Volume 68, Issue 6 Louisville Medicine | Page 16

MULTIPLE SCLEROSIS : A DISEASE IN EVOLUTION AUTHOR Roy Meckler , MD
ALL IN THE HEAD

MULTIPLE SCLEROSIS : A DISEASE IN EVOLUTION AUTHOR Roy Meckler , MD

Multiple sclerosis is a demyelinating disease of the brain and spinal cord , initially inflammatory in character and pathophysiology , but with some early concurrent and later predominant degenerative features . Common symptoms include anxiety and depression ; altered cognition ; impairment in balance ; bowel or bladder dysfunction ; sensorimotor deficit , with pattern dependent upon location of demyelination ; visual disturbance , such as double vision or optic neuritis ; speech difficulties ; spasticity ; and sexual dysfunction .

The history of the disease dates to 1380 with a description of a progressive illness of Saint Lidwina of Holland compatible with multiple sclerosis . It was not until 1868 however , that Jean-Martin Charcot published a series of three articles establishing the pathology of multiple sclerosis and its many clinical features , derived through brilliant clinical pathological correlations of his daily neurology rounds in Paris . The Salpetriere Hospital contained many paraplegic patients . The paraplegics who had sustained their symptoms traumatically were angry and frustrated , while a second group seemed to be indifferent to their symptoms . When Charcot preformed postmortem exams on this second group , they had disseminated white matter lesions of their brains , and he was able to establish the pathology of “ multiple sclerosis .”
The diagnosis of multiple sclerosis still remains clinical with criteria of pathology of white matter of the brain or spinal cord disseminated in space ( multiple locations of lesions ) and time ( occurring on at least two occasions ), or as the British label this disease “ disseminated sclerosis .” Subsequent diagnostic criteria have evolved to include MRI and evoked potentials to provide dissemination of lesions in space ( more than one lesion in more than one location ), or characteristic spinal fluid findings such as elevated immunoglobulin G ( IgG ) index and presence of oligoclonal bands or elevated myelin basic protein , excluding other causes .
In the US , the average age of onset is 34 although late life MS and MS in pediatric age range exist . The prevalence has increased to 363 per 100,000 with over 1 million MS patients in the US today . There is a 3:1 ratio of women to men . The incidence of MS is higher the farther you are from the equator , particularly in northern European Caucasians , with more progressive and or severe disease in African-American men .
The precise etiology of multiple sclerosis has not yet been established but probably represents a combination of at least three factors , beginning with genetic predisposition including human leukocyte antigen ( HLA ) system , particularly DR 15 and DQ 6 . The risk ratio for multiple sclerosis for the general population is 3.5 per 1,000 , or less than 0.5 %. The incidence of multiple sclerosis for the children of MS mothers is about 3.4 %, and for identical twins , the risk is 30 %. The risk in nonidentical twins is 5 %.
Another factor might be a slow infectious agent with possible relationship to the Epstein-Barr virus . The infection component is supported by epidemiologic statistics of populations emigrating from low incidence countries to high incidence and vice versa , before 15 years of age .
The third factor , immunology , underlies the pathophysiology of multiple sclerosis but simplifying an extraordinarily complex process is difficult . In the periphery of the body , there is antigen presentation to CD4 + cells prompting activation and proliferation of pro-inflammatory lymphocytes ( Th1 and TH 17 ) followed by secretion of pro inflammatory cytokines , resulting in upregulation of adhesion molecules . T-cells migrate across the blood-brain barrier and into the central nervous system ( CNS ), and B-cells activate and proliferate , with migration into the CNS . Monocytes migrate with macrophages into the CNS . MS is associated with regulatory T cell or T-REG dysfunction and impaired maturation . Once the blood-brain barrier into the CNS has been crossed , there is presentation of CNS antigen to T cells and reactivation with recruitment of other inflam-
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