Studies Show that “Liberation Therapy” for Multiple Sclerosis Doesn’t Work


Stephen Barrett, M.D.
May 2, 2018

In 2006, Paolo Zamboni, an Italian surgeon, proposed that the real cause of MS is something he called chronic cerebrospinal venous insufficiency (CCSVI) and claimed that blocked veins partially reverse blood flow from the brain, creating an iron overload that damages the brain. In 2009, Zamboni reported finding CCSVI in 100% of 65 MS patients and developed a procedure—venous percutaneous angioplasty (venous PTA)—in which veins in the neck or chest are widened by inflating a balloon within them or (rarely) inserting a stent [1]. The procedure soon became known as “liberation therapy.” Some proponents refer to it as Transvascular Autonomic Modulation (TVAM).

The scientific community was skeptical about Zamboni’s 2009 findings because decades of research and thousands of studies suggest that MS is an autoimmune disease. Moreover, Zamboni’s study had two major flaws. There was no control group, and the people who judged whether CCSVI was present knew whether or not the patients had MS. Nevertheless, Zamboni’s theories captured the attention of MS patients, clinics began offering the procedure, and anecdotal success stories were spread widely through the Internet. In 2012, The New York Times reported that 20,000 people worldwide had undergone angioplasty in their main neck veins [2].

Since 2009, hundreds of studies have explored various aspects of Zamboni’s claims. The correlation between CCSVI and MS was studied, using various imaging techniques and comparing MS patients to patients with other neurological diseases and to healthy subjects. In the end, no correlation was found between between CCSVI and MS. Researchers also studied the procodures used to open up the blocked veins. Four large studies now appear to have settled the issue:

  • In 2014, researchers who tested whether venous narrowing is a cause of multiple sclerosis reported no association between MS and narrowed veins. The study entailed 177 adults: 79 with multiple sclerosis, 55 siblings, and 43 unrelated controls, from three centers in Canada who underwent measurements with catheter venography and/or ultrasound testing to look for CCSVI as proposed by Zamboni. The study found that in all three groups, venous narrowing was equally common but insufficiency was rare [3]. In 2017, the Canadian research team reported the same conclusions in a similar study that used magnetic resonance imaging (MRIs) to study the veins [4].
  • In 2017, Canadian researchers reported that the results of a study that involved 104 MS patients. All had a catheter inserted into their blocked veins, but only 49 had their vessel walls pushed out by inflating a small balloon. A year later, the venoplasty group’s results were statistically the same as those in the sham group, as measured by brain imaging, standard assessments of MS symptoms, and the patients’ own self-assessments [5].
  • In 2017, Zamboni and twelve others reported what happened in a well-designed, randomized, controlled study that included 115 patients with relapsing-remitting MS who underwent either a venous PTA or a sham procedure at one of six centers. To maintain blinding, the treatment assignment was made known to the treating surgeon only on the day of the operation, but the patients, all other study investigators, and operating room and hospital personnel were blinded to assignment. The study found that the patients who underwent venous PTA did no better than those who underwent the sham procedure, the authors recommended against further use of CCSVI to treat MS patients [6].

In response to Zamboni’s 2017 report, neurologist Steven Novella called upon him to work actively to limit the harm caused by his promotional activities:

For now I give Zamboni credit for conducting a well-designed study, and for not spinning the results in his publication. He can fully redeem himself and even become a hero if he now campaigns against the monster he created, in the name of science and what’s best for patients. CCSVI is now a famous cautionary tale—what legacy in that tale will Zamboni ultimately make for himself?

The monster he created was substantial. His preliminary research, which should never have seen the light of day outside of wonky research journals for other experts, became a public sensation. News of a possible new treatment for MS spread throughout the MS community, with the usual exaggerations and anecdotes. The result was not pretty. Desperate patients understandably wanted access to a potential new treatment, and were largely unhappy when experts told them the treatment was not recommended. This led to conspiracy theories and general distrust between some patients and their MS doctors.

Of course all this was happening on the background of a general cultural movement in which expertise is easily dismissed, and trust of experts is threatened by memes spread on social media. It is hard to calculate the harm that was ultimately done to patients because of all this.

We know that several patients died receiving the liberation procedure—so there was some direct measurable harm. But how many other patients had suboptimal treatment for their MS because of their faith in a highly implausible new theory that was crashing almost as soon as it was published? How much money was funneled to quack clinics, and all the ultimate harm that they do, by patients seeking out the liberation procedure? [7]

Regulatory Actions

In 2012, the U.S. Food and Drug Administration warned that the Zamboni procedure was unproven and was associated with reports of death; stroke; detachment and migration of stents; damage to the treated vein; blood clots; cranial nerve damage; and abdominal bleeding [8]. In 2017, the FDA warned against the use of TVAM to treat Parkinson’s disease, fibromyalgia, multiple system atrophy, postural tachycardia syndrome (POTS), peripheral neuropathies, primary dysautonomia, and familial dysautonomia in addition to multiple sclerosis [9].

