Primary involvement of neurovascular coupling in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy

BackgroundCerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most frequent monogenic cause of cerebral ischemia, but reliable biomarkers to monitor the disease are lacking.Aims and objectivesTo evaluate cerebral autoregulation (CA), vasoreactivity (VR), and neurovascular coupling (NVC) in CADASIL patients through a battery of dynamic transcranial Doppler tests.MethodsWe screened our database for all pre-dementia CADASIL cases. We monitored cerebral blood flow velocity (CBFV) with transcranial Doppler, blood pressure, and expiratory carbon dioxide (CO2) non-invasively. CA was assessed by transfer function from the spontaneous oscillations of blood pressure to CBFV, VR with inhalation of CO2 at 5%, and hyperventilation and NVC by the CBFV response to visual stimulation.ResultsWe included 27 CADASIL patients and 20 healthy controls with similar age and sexes. CA and VR were similar between groups. However, NVC was significantly affected in CADASIL patients, with lower magnitudes of CBFV upsurge (overshoot 195 vs 26 +/- 6%, p=0.013; gain 12 +/- 7 vs 17 +/- 5%, p=0.003) and altered time behavior during visual stimulation (natural frequency 0.18 +/- 0.06 vs 0.24 +/- 0.06Hz, p=0.005; rate time 0.7 +/- 1.7 vs 2.7 +/- 3.5s, p=0.025).Conclusion Our results express a primary and selective involvement of the neurovascular unit in CADASIL rather than a generalized cerebral vasomotor disturbance. Functional cerebrovascular testing could be useful in patient evaluation and monitoring.