CD-ROM Today 1996 January/CD-ROM Today 1996 January.iso/dp/0401/04014.txt

Text File | 1994-01-17 | 19.6 KB | 392 lines

$Unique_ID{BRK04014}
$Pretitle{}
$Title{Multiple Sclerosis}
$Subject{Multiple Sclerosis MS Demyelinating Disease Disseminated Sclerosis
Amyotrophic Lateral Sclerosis (ALS) Charcot-Marie-Tooth Disease
Dejerine-Sottas Disease Friedreich's Ataxia Guillain-Barre Syndrome Chronic
Inflammatory Demyelinating Polyneuropathy Leukodystrophy }
$Volume{}
$Log{}

Copyright (C) 1984, 1985, 1986, 1987, 1988, 1989, 1990, 1991, 1992, 1993,
National Organization for Rare Disorders, Inc.

15:
Multiple Sclerosis

** IMPORTANT **
It is possible that the main title of the article (Multiple Sclerosis) is
not the name you expected.  Please check the SYNONYMS listing to find the
alternate name and disorder subdivisions covered by this article.

Synonyms

     MS
     Demyelinating Disease
     Disseminated Sclerosis
     Insular Sclerosis

Information on the following diseases can be found in the Related
Disorders section of this report:

     Amyotrophic Lateral Sclerosis (ALS)
     Charcot-Marie-Tooth Disease
     Dejerine-Sottas Disease
     Friedreich's Ataxia
     Guillain-Barre Syndrome
     Chronic Inflammatory Demyelinating Polyneuropathy
     Leukodystrophy

General Discussion

** REMINDER **
The Information contained in the Rare Disease Database is provided for
educational purposes only.  It should not be used for diagnostic or treatment
purposes.  If you wish to obtain more information about this disorder, please
contact your personal physician and/or the agencies listed in the "Resources"
section of this report.


Multiple Sclerosis is a chronic disorder of the central nervous system
(CNS) that causes the destruction of the covering (myelin sheath) over the
nerves.  The course of this disease is variable; it may advance, relapse,
remit, or stabilize.  The demyelinating plaques or patches scattered
throughout the central nervous system interfere with the ability of the
nerves to communicate (neurotransmission) and can cause a wide range of
neurological symptoms.

Symptoms

The symptoms of Multiple Sclerosis may vary greatly.  Some people may have
visual impairment (including blind spots), double vision (diplopia), or
involuntary rhythmic movements of the eyes (nystagmus).   People with
Multiple Sclerosis may also experience impairment of speech, numbness or
tingling sensation in the limbs and difficulty walking.  Dysfunction of the
bladder and bowel may also be present.  Multiple Sclerosis is rarely fatal;
the average life expectancy is 93 percent of that of the general population.
One in 5 Multiple Sclerosis patients experience one attack, followed by
little or no advance in the disorder.  Two-thirds of patients can walk
independently 25 years after diagnosis.  Approximately 50 percent of those
with Multiple Sclerosis pursue most of the activities they engaged in prior
to their diagnosis.  In some cases, however, paralysis of different
severities may make it necessary to use a cane, crutches, and other aids
while walking.  In a very small number of cases, the disease accelerates and
may result in life-threatening complications.

Causes

The exact cause of Multiple Sclerosis is not known.   An autoimmune
association, possibly in a viral or environmental setting, has been
suggested.  Autoimmune disorders are caused when the body's natural defenses
(antibodies, lymphocytes, etc.), against invading organisms suddenly begin to
attack perfectly healthy tissue.

The human T-lymphotropic virus (HTLV-1) has been proposed as another
possible cause.  The HTLV-1 virus is a retrovirus that has been associated
with other central nervous system disorders and certain blood malignancies.

An hereditary predisposition has been suggested, but it seems that other
factors need to be present as well.   A genetic predisposition means that a
person may carry a gene for a disease but it may not be expressed unless
something in the environment triggers the disease.

It has been proposed that a Multiple Sclerosis "susceptibility gene"
(MSSG) exists.  There is, as yet, no definite genetic pattern that can be
discerned.

Studies have shown that the siblings of a person with Multiple Sclerosis
are at a 10 to 15 percent higher risk of developing the disorder than the
general population, whose risk is 0.1 percent.  A Canadian study indicated
that the daughters of mothers with Multiple Sclerosis have a 5 percent risk
of developing the disease.  This may be accounted for the by an immune system
that may or may not foster the development of the disorder (histocompatible
antigens).

