Neurovascular changes in prolonged migraine aura in FHM with a novel ATP1A2 gene mutation
Neurovascular changes in prolonged migraine aura in FHM with a novel ATP1A2 gene mutation
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DOI：
10.1136/jnnp-2011-300843
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发表时间：
2012-02-01
影响因子：
11
通讯作者：
Sakai, Fumihiko
中科院分区：
文献类型：
--
作者：
Iizuka, Takahiro;Takahashi, Yuji;Sakai, Fumihiko
目的 报告具有新基因突变的家族性偏瘫性偏头痛 (FHM) 患者在持续先兆偏瘫性偏头痛 (HMPA) 发作超过 24 小时期间的脑血流变化。 方法 作者在 10 年的观察期内，对日本 FHM 家族的两名受影响个体的 8 次 HMPA 发作急性期和先兆症状恢复后进行了一系列神经影像学研究。作者还对该家族的三个个体的 CACNA1A、ATP1A2 和 SCN1A 基因的所有外显子进行了突变分析。 结果 每个患者都有一个“主要受影响的半球”，即在 HMPA 发作期间容易出现偏瘫。偏头痛先兆持续 4 至 12 天。第 1 至 4 天进行的神经影像学研究显示，5 次发作中偏瘫对侧受影响的半球灌注过度，3 次发作灌注不足，5 次发作大脑中动脉血管舒张，1 次发作血管源性渗漏增加并伴有皮质水肿。在“主要受影响的半球”中，过度灌注比灌注不足更频繁地发生，而在“非主要受影响的半球”中仅发生灌注不足。所有变化都是完全可逆的。作者在所有三个个体的 ATP1A2 基因中发现了一种新的杂合 p.H916L 突变。 结论 虽然灌注状态可能会因偏头痛的时间进程或与皮质扩散性抑郁相关的扫描时间而有所不同，但该家族中长期先兆症状通常与过度灌注和大脑中动脉血管舒张有关。过度灌注往往发生在“主要受影响的半球”，但 HMPA 的机制有待对其他 FHM2 病例进行进一步研究。
Objectives To report cerebral blood flow changes during attacks of hemiplegic migraine with prolonged aura (HMPA) longer than 24 h in patients with familial hemiplegic migraine (FHM) with a novel gene mutation.Methods The authors performed serial neuroimaging studies during acute stage and after recovery of aura symptoms in eight HMPA attacks in two affected individuals of the Japanese family of FHM during a 10-year-observational period. The authors also performed a mutational analysis for all exons of the CACNA1A, ATP1A2 and SCN1A genes in three individuals of this family.Results Each patient had an individual 'predominantly affected hemisphere,' that is, susceptible to hemiplegia during an HMPA attack. Migraine aura lasted 4 to 12 days. Neuroimaging studies performed on days 1 to 4 showed hyperperfusion in the affected hemisphere contralateral to hemiplegia in five attacks, hypoperfusion in three, middle cerebral artery vasodilation in five and augmented vasogenic leakage with cortical oedema in one. Hyperperfusion developed more frequently than hypoperfusion in the 'predominantly affected hemisphere,' whereas only hypoperfusion developed in the 'non-predominantly affected hemisphere.' All changes were fully reversible. The authors identified a novel heterozygous p.H916L mutation in the ATP1A2 gene in all three individuals.Conclusions Although the perfusion state could be different depending on the time course of migraine or the timing of scans in relation to cortical spreading depression, prolonged aura symptoms in this family were frequently associated with hyperperfusion and middle cerebral artery vasodilation. Hyperperfusion tended to occur in the 'predominantly affected hemisphere,' but the mechanism of HMPA awaits further investigations on additional cases of FHM2.