Amyotrophic Lateral Sclerosis
On this page:
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.
ALS causes weakness with a wide range of disabilities (see
section titled "What are the 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 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.
Return to top 
As many as 20,000 Americans have ALS, 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 ALS.
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
ALS. Not all familial ALS cases are due to the SOD1 mutation,
therefore other unidentified genetic causes clearly exist.
Return to top
The onset of ALS may be so subtle that the symptoms are
frequently overlooked. The earliest symptoms 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, 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 ALS, 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 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 ALS.
Return to top
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 ALS 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 symptoms of ALS 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 ALS. 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 ALS in the early
stages of the disease, patients may wish to obtain a second
neurological opinion.
Return to top
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 reactive 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 ALS.
Future research may show that many factors, including a genetic
predisposition, are involved in the development of ALS.
Return to top
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.
Return to top
The National Institute of Neurological Disorders and Stroke, part
of the National Institutes of Health, is the Federal Government's
leading supporter of biomedical research on ALS. The goals of this
research are to find the cause or causes of ALS, understand the
mechanisms involved in the progression of the disease, and develop
effective treatment.
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 ALS and prenatal
screening for the disease. This work with familial ALS could lead to
a greater understanding of sporadic ALS as well. Because familial
ALS 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
treatments for ALS.
Return to top
Human Brain and Spinal Fluid Resource Center
Return to top
The following organizations support research and in some cases
can provide information and support for patients and their
families.
ALS Association (ALSA)
Les Turner ALS Foundation
Muscular Dystrophy Association
Project ALS
BRAIN
Return to top
