ETIOLOGY
The cause of multiple sclerosis is unknown. It's considered to be an autoimmune disease. Like all
autoimmune disorders, it is more common in women, occurring about twice as often in women as in
men. MS also appears to involve genetic factors with HLA-DR2 in DR-positive families—having a greater
chance of developing the disease. The risk of concordant MS is 30% with monozygotic twins, 5% with
dizygotic twins, and between 2% and 4% for first-degree family members of people with MS.
Multiple genetic linkage studies have confirmed a linkage with the major histocompatibility region, as
well as less well-defined linkages to other zones that code for interleukins. MS is not increased in
children adopted into families with MS, which indicates that family aggregation of MS is due to genetic
factors rather than environmental. The specific cause of MS remains unknown.
PATHOPHYSIOLOGY
In patients with MS, the immune response triggers activation of immune cells (e.g., T cells, CD4+ helper
T cells, B cells) that cross the blood–brain barrier. In turn, these cells activate autoantigens, producing
autoimmune cytotoxic effects within the central nervous system (CNS) (this process can be viewed as a
form of “friendly fire”). Phagocytic activity of macrophages may also contribute to demyelination.
Myelin serves as an insulator, speeding up the conduction along nerve fibers from one node of Ranvier
to another (termed saltatory conduction). It also serves to conserve energy for the nerve because
depolarization occurs only at the nodes. Disruption of the myelin sheath and active demyelination slows
neural transmission and causes nerves to fatigue rapidly. With severe disruption, conduction block
occurs with resulting disruption of function.
An acute inflammatory event emerges. Edema and infiltrates (e.g., monocytes, macrophages, and
microglia) surround the acute lesion and can cause a mass effect (abnormally high pressures), further
interfering with the conductivity of the nerve fiber. Conceivably, this inflammation (which gradually
subsides) may, in part, account for the pattern of fluctuations in function that characterize this disease.
With repeat attacks, the anti-inflammatory processes become less effective and are unable to keep up.
During the early stages of MS, oligodendrocytes (myelin-producing cells) survive the initial insult and can
produce remyelination.
This process is often incomplete and, as the disease becomes more chronic, stalls altogether. Eventually,
the oligodendrocytes become involved and myelin repair cannot occur. One form of MS, primary-
progressive MS, appears to be associated exclusively with a disease of the oligodendrocytes.
Demyelinated areas eventually become filled with fibrous astrocytes and undergo a process called
gliosis. Gliosis refers to the proliferation of neuroglial tissue within the CNS and results in glial scars
(plaques). At this stage, the axon itself becomes interrupted and undergoes neurodegeneration. his is
believed to be the main cause of permanent neurological disability.
In advanced cases, there are both acute and degenerative lesions of varying size scattered throughout
the CNS (brain, brainstem, cerebellum, and spinal cord). Lesions primarily affect white matter early, with
lesions of gray matter evident in more advanced disease (type 1 lesions). Lesions may also include small
perivascular areas of demyelination (type 2 lesions) and pial surface lesions (type 3). Brain atrophy, the
loss of axons and myelin throughout the brain, is evident even in early stages of the disease and is
progressive. There are certain areas of predilection, such as the optic nerves, periventricular white
matter, spinal cord (corticospinal tracts, posterior white columns), and cerebellar peduncles.
REFERENCE:
Textbook: Delisa's physical medicine and rehabilitation 5th edition
Textbook: Physical Rehabilitation, 6th edition, Susan B. O’Sullivan, homas J. Schmitz, George D. Fulk.
