Acetazolamide improves cerebral hemodynamics in CADASIL.
BACKGROUND
Acetazolamide (ACZ), a carbonic anhydrase inhibitor, causes a rapid increase in cerebral blood flow (CBF) in patients with cerebrovascular diseases. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebrovascular disease caused by mutations in the NOTCH3 gene. Recent studies suggest that ACZ infusion significantly increases cerebral perfusion, even within areas of impaired cerebral vasoreactivity in CADASIL patients. This study evaluates the efficacy and tolerance of a 24-week treatment with 250 mg/d ACZ, which could be chronically implemented to improve cerebral hemodynamics in CADASIL.


METHODS
CADASIL patients (n=16) were treated with ACZ (250 mg) daily for 24 weeks. The mean blood flow velocity (MFV) of the middle cerebral artery (MCA) and CO(2)-induced cerebrovascular reactivity (CVR) were tested using transcranial Doppler sonography (TCD) before and after treatment.


RESULTS
After ACZ treatment, the MFV in the MCA was significantly greater at rest (57.68+/-12.7 cm/s versus 67.12+/-9.4 cm/s; P=0.001). Additionally, the CO(2)-induced vasoreactivity increased significantly (13.17+/- 6.9% versus 20.69+/-8.2%, P=0.004), and the pulsatility index (PI) decreased significantly (0.82+/-0.1 versus 0.73+/-0.08; P=0.001). The relative ACZ-induced enhancement of CO(2) vasoreactivity was not correlated with pretreatment MFV (SRCC=-0.122; P=0.659).


CONCLUSIONS
The present study provides the first evidence that ACZ therapy can increase CBF and CVR in CADASIL patients.
Huang
Li
L
Department of Neurology, Xiangya Hospital of Central South University, Hunan Province, Changsha, 410008, China. huangl200903@126.com
Yang
Qidong
Q
Zhang
Le
L
Chen
Xuan
X
Huang
Qing
Q
Wang
Hongxing
H
D000086:Acetazolamide / Q000627:therapeutic use*; D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D046589:CADASIL / Q000000981:diagnostic imaging / Q000188:drug therapy*; D002257:Carbonic Anhydrase Inhibitors / Q000627:therapeutic use; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020768:Middle Cerebral Artery / Q000000981:diagnostic imaging / Q000187:drug effects*; D018579:Patient Selection; D010865:Pilot Projects; D016896:Treatment Outcome; D014463:Ultrasonography
D002257:Carbonic Anhydrase Inhibitors; D000086:Acetazolamide