Hansen J M, Thomsen L L, Marconi R, Casari G, Olesen J, Ashina M
Danish Headache Centre and Department of Neurology, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Cephalalgia. 2008 Apr;28(4):367-75. doi: 10.1111/j.1468-2982.2008.01542.x. Epub 2008 Feb 22.
Familial hemiplegic migraine type 2 (FHM-2) and common types of migraine show phenotypic similarities which may indicate a common neurobiological background. The nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway plays a crucial role in migraine pathophysiology. Therefore, we tested the hypothesis that ATP1A2 mutations in patients with FHM-2 are associated with hypersensitivity to NO-cGMP pathway. Eight FHM-2 patients with R202Q, R763C, V138A and L764P mutations and nine healthy controls received intravenous infusions of 0.5 mug kg(-1) min(-1) glyceryl trinitrate (GTN) over 20 min. We recorded the following variables: headache intensity on a verbal rating scale; mean flow velocity in the middle cerebral artery (V(meanMCA)) by transcranial Doppler; diameter of the superficial temporal artery (STA) by ultrasound. The primary end-points were differences in incidence of migraine headache and area under the curve (AUC) for headache score during an immediate phase (0-120 min) and a delayed phase (2-14 h) after start of infusion. We found no difference in the incidence of reported migraine between FHM-2 patients, 25% (two out of eight), and controls, 0% (0 out of nine) (95% confidence interval -0.06, 0.56) (P = 0.21). The AUC(headache) in the immediate (P = 0.37) and delayed (P = 0.09) phase was not different between patients and controls. The GTN infusion resulted in a biphasic response in patients. During the immediate phase, the median peak headache occurred at 30 min and tended to be higher in patients, 1 (0, 3.8), than in controls, 0 (0, 1) (P = 0.056). During the delayed phase, the median peak headache occurred 4 h after the start of the infusion and was significantly higher in patients, 2.5 (0, 3), than in controls, 0 (0, 0) (P = 0.046). We found no difference in the AUC(VmeanMCA) (P = 0.77) or AUC(STA) (P = 0.53) between FHM-2 patients and controls. GTN infusion failed to induce more migraine in FHM-2 patients than in controls. The pathophysiological pathways underlying migraine headache in FHM-2 may be different from the common types of migraine.
2型家族性偏瘫性偏头痛（FHM-2）与常见类型的偏头痛表现出表型相似性，这可能表明存在共同的神经生物学背景。一氧化氮-环磷酸鸟苷（NO-cGMP）途径在偏头痛的病理生理学中起关键作用。因此，我们检验了以下假设：FHM-2患者中的ATP1A2突变与对NO-cGMP途径的超敏反应有关。8例携带R202Q、R763C、V138A和L764P突变的FHM-2患者和9名健康对照者接受了20分钟的静脉输注，输注速率为0.5μg kg⁻¹ min⁻¹的硝酸甘油（GTN）。我们记录了以下变量：采用言语评定量表评估的头痛强度；经颅多普勒测量大脑中动脉的平均血流速度（V(meanMCA)）；超声测量颞浅动脉（STA）的直径。主要终点是输注开始后即刻期（0 - 120分钟）和延迟期（2 - 14小时）偏头痛头痛的发生率差异以及头痛评分的曲线下面积（AUC）。我们发现FHM-2患者中报告偏头痛的发生率为25%（8例中的2例），与对照组的0%（9例中的0例）相比无差异（95%置信区间 -0.06, 0.56）（P = 0.21）。患者和对照组在即刻期（P = 0.37）和延迟期（P = 0.09）的AUC(头痛)无差异。GTN输注在患者中引起双相反应。在即刻期，头痛峰值中位数出现在30分钟，患者的头痛峰值倾向于高于对照组，患者为1（0, 3.8），对照组为0（0, 1）（P = 0.056）。在延迟期，头痛峰值中位数出现在输注开始后4小时，患者的头痛峰值显著高于对照组，患者为2.5（0, 3），对照组为0（0, 0）（P = 0.046）。我们发现FHM-2患者与对照组在AUC(VmeanMCA)（P = 0.77）或AUC(STA)（P = 0.53）方面无差异。GTN输注在FHM-2患者中诱发的偏头痛并不比对照组更多。FHM-2中偏头痛头痛的病理生理途径可能与常见类型的偏头痛不同。
