Association of single nucleotide polymorphisms of CACNA1A gene in migraine.

INTRODUCTION: Migraine is a chronic, neurovascular polygenic disease where genetic and environmental factors are involved in its etiology. Dysfunction of neuronal ion transportation can provide a model for predisposition for common forms of migraine. Mutations in genes encoding ion channels disturb the rhythmic function of exposed tissue that may also explain the episodic nature of migraine. Our aim was to study the single nucleotide polymorphisms of CACNA1A gene in migraine patients. MATERIALS AND METHODS: The subjects were the patients of migraine, in the age range of 18‑80 years, diagnosed by a Neurologist, as per the diagnostic criteria of International Headache Society (IHS) Classification 2004 after excluding other causes of headache by clinical examination and relevant investigations. The controls were the age and sex matched healthy persons from the same population excluding the relatives of patients. Only those patients and the controls, who voluntarily participated in the study, were taken and their blood samples were taken for the study. Deoxyribonucleic acid (DNA) extraction was performed according to the manufacturer’s protocol for Qiagen DNA extraction kits (Qiagen, Hilden, NRW, Germany). DNA content was quantified by spectrophotometric absorption (Nanodrop Spectrophotometer, BioLab, Scoresby, VIC, Australia). Polymerase chain reaction was performed using an iCycler Thermal Cycler (Bio‑Rad, Hercules, CA, USA). The polymorphic analysis of CACNA1A gene was carried out by two methods: Restriction fragment length polymorphism and sequencing. RESULTS: The study included a total of 25 patients of migraine, diagnosed on out‑patient department basis as per IHS Classification 2004 and compared with age and sex matched 25 healthy controls. Most of the patients 23 (92%) were below the age of 50 years. 20 of the patients (80%) were females and 5 (20%) were males. The polymorphic analysis of CACNA1A gene revealed the presence of only the wild form of the gene for the codon E993V in both case and control groups. CONCLUSION: In our study, we could not find any polymorphism of CACNA1A gene in the selected patients. Instead the wild type of genotype was found in both patients and controls. This negative result presented here, implies that if the CACNA1A gene is involved in typical migraine (with and without aura), its contribution is very modest and therefore difficult to discern. Nevertheless, there are other genes that could be considered potential candidates for typical migraine susceptibility for which further research is needed.

Migrânea com afasia: relato de uma família / Migraine with aphasia: report of a family

Descrevemos um família brasileira na qual a mae e três filhas apresentam episódios compatíveis com migrânea, acompanhados por alteraçao do conteúdo da linguagem (afasia), sem paresias. Alguns aspectos relativos à genética das migrâneas sao revisados.Chamamos a atençao para a necessidade de investigaçao genética para saber se é uma variante das formas conhecidas de migrânea, como a migrânea hemiplégica familiar.

Fisiopatologia da enxaqueca (ou migrânea) / The pathophysiology of migraine

A fisiopatologia da enxaqueca tem sofrido uma evoluçäo considerável, principalmente nos últimos quinze anos. O conhecimento dos mecanismos genéticos, incluindo a participaçäo do gene CACNL1A4 no cromossoma 19p13.1, que codifica a subunidade alfa-1 de um canal de cálcio, tipo P/Q, específico do cérebro, dos mediadores e neurotransmissores envolvidos com a inflamaçäo neurogênica, tais como o Peptídeo Relacionado ao Gene da Calcitonina (CGRP), a NK-1 e a SP; a influência do NO como molécula algógena fundamental na enxaqueca; o desenvolvimento de modelos experimentais, incluindo o modelo do extravasamento de plasma, conforme desenvolvido pelo grupo do Moskowitz; e novas técnicas de neuroimagem (PET, MR e MEG) säo alguns exemplos dos avanços alcançados. Isto tem propiciado o desenvolvimento de novos medicamentos antienxaquecosos. A depressäo alastrante de Leäo tem sido confirmada como o fenômeno neurofisiológico mais importante na enxaqueca: ativa o sistema trigeminovascular, induz vasodilataçäo mediada por CGRP e a expressäo de c-fos no núcleo do trigêmio, no tronco cerebral. A dor na migrânea näo é secundária à vasodilataçäo, o que näo mais justifica a divisäo das cefaléias em "vasculares" e "näo vasculares".

Enxaqueca vestibular na infância: diagnóstico e tratamento / Vestibular nigraine in children: diagnostic and treatment

Os autores estudam a enxaqueca vestibular em crianças, analisam os dados clínicos e os achados dos exames otoneurológicos. Por fim, avaliam os resultados obtidos com o uso de aspirina, em dosagens baixas, no tratamento da mesma