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$Unique_ID{BRK03454}
$Pretitle{}
$Title{Amyotrophic Lateral Sclerosis}
$Subject{Amyotrophic Lateral Sclerosis ALS Lou Gehrig's Disease Gehrig's
Disease Motor Neuron Disease Amyotrophic Lateral Sclerosis-Polyglucosan Bodies
Motor System Disease Focal and Slow Aran-Duchenne Muscular Atrophy Spinal
Muscular Atrophy Juvenile Spinal Muscular Atrophy Kugelberg-Welander Disease
Progressive Bulbar Palsy Benign Focal Amyotrophy Primary Lateral Sclerosis
Upper Motor Neuron Disease Infantile Spinal Muscular Atrophy
Werdnig-Hoffman Disease Wohlfart Disease Kugelberg-Welander Disease
Floppy Infant Syndrome Primary Lateral Sclerosis Kugelberg-Welander Syndrome
Focal Motor Neuron Disease Progressive Bulbar Palsy Progressive Muscular
Atrophy Pseudobulbar Palsy Benign Focal Amyotrophy}
$Volume{}
$Log{}

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

57:
Amyotrophic Lateral Sclerosis

** IMPORTANT **
It is possible that the main title of the article (Amyotrophic Lateral
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

     ALS
     Lou Gehrig's Disease
     Gehrig's Disease
     Motor Neuron Disease
     Amyotrophic Lateral Sclerosis-Polyglucosan Bodies
     Motor System Disease (Focal and Slow)
     Aran-Duchenne Muscular Atrophy

DISORDER SUBDIVISIONS:

     Spinal Muscular Atrophy
     Juvenile Spinal Muscular Atrophy (Kugelberg-Welander Disease)
     Progressive Bulbar Palsy
     Benign Focal Amyotrophy
     Primary Lateral Sclerosis (Upper Motor Neuron Disease)
     Infantile Spinal Muscular Atrophy (Werdnig-Hoffman Disease, Wohlfart-
     Disease, Kugelberg-Welander Disease and Floppy Infant Syndrome)

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

     Primary Lateral Sclerosis
     Kugelberg-Welander Syndrome
     Focal Motor Neuron Disease
     Progressive Bulbar Palsy
     Progressive Muscular Atrophy
     Pseudobulbar Palsy
     Benign Focal Amyotrophy

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.


Amyotrophic Lateral Sclerosis (ALS) is a disease of the skeletal muscle
nerve cells (motor neurons).  This disorder generally affects both upper and
lower motor neurons resulting in muscular weakness and the progressive
wasting of muscles that have lost their nerve supply.

There are a number of different forms of Amyotrophic Lateral Sclerosis
and other motor neuron diseases with similar symptoms.  These include:  Slow
Motor Neuron Disease, Focal Motor Neuron Disease, Spinal Muscular Atrophy
(Kugelberg-Welander Disease and Juvenile Spinal Muscular Atrophy),
Progressive Bulbar Palsy, Benign Focal Amyotrophy, Primary Lateral Sclerosis,
Infantile Spinal Muscular Atrophy (Werdnig-Hoffmann Disease), Wohlfart-
Kugelberg-Welander Disease, and Floppy Infant Syndrome.  (For more information
on these disorders, choose "Motor Neuron," "Primary Lateral Sclerosis,"
"Werdnig-Hoffman," and "Kugelberg-Welander" as your search terms in the Rare
Disease Database.)

Symptoms

The early symptoms of Amyotrophic Lateral Sclerosis (ALS) include slight
muscle weakness, clumsy hand movements, and/or difficulty performing tasks
that require delicate movements of the fingers and/or hands.  Muscular
weakness in the legs may cause tripping and falling.  People with Amyotrophic
Lateral Sclerosis may have difficulty swallowing (dysphagia), and speech may
be slowed.  Other symptoms of this disorder include progressive weakness of
the lips and impairment and/or loss of function of the tongue, mouth, and/or
voice box (bulbar symptoms).  Leg cramps may occur during the night, most
frequently in the calf and/or thigh muscles.  Amyotrophic Lateral Sclerosis
may progress quickly or slowly, and gradually additional muscles become
involved.

