Multiple sclerosis pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D.,


Multiple sclerosis is a disease of the central nervous system and it’s known to be multi factorial. Whatever the trigger is, it will lead to an acquired immune response followed by inflammatory reactions. These reactions lead to secretion of cytokines in the CNS parenchyma and activation of resident microglia. Microglia cells activate astrocytes to release more inflammatory cytokines, leading to recruitment and infiltration of circulatory leukocytes. This burst events cause destruction of myelin sheath and forms focal sclerotic white matter plaques, which are characteristic of multiple sclerotic disease. There is some evidence proving genetic involvement in onset of MS so that it increases the risk of developing MS from 0.1% in general population to 3% in those who have siblings with MS and 25% in those with a monozygote twin affected. Based on studies performed on post mortem brain tissue of patients with multiple sclerosis, there are four types of white matter lesion pathology. Damage to myelin sheath is prominent in type 1 and 2 while type 3 and 4 characteristic is dying oligodendrocytes. the etiology of oligodendrocytes death known to be multifactorial or followed by hypoxia, mitochondrial dysfunction and macrophages.



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  • There is some evidence proving genetic involvement in onset of MS so that it increases the risk of developing MS from 0.1% in general population to 3% in those who have siblings with MS and 25% in those with a monozygote twin affected.[26]
  • HLA alleles seems to have a huge relationship with MS susceptibility.[27]

Microscopic Pathology

Based on studies performed on post mortem brain tissue of patients with multiple sclerosis, there are four types of white matter lesion pathology:[28][8]

NOTE: Damage to myelin sheath is prominent in type 1 and 2 while type 3 and 4 characteristic is dying oligodendrocytes.[8][30] the etiology of oligodendrocytes death known to be multifactorial or followed by hypoxia, mitochondrial dysfunction and macrophages.[31][32]

Photomicrograph of a demyelinating MS-Lesion. Immunohistochemical staining for CD68 highlights numerous macrophages (brown) . Original Magnification 10x Source: Librepathology
Photomicrograph of a demyelinating MS-Lesion. Klüver-Barerra-Stain. Original Magnification 10x Source: Librepathology


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