title: Observations on the brain vasculature in multiple sclerosis: A historical perspective.
abstract: OBJECTIVE
  To review the literature on vascular aspects of multiple sclerosis (MS) specifically pathological observations of the perivenular distribution of MS lesions and venous pathology in MS.
  
  
  METHODS
  Comprehensive literature search from 2012 back to 1839.
  
  
  RESULTS
  One hundred and thirty two papers from 1839 to 2012 were included in this study. Multiple authors observed central venules in MS lesions as a feature of MS with the first specific mention by Rindfleisch in 1863. Recent high field strength MRI has reintroduced the perivenular distribution of MS lesions to a new generation, and has suggested that there is disease specificity to this distribution. In addition Putnam and others in the 1930s hypothesized that venous disease was causative for MS. Treatments based on these observations have included anticoagulation, hyperbaric oxygen therapy, and recently endovascular venous procedures. The significance of these findings in terms of MS pathogenesis has been debated over the same period of time.
  
  
  CONCLUSIONS
  While the controversy over venous disease in MS is new, the observation of perivenular MS plaques and venous theories about MS pathogenesis are as old as the history of MS research.
authors: Mellen Center, Cleveland Clinic, United States. Electronic address: rae-gra@ccf.org.
authors: Alex D
authors: AD
authors: Rae-Grant
authors: Case Western Reserve University, School of Medicine, United States.
authors: Clarissa
authors: C
authors: Wong
authors: Lerner Research Institute, Cleveland Clinic, United States.
authors: Rodica
authors: R
authors: Bernatowicz
authors: Mellen Center, Cleveland Clinic, United States.
authors: Robert J
authors: RJ
authors: Fox
keywords: CCSVI; History; Multiple sclerosis; Pathology; Vein; Venous