Amytrophic, Lou Gerig, Lou Gehrigs, Lougehrig
Amyotrophic lateral sclerosis (ALS), sometimes called Lou Gehrig's
disease, is a rapidly progressive, invariably fatal neurological disease
that attacks the nerve cells (neurons) responsible for controlling
voluntary muscles. The disease belongs to a group of disorders known as
motor neuron diseases, which are characterized by the gradual
degeneration and death of motor neurons.
Motor neurons are nerve cells located in the brain, brainstem, and
spinal cord that serve as controlling units and vital communication links
between the nervous system and the voluntary muscles of the body. Messages
from motor neurons in the brain (called upper motor neurons) are
transmitted to motor neurons in the spinal cord (called lower motor
neurons) and from them to particular muscles. In ALS, both the upper
motor neurons and the lower motor neurons degenerate or die, ceasing to
send messages to muscles. Unable to function, the muscles gradually
weaken, waste away (atrophy), and twitch (fasciculations) .
Eventually, the ability of the brain to start and control voluntary
movement is lost.
Lou Gehrig's Disease causes weakness with a wide range of disabilities (see
section titled "ALS Symptoms"). Eventually, all muscles under
voluntary control are affected, and patients lose their strength and the
ability to move their arms, legs, and body. When muscles in the diaphragm
and chest wall fail, patients lose the ability to breathe without
ventilatory support. Most people with ALS die from respiratory failure,
usually within 3 to 5 years from the onset of ALS symptoms. However, about 10
percent of ALS patients survive for 10 or more years.
Because ALS affects only motor neurons, the disease does not impair a
person's mind, personality, intelligence, or memory. Nor does it affect a
person's ability to see, smell, taste, hear, or recognize touch. Patients
usually maintain control of eye muscles and bladder and bowel
functions.
As many as 20,000 Americans have Lou Gehrig's disease, and an estimated 5,000 people in
the United States are diagnosed with the disease each year. ALS is one of
the most common neuromuscular diseases worldwide, and people of all races
and ethnic backgrounds are affected. ALS most commonly strikes people
between 40 and 60 years of age, but younger and older people also can
develop the disease. Men are affected more often than women.
In 90 to 95 percent of all ALS cases, the disease occurs apparently at
random with no clearly associated risk factors. Patients do not have a
family history of the disease, and their family members are not considered
to be at increased risk for developing Lou Gehrig's Disease.
About 5 to 10 percent of all ALS cases are inherited. The familial form
of ALS usually results from a pattern of inheritance that requires only
one parent to carry the gene responsible for the disease. About 20 percent
of all familial cases result from a specific genetic defect that leads to
mutation of the enzyme known as superoxide dismutase 1 (SOD1). Research on
this mutation is providing clues about the possible causes of motor neuron
death in Lou Gehrig's Disease. Not all familial ALS cases are due to the SOD1 mutation,
therefore other unidentified genetic causes clearly exist.
The onset of Lou Gehrig's disease may be so subtle that the symptoms are frequently
overlooked. The earliest symptoms of ALS may include twitching, cramping, or
stiffness of muscles; muscle weakness affecting an arm or a leg; slurred
and nasal speech; or difficulty chewing or swallowing. These general
complaints then develop into more obvious weakness or atrophy that may
cause a physician to suspect ALS.
The parts of the body affected by early symptoms of ALS depend on which
muscles in the body are damaged first. In some cases, ALS symptoms initially
affect one of the legs, and patients experience awkwardness when walking
or running or they notice that they are tripping or stumbling more often.
Some patients first see the effects of the disease on a hand or arm as
they experience difficulty with simple tasks requiring manual dexterity
such as buttoning a shirt, writing, or turning a key in a lock. Other
patients notice speech problems.
Regardless of the part of the body first affected by the disease,
muscle weakness and atrophy spread to other parts of the body as the
disease progresses. Patients have increasing problems with moving,
swallowing (dysphagia), and speaking or forming words
(dysarthria). Symptoms of upper motor neuron involvement include
tight and stiff muscles (spasticity) and exaggerated reflexes
(hyperreflexia) including an overactive gag reflex. An abnormal
reflex commonly called Babinski's sign (the large toe extends upward as
the sole of the foot is stimulated in a certain way) also indicates upper
motor neuron damage. Symptoms of lower motor neuron degeneration include
muscle weakness and atrophy, muscle cramps, and fleeting twitches of
muscles that can be seen under the skin (fasciculations).
To be diagnosed with amyotrophic lateral sclerosis, patients must have signs and symptoms of both
upper and lower motor neuron damage that cannot be attributed to other
causes.
