Lesional demyelinations of the central nervous system
Pre-active lesion here refers to lesions localized in the normal appearing white matter, without apparent loss of myelin but nevertheless showing a variable degree of oedema, small clusters of microglial cells with enhanced major histocompatibility complex class II antigen, CD45 and CD68 antigen expression and a variable number of perivascular lymphocytes around small blood vessels[20] Using high field MRI system, with several variants several areas show lesions, and can be spacially classified in infratentorial, callosal, juxtacortical, periventricular, and other white matter areas.
[24] The distribution of the lesions could be linked to the clinical evolution[25] Post-mortem autopsies reveal that gray matter demyelination occurs in the motor cortex, cingulate gyrus, cerebellum, thalamus and spinal cord.
[26] Cortical lesions have been observed specially in people with SPMS but they also appear in RRMS and clinically isolated syndrome.
It is known that two parameters of the cortical lesions, fractional anisotropy (FA) and mean diffusivity (MD), are higher in patients than in controls.
"Dawson's fingers" is the name for the lesions around the ventricle-based brain veins[32][33] of patients with multiple sclerosis and antiMOG associated encephalomyelitis[34] Though once thought to be specific of MS, it is known not to be the case.
[35] The condition is thought to be the result of inflammation or mechanical damage by blood pressure[30] around long axis of medular veins.
[39] The hallmark of MS is the lesion, which appears mainly in the white matter and shows macrophage mediated demyelination, BBB breakdown, inflammation and axon transection.
BBB is a tight vascular barrier between the blood and brain that should prevent the passage of antibodies through it, but in MS patients it does not work.
For unknown reasons special areas appear in the brain and spine, followed by leaks in the blood–brain barrier where immune cells infiltrate.
The attack of myelin starts inflammatory processes, which triggers other immune cells and the release of soluble factors like cytokines and antibodies.
These scars (sclerae) are the known plaques or lesions usually reported in MS. A repair process, called remyelination, takes place in early phases of the disease, but the oligodendrocytes are unable to completely rebuild the cell's myelin sheath.
Repeated attacks lead to successively less effective remyelinations, until a scar-like plaque is built up around the damaged axons.
According to the view of most researchers, a special subset of lymphocytes, called T helper cells, specifically Th1 and Th17,[40] play a key role in the development of the lesion.
Under laboratory conditions, stem cells are quite capable of proliferating and differentiating into remyelinating oligodendrocytes; it is therefore suspected that inflammatory conditions or axonal damage somehow inhibit stem cell proliferation and differentiation in affected areas[55] It is possible to predict how much and when lesion will recover[56] Related to this, it was found in 2016 that neural cells of primary progressive patients (PPMS) do have some kind of problem to protect neuroprotection against demyelination or oligodendrocytes, compared to healthy subjects.
Some genetics seem to underlie the problem as this was shown using Induced pluripotent stem cell (iPSC) as neural progenitor cells (NPC)[57] Four different damage patterns, known as Lassmann patterns,[58] have been identified by her team in the scars of the brain tissue in multiple sclerosis, and they are used sometimes as a basis for describing lesions in other demyelinating diseases.
