Multiple Sclerosis

Multiple sclerosis (MS) can be a horrible illness that does not respect age or class. Neil Cavuto, Captain Beefheart and Montel Williams are just three well-known people who have said that they have the illness. Here is a list of many other sufferers.

MS is a chronic, inflammatory disease that affects the central nervous system (CNS). MS can cause a wide variety of symptoms, including changes in sensation, visual problems, muscle weakness, depression, difficulties with coordination and speech, severe fatigue, and pain. The classic pathology is what is known as demyelination (loss of the myelin that insulates nerve cells). Since myelin is white, the lesions are typically fuond in the white matter of the CNS.

The cause remains unknown, though I shall have more to say about some of the MS theories. Amongst the candidates have been autoimmunity, slow viruses, myelinic enzymes and polio vaccination.

Most people begin to experience symptoms between 20 and 40 years old, and rarely after 50. The onset is usually insidious, though every now and then someone starts with sudden onset of a catastrophic neurological or visual problem. Symptoms are usually vague and the diagnosis is often missed in the early stages. Females are affected slightly more than males. MS seems to be a disease of temperate latitudes in both the Northern or Southern hemispheres and is rarely seen in equatorial regions. This association with latitude has fueled some of the viral theories as well as ideas to do with the impact of decreasing sunlight on vitamin D and cell membrane function.

One of the things that makes the disease such a great masquerader is that it is typically marked by apparently random exacerbations and remissions. As the disease progresses, the remissions become less complete and permanent deficit more apparent.

There is an enormous research literature on MS: over 35,000 papers at last count. But there have been some recent highlights.

There has recently been a major breakthrough in discovering the mechanism by which myelin forms. The finding from the Keck School of Medicine of the University of Southern California and the Institut de Recherches Cliniques de Montreal in Canada, could have a major impact on the treatment of multiple sclerosis and demyelination as a result of spinal cord injuries.

Jonah Chan and his colleagues showed that a protein, Par-3, is at the base of the myelination process. This protein becomes localized to one side of the myelin-forming cells that are known as Schwann cells, upon contact with the axon that is to be myelinated. Par-3 acts like a kind of molecular scaffold to set-up an "organizing centre" that brings together the key proteins essential for myelination, in particular a receptor for a molecule that is secreted by the neurons.

The researchers found that when they disrupted this organizing centre, cells could not form myelin normally. Importantly, their discovery demonstrates that Schwann cells need to become polarized so that they know which side is in contact with the axon to initiate wrapping and to bring essential molecules to this critical interface.

These studies open up some new possibilities that should help to identify other components that are recruited at the organizing center set-up by Par-3. In multiple sclerosis, or after injury, Schwann cells can re-myelinate axons of the central nervous system to some degree. Therefore, these experiments bring about the possibility that manipulating the Par-3 pathway might allow for more efficient re-myelination of damaged or diseased nerves.

In a separate study researchers from the Virginia Commonwealth University researchers have identified a unique mechanism of action of a new drug that shows great promise for the treatment of MS.

The researchers reported the unique action of FTY720, or Fingolimod, an immunosuppressant drug that was already known to affect the functioning of the immune system by preventing the egress of white blood cells from the lymph nodes into the blood. The article was published in Blood: The Journal of the American Society of Hematology, that appeared online on Sept. 28.

In this study, the research team found that FTY720 also inhibited the activity of a key enzyme called cPLA2, which is necessary for the production of inflammatory mediators, known as eicosanoids. Eicosanoids drive inflammatory disorders such as asthma and multiple sclerosis.

The inhibition of cPLA2 would shut down the entire inflammatory pathway, possibly without the side-effects caused by medications such as Vioxx, that have been withdrawn from the pharmaceutical market.

FTY720, is a drug developed by Novartis, has shown considerable therapeutic effects in a recent small, placebo-controlled clinical trial involving patients with relapsing multiple sclerosis. The study was published in the September 2006 issue of the New England Journal of Medicine by an international research team.

I could easily select a dozen more important papers published in the last year, but I am particularly interested in basic research that teaches us something new, and treatments that could fit into a comprehensive Integrated plan of treatment.

I am going to post more about the causes of this illness as well as less orthodox approaches to help the physical, psychological, social, subtle and spiritual aaspects of these illnesses.

Comments

[Richard Edlich]

I am a plastic surgeon who developed Multiple sclerosis in 1985. I have a chronic progressive form of MS. What do you think is a safe treatment program that is not associated with severe complicatiions?

Dr. Edlich

[Richard Petty]

Dear Richard,

I am sorry for the delay in responding: I'm not quite sure how we missed you note.

I hope that I provided an answer to your question in my post on Integrated Medicine and MS.

If I did not, then please drop me a note and I'll be happy to give a more detailed response.

Kind regards,

RP

[The Wife]

Hi, Dr. Petty.

My husband was diagnosed with MS about a year ago. It is believed that since he is only 32 years old and that he has more than 20 lesions on his brain that he may have developed MS in his early youth.

He, also, says that when he was around 12 years old something changed in him. He began to have rage control issues that were not treated successfully with Psychiatrists or Therapists.

I have been living with him now for 4 1/2 years. During this time, these rages have come and gone, but peaked about 1 year ago, before we knew he had MS. It has started to level off some, but it is still heightened.

With all that said, I believe that this may be directly related to 1 or more of the lesions on his brain. Do you think this could be directly related and if so, how do we go about getting this aspect of the disease under control?

[Richard Petty]

Thank you so much for your letter.

This sounds like an incredibly stressful situation.

Without a lot of information and a personal examination, it's hard to be sure about anyone's diagnosis and what might be causing what.

But there is absolutely no question that MS plaques in key regions of the brain can cause all kinds of behavioral changes. Assuming that the rage attacks aren't his personality - and you said that something changed when he was 12 - it is entirely possible that they could be the result of plaques in the pathways leading to the frontal lobes of the brain. I've seen a great many people with problems like this and also some who were thought to have bipolar disorder.

Treating these problems can be very hard, and we have to use medicines "off label." That being said we have often helped people with anticonvulsant medicines and even tiny doses of antipsychotics. We also use the comprehensive approach that I outlines in one of the other posts.

Without knowing the details, I don't know whether they would help your husband, but they would be worth discussing with the physicians who are treating him.

I do wish you both well.

Kind regards,

RP