A 1989 Australian study implied that a virus carried by cats might be
responsible.  Approximately 7 percent of domestic cats have been shown to
have a demyelinating disease that closely resembles Multiple Sclerosis.  Both
infected cats and patients have been tested and shown to be carrying a
morbillivirus (a virus that resembles the measles virus).  More research is
needed to determine whether this virus has a role in Multiple Sclerosis and
if it can be transmitted from cats.

Affected Population

Multiple Sclerosis affects approximately 58 in every 100,000 people,
numbering around 130,000 individuals.  The disorder may appear at any age,
although the diagnosis is most often made between 20 and 40 years of age.

Multiple Sclerosis is more common in Caucasian Americans than in
Americans of African or Oriental heritage.   In a few ethnic societies
(Eskimos, Bantus and American Indians), Multiple Sclerosis is rare or
absent.  This may hint at a genetic link to this disorder.   Multiple
Sclerosis seems to occur more often the moderate regions (temperate climates)
of the world.

Related Disorders

Symptoms of the following disorders can be similar to those of Multiple
Sclerosis.  Comparisons may be useful for a differential diagnosis:

Amyotrophic lateral sclerosis (ALS) is a disease of the motor neurons
that send signals to the skeletal muscles.  It generally affects both the
upper and the lower muscle groups and results in the progressive weakness and
wasting away of the muscles involved.  There are several varieties of
Amyotrophic Lateral Sclerosis.  The early symptoms may include slight
muscular weakness, clumsy hand movements and difficulty performing fine motor
tasks.  Weakness in the legs may result in clumsiness and tripping, and a
slowing of speech may also be present.  Other symptoms may include muscle
stiffness and coughing.  (For more information on this disorder, choose
"Amyotrophic Lateral Sclerosis" as your search term in the Rare Disease
Database).

Charcot-Marie-Tooth Disease (also known as CMT Disease) is a hereditary
neurological disorder characterized by muscle weakness and atrophy, primarily
in the muscles of the legs.  Symptoms of Type I Charcot-Marie-Tooth Disease
usually begin in middle childhood or teenage years with a deformity of the
foot characterized by a high arch and hyperextension of the toes
(gampsodactyl or claw-foot).  This produces a "stork leg" deformity.  With
time, Charcot-Marie-Tooth disease spreads to the upper extremities and
produces a "stocking-glove" pattern of diminished sensitivity.  There is a
decrease in the sensitivity to vibration, pain and temperature.   (For more
information on this disorder, choose "Charcot-Marie-Tooth Disease" as your
search term in the Rare Disease Database).

Dejerine-Sottas Disease is a rare progressive hereditary disorder that
causes the enlargement of the peripheral nerves and the loss of myelin.  This
results in a burning or tingling sensation in the limbs, generalized muscle
weakness and the loss of coordination in the hands and forearms.  Weakness in
the back of the legs eventually spreads to the front of the legs resulting in
difficulty and pain when walking.  Mild vision problems may also be present.
(For more information on this disorder, choose "Dejerine-Sottas Disease" as
your search term in the Rare Disease Database).

Friedrich's Ataxia is a progressive hereditary disorder that affects the
neuromuscular system.  It is generally diagnosed in childhood or adolescence.
There are slow degenerative changes of the spinal cord and the brain that
affect speech and motor coordination.  These changes may produce an unsteady
walk or numbness and weakness in the arms and legs.  The legs generally
become progressively weaker resulting in a staggering, lurching walk or
trembling when standing still.   (For more information on this disorder,
choose "Friedreich's Ataxia" as your search term on the Rare Disorder
Database).

Guillain-Barre Syndrome (Acute Idiopathic Polyneuritis) is a rare rapidly
progressive polyneuropathy.  Although the exact cause is not known, a
gastrointestinal virus or respiratory infection precedes the onset of the
syndrome in almost half the cases.  The myelin sheath that covers the nerves
is damaged and results in muscle weakness.  The symptoms may include a
burning or tingling sensation in the feet followed by weakness of the legs.
Eventually the torso, upper limbs and face may be affected.  (For more
information on this disorder, choose "Guillain-Barre Syndrome" as your search
term in the Rare Disease Database).

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is a rare
disorder in which there is swelling of the nerve roots and the destruction of
the covering (myelin sheath) over the nerves.  This causes weakness,
paralysis and impairment of motor function especially in the limbs.  Symptoms
may include burning, numbness or tingling of the hands and feet or the arms
and legs.  Reflexes may be weakened or absent, and the muscles of the face
may become weak.  Other symptoms may include difficulty in walking and
respiratory problems.  (For more information on this disorder, choose
"Chronic Inflammatory Demyelinating Polyneuropathy" as your search term on
the Rare Disease Database).