Although the sequence of emerging ALS symptoms and the rate of disease
progression vary from person to person, eventually patients will not be
able to stand or walk, get in or out of bed on their own, or use their
hands and arms. Difficulty swallowing and chewing impair the patient's
ability to eat normally and increase the risk of choking. Maintaining
weight will then become a problem. Because the disease usually does not
affect cognitive abilities, patients are aware of their progressive loss
of function and may become anxious and depressed. Health care
professionals need to explain the course of the disease and describe
available treatment options so that patients can make informed decisions
in advance. In later stages of the disease, patients have difficulty
breathing as the muscles of the respiratory system weaken. Patients
eventually lose the ability to breathe on their own and must depend on
ventilatory support for survival. Patients also face an increased risk of
pneumonia during later stages of Lou Gehrig's Disease.
No one test can provide a definitive diagnosis of ALS, although the
presence of upper and lower motor neuron signs in a single limb is
strongly suggestive. Instead, the diagnosis of Lou Gehrig's disease is primarily based on
the symptoms and signs the physician observes in the patient and a series
of tests to rule out other diseases. Physicians obtain the patient's full
medical history and usually conduct a neurologic examination at regular
intervals to assess whether symptoms such as muscle weakness, atrophy of
muscles, hyperreflexia, and spasticity are getting progressively
worse.
Because ALS symptoms can be similar to those of a wide variety of
other, more treatable diseases or disorders, appropriate tests must be
conducted to exclude the possibility of other conditions. One of these
tests is electromyography (EMG), a special recording technique that
detects electrical activity in muscles. Certain EMG findings can support
the diagnosis of ALS. Another common test measures nerve conduction
velocity (NCV). Specific abnormalities in the NCV results may suggest,
for example, that the patient has a form of peripheral neuropathy (damage
to peripheral nerves) or myopathy (muscle disease) rather than amyotrophic lateral sclerosis. The
physician may order magnetic resonance imaging (MRI), a noninvasive
procedure that uses a magnetic field and radio waves to take detailed
images of the brain and spinal cord. Although these MRI scans are often
normal in patients with ALS, they can reveal evidence of other problems
that may be causing the symptoms, such as a spinal cord tumor, a herniated
disk in the neck, syringomyelia, or cervical spondylosis.
Based on the patient's symptoms and findings from the examination and
from these tests, the physician may order tests on blood and urine samples
to eliminate the possibility of other diseases as well as routine
laboratory tests. In some cases, for example, if a physician suspects that
the patient may have a myopathy rather than ALS, a muscle biopsy may be
performed.
Infectious diseases such as human immunodeficiency virus (HIV), human
T-cell leukemia virus (HTLV), and Lyme disease can in some cases cause
ALS-like symptoms. Neurological disorders such as multiple sclerosis,
post-polio syndrome, multifocal motor neuropathy, and spinal muscular
atrophy also can mimic certain facets of the disease and should be
considered by physicians attempting to make a diagnosis.
Because of the prognosis carried by this diagnosis and the variety of
diseases or disorders that can resemble Lou Gehrig's disease in the early stages of the
disease, patients may wish to obtain a second neurological opinion.
The cause of ALS is not known, and scientists do not yet know why ALS
strikes some people and not others. An important step toward answering
that question came in 1993 when scientists supported by the National
Institute of Neurological Disorders and Stroke (NINDS) discovered that
mutations in the gene that produces the SOD1 enzyme were associated with
some cases of familial ALS. This enzyme is a powerful antioxidant that
protects the body from damage caused by free radicals. Free radicals are
highly unstable molecules produced by cells during normal metabolism. If
not neutralized, free radicals can accumulate and cause random damage to
the DNA and proteins within cells. Although it is not yet clear how the
SOD1 gene mutation leads to motor neuron degeneration, researchers have
theorized that an accumulation of free radicals may result from the faulty
functioning of this gene. In support of this, animal studies have shown
that motor neuron degeneration and deficits in motor function accompany
the presence of the SOD1 mutation.
Studies also have focused on the role of glutamate in motor neuron
degeneration. Glutamate is one of the chemical messengers or
neurotransmitters in the brain. Scientists have found that, compared to
healthy people, ALS patients have higher levels of glutamate in the serum
and spinal fluid. Laboratory studies have demonstrated that neurons begin
to die off when they are exposed over long periods to excessive amounts of
glutamate. Now, scientists are trying to understand what mechanisms lead
to a buildup of unneeded glutamate in the spinal fluid and how this
imbalance could contribute to the development of ALS.
