CCSVI in Multiple Sclerosis: Is It the End?
Received Date: Dec 20, 2017 / Accepted Date: Jan 26, 2018 / Published Date: Feb 02, 2018
It was published the long awaited Italian clinical trial investigating the safety and efficacy of a venous percutaneous transluminal angioplasty (PTA) to treat patients with multiple sclerosis. According to the authors, venous PTA has proven to be a safe but largely ineffective technique; the treatment cannot be recommended in patients with MS .
Anyone who read the seven-page study, however, would have found a second, somewhat contradictory conclusion- that MRI results showed some people with MS, a degenerative condition of unknown origin, benefitted from improved cerebral blood flow, and further study was warranted. The delayed effect of venous PTA six months after the procedure on the magnetic resonance biomarker suggests a possibility that PTA may produce benefit for a sub-group of patients with MS. According to the authors this should be further analysed and investigated .
Eight years ago, Paolo Zamboni, an Italian vascular surgeon, created a firestorm in the MS community with his hypothesis that MS, long believed to be an autoimmune disease, could have a vascular connection. His research indicated people with MS had restricted venous flow from the brain and spinal cord, a condition he named as chronic cerebro-spinal venous insufficiency, or CCSVI. His small 65 person observational study found PTA of venous structures in patients with CCSVI is safe, and especially in patients with RR, the clinical course positively influenced clinical and quality of life’s parameters of the associated MS compared with the preoperative assessment .
MS neurologists, the official MS gatekeepers, dismissed, even mocked Zamboni’s theory and the scientific integrity of his research. Nonetheless, thousands of Italians with MS sought treatment, spurred by anecdotal reports of improvements spread on social media. (Incidence of MS is high in Italy. In Italy, people with MS pressed to have venoplasty for MS covered by healthcare in Italy that it is covered for other diseases). They also called for a randomized, double-blinded placebo-controlled trial of the sort used to test new drugs.
Reported responses to CCSVI treatment were as varied as the MS population itself: some people experienced lasting benefits in terms of renewed energy, better balance and improved bladder control . For others, early improvements vanished with time; a percentage saw no benefit and experienced complications; three deaths were associated with the treatment . In time, the idea that CCSVI was the cause of MS, and that treating it could be a cure, was abandoned; people with MS, many of them disillusioned with or unable to take MS drugs, sought symptom relief and improved quality of life.
Zamboni’s theory propelled wide-ranging research and the creation of a multidisciplinary society (ISNVD) to investigate neuro-vascular diseases.MS neurologists conducted research reluctan tly; their studies found that CCSVI is not associated with MS .
Zamboni was the principal investigator and senior author of the newly published Italian study, named “Brave Dreams” (Brain Drainage Exploited against Multiple Sclerosis) .
The study wanted to provide an answer regarding the efficacy of PTA on patients' functional disability in balance, motor, sensory, visual and bladder function, cognitive status, and emotional status, which are meaningful clinical outcomes, beyond investigating the effects on inflammation. In fact, an important part of patients' expectations, sustained and amplified by anecdotal data, has to do precisely with these functional aspects.
The study was rigorously designed but marred by limitations. One was its small size. Originally designed for 430 participants, only 115 patients were enrolled (76 had PTA; 39 received a sham procedure, the surgical equivalent of placebo); as such it was underpowered to answer the questions it sought to investigate. The low enrolment is explained in the study as the result of MS patients’ lack of willingness to undergo the sham procedure.
The data did confirm a high prevalence- 74 percent of CCSVI in people with MS.. It also found various and complex types of venous malformations, including closed jugular vein valves. Only 53 percent of people who received PTA had blood flow restored, it was ineffective for the remainder.
The study concluded that PTA did not result in functional improvements (for example, improvements in gait, balance, bladder control, fatigue, etc.), nor did it reduce the mean number of new combined brain lesions on MRI at 12 months.
The one aspect of the study that calls for further inquiry is the finding that 77 per cent of treated patients, 22 per cent more than the sham group, were free of gadolinium-enhancing lesions at 12 months. The importance of this was explained in the study: “Gadolinium enhancement is a marker of damage to the blood - brain barrier, whose time course depends on lymphatic drainage, and hence on venous drainage from the skull”.
The study was accompanied too by an editorial written by three MS neurologists that is scathing in its denouncement of CCSVI, CCSVI advocacy and the role of social media in spreading ineffective medicine. The study is rigorous and definitive, the authors declare and its result is unequivocal .
But is it really so?
On August 16, 2017 it was published a new interesting study titled “Factors influencing the hemodynamic response to balloon angioplasty in the treatment of outflow anomalies of internal jugular veins”.
According to the authors their study identified the factors that influence and could predict the efficacy of percutaneous transluminal angioplasty in the treatment of the internal jugular veins’ anomalies .
Conflict of Interest
- Zamboni P, Tesio L, Galimberti S, Massacesi L, Salvi F, et al. (2017) Efficacy and safety of extracranial vein angioplasty in multiple sclerosis: A randomized clinical trial. JAMA Neurol 75: 35-43.
- Zamboni P, Galeotti R, Menegatti E, Malagoni AM, Gianesini S, et al. (2009) A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency. J Vasc Surg 50: 1348-1358.
- Bavera PM (2015) May symptoms of chronic cerebrospinal venous insufficiency be improved by venous angioplasty? An independent 4 year follow up on 366 cases. Veins and Lymphatics 4: 3.
- Dake MD, Dantzker N, Bennett WL, Cooke JP (2012) Endovascular correction of cerebrovenous anomalies in multiple sclerosis: A retrospective review of an uncontrolled case series. Vasc Med 17: 131-137.
- Comi G, Battaglia MA, Bertolotto A, Del Sette M, Ghezzi A, et al. (2013) Observational case-control study of the prevalence of chronic cerebrospinal venous insufficiency in multiple sclerosis: Results from the CoSMo study. Mult Scler J 19: 1508-1517.
- Green AJ, Hooman K, Josephson SA (2017) Combating the spread of ineffective medical procedures: A lesson learned from multiple sclerosis. JAMA Neurol 75: 15-17.
- Giaquinta A, Beggs CB, Veroux M, De Marco E, Sanzone A, et al. (2017) Factors influencing the hemodynamic response to balloon angioplasty in the treatment of outflow anomalies of internal jugular veins. J Vasc Surg Venous Lymphat Disord 5: 777-788.
Citation: Rasman A (2018) CCSVI in Multiple Sclerosis: Is It the End? J Mult Scler 5: 216. DOI: 10.4172/2376-0389.1000216
Copyright: © 2018 Rasman A. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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