Multiple Sclerosis: Could This Be The Cure?

Multiple sclerosis (MS) is a chronic disease characterized by pain and disability. 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 that include the spinal cord, the brain and the optic nerves. MS usually affects people between 20 and 50 years old but it has been reported in children as young as two. There may be some genetic factors involved but MS in not directly inherited. It is more common in women than in men and in Caucasians of northern European ancestry than in other ethnic groups.

MS is widely believed to be an autoimmune disorder, when the body attacks the myelin, the fatty sheath that serves as cover and insulation of the nerve cells. It is not clear how immune cells, which are found in the blood cross the so-called brain-blood barrier to attack the myelin. As the disease progresses, myelin degradation also progresses and scar tissue called sclerosis or lesions are formed. Damage to the myelin, which is the main insulator of the nerve fibers causes disruption in the conductivity of the nerves. Eventually, the nerves under the myelin sheath also get damaged, causing further disruption in the impulses travelling between the brain and the spinal cord.

Like most diseases, early detection of MS is important in its management. 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.

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.

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 side effects, some of them serious. And, treatment greatly depends on the disease course and the stage when detected.

There is no known cure, but could there be one on the horizon? Last year, a new theory and possible treatment for MS was put forward by an Italian doctor that can change the established concept of MS being an autoimmune disease. In 1995, 37-year old Elena, wife of Paolo Zamboni, was diagnosed with MS. 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. 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.

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. 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. 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. 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. 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."

Over the years, Zamboni and his colleagues continued to conduct research on the blood flow dynamics of the brain in MS patients. Zamboni's theory is now popularly known as Chronic Cerebrospinal Venous Insufficiency (CCSVI), although he personally refers to it as the "liberation theory" because it "liberated" his wife.

The treatment of CCSVI in MS patients is quite simple and is similar to angioplasty where 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.

In 2009, Zamboni and colleagues reported the results of a pilot study of MS patients with CCSVI. 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 are being planned.

The medical establishment remains cautious, even openly skeptical about Zamboni's theory and treatment procedure. They also warn that the media hype is raising patients' hopes before the procedure can be thoroughly tested.

The National MS Society is quite vocal about discouraging patients from having the procedure until further tests have been done. Others dismiss the positive clinical outcomes as "placebo effect." The Multiple Sclerosis Society of Canada (MSS) stated "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 in Toronto' "There is not a shred of real evidence anywhere that messing around with these veins does anything to help MS patients.

There are also experts, however, who are more open-minded and are willing to give Zamboni and his CCSVI the benefit of doubt and a chance to prove themselves. 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. 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."

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. Other tests and studies are being planned.

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. 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?

Nevertheless, CCSVI is now on the table. Ultimately this could be the cure for some if not the majority of MS patients. It's worth pursuing.


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