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Reduced Cerebrovascular CO2 Reactivity in CADASIL: A Transcranial Doppler Sonography Study

Background and Purpose— Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukencephalopathy (CADASIL) is a hereditary angiopathy caused by mutations in Notch3. Cerebral microvessels show an accumulation of granular osmiophilic material in the vicinity of degenerating vascular smooth muscle cells. To study cerebrovascular function in CADASIL, we performed measurements on cerebral hemodynamics by using transcranial Doppler sonography. Methods— Middle cerebral artery (MCA) mean blood flow velocity (MFV), cerebrovascular CO2 reactivity, and the resistance index were measured by bilateral transcranial Doppler sonography in 29 CADASIL individuals (mean age, 49.0±2.4 years) and an equal number of age- and sex-matched control subjects. Results— Compared with control subjects, CO2 reactivity was reduced in CADASIL (33.4±2.7% versus 45.3±3.0%;P <0.01). This difference remained significant when only nondisabled CADASIL individuals (Rankin=0, n=21) were included in the analysis (P <0.05). CO2 reactivity was significantly lower in disabled than in nondisabled CADASIL individuals (24.5±2.7% versus 36.8±3.4%;P <0.05). MCA MFV was reduced in CADASIL (45.6±2.2 cm/s versus 54.2±2.4 cm/s;P <0.05) and correlated negatively with age both in affected individuals (r =−0.314;P <0.05) and control subjects (r =−0.339;P <0.05). Resistance index was not significantly altered (59.0±1.0% versus 57.7±1.2%;P =0.42). Conclusions— In CADASIL, there is a reduction of both CO2 reactivity and basal MCA MFV. The reduced CO2 reactivity suggests functional impairment of cerebral vasoreactivity probably related to vascular smooth muscle cell dysfunction. The reduction of CO2 reactivity in nondisabled CADASIL individuals suggests an early role of impaired cerebral vasoreactivity in the evolution of the disease.