Multiple Sclerosis – Overview

It all starts with some neurological symptom(s). Whether it is loss of vision, numbness, double vision, or weakness, the symptoms are likely to fade away after a few weeks or a few months. This event is called a clinically isolated syndrome.

So, what is next? The answer is “Who knows!” Based on the range of statistical variables described elsewhere, there is a significant chance of recurrence. Appearance of some new neurological symptoms means that clinically isolated syndrome has converted into multiple sclerosis.

At the stage of the clinically isolated syndrome it is not possible to know what the future holds. The future disease course might be very aggressive with frequent relapses and rapid accumulation of disability, or the relapses might be occasional and mild, if any. Each new relapse leaves its own imprint on the brain or the spinal cord tissues. The recovery after relapses might be relatively complete or incomplete. Even in cases of clinically complete recovery, most of the time, the lesions on the brain MRI will remain very well noticeable for years. Basically, there is a gradual accumulation of the lesion load over time, which translates into the accumulation of disability. The most troubling form of disability is a problem with ambulation.

Modern “disease modifying treatment” strategies are aimed at the relapse rate reduction. The rational is that fewer relapses will eventually translate into less disability accumulation over time. Unfortunately, it is not so simple.

In order to understand it better, I will compare MS with multiple strokes. Any person, who has multiple strokes, loses some brain function with each subsequent one. Multiple stroke victims also accumulate some disability over time. MRI detectable lesions in MS might look small compared to the stroke related ones but they cause much more disability. There is a good reason for the discrepancy.
One of the MS features is fatigue. This fatigue is not much like a physical tiredness but rather a sense of general exhaustion. Some MS sufferers name fatigue as the major reason for the poor quality of life. Stroke sufferers don’t experience anything alike! Why is that?

Unlike strokes that destroy only some limited portion of the brain, multiple sclerosis is a whole brain disease.

A conventional MRI simply does not show everything that is going wrong in the brains of MS patients. Besides classical MS plaques MRI may only show some generalized nonspecific brain atrophy.
More sophisticated fMRI of the brain will reveal abnormalities that are well beyond the MS specific lesions. Multiple sclerosis is not a local problem. It is a wide-spread brain and spinal cord disease involving both, white and gray matter. It is time to talk about the “degeneration stage” of MS.

At some point of the disease course relapsing remitting MS may convert into a progressive form of MS, which is not associated with relapses. There is a gradual, rather than a stepwise progression of disability. Whether this scenario develops after a relapsing remitting course, or it starts as progressive form at the onset of the disease, does not matter much.

The point is that this type of disease progression has a totally different mechanism from relapsing-remitting form. MRI at this stage shows only mild and faint new MRI lesions, which often lack classical features of the new active MS plaques. Immune modulating and immune suppressive treatments do nothing for progressive form of MS. Why?
It is, probably, because autoimmune mechanisms play a minimal role at this stage of MS. Moreover, generalized brain atrophy is seen on the MRI in relapsing remitting form.
It means that chronic whole brain involvement starts much sooner in the disease course than it becomes clinically evident.

Details of the MS disease modifying strategies are described separately. Here I will only mention the major hurdles of MS treatment.

Considering lack of any effective treatment during the stage of “neurodegeneration”, it is logical to assume that all aggressive MS treatment has to be done before the “flame of active disease” is burned down.

Again, it is not so easy! The disease modifying treatment in multiple sclerosis is everything but benign. Drugs have their own side effects, sometimes serious. Withdrawal of some medications due to side effects may cause severe fulminant progression of MS. Even the most aggressive treatment does not guarantee lack of relapses.

In mild forms of MS the disease itself may be less disabling than the treatment side effects. Even the oldest and the safest medications, such as Copaxone and interferons, require regular frequent injections and, yet, they are associated with only 30% reduction of relapse rate!

There is no proof that any of the disease modifying agents is able to prevent or delay disability in the long run. It is not known if relapse preventive management is also able to prevent or delay chronic degenerative changes in the brain. Most of the disease modifying agents have been introduced into MS management relatively recently. Sufficient scientific data about their long term effects has not been accumulated yet.

In conclusion, diagnostic criteria of MS are very well established, while treatment of  multiple sclerosis is a “Wild West” at this point. There are 19 medications for MS treatment on the market as of 2016. They do prevent relapses but their long term hazard to benefit ratio and the ability to prevent MS related disability remain largely unknown.