1. Overview of Multiple Sclerosis  Valerie Robinson, D.O. 

2. What is it? Multiple sclerosis Multiple sclerosis is an inflammatory demyelinating disease, likely auto-immune. Affects the CNS multifocal Causes multifocal areas of demyelination Most commonly affects women of childbearing age who are of Northern European descent. There is a multiple-gene component Siblings 3-5%, Twins 20-40%

3. Signs and Symptoms Relapses and Remissions Optic neuritis Internuclear opthomoplegia Sensory irregularities Pain Vertigo Muscle weakness, spasticity, paraparesis or paraplegia Bowel/bladder/sexual dysfunction

4. Signs and Symptoms Fatigue Depression Cognitive dysfunction Difficulty with coordination McDonald’s criteria – multiple lesions are separated in space and time Uhthoff’s phenomenon – worsening of symptoms when the body temp increases Lhermitte’s sign – feeling of electric shock running down back and limbs upon neck flexion

5. Diagnosis Clinical judgment Clinical judgment confirmed by the following: MRI shows demyelinated plaques that meet McDonald’s criteria CSF analysis: increased IgG, oligoclonal bands Abnormal evoked potentials (visual, somatosensory, and brainstem auditory) Onset between age 15 and 50 Before 16 is considered pediatric = 5%

6. Exacerbations/Relapses Acute neurologic impairment causing loss of function or severe discomfort. Pregnancy, particularly 2-3 months post- partum Stress Random

7. Types of MS Relapsing-remitting (RRMS): Relapsing-remitting (RRMS): clear relapses with full or partial recovery. No progression between relapses. Primary-progressive (PPMS): Primary-progressive (PPMS): From onset, disease progresses with occasional plateaus and temporary minor improvements. Secondary-progressive (SPMS): Secondary-progressive (SPMS): Onset as RRMS then begins to progress. With or without relapses, minor improvements and plateaus. Progressive-relapsing (PRMS): Progressive-relapsing (PRMS): From onset, disease progresses. It has occasional clear relapses with full or partial recovery. Progression continues between relapses.

8. Differential CVA/TIA Malignancy Spinal cord injury or compression A-V malformations Lupus Sjogren’s Cerebellitis Infections: such as meningitis, human T- lymphocytic virus type 1, HIV, syphilis

9. Treatment of Progressive Immunosuppression Immunosuppression – Azathioprine – Cladribine – Dalfampridine –  Glucocorticoids –  Cyclophosphamide – Cyclosporine Stem sell transplant – Glatiramer acetate –  Interferon –  Methotrexate – Mitoxantrone – Natalizumab – Rituximab Total lymphoid irradiation

10. Treatment of Relapsing Glucocorticoids #1 Glucocorticoids Interferon Glatiramer acetate Natalizumab Plasma exchange if poor response to steroids Methylprednisolone 1 gram IV QD x 3-7 days Methylprednisolone 1 gram IV QD x 3-7 days – Pediatric: 20-30 mg/kg QD x 5 days May follow with a prednisone taper for residual disability

11. References Up-to-Date – Diagnosis of multiple sclerosis in adults – Epidemiology and clinical features of multiple sclerosis in adults – Treatment of progressive multiple sclerosis in adults – Treatment of acute exacerbations of multiple sclerosis in adults – Treatment of relapsing-remitting multiple sclerosis in adults – Treatment and prognosis of pediatric multiple sclerosis