New studies question vascular multiple sclerosis hypothesis and treatment

Aug 02, 2010

Two important new studies challenge the controversial hypothesis that venous congestion—chronic cerebrospinal venous insufficiency (CCSVI)—contributes to the development of multiple sclerosis (MS). This theory has resulted in many multiple sclerosis patients receiving experimental endovascular angioplasty, a treatment for multiple sclerosis unproved by clinical trials. The studies refuting the chronic cerebrospinal venous insufficiency theory with the first negative medical evidence on the subject, are available today in Annals of Neurology.

For nearly 150 years it has been known that focal multiple sclerosis lesions tend to develop around cerebral veins that are thought to the portal by which inflammatory cells targeting myelin enter the brain. However, a 2009 study by Zamboni and colleagues offered an alternative theory suggesting that chronically impaired venous drainage from the CNS—a term that he labeled Chronic Cerebrospinal Venous Insufficiency or CCSVI—leads to multiple sclerosis development.(1) Zamboni and colleagues also claimed that endovascular angioplasty was markedly effective in multiple sclerosis patients.(2) Zamboni's work gained much attention in the press, especially their report that ultrasound diagnosis of chronic cerebrospinal venous insufficiency perfectly matched an multiple sclerosis diagnosis with 100% sensitivity and 100% specificity.

"These two papers should add a note of caution for MS patients and physicians who are contemplating interventions for possible venous abnormalities based on the findings of Zamboni. At this time, the theory must be considered unconfirmed and unproved. Such interventions carry risk, and several people have already been harmed by the inappropriate application of venous angioplasty and stenting for MS," says Stephen L Hauser MD, the Robert A Fishman Distinguished Professor and Chair of the Department of Neurology at the University of California, San Francisco, and editor-in-chief of the Annals of Neurology. A previously published review of the evidence in the Annals by Khan and colleagues noted that treatment procedures, based upon these findings, have included placing stents in the jugular veins of multiple sclerosis patients which led to serious injury in some cases.

In the current issue of the Annals, Florian Doepp MD and colleagues in Germany performed an extended extra- and transcranial color-coded sonography study on 56 multiple sclerosis patients (36 female; 20 male) and 20 control subjects (12 female; 8 male). The analysis included extracranial venous blood volume flow, internal jugular vein flow analysis during Valsalva maneuver, as well as tests included in the chronic cerebrospinal venous insufficiency criteria.

Results showed that blood flow direction was normal in all participants, excluding 1 subject with relapsing-remitting multiple sclerosis. Furthermore, the research team noted that blood volume flow in both groups were equal in the supine body position. In summary, the researchers determined that none of the study participants fulfilled more than 1 criterion for chronic cerebrospinal venous insufficiency.

"Our results call into question the existence of CCSVI in a large proportion of patients with MS," said Dr Doepp. "We did not find supporting evidence that cerebral venous congestion plays a significant role in the development of MS. Further studies are needed to clarify the difference between MS patients and healthy subjects in blood volume flow regulation," concluded Dr Doepp.

A second study by researchers at Umeå University in Sweden also concluded that chronic cerebrospinal venous insufficiency does not contribute to the development of multiple sclerosis. The Swedish research team led by Peter Sundström MD PhD, tested the vital component of the chronic cerebrospinal venous insufficiency theory—the obstructed internal jugular vein flow—in 21 multiple sclerosis patients and 20 healthy controls using MRI with phase contrast (PC-MRI).

"Using PC-MRI, we were not able to reproduce the findings by Zamboni et al. which suggest CCSVI contributes to the development of MS," said Dr Sundström. The researchers found no significant differences between the multiple sclerosis group and control group relating to total internal jugular vein blood flow. "Our study found no support for using endovascular procedures such as angioplasty or stenting to treat MS patients," Dr Sundström affirmed.

(1) Zamboni P, Galeotti R, Menegatti E, et al. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2009;80:392.

(2) Zamboni P, Galeotti R, Menegatti E, et al. A prospective openlabel study of endovascular treatment of chronic cerebrospinal venous insufficiency. J Vasc Surg 2009;50:1348.

Source: News Release
Wiley-Blackwell
August 2, 2010