Amyotrophic 

Lateral Sclerosis

U.S. DEPARTMENT OF HEALTH

AND HUMAN SERVICES

National Institutes of Health

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Amyotrophic Lateral 

Sclerosis

What is amyotrophic lateral 

sclerosis (ALS)?

A myotrophic lateral sclerosis (ALS) is a 

rare neurological disease that affects nerve 

cells (neurons) in the brain and spinal cord that 

control voluntary muscle movement. Voluntary 

muscles produce movements like chewing, 

walking, breathing and talking. The disease is 

progressive, meaning the symptoms get worse 

over time. Currently, there is no cure for ALS 

and no effective treatment to halt, or reverse, 

the progression of the disease. 

ALS belongs to a wider group of disorders 

known as motor neuron diseases, which are 

caused by gradual deterioration (degeneration) 

and death of motor neurons. Motor neurons are 

nerve cells that extend from the brain to the 

spinal cord and to muscles throughout the body. 

These motor neurons initiate and provide vital 

communication links between the brain and the 

voluntary muscles. 

Messages from motor neurons in the brain 

(called upper motor neurons) are transmitted to 

motor neurons in the spinal cord and to motor 

nuclei of brain (called lower motor neurons) and 

from the spinal cord and motor nuclei of brain 

to a particular muscle or muscles. 
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In ALS, both the upper motor neurons and 

the lower motor neurons degenerate or die, and 

stop sending messages to the muscles. Unable 

to function, the muscles gradually weaken, start 

to twitch (called fasciculations), and waste away 

(atrophy). Eventually, the brain loses its ability 

to initiate and control voluntary movements.

Early symptoms of ALS usually include muscle 

weakness or stiffness. Gradually all muscles 

under voluntary control are affected, and 

individuals lose their strength and the ability 

to speak, eat, move, and even breathe. 

Most people with ALS die from respiratory 

failure, usually within 3 to 5 years from when 

the symptoms first appear. However, about 

10 percent of people with ALS survive for 

10 or more years.

Who gets ALS?

I

n 2016 the Centers for Disease Control and 

Prevention estimated that between 14,000 - 

15,000 Americans have ALS. ALS is a common 

neuromuscular disease worldwide. It affects 

people of all races and ethnic backgrounds. 

There are several potential risk factors for 

ALS, including:

• Age. Although the disease can strike at any 

age, symptoms most commonly develop 

between the ages of 55 and 75. 

• Gender. Men are slightly more likely than 

women to develop ALS. However, as we 

age, the difference between men and 

women disappears.
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• Race and ethnicity. Most likely to develop 

the disease are Caucasians and non-Hispanics. 

Some studies suggest that military veterans are 

about 1.5 to 2 times more likely to develop ALS. 

Although the reason for this is unclear, possible 

risk factors for veterans include exposure to lead, 

pesticides, and other environmental toxins. ALS 

is recognized as a service-connected disease by 

the U.S. Department of Veterans Affairs. 

Sporadic ALS

The majority of ALS cases (90 percent or more) 

are considered sporadic. This means the disease 

seems to occur at random with no clearly 

associated risk factors and no family history of 

the disease. Although family members of people 

with sporadic ALS are at an increased risk for 

the disease, the overall risk is very low and most 

will not develop ALS.

Familial (Genetic) ALS

About 5 to 10 percent of all ALS cases are 

familial, which means that an individual 

inherits the disease from his or her parents. 

The familial form of ALS usually only requires 

one parent to carry the gene responsible for 

the disease. Mutations in more than a dozen 

genes have been found to cause familial ALS. 

About 25 to 40 percent of all familial cases 

(and a small percentage of sporadic cases) 

are caused by a defect in a gene known as 

“chromosome 9 open reading frame 72,” or 

C9ORF72. Interestingly, the same mutation can 

be associated with atrophy of frontal-temporal 

lobes of the brain causing frontal-temporal 

lobe dementia. Some individuals carrying this 
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mutation may show signs of both motor neuron 

and dementia symptoms (ALS-FTD). Another 

12 to 20 percent of familial cases result from 

mutations in the gene that provides instructions 

for the production of the enzyme copper-zinc 

superoxide dismutase 1 (SOD1).

