Potential Involvement of Impaired Venous Outflow from the Brain in Neurodegeneration: Lessons Learned from the Research on Chronic Cerebrospinal Venous Insufficiency

Abstract

About 10 years ago, the so-called chronic cerebrospinal venous insufficiency syndrome was discovered. This clinical entity, which is associated with extracranial venous abnormalities that impair venous outflow from the brain, was initially found exclusively in multiple sclerosis patients. Currently, we know that such venous lesions can also be revealed in other neurological pathologies, including Alzheimer’s and Parkinson’s diseases. Although direct causative role of chronic cerebrospinal venous insufficiency in these neurological diseases still remains elusive, in this paper, we suggest that perhaps an abnormal venous drainage of the brain affects functioning of the glymphatic system, which in turn results in the accumulation of pathological proteins in the cerebral tissue (such as β-synuclein, β-amyloid and α-synuclein) and triggers the venous outflow from the cranial cavity and circulation of the cerebrospinal fluid in the settings of neurodegenerative disease.

Potential Role of Venular Amyloid in Alzheimer’s Disease Pathogenesis

“…Recently, there has been increased importance in studying the pathology of veins and venules, not only in the context of AD or CAA, but also in small vessel disease and dementia overall [30,45,46]. Venous pathology has been shown to contribute to vascular dysfunction in AD, resulting in white matter hyperintensities and microinfarcts, and potentially induction of ischemia [30,[45][46][47][48]. However, more research is necessary to understand the role of veins and venules in AD and CAA.…”

“…been shown to contribute to vascular dysfunction in AD, resulting in white matter hyperintensities and microinfarcts, and potentially induction of ischemia [30,[45][46][47][48]. However, more research is necessary to understand the role of veins and venules in AD and CAA.…”

Cerebral Venous Reflux and Cerebral Amyloid Angiopathy: An Magnetic Resonance Imaging/Positron Emission Tomography Study

“…Venous system dysfunction has been linked to a variety of brain disorders, including Alzheimer and Parkinson disease. 2 Several reports have indicated that IJV reflux and increased central venous pressure, typically measured by neck sonography, are associated with white matter changes in Alzheimer disease and in elderly individuals. 4,5,30 Chronic venous insufficiency in the dural venous sinuses and compromised jugular drainage also A, Among patients with spontaneous intracerebral hemorrhage (ICH) with cerebral amyloid angiopathy (CAA)-ICH or non-CAA ICH, patients with CVR have higher cerebral amyloid load.…”

“…Cerebral venous reflux is a manifestation of abnormal cerebral venous circulation due to systemic venous congestion, increased cerebral venous pressure, or age-related degeneration of venous valves. 1 Abnormal cerebral venous circulation may be associated with decreased cerebral perfusion, cerebral microvascular damage, impaired cerebral autoregulation, and altered cerebrospinal fluid dynamics 2,3 ; all of the features are closely related to central nervous system pathology.…”

“…7 However, the dominant microangiopathy involved in cerebral venous outflow insufficiency remains poorly understood and few studies have investigated the effects of CVR in CAA or hypertensive SVDs. Based on preliminary evidence that indicates cerebral venous outflow potentially contributes to accumulation of pathological proteins such as Aβ (amyloid-β), 2,8 we hypothesized that CVR is more closely associated with CAA and a higher cerebral amyloid burden than to hypertensive SVD.…”