Cerebrovascular reactivity and dynamic autoregulation in nondemented patients with CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)

Abstract

Reduced cerebrovascular reactivity has been reported in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and the measurement has been suggested as a useful surrogate marker of disease progression. Previous studies have not determined whether cerebral autoregulation is also impaired. We measured dynamic cerebral autoregulation and carbon dioxide reactivity in 24 nondemented CADASIL patients and 20 controls, using transcranial Doppler ultrasound (TCD). No impairment in either measure was found in the CADASIL group. We conclude that either cerebrovascular reactivity and autoregulation are not impaired in early disease, or that TCD may not be a sufficiently sensitive tool to detect haemodynamic changes in early disease. TCD is unlikely to be useful for disease monitoring in patients without advanced disease.

Proteome Analysis of Cultivated Vascular Smooth Muscle Cells from a CADASIL Patient

“…This conforms to the reduction of blood flow in the peripapillary retina demonstrated by scanning laser Doppler flowmetry (27). Furthermore, the reduced cerebral blood flow in CADASIL is associated with increased distal cerebrovascular resistance (28) and it can be decreased by administration of acetazolamide (29) or carbon dioxide (28,30). In addition, it was recently shown that CADASIL patients have enhanced maximal constriction response to angiotensin II in the resistance arteries (31).…”

Disturbed integrin expression in the vascular media in CADASIL

“…In experimental investigations, impaired cerebral vasoreactivity in a transgenic mouse model of CADASIL was observed [13]. Also clinical studies on CADASIL patients demonstrated abnormal vasoreactivity [9,26] and a reduced cerebral blood flow [20,23] in the course of the disease. Integrin subunit β1 as a part of α1β1 and α5β1 integrin receptors is involved in vasoconstriction and transfer of signals originating from ECM and regulating permeability of calcium channels on VSMCs and myocytic voltage value.…”

Impaired Endothelial Function of Forearm Resistance Arteries in CADASIL Patients

“…14 Another transcranial Doppler study showed only reduced basal blood flow velocity, but preserved increase in response to CO 2 and to blood pressure reduction. 26 A reduction of basal blood flow in CADASIL patients has also been described in cerebral white matter with PET 27 and in retinal vessels. 28 The reduced endothelial function in smaller resistance arteries that we showed in this study may be a key element in the development of ischemic lesions in CADASIL patients especially in the brain, which is the organ with the highest degree of autoregulation of blood flow.…”