Regarding MS and your cerebral venous drainage

Dr. Weeks’ Comment:   Science marches on (delightfully!)  and,  in the process, experts become embarrassed, truth morphs and conventional wisdom is trumped by actual observations and common sense. Also, markets shudder and businesses become obsolete.  How would you like to be in the camera film business or the classic non-digital watch business

(Historical fact: Swiss watch makers were pitched the digital watch option initially and turned up their nose  …  big mistake.   HUGE. )

Now, Dr. Zamboni is shaking up the MS world.

What do you think of this research?

The stakes are high:  if he is right, billion of dollars of sales of MS drugs evaporate… overnight as patients get a surgical correction.

At the Weeks Clinic, we refer appropriate patients for MRV  testing to see if a pinched vein is causing their  MS symptoms.


J Vasc Surg. 2009 Dec;50(6):1348-58.e1-3.

A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency.

Zamboni P, Galeotti R, Menegatti E, Malagoni AM, Gianesini S, Bartolomei I, Mascoli F, Salvi F.

Vascular Diseases Center, University of Ferrara, Ferrara, Italy. zmp@unife.it

OBJECTIVE: Chronic cerebrospinal venous insufficiency (CCSVI) is characterized by combined stenoses of the principal pathways of extracranial venous drainage, including the internal jugular veins (IJVs) and the azygous (AZY) vein, with development of collateral circles and insufficient drainage shown by increased mean transit time in cerebral magnetic resonance (MR) perfusion studies. CCSVI is strongly associated with multiple sclerosis (MS). This study evaluated the safety of CCSVI endovascular treatment and its influence on the clinical outcome of the associated MS. METHODS: Sixty-five consecutive patients with CCSVI, subdivided by MS clinical course into 35 with relapsing remitting (RR), 20 with secondary progressive (SP), and 10 with primary progressive (PP) MS, underwent percutaneous transluminal angioplasty (PTA). Mean follow-up was 18 months. Vascular outcome measures were postoperative complications, venous pressure, and patency rate. Neurologic outcome measures were cognitive and motor function assessment, rate of MS relapse, rate of MR active positive-enhanced gadolinium MS lesions (Gad+), and quality of life (QOL) MS questionnaire. RESULTS: Outpatient endovascular treatment of CCSVI was feasible, with a minor and negligible complication rate. Postoperative venous pressure was significantly lower in the IJVs and AZY (P < .001). The risk of restenosis was higher in the IJVs compared with the AZY (patency rate: IJV, 53%; AZY, 96%; odds ratio, 16; 95% confidence interval, 3.5-72.5; P < .0001). CCSVI endovascular treatment significantly improved MS clinical outcome measures, especially in the RR group: the rate of relapse-free patients changed from 27% to 50% postoperatively (P < .001) and of MR Gad+ lesions from 50% to 12% (P < .0001). The Multiple Sclerosis Functional Composite at 1 year improved significantly in RR patients (P < .008) but not in PP or SP. Physical QOL improved significantly in RR (P < .01) and in PP patients (P < .03), with a positive trend in SP (P < .08). Mental QOL showed significant improvement in RR (P < .003) and in PP (P < .01), but not in SP. CONCLUSIONS: PTA of venous strictures in patients with CCSVI is safe, and especially in patients with RR, the clinical course positively influenced clinical and QOL parameters of the associated MS compared with the preoperative assessment. Restenosis rates are elevated in the IJVs but very promising in the AZY, suggesting the need to improve endovascular techniques in the former. The results of this pilot study warrant a subsequent randomized control study.

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J Cereb Blood Flow Metab. 2009 Dec;29(12):1867-78. Epub 2009 Sep 2.

Anomalous venous blood flow and iron deposition in multiple sclerosis.

Singh AV, Zamboni P.

Department of Physics, European School of Molecular Medicine (SEMM), IFOM-IEO Campus, Centro Interdisciplinare Materiali e Interfacce Nanostrutturati, University of Milan, Milan, Italy.

Multiple sclerosis (MS) is primarily an autoimmune disorder of unknown origin. This review focuses iron overload and oxidative stress as surrounding cause that leads to immunomodulation in chronic MS. Iron overload has been demonstrated in MS lesions, as a feature common with other neurodegenerative disorders. However, the recent description of chronic cerebrospinal venous insufficiency (CCSVI) associated to MS, with significant anomalies in cerebral venous outflow hemodynamics, permit to propose a parallel with chronic venous disorders (CVDs) in the mechanism of iron deposition. Abnormal cerebral venous reflux is peculiar to MS, and was not found in a miscellaneous of patients affected by other neurodegenerative disorders characterized by iron stores, such as Parkinson’s, Alzheimer’s, amyotrophic lateral sclerosis. Several recently published studies support the hypothesis that MS progresses along the venous vasculature. The peculiarity of CCSVI-related cerebral venous blood flow disturbances, together with the histology of the perivenous spaces and recent findings from advanced magnetic resonance imaging techniques, support the hypothesis that iron deposits in MS are a consequence of altered cerebral venous return and chronic insufficient venous drainage.

PMID: 19724286 [PubMed – in process]

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Funct Neurol. 2009 Jul-Sep;24(3):133-8.

The severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis is related to altered cerebrospinal fluid dynamics.

Zamboni P, Menegatti E, Weinstock-Guttman B, Schirda C, Cox JL, Malagoni AM, Hojanacki D, Kennedy C, Carl E, Dwyer MG, Bergsland N, Galeotti R, Hussein S, Bartolomei I, Salvi F, Zivadinov R.

Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular picture that shows a strong association with multiple sclerosis (MS). The aim of this study was to investigate the relationship between a Doppler cerebral venous hemodynamic insufficiency severity score (VHISS) and cerebrospinal fluid (CSF) flow dynamics in 16 patients presenting with CCSVI and relapsing-remitting MS (CCSVI-MS) and in eight healthy controls (HCs). The two groups (patients and controls) were evaluated using validated echo-Doppler and advanced 3T-MRI CSF flow measures. Compared with the HCs, the CCSVI-MS patients showed a significantly lower net CSF flow (p=0.027) which was highly associated with the VHISS (r=0.8280, r2=0.6855; p=0.0001). This study demonstrates that venous outflow disturbances in the form of CCSVI significantly impact on CSF pathophysiology in patients with MS.

PMID: 20018140 [PubMed – in process]

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Dr. Weeks’ Comment:   Science marches on (delightfully!)  and,  in the process, experts become embarrassed, truth morphs and conventional wisdom is trumped by actual observations and common sense. Also, markets shudder and businesses become obsolete.  How would you like to be in the camera film business or the classic non-digital watch business (Historical fact: Swiss watch…
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