[Clinical features in 4 Chinese families with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)].
OBJECTIVE
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is an inherited cerebral arteriolar disease in adulthood, which is caused by NOTCH3 gene mutation. The main symptoms were migraine, cerebral stroke, later with mood disorders and dementia in Caucasian patients. Recently, the disease was also recognized in Asian patients, in whom the migraine is rarely reported. In order to give the clinical features of Chinese patients, we described the clinical symptoms in 4 CADASIL families.


METHODS
CADASIL was diagnosed by the investigation of ultra-structure changes of arteriole in sural nerve and NOTCH3 gene mutation in the 4 index cases. Detailed clinical and routine laboratory examinations were performed in these 4 patients, including electrocardiography, nerve conduction velocity, serum glycogen, and serum homocysteine. Additionally, we also collected the clinical data of the other 83 family members through interviews and the available medical records.


RESULTS
Of the 83 persons, 29 were classified as clinical suspected patients, who presented one or more of the disease-related neurological symptoms, such as cerebral ischemic events and the cognitive impairment. All of them showed no common risk factors for stroke, such as diabetic mellitus, hypertension, and heart disease. The clinical suspected patients distributed in every consecutive generations and involved both sexes, which was according to the autosomal dominant inherited pattern. The onset age of the disease ranged from 28 to 70-year-old and mainly between the 4th and the 5th decades. The main symptoms were recurrent episodic vertigo, with or without hemiplegia. At the same time or a little bit later, the cognitive impairment was developed in some patients. Compared with the typical presentations of the disease in European patients, none of our 29 patients showed migraine,one index case showed mild sensory disturbance in extremities. Elevated serum homocysteine level and abnormal of nerve conduction study in two index cases (3 and 4) were noticed.


CONCLUSIONS
The onset age of the disease of our patients is similar to that of Caucasian patients. The main symptoms were stroke and dementia. Involvement of post circulation system was the main clinical feature for ischemic events in our patients. Dementia could be found in the early stage of disease. Migraine should not be regarded as a common clinical feature in our patients. The involvement of the peripheral nerves expanded the disease expression outside the central nervous system.
Department of Neurology, Peking University First Hospital, Beijing 100034, China.
He
H
Lv
Sheng
S
Yao
Wei
W
Zhang
Zhao-xia
ZX
Wang
Yi-ning
YN
Huang
Xiao-yuan
XY
Niu
Zhuo
Z
Zhang
Yun
Y
Yuan
D000328:Adult; D046589:CADASIL / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D006003:Glycogen / Q000097:blood; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000648:ultrastructure; D009154:Mutation; D010375:Pedigree; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics
C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D006710:Homocysteine; D006003:Glycogen