Investigating the Association between the Intracranial Small Artery Disease and Cerebral Venous Outflow Impairment

Intracranial small artery disease is the most common cause of ischemic stroke in Asian populations. We have reported that cerebral venous outflow impairment or jugular venous reflux linked to several neurological disorders, including transient global amnesia, transient monocular blindness, leukoaraiosis. In addition, our previous studies have found internal jugular reflux is associated with the increase of resistance of retrobulbar arterioles; other studies also found patients with venous outflow impairment had retinal arteriole narrowing. In addition, in our recent study we found more than half of so called “transverse sinus hypoplasia” was not real hypoplasia, and it was a result of downstream venous obstruction. Moreover, based on the Poiseuille law, we estimate the venous gradient was 7 times higher than people without such TS hypoplasia. The cerebral autoregulation was impaired in these subjects. Whether cerebral venous outflow impairment could lead to intracranial small artery disease remain unknown. Our hypothesis is that impaired venous outflow may cause blood flow stasis, higher intracranial arterial resistance, which further causes small artery arteriolar sclerosis, and as a result, we expect acute stroke patients with venous outflow impairment linked to lacunae, white matter disease and impaired cerebral autoregulation. The aim of this study is to test above-mentioned hypothesis that patients with cerebral venous outflow impairment and jugular venous reflux have a higher probability of intracranial small artery disease. This is a three-year study, we will recruit 500 acute stroke patients with ultrasound and MR examinations, and recruit 100 health individuals with ultrasound examination as control. All patients will receive our standardized ultrasound examination. The inclusion criteria are age >20 and given inform consent. The exclusion criteria include history of neck trauma, end stage renal disease and receiving hemodialysis, and those having inadequate temporal insonation windows. The protocol of ultrasound examinations include extracranial, intracranial and orbital arteries and veins, the branch of internal jugular veins and cerebral autoregulation tests.