Multiple Sclerosis

• Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) which is characterised by demyelination. It is the most common progressive neurological disorder in high-income countries, and in young adults.
• MS is an autoimmune inflammatory process in the central nervous system thought to likely be mediated by aberrant T-cell activation
• Clinically isolated syndrome (CIS) is an otherwise unexplained clinical episode of neurologic dysfunction, and radiologically isolated syndrome (RIS) is evidence of white matter pathology on neuroimaging not attributable to any other pathology in the absence of clinical symptoms.
• Both clinically and radiologically isolated syndrome have features suggestive of MS but they do not meet the McDonald's diagnostic criteria
• The diagnosis of multiple sclerosis requires at least two attacks separated in time and space with characteristic MRI findings or one attack with typical MRI changes and no alternative explanation
• Relapsing-remitting MS (RRMS) is by far the most common form of disease at presentation, encompassing approximately 85% of patients.

  RRMS constitutes unpredictable attacks of neurological dysfunction (lasting >24 hours in the absence of fever), followed by relief of symptoms though patients may not return fully to baseline function
• Secondary progressive MS initially presents as RRMS, then later declines steadily and progressively without remission
• Primary progressive MS is a steady, progressive worsening of disease severity from the onset without remission
• Risk factors for MS include:

  • Family history
  • Female sex
  • Age between 25-35
  • Other co-existing autoimmune diseases
  • Smoking
  • Previous EBV infection
  • Vitamin D deficiency
• Most common symptoms of MS on initial presentation:

  • Limb numbness/tingling
  • Limb weakness (subacute onset)
  • Cerebellar symptoms - loss of balance, diplopia, dysarthria, intention tremor
• Certain phenomena are also considered characteristic of MS:

  • Uhthoff’s phenomenon: worsening of symptoms on exercise/in warm environments (e.g. in a bath).
  • Lhermitte’s phenomenon: lightning-shock pain down the spine on flexion of the neck secondary to cervical cord plaque formation
• Central symptoms of MS:

  • Motor - loss of power and spasticity
  • Sensory - increased sensitivity to pain, tingling, burning and paraesthesia
  • Cerebellar - loss of balance, diplopia, dysarthria and intention tremor
  • Fatigue
  • Depression
• Ophthalmic symptoms of MS:

  • nystagmus
  • optic neuritis - pain on eye movement, visual field defect and loss of colour vision
  • diplopia
• Urinary symptoms of MS include urinary frequency, urgency, and urinary incontinence
• GI symptoms of MS include constipation and/or diarrhoea
• MS is characterised by demyelination and oligodendrocytes
• in MS there is local areas of demyelination called plaques in the white matter - this is where the axons are
• Investigations for MS:

  • FBC - WCC for infection
  • CRP - inflammatory process
  • LFTs - hepatic pathology can mimic MS
  • U&Es - electrolyte disturbances
  • TFTs
  • Vitamin B12 and folate
  • HbA1c
• MRI brain and spine with contrast is used to diagnose MS - it will show T2 hyper intense white matter plaques
• Lumbar puncture is also useful in the diagnosis of MS

  will show high protein and oligoclonal bands in the CSF
• Treatment of an MS relapse:

  • 500mg methyl prednisone for 5 days
  • 1g IV methyl prednisone for 3-5 days
• Treatment options for MS:

  • injectable disease modifying drugs - beta IFN
  • oral disease modifying drugs - dimethyl fumerate
  • monoclonal antibody therapies - alemtuzumab
  • Anticholinergics for incontinence
• Plasmapheresis is also an option if the exacerbation is non-responsive to steroids