unpredictable disease of the central nervous system, multiple sclerosis
(MS) can range from relatively benign to somewhat disabling to
devastating, as communication between the brain and other parts of the
body is disrupted. Many investigators believe MS to be an
autoimmune disease -- one in which the body, through its immune system,
launches a defensive attack against its own tissues. In the case of MS,
it is the nerve-insulating myelin that comes under assault. Such
assaults may be linked to an unknown environmental trigger, perhaps a
an MS attack, inflammation occurs in areas of the white matter*
of the central nervous system in random patches called plaques.
This process is followed by destruction of myelin, the fatty
covering that insulates nerve cell fibers in the brain and spinal cord.
Myelin facilitates the smooth, high-speed transmission of
electrochemical messages between the brain, the spinal cord, and the
rest of the body; when it is damaged, neurological transmission of
messages may be slowed or blocked completely, leading to diminished or
lost function. The name "multiple sclerosis" signifies both
the number (multiple) and condition (sclerosis, from the Greek term for
scarring or hardening) of the demyelinated areas in the central
people experience their first symptoms of MS between the ages of 20 and
40; the initial symptom of MS is often blurred or double vision,
red-green color distortion, or even blindness in one eye. Most MS
patients experience muscle weakness in their extremities and difficulty
with coordination and balance. These symptoms may be severe enough
to impair walking or even standing. In the worst cases, MS can produce
partial or complete paralysis. Most people with MS also exhibit
paresthesias, transitory abnormal sensory feelings such as numbness,
prickling, or "pins and needles" sensations. Some may
also experience pain. Speech impediments, tremors, and dizziness
are other frequent complaints. Occasionally, people with MS have hearing
loss. Approximately half of all people with MS experience cognitive
impairments such as difficulties with concentration, attention, memory,
and poor judgment, but such symptoms are usually mild and are frequently
overlooked. Depression is another common feature of MS.
What Causes MS?
Scientists have learned a great deal about MS in recent years;
still, its cause remains elusive. Many investigators believe MS to
be an autoimmune disease-one in which the body, through its
immune system, launches a defensive attack against its own tissues.
In the case of MS, it is the nerve-insulating myelin that comes
under assault. Such assaults may be linked to an unknown
environmental trigger, perhaps a virus.
The Immune System
To understand what is happening when a person has MS, it is first
necessary to know a little about how the healthy immune system
works. The immune system - a complex network of specialized cells
and organs - defends the body against attacks by "foreign"
invaders such as bacteria, viruses, fungi, and parasites. It does
this by seeking out and destroying the interlopers as they enter the
body. Substances capable of triggering an immune response are called
The immune system displays both enormous diversity and
extraordinary specificity. It can recognize millions of distinctive
foreign molecules and produce its own molecules and cells to match
up with and counteract each of them. In order to have room for
enough cells to match the millions of possible foreign invaders, the
immune system stores just a few cells for each specific antigen.
When an antigen appears, those few specifically matched cells are
stimulated to multiply into a full-scale army. Later, to prevent
this army from overexpanding, powerful mechanisms to suppress the
immune response come into play.
T cells, so named because they are processed in the
thymus, appear to play a particularly important role in MS. They
travel widely and continuously throughout the body patrolling for
foreign invaders. In order to recognize and respond to each specific
antigen, each T cell's surface carries special receptor
molecules for particular antigens.
T cells contribute to the body's defenses in two major ways.
Regulatory T cells help orchestrate the elaborate immune system. For
instance, they assist other cells to make antibodies,
proteins programmed to match one specific antigen much as a key
matches a lock. Antibodies typically interact with circulating
antigens, such as bacteria, but are unable to penetrate living
cells. Chief among the regulatory T cells are those known as helper
(or inducer) cells. Helper T cells are essential for activating the
body's defenses against foreign substances. Yet another subset of
regulatory T cells acts to turn off, or suppress, various immune
system cells when their job is done.
Killer T cells, on the other hand, directly attack diseased or
damaged body cells by binding to them and bombarding them with
lethal chemicals called cytokines. Since T cells can attack
cells directly, they must be able to discriminate between
"self" cells (those of the body) and "nonself"
cells (foreign invaders). To enable the immune system to distinguish
the self, each body cell carries identifying molecules on its
surface. T cells likely to react against the self are usually
eliminated before leaving the thymus; the remaining T cells
recognize the molecular markers and coexist peaceably with body
tissues in a state of self-tolerance.
In autoimmune diseases such as MS, the detente between the immune
system and the body is disrupted when the immune system seems to
wrongly identify self as nonself and declares war on the part of the
body (myelin) it no longer recognizes. Through intensive research
efforts, scientists are unraveling the complex secrets of the
malfunctioning immune system of patients with MS.
Components of myelin such as myelin basic protein have
been the focus of much research because, when injected into
laboratory animals, they can precipitate experimental allergic
encephalomyelitis (EAE), a chronic relapsing brain and spinal
cord disease that resembles MS. The injected myelin probably
stimulates the immune system to produce anti-myelin T cells that
attack the animal's own myelin.
Investigators are also looking for abnormalities or malfunctions
in the blood/brain barrier, a protective membrane that
controls the passage of substances from the blood into the central
nervous system. It is possible that, in MS, components of the immune
system get through the barrier and cause nervous system damage.
Scientists have studied a number of infectious agents (such as
viruses) that have been suspected of causing MS, but have been
unable to implicate any one particular agent. Viral infections are
usually accompanied by inflammation and the production of gamma interferon,
a naturally occurring body chemical that has been shown to worsen
the clinical course of MS. It is possible that the immune response
to viral infections may themselves precipitate an MS attack. There
seems to be little doubt that something in the environment is
involved in triggering MS.
