Multiple Sclerosis: Could This Be The Cure?

The HWN Team | Cutting Edge
Multiple Sclerosis: Could This Be The Cure?

image by: BruceBlaus

Currently, there is no cure for MS. However 'the Zamboni' a new theory and possible treatment challenges the established concept of MS being an autoimmune disease

MS is a chronic disease characterized by pain and disability. It is more common in women than in men and in Caucasians of northern European ancestry than in other ethnic groups. There is no known cure, but could there be one on the horizon?

MS usually affects people between 20 and 50 years old but it has been reported in children as young as two. Lately, there are reports of increasing incidence of pediatric MS.1 There may be some genetic factors involved but MS in not directly inherited.

The National MS Society gives the following figures:2

  • MS affects 2.1 million people worldwide
  • In the U.S. 400,000 people have MS
  • Life expectancy among MS patients is reduced by 10 to 15 years.

The most common symptoms of MS are vision problems, muscle weakness, numbness and loss of balance and coordination. In extreme cases, hearing loss, speech impediment, paralysis and cognitive impairment may also manifest. This debilitating disease affects the organs of central nervous system (CNS) that include the spinal cord, the brain and the optic nerves.3

MS is widely believed to be an autoimmune disorder, mainly for lack of a better cause. Myelin, the fatty sheath that serves as cover and insulation of the nerve cells becomes inflammed. As the disease progresses, myelin degradation forms scar tissue called sclerosis or lesions which causes disruption in nerve conductivity. Eventually, even the nerves under the myelin sheath  are damaged, causing further disruption in the impulses travelling between the brain and the spinal cord.

There are four stages of MS namely:

Relapsing-Remitting MS
This course of MS by attacks, flare ups or relapses with partial or complete recovery periods (remissions) in between. This accounts for 85% of initial MS diagnoses.

Primary-Progressive MS
This MS course is characterized by gradual progression without any distinct relapses or remission periods. This accounts for 10% of all initial MS diagnoses.

Secondary-Progressive MS
The relapsing-remitting MS may progress into this course wherein the flare ups and recoveries become less distinct. About 50% of those initially diagnosed with the first course of MS will eventually develop the secondary progressive type within 10 years.

Progressive-Relapsing MS
This is the rarest of all MS courses, characterized by steady progression but with distinct attacks and without without remission periods. This accounts for about 5% of all MS cases.4

The McDonald diagnostic criteria for MS (2005) is the recognized criteria for diagnosing MS. There must be objective evidence of two separate CNS lesions compatible with MS, separated both in space and time of occurrence and other potential causes for the CNS lesions must have been ruled out or excluded before one can be labeled with MS.5

MS remains a very difficult disease to diagnose for the following reasons

The majority of MS cases are the relapsing-remitting type, e.g. the symptoms may come and go. Up to now, no single lab test can give a positive-negative answer for MS. Early symptoms are difficult to interpret and may be similar to other more common diseases.

Magnetic resonance imaging (MRI) is currently the gold standard in detecting MS even when clinical and laboratory findings are not conclusive. MRI is especially effective in detecting small structural changes in the spinal cord and the brain.

Parallel to imaging techniques, the search for biomarkers for multiple sclerosis has also made progress. The most promising source of biomarkers for MS is the cerebrospinal fluid (CSF). Certain proteins and metabolites can be isolated from CSF and concentrations of these proteins tend to differ between people with MS and without MS. Thus proteins can potentially be used as markers of presence and stage of MS. Currently, although there many candidate substances, the ideal biomarker for MS remains elusive.6

Similarly the treatment for MS continues to remain just as difficult as making the diagnosis.

Over the years, drugs have been developed and approved that slow down the progression and minimize the severity of MS attacks..Unfortunately, many of these MS drugs are associated with a lot of side effects, some of them serious.

And, the benefits of treatment greatly depend on the disease course and the stage when detected. Recent research evidence strongly supports this. In one study, researchers observed that poor management of the first two attacks in patients with relapsing-remitting MS can lead to poor outcome 5 years later.7 Canadian researchers report that diagnostic delays in MS patients were associated with referral delays which in turn are associated with higher degree of disability at the first clinic visit.8

However, in 2009 a new theory and possible treatment for MS was put forward by an Italian doctor that challenged the conventional thinking of MS as an autoimmune disease.

Besides causing media frenzy, the 'Zamboni' procedure raised patients’ hopes, and sent both the support and research organizations, to put it mildly, into a state of panic.

