Multiple Sclerosis Rohith M. Reddy

Multiple sclerosis (MS) involves an immune-mediated process in which an abnormal response of the body’s immune system is directed against the central nervous system -CNS: composed of the brain, spinal cord and optic nerves The exact antigen — or target that the immune cells are sensitized to attack — remains unknown, which is why MS is considered by many experts to be "immune-mediated" rather than "autoimmune.” DEFINITION

EPIDEMIOLOGY -MS is the most common demyelinating disease - It’s more common in females then males -The disorder is most commonly diagnosed between ages 20 and 40, but can be seen at any age. -The most common thought is that a virus or gene defect, or both, are to blame. Environmental factors may play a role. -Family history of MS or living in an part of the world where MS is more common, increases risk developing MS.

PATHOGENESIS Autoimmune disease initiated by -genetic factors, ex: HLA-DR2 -Environmental triggers -Microbial pathogens. EBV, Human herpes virus 6, Chylamyophilia phenumoniae, Vitamin D, Sun exposure -Environmental trigger activates helper T cells who antigen- specific receptors recognize CNS myelin basic protein as an antigen. Demyelination diseases:  Destruction of normal myelin ex- multiple sclerosis  Destruction of oligodendrocytes ex- MS and slow virus infections  Production of abnormal myelin ex- MS T cells release cytokines that activate macrophages, which also release cytokines (ex- TNF a) that destroy the myelin sheath as well as oligodendrocytes that synthesize myelin( type 4 hypersensitivity). Antibodies directed against the myelin sheath and oligodendrocytes may also be involved( type 2 hypersensitivity).

SCHEMATIC DIAGRAM

DEMYLINATION MECHANISM

SIGNS AND SYMPTOMS

RISK FACTORS

Microscopic and Gross Findings Inflammatory infiltrate in places predominantly composed of CD4 T cells and microglial cells with phagocytized lipid. Demyelinating plaques occur in white mater of CNS. Laboratory findings Increased CSF leukocyte count- primarily CD4 T lymphocytes Increased CSF protein- Primarily an y-globulins Increased CSF myelin basic protein- indicates active disease Normal CSF glucose High-resolution electrophoresis shows oligoclonal bands. -Discrete band of protein in the y-globulin region -sign of demyelination MRI is extremely sensitive in detecting demyelinating plaques DIAGNOSIS

TREATMENT 1. Acute relapse -High dose methylprednisolone 2. Chronic -Disease modifying drugs—e.g., interferon-beta - Monoclonal antibody—natalizumab - cytotoxic—cyclophosphamide; methotrexate; azathioprine PROGNOSIS - Varies with the type of disease - On average, ~70% of patients with MS are alive 23 years after their diagnosis

CASE STUDY Ms. Hima is a 35 year old white female. She came to Neurology Clinic for evaluation of her long-term neurologic complaints. The patient relates that for many years she had noticed some significant changes in neurologic functions, particularly heat intolerance precipitating a stumbling gait and a tendency to fall. Her visual acuity also seemed to change periodically during several years. Two months ago the patient was working very hard and was under a lot of stress. She got sick with a flu and her neurologic condition worsened. At that time, she could not hold objects in her hands, had significant tremors and severe exhaustion. She also had several bad falls. Since that time she had noticed arthralgia on the right and subsequently on the left side of her body. Then, the patient abruptly developed a right hemisensory deficit after several days of work. The MRI scan was performed at that time and revealed a multifocal white matter disease - areas of increased T2 signal in both cerebral hemispheres. Spinal tap was also done which revealed the presence of oligoclonal bands in CSF. Visual evoked response testing was abnormal with slowed conduction in optic nerves.

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