In addition, increasing scientific evidence suggests that
genetics may play a role in determining a person's susceptibility to
MS. Some populations, such as Gypsies, Eskimos, and Bantus, never
get MS. Native Indians of North and South America, the Japanese, and
other Asian peoples have very low incidence rates. It is unclear
whether this is due mostly to genetic or environmental factors.
In the population at large, the chance of developing MS is less
than a tenth of one percent. However, if one person in a family has
MS, that person's first-degree relatives-parents, children, and
siblings-have a one to three percent chance of getting the disease.
For identical twins, the likelihood that the second twin may
develop MS if the first twin does is about 30 percent; for fraternal
twins (who do not inherit identical gene pools), the likelihood is
closer to that for non-twin siblings, or about 4 percent. The fact
that the rate for identical twins both developing MS is
significantly less than 100 percent suggests that the disease is not
entirely genetically controlled. Some (but definitely not all) of
this effect may be due to shared exposure to something in the
environment, or to the fact that some people with MS lesions
remain essentially asymptomatic throughout their lives.
Further indications that more than one gene is involved in MS
susceptibility comes from studies of families in which more than one
member has MS. Several research teams found that people with MS
inherit certain regions on individual genes more frequently than
people without MS. Of particular interest is the human leukocyte
antigen (HLA) or major histocompatibility complex region
on chromosome 6. HLAs are genetically determined proteins that
influence the immune system.
The HLA patterns of MS patients tend to be different from those
of people without the disease. Investigations in northern Europe and
America have detected three HLAs that are more prevalent in people
with MS than in the general population. Studies of American MS
patients have shown that people with MS also tend to exhibit these
HLAs in combination-that is, they have more than one of the three
HLAs-more frequently than the rest of the population. Furthermore,
there is evidence that different combinations of the HLAs may
correspond to variations in disease severity and progression.
Studies of families with multiple cases of MS and research
comparing genetic regions of humans to those of mice with EAE
suggest that another area related to MS susceptibility may be
located on chromosome 5. Other regions on chromosomes 2, 3, 7, 11,
17, 19, and X have also been identified as possibly containing genes
involved in the development of MS.
These studies strengthen the theory that MS is the result of a
number of factors rather than a single gene or other agent.
Development of MS is likely to be influenced by the interactions of
a number of genes, each of which (individually) has only a modest
effect. Additional studies are needed to specifically pinpoint which
genes are involved, determine their function, and learn how each
gene's interactions with other genes and with the environment make
an individual susceptible to MS. In addition to leading to better
ways to diagnose MS, such studies should yield clues to the
underlying causes of MS and, eventually, to better treatments or a
way to prevent the disease.
What is the Course of MS?
Each case of MS displays one of several patterns of presentation
and subsequent course. Most commonly, MS first manifests itself as a
series of attacks followed by complete or partial remissions as
symptoms mysteriously lessen, only to return later after a period of
stability. This is called relapsing-remitting (RR) MS.
Primary-progressive (PP) MS is characterized by a gradual clinical
decline with no distinct remissions, although there may be temporary
plateaus or minor relief from symptoms. Secondary-progressive (SP)
MS begins with a relapsing-remitting course followed by a later
primary-progressive course. Rarely, patients may have a
progressive-relapsing (PR) course in which the disease takes a
progressive path punctuated by acute attacks. PP, SP, and PR are
sometimes lumped together and called chronic progressive MS.
In addition, twenty percent of the MS population has a benign
form of the disease in which symptoms show little or no progression
after the initial attack; these patients remain fully functional. A
few patients experience malignant MS, defined as a swift and
relentless decline resulting in significant disability or even death
shortly after disease onset. However, MS is very rarely fatal and
most people with MS have a fairly normal life expectancy.
Studies throughout the world are causing investigators to
redefine the natural course of the disease. These studies use a
technique called magnetic resonance imaging (MRI) to
visualize the evolution of MS lesions in the white matter of the
brain. Bright spots on a T2 MRI scan indicate the presence of
lesions, but do not provide information about when they developed.
Because investigators speculate that the breakdown of the
blood/brain barrier is the first step in the development of MS
lesions, it is important to distinguish new lesions from old. To do
this, physicians give patients injections of gadolinium, a
chemical contrast agent that normally does not cross the blood/brain
barrier, before performing a scan. On this type of scan, called T1,
the appearance of bright areas indicates periods of recent disease
activity (when gadolinium is able to cross the barrier). The ability
to estimate the age of lesions through MRI has allowed investigators
to show that, in some patients, lesions occur frequently throughout
the course of the disease even when no symptoms are present.
Can Life Events Affect the Course of MS?
While there is no good evidence that daily stress or trauma
affects the course of MS, there is data on the influence of
pregnancy. Since MS generally strikes during childbearing years, a
common concern among women with the disease is whether or not to
have a baby. Studies on the subject have shown that MS has no
adverse effects on the course of pregnancy, labor, or delivery; in
fact symptoms often stabilize or remit during pregnancy. This
temporary improvement is thought to relate to changes in a woman's
immune system that allow her body to carry a baby: because every
fetus has genetic material from the father as well as the mother,
the mother's body should identify the growing fetus as foreign
tissue and try to reject it in much the same way the body seeks to
reject a transplanted organ. To prevent this from happening, a
natural process takes place to suppress the mother's immune system
in the uterus during pregnancy.
