Medically Fit For Exams
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Multiple Sclerosis

Definition

An autoimmune demyelinating condition, affecting central and peripheral neurons, with characteristic patterns of functional loss

 

Risk factors

  • Female
  • Other autoimmune
  • EBV
  • Vit D deficiency
  • White/European
  • Smoking
  • Genetics

 

Differential diagnoses

  • Motor neurone disease
  • ALS
  • Guillain-Barré syndrome
  • Fibromyalgia
  • Stroke
  • Parkinson’s
  • Epilepsy

 

Epidemiology

  • More common the further north of the equator, possible link with vitamin D deficiency
  • More common in females
  • Onset normally 20-50

 

Aetiology

  • Autoimmune, may be triggered by EBV (molecular mimicry)
  • Demyelination

 

Clinical features

  • Can affect any myelinated neuron, but typically affects:
    • Optic nerve
      • Optic neuritis (pain)
      • Blurred vision
      • Episcleritis
      • Papilloedema, optic disk pallor
      • RAPD
      • Reduced colour vision
      • Visual symptoms worse in high temperature (slower conduction in heat)
    • Brainstem
      • Diplopia (CN3)
      • Vertigo/dizziness
      • Facial numbness/weakness (CN5,7)
      • Dysarthria (cerebellum)
      • Dysphagia (CN9,10)
    • Spinal cord
      • Paraparesis (partial paralysis of lower limbs) – result of plaque in cervical or thoracic cord
      • Paraesthsia (reduced or changed sensation) – numbness, tingling, water trickling, reduced proprioception etc
      • Lhermitte’s sign (feeling of electrical shock passing down body)
      • Sensation of tight band in abdomen or chest
      • Urinary symptoms – incontinence, urinary retention
      • Faecal incontinence
      • Sexual dysfunction
    • Other symptoms include:
      • Fatigue
      • Depression
      • Neuropathic pain
  • Are four main patterns of disease progression:
    • Relapsing-remitting accounts for about 85%
    • About 60% progress to secondary progressive
    • Primary progressive account for about 10%
    • Progressive relapsing accounts for about 5%

Pathophysiology

  • T cells gain entry across the BBB (which they do not cross in health), and they recognise myelin surface proteins as foreign (brain-specific peptides are not expressed in the thymus during T cell training)
  • May have been previously exposed to pathogens with antigens similar to that on myelin, which would predispose them to become activated on encountering brain myelin, eg EBV
  • Activated T cells release cytokines which:
    • Degrade the BBB, allowing entry of other immune cells such as B cells (which produce antibodies against myelin) and more T cells
    • Directly degrade myelin
    • Initiate inflammatory response
  • Activated T cells differentiate into Th17, which can be autoreactive, and directly damages myelin
  • Oligodendrocytes act to remyelinate axons, which account for the remission stages, although oligodendrocytes are damaged as the disease progresses, and slow their ability to regenerate
  • Long term inflammation and disruption of axonal signalling (from demyelination) leads to degeneration in the neurons
  • The chronic inflammatory state adds to this axonal damage, which results in many of the symptoms associated with loss of function
  • Damaged to neurons leads to scarring (sclerosis) at multiple locations - plaques

 

Investigations

  • Neurological exam, including fundoscopy
  • MRI brain and spinal cord to assess for plaques
  • Exclusion of other causes
    • FBC
    • Thyroid function
    • Vit B12
    • Metabolic screen
  • Lumbar puncture/CSF evaluation
    • 80% of MS have raised levels of immune cells
  • Evoked potentials/conduction testing

 

Management

  • Immunosuppressant medication
  • Beta - interferon therapy - disease modifying, reduces severity and frequency of relapses, for use in relapsing-remitting MS
  • Biologics eg fingolimod, natalizumab
  • Corticosteroids to increase speed of remission following relapse

 

Prognosis

  • Life expectancy is reduced by months to a few years
  • Quality of life may be affected as a result of the disability and loss of function that goes with MS
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