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Multiple Sclerosis. Dayna Ryan, PT, DPT Winter 2012. Pathology . Primarily known as a disease of CNS myelin (demyelination) Recent evidence shows early involvement of CNS axons as well Lesions numerous in cerebrum, brainstem, cerebellum, SC, optic nerve and chiasm.

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Multiple Sclerosis

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    1. Multiple Sclerosis Dayna Ryan, PT, DPT Winter 2012

    2. Pathology • Primarily known as a disease of CNS myelin (demyelination) • Recent evidence shows early involvement of CNS axons as well • Lesions numerous in cerebrum, brainstem, cerebellum, SC, optic nerve and chiasm

    3. Multiple Sclerosis: Plaques Bright spots are areas of plaques

    4. Etiology • Autoimmune • Infectious agent, viral or bacterial • Environment has an effect with higher incidence in the Northern U.S. • migration south before age 15 decreases the risk • may be related to decreased vitamin D generation in more wintery climates • Genetic link makes people more susceptible to the disease • Recent evidence (2010): increased risk of developing MS after Epstein-Barr Virus infection

    5. Histology

    6. Immune Cell Participation in MS 1. Peripheral activation of T cells 2. Adhesion to endothelial cell wall 3. Chemo-attraction 4. Invasion through blood-brain barrier 5. Reactivation in CNS – can damage myelin and axons

    7. CD8 T cells and acute axonal damage

    8. MS Relative Incidence Worldwide • Possible link with Vitamin D and amount of sunlight exposure at different latitudes • Possible link with infectious diseases From:

    9. MS Signs and Symptoms • Motor: • Spasticity • Weakness • Coordination (cerebellar) • Sensory • Paresthesias • Numbness • Visual (optic neuritis) • Scotoma (blind spot) • Diplopia • Nystagmus • Cognitive changes • Depression • Fatigue • Often most disabling condition • Sleep disorders • Autonomic • Pulmonary dysfunction

    10. MS Signs and Symptoms • Brainstem S/S • Gaze palsies • Nystagmus (if CN VIII involved) • Dysarthria • Vertigo • Cerebellar S/S • Hypotonia • Dysarthria • Ataxia • Decreased coordination • Trunk weakness • Postural and movement disorders

    11. MS Signs and Symptoms • Cerebral S/S • Optic neuritis – plaques commonly occur on CN II • May cause unilateral vision loss, often with pain in the eye • Scotoma = blind spots • Blurred vision or diplopia  can become blind • Abnormal visual fields • Depression • Progressive cognitive dysfunction • Memory loss • Loss of higher order functioning

    12. Historic Perspective on Diagnosis of MS • Before the advent of MRI, diagnosis would not occur until several instances of MS occurred over a period of years. • Some patients reported a time lag of up to 15 years from the onset of symptoms to the time of diagnosis. • As late as 1998, the average time from onset of symptoms to time of diagnosis was approximately 4 years (Ebers GC & Sadovnick AD 1998).

    13. Diagnostic Process • Patient history • MRI • Increased levels of immunoglobulin G (IgG) in the cerebrospinal fluid • The diagnosis of MS is only given to patients who either have persistent symptoms of MS with MRI evidence of MS plaques or to patients who have repeated exacerbations with MRI evidence of MS plaques. • Kurtzke Expanded Disability Status Scale

    14. Clinically Isolated Syndrome (CIS) • Diagnosis of CIS given to patients who present with first incident of neurologic symptoms that last at least 24 hours and are caused by inflammation/demyelination in one or more areas of the CNS • People with CIS who have brain lesions on MRI are at high risk of having a 2nd neurologic episode and being diagnosed with MS • Risk of being diagnosed with MS is lower for if no MRI evidence of neurologic lesions.

    15. MS Classification • Clearly defined flare-ups (relapses) or episodes of acute worsening of neurologic function • These are followed by partial or complete recovery periods (remissions) between attacks that are free of disease progression • Most common form of MS at time of initial diagnosis (Approximately 85% at onset) Relapsing-Remitting

    16. MS Classification • Initial period of relapsing-remitting disease followed by a steady worsening disease course with or without occasional flare-ups, minor remissions (recoveries) or plateaus • If left untreated, 50% of people with relapsing-remitting MS develop this form of the disease within 10 years of initial diagnosis Secondary Progressive

    17. Relapsing – Remitting MS Progression Exacerbation Pre-Clinical Relapsing- Remitting Secondary Progressive Nerve Cell Loss

    18. MSClassification • Nearly continuous worsening of disease from the onset, with no distinct relapses or remissions • Many variations in rate of progression over time, occasional plateaus, and temporary minor improvements • Relatively rare - Approximately 10% at onset Primary Progressive

    19. MS Classification • Steadily worsening disease from the onset • Also have clear acute flare-ups (relapses), with or without recovery • In contrast to relapsing-remitting MS, the periods between relapses are characterized by continuing disease progression • Relatively rare – approximately 5% at onset Progressive Relapsing

    20. Below is a graph showing the average time a person spends in each EDSS level. Progression of MS • Average time spent in each EDSS level

    21. Disease Modifying Agents • Avonex (Interferon beta 1-a) • weekly intermuscular injections • Betaseron (Interferon beta 1-b) • subcutaneous injection every other day • Rebif (Interferon beta 1-a) • Subcutaneous injections 3x/week • Common side effects: • Flu-like symptoms (headache, fatigue, muscle aches, fever) • Depression/anxiety • Liver problems • Blood problems • Thyroid problems • Allergic problems • Seizures (Avonex)

    22. Disease Modifying Agents • Copaxone (glutimer acetate) • Daily subcutaneous injections • Novantrone (mitroxantrone) • Intervenous injections every 3 months for max of 2-3 years • Tysabri (natalizumab) • Intervenous infusion every 4 weeks

    23. Symptom Management • Spasticity • Baclofen • Bladder problems • Cholinergics • Depression • Anti-depressants • Fatigue • Anti-depressants • Heat sensitivity • Fans • Good hydration • Cooling vests

    24. Complimentary and Alternative Therapies (CAM) • Acupuncture • Bee venom therapy • Marijuana • Yoga • Tai Chi • Reiki • Polarity therapy • Mushrooms • Herbs • Frequently used • Need to ask about these when taking history

    25. Disease Progression • Course is highly variable across patients • Life span modestly reduced on average • Mean of one exacerbation per year (more frequent earlier in disease) • Exacerbations commonly occur following viral infections • Approximately 2/3 of patients with MS develop a progressive phase with residual disabilities • In 50% of cases, cause of death is attributable to MS (pneumonia, pulmonary embolism, bacterial sepsis from UTI or decubiti)

    26. Prognosis • Better prognosis with: • Acute onset • Female gender • Younger age of onset • Higher degree of remission after 1st attack • Initial presentation limited to eyes or sensory symptoms • Initial attack limited to one area of the CNS • Worse prognosis with: • Onset after age 35 • Early cerebellar or lower brainstem symptoms • Primary progressive course occurs • More lesions in initial MRI

    27. Other MS Resources • National Multiple Sclerosis Society • Multiple Sclerosis Association of America • Multiple Sclerosis Foundation