However, women with MS who are considering pregnancy need to be
aware that certain drugs used to treat MS should be avoided during
pregnancy and while breast feeding. These drugs can cause birth
defects and can be passed to the fetus via blood and to an infant
via breast milk. Among them are prednisone, corticotropin,
azathioprine, cyclophosphamide, diazepam, phenytoin, carbamazepine,
Unfortunately, between 20 and 40 percent of women with MS do have
a relapse in the three months following delivery. However, there is
no evidence that pregnancy and childbirth affect the overall course
of the disease one way or the other. Also, while MS is not in itself
a reason to avoid pregnancy and poses no significant risks to the
fetus, physical limitations can make child care more difficult. It
is therefore important that MS patients planning families discuss
these issues with both their partner and physician.
What are the Symptoms of MS?
Symptoms of MS may be mild or severe, of long duration or short,
and may appear in various combinations, depending on the area of the
nervous system affected. Complete or partial remission of symptoms,
especially in the early stages of the disease, occurs in
approximately 70 percent of MS patients.
The initial symptom of MS is often blurred or double vision,
red-green color distortion, or even blindness in one eye.
Inexplicably, visual problems tend to clear up in the later stages
of MS. Inflammatory problems of the optic nerve may be diagnosed as retrobulbaror
optic neuritis. Fifty-five percent of MS patients will have
an attack of optic neuritis at some time or other and it will be the
first symptom of MS in approximately 15 percent. This has led to
general recognition of optic neuritis as an early sign of MS,
especially if tests also reveal abnormalities in the patient's
Most MS patients experience muscle weakness in their extremities
and difficulty with coordination and balance at some time during the
course of the disease. These symptoms may be severe enough to impair
walking or even standing. In the worst cases, MS can produce partial
or complete paralysis. Spasticity-the involuntary increased
tone of muscles leading to stiffness and spasms-is common, as is fatigue.
Fatigue may be triggered by physical exertion and improve with rest,
or it may take the form of a constant and persistent tiredness.
Most people with MS also exhibit paresthesias, transitory
abnormal sensory feelings such as numbness, prickling, or "pins
and needles" sensations; uncommonly, some may also experience
pain. Loss of sensation sometimes occurs. Speech impediments,
tremors, and dizziness are other frequent complaints. Occasionally,
people with MS have hearing loss.
Approximately half of all people with MS experience cognitive
impairments such as difficulties with concentration, attention,
memory, and poor judgment, but such symptoms are usually mild and
are frequently overlooked. In fact, they are often detectable only
through comprehensive testing. Patients themselves may be unaware of
their cognitive loss; it is often a family member or friend who
first notices a deficit. Such impairments are usually mild, rarely
disabling, and intellectual and language abilities are generally
Cognitive symptoms occur when lesions develop in brain areas
responsible for information processing. These deficits tend to
become more apparent as the information to be processed becomes more
complex. Fatigue may also add to processing difficulties. Scientists
do not yet know whether altered cognition in MS reflects problems
with information acquisition, retrieval, or a combination of both.
Types of memory problems may differ depending on the individual's
disease course (relapsing-remitting, primary-progressive, etc.), but
there does not appear to be any direct correlation between duration
of illness and severity of cognitive dysfunction. .
Depression, which is unrelated to cognitive problems, is another
common feature of MS. In addition, about 10 percent of patients
suffer from more severe psychotic disorders such as manic-depression
and paranoia. Five percent may experience episodes of inappropriate
euphoria and despair-unrelated to the patient's actual emotional
state-known as "laughing/weeping syndrome." This syndrome
is thought to be due to demyelination in the brainstem, the area of
the brain that controls facial expression and emotions, and is
usually seen only in severe cases.
As the disease progresses, sexual dysfunction may become a
problem. Bowel and bladder control may also be lost.
In about 60 percent of MS patients, heat-whether generated by
temperatures outside the body or by exercise-may cause temporary
worsening of many MS symptoms. In these cases, eradicating the heat
eliminates the problem. Some temperature-sensitive patients find
that a cold bath may temporarily relieve their symptoms. For the
same reason, swimming is often a good exercise choice for people
The erratic symptoms of MS can affect the entire family as
patients may become unable to work at the same time they are facing
high medical bills and additional expenses for housekeeping
assistance and modifications to homes and vehicles. The emotional
drain on both patient and family is immeasurable. Support groups
(listed on a card in the pocket at the back of this pamphlet) and
counseling may help MS patients, their families, and friends find
ways to cope with the many problems the disease can cause.
Possible Symptoms of Multiple Sclerosis
Impairment of pain, temperature, touch senses
Pain (moderate to severe)
How is MS Diagnosed?
There is no single test that unequivocally detects MS. When faced
with a patient whose symptoms, neurological exam results, and
medical history suggest MS, physicians use a variety of tools to
rule out other possible disorders and perform a series of laboratory
tests which, if positive, confirm the diagnosis.
Imaging technologies such as MRI can help locate central nervous
system lesions resulting from myelin loss. MRI is painless,
noninvasive, and does not expose the body to radiation. It is often
used in conjunction with the contrast agent gadolinium, which helps
distinguish new plaques from old. However, since these lesions can
also occur in several other neurological disorders, they are not
absolute evidence of MS.
Several new MRI techniques may help quantify and characterize MS
lesions that are too subtle to be detected using conventional MRI
scans. While standard MRI provides an anatomical picture of lesions,
magnetic resonance spectroscopy (MRS) yields information
about the brain's biochemistry; specifically, it can measure the
brain chemical N-acetyl aspartate. Decreased levels of this chemical
can indicate nerve damage.
