multiple sclorosis, multiple scerosis
Although multiple sclerosis (MS) was first diagnosed in 1849, the
earliest known description of a person with possible MS dates from
fourteenth century Holland. An unpredictable disease of the central
nervous system, MS can range from relatively benign to somewhat disabling
to devastating as communication between the brain and other parts of the
body is disrupted.
The vast majority of patients are mildly affected, but in the worst
cases MS can render a person unable to write, speak, or walk. A physician
can diagnose MS in some patients soon after the onset of the illness. In
others, however, physicians may not be able to readily identify the cause
of the symptoms, leading to years of uncertainty and multiple diagnoses
punctuated by baffling symptoms that mysteriously wax and wane.
Once a diagnosis of Multiple Sclerosis is made with confidence, patients must consider a
profusion of information-and misinformation-associated with this complex
disease. This brochure is designed to convey the latest information on the
diagnosis, course, and possible Multiple Sclerosis treatment, as well as highlights of
current research. Although a pamphlet cannot substitute for the advice and
expertise of a physician, it can provide patients and their families with
information to understand MS better so that they can actively participate
in their care and treatment.
During 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 nervous system.
No one knows exactly how many people have Multiple Sclerosis. It is believed that,
currently, there are approximately 250,000 to 350,000 people in the United
States with MS diagnosed by a physician. This estimate suggests that
approximately 200 new cases are diagnosed each week.
Most people experience their first multiple sclerosis symptoms between the ages of
20 and 40, but a diagnosis is often delayed. This is due to both the
transitory nature of the disease and the lack of a specific diagnostic
test-specific symptoms and changes in the brain must develop before the
diagnosis is confirmed.
Although scientists have documented cases of MS in young children and
elderly adults, symptoms rarely begin before age 15 or after age 60.
Whites are more than twice as likely as other races to develop MS. In
general, women are affected at almost twice the rate of men; however,
among patients who develop the multiple sclerosis symptoms at a later age, the gender
ratio is more balanced.
MS is five times more prevalent in temperate climates-such as those
found in the northern United States, Canada, and Europe-than in tropical
regions. Furthermore, the age of 15 seems to be significant in terms of
risk for developing the disease: some studies indicate that a person
moving from a high-risk (temperate) to a low-risk (tropical) area before
the age of 15 tends to adopt the risk (in this case, low) of the new area
and vice versa. Other studies suggest that people moving after age 15
maintain the risk of the area where they grew up.
These findings indicate a strong role for an environmental factor in
the cause of MS. It is possible that, at the time of or immediately
following puberty, patients acquire an infection with a long latency
period. Or, conversely, people in some areas may come in contact with an
unknown protective agent during the time before puberty. Other studies
suggest that the unknown geographic or climatic element may actually be
simply a matter of genetic predilection and reflect racial and ethnic
susceptibility factors.
Periodically, scientists receive reports of MS "clusters." The most
famous of these MS "epidemics" took place in the Faeroe Islands north of
Scotland in the years following the arrival of British troops during World
War II. Despite intense study of this and other clusters, no direct
environmental factor has been identified. Nor has any definitive evidence
been found to link daily stress to MS attacks, although there is evidence
that the risk of worsening is greater after acute viral illnesses.
MS is a life-long chronic disease diagnosed primarily in young adults
who have a virtually normal life expectancy. Consequently, the economic,
social, and medical costs associated with the disease are significant.
Estimates place the annual costs of MS in the United States in excess of
$2.5 billion.
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 antigens.
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.
Genetics
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 multiple sclerosis 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 multiple sclerosis 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.
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 multiple sclerosis, 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.
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 multiple sclerosis 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, and baclofen.
Unfortunately, between 20 and 40 percent of women with multiple sclerosis 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.
Multiple Sclerosis symptoms 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 multiple sclerosis 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 multiple sclerosis 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 spinal fluid.
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 spared.
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 multiple sclerosis 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 with MS.
The erratic symptoms of multiple sclerosis 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
-
Muscle weakness
-
Spasticity
-
Impairment of pain, temperature, touch senses
-
Pain (moderate to severe)
-
Ataxia
-
Tremor
-
Speech disturbances
-
Vision disturbances
-
Vertigo
-
Bladder dysfunction
-
Bowel dysfunction
-
Sexual dysfunction
-
Depression
-
Euphoria
-
Cognitive abnormalities
-
Multiple Sclerosis Index
When faced with a patient whose symptoms, neurological examination, 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-often used in conjunction with the
contrast agent gadolinium, which helps distinguish new plaques from old on
MRI (see section on "What is the Course of MS?")-can help locate central
nervous system lesions resulting from myelin loss. However, since these
lesions can also occur in several other neurological disorders, they are
not absolute evidence of MS. Magnetic resonance spectroscopy (MRS) is a
new tool being used to investigate MS. Unlike MRI, which provides an
anatomical picture of lesions, MRS yields information about the
biochemistry of the brain in MS.
