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Multiple sclerosis

Multiple Sclerosis

Multiple Sclerosis (MS) is a chronic, often disabling disease that randomly
attacks the central nervous system (brain and spinal cord). The progress,
severity and specific symptoms of the disease can not be predicted; symptoms may
range from tingling and numbness to paralysis and blindness. MS is a devastating
disease because people live with its unpredictable physical and emotional
effects for the rest of their lives. MS is a well-known disease, but poorly
understood. In the United States there are approximately 200 new cases diagnosed
each week; MS is a common disease and not always caused by genetics. Therefore,

I feel we all need to have a better understanding of this disease that has no
cure yet. I hope to make MS more understanding in my paper. In my paper I will
explain what MS is, who gets MS, what MS has to do with the metabolism, some new
techniques being used to pinpoint genetic factors, what some of the symptoms of

MS is, and some treatments for MS. Multiple Sclerosis Multiple sclerosis (MS) is
a progressive disabling illness that affects nerve cells in the brain and spinal
cord (Bernard). Under normal conditions these nerve cells are surrounded by an
insulating sheath made of fatty "myelin," which speeds the passage of
nerve impulses. In MS, this myelin sheath is inflamed or damaged, disrupting
nerve impulses and leaving areas of scarring (sclerosis). The disruption of
nerve signals within the brain and spinal cord causes a variety of symptoms that
may affect vision, sensation, and body movements. "These symptoms usually wax
and wane through a series of relapses (episodes when symptoms suddenly get
worse) alternating with remissions (periods of recovery, when symptoms
improve)." (Brunnscheiler) For many patients, a long history of MS attacks
over several decades leads to slowly progressing disability, but for others the
disability is more rapid and severe. 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. (Melvin) No one knows exactly how many people
have MS. It is believed that, currently, there are approximately 250,000 to

350,000 people in the United States with MS diagnosed by a physician. (Boyden)

This estimate suggests that approximately 200 new cases are diagnosed each week.

Also, MS is the most common nerve disease to develop in young persons after
birth, and it affects over 1 million young adults worldwide. "Close relatives
of a person with MS are 8 times more likely than average to develop the disease
themselves, and children of a person with MS run 30 to 50 times the average
risk." (Waxman) Most people experience their first symptoms of MS 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. (Health Central) 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 symptoms of MS at a later age, the
gender ratio is more balanced. (Waxman) 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. (Hofmann) "The immune
system displays both enormous diversity and extraordinary specificity." (Hofmann)

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. " (

Kaser) 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. " (Kaser) 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. ( Kaser) 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." (Hauser) 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. (Leuven) 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." (Mayo Clinic)

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. "The genes a person
inherits may help determine whether that person is at increased risk for
developing MS." ( Melvin) While there is evidence from studies that this
genetic component exists, it appears to be only one factor among several. Most
likely an individual’s genetic blueprint ultimately determines if that
individual will be susceptible to a triggering factor, which in turn initiates
the autoimmune process that leads to the development of MS. In the past few
years, scientists have developed a set of tools that gives them the ability to
pinpoint the genetic factors that make a person susceptible to MS. "These
tools are the methods of molecular genetics—techniques used to isolate and
determine the chemical structure of genes." (Colin) In the 1980s, scientists
began to apply the tools of molecular genetics to human diseases caused by
defects in single genes. This work led to major advances in understanding
diseases such as Duchenne muscular dystrophy and cystic fibrosis. The situation
for diseases such as multiple sclerosis is more complicated. Scientists now
believe that a person is susceptible to multiple sclerosis only if he or she
inherits an unlucky combination of several genes. (Colin) Advances in molecular
genetics and the identification of large families in which several members have

MS—"multiplex" MS families—have made possible research to uncover

MS susceptibility genes. "Since 1991, the National MS Society has supported an
international project searching for these genes." ( National Multiple

Sclerosis Society) However, even though genetic (inherited) factors seem to play
a large role in the development of MS, no single MS gene has been identified so
far. Instead, scientists suspect that MS develops because of the influence of
several genes acting together. Many multiplex families from throughout the world
have agreed to participate in these studies. The researchers are looking for
patterns of genetic material that are consistently inherited by people with MS.

