg were effective in the acute treatment of menstrual migraine attacks in a prospective, double-blind, placebo-controlled, crossover study in women diagnosed with menstrual migraine (n = 115). For menstrual migraine attacks, headache relief 4 h postdose was reported by 67% of sumatriptan-treated patients compared with 33% of placebo-treated patients. Sumatriptan injection and tablets were generally well tolerated in these studies, in which adverse events were characteristic of those typically observed in sumatriptan acute migraine clinical trials. These data demonstrate that sumatriptan injection and tablets are effective and well tolerated in the treatment of menstrual migraine.     

Whole blood and plasma histamine in common migraine

Whole blood and plasma histamine levels were measured in 27 non-medicated patients with common migraine. In nine cases blood was drawn 1-2 h after the onset of a migraine attack. The whole blood histamine levels of migraineurs and controls did not differ significantly. In contrast, histamine levels were significantly increased in plasma from patients both during and between migraine attacks, as compared with controls (p less than 0.001). Finally, plasma taken from migraine patients induced a significantly greater release of histamine from control whole blood than did plasma taken from control subjects (p less than 0.01).     

A clinical study of migraine evolution

BACKGROUND: The buildup time of migraine headaches has not been well delineated in publications to date and we are aware of patients whose migraines last well over 72 hours. More concentration on these factors in the assessment of patients might lead to more appropriate therapeutic choices. METHOD: Prospective ascertainment of such data through a questionnaire completed by 253 informed and willing patients with IHS migraine with or without aura consulting Canadian headache specialists. Data were electronically sent to a central computer from each center, tabulated and analyzed using standard statistical parameters. RESULTS: In 253 patients with migraine ascertained using applied IHS criteria, nausea was a feature in over 90% of cases, especially in those with aura. This inhibited the ingestion of oral medications in about a quarter of all subjects. The time to build from no pain to moderate/severe pain was shorter in subjects with auras and was less than 2 hours in 97% of those with and 86% of those without auras. However, we also identified a group of subjects with migraine (over 10% of all) in whom the build time to maximum pain is delayed for over 2 hours. Nausea was experienced by 91.7% of subjects, slightly but significantly later in those without auras. While most headaches in each group lasted from 4 to 72 hours, 24.3% of those with and 20.6% of those without aura expected to experience pain for more than 72 hours, while in untreated cases disability due to pain, nausea, or malaise usually persisted for over 3 days in 24.3% and 16.7% of those with and without aura, respectively. One-fifth of migraineurs may be in pain and/or disabled by accompanying symptoms for over 3 days in a typical migraine attack. Over half of our subjects reported that their medications worked well or excellently. CONCLUSIONS: Attacks of migraine in real-life clinical situations vary somewhat from the IHS criteria in that they are more often associated with nausea that interferes with oral therapy; can persist for over 72 hours; may have slow (>2 hours) buildup to maximum pain in 10% of cases; and may cause disability for over 3 days. Nevertheless, current therapeutic regimens (including prescribed medications) work well for a substantial majority.     

Dihydroergokryptine versus dihydroergotamine in migraine prophylaxis: a double-blind clinical trial

Dihydroergokryptine has been evaluated in the prophylaxis of headache attacks in patients with migraine without aura. The study was controlled vs dihydroergotamine with a double-blind crossover design. After a 1-month run-in period, 30 patients were randomized into two groups and submitted to 4 months treatment with dihydroergokryptine 10 mg b.i.d. or dihydroergotamine (controlled release) 5 mg b.i.d. The treatment was repeated in crossover after 2 months washout. The clinical patients' evaluation was determined by monthly Pain Total Index recording, headache daysmonth and analgesic consumption. The patients were considered responsible when Pain Total Index decreased by 50% or more in 1 or more months of each treatment period; otherwise the patients were considered unresponsive. The response rate to dihydroergokryptine was 66% while 48% of cases were responsive to dihydroergotamine. The response rate to both treatments was 41%, while 26 % did not respond to either treatment. Seven cases unresponsive to dihydroergotamine responded positively to dihydroergokryptine while two cases only, resistant to dihydroergokryptine, responded positively to dihydroergotamine. Three cases dropped out during treatment with dihydroergotamine due to gastric pain and nausea, while they did not show any side effects during dihydroergokryptine therapy. During treatment with dihydroergokryptine there was one case of skin rash which disappeared after drug withdrawal. In conclusion, dihydroergokryptine appears to be an effective drug for the prophylaxis of migraine attacks.     

Frovatriptan as preemptive treatment for fasting-induced migraine

Objective.— To examine frovatriptan's efficacy as preemptive treatment for fasting‐induced migraine. Background.— Fasting is a common migraine trigger that cannot always be avoided. The development of a short‐term preemptive approach would be of benefit. Because of its longer half‐life, frovatriptan has been effectively used for short‐term daily use to prevent menstrually related migraines and might prove useful in the prevention of fasting‐induced migraine. Methods.— This was a double‐blind, placebo‐controlled, randomized, parallel‐group trial. Subjects.— With a history of fasting‐induced episodic migraine were randomly assigned to receive either frovatriptan (5.0 mg) or placebo (ratio 1:1). Subjects.— Took a single dose of study medication at the start of their 20‐hour fast. Information about headache intensity, associated symptoms, and use of rescue medication was captured at defined time points from the start of the fast through 20 hours post‐fast. Results.— Of the 75 subjects screened, 74 subjects were randomized and 71 subjects completed the study. Demographic characteristics of the placebo and frovatriptan treatment groups were not statistically different. Thirty‐three subjects received active drug. Twelve (36.4%) developed a headache between 6 and 20 hours after the start of the fast (1/33 mild, 11/33 moderate or severe). In the placebo group, 18/34 (52.9%) developed a headache (4/34 mild, 14/34 moderate or severe). The difference between the 2 treatment groups did not achieve statistical significance; Pearson chi‐square, P = .172. Kaplan‐Meier survival analysis showed no difference between the 2 treatment groups with respect to the time of onset of headache of any intensity (log rank, P = .264) and for the time of onset of a moderate or severe intensity (log rank, P = .634). Conclusion.— More subjects on placebo developed a headache than those on frovatriptan. Perhaps because of the small number of subjects involved, the differences in headache incidences observed did not achieve statistical significance.