Other symptoms of Amyotrophic Lateral Sclerosis may include the
uncontrolled twitching of muscles (fasciculations), stiffness in the legs,
and/or coughing.  People with this disorder may also have exaggerated deep
muscle reflexes.  Severe weight loss occurs in approximately 5 percent of
cases.  As the ability to move becomes progressively impaired, people with
this disease are at increased risk for respiratory failure and abnormally low
levels of oxygen in the blood (anoxia).  People with Amyotrophic Lateral
Sclerosis are also at increased risk for acute inflammation of the lungs,
caused by the inhalation of food or stomach contents (aspiration pneumonia).
An overall decrease in the ability to move may also result in inadequate
nutrition.

Muscle biopsy and electromyographic testing may be used to determine the
particular type of Amyotrophic Lateral Sclerosis that a person has.  Twenty
percent of all people with Amyotrophic Lateral Sclerosis experience a gradual
stabilization of symptoms and may maintain at that level (plateau) for a few
years.

Causes

The exact cause of Amyotrophic Lateral Sclerosis is unknown.  Allergic
responses, infectious and/or viral agents have been proposed as possible
causes of this disorder, but none has been proven.  Approximately 5 to 10
percent of all cases of Amyotrophic Lateral Sclerosis are hereditary.

Researchers have found the defective gene responsible for the inherited
form of Amyotrophic Lateral Sclerosis.  The gene is inherited as an autosomal
dominant genetic trait and is located on the long arm of chromosome 21.  In
the small percentage of cases that are inherited, it is not yet known if this
defective gene causes Amyotrophic Lateral Sclerosis or predisposes a person
to this disease.   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.

In 1992 researchers at Johns Hopkins Hospital proposed that glutamate, an
amino acid responsible for carrying messages between brain cells (neurons),
may have a role in causing ALS.  Glutamate in large quantities may kill
neurons.  In the brain, after glutamate does its' job of transmitting
messages, it is reabsorbed by a special protein called a "transporter".  In
ALS researchers suspect that this transporter is defective and may not absorb
enough glutamate.  These studies were conducted on brain tissue donated by
ALS patients who had died.  More research is needed to determine if this
theory about glutamate is accurate, and if drugs can be developed to alter
the glutamate absorption process.

There is no difference in the symptoms of the sporadic or familial forms
of Amyotrophic Lateral Sclerosis.  Therefore, the discovery of the location of
this gene may benefit people with both forms of the disorder (inherited or
non-inherited).

Affected Population

Amyotrophic Lateral Sclerosis is a rare disorder that affects approximately
25,000 people in the United States.  Generally symptoms appear between 40 and
70 years of age.  Amyotrophic Lateral Sclerosis affects more males than
females.  Approximately 60 percent of those affected are men; 40 percent of
affected individuals are women.

Related Disorders

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

Primary Lateral Sclerosis is a rare neurological disorder characterized
by progressive weakness of the muscles of the face, arms, and legs.  The loss
of neurological function occurs slowly and results in spastic movements of
the hands, feet, and/or legs.  Dragging of the feet is typically followed by
the inability to walk.  Sensory function and intellectual capabilities are
generally unaffected.  (For more information on this disorder, choose
"Primary Lateral Sclerosis" as your search term in the Rare Disease
Database.)

Kugelberg-Welander Syndrome (Spinal Muscular Atrophy) is a rare inherited
neurological disorder characterized by the progressive degeneration of the
motor neurons.  The symptoms of this disorder include progressive weakness
and loss of muscle tissue, especially in the legs and an uncoordinated gait.
This is typically accompanied by a loss of reflexes in the legs.  People with
Kugelberg-Welander Syndrome may have difficulty climbing stairs and may lose
bowel control.  (For more information on this disorder, choose "Kugelberg-
Welander" as your search in the Rare Disease Database.)

