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Multiple sclerosis
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  • 1. Case history • A 32yrs old lady is brought to ER with c/o gradually developing weakness of left half of body for last 5 days. Now there is weakness of right arm as well. No h/o fever, headache, vomiting or unconsciousness.
  • 2. O/E • GPE • CNS: Power normal 2/5 in left arm & leg 3/5 in right arm left facial nerve palsy LMN type left plantar upgoing reflexes brisk on left side
  • 3. • What is your DD? • How will you proceed?
  • 4. How will you explain the disease?
  • 5. Case history • A 35 yr old gentleman presents with sudden onset paraplegia. O/E there is UMN paraplegia with a sensory level at T8. • h/o sudden transient unilateral visual loss 7 yrs back. • Whats the pathology?
  • 6. Case history • A young girl of age 17 presents in opd with c/o diplopia & unsteadiness developing over 2months. O/E : • Features of right cerebellar lesion • Bilaterally upgoing plantars • Left lateral rectus palsy All routine labs are normal
  • 7. Give your diagnosis?
  • 8. Case history • A diagnosed patient of multiple sclerosis presents with complaints of severe excruciating pain over left half of face. There is electric spark like sensation. Pain aggravates even on touching the face. Its not relieved even by use of NSAIDs. • What is the underlying problem?
  • 9. Definition • Chronic inflammatory demyelinating disorder affecting CNS characterized by relapses and remissions
  • 10. • Also called as disseminated sclerosis or encephalomyelitis disseminata • French neurologist Jean Martin Charcot was the first to recognize multiple sclerosis as a distinct separate disease in 1868
  • 11. Epidemiology • • • Male: Female= 1:2 Peak age of onset is in the fourth decade Incidence varies with latitude, low in equatorial areas and higher in temperate zones • More relapses occur during spring and summer
  • 12. Aetiology Genetic factors • Environmental factors • Autoimmune factors The risk of familial recurrence is 15% with highest being for first degree relatives. Monozygotic twin concordance is 35%
  • 13. Pathology • The major target is the myelin- producing OLIGODENDROCYTES of the central nervous system • An underlying autoimmune mechanism may be involved as there are increased number of activated T lymphocytes in the CSF and increased immunoglobulin synthesis in CNS
  • 14. Pathology It involves the triad of: • Inflammation • Demyelination • Scarring (gliosis)
  • 15. Pathogenesis • CNS inflammation in MS starts with entry of • • activated T lymphocytes through blood brain barrier The resulting inflammatory cascade releases cytokines and initiates destruction of oligodendrocyte-myelin unit by macrophages Demyelination mostly occurs in periventricular regions of brain, optic nerves and subpial regions of spinal cord
  • 16. Precipitating factors • • • • Infection Trauma Surgery Emotional and physical stress
  • 17. Common presentations • Optic neuritis • Bilateral internuclear ophthalmoplegia is • • • • • characteristic of MS Relapsing and remmitting sensory symptoms Subacute painless spinal cord lesion Acute brain stem syndrome Subacute loss of function of upper limb (dorsal column deficit) 6th cranial nerve palsy
  • 18. Other symptoms and syndromes • Afferent pupillary deficit and optic atrophy (previous optic neuritis) • Lhermitte´s symptom (tingling in spine or limbs on neck flexion) • Progressive non-compressive paraperesis (Devic´s variant)
  • 19. Clinical features • Uhthoff´s symptom; transient unilateral • • • • visual loss or blurring after hot shower or exercise Partial Brown-Sequard syndrome Postural (rubral , Holmes ) tremor Trigeminal neuralgia Recurrent facial palsy
  • 20. Variants of MS • • • Relapsing remitting (80%) Primary progressive (10-20%) Fulminant (<10%) Marburg´s variant • Secondary progressive
  • 21. Diagnosis A diagnosis of multiple sclerosis requires the demonstration of lesions in more than one anatomical site at more than one time for which there is no other explanation
  • 22. INVESTIGATIONS • No specific diagnostic test for multiple sclerosis. • Diagnosis is mainly clinical & tests are done to confirm the diagnosis and to exclude other conditions. • Investigations can also predict prognosis after first episode.
  • 23. INVESTIGATIONS IN A PT SUSPECTED TO HAVE MS • Exclude other structural disease & identify plaques of demyelination: MRI , Myelography • Demonstrate other sites of involvement: MRI ,evoked potentials • Demonstrate inflammatory nature: CSF examination (oligoclonal bands) • Exclude other conditions: CXR, ACE levels, serum B12, antinuclear & antiphospholipid antibodies.
  • 24. MRI BRAIN showing high signal areas
  • 25. Same MRI after few months
  • 26. Multiple Sclerosis and Pregnancy
  • 27. ACUTE RELAPSE Pulses of high-dose methylprednisolone either IV 1gm daily for 3 days or orally 500mg daily for 5 days, shorten the duration of relapse but do not affect long-term outcome. So long use of steroids should be avoided.
  • 28. PREVENTING RELAPSES • Immunosuppressive agents like azathioprine reduces relapse rate. • Subcutaneous or IM interferon beta-1a/b reduces the number of relapses by about 30% with a small effect on longterm disability • Glatiramer acetate has similar effects.
  • 29. Immune modulation therapy • • • • • • • • • Interferon beta Glatiramer acetate Azathioprine Cyclophosphamide Mitoxantrone IV immunoglobulins Plasmapharesis Monoclonal antibodies to beta integrins (eg natalizumab) Monoclonal antibodies to lymphocyte epitopes ( eg campath1-H)
  • 30. NON SPECIFIC THERAPIES • Special diets including gluten free or linoleic acid supplements • Hyperbaric oxygen are being used but of no proven benefit.
  • 31. COMPLICATIONS • • • • • • • Ataxia Spasticity Dysaesthesias Bladder symptoms Impotence Fatigue Depression
  • 32. PROGNOSIS • About 15% of those having an attack of • • • • demyelination do not suffer any more events. If optic neuritis is initial manifestation, there may be no recurrence. In relapsing remitting disease, there are on average 1- 2 relapses every 2 years. Approximately 5% of patients die within 5yrs of onset. 33% patients are dependant by 10yrs rising to 50% after 15 yrs.