Leukodystrophy is the name given to a group of very rare, progressive,
metabolic, genetic diseases that affect the brain, spinal cord and often the
peripheral nerves.  Each of the leukodystrophies will affect one of the
chemicals that make up the myelin sheath that covers the nerve fibers or it
may affect the white matter of the brain.  Most of the leukodystrophies are
present at birth but some may appear more slowly over time and even into
adulthood.  Leukodystrophy causes the patient to have problems with movement,
vision, hearing, feeling and thinking.  This can result in difficulty
walking, stiffness, a "floppy" feeling in the muscles, paralysis or
convulsions.  (For more information on this disorder, choose "Leukodystrophy"
as your search term on the Rare Disease Database).

Therapies:  Standard

Multiple Sclerosis has no known prevention or cure.  Common treatments may
include the administration of ACTH (adrenocorticotropic hormone), prednisone
or other corticosteroid drugs to help reduce the severity of recurrent
attacks.   These drugs do not slow down or stop the progression of this
disorder.  A wide variety of drugs are prescribed to treat symptoms.  These
may include muscle relaxants and anticonvulsants to help reduce muscle
spasms.  Antidepressants, aspirin or acetaminophen may also help ease pain.
Physical therapy and exercise programs (especially aquatic or water therapy)
may be of value in some patients.

Therapies:  Investigational

Research into the treatment of Multiple Sclerosis is vigorously underway.
The drug cyclophosphamide is being tested and some patients experience
temporary beneficial effects.  Maintenance booster shots of cyclophosphamide
are now being tested to see if these effects can be prolonged.

Beta-interferon injections given directly into the spinal canal
(intrathetically) appear to cut the rate of progressive recurrent episodes in
half for some Multiple Sclerosis patients in experimental trials.

Other trials are underway using blood plasma replacement (plasmapheresis)
in Multiple Sclerosis.  This procedure is a method for removing unwanted
substances (toxins, metabolic substances and plasma parts) from the blood.
Blood is removed from the patient and blood cells are separated from plasma.
The patient's plasma is then replaced with other human plasma and the blood
is transfused back into the patient.  This therapy is still under
investigation to analyze side effects and effectiveness.  More research is
needed before plasmapheresis can be recommended for use in all but the most
severe cases of Multiple Sclerosis.

Also under study is the use of monoclonal antibodies, alpha-interferon,
amantadine, and the anti-gout drug colchicine for use in the treatment of
Multiple Sclerosis.

A two-year clinical trial of the orphan drug copolymer I (COP-1), a
synthetic polypeptide developed in Israel indicated that in fifty patients
with relapsing-remitting Multiple Sclerosis the average number of attacks per
patient was significantly lower for the group treated with copolymer I.  An
International trial of several hundred patients is currently underway.  This
orphan drug is manufactured by Lemmon Pharmaceuticals, P.O. Box 904,
Sellersville, PA, 18960.  This drug is currently available under a "Treatment
IND" to patients who are not in a clinical trial.  Contact Lemmon
Pharmaceuticals for more information.

Intravenous injection of 4-aminopyridine is also being studied in the
hope that this drug may be capable of improving conduction in demyelinated
nerve pathways.  Twelve Multiple Sclerosis patients were treated at Rush
Medical College in Chicago with 4-aminopyridine.  Of the twelve patients
treated, ten showed varying degrees of improvement in vision, eye movement,
coordination and walking.  These effects lasted for about four hours.  More
study of this drug is needed to determine its safety and find a way to
prolong its effects.

Studies of hyperbaric oxygen treatment for Multiple Sclerosis has led to
the conclusion that it is not helpful in the management of this disorder.

Researchers working with specific antibody treatments (monoclonal
antibodies) are trying to find a way to halt disease progression in Multiple
Sclerosis patients.  These antibodies may block the autoimmune process of
Multiple Sclerosis, and appear to have caused no adverse effects in initial
clinical testing.  One promising candidate is an antibody to the immune
response antigen, which may interrupt the symptoms of the disorder but leave
the immune system intact.  Chimeric M-T412 (Human Murine) IgG monoclonal
Anti-CD4 is one of these new antibody treatments being tested.  It is
manufactured by Centocor, Inc., 244 Great Valley Parkway, Malvern, PA, 19355.

Another biologic agent being tested for the treatment of Multiple
Sclerosis is Myelin, developed by Autoimmune, Inc., 75 Francis St., Boston,
MA, 02115.

Other research is aimed at immune suppressing drugs.  Recent research,
however, on the use of Cyclosporine (an immune suppressant prescribed for
organ transplant patients to avoid rejection of a transplanted organ) has
indicated that the therapeutic dose required for Multiple Sclerosis patients
is much to high.  This can lead to unacceptable side effects.

