Reza Forghani MD, PhD, Presenter: Stockholder, Real-Time Radiology, Inc Junior Partner, Clarke Radiology, Montreal Canada

Wendy Atkinson MS, Abstract Co-Author: Nothing to Disclose

Gregory R. Wojtkiewicz MSC, Abstract Co-Author: Nothing to Disclose

Benjamin Pulli MD, Abstract Co-Author: Nothing to Disclose

Yoshiko Iwamoto, Abstract Co-Author: Nothing to Disclose

Ralph Weissleder MD, PhD, Abstract Co-Author: Nothing to Disclose

John Chen MD, PhD, Abstract Co-Author: Research grant, Pfizer Inc

Demyelinating multiple sclerosis (MS) plaques result from an immune-mediated inflammatory response. However, the etiology for the abnormal inflammation is not known. Recently, an alternative hypothesis has been proposed attributing MS plaques to chronically impaired venous drainage secondary to stenosis of the internal jugular (IJV) and other veins, with angioplasty of extracranial venous strictures as a possible treatment. To test the validity of this hypothesis, we generated a mouse model by ligating both IJVs and assessed for the presence of demyelinating plaques.

Surgical ligation of the IJVs (n=16; IJL) or sham surgery without vein ligation (n=11; controls) was performed on 34 SJL mice between 8 and 12 weeks old. Mice were followed clinically using the experimental autoimmune encephalomyelitis (EAE) scoring system to evaluate for neurologic disease up to the ages of 5-8 months. A subset of mice was also evaluated by gadolinium-enhanced MRI of the brain, CT venogram, and Tc99m-exametazime brain scintigraphy by gamma counter. Frozen sections of brain were stained with luxol fast blue to assess for demyelination and immunohistochemistry performed for the inflammatory enzyme myeloperoxidase (MPO) and the MAC-3 antigen to assess for inflammatory cell infiltration.

16 IJL mice and 11 controls were followed up to 6 months. None of the mice showed any motor neurological deficits. Brain MRI was performed on 9 IJL mice and 3 control mice at 6 months post surgery. No white matter lesions or abnormal enhancement was identified to suggest blood-brain barrier breakdown. In addition, we did not observe any evidence of inflammation using the myeloperoxidase-specific molecular imaging agent MPO-Gd. CT venogram confirmed ligated IJVs in 6 mice with evidence of minor collateral formation. After intravenous administration of Tc99m-exametazime, brain tracer activity was 8.3 (IJL mice) versus 7.1 in controls (p = 0.024) by gamma counter, consistent with altered hemodynamics in IJL mice. Immunohistochemistry was performed on 12 IJL brains and 7 control brains and did not show any evidence of demyelination or inflammatory cell infiltration.

Our studies do not support a cause-effect relationship between IJV ligation and development of inflammatory or demyelinating plaques.

These animal experiments do not support the hypothesis that IJ stenosis results in MS.

Forghani, R, Atkinson, W, Wojtkiewicz, G, Pulli, B, Iwamoto, Y, Weissleder, R, Chen, J, Experimental Ligation of the Internal Jugular Vein Does Not Result in Significant Brain Inflammation or Demyelination.  Radiological Society of North America 2011 Scientific Assembly and Annual Meeting, November 26 - December 2, 2011 ,Chicago IL. http://archive.rsna.org/2011/11007174.html