Autoimmune responses—which occur when the body's immune system attacks
normal cells—have been suggested as one possible cause for motor neuron
degeneration in ALS. Some scientists theorize that antibodies may directly
or indirectly impair the function of motor neurons, interfering with the
transmission of signals between the brain and muscles.
In searching for the cause of ALS, researchers have also studied
environmental factors such as exposure to toxic or infectious agents.
Other research has examined the possible role of dietary deficiency or
trauma. However, as of yet, there is insufficient evidence to implicate
these factors as causes of Lou Gehrig's Disease.
Future research may show that many factors, including a genetic
predisposition, are involved in the development of ALS.
No cure has yet been found for ALS. However, the Food and Drug
Administration (FDA) has approved the first drug treatment for the
disease—riluzole (Rilutek). Riluzole is believed to reduce damage to motor
neurons by decreasing the release of glutamate. Clinical trials with ALS
patients showed that riluzole prolongs survival by several months, mainly
in those with difficulty swallowing. The drug also extends the time before
a patient needs ventilation support. Riluzole does not reverse the damage
already done to motor neurons, and patients taking the drug must be
monitored for liver damage and other possible side effects. However, this
first disease-specific therapy offers hope that the progression of ALS may
one day be slowed by new medications or combinations of drugs.
Other treatments for ALS are designed to relieve symptoms and improve
the quality of life for patients. This supportive care is best provided by
multidisciplinary teams of health care professionals such as physicians;
pharmacists; physical, occupational, and speech therapists; nutritionists;
social workers; and home care and hospice nurses. Working with patients
and caregivers, these teams can design an individualized plan of medical
and physical therapy and provide special equipment aimed at keeping
patients as mobile and comfortable as possible.
Physicians can prescribe medications to help reduce fatigue, ease
muscle cramps, control spasticity, and reduce excess saliva and phlegm.
Drugs also are available to help patients with pain, depression, sleep
disturbances, and constipation. Pharmacists can give advice on the proper
use of medications and monitor a patient's prescriptions to avoid risks of
drug interactions.
Physical therapy and special equipment can enhance patients'
independence and safety throughout the course of ALS. Gentle, low-impact
aerobic exercise such as walking, swimming, and stationary bicycling can
strengthen unaffected muscles, improve cardiovascular health, and help
patients fight fatigue and depression. Range of motion and stretching
exercises can help prevent painful spasticity and shortening (contracture)
of muscles. Physical therapists can recommend exercises that provide these
benefits without overworking muscles. Occupational therapists can suggest
devices such as ramps, braces, walkers, and wheelchairs that help patients
conserve energy and remain mobile.
ALS patients who have difficulty speaking may benefit from working with
a speech therapist. These health professionals can teach patients adaptive
strategies such as techniques to help them speak louder and more clearly.
As ALS progresses, speech therapists can help patients develop ways for
responding to yes-or-no questions with their eyes or by other nonverbal
means and can recommend aids such as speech synthesizers and
computer-based communication systems. These methods and devices help
patients communicate when they can no longer speak or produce vocal
sounds.
Patients and caregivers can learn from speech therapists and
nutritionists how to plan and prepare numerous small meals throughout the
day that provide enough calories, fiber, and fluid and how to avoid foods
that are difficult to swallow. Patients may begin using suction devices to
remove excess fluids or saliva and prevent choking. When patients can no
longer get enough nourishment from eating, doctors may advise inserting a
feeding tube into the stomach. The use of a feeding tube also reduces the
risk of choking and pneumonia that can result from inhaling liquids into
the lungs. The tube is not painful and does not prevent patients from
eating food orally if they wish.
When the muscles that assist in breathing weaken, use of nocturnal
ventilatory assistance (intermittent positive pressure ventilation
[IPPV] or bilevel positive airway pressure [BIPAP]) may be used to
aid breathing during sleep. Such devices artificially inflate the
patient's lungs from various external sources that are applied directly to
the face or body. When muscles are no longer able to maintain oxygen and
carbon dioxide levels, these devices may be used full-time.
Patients may eventually consider forms of mechanical ventilation
(respirators) in which a machine inflates and deflates the lungs. To be
effective, this may require a tube that passes from the nose or mouth to
the windpipe (trachea) and for long-term use, an operation such as a
tracheostomy, in which a plastic breathing tube is inserted directly in
the patient's windpipe through an opening in the neck. Patients and their
families should consider several factors when deciding whether and when to
use one of these options. Ventilation devices differ in their effect on
the patient's quality of life and in cost. Although ventilation support
can ease problems with breathing and prolong survival, it does not affect
the progression of ALS. Patients need to be fully informed about these
considerations and the long-term effects of life without movement before
they make decisions about ventilation support.
