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
  • Pain; anaesthesia; numbness; trigeminal neuralgia
  • Proprioceptive loss
• 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