Evoked potential tests, which measure the speed of the brain's response
to visual, auditory, and sensory stimuli, can sometimes detect lesions the
scanners miss. Like imaging technologies, evoked potentials are helpful
but not conclusive because they cannot identify the cause of lesions.
The physician may also study the patient's cerebrospinal fluid
(the colorless liquid that circulates through the brain and spinal cord)
for 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.
Because there is no single test that unequivocally detects MS, it is
often difficult for the physician to differentiate between an MS attack
and symptoms that can follow a viral infection or even an immunization.
Many doctors will tell their patients they have "possible MS." If, as time
goes by, the patient's symptoms show the characteristic
relapsing-remitting pattern, or continue in a chronic and progressive
fashion, and if laboratory tests rule out other likely causes, or specific
tests become positive, the diagnosis may eventually be changed to
"probable MS."
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. The
physician 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-a process that can take
months or even years-before a physician can make a definitive diagnosis of
MS.
Definite MS Consistent course (relapsing-remitting course with
at least 2 bouts separated by at least 1 month, or
slow or stepwise progressive course for at least 6
months)
Documented neurologic signs of lesions in more than
one site of brain or spinal cord white matter
Onset of symptoms between 10 and 50 years of age
Absence of other more likely neurologic explanation
Probable MS History of relapsing-remitting symptoms
Signs not documented and only one current sign
commonly associated with MS
Documented single bout of symptoms with signs of
more than one white matter lesion; good recovery,
then variable symptoms and signs
Absence of other more likely neurologic explanation
Possible MS History of relapsing-remitting symptoms
No documentation of signs establishing more than one
white matter lesion
Absence of other more likely neurologic explanation
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.
Until recently, the principal medications physicians used for multiple sclerosis treatment
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. Two forms of beta
interferon (Avonex and Betaseron) have now been approved by the Food and
Drug Administration for treatment of relapsing-remitting MS. A third form
(Rebif) is marketed in Europe. 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.
Immunotherapy
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. 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 fungal
infections.
Over the years, MS investigators have studied a number of
immunosuppressant treatments. Among the therapies being studied are
cyclosporine (Sandimmune), cyclophosphamide (Cytoxan), methotrexate,
azathioprine (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 drugs linomide (Roquinimex), cladribine (Leustatin), and
mitoxantrone.
Two other experimental multiple sclerosis treatments - one involving the use of monoclonal
antibodies and the other involving plasma exchange, or plasmapheresis -
may have fewer dangerous side effects. Monoclonal antibodies 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. Plasmapheresis is a procedure in
which blood is removed from the patient, and the plasma is separated from
other blood substances, which may contain antibodies and other
immmunologically active products. These other blood substances are
discarded and the plasma is then transfused back into the patient. Because
their worth as treatments for MS has not yet been proven, these
experimental treatments remain 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), have shown promise in treating people in the early stages of
relapsing-remitting MS. Copolymer I, unlike so many drugs tested for the
treatment of MS, seems to have few side effects. Recent trial data
indicate that copolymer I can reduce the relapse rate by almost one third.
In addition, patients given copolymer I were more likely to show
neurologic improvement than those given a placebo. The Food and Drug
Administration has made the drug available to people with early
relapsing-remitting MS through its "Treatment IND" program and is
currently reviewing data from a large-scale study to determine whether or
not to approve the drug for marketing.
Investigators are also looking at the possibility of developing a multiple sclerosis 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 effective.
Cytokines
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.
Remyelination
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 diet.
Unproven Therapies
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 multiple sclerosis symptoms. Drugs Used to Treat Multiple Sclerosis
Drugs currently available to patientsSteroids
Adrenocorticotropic hormone (ACTH) Prednisone Prednisolone
Methylprednisolone Betamethasone Dexamethasone Interferons Beta
interferons (Avonex, Betaseron) Beta interferon (Rebif)-available in
Europe only
Some experimental therapiesAlpha interferon Cyclosporine
(Sandimmune) Cyclophosphamide (Cytoxan) Methotrexate Azathioprine (Imuran)
Linomide (Roquinimex) Cladribine (Leustatin) Mitoxantrone Aminopyridine,
derivatives of Copolymer I (Copaxone) Rolipram Interleukin 4 (IL-4)
Retinoids Total lymphoid irradiation Monoclonal antibodies Plasma exchange
or plasmapheresis Bone marrow transplantation Peptide therapy Various MS
vaccines Protein antigen feeding Transforming growth factor beta (TGF)
Intravenous immunoglobulin (IVIg)
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 multiple sclerosis 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 multiple sclerosis characteristics. 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.
