By: Dr. James Stark
Although there is still work to be done, in recent years the scientific advances in the field of Multiple Sclerosis have revolutionized the understanding, diagnosis and treatment of this disease. There are a number of reasons why the cause of MS has remained elusive to researchers. One issue is that the initial events, which eventually result in MS, often pre-date symptoms or clinical presentation by many years. Another complicating factor is the immune system itself. There are many cell types and subtle variations among cell types that all interact in a very complex manner. While attempting to single out the role of a single cell type in a laboratory dish may be possible, understanding the function of each cell in the human body becomes more complex. This daunting task, however, has not deterred the dedicated researchers in the MS community from continuing their work and rapidly advancing our knowledge base.
In autoimmune diseases, the body’s own immune system wrongly identifies something that normally should be present in the body as foreign. Why this happens is not fully understood, but is likely a complex interplay of a genetic predisposition to a hyper-reactive immune system as well as various environmental factors. One theory in MS is that at some point in a patient’s life, patients had an infection which the immune system fought off. The immune system remembers infections so that it can more easily fight off the infection again in the future. ‘Molecular mimicry’ is a theory in which a part of the infective organism, possibly a sequence of proteins, literally looks like a protein sequence that normally appears in the body. The immune cells recognize this protein sequence as abnormal, recruit more immune cells in to fight off the ‘problem’ and this leads to inflammation and swelling. Eventually, the immune system realizes that it is not supposed to be attacking this part of the body and corrects the problem. How the immune system does this is unclear.
Autoimmune Target in MS: Myelin
In Multiple Sclerosis, immune cells target a certain cell type called oligodendrocytes, which are only located in the central nervous system (the brain and spinal cord.) Oligodendrocytes are special types of neurons (or brain cells) which produce something called myelin. Myelin is a fatty substance which coats nerves allowing them to conduct electricity much more quickly and efficiently. In this regard, they act much like the insulation on wire cables or water pipes. That is why when the immune system attacks and damages oligodendrocytes, we call that demyelination. Importantly, the immune cells often don’t destroy the nerve, just the coating around the nerve. When the immune system stops the attack, the myelin is able to regrow and resume its function. This is called remyelination. Remyelination does not always occur however and, when it does occur, it is never as good as if there had never been damage in the first place. Over time, with repeated episodes of demyelination, the nerve is unable to remyelinate and the nerve may die. Remyelination helps explain why, after a relapse, patients often recover after several weeks or months even without treatment.
While there are a variety of demyelinating diseases, MS is by far the most common. The prevalence of MS varies by region which further highlights the role of the environment in MS. The incidence increases with further distance from the equator (which may be related to vitamin D) and various pockets of abnormally high incidence can be seen. The prevalence of MS in the US is often quoted as approximately 400,000. However, with the increased awareness of the disease among the medical community as well as improvements in diagnosis from widespread MRI use, that number is certainly much higher. There is some debate as to whether the incidence of MS is rising, or whether we are just better at recognizing and diagnosing the disease. MS is the leading cause of disability in young adults. It affects women approximately three times more than men and that disparity may also be increasing.
MS can affect almost any part of the brain and spinal cord, although it has a predisposition to places with large amounts of myelin. That is why certain symptoms are considered classic for MS, such as optic neuritis (inflammation of the optic nerve). However, MS can produce a wide variety of symptoms depending on what part of the brain is involved. The circuitry of many parts of the brain has significant redundancy, or overlap, built in. Because of this, MS activity sometimes does not cause any symptoms. That is why upon initial presentation, we often find evidence of old lesions. That is also why it is generally advisable to occasionally monitor patients for asymptomatic activity with MRI’s, especially early on in the disease course.