Magnetization transfer imaging (MTI) is able to detect
white matter abnormalities before lesions can be seen on standard
MRI scans by calculating the amount of "free" water in
tissues. Demyelinated tissues and damaged nerves show increased
levels of free" (versus "bound") water particles.
Diffusion-tensor magnetic resonance imaging (DT-MRI or
DTI) measures the random motion of water molecules. Individual water
molecules are constantly in motion, colliding with each other at
extremely high speeds. This causes them to spread out, or diffuse.
DT-MRI maps this diffusion to produce intricate, three-dimensional
images indicating the size and location of demyelinated areas of the
brain. Changes in this process can then be measured and correlated
with disease progression.
Functional MRI (fMRI) uses radio waves and a strong
magnetic field to measures the correlation between physical changes
in the brain (such as blood flow) and mental functioning during the
performance of cognitive tasks.
In addition to helping scientists and physicians better
understand how MS develops-an important first step in devising new
treatments-these approaches offer earlier diagnosis and enhance
efforts to monitor disease progression and the effects of treatment.
Other tests that may be used to diagnosis MS include visual
evoked potential (VEP) tests and studies of cerebrospinal fluid
(the colorless liquid that circulates through the brain and spinal
cord). VEP tests measure the speed of the brain's response to visual
stimuli. VEP can sometimes detect lesions that the scanners miss and
is particularly useful when abnormalities seen on MRI do not meet
the specific criteria for MS. Auditory and sensory evoked potentials
have also been used in the past, but are no longer believed to
contribute significantly to the diagnosis of MS. Like imaging
technologies, VEP is helpful but not conclusive because it cannot
identify the cause of lesions.
Examination of cerebrospinal fluid can show cellular and chemical
abnormalities often associated with MS. These abnormalities include
increased numbers of white blood cells and higher-than-average
amounts of protein, especially myelin basic protein and an antibody
called immunoglobulin G. Physicians can use several different
laboratory techniques to separate and graph the various proteins in
MS patients' cerebrospinal fluid. This process often identifies the
presence of a characteristic pattern called oligoclonal bands.
While it can still be difficult for the physician to
differentiate between an MS attack and symptoms that can follow a
viral infection or even an immunization, our growing understanding
of disease mechanisms and the expanded use of MRI is enabling
physicians to diagnose MS with far more confidence than ever before.
Today, most patients who undergo a diagnostic evaluation for MS will
be classified as either having MS or not having MS, although there
are still cases where a person may have the clinical symptoms of MS
but not meet all the criteria to confirm a diagnosis of MS. In these
cases, a diagnosis of "possible MS" is used.
A number of other diseases may produce symptoms similar to those
seen in MS. Other conditions with an intermittent course and MS-like
lesions of the brain's white matter include polyarteritis, lupus
erythematosus, syringomyelia, tropical spastic paraparesis, some
cancers, and certain tumors that compress the brainstem or spinal
cord. Progressive multifocal leukoencephalopathy can mimic the acute
stage of an MS attack. Physicians will also need to rule out stroke,
neurosyphilis, spinocerebellar ataxias, pernicious anemia, diabetes,
Sjogren's disease, and vitamin B12 deficiency. Acute transverse
myelitis may signal the first attack of MS, or it may indicate
other problems such as infection with the Epstein-Barr or herpes
simplex B viruses. Recent reports suggest that the neurological
problems associated with Lyme disease may present a clinical picture
much like MS.
Investigators are continuing their search for a definitive test
for MS. Until one is developed, however, evidence of both multiple
attacks and central nervous system lesions must be found before a
diagnosis of MS is given.
Can MS be Treated?
There is as yet no cure for MS. Many patients do well with no
therapy at all, especially since many medications have serious side
effects and some carry significant risks. Naturally occurring or
spontaneous remissions make it difficult to determine therapeutic
effects of experimental treatments; however, the emerging evidence
that MRIs can chart the development of lesions is already helping
scientists evaluate new therapies.
In September 2010 the U.S. Food and Drug Administration approved
oral administration of the drug fingolimod (Gilenya) to reduce the
frequency of outbreaks in persons with relapsing-remitting MS.
The drug works by keeping some T and B cells in the lymph
glands and preventing them from traveling through and collecting in
the central nervous system.
In the past, the principal medications physicians used to treat
MS were steroids possessing anti-inflammatory properties; these
include adrenocorticotropic hormone (better known as ACTH),
prednisone, prednisolone, methylprednisolone, betamethasone, and
dexamethasone. Studies suggest that intravenous methylprednisolone
may be superior to the more traditional intravenous ACTH for
patients experiencing acute relapses; no strong evidence exists to
support the use of these drugs to treat progressive forms of MS.
Also, there is some indication that steroids may be more appropriate
for people with movement, rather than sensory, symptoms.
While steroids do not affect the course of MS over time, they can
reduce the duration and severity of attacks in some patients. The
mechanism behind this effect is not known; one study suggests the
medications work by restoring the effectiveness of the blood/brain
barrier. Because steroids can produce numerous adverse side effects
(acne, weight gain, seizures, psychosis), they are not recommended
for long-term use.
One of the most promising MS research areas involves naturally
occurring antiviral proteins known as interferons. Three forms of
beta interferon (Avonex, Betaseron, and Rebif) have now been
approved by the Food and Drug Administration for treatment of
relapsing-remitting MS. Beta interferon has been shown to reduce the
number of exacerbations and may slow the progression of physical
disability. When attacks do occur, they tend to be shorter and less
severe. In addition, MRI scans suggest that beta interferon can
decrease myelin destruction.