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 carbamazapine 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 recommend codeine.
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 syndrome.
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
|
Symptom |
Drug |
|
Spasticity |
Baclofen (Lioresal)
Tizanidine (Zanaflex)
Diazepam (Valium)
Clonazepam (Klonopin)
Dantrolene (Dantrium) |
|
Optic neuritis |
Methylprednisolone (Solu-Medrol)
Oral steroids |
|
Fatigue |
Antidepressants
Amantadine (Symmetrel)
Pemoline (Cylert) |
|
Pain |
Aspirin or acetaminophen
Antidepressants
Codeine |
|
Trigeminal neuralgia |
Carbamazapine, other anticonvulsant |
|
Sexual dysfunction |
Papaverine injections(in men) |
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, stand out.
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 effects.
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 multiple sclerosis 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 animal models.
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 multiple sclerosis.
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.
Keeping on Top of Your Condition
Keeping in tune with your disease or condition not only makes treatment less intimidating but also increases its chance of success, and has been shown to lower a patients risk of complications. As well, as an informed patient, you are better able to discuss your condition and treatment options with your physician.
A new service available to patients provides a convenient means of staying informed, and ensures that the information is both reliable and accurate. If you wish to find out more about HealthNewsflash's innovative service, take the tour.
The National Institute of Neurological Disorders and Stroke (NINDS) is
the Federal Government's leading supporter of biomedical research on
nervous system disorders, including MS. The NINDS conducts research on MS
in its own laboratories at the National Institutes of Health in Bethesda,
MD, and supports research at institutions worldwide. The Institute also
sponsors an active public information program. Information on the NINDS
and its research programs is also available on the World Wide Web at:
http://www.ninds.nih.gov.
For information on other 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)
at:
BRAIN
P.O. Box 5801
Bethesda, Maryland
20824
800-352-9424
http://www.ninds.nih.gov/
In addition, a number of private organizations offer a variety of
services and information that can help those affected by MS. They
include:
National Multiple Sclerosis Society
733 3rd
Avenue, 6th Floor
New York, NY 10017-3288
212-986-3240
800-FIGHTMS (344-4867)
212-986-7981 (fax)
nat@nmss.org
http://www.nmss.org//
The National Multiple Sclerosis Society (NMSS) provides MS-related
services and information in the United States and is a major source of
funds for MS-related basic, clinical, and health policy research. Staff in
the national office's Information Resource Center answer some 45,000
inquiries a year. Volunteers and staff in the Society's local chapters and
branches offer information and referrals, peer support, professional
counseling, loans of medical equipment, physical fitness programs,
legislative advocacy, assistance obtaining benefits, employment
assistance, and social or recreational events. The NMSS raises funds that
support a broad research effort into the cause, prevention, and more
effective treatment of MS and into the major health care policy issues
that affect people with MS. The Society's educational programs provide
both information services and publications. Its national publications
include an array of professional/client/family educational materials and
two general interest periodicals,"Inside MS" and "Inside MS Bulletin." The
NMSS is a member of the International Federation of Multiple Sclerosis
Societies, and can often provide referrals to sources of MS information in
other areas of the world.
Multiple Sclerosis Association of America
706
Haddonfield Road
Cherry Hill, NJ 08002
856-488-4500
800-532-7667
856-661-9797 (fax)
msaa@msaa.com
http://www.msaa.com/
The Multiple Sclerosis Association of America (MSA) has several
regional offices in the United States. It focuses primarily on mechanisms
for coping with MS-related disabilities. The Association publishes a
bimonthly newsletter, "The Motivator," which contains feature stories
about patients, health tips, medical updates, and occasionally referral
information. Educational information is available nationwide-in the New
Jersey area, the Association lends equipment such as wheelchairs to
patients and holds meetings of patient support groups. MSA's most recent
major undertaking is a new housing complex for people disabled by MS.
Multiple Sclerosis Foundation, Inc.
