Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Danish Headache Knowledge Center, Rigshospitalet-Glostrup, Valdemar Hansens Vej 5, DK-2600 Glostrup, Denmark.
Brain. 2021 Sep 4;144(8):2322-2332. doi: 10.1093/brain/awab136.
Migraine afflicts more than one billion individuals worldwide and is a leading cause of years lived with disability. In about a third of individuals with migraine aura occur in relation to migraine headache. The common pathophysiological mechanisms underlying migraine headache and migraine aura are yet to be identified. Based on recent data, we hypothesized that levcromakalim, an ATP-sensitive potassium channel opener, would trigger migraine attacks with aura in patients. In a randomized, double-blind, placebo-controlled, crossover study, 17 patients aged 21-59 years and diagnosed with migraine with aura exclusively were randomly allocated to receive an infusion of 0.05 mg/min levcromakalim or placebo (isotonic saline) on two different days (ClinicalTrials.gov, ID: NCT04012047). The primary end points were the difference in incidence of migraine attacks with or without aura, headache and the difference in the area under the curve for headache intensity scores (0-12 h). Seventeen patients completed the study. Fourteen of 17 (82%) patients developed migraine attacks with and without aura after levcromakalim compared with 1 of 17 (6%) after placebo (P < 0.001). Ten patients (59%) developed migraine with aura after levcromakalim compared with none after placebo (P = 0.002). One additional patient reported 'possible' aura, only partially fulfilling the criteria. Levcromakalim is likely a novel migraine aura-inducing substance in humans. These findings highlight the ATP-sensitive potassium channel as a shared target in migraine aura and migraine headache. Likely, ATP-sensitive potassium channel opening leads to triggering of aura and headache, respectively, via distinct mechanisms.
偏头痛影响着全球超过 10 亿人，是导致残疾年数的主要原因之一。在大约三分之一有偏头痛先兆的人中，偏头痛先兆与偏头痛头痛有关。偏头痛头痛和偏头痛先兆的常见病理生理机制尚未确定。基于最近的数据，我们假设 ATP 敏感性钾通道开放剂 levcromakalim 会在有先兆偏头痛的患者中引发偏头痛发作。在一项随机、双盲、安慰剂对照、交叉研究中，17 名年龄在 21-59 岁之间、仅被诊断为有先兆偏头痛的患者被随机分配到在两天内接受 0.05mg/min levcromakalim 或安慰剂（等渗盐水）输注（ClinicalTrials.gov，ID：NCT04012047）。主要终点是有或无先兆偏头痛发作的发生率差异、头痛和头痛强度评分曲线下面积差异（0-12 小时）。17 名患者完成了研究。与安慰剂相比，17 名患者中有 14 名（82%）在接受 levcromakalim 后出现有或无先兆偏头痛发作，而 17 名患者中有 1 名（6%）（P<0.001）。与安慰剂相比，10 名患者（59%）在接受 levcromakalim 后出现偏头痛先兆，而无一例在接受安慰剂后出现（P=0.002）。另有一名患者报告“可能”出现先兆，仅部分符合标准。Levcromakalim 很可能是一种新的人类偏头痛先兆诱导物质。这些发现强调了 ATP 敏感性钾通道是偏头痛先兆和偏头痛头痛的共同靶点。可能是 ATP 敏感性钾通道的开放分别通过不同的机制导致先兆和头痛的触发。
