page_title: Pathophysiology of multiple sclerosis
section_title: MS lesion development
hierarchical_section_title: Pathophysiology of multiple sclerosis / Physiology of MS / MS lesion development
caption_attribution_description: English: This image shows the four different types of glial cells found in the central nervous system: Ependymal cells &#40;light pink&#41;, Astrocytes &#40;green&#41;, Microglial cells &#40;red&#41;, and Oligodendrocytes (functionally similar to Schwann cells in the PNS) &#40;light blue&#41;.
context_page_description: Multiple sclerosis is an inflammatory demyelinating disease of the CNS in which activated immune cells invade the central nervous system and cause inflammation, neurodegeneration, and tissue damage. The underlying cause is currently unknown. Current research in neuropathology, neuroimmunology, neurobiology, and neuroimaging, together with clinical neurology, provide support for the notion that MS is not a single disease but rather a spectrum.
  There are three clinical phenotypes: relapsing-remitting MS, characterized by periods of neurological worsening following by remissions; secondary-progressive MS, in which there is gradual progression of neurological dysfunction with fewer or no relapses; and primary-progressive MS, in which neurological deterioration is observed from onset.
  Pathophysiology is a convergence of pathology with physiology. Pathology is the medical discipline that describes conditions typically observed during a disease state; whereas physiology is the biological discipline that describes processes or mechanisms operating within an organism.
context_section_description: MS lesions develop inside NAWM areas. Their shape is influenced by their activity
  The most accepted sequence of events is first NAWM appearance, then the so-called pre-active lesions, with activated microglia, and finally the BBB breakdown, which enables the entry of T-cells to the CNS. This marks the beginning of an autoimmune attack which destroys myelin in active lesions. When the attack is resolved, a characteristic glial scar is formed by astrocytes.
  Current models can be divided into two categories: inside-out and outside-in. In the former, it is hypothesized that a problem in CNS cells produces an immune response that destroys myelin and subsequently breaks the BBB. In latter, an external factor produces BBB leaks, enters the CNS, and destroys myelin and axons. Whatever the underlying condition for MS is, it appears that damage is triggered by an unknown soluble factor in the CSF, potentially produced in meningeal areas; this factor can diffuse into the cortical parenchyma and destroy myelin either directly or indirectly through microglia activation.
  The evolution of a preactive lesion is related to microglia reactivity. Increased expression of pro-inflammatory cell surface markers have been observed in NAWM and "initial" lesions, corresponding to a so-called loss of homeostatic microglial equilibrium.
  Some authors report active lesion formation before BBB breakdown; others point to adipsin as a factor of the breakdown.
  MS lesions are driven mainly by T-cells. It has been found recently that B-cells are also involved.
caption: Illustration of the four different types of glial cells found in the central nervous system: ependymal cells, astrocytes, microglial cells, and oligodendrocytes
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