Multiple Sclerosis

Overview

  • An inflammatory, demyelinating disorder of the CNS
  • Characterised by neural plaques disseminated in time and space
  • More common in females (3:1); usually presents in early adulthood (20s, early 30s)

Aetiology

  • Genetic predisposition (family history)
  • Geography (more common the further away from the equator you live)
  • Immune mediated (mechanisms are still unclear)

Clinical Course/Type

  • Relapsing remitting; secondary progressive (NB nearly 60% of relapsing/remitting will become secondary progressive)
  • Relapsing progressive
  • Primary progressive

Clinical Features

  • Visual Loss
    • Optic Neuritis
      • Painful visual loss
      • Lasts 1-2 weeks- most improve after that
      • Classic sign is an RAPD
        • On moving the penlight to the affected eye- both pupils dilate
  • Pyramidal dysfunction
    • UMN dysfunction
      • Weakness; spasticity; hyperreflexia
  • Sensory symptoms
  • Lower urinary tract dysfunction
    • Increased tone at bladder neck
    • Detrusor hypersensitivity
    • Detrusor sphyncteric dysenergia
      • All 3 of the above cause frequency; nocturia; urgency; urge incontinence; retention
  • Cerebellar/brainstem features
    • gait/vestibular problems
    • Facial weakness (+/- forehead involvement)
  • Cognitive impairment

Investigations

  • MRI- brain and spine
    • hyperdense plaques
    • brain atrophy (early sign)
  • CSF
    • Oligoclonal bands (protein analysis)
  • Neurophysiology
    • Visual evoked response
      • Electrode measures response to strobe light
      • Delayed in MS
  • Bloods
    • Negative for most tests

Diagnosis

  • At least two episodes demonstrating disseminating lesions in time/space
  • McDonald Criteria

Treatment

Acute Treatment

  • Mild attack- symptomatic tx
    • Pyramidal dysfunction
      • Weakness/spasticity
        • Physio/OT
        • Anti-spasmodics
          • Baclofen, tizanidine
          • IM botulinum
          • Intrathecal baclofen/phenol (more used for relapses with severe spasticity)
        • Nerve blocks
    • Lower Urinary Tract Dysfunction
      • Anticholinergics
        • Oxybutynin
      • Catheterisation (autonomous intermittent or permanent)
      • Desmopressin may be used to reduce the risk of over-filling symptoms (less commonly used)
      • Rarely, bladder drilling
    • Fatigue
      • Amantadine
      • Modafinil if sleepy
      • Hyperbaric oxygen
    • Sensory Symptoms
      • Anticonvulsants
        • Gabapentin
      • Antidepressants
        • Amitriptyline
      • TENS
  • Moderate attacks
    • Oral prednisolone
  • Severe attacks
    • IV Prednisolone

Disease modifying therapy (long-term tx)

  • Interferon Beta (Avonex, Rebif, Betaseron)
    • Decrease relapse rate by 1/3
    • Decrease severity of relapses by 50%
Mode of action for interferon beta: multiple antiinflammatory actions
  • Glitiramer Acetate (Copaxone)
    • Slower mode of onset (6-9 months); S/C injection
    • Similar effect on relapses as interferon but better tolerated
    • (Effect on MRI less pronounced)
  • Tysabri (natalizumab)
    • 3rd line
    • Works as an antibody that antagonises integrins that allow inflammatory cells to cross the endothelium and by deactivating inflammatory cells
    • Much more effective; much more expensive
    • Possible association with prion diseases and progressive multifocal leukoencephalopathy
  • Others
    • Mitoxantrone
      • Used in RPMS
      • 12 infusions over 2 years
      • Cardiotoxicity is dose related
    • Fingolimod (awaiting NICE/SMC guidance)
      • S1P modulator
      • >50% reduction in relapse rate; oral agent
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