Reduced cerebrovascular CO(2) reactivity in CADASIL: A transcranial Doppler sonography study.
OBJECTIVE
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 CO(2) 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, CO(2) 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). CO(2) 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 CO(2) reactivity and basal MCA MFV. The reduced CO(2) reactivity suggests functional impairment of cerebral vasoreactivity probably related to vascular smooth muscle cell dysfunction. The reduction of CO(2) reactivity in nondisabled CADASIL individuals suggests an early role of impaired cerebral vasoreactivity in the evolution of the disease.
Pfefferkorn
T
T
Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-Universität München.
von Stuckrad-Barre
S
S
Herzog
J
J
Gasser
T
T
Hamann
G F
GF
Dichgans
M
M
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001783:Blood Flow Velocity; D002245:Carbon Dioxide / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D015161:Dementia, Multi-Infarct / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D006935:Hypercapnia / Q000378:metabolism; D016857:Hypocapnia / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020768:Middle Cerebral Artery / Q000000981:diagnostic imaging; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D000071656:Receptor, Notch3; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D017585:Ultrasonography, Doppler, Transcranial; D014655:Vascular Resistance
C499374:NOTCH3 protein, human; D011518:Proto-Oncogene Proteins; D000071656:Receptor, Notch3; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D002245:Carbon Dioxide