Investigators speculate that the effects of beta interferon may
be due to the drug's ability to correct an MS-related deficiency of
certain white blood cells that suppress the immune system and/or its
ability to inhibit gamma interferon, a substance believed to be
involved in MS attacks. Alpha interferon is also being studied as a
possible treatment for MS. Common side effects of interferons
include fever, chills, sweating, muscle aches, fatigue, depression,
and injection site reactions.
Scientists continue their extensive efforts to create new and
better therapies for MS. Goals of therapy are threefold: to improve
recovery from attacks, to prevent or lessen the number of relapses,
and to halt disease progression. Some therapies currently under
investigation are discussed below.
As evidence of immune system involvement in the development
of MS has grown, trials of various new treatments to alter or
suppress immune response are being conducted. Most of these
therapies are, at this time, still considered experimental.
Results of recent clinical trials have shown that immunosuppressive
agents and techniques can positively (if temporarily) affect the
course of MS; however, toxic side effects often preclude their
widespread use. In addition, generalized immunosuppression
leaves the patient open to a variety of viral, bacterial, and
Over the years, MS investigators have studied a number of
immunosuppressant treatments. One such treatment, Novantrone
(mitoxantrone), was approved by the
FDA for the treatment of advanced or chronic MS. Other therapies
being studied are cyclosporine (Sandimmune),
(Imuran), and total lymphoid
irradiation (a process whereby the MS patient's lymph nodes are
irradiated with x-rays in small doses over a few weeks to
destroy lymphoid tissue, which is actively involved in tissue
destruction in autoimmune diseases). Inconclusive and/or
contradictory results of these trials, combined with the
therapies' potentially dangerous side effects, dictate that
further research is necessary to determine what, if any, role
they should play in the management of MS. Studies are also being
conducted with the immune system modulating drug cladribine
Another potential treatment for MS is
monoclonal antibodies, which are identical, laboratory-produced
antibodies that are highly specific for a single antigen. They
are injected into the patient in the hope that they will alter
the patient's immune response. One monoclonal antibody, natalizumab
(Tysabri), was shown in clinical
trials to significantly reduce the frequency of attacks in
people with relapsing forms of MS and was approved for marketing
by the U.S. Food and Drug Administration (FDA) in 2004.
However, in 2005 the drug’s manufacturer voluntarily
suspended marketing of the drug after several reports of
significant adverse events. In 2006, the FDA again
approved sale of the drug for MS but under strict treatment
guidelines involving infusion centers where patients can be
monitored by specially trained physicians.
Another experimental treatment for MS is
plasma exchange, or plasmapheresis.
Plasmapheresis is a procedure in
which blood is removed from the patient and the blood plasma is
separated from other blood substances that may contain
antibodies and other immunologically
active products. These other blood substances are discarded and
the plasma is then transfused back into the patient. Because its
worth as a treatment for MS has not yet been proven, this
experimental treatment remains at the stage of clinical testing.
Bone marrow transplantation (a procedure in which bone marrow
from a healthy donor is infused into patients who have undergone
drug or radiation therapy to suppress their immune system so
they will not reject the donated marrow) and injections of venom
from honey bees are also being
studied. Each of these therapies carries the risk of potentially
severe side effects.
Therapy to Improve Nerve Impulse Conduction
Because the transmission of electrochemical messages between the
brain and body is disrupted in MS, medications to improve the
conduction of nerve impulses are being investigated. Since
demyelinated nerves show abnormalities of potassium activity,
scientists are studying drugs that block the channels through which
potassium moves, thereby restoring conduction of the nerve impulse.
In several small experimental trials, derivatives of a drug called
aminopyridine temporarily improved vision, coordination, and
strength when given to MS patients who suffered from both visual
symptoms and heightened sensitivity to temperature. Possible side
effects of these therapies include paresthesias (tingling
sensations), dizziness, and seizures.
Therapies Targeting an Antigen
Trials of a synthetic form of myelin basic protein, called
copolymer I (Copaxone), were successful, leading the FDA to approve
the agent for the treatmernt of relapsing-remitting MS. Copolymer I,
unlike so many drugs tested for the treatment of MS, has few side
effects, and studies indicate that the agent can reduce the relapse
rate by almost one third. In addition, patients given copolymer I
are more likely to show neurologic improvement than those given a
Investigators are also looking at the possibility of developing
an MS vaccine. Myelin-attacking T cells were removed, inactivated,
and injected back into animals with experimental allergic
encephalomyelitis (EAE). This procedure results in destruction of
the immune system cells that were attacking myelin basic protein. In
a couple of small trials scientists have tested a similar vaccine in
humans. The product was well-tolerated and had no side effects, but
the studies were too small to establish efficacy. Patients with
progressive forms of MS did not appear to benefit, although
relapsing-remitting patients showed some neurologic improvement and
had fewer relapses and reduced numbers of lesions in one study.
Unfortunately, the benefits did not last beyond two years.
A similar approach, known as peptide therapy, is based on
evidence that the body can mount an immune response against the T
cells that destroy myelin, but this response is not strong enough to
overcome the disease. To induce this response, the investigator
scans the myelin-attacking T cells for the myelin-recognizing
receptors on the cells' surface. A fragment, or peptide, of those
receptors is then injected into the body. The immune system
"sees" the injected peptide as a foreign invader and
launches an attack on any myelin-destroying T cells that carry the
peptide. The injection of portions of T cell receptors may heighten
the immune system reaction against the errant T cells much the same
way a booster shot heightens immunity to tetanus. Or, peptide
therapy may jam the errant cells' receptors, preventing the cells
from attacking myelin.
