for an overview of the neurological assessment see:

• neurology

• an auto-immune 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 remains to be fully elucidated:
  • more than 230 genetic loci associated with susceptibility to the disease
    • a 2023 study revealed these genetic variants associated with a risk of developing MS 'travelled' with the Yamnaya people - livestock herders who migrated over the Pontic Steppe into North-Western Europe 5000yrs ago which partly explains higher prevalence of MS in Northern Europe than in Southern Europe ¹⁾
    • these genetic variants provided a survival advantage to the Yamnaya people, most likely by protecting them from catching infections from their sheep and cattle.
  • 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
    • it seems EBV has a complicated and multidimensional role in MS formation and progression, which may explain the high level of illness heterogeneity across individuals. Stimulating EBV-expanded polyclonal T cell lines with 9 candidate CNS autoantigens revealed a high level of autoreactivity and indicate a far-reaching ability of the virus-induced T cell compartment to damage the CNS.²⁾
  • the GIT microbiome
    • a 2025 study suggests Eisenbergiella tayi and Lachnoclostridium in the gut microbiome may trigger MS ³⁾

• it is thought that an imbalance of immunosuppressive regulator T cells (Treg) and immune system activating effector CD4+ T cells which are primed to target myelin in nerve cells results in inflammatory response targeting the myelin sheaths which then impairs neuronal transmission of those neurons
  • a 2023 study in mice showed that injecting engineered biodegradable polymeric microparticles (Tol-MPs) designed to deliver three key therapeutic agents to increase myelin-specific Treg cells was able to halt inflammation and allow time for repair in the mouse model of MS - autoimmune encephalomyelitis (EAE) with all mice showing reversal of symptoms and a third fully recovering.⁴⁾
    • the 3 components were:
      • a fusion of the protein interleukin-2 (IL-2), which stimulates T cell production and growth, and an antibody that blocks certain binding sites on IL-2 to optimize the ones relevant to Treg expansion.
      • a major histocompatibility complex (MHC) class II molecule with a myelin peptide (protein fragment) presented on its surface to immunologically select myelin-specific (and therefore, protective of the nerve cell covering) Tregs rather than other T cell types.
      • rapamycin, an immunosuppressant drug that helps lower the number of effector T cells

• 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
    • see also transient ischaemic attack (TIA)
• 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

• 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

• 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

• 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

George Jelinek's holism study for overcoming MS