Venous haemodynamic and cerebrospinal fluid anomalies associated with multiple sclerosis

Abstract

This critical synopsis of prior work by Clive Beggs is submitted in support of a PhD by published work. The work focuses on venous and cerebrospinal fluid (CSF) anomalies associated with multiple sclerosis (MS) and other neurological diseases. MS is characterized by focal inflammatory lesions, which are often venocentric. Recently a vascular syndrome, chronic cerebrospinal venous insufficiency (CCSVI) has been linked with MS. This syndrome, which is characterized by constricted cerebral venous outflow, has become mired in controversy, with various studies producing conflicting findings, with the result that the science associated with CCSVI has become obscured. Clive Beggs work seeks to bring clarity to the debate surrounding CCSVI by characterizing physiological changes associated with constricted cerebral venous outflow. The work submitted here involves collaborative studies with Robert Zivadinov (University of Buffalo), Paolo Zamboni (University of Ferrara), and Chih- Ping Chung (National Yang Ming University of Medicine). The key findings of these studies are: (i) MS patients, diagnosed with CCSVI, exhibit greatly increased hydraulic resistance of the cerebral venous drainage system; (ii) MS patients experience loss of the small cerebral veins; (iii) MS patients exhibit reduced CSF bulk flow, consistent with mild venous hypertension; (iv) MS patients exhibit increased CSF pulsatility in the Aqueduct of Sylvius, which appears to be linked with mild venous hypertension associated with CCSVI; and (v) jugular venous reflux is associated with white matter and parenchymal volumetric changes in Alzheimer’s patients. Collectively, these findings suggest that extracranial venous anomalies are associated with changes in the intracranial physiology.