The phenotypic spectrum of CADASIL:: Clinical findings in 102 cases
The phenotypic spectrum of CADASIL:: Clinical findings in 102 cases
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DOI：
10.1002/ana.410440506
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发表时间：
1998-11-01
影响因子：
11.2
通讯作者：
Gasser, T
中科院分区：
文献类型：
--
作者：
Dichgans, M;Mayer, M;Gasser, T
脑常染色体显性动脉病变伴皮层下梗死和白质脑病（CADASIL）是一种越来越被认可的常染色体显性疾病，可在成年早期导致脑血管症状。本研究描述了来自29个活检证实的CADASIL家族的102名受影响个体的表型谱和疾病的自然史。复发性脑缺血发作（短暂性脑缺血发作[TIA]或中风）是71%的病例中最常见的表现（平均发病年龄46.1岁，范围30-66岁，SD 9.0岁）。48%的病例出现了认知缺陷。痴呆（28%）常伴有步态障碍（90%）、尿失禁（86%）和假性球麻痹（52%）。39例（38%）患者有偏头痛病史（平均发病年龄26.0岁，标准差8.2岁），其中87%的患者为先兆偏头痛。30%的病例存在精神障碍，其中适应障碍（24%）是最常见的诊断。10例患者（10%）有癫痫发作史。为了描述缺血性缺陷的功能后果，我们研究了不同年龄组的残疾程度。所有45岁以上的人群都出现了全方位的残疾。在60岁以上的患者中，55%的人在没有帮助的情况下无法行走。然而，这个年龄组中有14%的人完全没有残疾。Kaplan-Meier分析显示中位生存时间为男性64岁，女性69岁。对18个多重家族的调查揭示了显著的家族内变异。
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an increasingly recognized autosomal dominant disorder that leads to cerebrovascular manifestations in early adulthood. This study delineates the phenotypic spectrum and the natural history of the disease in 102 affected individuals from 29 families with biopsy-proven CADASIL. Recurrent ischemic episodes (transient ischemic attack [TIA] or stroke) were the most frequent presentation found in 71% of the cases (mean age at onset, 46.1 years; range, 30-66 years; SD, 9.0 years). Forty-eight percent of the cases had developed cognitive deficits. Dementia (28%) was frequently accompanied by gait disturbance (90%), urinary incontinence (86%), and pseudobulbar palsy (52%). Thirty-nine patients (38%) had a history of migraine (mean age at onset, 26.0 years; SD, 8.2 years), which was classified as migraine with aura in 87% of the cases. Psychiatric disturbances were present in 30% of the cases, with adjustment disorder (24%) being the most frequent diagnosis. Ten patients (10%) had a history of epileptic seizures. To delineate the functional consequences of ischemic deficits, we studied the extent of disability in different age groups. The full spectrum of disability was seen in all groups older than age 45. Fifty-five percent of the patients older than age 60 were unable to walk without assistance. However, 14% in this age group exhibited no disability at all. Kaplan-Meier analysis disclosed median survival times of 64 years (males) and 69 years (females). An investigation of the 18 multiplex families revealed marked intrafamilial variations.