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Friday, June 19, 2015

Think of Multiple Sclerosis as a Leaking Swimming Pool [Video]

A new way of looking at the neurodegenerative disorder could lead to more and better treatments

For 20 years neurologists have divided the neurological disorder multiple sclerosis (MS) into four distinct categories—subtypes that are supposed, in part, to help patients get the right treatments. But a new theory erases the distinctions between these groups and suggests that MS is a single disease after all. The idea was developed by Stephen Krieger, a neurologist at Icahn School of Medicine at Mount Sinai in New York City, and presented in late April at the American Academy of Neurology (AAN) annual meeting in Washington, D.C. If the theory holds up, it could lead to more effective management for a wider range of patients.

brain scan chart

MS lesions do not always cause observable symptoms, even if these neurological scars are detectable on a brain scan
Credit: Courtesy of Stephen Krieger

In MS the body produces antibodies that attack the central nervous system, i.e. the brain and spinal cord. Specifically these antibodies ravage myelin, a fatty substance that insulates neurons, allowing them to conduct electricity. The nerves develop scars or sclerotic lesions (sclerosis is Greek for hard) in the aftermath of such attacks. As a result, patients can suffer from weakness, pain and walking difficulties—not to mention vision loss and a host of undesirable bowel, bladder and psychiatric ills.
The current classification system arose as a way to describe the various ways MS symptoms tend to unfold. The most common type of MS is called relapsing-remitting disease; patients experience flare-ups—in which, for example, they suddenly lose vision in one eye—followed by periods of neurologic normalcy. Presumably their immune system has gone into overdrive when the flare-ups occur and then the activity subsides for months or even years.
Less common are primary and secondary progressive MS. In the former, symptoms progress from the get-go and never remit; in the latter, patients first experience relapses and remissions but then progress to continuously worsening symptoms. Finally there’s progressive-relapsing MS in which patients experience continuously progressive disease on top of which more severe exacerbations occur. Krieger’s hypothesis is a metaphoric reunion of these four otherwise separate divisions of disease—one that can perhaps best be explained by analogy with a swimming pool in need of repair.
Imagine a pool with mountains rising up from the bottom. The mountains represent scars in the central nervous system; the water surface is the threshold at which symptoms appear. Lesions below the water line do not cause symptoms whereas those jutting out of the water do.
The water surface can also be seen as the body's neurologic reserve capacity. Our brains are astoundingly resilient: If one part of the brain is injured, neighboring neurons can step in and take over. But according to Krieger, as we age and as MS progresses, not only does the scarring worsen (that is, the mountains grow higher), the brain also loses its ability to compensate for injured tissue—meaning water starts draining out of the pool and more lesions and resulting symptoms become apparent.
Krieger calls his view of MS the topographical model (referring to the mountains jutting out of the water). He believes his concept unites the MS categories and demonstrates the relationship between relapsing and progressive disease. Relapsing-remitting patients have mountains that temporarily rise above the waterline but then sink again. In those with the other three forms of MS—the more consistently progressive forms—the mountains emerge above the surface but never recede and the symptoms never go away.
If Krieger’s hypothesis is correct, the four MS divisions could be reenvisioned as different stages or different expressions of the same disease. It’s not that the disease completely goes away during ‘remission,’ Krieger explains. "We can see old lesions there on MRI the whole time." But the brain’s ability to compensate for the effects of the lesions declines.
In other words, after the immune system’s assault has waned and a patient with relapsing-remitting disease is symptom-free, some of the neurons are nonetheless still scarred. The nervous system, however, is somehow able to compensate—until one day it cannot and the disease is considered progressive. This could explain why many patients look and feel better than their brain scans would suggest; and also why some patients, in Krieger’s words, catch up to their MRI."
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