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
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)
a 2025 study suggests Eisenbergiella tayi and Lachnoclostridium in the gut microbiome may trigger MS 3)
pathophysiology
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
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)
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: