Reduced cerebrovascular CO2 reactivity in CADASIL - A transcranial Dopplersonography study

Background and Purpose-Cerebral autosomal dominant arteriopathy with subcor tical infarcts and leukencephalopathy (CADASIL) is a hereditary angiopathy caused by mutations in Notch3. Cerebral microvessels show an accumulation o f granular osmiophilic material in the vicinity of degenerating vascular sm ooth muscle cells. To study cerebrovascular function in CADASIL, we perform ed measurements on cerebral hemodynamics by using transcranial Doppler sono graphy. Methods-Middle cerebral artery (MCA) mean blood flow velocity (MFV), cerebr ovascular CO2 reactivity, and the resistance index were measured by bilater al 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 CADAS IL (33.4+/-2.7% versus 45.3+/-3.0%; P<0.01). This difference remained signi ficant when only nondisabled CADASIL individuals (Rankin=0, n=21) were incl uded in the analysis (P<0.05). CO2 reactivity was significantly lower in di sabled 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 indi viduals (r= -0.314; P<0.05) and control subjects (r= -0.339; P<0.05). Resis tance 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 bas al MCA MFV. The reduced CO2 reactivity suggests functional impairment of ce rebral vasoreactivity probably related to vascular smooth muscle cell dysfu nction. The reduction of CO2 reactivity in nondisabled CADASIL individuals suggests an early role of impaired cerebral vasoreactivity in the evolution of the disease.