| **NEUROLOGICAL DISEASE CLUSTERS**

**Jerry S. Wolinsky, MDProfessor of NeurologyUniversity of Texas-Houston, Health Science Center**

Major neurological immune mediated diseases includemultiple sclerosis (MS), Guillain-Barr� syndrome, chronic inflammatory demyelinatingpolyradiculopathy, myasthenia gravis, dermatomyositis, and collagen vascular diseases withCNS expressions such as systemic lupus erythematosis and Sjogren’s syndrome.

Of these, MS stands out as the most common of the CNSautoimmune disease that overwhelmingly, preferentially affects women. Epidemiologic datasuggest that between 250,000 to 350,000 Americans have MS and the disease is increasing.

Nearly 3 out of 4 of those afflicted are women. MS strikeswomen most frequently as they begin to assert their independence, assume professionalroles and begin families.

For most women, MS presents with a typical relapsing andremitting course. Individual attacks are characterized by rapidly evolving neurologicdysfunction. Symptoms typically reach a maximum over the course of several days to severalweeks, plateau, and then subside.

Symptoms are quite varied, reflecting the multitude offunctions controlled by the brain. Rapid development of visual loss in one eye, evolutionof ascending numbness on one side of the body, marked instability of gait, weakness of oneor more limbs, and combinations of these symptoms are common.

Individual attacks vary in severity from mild to a completeinability to function that demands hospital care. Attacks are unpredictable. They shatterfuture expectations, denying any illusion of control over one’s life. With increasingnumbers of attacks, there is less complete recovery, disability accumulates over time. Asubstantial proportion of all MS patients move into a progressive disease phase withcontinued neurologic deterioration between attacks.

MS is in part genetically controlled. Undoubtedly, severalgenes contribute to susceptibility and may condition the course of the disease. To date,the major histocompatibility antigen gene locus is the only one clearly implicated. Theimportance of this gene’s product in presenting foreign proteins to the immune systemis unquestioned.

However, environmental factors clearly influence diseaseonset and attacks. There are marked geographical differences in MS prevalence, withgenerally increased prevalence in either direction from the equator. While predominantly adisease of Caucasians, racial restrictions are rapidly overcome when individuals migratefrom geographical low risk to high risk areas. About 1/3 of all attacks are triggered bynonspecific viral infections.

Remarkable advances in understanding the dynamics of MS asa disease have come from the application of magnetic resonance imaging (MRI) andspectroscopy. Recurrent focal inflammation and demyelinating activity as measured byserial MRIs greatly exceeds clinically measured events. These new observations suggestthat MS is more a continuous than an episodic disease. This type of clinical coursedemands treatments that are safe, can be administered early and continuously in thedisease in order to prevent further attacks, and that are proven to limit accumulateddisability.

Research based on animal model paradigms and carried outwhen possible in parallel fashion in man support the hypothesis that MS is a T-cellmediated, organ-specific autoimmune disease. Likely, those with MS have lost the abilityto regulate potentially autoreactive cells that are present in all individuals. Theseautoreactive cells have the potential to orchestrate a directed attack on CNS myelin byrecognizing protein and possible other components of the myelin sheath.

New medications that appear to improve immunoregulationwithout crippling important components of the immune defenses against foreign invadingagents are beginning to improve the outlook for patients with MS.

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