6350 North
Andrews Avenue
Fort Lauderdale, FL 33309
954-776-6805
800-MSFocus (673-6287)
954-351-0630 (fax)
support@msfocus.org
http://www.msfacts.org/
Founded in December 1986, the Multiple Sclerosis Foundation, Inc.
provides educational information and supports MS research, including
investigations of "alternative" or holistic therapies. The Foundation has
an MS library and acts as a clearinghouse for information on the disease.
Its staff can make referrals to support groups and MS research centers.
Publications include a brochure on MS and a newsletter entitled "MS
Focus."
Other voluntary health agencies that can provide general information on
MS or symptoms associated with MS include:
National Organization for Rare Disorders (NORD)
55
Kenosia Avenue
P.O. Box 1968
Danbury, CT 06813-1968
(203)
744-0100
(800) 999-6673 (voicemail only)
Fax: (203) 798-2291
http://www.rarediseases.org/
NORD acts as a clearinghouse for information about rare disorders and
seeks to foster communication among voluntary health agencies, the
government, the pharmaceutical industry, academia, and individuals. It
encourages, promotes, and supports scientific research and accumulates and
disseminates information on orphan drugs and devices. NORD publishes a
general organization brochure, a pamphlet entitled "Physicians Guide to
NORD Services," and a newsletter, "Orphan Disease Update," which includes
research and medical updates, legislative action, personal stories, and
letters from readers.
National Ataxia Foundation
2600 Fernbrook Lane,
Suite 119
Minneapolis, Minnesota 55447-4752
763-553-0020
763-553-0167 (fax)
naf@ataxia.org
www.ataxia.org/
The Foundation sponsors support groups and promotes ataxia research.
Its publications include a newsletter called "Generations" that contains
features, research updates, questions and answers about ataxia, and
support group news. Information on exercise, a guidebook on speech and
swallowing problems, a resource book of chapters and related groups
worldwide, and a specialist referral guide are also available.
International Essential Tremor Foundation
7046 W.
105th St.
Overland Park, KS 66212-1803
913-341-3880
888-387-3667
913-341-1296 (fax)
staff@essentialtremor.org
http://www.essentialtremor.org/
The International Tremor Foundation provides patient and family
services, public education materials, and referrals to support groups and
physicians specializing in the treatment of essential or familial tremor.
It publishes a fact sheet describing the Foundation and a quarterly
newsletter containing information on research advances, questions and
answers from readers, and advice on coping with tremor. The Foundation
also supports neurologic research on tremor disorders.
Well Spouse Foundation
63 West Main
Street
Freehold, NJ 07728
(732) 577-8899
(800) 838-0879
http://www.wellspouse.org/
The Well Spouse Foundation provides peer support for spouses of people
with MS and other disorders and promotes individual chapter meetings. It
also has advocacy representatives in several states. It publishes a
quarterly newsletter containing feature and patient stories, chapter news,
a "bookshelf," and coping advice.
Paralyzed Veterans of America (PVA)
801 18th
Street, NW
Washington, DC 20006-3517
info@pva.org
202-USA-1300
(872-1300) or 800-424-8200
Fax: 202-785-4452
http://www.pva.org/
The Paralyzed Veterans of America works to help members and their
families, as well as all veterans and people with disabilities. Offers
expertise on a wide variety of issues involving the special needs of
veterans of the armed forces who have experienced spinal cord
dysfunction.
In addition to the NINDS, there are several other Federal Government
agencies that may be able to provide information on MS. They are the:
Food and Drug Administration
Public Affairs Office
Rockville, MD 20857
301-827-4573
888-INFO-FDA (463-6332)
http://www.fda.gov/
The Food and Drug Administration (FDA) is the agency within the Federal
Government that regulates drugs and medical devices. FDA staff may be able
to provide information on the status and location of certain clinical
trials of experimental medications and other therapies. It can also
provide information about medications already on the market.
National Rehabilitation Information Center
4200
Forbes Boulevard, Suite 202
Lanham, MD 20706-4829
301-562-2400
800-346-2742
naricinfo@heitechservices.com
http://www.naric.com/
Funded by the Federal Government's National Institute on Disability and
Rehabilitation Research (NIDRR), the National Rehabilitation Information
Center (NARIC) functions as an information center and maintains a library
with more than 30,000 documents on all aspects of disability and
rehabilitation including medical rehabilitation, independent living,
physical disabilities, and special education programs. The Center's staff
collects and disseminates the results of federally funded research
projects. NARIC publishes several brochures, including a newsletter
entitled "NARIC Quarterly" that contains information about projects funded
by NIDRR and new publications produced by NARIC and other
organizations.
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