Despite these promising early results, there are some major
obstacles to developing vaccine and peptide therapies. Individual
patients' T cells vary so much that it may not be possible to
develop a standard vaccine or peptide therapy beneficial to all, or
even most, MS patients. At this time, each treatment involves
extracting cells from each individual patient, purifying the cells,
and then growing them in culture before inactivating and chemically
altering them. This makes the production of quantities sufficient
for therapy extremely time consuming, labor intensive, and
expensive. Further studies are necessary to determine whether
universal inoculations can be developed to induce suppression of MS
patients' overactive immune systems.
Protein antigen feeding is similar to peptide therapy, but is a
potentially simpler means to the same end. Whenever we eat, the
digestive system breaks each food or substance into its primary
"non-antigenic" building blocks, thereby averting a
potentially harmful immune attack. So, strange as it may seem,
antigens that trigger an immune response when they are injected can
encourage immune system tolerance when taken orally. Furthermore,
this reaction is directed solely at the specific antigen being fed;
wholesale immunosuppression, which can leave the body open to a
variety of infections, does not occur. Studies have shown that when
rodents with EAE are fed myelin protein antigens, they experience
fewer relapses. Data from a small, preliminary trial of antigen
feeding in humans found limited suggestion of improvement, but the
results were not statistically significant. A multi-center trial is
being conducted to determine whether protein antigen feeding is
As our growing insight into the workings of the immune system
gives us new knowledge about the function of cytokines, the powerful
chemicals produced by T cells, the possibility of using them to
manipulate the immune system becomes more attractive. Scientists are
studying a variety of substances that may block harmful cytokines,
such as those involved in inflammation, or that encourage the
production of protective cytokines.
A drug that has been tested as a depression treatment, rolipram,
has been shown to reduce levels of several destructive cytokines in
animal models of MS. Its potential as a therapy for MS is not known
at this time, but side effects seem modest. Protein antigen feeding,
discussed above, may release transforming growth factor beta (TGF),
a protective cytokine that inhibits or regulates the activity of
certain immune cells. Preliminary tests indicate that it may reduce
the number of immune cells commonly found in MS patients' spinal
fluid. Side effects include anemia and altered kidney function.
Interleukin 4 (IL-4) is able to diminish demyelination and
improve the clinical course of mice with EAE, apparently by
influencing developing T cells to become protective rather than
harmful. This also appears to be true of a group of chemicals called
retinoids. When fed to rodents with EAE, retinoids increase levels
of TGF and IL-4, which encourage protective T cells, while
decreasing numbers of harmful T cells. This results in improvement
of the animals' clinical symptoms.
Some studies focus on strategies to reverse the damage to myelin
and oligodendrocytes (the cells that make and maintain myelin
in the central nervous system), both of which are destroyed during
MS attacks. Scientists now know that oligodendrocytes may
proliferate and form new myelin after an attack. Therefore, there is
a great deal of interest in agents that may stimulate this reaction.
To learn more about the process, investigators are looking at how
drugs used in MS trials affect remyelination. Studies of animal
models indicate that monoclonal antibodies and two immunosuppressant
drugs, cyclophosphamide and azathioprine, may accelerate
remyelination, while steroids may inhibit it. The ability of
intravenous immunoglobulin (IVIg) to restore visual acuity and/or
muscle strength is also being investigated.
Over the years, many people have tried to implicate diet as a
cause of or treatment for MS. Some physicians have advocated a diet
low in saturated fats; others have suggested increasing the
patient's intake of linoleic acid, a polyunsaturated fat, via
supplements of sunflower seed, safflower, or evening primrose oils.
Other proposed dietary "remedies" include megavitamin
therapy, including increased intake of vitamins B12 or C; various
liquid diets; and sucrose-, tobacco-, or gluten-free diets. To date,
clinical studies have not been able to confirm benefits from dietary
changes; in the absence of any evidence that diet therapy is
effective, patients are best advised to eat a balanced, wholesome
MS is a disease with a natural tendency to remit spontaneously,
and for which there is no universally effective treatment and no
known cause. These factors open the door for an array of
unsubstantiated claims of cures. At one time or another, many
ineffective and even potentially dangerous therapies have been
promoted as treatments for MS. A partial list of these
"therapies" includes: injections of snake venom,
electrical stimulation of the spinal cord's dorsal column, removal
of the thymus gland, breathing pressurized (hyperbaric) oxygen in a
special chamber, injections of beef heart and hog pancreas extracts,
intravenous or oral calcium orotate (calcium EAP), hysterectomy,
removal of dental fillings containing silver or mercury amalgams,
and surgical implantation of pig brain into the patient's abdomen.
None of these treatments is an effective therapy for MS or any of
Are Any MS Symptoms Treatable?
While some scientists look for therapies that will affect the
overall course of the disease, others are searching for new and
better medications to control the symptoms of MS without triggering
intolerable side effects.
Many people with MS have problems with spasticity,
a condition that primarily affects the lower limbs. Spasticity can
occur either as a sustained stiffness caused by increased muscle
tone or as spasms that come and go, especially at night. It is
usually treated with muscle relaxants and tranquilizers. Baclofen (Lioresal),
the most commonly prescribed medication for this symptom, may be
taken orally or, in severe cases, injected into the spinal cord.
Tizanidine (Zanaflex), used for years in Europe and now approved in
the United States, appears to function similarly to baclofen.
Diazepam (Valium), clonazepam (Klonopin), and dantrolene (Dantrium)
can also reduce spasticity. Although its beneficial effect is
temporary, physical therapy may also be useful and can help prevent
the irreversible shortening of muscles known as contractures.
