Pathophysiology of MS
MS is characterized by CNS inflammation, demyelination, axonal injury and neurodegeneration. Current consensus dictates that it is an autoimmune disorder. However, to date, no specific precipitating antigen has been found. A general consensus is that MS begins with the formation of acute inflammatory lesions characterized by breakdown of the blood-brain barrier (BBB). These lesions are often clinically ‘silent’ and have been estimated to be about ten times more frequent than episodes of clinical worsening (Stone et al., 1995). Disruption of the BBB typically lasts for about a month and then resolves, leaving an area of damage that can be visualized by conventional magnetic resonance imaging. During the early disease stages of RRMS, the …show more content…
Autoreactive T cells, which are believed to be activated outside the CNS, cross the blood-brain barrier where they encounter their specific antigen-presenting macrophages and/or dendritic cells. This leads to secretion of proinflammatory cytokines stimulating microglial cells and astrocytes, which in turn recruits additional inflammatory cells, inducing antibody production by plasma cells. This inflammatory cascade causes tissue damage and lesion formation. The oligodendrocytes holds a certain capacity for remyelination, and the damage can be repaired to some extent. As the disease progresses this repair capacity seems to be exhausted and formation of more permanent tissue damage is observed as ‘black holes’ on T1-weighted magnetic resonance images. The brain cortex is also affected from early on in the disease, with the presence of inflammation and neurodegeneration finally leading to cortical atrophy. Axonal loss is generally regarded as being secondary to demyelination (‘outside-in’ model), however a recent theory suggests that primary axonal injury may initiate secondary inflammation and demyelination (‘inside-out’ model). Whether one process predominates or both occur simultaneously
MS is characterized by CNS inflammation, demyelination, axonal injury and neurodegeneration. Current consensus dictates that it is an autoimmune disorder. However, to date, no specific precipitating antigen has been found. A general consensus is that MS begins with the formation of acute inflammatory lesions characterized by breakdown of the blood-brain barrier (BBB). These lesions are often clinically ‘silent’ and have been estimated to be about ten times more frequent than episodes of clinical worsening (Stone et al., 1995). Disruption of the BBB typically lasts for about a month and then resolves, leaving an area of damage that can be visualized by conventional magnetic resonance imaging. During the early disease stages of RRMS, the …show more content…
Autoreactive T cells, which are believed to be activated outside the CNS, cross the blood-brain barrier where they encounter their specific antigen-presenting macrophages and/or dendritic cells. This leads to secretion of proinflammatory cytokines stimulating microglial cells and astrocytes, which in turn recruits additional inflammatory cells, inducing antibody production by plasma cells. This inflammatory cascade causes tissue damage and lesion formation. The oligodendrocytes holds a certain capacity for remyelination, and the damage can be repaired to some extent. As the disease progresses this repair capacity seems to be exhausted and formation of more permanent tissue damage is observed as ‘black holes’ on T1-weighted magnetic resonance images. The brain cortex is also affected from early on in the disease, with the presence of inflammation and neurodegeneration finally leading to cortical atrophy. Axonal loss is generally regarded as being secondary to demyelination (‘outside-in’ model), however a recent theory suggests that primary axonal injury may initiate secondary inflammation and demyelination (‘inside-out’ model). Whether one process predominates or both occur simultaneously