The public warnings paralleled FDA actions intended to curb the activities of Michael Arata, M.D., who operates Synergy Health Concepts in Newport Beach, California. Synergy’s Web site describes Arata as “the most experienced CCSVI physician in the United States, having performed over 1500 procedures.” [10] In 2012, the FDA notified Synergy and Arata that their CCSVI research did not comply with federal regulations. In 2016 and 2017, the FDA noted that he was still out of compliance and that proceedings are under way to disqualify Arata as an investigator [11,12].

James McGuckin, Jr., M.D. who specialized in vascular and interventional radiology, has also been targeted by regulators. McGuckin, who specialized in vascular and interventional radiology, founded and is Chief Executive Officer of Vascular Access Centers, which has facilities in several states. In 2013, the FDA notified him that activities related to stenting procedures did not comply with applicable federal research regulations [13]. In 2014, the Washington Medical Quality Assurance Commission
charged him with unprofessional conduct related to his management of seven patients. The complaint alleged:

  • Between 2010 and 2013, McGuckin diagnosed patients with CSVI and performed balloon angioplasties or inserted stents that he claimed would clear the blockage and improve their multiple sclerosis (MS).
  • In 2011, McGuckin created an unreasonable risk of harm to seven patients by performing these procedures without evidence that they had a vascular disease. He also failed to meet the standard of care in performing an experimental treatment on MS patients without adhering to a proper Institutional Review Board protocol, failed to obtain an approved FDA Investigational Device Exemption, and misrepresented his findings in patient chart notes.
  • His documentation contained multiple discrepancies, improper patient assessments, and inaccurate procedure notes [14].

In 2015, McGuckin signed a consent order in which he agreed to (a) stop performing angioplasty or stenting for CCSVI or MS patients in the State of Washington, (b) pay a $17,500 fine, (c) issue refunds to certain patients, (d) successfully complete an ethics course, and (e) comply with monitoring provisions set by the Commission [15]. The Washington action triggered similar restrictions by licensing boards in Florida, Georgia, Illinois, Indiana, Louisiana, Maine, Maryland, New York, North Carolina, Texas, Tennessee, and Virginia. McGuckin’s Washington medical license expired in November 2015 and was not renewed, but he remains licensed in the other states.

A lengthy investigative report published by the Milwaukee Journal Sentinel has concluded that about 30 doctors have performed unproven procedures for CCSVI but state licensing boards have given insufficient attention to this problem [16].

References

  1. Zamboni P and others. A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency. Journal of Vascular Surgery 50:1348-1358, 2009.
  2. Tullis P. Controversial ‘cure’ for M.S. The New York Times, Oct 6, 2012.
  3. Traboulsee AL and others. Prevalence of extracranial venous narrowing on catheter venography in people with multiple sclerosis, their siblings, and unrelated healthy controls: a blinded, case-control study. The Lancet 383:138-145, 2014.
  4. Martin N and others. Prevalence of extracranial venous narrowing on magnetic resonance venography is similar in people with multiple sclerosis, their siblings, and unrelated healthy controls: a blinded, case-control study. Canadian Association of Radiology Journal 68:202-209, 2017.
  5. Amos H. Controversial “liberation therapy” fails to treat multiple sclerosis: study. University of British Columbia News, March 8, 2017.
  6. Zamboni P and others. Efficacy and safety of extracranial vein angioplasty in multiple sclerosis: A randomized clinical trial. JAMA Neurology, Nov 18, 2017.
  7. Novella S. Liberation procedure for multiple sclerosis: The final chapter. Neurologica Blog, Dec 1, 2017.
  8. Chronic cerebrospinal venous insufficiency treatment in multiple sclerosis patients. FDA safety alert, May 12, 2012.
  9. FDA concern over experimental procedures that use balloon angioplasty devices to treat autonomic dysfunction: FDA safety communication, March 8, 2017.
  10. Michael A. Arata, M.D. Synergy Health Concepts Web site, accessed May 2, 2018.
  11. Newman RW. Notice of initiation of disqualification proceedings. Sept 13, 2016.
  12. Plaisier MK. Follow-up letter offering a regulatory hearing. June 21, 2017.
  13. Silverman SD. Letter to James F. McGuckin, Jr., M.D., April 11, 2013.
  14. Statement of charges. In the matter of the license to practice as a physician and surgeon of James F. McGuckin, MD. State of Washington Medical Quality Assurance Commission, Case No. M2013-185, Nov 25, 2014.
  15. Stipulated findings of fact, conclusions of law, and agreed order. In the matter of the license to practice as a physician and surgeon of James F. McGuckin, MD. State of Washington Medical Quality Assurance Commission, Case No. M2013-185, Oct 1, 2015.
  16. Farber J and others. From hope to medical nightmare: Despite FDA warnings, state boards lag in taking action on controversial MS treatment. Milwaukee Journal Sentinel, March 25, 2018.

This article was posted on May 2, 2018