Chabriat H, Vahedi K, Iba-Zizen M T, Joutel A, Nibbio A, Nagy T G, Krebs M O, Julien J, Dubois B, Ducrocq X
Service de Neurologie, Hôpital Saint-Antoine, Paris.
Lancet. 1995 Oct 7;346(8980):934-9. doi: 10.1016/s0140-6736(95)91557-5.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited arterial disease of the brain recently mapped to chromosome 19. We studied 148 subjects belonging to seven families by magnetic resonance imaging and genetic linkage analysis. 45 family members (23 males and 22 females) were clinically affected. Frequent signs were recurrent subcortical ischaemic events (84%), progressive or stepwise subcortical dementia with pseudobulbar palsy (31%), migraine with aura (22%), and mood disorders with severe depressive episodes (20%). All symptomatic subjects had prominent signal abnormalities on MRI with hyperintense lesions on T2-weighted images in the subcortical white-matter and basal ganglia which were also present in 19 asymptomatic subjects. The age at onset of symptoms was mean 45 (SD [10-6]) years, with attacks of migraine with aura occurring earlier in life (38.1 [8.03] years) than ischaemic events (49.3 [10.7] years). The mean age at death was 64.5 (10.6) years. On the basis of MRI data, the penetrance of the disease appears complete between 30 and 40 years of age. Genetic analysis showed strong linkage to the CADASIL locus for all seven families, suggesting genetic homogeneity. CADASIL is a hereditary cause of stroke, migraine with aura, mood disorders and dementia. The diagnosis should be considered not only in patients with recurrent small subcortical infarcts leading to dementia, but also in patients with transient ischaemic attacks, migraine with aura or severe mood disturbances, whenever MRI reveals prominent signal abnormalities in the subcortical white-matter and basal ganglia. Clinical and MRI investigations of family members are then crucial for the diagnosis which can be confirmed by genetic linkage analysis. The disease is probably largely undiagnosed.
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）是一种新近定位到19号染色体的遗传性脑动脉疾病。我们通过磁共振成像和基因连锁分析对7个家族的148名受试者进行了研究。45名家族成员（23名男性和22名女性）有临床症状。常见症状为反复发生的皮质下缺血事件（84%）、伴有假性延髓麻痹的进行性或阶梯式皮质下痴呆（31%）、有先兆偏头痛（22%）以及伴有严重抑郁发作的情绪障碍（20%）。所有有症状的受试者在MRI上均有明显的信号异常，T2加权像上皮质下白质和基底节有高信号病变，19名无症状受试者也有这些病变。症状出现的平均年龄为45（标准差[10 - 6]）岁，有先兆偏头痛发作的年龄（38.1[8.03]岁）早于缺血事件（49.3[10.7]岁）。平均死亡年龄为64.5（10.6）岁。根据MRI数据，该疾病在30至40岁之间的外显率似乎是完全的。基因分析显示所有7个家族均与CADASIL基因座有很强的连锁关系，提示基因同质性。CADASIL是中风、有先兆偏头痛、情绪障碍和痴呆的遗传性病因。不仅在患有导致痴呆的反复小皮质下梗死的患者中应考虑该诊断，而且在患有短暂性脑缺血发作、有先兆偏头痛或严重情绪障碍的患者中，只要MRI显示皮质下白质和基底节有明显的信号异常，也应考虑该诊断。然后，对家族成员进行临床和MRI检查对于诊断至关重要，基因连锁分析可证实该诊断。该疾病可能在很大程度上未被诊断出来。
