The only thing liberated was their wallets

Patients are left with costs as discredited MS therapy circles the drain, writes Colby Cosh
Bad medicine: Zamboni’s MS study made insupportable claims, new journal studies show
Alessandro Vincenzi

“Liberation therapy” for multiple sclerosis is dead; yet long will it live, not only in the hearts of desperate MS patients, but in their bank balances too. In 2009 an Italian physician named Paolo Zamboni issued a study claiming that MS sufferers had poor rates of blood outflow from their brains. He proposed a complex new etiological theory of MS on this basis, proclaiming the existence of a new syndrome: “chronic cerebrospinal venous insufficiency,” or CCSVI.

Zamboni’s study made bold, almost patently insupportable claims about differences between the blood vessels of MS sufferers and healthy persons. His theory of CCSVI seemed to contradict much that is known about MS and failed to account for obvious features like the midlife age of typical onset. The research got little attention outside Canada, a country hit hard by the global north-south gradient of MS rates. Inside Canada, it only took one round of zingy, insufficiently critical news stories by CTV and the Globe and Mail to make Zamboni a hero.

Hundreds of patients, perhaps thousands, have travelled the globe seeking venous angioplasty for MS symptoms, usually against doctors’ advice, and millions of dollars have been invested in CCSVI and “liberation therapy” surveillance after pressure was applied by shouting patients and opportunistic backbench politicians. But after years of empirical setbacks for the whole notion of CCSVI, it is all looking like money down the drain.

The first question to be answered about CCSVI ought to have been, “Is there actually any such thing?” Attempts to reproduce Zamboni’s results have met with mass consternation; researchers cannot even get to the point of determining whether CCSVI is treatable because they cannot detect it as promised. Radiological imaging does not seem to exhibit consistent relevant differences between MS sufferers and healthy patients, and Zamboni’s original criteria for a CCSVI diagnosis are hardly even coherent or well-specified enough for practical use.

The April issue of the Journal of Vascular and Interventional Radiology, for example, contains a report of a Texas study of 276 MS patients and 70 healthy controls: ultrasounds of their necks produced “findings consistent with CCSVI” in four per cent of the MS group—and in seven per cent of the non-MS group. Examples of results like this could be compounded ad nauseam: the Texas paper is not even the only negative CCSVI-Zamboni result in that issue of that journal.

What went wrong? For those seeking an answer, I would recommend a paper open-published in late February by the Journal of Cerebral Blood Flow & Metabolism. Conveniently, its title is: “What went wrong? The flawed concept of cerebrospinal venous insufficiency.” This paper is important because the doctors who wrote it are among the leaders in using ultrasound and other means to study normal venous blood flow. Zamboni depended on their research for background when he was trying to devise diagnostic criteria for CCSVI. If CCSVI were real, they might be expected to be the first to applaud.

They’re not applauding. The authors go point by point through Zamboni’s proposed criteria, showing how he repeatedly misinterpreted earlier literature on vein behaviour and confused abnormal blood flow events with harmless typical ones. They emphasize the basic implausibility of Zamboni’s theory and show that it conflicts with non-Zambonian findings on MS and venous drainage. And they criticize the “open-label” nature of early CCSVI studies and patient registries assembled on the fly for political reasons. The best-designed of these, the authors note, was probably one paid for by the government of Newfoundland; a brusque June 2012 press release announced no evidence of objective benefit, but no peer-reviewed publication of the results has followed.

The “What went wrong?” paper concludes unequivocally that “only a complete halt to [liberation] therapy seems sensible.” The story of CCSVI will not be over until the last frustrated Canadian pays the last Bulgarian or Bengali doctor to be “liberated” for the last time; but from a scientific standpoint, the proverbial fat lady is about halfway between the main performance and the encore. On web forums for MS patients, liberation therapy is already receding into the shadow world of I’ll-try-anything curatives, there to linger with cobra venom and upper-cervical chiropractic.

It would be nice to be able to ladle out guilt for this ignoble episode in medical history, but it is not clear that even Zamboni, whose wife has MS, did anything consciously wrong. On the other hand, the doctor is not likely to miss any meals because he messed up. A Canadian MS patient who forked over for repeated unnecessary angioplasties might.

For more Colby Cosh, visit his blog at macleans.ca/colbycosh