DeCure for Migraine, familial hemiplegic, 1

Molecular factors in migraine

Abstract// Marta Kowalska 1 , Michał Prendecki 1 , Wojciech Kozubski 2 , Margarita Lianeri 1 and Jolanta Dorszewska 1 1 Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland 2 Chair and Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland Correspondence to: Jolanta Dorszewska, email: // Keywords : gene polymorphisms, biochemical factors, migraine Received : October 07, 2015 Accepted : May 05, 2016 Published : May 14, 2016 Abstract Migraine is a common neurological disorder that affects 11% of adults worldwide. This disease most likely has a neurovascular origin. Migraine with aura (MA) and more common form - migraine without aura (MO) – are the two main clinical subtypes of disease. The exact pathomechanism of migraine is still unknown, but it is thought that both genetic and environmental factors are involved in this pathological process. The first genetic studies of migraine were focused on the rare subtype of MA: familial hemiplegic migraine (FHM). The genes analysed in familial and sporadic migraine are: MTHFR , KCNK18 , HCRTR1, SLC6A4, STX1A , GRIA1 and GRIA3 . It is possible that migraine is a multifactorial disease with polygenic influence. Recent studies have shown that the pathomechanisms of migraine involves both factors responsible for immune response and oxidative stress such as: cytokines, tyrosine metabolism, homocysteine; and factors associated with pain transmission and emotions e.g.: serotonin, hypocretin-1, calcitonin gene-related peptide, glutamate. The correlations between genetic variants of the HCRTR1 gene, the polymorphism 5-HTTLPR and hypocretin-1, and serotonin were observed. It is known that serotonin inhibits the activity of hypocretin neurons and may affect the appearance of the aura during migraine attack. The understanding of the molecular mechanisms of migraine, including genotype-phenotype correlations, may contribute to finding markers important for the diagnosis and treatment of this disease.

Safety and efficacy of flunarizine in childhood migraine: 11 years’ experience, with emphasis on its effect in hemiplegic migraine

AbstractAIM: The aim of this study was to report a single-centre experience of flunarizine in childhood migraine with focus on safety and efficacy. METHOD: We conducted a retrospective observational audit of 72 individuals (40 male, 32 female; mean age 13y; age range 1y 6mo-17y) at a tertiary paediatric neurology unit between 1998 and 2009. Children were included if they had a diagnosis of migraine and at least one follow-up assessment and a minimum of 3 months' treatment with flunarizine. RESULTS: Of 102 individuals identified, 30 were excluded for the following reasons: no outcome data (n=13), non-migraineurs (n=9), missing records (n=4), or inadequate treatment duration (n=4). Of the final cohort (72 individuals), 44 had migraine without aura, 15 had migraine with aura or childhood migraine equivalents, eight had sporadic hemiplegic migraine, and five had familial hemiplegic migraine. The median age was 13 years (1y 6mo-17y) and median duration of migraine was 48 months. Starting dose was 5mg. Other doses used were 2.5mg (three individuals), 7.5mg (one individual), and 10mg (six individuals). Treatment duration was 12 months. Successful prophylaxis, defined as at least a 50% reduction in attack frequency, was observed in 57% (41/72). Response rate was higher among those with hemiplegic migraines (85%) than in those who did not have hemiplegic migraines (51%). Side effects were noted in 15 (21%) individuals (depression, n=6; weight gain/increased appetite, n=5; tiredness/sedation, n=2; and worsening headache, n=2), and led to discontinuation of treatment in 13. INTERPRETATION: In our cohort of children with migraine, flunarizine appears to be more effective in the hemiplegic migraine group. Adverse effects were seen in one-fifth of the individuals, leading to discontinuation in 18%.

Sporadic Hemiplegic Migraine With Permanent Neurological Deficits

AbstractBy definition, the neurologic impairments of hemiplegic migraine are reversible. However, a few cases of permanent neurologic deficits associated with hemiplegic migraine have been reported. Herein, we present the case of a patient with permanent impairments because of hemiplegic migraine despite normalization of associated brain magnetic resonance imaging abnormalities. Cases like these suggest the need to consider aggressive prophylactic therapy for patients with recurrent hemiplegic migraine attacks.

Sporadic Hemiplegic Migraine: A Separate Entity

AbstractThe clinical characteristics of 105 patients with sporadic hemiplegic migraine (SHM) were compared with those of patients with migraine with typical aura (MA) and patients with familial hemiplegic migraine (FHM) in a study at the Danish Headache Center, Glostrup Hospital, Gentofte Hospital, University of Copenhagen, and the John F Kennedy Institute, Denmark.

Prolonged hemiplegic migraine

AbstractHemiplegic migraine is a rare form of migraine variant. It is characterized by recurrent attacks of headache associated with temporary neurological deficit, usually unilateral hemiparesis or hemiplegia. It can be difficult to distinguish from migrainous stroke clinically, and a full neurological work-up and careful review of medical history and symptoms are necessary for the diagnosis. Two forms of hemiplegic migraine are known: familial and sporadic, phenotypically similar, differentiated by the absence of family history of similar attacks in the sporadic form. We report a case of sporadic hemiplegic migraine with unusually prolonged deficit and progression to quadriplegia with complete return to baseline 7 days after onset. Diffusion weighted images helped in excluding infarction.

AbstractMigraine is a multifactorial disease, manifested by intense bouts of recurrent headaches. Molecular mechanisms of migraine attack are not clear. In this study, we carried out the analysis of molecular processes in the pathogenesis of a rare hereditary form of migrainefamilial hemiplegic migraine type I. Constructed hypothetical signaling pathways allowed us to understand the causes of a migraine attack and identify key molecules and signaling pathways for further experimental and clinical studies.

MECCANISMI PATOGENETICI NELLA EMICRANIA EMIPLEGICA FAMILIARE E SPORADICA:DESCRIZIONE DI TRE NUOVE MUTAZIONI DEL GENE ATP1A2

AbstractFamilial hemiplegic migraine (FHM) is a rare, autosomal-dominant, form of migraine with aura. Sporadic hemiplegic migraine (SHM) is a heterogeneous disorder, where some patients may have a pathophysiology identical to FHM, with a mutation in one of the FHM genes (CACNA1A, ATP1A2, SCN1A), but others, possibly the majority, may have a different pathophysiologic background. In our study we have described 24 patients (13 FHM and 11 SHM) and their genetic screenings, positive for mutations only in 3 cases, 2 of them in apparently sporadic cases. All the mutations, 2 missense and 1 nonsense, are in ATP1A2 gene. Our results confirm a more frequent involvement of the ATP1A2 gene in the sporadic cases and, in our opinion, an identical pathogenesis of the Familial and the Sporadic forms. Moreover, the absence of mutations in the HM genes in the other 12 familial cases is probably the result of the involvement of many other genes and it underlines the crucial role of a biobank like this one.