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Adult brain tumors: Pathology review
Central nervous system infections: Pathology review
Cerebral vascular disease: Pathology review
Congenital neurological disorders: Pathology review
Dementia: Pathology review
Demyelinating disorders: Pathology review
Headaches: Pathology review
Movement disorders: Pathology review
Neurocutaneous disorders: Pathology review
Neuromuscular junction disorders: Pathology review
Pediatric brain tumors: Pathology review
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Multiple Sclerosis Features and Mechanisms
Multiple Sclerosis Interventions
Multiple Sclerosis Symptoms and Diagnosis
multiple sclerosis p. 539
multiple sclerosis p. 727
Daclizumab p. NaN
heart murmur with p. 296
HLA-DR2 and p. 98
IFN- β for p. 200
internuclear ophthalmoplegia p. 560
natalizumab for p. 120
oligodendroglia in p. 505
presentation p. 727
recombinant cytokines for p. NaN
as type IV hypersensitivity p. 111
multiple sclerosis p. 539, 727
Multiple sclerosis is a demyelinating disease of the central nervous system, which includes the brain and the spinal cord.
Myelin is the protective sheath that surrounds the axons of neurons, allowing them to quickly send electrical impulses.
This myelin is produced by oligodendrocytes, which are a group of cells that support neurons.
In multiple sclerosis, demyelination happens when the immune system inappropriately attacks and destroys the myelin, which makes communication between neurons break down, ultimately leading to all sorts of sensory, motor, and cognitive problems.
Now, the brain, including the neurons in the brain, is protected by things in the blood by the blood brain barrier, which only lets certain molecules and cells through from the blood.
For immune cells like T and B cells that means having the right ligand or surface molecule to get through the blood brain barrier, this is kind of like having the a VIP pass to get into an exclusive club.
Once a T cell makes its way in it can get activated by something it encounters - in the case of multiple sclerosis, it’s activated by myelin.
Once the T-cell gets activated, it changes the blood brain barrier cells to express more receptors, and this allows immune cells to more easily bind and get in, it’s kind of like bribing the bouncer to let in a lot of people.
Now, multiple sclerosis is a type IV hypersensitivity reaction, or cell-mediated hypersensitivity. And this means that those myelin specific T-cells release cytokines like IL-1, IL-6, TNF-alpha, and interferon-gamma, and together dilate the blood vessels which allows more immune cells to get in, as well as directly cause damage to the oligodendrocytes.
The cytokines also attract B-cells and macrophages as part of the inflammatory reaction.
Those B-cells begin to make antibodies that mark the myelin sheath proteins, and then the macrophages use those antibody markers to engulf and destroy the oligodendrocytes.
Without oligodendrocytes, there’s no myelin to cover the neurons, and this leaves behind areas of scar tissue, also called plaques or sclera.
In multiple sclerosis, these immune attacks typically happen in bouts.
In other words, an autoimmune attack on the oligodendrocytes might happen, and then regulatory T cells will come in to inhibit or calm down the other immune cells, leading to a reduction in the inflammation.
Early on in multiple sclerosis, the oligodendrocytes will heal and extend out new myelin to cover the neurons, which is a process called remyelination.
Unfortunately, though, over time as the oligodendrocytes die off the remyelination stops and the damage becomes irreversible with the loss of axons.
Just like other autoimmune diseases, the exact cause of multiple sclerosis is unknown, but is linked to both genetic and environmental factors.
Genetic risk factors include being a woman and having genes that encode a specific type of immune molecule called HLA-DR2 which is used to identify and bind to foreign molecules.
Environmental risk factors might include infections as well as vitamin D deficiency, which is an interesting one because it might help explain why the rates of multiple sclerosis are higher at the northern and southern poles compared to the equator where there’s a lot more sunlight.
Multiple sclerosis is a progressive, demyelinating disease on the central nervous system, characterized by the destruction of myelin, the protective sheath surrounding nerve cells, as well as inflammation and scarring of nerve fibers.
Damage to these nerves disrupts the ability of parts of the nervous system to transmit impulses, resulting in a wide range of signs and symptoms, including physical, mental, and sometimes psychiatric problems. Symptoms vary widely, but they may include muscle weakness, fatigue, vision problems, balance and coordination problems, and problems with memory and thinking.
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