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ms

multiple sclerosis (MS)

for an overview of the neurological assessment see:

introduction

  • an immune-mediated disorder of the central nervous system
  • untreated MS results in significant physical disability during the prime of life for many with the disease
  • usually diagnosed in persons aged 15-45yrs with females ~twice risk of males
  • prevalence is ~75 per 100,000

aetiology

  • aetiology remains to be fully elucidated:
    • more than 100 genetic loci associated with susceptibility to the disease
    • significant environmental factors:
      • living in low latitudes prior to age 15yrs appears to be protective
      • tropical populations have low risk
      • higher rates in northen Europe
      • relative vitamin D deficiency
      • ?role of sunlight and epigenetics in mother
    • viral infections such as EBV

diagnosis

  • suspect in patients with:
    • optic neuritis
      • 20% of patients with MS present initially with optic neuritis - visual impairment (perhaps color impairment), pain on ocular movement, and sometimes phosphenes (flashes)
      • Uhthoff phenomenon - exacerbation of symptoms induced by exercise, a hot meal, or a hot bath
      • Pulfrich effect - latencies between the eyes are unequal, resulting in a sense of disorientation in moving traffic
    • diplopia from an internuclear ophthalmoplegia (INO)
      • adduction deficit of the ipsilateral eye is present, with horizontal gaze nystagmus in the contralateral abducting eye.
      • lesion involves the medial longitudinal fasciculus (MLF)
    • diplopia due to 6th nerve palsy
    • persistent fatigue
      • one should exclude more common causes of fatigue
    • repeated unexplained neurology (eg. paraesthesiae) lasting > 24hrs
      • sine qua non of MS is that symptomatic episodes are 'separated in time and space'
      • episodes occur months or years apart and affect different nerves
  • remember there is an extensive list of differential diagnoses so don't give the diagnosis too hastily!
  • MRI scan is usually the main diagnostic modality

immunomodulator drug treatment

practicalities of treatment

  • Disease-modifying therapy should be considered in any patient with a first episode of demyelination where supporting evidence in the form of MRI and CSF findings strongly support a diagnosis of MS, or when relapsing-remitting MS has been diagnosed.
  • Patients with active relapsing-remitting disease (2 relapses in 2 years) should be offered beta-interferon, glatiramer acetate, natalizumab, fingolimod, teriflunomide, dimethyl fumarate or alemtuzumab.
  • In very rapidly progressive MS, or when disease fails to respond to standard therapies, the use of immunosuppressive therapies such as mitoxantrone/cyclophosphamide, rituximab, autologous stem cell therapy or combination therapy should be considered carefully
    • ref Broadley, Barnett, King et al MJA 2015 203(3) 3 August

parenteral agents

  • natalizumab (Tysabri) - monthly infusions, risk of Progressive Multifocal Leucoencephalopathy in patients who are JC virus positive
  • alemtuzumab (Lemtrada) - 5 day IV course administered then 3 day course 1 year later, monthly surveillance required due to risk of ITP, Graves' disease, and autoimmune renal complications (anti-GBM antibody glomerulonephritis)
  • beta interferon - safety confirmed over two decades of use, modest efficacy at reducing relapses, noted to have some side effects
  • glatiramer acetate - may act as a decoy target for immune cells

oral agents

  • fingolimod - appears to be safe, reasonably well tolerated
  • teriflunomide - efficacy appears to lie somewhere between the two other oral drugs and the injectable therapies; safety profile so far reassuring
  • dimethyl fumarate
    • a hazardous chemical, when taken orally is rapidly converted to monomethyl fumarate then further metabolised with terminal half-life of 1 hr; most of the dose is exhaled as carbon diaoxide
    • doses of 240mg bd or tds appear to reduce development of new gadolinium-enhancing lesions on MRI
    • adverse reactions include flushing, abdo pain, nausea, vomiting, diarrhoea, lymphopenia, progressive multifocal leukoencephalopathy, raised liver function tests (LFTs), proteinuria
other sources of information on the research into diet and potentially modifiable lifestyle factors go to:
ms.txt · Last modified: 2018/09/16 13:05 (external edit)