"The Contribution of Extra Cranial Venous Drainage to Neuro-Inflammation in Multiple Sclerosis" - Paolo Zamboni -

Abstract
The role of the extracranial veins in the pathogenesis of inflammatory neurological/neurodegenerative diseases remains largely unknown and under-investigated. A condition named chronic cerebrospinal venous insufficiency (CCSVI) strikes the main extracranial veins and determines a slight increase in pressure up to the brain venules. The condition is linked with a recently-described chain of pathophysiologic events. Impaired CSF diffusion into the brain parenchyma between the peri-arterial and the perivenous spaces contributes to a worsened protein clearance. Furthermore, restricted venous outflow through the jugular veins reduces perfusion and the energy available to oligodendrocytes for myelin synthesis. Both peptide waste and myelin debris represent a strong chemotactic signaling. Increased transmural pressure in the CCSVI condition may also facilitate blood-brain barrier leakage and red blood cells extravasation. Consequently, iron stores are increased and likely linked to inflammation and degeneration. The contribution of the impaired venous function to neuroinflammation/degeneration warrants further studies in this direction.