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• Multiple Sclerosis


  Autoimmune (HLA-DR2), more common in females between 20 and 40
• Environmental factors


  • EBV
  • HHV6
  • Smoking
  • Low Vit D & sunlight exposure
• Multiple Sclerosis


  • Combination of types IV (T cell mediated reaction, mainly against myelin basic proteins) and II (antibodies against oligodendrocytes and myelin) hypersensitivity reactions
  • Interplay between genes and environment
• Multiple Sclerosis


  1. Progressive demyelination in the CNS

  2. Only oligodendrocytes are affected

  3. Affects the white matter of brain & spinal cord

  4. Never affects peripheral nerves
• Plaques


  Classic location: angles of lateral ventricles
• Common sites for plaques


  • Optic nerve
  • Periventricular white matter
  • Brainstem and its cerebellar connections
  • Cervical spinal cord (corticospinal tract and posterior columns)
• Clinical patterns


  • Relapsing-remitting (most common pattern, 85%)
  • Secondary progressive
  • Primary progressive (10%)
  • Relapsing-progressive
• Symptoms and signs


  • Fatigue
  • Posterior column affected: paresthesia, loss of vibration sensation
  • Pyramidal tract (UMNL): weakness, spasticity, exaggerated deep tendon reflexes, Babinski sign
  • Optic nerve: optic neuritis/atrophy, monocular visual loss, pain on eye movement, central scotoma, decreased pupillary reaction to light
  • MLF: bilateral intranuclear ophthalmoplegia (pathognomonic)
  • Cerebellar: nystagmus, intention tremor, dysarthria (scanning speech, drunk-like)
  • Brainstem: cranial nerves affected: diplopia, vertigo, dysphagia, dysarthria, facial weakness/numbness
  • Autonomic: constipation, urge incontinence, sexual dysfunction
  • Cerebral: dementia, depression, cognitive decline, memory loss, personality
  • Neuropathic pain: hyperesthesia, trigeminal neuralgia
  • Lhermitte sign: tingling electric shock-like sensation that radiates to the arms, down the back, or into the legs on flexion of the patient's neck
  • Uhthoff's sign: increased symptoms with hot weather & hot bath
• MRI


  • Most specific & sensitive for periventricular lesions
• CSF


  • IgG oligoclonal bands (not specific)
  • High protein (gamma globulins)
  • Cells (CD4 T cells and monocytes)
• Diagnosis of multiple sclerosis


  • Must have dissemination in time and space (McDonald criteria)
• Acute attack treatment


  1. Pulse IV high dose methylprednisolone: 1gm/100cc NS over 1 to 2 hours for 3 to 5 days

  2. (to control relapses and decrease severity)
• Disease-modifying agents


  • Interferon beta-1a (IM) and beta-1b (SC)
  • Glatirameracetate
  • Natalizumab
  • Fingolimod
  • Dimethylfumerate
  • Teriflunomide
• Interferon beta-1a and beta-1b


  • Antiviral peptide; switches cytokines to anti-inflammatory
  • Decreases relapse rate by 1/3
  • Side effects: flu-like symptoms
• Glatirameracetate


  Antigenically similar to myelin binding protein
• Natalizumab


  • Anti-adhesion monoclonal antibody
  • 2nd line due to serious side effect: JC virus activation
  • Progressive multifocal leukoencephalopathy
  • Look for JC virus serology before starting
  • If suspected, D/C, plasma exchange, LP to look for JC DNA
• Fingolimod


  • Prevents SIP signal
  • Imprisons lymphocytes in LNs
  • Side effects: conduction problems
• Dimethylfumerate


  May cause lymphopenia
• Symptomatic relief


  • Physiotherapy
  • Occupational therapy
  • Muscle relaxants
  • Baclofen
  • Dantrolene
  • Benzodiazepines
• Good prognostic indicators


  • Female
  • Young
  • Sensory or optic symptoms only
  • Low early relapse rate in the first 2 years
• Bad prognostic indicators


  • Male
  • Motor or cerebellar symptoms
  • Disability
  • Poor recovery after first relapse
  • High lesion load on MRI