The origins of multiple sclerosis (MS) have long remained elusive and older theories, including that of autoimmunity, have been widely questioned. In recent years, researchers have consistently demonstrated that the immune changes in MS developed after the presence of brain lesions. In addition, in first describing MS, Marie Charcot noted vascular changes in the brain that she couldn’t explain. Other scientists have made similar observations.
Viral infections, particularly Epstein-Barr virus and cytomegalovirus have been implicated as potential immune triggers. Other suspected causes included industrial chemicals and toxins, low vitamin D levels, and brain injuries.
Dr. Zamboni’s Work
Dr. Paolo Zamboni is a professor of vascular medicine at the University of Ferrara as well as the Director of their Vascular Center. When his wife was diagnosed with MS in 1995 he began to rigorously study this disorder. Poring over brain imaging studies, he too noted vascular changes. With his expertise, he realized that the changes he was seeing in the cerebrosinal vasculature of MS patients paralleled the changes observed in the legs of patients with peripheral artery disease.
Dr. Zamboni concluded that in MS the veins that drain the brain and spinal cord are blocked or damaged. Consequently, surrounding tissue is damaged. Dr. Zamboni calls the disease process in MS one of chronic cerebrospinal venous insufficiency (CCSVI).
Vascular Changes in MS
Specifically, Dr. Zamboni noted that the lesions seen in MS all occur adjacent to veins and expand in the direction opposite normal blood flow. This suggested that there was venous involvement and that a countercurrent, chaotic blood flow was likely eliciting damage similar to that seen in his chronic vascular disease (CVD) research.
Vascular Disease
In vascular disease, veins become stretched or varicose. This occurs because veins have very thin weak walls with little muscle supporting them. Veins can be compared as strings relative to the thick ropy arteries. When blood becomes backed up in veins, veins need to expand and widen.
This, in turn, affects valves. The valve flaps become so far apart that they don’t function properly. This impairs venous return. The blood has nothing to hold it back so it slips back down the vein through the poorly functioning valves.
The resulting congestion causes a backup of fluid. The fluid migrates through the vein wall and out into the tissue. In peripheral artery disease affecting the legs, this is seen as a swollen, edematous ankle. Wherever it occurs, if this disease process persists, fluid from the circulation migrates out leaking red blood cells as well.
Iron deposits resulting from red blood cell protein (hemoglobin) accumulations trigger an immune response. Excess iron deposits and the presence of iron pigment (hemosiderin) granules are the hallmark of chronic vascular disease (CVD). Hemosiderin is present in the brain lesions of MS.
Immune Response
The immune system changes, such as an influx of cytokines, are characteristic of both chronic vascular disease and MS. The tissue changes seen in biopsies of lesions collected by Dr. Zamboni support these findings.
The immune process that occurs in response to these lesions is a true immunological defect but lacks the characteristic changes that occur in autoimmune diseases. For instance, serum from patients with MS will not cause MS in other species.
Surgical Success
Dr. Zamboni has placed stents, to widen the jugular veins affected by stenosis in the brains of patients with MS. The results have been impressive and it is thought that this surgery will halt the disease process. To date, patients who have surgery in Italy and at Stanford University have shown good improvement.
However, the surgical program implemented by Dr. Dake at Stanford University has been halted until sufficient evidence from clinical trials is available. Studies to date have supported Dr. Zamboni’s findings, and the results of a large study being conducted in Buffalo, New York will be available in February 2010.
What This Means
Although MS has been a disease primarily treated by neurologists and by a number of medications used to slow the inflammatory process, a consultation with a vascular specialist may be the next step in the history of treatment for MS. Drugs like low dose naltrexone (LDN) still play an important role in restoring homeostasis and enhancing the healing process. And until Dr. Zamboni’s surgical results have been confirmed by clinical trials, MS patients must wait for the next chapter in this story.
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