Migraine genetics: An update

A growing interest in genetic research in migraine has resulted in the identification of several chromosomal regions that are involved in migraine. However, the identification of mutations in the genes for familial hemiplegic migraine (FHM) forms the only true molecular genetic knowledge of migraine thus far. The increased number of mutations in the FHM1 (CACNA1A) and the FHM2 (ATP1A2) genes allow studying the relationship between genetic findings in both genes and the clinical features in patients. A wide spectrum of symptoms is seen in patients. Additional cerebellar ataxia and (childhood) epilepsy can occur in FHM1 and FHM2. Functional studies show a dysfunction in ion transport as the key factor in the pathophysiology of (familial hemiplegic) migraine that predict an increased susceptibility to cortical spreading depression—the underlying mechanism of migraine aura.     

Migraine treatment in developmental age: guidelines update

There is a serious lack of controlled studies on the pharmacological treatment of primary migraine in the developmental age; there is, consequently, an urgent need for new, evidence-based approaches to this long-neglected field of research. Moreover, previous studies have stated that the placebo response is greater in pediatric patients than in adults and that a reduction in the attack frequency in the absence of any pharmacological treatment is observed more frequently in pediatric migraine patients than in adults. Besides these preliminary considerations, the shorter duration of migraine attacks and other characteristic semeiological features of the clinical picture in children are such that the design of randomized controlled trial (RCT) is more problematic in the developmental age than in the adult. Bearing in mind all these weak points, the aim of this review was to summarize and update recent guidelines for the treatment of primary migraine in children and adolescents. The most recent guidelines are those published by the Italian Society for the study of Headache, the French Society for the study of Migraine and Headache, and the American Academy of Neurology. We have incorporated into these guidelines the results from the few, recent RCTs, clinical controlled trials, open-label studies, meta-analyses and reviews that have been published since 2004; owing to the lack of strong evidence in this field of research, we have sometimes even mentioned pilot non-controlled studies, case series and expert opinions. Lastly, evidence was classified and the recommendations were categorized according to different levels.     

Refractory Migraine and Chronic Migraine: Pathophysiological Mechanisms

Despite increased understanding of primary headaches and their treatment, the underlying causes of refractory migraine remain unknown. This note considers potential genetic, structural, functional and pharmacological factors that could contribute to this relatively intractable condition. Further understanding of refractory migraine will require the use of medical imaging technologies, clinical experimental medicine studies on novel pharmacological agents and astute observations in clinical practice to direct potential novel therapeutic approaches.     

Migraine headaches

Once the definitive diagnosis of migraine has been formulated, the physician has many options available for abortive and prophylactic therapy. Nonpharmacologic modalities, including behavioral modification methods such as biofeedback training, may also be considered. Migraine does not necessarily have to disrupt the lives of those afflicted. The patient with mixed headache presents a more difficult diagnostic and therapeutic problem. These patients can also be helped when the disorder is identified, and inpatient therapy for these patients may be required.     

Migraine genetics

The genetics of migraine is a fascinating and moving research area. Familial hemiplegic migraine, a rare subtype of migraine with a Mendelian pattern of inheritance, is caused by mutations in the chromosome 19 CACNA1A gene in approximately 75% of the families. The finding of mutations in an ionchannel subunit defines migraine as a channelopathy (eg, epilepsy). The genetics of the more frequent variants, migraine with and without aura, is more complex. Several loci have been studied in families and case-control studies, but need to be confirmed.