Multiple Sclerosis

Cell-mediated autoimmune condition characterised by repeated episodes of inflammation of the nervous tissue in the brain and spinal cord, causing loss of the insulating myelin sheath

Aetiology

  • Greater incidence in females (3:1)
  • Presentation is typically between 20 and 40 years of age
  • Much more common in white populations and with increasing distance from the equator
  • Causes of MS are not completely understood but the autoimmune process appears to be caused both by genetic and environmental factors
    • At least 60 genes have been implicated in the development of MS, with the majority of these relating to immune system function and regulation, including HLA and MHC polymorphisms
    • Environmental factors which have been implicated include viral infections (e.g. EBV), and vitamin D deficiency

Pathophysiology

  • T-cell-mediated autoimmune disease that causes an inflammatory process mainly within the white matter of the brain and spinal cord
  • Plaques of demyelination occur anywhere in CNS white matter but have a predilection for certain sites including the optic nerves, the brainstem and its cerebellar connections and the cervical cord (corticospinal tracts and posterior columns)
  • Peripheral myelinated nerves are not directly affected in MS

Pathophysiology of lower urinary tract dysfunction

  • Increased tone at bladder neck
  • Detruser hypersensitivity
  • Detruser sphyncteric dyssenergia

Patterns of MS

  • Relapsing-remitting MS (RRMS) (85-90%) - symptoms occur in attacks (relapses) with a characteristic time course: onset over days and typically recovery, either partial or complete, over weeks
  • Secondary progressive MS - this late stage of MS consists of gradually worsening disability progressing slowly over years; some 75% of patients with relapsing-remitting MS will eventually evolve into a secondary progressive phase by 35 years after onset
  • Primary progressive MS (PPMS) (10-15%) - characterized by gradually worsening disability without relapses or remissions
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Clinical presentation

  • Pyramidal dysfunction
    • Increased tone
    • Spasticity
    • Weakness
    • Affects extensors of upper limbs and flexors of lower limbs
  • Optic neuritis
    • Painful visual loss over 1-2 weeks - blurred vision in one eye and loss (or reduction) in colour vision
    • Most improve
    • RAPD (relative afferent pupilary defect) on examination
  • Sensory symptoms
    • Pain
    • Paraesthesia
    • Dorsal column loss - proprioception and vibration
    • Numbness
    • Trigeminal neuralgia
  • Lower urinary tract dysfunction
    • Increased frequency and urgency
    • Nocturia
    • Urge incontinence
    • Retention
  • Cerebellar dysfunction
    • Dysarthria
    • Ataxia
    • Intention tremor
    • Past pointing
    • Pendular reflexes
    • Dysdiadokinesis
  • Brainstem dysfunction
    • Diplopia - CN VI palsy
    • Facial weakness - CN VII palsy
  • Internuclear opthalmoplegia
    • Involves the medial longitudinal fasciculus
    • Distortion of binocular vision
    • Failure of adduction - diplopia
    • Nystagmus in abducting eye
    • Lag
  • Fatigue
    • Physical and cognitive
    • Sense of exhausation

Investigations

Bloods

  • Before referring to a neurologist, exclude differential diagnoses by checking FBC, inflammatory markers, U&E, LFT, TFT, glucose, HIV serology, calcium and B12 levels

Neurophysiology

  • Can detect demyelination in apparently unaffected pathways with characteristic delays

MRI

  • Periventricular lesions
  • Discrete white matter abnormalities
  • Areas of focal demyelination
  • Active inflammatory plaques can be distinguished from inactive ones by using a contrast agent

CSF

  • Oligoclonal bands present in 90+% of cases - distinct bands of IgG on Western blot that are unmatched with serum testing

Management

Acute relapse

  • Mild - symptomatic treatment
  • Moderate - oral steroids
  • Severe - admit/IV steroids

Symptomatic treatment

Pyramidal dysfunction
  • Physiotherapy
  • Occupational therapy
  • Anti-spasmodic agent e.g. oral baclofen, oral tizanidine, botulinum toxin, intrathecal baclofen
Sensory symptoms
  • Anticonvulsant e.g. gabapentin
  • Antidepressant e.g. amitriptyline
  • TENS machine
  • Acupuncture
  • Lignocaine infusion
Lower urinary tract dysfunction
  • Bladder drill
  • Anti-cholinergics e.g. oxybutynin
  • Desmopressin
  • Catheterisation
Fatigue
  • Amantadine
  • Modafinil if sleepy
  • Hyperbaric oxygen

Disease modifying therapy

First line
  • Tecfedira, aubagio
  • Interferon beta
  • Glitiramer acetate
Second line
  • Monoclonal antibody - tysabri, ocrevus, lemtrada
  • Fingolimod, cladrabine
Third line
  • Mitoxantrone
  • HSCT (stem cell transplantation)