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Demyelinating diseases Slide 1 Demyelinating diseases Slide 2 Demyelinating diseases Slide 3 Demyelinating diseases Slide 4 Demyelinating diseases Slide 5 Demyelinating diseases Slide 6 Demyelinating diseases Slide 7 Demyelinating diseases Slide 8 Demyelinating diseases Slide 9 Demyelinating diseases Slide 10 Demyelinating diseases Slide 11
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Demyelinating diseases

  1. 1. Demyelinating diseases Multiple sclerosis Central pontine myelinolysis Transverse myelitis Guillain-Barre syndrome
  2. 2. Characteristic Inflammatory Mostly acute onset Commonly relapsing-remitting course
  3. 3. Multiple sclerosis  An inflammatory demyelinating disease  Affects brain & spinal cord  Common in young- ~40 years, females  Classification- based on course  Relapsing-remitting- accretive deficits over long-term  2° progressive- progressive neurologic decline, following relapsing-remitting course  1° progressive- relentless progression without remission  Progressive relapsing- steady neurologic decline with few relapses
  4. 4. Cause & pathophysiology  Cause- exactly not known  Genetic propensity- HLA-DR15 & DQ6 increase risk  Infection- possible trigger of inflammatory response- HHV, MMR  Other- decreased sunlight exposure, smoking, stress, vaccinations, toxins  Pathophysiology-  Plaques in white matter of brain, rarely peripheral, due to damage to oligodendrocytes  Inflammation, mediated predominantly by T-cells that enter CNS through permeable blood-brain barrier
  5. 5. Clinical  Manifestation- gradually progressive  Paresthesias, weakness, ataxia  Dysarthria, dysphagia, diplopia, impaired vision  Acute/chronic pain, cognitive impairment  Depression & mood changes  Dx-  MRI- plaques, specially at multiple sites  CSF- oligoclonal bands of IgG, s/o inflammation  Impaired visual or sensory evoked potantials
  6. 6. Treatment  Aims- returning function after an acute attack, preventing new attacks, preventing disability  Acute attack- IV methylprednisolone ± plasmapheresis  Disease modifiers-  Interferon β-1a/1b  Glatiramer  Mitoxantrone  Natalizumab  Supportive treatment  Px- mean years to death since onset is ~30 years; Females, relapsing-remitting type, early age & optic neuritis at onset, fewer attacks are associated with a better course
  7. 7. Central pontine myelinolysis  Osmotic demyelination syndrome  Causes-  Rapid correction of hyponatremia, specially chronic  Associated with alcoholism, hyperemesis gravidarum, SCT  s/s- due to myelinolysis of corticobulbar & corticospinal tracts, in pons- LOC, quadriparesis, dysarthria, dysphagia, diplopia etc.  Dx- clinical + MRI  Rx- supportive only  Prevention- slow correction of hyponatremia- ~0.5 mEq/L/hr
  8. 8. Transverse myelitis  Acute demyelination of spinal cord, following viral infection or vaccination  s/s- depend on site of spinal cord involvement- sensory level & radicular pain define level  DDx- trauma, epidural metastasis, infarction  Dx- MRI  Rx- high-dose steroids + supportive  Px- poor in majority
  9. 9. Guillain-Barre syndrome  An autoimmune disease affecting peripheral nerves- ~80% myelin, ~20% axon  Triggers- C.jejuni, influenza virus/vaccine  Classification-  AIDP- ascending LMN type paralysis, most common  Miller-Fisher- descending paralysis; presents with ophthalmoplegia, ataxia, areflexia  AMAN- acute motor axonal neuropathy  AMSAN- acute motor sensory axonal neuropathy  Acute panautonomic neuropathy  Bickerstaff brainstem encephalitis- altered sensorium, ophthalmoplegia, ataxia, hyperreflexia
  10. 10. Clinical- classic AIDP  s/s- progression over days- <4 weeks  Symmetrical ascending palsy, legs upwards; with areflexia  May affect lower cranial nerves- dysphagia  Facial weakness common, eyes spared  Deep, dull-aching pain, with numbness & tingling  Transient bladder dysfunction  Dx- CSF-raised protein, normal cells; EMG & NCV  Rx- IVIG- 400 mg/kg/d x 5 days or plasmapheresis- 50 ml/kg exchange, 4 times over a week  Px- ~80% complete recovery, ~10%- severe disability, ~10%- CIDP; poor Px- age >40, preceding diarrhea, requiring mechanical ventilation, high anti-GM1 titres
  11. 11. CIDP- Chronic inflammatory demyelinating polyneuropathy  A progressive inflammatory neuropathy over >8 weeks  s/s- symmetrical  Weakness, numbness/tingling, dull aching pain  Autonomic- orthostatic hypotension, bowel-bladder dysfunction, arrythmia  Muscle atrophy, fasciculation, areflexia  Dx- clinical + EMG/NCV ± sural nerve biopsy  Rx- steroids, IVIG, plasmapheresis & immunosuppressives- cyclophosphamide, azathioprine, mycophenolate mofetil, rituximab
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