Long-term prognosis and causes of death in CADASIL: a retrospective study in 411 patients
Long-term prognosis and causes of death in CADASIL: a retrospective study in 411 patients
复制标题
DOI：
10.1093/brain/awh282
复制
发表时间：
2004-11-01
期刊：
影响因子：
14.5
通讯作者：
Dichgans, M
中科院分区：
文献类型：
--
作者：
Opherk, C;Peters, N;Dichgans, M
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）是一种由NOTCH 3基因突变引起的遗传性血管病。临床过程是高度可变的。关于CADASIL患者的长期预后和死亡原因知之甚少。同样，性别和NOTCH 3基因型对疾病进展的影响在很大程度上仍未得到研究。我们确定了411例明确诊断为CADASIL的受试者（196例男性，215例女性）。系统地确定了卒中、制动和死亡的发病年龄以及死亡原因和死亡原因发病时的临床状态。使用Weibull回归模型计算至事件发生的时间，以性别和NOTCH 3基因型作为协变量。在研究期间，有73名患者死亡。男性卒中发病时的中位年龄为50.7岁[95%置信区间（CI）= 48.2-53.1岁]，女性为52.5岁（95% CI = 50.0-54.9岁）（P = n.s.）。在没有帮助的情况下无法行走的发病年龄中位数[男性58.9岁（95% CI = 56.6-61.3岁）;女性62.1岁（59.7-64.4岁）]、卧床不起[男性62.1岁（59.6-64.7岁），妇女66.5岁（63.9-69.1岁）;和死亡[男性64.6岁（61.7-67.6岁）;女性70.7岁（67.6-73.9岁）]男性明显低于女性（所有P均小于或等于0.01）。男性的中位生存时间明显短于德国寿命表的预期（64.6年对69.3年，P = 0.01）。相比之下，女性的中位生存时间没有显著降低（70.7年对72.2年）。C117 F突变与较低的死亡年龄相关，C174 Y突变与较低的中风、制动和死亡发病年龄相关（校正P值
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary angiopathy caused by mutations in the NOTCH3 gene. The clinical course is highly variable. Little is known about the long-term prognosis and the causes of death in CADASIL patients. Likewise, the impact of gender and NOTCH3 genotype on disease progression remains largely unexplored. We identified 411 subjects (196 men, 215 women) with a definite diagnosis of CADASIL. Age at onset for stroke, immobilization and death as well as the causes of death and clinical status at onset of the cause of death were determined systematically. Weibull regression models were used to calculate times to event, with gender and NOTCH3 genotype as covariates. At the time of the study, 73 patients had died. The median age at onset for stroke was 50.7 years [95% confidence interval (CI) = 48.2-53.1 years] in men and 52.5 years (95% CI = 50.0-54.9 years) in women (P = n.s.). The median ages at onset for inability to walk without assistance [men 58.9 years (95% CI = 56.6-61.3 years); women 62.1 years (59.7-64.4 years)], bedriddenness [men 62.1 years (59.6-64.7 years), women 66.5 years (63.9-69.1 years); and death [men 64.6 years (61.7-67.6 years); women 70.7 years (67.6-73.9 years)] were significantly lower in men than in women (all P less than or equal to 0.01). The median survival time of men was significantly shorter than expected from German life tables (64.6 versus 69.3 years, P = 0.01). In contrast, the median survival time of women was not significantly reduced (70.7 versus 72.2 years). The C117F mutation was associated with a lower age at death and the C174Y mutation with a lower age at onset for stroke, immobilization and death (adjusted P values