The orphan drug Betaseron is being tested on patients with a relapsing
and remitting form of Multiple Sclerosis.  Betaseron is manufactured by
Triton Biosciences.  More research is needed to determine if Betaseron (a
form of beta-interferon) will be a safe and effective treatment for Multiple
Sclerosis.

Infusion of the drug Baclofen by a surgically implanted pump is being
studied by scientists for the treatment of spasticity associated with
Multiple Sclerosis.  Infusion of the drug directly into the spinal space,
rather than oral administration, seems to provide patients with better relief
of spasticity and may improve muscle tone for longer periods of time.
Smaller quantities of Baclofen seem to be needed when it is infused rather
than given orally.  More research is needed to provide evidence of the safety
and effectiveness of this type of Baclofen administration.

Alpha interferon has been used experimentally on people with Multiple
Sclerosis.  Preliminary evidence suggests that alpha interferon may delay
attacks, leading to progressively fewer attacks of Multiple Sclerosis in some
people.

Radiation treatments are being used experimentally to reduce tissues that
produce T cells (cells that are produced in the bone marrow and mediate
immune responses) in Multiple Sclerosis patients.  Lymphoid irradiation is
directed at the spleen and lymph nodes in the neck, armpit, chest, abdomen
and groin.

Elan Drug Co., is testing EL-970 as a treatment for Multiple Sclerosis.
It is hoped that this drug may improve nerve conduction in a number of
Multiple Sclerosis patients, increasing their visual and motor abilities.
EL-970 was licensed from Rush-Presbyterian-St. Lukes Medical Center in
Chicago.

Researchers at the University of Pennsylvania are studying the use of
Photopheresis as a treatment for Multiple Sclerosis.  Photopheresis has been
used to treat other types of diseases such as cancer and skin problems.  In
this method of treating the blood, the drug 8-MOP is given to the person
orally.  Then the blood is removed and radiated with ultraviolet light, and
then returned to the body.  The patient does not receive radiation, but the
treated blood's cell structure is altered to stimulate the immune system.  It
is hoped that this may lead to an increase the body's defense against
Multiple Sclerosis.

Clinical trials are underway to study the role of T-cell receptor
repertoire in Multiple Sclerosis.  Interested persons may wish to contact:

     Dr. David H. Mattson
     University of Rochester
     601 Elmwood Ave., Box 605
     Rochester, NY  14642
     [phone]

This disease entry is based upon medical information available through
February 1993.  Since NORD's resources are limited, it is not possible to
keep every entry in the Rare Disease Database completely current and
accurate.  Please check with the agencies listed in the Resources section for
the most current information about this disorder.

Resources

For more information on Multiple Sclerosis, please contact:

     National Organization for Rare Disorders (NORD)
     P.O. Box 8923
     New Fairfield, CT  06812-1783
     [phone]

The National Multiple Sclerosis Society maintains over 120 chapters
throughout the United States which provide direct services to people with MS
and their families, including occupational and physical therapy, support
groups, clinics, and professional and public education.  Information about
chapters can be obtained from the national office.

     National Multiple Sclerosis Society, National Headquarters
     733 Third Ave.
     New York, NY  10017-3288
     [phone]
     [phone]

     NIH/National Institute of Neurological Disorders & Stroke (NINDS)
     9000 Rockville Pike
     Bethesda, MD  20892
     [phone]
     [phone]


References

MENDELIAN INHERITANCE IN MAN, 10th Ed.:  Victor A. McKusick, Editor:  Johns
Hopkins University Press, 1992.  Pp. 317-318.

CECIL TEXTBOOK OF MEDICINE, 19th Ed.:  James B. Wyngaarden, and Lloyd H.
Smith, Jr., Editors; W.B. Saunders Co., 1990.  Pp. 2196-2102.

INTRATHECAL BACLOFEN FOR SEVERE SPASTICITY, R.D. Penn, et al.; New Eng J
Med (June 8, 1989, issue 320 (23)).  Pp. 1517-1521.

TREATMENT OF MULTIPLE SCLEROSIS WITH HYPERBARIC OXYGEN.  RESULTS OF A
NATIONAL REGISTRY, E.P. Kidwell et al.; Arch Neurol (Feb. 1991; 48(2)):  Pp.
195-199.

THE SUPRASPINAL ANXIOLYTIC EFFECT OF BACLOFEN FOR SPASTICITY, S.R.
Hinderer; Am J Med Rehabil (Oct. 1990; (69(5)):  Pp. 254-258.

HIGH DOSE ORAL BACLOFEN:  EXPERIENCE IN PATIENTS WITH MULTIPLE SCLEROSIS,
G.D. Ehrlich et al.; Neurology (March 1991; (41(3)):  Pp. 335-43.