Concepts and mechanisms of migraine chronification

Migraine is a chronic recurrent disorder with episodic manifestations that is progressive in some individuals. Migraine progresses clinically, physiologically, and anatomically. Progression may be a consequence of the mechanisms that generate the migraine attacks (eg, cortical spreading depression) or it may be a function of the activations generated by the attacks (eg, lesions in the periaqueductal gray area), a hypothesis supported by the increase in lesions with attack frequency. Progression may also be partially explained by common genetic or environmental risk factors. Finally, migraine with aura is associated with an elevated Framingham score and with risk factors for cardiovascular disease. Research on this issue is in its infancy and cautions are necessary before extrapolating this information into clinical practice.     

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.     

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.     

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.     

Migraine and Stroke: A Continuum of Association in Adults

Migraine and stroke are the most common neurovascular disorders affecting adults. Migraine, particularly with aura, is associated with increased stroke risk both during and between attacks; as such, migraine may be viewed as a potentially modifiable risk factor for stroke. The exact mechanism by which migraine can predispose to stroke remains uncertain.     

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.     

Effect of low-intensity acenocoumarol on frequency and severity of migraine attacks

OBJECTIVE: To investigate the effect of low-intensity acenocoumarol treatment (target INR 1.5 to 2.0) on the frequency and severity of migraine attacks. BACKGROUND: The positive effect of anticoagulation on migraine has been described in case reports and observational studies. METHODS: We conducted a randomized, open, crossover study in migraine patients. After a run-in period of 8 weeks, all patients received acenocoumarol or propranolol during a period of 12 weeks and, after a washout period of 2 weeks, propranolol or acenocoumarol during a second period of 12 weeks. RESULTS: Nineteen patients fulfilling the criteria were included. In 12 patients with complete data collection, only one good responder could be noted. In the other patients, treatment with low-intensity acenocoumarol did not show improvement of migraine symptoms compared with the run-in period. Treatment with propranolol showed a trend towards improvement compared with the run-in period. No serious adverse events were observed. CONCLUSIONS: Overall, low-intensity acenocoumarol treatment has no prophylactic effect in migraine patients.     

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).     

Screening and behavioral management: obesity and weight management

Individuals with migraine headaches who are obese or overweight may be at elevated risk for experiencing more frequent migraines and for developing chronic migraine. This makes it imperative that clinicians consider including weight management as part of a migraine treatment plan in situations where the patient is overweight or obese. Weight loss and weight maintenance therapy should employ a combination of behavioral strategies, in particular nutritional education, dietary intervention, and exercise counseling, as a first line intervention. Weight loss medications are considered a secondary treatment; however, when weight loss medications are used, it is vital to monitor the influence of the medication on headache. Similarly, a clinician considering migraine prophylaxis needs to consider whether the pharmacologic agent being considered influences weight gain or loss.     

Tolerance to the beneficial effects of prophylactic migraine drugs: a systematic review of causes and mechanisms

Loss of benefit of a previously effective treatment regimen, also known as tolerance, can be an important barrier to the successful preventive treatment of migraine. We undertook a systematic review of the literature to identify the prevalence and possible mechanisms of drug tolerance in migraine prophylaxis. Results demonstrate that the frequency of tolerance to prophylactic migraine treatment is unknown, but available data support an estimate that it occurs in 1-8% of patients receiving prophylaxis. Four broad types of tolerance were identified that are likely to be relevant to migraine prophylaxis. These are pharmacokinetic, pharmacodynamic, behavioral, and cross tolerance. The mechanisms that underlie these types of tolerance determine whether their effects can be overcome or minimized. For example, certain forms of tolerance may be affected by manipulation of environmental cues associated with drug administration, by the order in which drugs are used, and by the concomitant use of other medications. Many medications used for migraine prophylaxis exert their effects through the endogenous opioid system. The implications of this finding are explored, particularly the parallels between medication overuse headache and tolerance to migraine prophylaxis. Given the many ways in which tolerance to migraine medications may develop, in some ways it is not surprising that migraine-preventive drugs stop working; it is more surprising that in many cases they do not.     

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.     

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.     

The Stress and Migraine Interaction

There are several ways in which stress may interact with migraine in those predisposed to migraine attacks. These interactions may result from biochemical changes related to the physiological stress response, as, for example, the release of corticotrophin releasing hormone, or from changes induced by the psychological response to stressors. Stress is the factor listed most often by migraine sufferers as a trigger for their attacks, but in addition there is evidence that stress can help initiate migraine in those predisposed to the disorder, and may also contribute to migraine chronification. Migraine attacks themselves can act as a stressor, thereby potentially leading to a vicious circle of increasing migraine frequency. Since the important factor in the stress–migraine interaction is likely the individual's responses to stressors, rather than the stressors themselves, the acquisition of effective stress management skills has the potential to reduce the impact of stressors on those with migraine.     

Human Studies in the Pathophysiology of Migraine: Genetics and Functional Neuroimaging

The expansion of technologies available for the study of migraine pathophysiology has evolved greatly over the last 15 years. Two areas of rapid progress are investigations focusing on the genetics of migraine and others utilizing novel functional neuroimaging techniques. Genetic studies are increasingly focusing on sporadic migraine and the utilization of unbiased searches of the human genome to identify novel variants associated with disease susceptibility. At the same time, neuroimaging studies have provided novel insights into the altered neuronal and network dynamics of the migrainous brain. These 2 parallel approaches provide complementary insights into the complexity and heterogeneity of migraine.