In 1995, 37-year old Elena, wife of Paolo Zamboni, was diagnosed with MS.9 The vascular surgeon and professor of medicine at the University of Ferrara in Italy started an intensive research on the disease to help his wife. At that time, the current medical evidence couldn’t give him answers so he started looking into the past. Some of the old medical literature he found referred to a theory that MS symptoms were brought about by accumulation of iron that causes inflammation and block blood vessels in the brain.

With further research of his own using state-of-the-art imaging techniques, Zamboni arrived at his theory that MS is not an autoimmune disease but a vascular disease.10 According to Zamboni’s observations, in 90% of people diagnosed with MS, abnormalities were observed in the veins draining the blood away from the brain, abnormalities which are not present in people without MS. The vessels are either blocked or malformed, making the draining of the blood inefficient. 

This is the basis of his rather controversial but novel and ground-breaking theory. He hypothesized that iron build up is damaging the blood vessels, allowing cells in the blood to cross the brain-blood barrier to damage the myelin. From this premise, Zamboni went one step further and performed a simple procedure on his wife to unclog the veins and restore normal blood flow from the brain. That was 3 years ago and she hasn’t had an attack since then.

When Zamboni published his theory in 2006, it was met with a lot of skepticism. He compared his vascular problem theory with iron-dependent inflammation in the lower legs when the venous drainage in the lower extremities is obstructed. In his ground breaking paper, he cited similarities and parallels in the pathophysiology of MS and chronic venous disease.  In his early research, Zamboni documented during a duplex scanning examination on the carotid arteries of a patient “an unexpected reflux from the chest into the internal jugular vein after the patient coughed involuntarily", a phenomenon observed in other MS patients.

Zamboni and colleagues assessed 58 patients with relapsing-remitting MS and compared them to 60 healthy controls without MS.11 The study participants underwent transcranial color-coded duplex sonography (TCCS) to assess the blood flow dynamics in and out of the brain. The results showed that reflux or bidirectional flow occurred more commonly in MS patients compared to controls. The severity of backflow towards the subcortical grey matter of the brain closely corresponded to the severity of the MS symptoms as indicated by disability scores.

Zamboni and his colleagues concluded that “Our study of MS patients demonstrated significant haemodynamic alterations detected in veins anatomically related to plaque disposition. Our findings should contribute towards understanding the role of altered venous flow and tissue drainage in the MS inflammatory chain, as well as in the neurodegenerative process.”  

Over the years, Zamboni and his colleagues continued to conduct research on the blood flow dynamics of the brain in MS patients and even produced a list of reproducible clinical parameters using Doppler sonography techniques that can help in the early diagnosis of MS.12,13

Zamboni's theory is now popularly known as Chronic Cerebrospinal Venous Insufficiency (CCSVI)

The treatment of CCSVI in MS patients is quite simple and is similar to catheterization angioplasty. Zamboni personally refers to it as the "liberation theory" because it "liberated" his wife from MS. A catheter is inserted in blood vessels in the leg and pushed up to the neck and brain. A balloon is then inflated to clear the blockage and restore normal blood flow. Basically the procedure can be done in an outpatient clinic and lasts for just about an hour. 

In 2009, Zamboni and colleagues reported the results of a pilot study of MS patients with CCSVI using the above-described treatment procedure.14 Six-five patients clinically diagnosed with MS underwent surgery to clear blocked vessels. 35 of the patients had relapsing-remitting MS, 20 had secondary progressive MS, and 10 had primary progressive MS. Among the patients, blockages were identified in the internal jugular veins and the azygous vein.

Positive clinical outcomes were most evident in the relapsing-remitting patients with a relapse-free rate of 50%. Physical and mental outcomes also significantly improved in most of the patients even up to 3 years after surgery. More trials of the procedure are being planned.

As one would expect, the medical establishment remains cautious, even openly skeptical about Zamboni's theory and treatment procedure.

The National MS Society is quite vocal about discouraging patients from having the procedure until further tests have been done. Some people branded it at as the “occult art of CCSVI. Others dismiss the positive clinical outcomes as placebo effect”.15,16

The Multiple Sclerosis Society of Canada (MSS) was quoted to say cautiously “Many questions remain about how and when this phenomenon might play a role in nervous system damage seen in MS, and at the present time there is insufficient evidence to suggest that this phenomenon is the cause of MS.” According to Dr. Paul O'Connor, a neurologist at Toronto's St. Michael's Hospital  "There is not a shred of real evidence anywhere that messing around with these veins does anything to help MS patients. If there is no treatment for this condition, there is no need to detect it"

There are also experts, though, who are more open-minded and willing to give Zamboni and his CCSVI the benefit of doubt.

