The Pathology of the Internal Jugular Vein Wall in Multiple Sclerosis

Abstract

In the last years it has been described a condition named Chronic Cerebrospinal Venous Insufficiency (CCSVI), frequently but not exclusively associated to Multiple Sclerosis (MS), which generated a strong scientific controversy about the epidemiological prevalence and the possible role in the complex, multi-factorial MS ethio-pathogenesis.However, CCSVI description also stimulated a considerable research activity on the extracranial veins. Among the fields of interest, the pathology of the Internal Jugular Veins (IJVs) was deeply investigated by some groups, so improving our knowledge in an underestimated field of MS research. Currently, the available papers clearly show the presence of abnormalities in the IJV wall of MS patient's respect to control tissue. In the tunica intima a significant derangement and loss of the endothelial cells have been described. Interestingly scanning electronic microscopy showed absence of endothelium in the defective jugular valves. In the adventitia it has been described an inverted ratio between type I and type III collagen, with prevalence of the latter. Finally, in the adventitia layer it has been found the presence of calcifications arranged around the vena venarum. Assessment of immune cells in the three IJV layers did not demonstrate increased infiltration. Current studies do not clarify the origin of the pathology of the IJV in patients with MS. Congenital, infectious, or even post thrombotic ethiology have been advocated. Finally, the review summarizes studies which link the CCSVI pathophysiology to the complex MS pathogenesis, and particularly to the impact of restricted brain outflow on the cerebral spinal fluid dynamics and cerebral perfusion.

Effects of Venous Angioplasty on Cerebral Lesions in Multiple Sclerosis: Expanded Analysis of the Brave Dreams Double-Blind, Sham-Controlled Randomized Trial

“…When hypoplasia, external compression, and/or intraluminal defects (eg, defective valve and/or septum) of the internal jugular and/or azygos vein are diagnosed, the condition is known as chronic cerebrospinal venous insufficiency (CCSVI). [1][2][3][4][5][6][7][8][9] The reported prevalence of CCSVI in multiple sclerosis (MS) patients and in healthy controls is highly heterogeneous in the literature, as reported by 2 metaanalyses. 10,11 This has generated considerable scientific controversy about the association between MS and CCSVI and therefore about the role of venous balloon angioplasty in improving symptoms and/or the natural history of MS. 12 However, National Institute for Health and Care Excellence (NICE) guidance encouraged further research in the form of robust randomized controlled trials (RCT).…”

Anatomy of venous abnormalities in multiple sclerosis patients

“…Finally, in the adventitia layer the presence of calcifications arranged around the vena venarum has been found. Pedriali and Zamboni believe that published evidence clearly shows the presence of abnormalities in the walls of the IJVs in MS patients [6]. Current studies do not clarify the origin of the pathology of the IJV in MS patients.…”

New Criteria Reduce Inter-Observer Variability in Chronic Cerebrospinal Venous Insufficiency: A Case Control Study

“…This fact sharply contrasts with the finding of significant intraluminal (septa, webs, membranes, fixed and rudimental valves, or wall stenosis) or valvular (tricuspid valves, enlarged and malposition valve leaflets, small accessory valve leaflets) abnormalities during post-mortem examinations or surgical procedures. [42][43][44] These defective valves reduce the normal venous outflow from the brain as proven with different methodologies for flow assessment. [45][46][47] Beyond the deeply held convictions of individual researchers, the heterogeneity of Doppler studies can be reduced to three variables: the participant observed, the measuring instrument and procedure, and the observer.…”