Surgery to reduce spasticity is rarely appropriate in MS.
Weakness and ataxia (incoordination)
are also characteristic of MS. When weakness is a problem, some
spasticity can actually be beneficial by lending support to weak
limbs. In such cases, medication levels that alleviate spasticity
completely may be inappropriate. Physical therapy and exercise can
also help preserve remaining function, and patients may find that
various aids-such as foot braces, canes, and walkers-can help them
remain independent and mobile. Occasionally, physicians can provide
temporary relief from weakness, spasms, and pain by injecting a drug
called phenol into the spinal cord, muscles, or nerves in the arms
or legs. Further research is needed to find or develop effective
treatments for MS-related weakness and ataxia.
Trouble with walking is a major problem in people with MS.
The drug dalfampridine (Ampyra) may improve walking, and
walking speeds, in these individuals.
Although improvement of optic symptoms usually
occurs even without treatment, a short course of treatment with
intravenous methylprednisolone (Solu-Medrol) followed by treatment
with oral steroids is sometimes used. A trial of oral prednisone in
patients with visual problems suggests that this steroid is not only
ineffective in speeding recovery but may also increase patients'
risk for future MS attacks. Curiously, prednisone injected
directly into the veins-at ten times the oral dose-did seem to
produce short-term recovery. Because of the link between optic
neuritis and MS, the study's investigators believe these findings
may hold true for the treatment of MS as well. A follow-up study of
optic neuritis patients will address this and other questions.
Fatigue, especially in the legs, is a common
symptom of MS and may be both physical and psychological. Avoiding
excessive activity and heat are probably the most important measures
patients can take to counter physiological fatigue. If psychological
aspects of fatigue such as depression or apathy are evident,
antidepressant medications may help. Other drugs that may reduce
fatigue in some, but not all, patients include amantadine (Symmetrel),
pemoline (Cylert), and the still-experimental drug aminopyridine.
People with MS may experience several types of pain.
Muscle and back pain can be helped by aspirin or acetaminophen and
physical therapy to correct faulty posture and strengthen and
stretch muscles. The sharp, stabbing facial pain known as trigeminal
neuralgia is commonly treated with carbamazepine or other
anticonvulsant drugs or, occasionally, surgery. Intense tingling and
burning sensations are harder to treat. Some people get relief with
antidepressant drugs; others may respond to electrical stimulation
of the nerves in the affected area. In some cases, the physician may
As the disease progresses, some patients develop bladder
malfunctions. Urinary problems are often the result of
infections that can be treated with antibiotics. The physician may
recommend that patients take vitamin C supplements or drink
cranberry juice, as these measures acidify urine and may reduce the
risk of further infections. Several medications are also available.
The most common bladder problems encountered by MS patients are
urinary frequency, urgency, or incontinence. A small number of
patients, however, retain large amounts of urine. In these patients,
catheterization may be necessary. In this procedure, a catheter or
drainage tube is temporarily inserted (by the patient or a
caretaker) into the urethra several times a day to drain urine from
the bladder. Surgery may be indicated in severe, intractable cases.
Scientists have developed a "bladder pacemaker" that has
helped people with urinary incontinence in preliminary trials. The
pacemaker, which is surgically implanted, is controlled by a
hand-held unit that allows the patient to electrically stimulate the
nerves that control bladder function.
MS patients with urinary problems may be reluctant to drink
enough fluids, leading to constipation. Drinking
more water and adding fiber to the diet usually alleviates this
condition. Sexual dysfunction may also occur,
especially in patients with urinary problems. Men may experience
occasional failure to attain an erection. Penile implants, injection
of the drug papaverine, and electrostimulation are techniques used
to resolve the problem. Women may experience insufficient
lubrication or have difficulty reaching orgasm; in these cases,
vaginal gels and vibrating devices may be helpful. Counseling is
also beneficial, especially in the absence of urinary problems,
since psychological factors can also cause these symptoms. For
instance, depression can intensify symptoms of
fatigue, pain, and sexual dysfunction. In addition to counseling,
the physician may prescribe antidepressant or antianxiety
medications. Amitriptyline is used to treat laughing/weeping
Tremors are often resistant to therapy, but can
sometimes be treated with drugs or, in extreme cases, surgery.
Investigators are currently examining a number of experimental
treatments for tremor.
Drugs Used to Treat Symptoms of Multiple Sclerosis
Aspirin or acetaminophen
Papaverine injections(in men)
What Recent Advances Have Been Made in MS Research?
Many advances, on several fronts, have been made in the war
against MS. Each advance interacts with the others, adding greater
depth and meaning to each new discovery. Four areas, in particular,
Over the last decade, our knowledge about how the immune system
works has grown at an amazing rate. Major gains have been made in
recognizing and defining the role of this system in the development
of MS lesions, giving scientists the ability to devise ways to alter
the immune response. Such work is expected to yield a variety of new
potential therapies that may ameliorate MS without harmful side
New tools such as MRI have redefined the natural history of MS
and are proving invaluable in monitoring disease activity.
Scientists are now able to visualize and follow the development of
MS lesions in the brain and spinal cord using MRI; this ability is a
tremendous aid in the assessment of new therapies and can speed the
process of evaluating new treatments.
Other tools have been developed that make the painstaking work of
teasing out the disease's genetic secrets possible. Such studies
have strengthened scientists' conviction that MS is a disease with
many genetic components, none of which is dominant. Immune
system-related genetic factors that predispose an individual to the
development of MS have been identified, and may lead to new ways to
treat or prevent the disease.