According to Bianca Weinstock-Guttman, an associate professor of neurology at the State University of New York at Buffalo “If this is proven correct, it will be a very, very big discovery because we'll completely change the way we think about MS, and how we'll treat it”

Mark Haacke, world-renowned imaging expert and an adjunct professor at McMaster University in Hamilton, is urging patients to send him MRI scans of their heads and necks in order to further check out the Zamboni theory. Haacke says. “Patients need to speak up and say they want something like this investigated … to see if there's credence to the theory." 

Yves Savoie, President & CEO, of MSS Canada issued the following statement: “These early results are encouraging and show that this warrants more study. This is truly a new avenue to explore in MS research, and we want to be a part of furthering this investigation.” In fact, MSS of Canada held a web streaming event on CCSVI on Wednesday, April 7, 2010, 1 to 3 pm ET. The speakers include Yves Savoie, President & CEO, of the Society, Dr. Jock Murray, Founding Director Dalhousie MS Clinic, and Karen Torrie-Racine, an MS patient.

Research institutes are also scrambling to test Zamboni’s hypothesis. Researchers at Buffalo Neuroimaging Analysis Center led by Robert Zivadinov conducted ultrasound checks of 280 people with MS, 161 healthy people, and 60 with other neurological conditions.

The researchers reported that 62.2% of MS patients exhibited the vein problem described by Zamboni. When borderline cases were excluded, the positive findings went down to 56%. 25% of healthy people have similar anomalies. Zivadinov also observed that the vein anomaly is more common and pronounced in people with advanced MS. The results of the study as such are not exclusive enough to prove the CCSVI theory, according to Zivadinov.

So, is there an evolving consensus? Some doctors, who have been under pressure from their patients think that while the hypothesis is being tested, patients could nevertheless be screened for CCSVI and treated.17 Others, however, believe this is not feasible, not to mention unethical. The testing will cost a lot of money and the procedure can lead to complications.

The ethical issue, as usual, is a double-edged sword: Is it ethical to perform an unproven procedure on a patient? Is it ethical to withhold a patient a treatment that can potentially relieve pain and disability? The answers to these patients are blurry gray in a yes-no spectrum.

The Bottom Line

The liberation treatment or CCSVI is now on the table with research and clinical studies underway to prove or disapprove the 'Zamboni'. Ultimately this could be the elusive cure for some MS patients. It's worth considering.

Published March 29, 2010, updated July 24, 2012


References

  1. Venkateswaran S et al, Pediatric multiple sclerosis, Neurologist. 2010 Mar;16(2):92-105
  2. Just the Facts 2008-2009, General Information on MS, The National MS Society
  3. Joy JE and Johnston RB (Eds) Multiple Sclerosis: Current Status and Strategies for the Future, National Academies Press 2001
  4. The Four Courses of MS, The National MS Society
  5. Hurwitz BJ, The diagnosis of multiple sclerosis and the clinical subtypes, Ann Indian Acad Neurol. 2009 Oct;12(4):226-30
  6. Ottervald J et al, Multiple sclerosis: Identification and clinical evaluation of novel CSF biomarkers, J Proteomics, 2010 Jan 20 [Epub ahead of print]
  7. Scott TF et al, Poor recovery after the first two attacks of multiple sclerosis is associated with poor outcome five years later, J Neurol Sci. 2010 Mar 3 [Epub ahead of print]
  8. Kingwell E et al, Factors associated with delay to medical recognition in two Canadian multiple sclerosis cohorts, J Neurol Sci. 2010 Mar 2 [Epub ahead of print]
  9. Picard A et al, Researcher's labour of love leads to MS breakthrough, The Globe and Mail 20 Nov 2009
  10. Zamboni P, The Big Idea: Iron-dependent inflammation in venous disease and proposed parallels in multiple sclerosis, J R Soc Med. 2006 November; 99(11): 589–593
  11. Zamboni P, Menegatti E, Bartolomei I et al, Intracranial venous haemodynamics in multiple sclerosis, Curr Neurovasc Res. 2007 Nov;4(4):252-8
  12. Zamboni P, Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis, J Neurol Neurosurg Psychiatry. 2009 Apr;80(4):392-9. Epub 2008 Dec 5
  13. Menegatti E, Zamboni P, Doppler haemodynamics of cerebral venous return, Curr Neurovasc Res. 2008 Nov;5(4):260-5
  14. Zamboni P, A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency, J Vasc Surg. 2009 Dec;50(6):1348-58.e1-3
  15. Rose C, Zamboni and the Occult Art of CCSVI, Panaceia or Hygeia February 10, 2010
  16. Blackwell T, Is new MS research the real thing or a media-driven frenzy, National Post, January 23, 2010
  17. Chronic Cerebrospinal Venous Insufficiency (CCSVI) Research, The Buffalo Neuroimaging Analysis Center

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