Reduced Cerebrovascular CO2 Reactivity in CADASIL
Background and Purpose: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (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 (VSMC). To study cerebrovascular function in CADASIL we performed measurements on cerebral hemodynamics using transcranial Doppler sonography (TCD). Methods: Middle cerebral artery (MCA) mean blood flow velocity (MFV), cerebrovascular CO2 reactivity, and the resistance index (RI) were measured by bilateral TCD in 29 CADASIL individuals (mean age 49.0±2.4 years) and an equal number of age- and sex-matched controls. Results: Compared to controls, CO2 reactivity was reduced in CADASIL (33.4±2.7% vs. 45.3±3.0%; p<0.01). This difference remained significant when non-disabled CADASIL individuals (Rankin=0) were compared to matched controls (36.8±3.4% vs. 48.6±3.9%; p<0.05). CO2 reactivity was significantly lower in disabled than in non-disabled CADASIL individuals (24.5±2.7 vs. 36.8+3.4%; p<0.05). MCA MFV was reduced in CADASIL (45.6±2.2 vs. 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 controls (r=-0.339; p<0.05). RI was not significantly altered (59.0±1.0 vs. 57.7±1.2; p=0.42). Conclusions: In CADASIL there is a reduction of both CO2 reactivity and basal MCA MFV, whereas vascular resistance appears to be normal. The reduced CO2 reactivity suggests functional impairment of cerebral vasoreactivity probably related to VSMC dysfunction. The reduction of CO2 reactivity in non-disabled CADASIL individuals suggests an early role of impaired cerebral vasoreactivity in the evolution of the disease.