In fact, a treatment that may actually slow the course of the
disease has been found and a growing number of therapies are now
available that effectively treat some MS symptoms. In addition,
there are a number of treatments under investigation that may
curtail attacks or improve function of demyelinated nerve fibers.
Over a dozen clinical trials testing potential therapies are under
way, and additional new treatments are being devised and tested in
What Research Remains to be Done?
The role of genetic risk factors, and how they can be modified,
must be more clearly defined. Environmental triggers, such as
viruses or toxins, need to be investigated further. The specific
cellular and subcellular targets of immune attack in the brain and
spinal cord, and the subsets of T cells involved in that attack,
need to be identified. Knowledge of these aspects of the disease
will enable scientists to develop new methods for halting-or
reversing and repairing-the destruction of myelin that causes the
symptoms of MS.
What is the Outlook for People With MS?
The 1990s-proclaimed the "Decade of the Brain" in 1989
by President Bush and Congress-have seen an unparalleled explosion
of knowledge about neurological disorders. New technologies are
forcing even complex diseases like MS to yield up their secrets.
These burgeoning opportunities in the field of neurological research
have prompted the National Advisory Neurological Disorders and
Stroke Council to suggest that an effective treatment for and the
cause of MS may be found during the Decade of the Brain. The former
has already been achieved; scientists continue to diligently search
for the latter. Their dedication is the best hope for a cure, or,
better yet, a way to prevent MS altogether.
How Can I Help Research?
The NINDS contributes to the support of the Human Brain and
Spinal Fluid Resource Center in Los Angeles. This bank supplies
investigators around the world with tissue from patients with
neurological and other disorders. Tissue from individuals with MS is
needed to enable scientists to study this disorder more intensely.
Prospective donors may contact:
For more information on neurological disorders or research programs
funded by the National Institute of Neurological Disorders and Stroke,
contact the Institute's Brain Resources and Information Network (BRAIN)
such as prednisone taken by mouth or methylprednisolone given
intravenously for short periods to relieve acute symptoms have been the
main form of therapy for decades. Treatment with high-dose steroids for
MS and other disorders may impair long-term memory, according to a
report in the medical journal Neurology. The good news is that mental
functioning usually returns to normal a few days after stopping the
reduces the frequency of relapses. Other promising treatments still
under investigation include other interferons, oral myelin, and
glatiramer to help keep the body from attacking its own myelin. The
benefits of plasmapheresis and IV gamma globulins haven't been
established, and these treatments aren't practical for long-term
therapy. Treatment with Marinol, a synthetic cannabinoid chemical, can
reduce the pain often experienced by people with MS.
clinical trial has shown that injections of colchicine (an
anti-inflammatory compound extracted from the herb meadow saffron) can
be effective in relieving symptoms and in promoting general stamina.
Oral colchicine can also be used. While there are side effects,
including gastrointestinal symptoms, they can usually be managed by
altering the dose. As existing drugs for MS can be quite toxic, the use
of colchicine is a promising alternative and patients should be able to
take it safely throughout their lives.
that MS could be an inflammotory disease provoked by bacteria and
viruses, we offer special treatment for nanobacteria
and postvaccination syndrome.
mentioned oils are anti-inflammatory fatty acids that also help build
strong nerves. The proper zinc/copper combination is important to
improve levels of a major antioxidant, superoxide dismutase. Dosage
should be adjusted with their blood levels.
are very effective in both prevention and treatment of MS include cod
liver oil (omega-3), flaxseed and evening primrose oil, borage and black
currant oils, amino acids (N-acetylcysteine, glutathione,
phosphatidylcholine, etc), minerals (zinc, selenium, manganese,
magnesium) and B-vitamin complex, especially inositol, B1, folinic acid
and B12 (methylcobalamin). The latter should be taken as a sublingual
tablets for enhanced absorption or given in injections.
acid (ALA) is a powerful antioxidant and has been helpful in a mouse
study and recently showed biochemical marker improvement in a human
trial. Alpha Lipoic Acid (ALA).
has been used successfully in the treatment of many autoimmune disorders
including MS, Lupus and fibromyalgia. DHEA regulates the immune system
and maintains the metabolic and structural integrity of the nervous
E and other antioxidants like vitamin
A, beta carotene and vitamin
C. These supplements are strong nerve protectors.Coenzyme
Q10 is a catalyst in providing cellular energy and it's also a
strong nerve protector.
Dosages depend on
the severity of the illness and the patient's tolerance for these
tissue salts can be helpful as a safe anti-inflammatory and
antispasmodic and to relieve cramps, improve circulation
and support nervous system health.
has been found helpful in reducing fatigue in patients with multiple
sclerosis. Curcumin blocks the
progression of multiple sclerosis in a laboratory study. Ginkgo
biloba have shown intriguing
preliminary evidence of efficacy.
D - Consider getting
more vitamin D. Recent studies have shown that women who had the
highest amounts of vitamin D in their systems were 40% less likely to
suffer from multiple sclerosis. While vitamin D may not cure your MS
if you have it, it is certainly beneficial to your symptoms and
condition, and should form a core part of good treatments for multiple
appears to be an association between vitamin D levels and MS relapse
By far the best way to obtain your supply of vitamin D is to expose
your bare skin to sunlight, allowing your body to produce the vitamin.
Of course, sunburn can be harmful to health, so be sure to carry this
out sensibly, starting with low periods of sun exposure.
Disclaimer: This information is intended as a guide only. This information isoffered to you with the
understanding that it not be interpreted as medical or professional advice.
medical information needs to be carefully reviewed with your health care