Social workers and home care and hospice nurses help patients,
families, and caregivers with the medical, emotional, and financial
challenges of coping with ALS, particularly during the final stages of the
disease. Social workers provide support such as assistance in obtaining
financial aid, arranging durable power of attorney, preparing a living
will, and finding support groups for patients and caregivers. Home care
nurses are available not only to provide medical care but also to teach
caregivers about tasks such as maintaining respirators, giving tube
feedings, and moving patients to avoid painful skin problems and
contractures. Home hospice nurses work in consultation with physicians to
ensure proper medication, pain control, and other care affecting the
quality of life of patients who wish to remain at home. The home hospice
team can also counsel patients and caregivers about end-of-life issues.
Scientists are seeking to understand the mechanisms that trigger
selective motor neurons to degenerate in ALS and to find effective
approaches to halt the processes leading to cell death. This work includes
studies in animals to identify the means by which SOD1 mutations lead to
the destruction of neurons. The excessive accumulation of free radicals,
which has been implicated in a number of neurodegenerative diseases
including ALS, is also being closely studied. In addition, researchers are
examining how the loss of neurotrophic factors may be involved in
ALS. Neurotrophic factors are chemicals found in the brain and spinal cord
that play a vital role in the development, specification, maintenance, and
protection of neurons. Studying how these factors may be lost and how such
a loss may contribute to motor neuron degeneration may lead to a greater
understanding of ALS and the development of neuroprotective strategies. By
exploring these and other possible factors, researchers hope to find the
cause or causes of motor neuron degeneration in ALS and develop therapies
to slow the progression of the disease.
Researchers are also conducting investigations to increase their
understanding of the role of programmed cell death or apoptosis in
ALS. In normal physiological processes, apoptosis acts as a means to rid
the body of cells that are no longer needed by prompting the cells to
commit "cell suicide." The critical balance between necessary cell death
and the maintenance of essential cells is thought to be controlled by
trophic factors. In addition to ALS, apoptosis is pervasive in other
chronic neurodegenerative conditions such as Parkinson's disease and
Alzheimer's disease and is thought to be a major cause of the secondary
brain damage seen after stroke and trauma. Discovering what triggers
apoptosis may eventually lead to therapeutic interventions for ALS and
other neurological diseases.
Scientists have not yet identified a reliable biological marker for
ALS—a biochemical abnormality shared by all patients with the disease.
Once such a biomarker is discovered and tests are developed to detect the
marker in patients, allowing early detection and diagnosis of ALS,
physicians will have a valuable tool to help them follow the effects of
new therapies and monitor disease progression.
NINDS-supported researchers are studying families with ALS who lack the
SOD1 mutation to locate additional genes that cause the disease.
Identification of additional ALS genes will allow genetic testing useful
for diagnostic confirmation of Lou Gehrig's disease and prenatal screening for the disease.
This work with familial ALS could lead to a greater understanding of
sporadic ALS as well. Because familial amyotrophic lateral sclerosis is virtually indistinguishable
from sporadic ALS clinically, some researchers believe that familial ALS
genes may also be involved in the manifestations of the more common
sporadic form of ALS. Scientists also hope to identify genetic risk
factors that predispose people to sporadic ALS.
Potential therapies for ALS are being investigated in animal models.
Some of this work involves experimental treatments with normal SOD1 and
other antioxidants. In addition, neurotrophic factors are being studied
for their potential to protect motor neurons from pathological
degeneration. Investigators are optimistic that these and other basic
research studies will eventually lead to ALS treatments.
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 following organizations support research and in some cases can
provide information and support for patients and their families.
The ALS Association (ALSA)
27001 Agoura Road, Suite 150
Calabasas Hills, California 91301-5104
(818) 880-9007
(800)
782-4747
http://www.alsa.org/
Center for Neurologic Study
9850 Genesee Avenue, Suite
320
LaJolla, California 92037
(858) 455-5463
http://www.cnsonline.org/
Forbes Norris ALS Research Center
California Pacific Medical
Center
2324 Sacramento Street
San Francisco, California
94115
(415) 923-3604
Les Turner ALS Foundation
8142 North Lawndale Avenue
Skokie,
Illinois 60076-3322
(847) 679-3311
(888) ALS-1107
http://www.lesturnerals.org/
The Muscular Dystrophy Association
3300 East Sunrise
Drive
Tucson, Arizona 85718-3208
(520) 529-2000
(800)
572-1717
http://www.mdausa.org/
Project ALS
511 Avenue of the Americas
Suite 341
New York, NY
10011
(212) 969-0329
(800) 603-0270
http://www.projectals.org/
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