Focal Motor Neuron Disease affects only one area of the body, most
commonly the shoulder girdle.  The disease progresses over several months,
leaving the patient with a fixed impairment of function.  Some patients later
develop more extensive motor neuron disease.  If focal motor neuron disease
is considered as a diagnosis, care should be taken to exclude other causes of
focal atrophy.

Progressive Bulbar Palsy is a variant of Amyotrophic Lateral Sclerosis
characterized by weakness and wasting (atrophy) of the muscles innervated by
the cranial nerves (i.e., lips, tongue, and voice box).  Symptoms may include
difficulty speaking and swallowing.

Progressive Muscular Atrophy is a variant of Amyotrophic Lateral
Sclerosis characterized by lower motor neuron involvement.  This form of the
disease is characterized by weakness and wasting (atrophy) of the muscles of
the lower body, particularly the legs.  If upper motor neuron symptoms do not
occur, usually within two years, then it is unlikely that Amyotrophic Lateral
Sclerosis will develop.

Pseudobulbar Palsy is a variant of Amyotrophic Lateral Sclerosis
characterized by spastic muscle weakness and the loss of muscles that are
innervated by the cranial nerves.  Typically the tongue, throat, and face are
affected.  The eyes are not affected.  Some people with this disorder also
experience uncontrollable laughing and/or weeping.

Benign Focal Amyotrophy is a variant in which muscle weakness and wasting
are limited to a single limb.  The early symptoms of this disorder may
resemble those of Amyotrophic Lateral Sclerosis.

Therapies:  Standard

The treatment of Amyotrophic Lateral Sclerosis generally requires a team
approach and may include physicians, physical therapists, speech
pathologists, pulmonary therapists, medical social workers, and nurses.

Several drugs are used to alleviate the symptoms of Amyotrophic Lateral
Sclerosis.  Baclofen may reduce muscle spasms in some patients.  Patients
troubled by leg cramps may benefit from quinine compounds.  The uncontrolled
twitching of small muscles (fasciculations), which may interfere with sleep,
may respond to the administration of muscle relaxant drugs such as diazepam.
Some ALS patients, who have a defect in the transmission of nerve impulses in
the area where nerves and muscles meet (neuromuscular junction), may
temporarily feel stronger while taking pyridostigmine.

It is essential that people with Amyotrophic Lateral Sclerosis maintain
proper nutrition.  It has been shown that vitamin therapy does not affect the
course of Amyotrophic Lateral Sclerosis.  Soft foods should be carefully
chosen for patients who have difficulty swallowing (dysphagia).

Physical therapy is very important and should consist of daily range-of-
motion exercises.  These exercises can help maintain the flexibility of
affected joints and prevent the fixation of muscles (contractures).

Communication devices can be useful for patients with Amyotrophic Lateral
Sclerosis who have difficulty speaking (dysarthria); these devices may
include the use of codes involving eye movement (extraocular).  For those
patients who are able to use their hands, the use of written messages,
typing, or the use of small computers with artificial speech articulation may
help to combat feelings of isolation.

Respiratory aids are often needed in advanced stages of Amyotrophic
Lateral Sclerosis.  Portable breathing machines can be attached to
wheelchairs to help patients maintain mobility.

Therapies:  Investigational

There is extensive ongoing research on the cause and treatment of Amyotrophic
Lateral Sclerosis.  This research is in the areas of nerve growth factors,
axonal transport, androgen receptors in motor neurons, alterations in DNA and
RNA, and metabolic studies of the neuromuscular junction.

Some evidence suggests that defective metabolism of the amino acid,
glutamate, may be responsible for degeneration of the nerve cells in the
muscles of patients with Amyotrophic Lateral Sclerosis.  Scientists are
studying the "building blocks of proteins" (amino acids) to determine if they
can prevent the toxic effects of glutamate.  The amino acids that are being
studied include L-leucine, L-isoleucine, and L-valine.