These recognizable patterns are called "DNA markers." (Melvin) When
one of these markers is identified, scientists focus on that area, seeking
additional markers closer to that gene. Eventually the location of that gene can
be identified. This process of moving closer to the gene until it is identified
has to be repeated for each of the marker regions from the multiplex families.
(Melvin) By 1996, as many as 20 locations that may contain genes contributing to

MS were identified, but no single gene was shown to have a major influence on
susceptibility to MS. (Melvin) Research will likely find that other, as yet
unidentified, genes contribute to MS. After the location of each susceptibility
gene is identified, the role that the gene plays in the immune system and
neuralgic aspects of people with MS will have to be determined. Because the
immune system is so involved in MS, many scientists think at least some of the
susceptibility genes are related to the immune system. Already there have been
reports linking some immune system genes to MS. 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. ( Kaser) 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. ( Kaser) 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.
(Hauser) 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." (Ronthal)

Finding the genes responsible for susceptibility to MS may lead to the
development of new and more effective ways to treat the disease. Such research
could also uncover the basic cause of the disease and help predict the course of
the disease in an individual. This would make it easier for physicians to tailor
therapies and provide information to help people make life decisions. Another
possible benefit may be the early diagnosis of people in families where one or
more member already has MS. Many physicians believe that the earlier MS is
diagnosed and treatment begun, the better the outcome will be. 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." (Brunnscheiler) Inexplicably, visual problems tend to clear up in
the later stages of MS. Inflammatory problems of the optic nerve may be
diagnosed as retrobulbar or 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 spinal fluid. (National Multiple Sclerosis

Society) 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." (Brunnscheiler) 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. (Brunnscheiler
; National Multiple Sclerosis Society) 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. (Brunnscheiler) "Cognitive symptoms occur when
lesions develop in brain areas responsible for information processing." (Brunnscheiler)

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. (National Multiple Sclerosis Society) "Depression, which is
unrelated to cognitive problems, is another common feature of MS. (Brunnscheiler)

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. (National Multiple Sclerosis Society) As the disease progresses,
sexual dysfunction may become a problem. Bowel and bladder control may also be
lost. (Health Central) 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 with MS." (Wenzel) 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. Counseling may help MS patients, their
families, and friends find ways to cope with the many problems the disease can
cause. (Lambert) "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." (Health Central) 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 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. (Mayo Clinic) 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." (Bernard) 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
exacerbation’s 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. (Mayo

Clinic) 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. (Mayo Clinic) "Common
side effects of interferons include fever, chills, sweating, muscle aches,
fatigue, depression, and injection site reactions." (Health Central)

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. In
conclusion, MS is a disease that is well known but poorly understood by the
medical and nursing community as well as the general public. It has no known
cure and the genes that are accountable for it have yet been pin pointed. The

