Watanabe-Hosomi Akiko, Mizuta Ikuko, Koizumi Takashi, Yokota Isao, Mukai Mao, Hamano Ai, Kondo Masaki, Fujii Akihiro, Matsui Masaru, Matsuo Koushun, Ito Keita, Teramukai Satoshi, Yamada Kei, Nakagawa Masanori, Mizuno Toshiki
Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Neurology, Fukuchiyama City Hospital, Kyoto, Japan.
Clin Neuropharmacol. 2020 Sep/Oct;43(5):146-150. doi: 10.1097/WNF.0000000000000402.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an orphan disease clinically characterized by migraine, recurrent strokes, and dementia. Currently, there are no disease-modifying therapies, and it is difficult to prevent cerebral ischemic events in CADASIL patients by conventional antithrombotic medication. We hypothesized that an antimigraine agent, lomerizine hydrochloride, may prevent strokes in CADASIL patients, based on its effect on increasing cerebral blood flow.
This was an open-labeled clinical trial in which 30 adult CADASIL patients received lomerizine at 10 mg/d. Numbers of symptomatic strokes during the 2 years after the start of lomerizine administration were compared with those in the 2 years before its initiation. The effect of lomerizine on preventing strokes was evaluated based on the incidence rate ratio (IR) calculated with the Mantel-Haenszel method.
When including all 30 patients (analysis 1), the IR was less than 1 (0.46; 95% confidence interval [CI], 0.19-1.12) but did not reach significance. To evaluate the effect of lomerizine on secondary prevention, subgroups of 15 patients with stroke episodes occurring any time before lomerizine administration (analysis 2) and 10 patients with stroke episodes during the 2 years before lomerizine administration (analysis 3) were analyzed. The IR values were 0.33 (95% CI, 0.12-0.94) in analysis 2 and 0.17 (95% CI, 0.04-0.67) in analysis 3.
Our results suggest the effect of lomerizine on preventing secondary stroke in CADASIL patients.
伴有皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病（CADASIL）是一种罕见病，临床特征为偏头痛、复发性中风和痴呆。目前，尚无改善病情的疗法，且常规抗血栓药物难以预防CADASIL患者的脑缺血事件。基于其增加脑血流量的作用，我们推测抗偏头痛药物盐酸洛美利嗪可能预防CADASIL患者的中风。
这是一项开放标签的临床试验，30例成年CADASIL患者接受10mg/d的洛美利嗪治疗。将洛美利嗪给药开始后2年期间有症状中风的次数与给药前2年的次数进行比较。基于用Mantel-Haenszel方法计算的发病率比（IR）评估洛美利嗪预防中风的效果。
纳入所有30例患者时（分析1），IR小于1（0.46；95%置信区间[CI]，0.19 - 1.12），但未达到显著性。为评估洛美利嗪对二级预防的效果，对在洛美利嗪给药前任何时间发生中风事件的15例患者亚组（分析2）和在洛美利嗪给药前2年期间发生中风事件的10例患者亚组（分析3）进行了分析。分析2中的IR值为0.33（95%CI，0.12 - 0.94），分析3中的IR值为0.17（95%CI，0.04 - 0.67）。
我们的结果提示洛美利嗪对预防CADASIL患者的继发性中风有效果。
