Definition

A demyelinating disorder that is immune-mediated, characterized by

preferential destruction of central nervous system (CNS) myelin.
A chronic disease characterized by inflammation, demyelination,
gliosis (scarring), and neuronal loss.
Course of the disease can be relapsing-remitting or progressive.
Longo DL, Fauci AS, et al. Harrisons Principle of Internal Medicine, 18
th
Edition

Anatomy
Myelin
An insulating layer, or sheath, that forms around nerves, including
those in the brain and spinal cord. It is made up of protein and
fatty substances.
The purpose of the myelin sheath is to allow electrical impulses to
transmit quickly and efficiently along the nerve cells. If myelin is
damaged, the impulses slow down.

Calabresi PA. Multiple sclerosis and demyelinating conditions of the central nervous system.
In: Goldman L, Schafer AI, eds. Cecil Medicine. 24th ed. 2011
Anatomy
New MS lesions begin with perivenular cuffing by inflammatory
mononuclear cells (predominantly T cells and macrophages) which
also infiltrate the surrounding white matter.
At sites of inflammation, the blood-brain barrier (BBB) is disrupted
but the vessel wall is preserved.
Involvement of the humoral immune system is also evident wherein
small numbers of B lymphocytes also infiltrate the nervous system,
and myelin-specific autoantibodies are present on degenerating
myelin sheaths.
Longo DL, Fauci AS, et al. Harrisons Principle of Internal Medicine, 18
th
Edition

Anatomy
As lesions evolve or worsen, there is prominent astrocytic
proliferation (gliosis).
Surviving oligodendrocytes (those that differentiate from precursor
cells can partially remyelinate the surviving naked axons producing
so-called shadow plaques.
In many lesions, oligodendrocyte precursor cells are present in large
numbers but fail to differentiate and remyelinate.
Longo DL, Fauci AS, et al. Harrisons Principle of Internal Medicine, 18
th
Edition
Anatomy
Over time, ectopic lymphocyte follicles appear in perivascular and
perimeningeal regions, consisting of aggregates of T and B cells and
resembling secondary lymphoid structures.
Although relative sparing of axons is typical of MS, partial or total
axonal destruction can also occur, especially within highly
inflammatory lesions.
MS is not solely a disease of myelin, and neuronal pathology is
increasingly recognized as a major contributor to irreversible
neurologic disability. Inflammation and plaque formation are present
in the cerebral cortex, and significant axon loss indicating death of
neurons is widespread, specially in advanced cases.
Longo DL, Fauci AS, et al. Harrisons Principle of Internal Medicine, 18
th
Edition
Clinical Signs and Symptoms
MS can cause a wide variety of clinical features.
Many signs and symptoms are characteristic, and a few are virtually
pathognomonic for the disorder.
Sensory symptoms are the most common presenting manifestation in
MS (21 to 55 percent) and ultimately develop in nearly all patients.
Goetz, Christopher, Goetz: Textbook of Neurology, 2
nd
Edition
Longo DL, Fauci AS, et al. Harrisons Principle of Internal Medicine, 18
th
Edition
Clinical Signs and Symptoms
Longo DL, Fauci AS, et al. Harrisons Principle of Internal Medicine, 18
th
Edition