Other scientists are studying the orphan drug L-threonine (Threostat),
which may increase the amino acid glycine (an inhibitory neurotransmitter);
this might "neutralize" the excess glutamate found in patients with
Amyotrophic Lateral Sclerosis.  The long term safety and effectiveness of
these experimental treatments must be assessed before they are recommended
for Amyotrophic Lateral Sclerosis patients.  In 1990 Dr. Rup Tandan of the
University of Vermont, Burlington, VT, received a grant award from the FDA's
Office of Orphan Product Development for his work on L-threonine and Branched
Chain Amino Acids in Amyotrophic Lateral Sclerosis.

The orphan drug Insulin-Like Growth Factor-1 (Myotrophin) is being
investigated as a treatment for patients with Amyotrophic Lateral Sclerosis.
The drug is made by Cephalon, Inc., 145 Brandywine Parkway, West Chester, PA,
19380.  More study is needed to determine the longterm safety and
effectiveness of this drug as a treatment for this disorder.

The orphan drug Human Ciliary Neurotrophic Factor is also being tested as
a treatment for people with Amyotrophic Lateral Sclerosis.  The drug is
manufactured by Regeneron Pharmaceuticals, 777 Old Saw Mill River Road,
Tarrytown, NY, 10591.  Clinical studies are underway to determine the safety
and effectiveness of this drug.

Genetic research is underway on the hereditary form of Amyotrophic
Lateral Sclerosis (ALS) to determine the role of the gene that causes this
disorder.  Once scientists understand the substance that this gene is
supposed to manufacture, research on new treatments may be possible.

The orphan drug Riluzole is being tested for the treatment of ALS.  The
drug is sponsored by Rhone-Poulenc Rorer Pharm. of Collegeville, PA.

This disease entry is based upon medical information available through
April 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 Amyotrophic Lateral Sclerosis, please contact:

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

     The Amyotrophic Lateral Sclerosis Society
     21021 Ventura Blvd., Suite 321
     Woodland Hills, CA  91364
     [phone]

For the childhood forms of Motor Neuron disease:

     Families of Spinal Muscular Atrophy
     P.O. Box 1465
     Highland Park, IL  60035
     [phone]

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

References

THE MERCK MANUAL 16th ed.  R. Berkow, et al:  eds; Merck, Sharp & Dohme
Research Laboratories, 1992.  P. 1512.

MENDELIAN INHERITANCE IN MAN, 10th Ed.:  Victor A. McKusick, Editor:
Johns Hopkins University Press, 1992.  Pp. 71-72.

CECIL TEXTBOOK OF MEDICINE, 19th Ed.:  James B. Wyngaarden, and Lloyd H.
Smith, Jr., Editors; W.B. Saunders Co., 1990.  Pp. 2141-2142.

BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief;
Blackwell Scientific Publications, 1990.  Pp. 110-111.

PRINCIPLES OF NEUROLOGY, 4th Ed.; Raymond D. Adams, M.D. and Maurice
Victor, M.D., Editors; McGraw-Hill Information Services Company, 1989.  Pp.
935-935, 953-954.

AMYOTROPHIC LATERAL SCLEROSIS:  H. Mitsumoto; Arch Neurol (Feb. 1988; 45).
Pp. 189-202.

MOTOR NEURON DISEASE (AMYOTROPHIC LATERAL SCLEROSIS).  D.B. Williams; Mayo
Clin Proc (Jan. 1991; 66(1)).  Pp. 54-82.

L-THREONINE AS A SYMPTOMATIC TREATMENT FOR AMYOTROPHIC LATERAL SCLEROSIS
(ALS).  J.B. Roufs; Med Hypotheses (Jan. 1991; 34(1)).  Pp. 20-23.