United States is capable of finding a cure for this disease; over the years,
medical researchers have found cures for many diseases that were thought
incurable. Not only time and money are needed to find a cure for this disease,
but faith and heart are needed to realize the importance Glossary antibodies --
proteins made by the immune system that bind to structures (antigens) they
recognize as foreign to the body. antigen -- a structure foreign to the body,
such as a virus. The body usually responds to antigens by producing antibodies.
ataxia -- a condition in which the muscles fail to function in a coordinated
manner. autoimmune disease -- a disease in which the body's defense system
malfunctions and attacks a part of the body itself rather than foreign matter.
blood/brain barrier -- a membrane that controls the passage of substances from
the blood into the central nervous system. cerebrospinal fluid -- the colorless
liquid, consisting partially of substances filtered from blood and partially by
secretions released by brain cells, that circulates around and through the
cavities of the brain and spinal cord. Physicians use a variety of
tests--electrophoresis, isoelectric focusing, capillary isotachophoresis, and
radioimmunoassay--to study cerebrospinal fluid for abnormalities often
associated with MS. cytokines -- powerful chemical substances secreted by T
cells. Cytokines are an important factor in the production of inflammation and
show promise as treatments for MS. demyelination -- damage caused to myelin by
recurrent attacks of inflammation. Demyelination ultimately results in nervous
system scars, called plaques, which interrupt communications between the nerves
and the rest of the body. experimental allergic encephalomyelitis (EAE) -- a
chronic brain and spinal cord disease similar to MS which is induced by
injecting myelin basic protein into laboratory animals. fatigue -- tiredness
that may accompany activity or may persist even without exertion. gadolinium --
a chemical compound given during MRI scans that helps distinguish new lesions
from old. human leukocyte antigens (HLAs) -- antigens, tolerated by the body,
that correspond to genes that govern immune responses. Also known as major
histocompatibility complex. immunoglobulin G (IgG) -- an antibody-containing
substance produced by human plasma cells in diseased central nervous system
plaques. Levels of IgG are increased in the cerebrospinal fluid of most MS
patients. immunosuppression -- suppression of immune system functions. Many
medications under investigation for the treatment of MS are immunosuppressants.
interferons -- cytokines belonging to a family of antiviral proteins that occur
naturally in the body. Gamma interferon is produced by immune system cells,
enhances T-cell recognition of antigens, and causes worsening of MS symptoms.

Alpha and beta interferon probably exert a suppressive effect on the immune
system and may be beneficial in the treatment of MS. lesion -- an abnormal
change in the structure of an organ due to disease or injury. magnetic resonance
imaging (MRI) -- a non-invasive scanning technique that enables investigators to
see and track MS lesions as they evolve. myelin -- a fatty covering insulating
nerve cell fibers in the brain and spinal cord, myelin facilitates the smooth,
high-speed transmission of electrochemical messages between these components of
the central nervous system and the rest of the body. In MS, myelin is damaged
through a process known as demyelination, which results in distorted or blocked
signals. myelin basic protein (MBP) -- a major component of myelin. When myelin
breakdown occurs (as in MS), MBP can often be found in abnormally high levels in
the patient's cerebrospinal fluid. When injected into laboratory animals, MBP
induces experimental allergic encephalomyelitis, a chronic brain and spinal cord
disease similar to MS. oligodendrocytes -- cells that make and maintain myelin.
optic neuritis -- an inflammatory disorder of the optic nerve that usually
occurs in only one eye and causes visual loss and sometimes blindness. It is
generally temporary. paresthesias -- abnormal sensations such as numbness,
prickling, or "pins and needles." plaques -- patchy areas of
inflammation and demyelination typical of MS, plaques disrupt or block nerve
signals that would normally pass through the regions affected by the plaques.
receptor -- a protein on a cell's surface that allows the cell to identify
antigens. retrobulbar neuritis -- an inflammatory disorder of the optic nerve
that is usually temporary. It causes rapid loss of vision and may cause pain
upon moving the eye. spasticity -- involuntary muscle contractions leading to
spasms and stiffness or rigidity. In MS, this condition primarily affects the
lower limbs. T cells -- immune system cells that develop in the thymus gland.

Findings suggest that T cells are implicated in myelin destruction. transverse
myelitis -- an acute spinal cord disorder causing sudden low back pain and
muscle weakness and abnormal sensory sensations in the lower extremities.

Transverse myelitis often remits spontaneously; however, severe or long-lasting
cases may lead to permanent disability. white matter -- nerve fibers that are
the site of MS lesions and underlie the gray matter of the brain and spinal


Bernard, Bobby. "Multiple Sclerosis Continues to Puzzle Scientists." The

Vermillion March 1998. Brunnscheiler, H. "Problems Associated with MS" (July

28, 1999) "Inteli Health" (28 July 1999).

Boyden, Kathleen M. "Compolmer-1 in the Treatment of Multiple Sclerosis."

Journal of Neuroscience

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