Multiple sclerosis

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.

Together these genetic and environmental influences might lead to the body not killing off immune cells that target myelin.

So it turns out that there are four main types of multiple sclerosis based on the pattern of symptoms over time. To break this down, we can use this graph with time on the x-axis, where time refers to the lifespan of the individual, and disability on the y-axis.

The first, and by far the most common pattern of multiple sclerosis, is called relapsing-remitting multiple sclerosis or RRMS. This condition is what we just described, bouts of autoimmune attacks happening months, or even years, apart, and causing an increase in the level of disability.

For example, during a bout a person may lose some vision, but then it may be followed by improvement if there’s remyelination.

Unfortunately, though, more often than not, the remyelination process is not complete so there is often some residual disability that remains, and that means that with each attack, more and more of the central nervous system gets irreversibly damaged.

In the relapsing-remitting multiple sclerosis type there’s typically no increase in disability between bouts, so the line stays flat during that time.

Now, the second type is called secondary progressive multiple sclerosis or SPMS which initially is pretty similar to the relapse-remitting type, but over time the immune attack becomes constant which causes a steady progression of disability.

The third type is primary-progressive multiple sclerosis or PPMS, which is basically one constant attack on myelin which causes a steady progression of disability over a person’s lifetime.

The final type is progressive relapsing multiple sclerosis or PRMS, which is also one constant attack but this time there are bouts superimposed during which the disability increases even faster.

Specific symptoms varying a lot from person to person, and largely depend on the location of the plaques.