What are the symptoms?

The onset of ALS can be so subtle that the 

symptoms are overlooked but gradually these 

symptoms develop into more obvious weakness 

or atrophy that may cause a physician to suspect 

ALS. Some of the early symptoms include:

• fasciculations (muscle twitches) in the arm, 

leg, shoulder, or tongue 

• muscle cramps 

• tight and stiff muscles (spasticity)

• muscle weakness affecting an arm, a leg, neck 

or diaphragm. 

• slurred and nasal speech 

• difficulty chewing or swallowing.

For many individuals the first sign of ALS may 

appear in the hand or arm as they experience 

difficulty with simple tasks such as buttoning 

a shirt, writing, or turning a key in a lock. In 

other cases, symptoms initially affect one of the 

legs, and people experience awkwardness when 

walking or running or they notice that they are 

tripping or stumbling more often. 

When symptoms begin in the arms or legs, 

it is referred to as “limb onset” ALS. Other 

individuals first notice speech or swallowing 

problems, termed “bulbar onset” ALS. 
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Regardless of where the symptoms first appear, 

muscle weakness and atrophy spread to other 

parts of the body as the disease progresses. 

Individuals may develop problems with moving, 

swallowing (dysphagia), speaking or forming 

words (dysarthria), and breathing (dyspnea). 

Although the sequence of emerging symptoms 

and the rate of disease progression vary from 

person to person, eventually individuals will not 

be able to stand or walk, get in or out of bed on 

their own, or use their hands and arms. 

Individuals with ALS usually have difficulty 

swallowing and chewing food, which makes it 

hard to eat normally and increases the risk of 

choking. They also burn calories at a faster rate 

than most people without ALS. Due to these 

factors, people with ALS tend to lose weight 

rapidly and can become malnourished. 

Because people with ALS usually retain their 

ability to perform higher mental processes such 

as reasoning, remembering, understanding, 

and problem solving, they are aware of their 

progressive loss of function and may become 

anxious and depressed. 

A small percentage of individuals may experience 

problems with language or decision-making, 

and there is growing evidence that some may 

even develop a form of dementia over time. 

Individuals with ALS will have difficulty 

breathing as the muscles of the respiratory 

system weaken. They eventually lose the ability 

to breathe on their own and must depend on 

a ventilator. Affected individuals also face an 

increased risk of pneumonia during later stages 
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of the disease. Besides muscle cramps that may 

cause discomfort, some individuals with ALS 

may develop painful neuropathy (nerve disease 

or damage).

What causes ALS?

T he cause of ALS is not known, and scientists 

have not discovered why ALS strikes some 

people and not others. However, evidence from 

scientific studies suggests that both genetics 

and environment play a role in the development 

of ALS. 

Genetics

An important step toward determining ALS 

risk factors was made in 1993 when scientists 

supported by the National Institute of 

Neurological Disorders and Stroke (NINDS) 

discovered that mutations in the SOD1 gene 

were associated with some cases of familial ALS. 

Although it is still not clear how mutations 

in the SOD1 gene lead to motor neuron 

degeneration, there is increasing evidence 

that the gene playing a role in producing 

mutant SOD1 protein can become toxic. 

Since then, more than a dozen additional 

genetic mutations have been identified, many 

through NINDS-supported research, and 

each of these gene discoveries is providing new 

insights into possible mechanisms of ALS.

The discovery of certain genetic mutations 

involved in ALS suggests that changes in the 

processing of RNA molecules may lead to 

ALS-related motor neuron degeneration. 

RNA molecules are one of the major 
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macromolecules in the cell involved in directing 

the synthesis of specific proteins as well as gene 

regulation and activity.

Other gene mutations indicate defects in the 

natural process in which malfunctioning 

proteins are broken down and used to build new 

ones, known as protein recycling. Still others 

point to possible defects in the structure and 

shape of motor neurons, as well as increased 

susceptibility to environmental toxins. Overall, 

it is becoming increasingly clear that a number 

of cellular defects can lead to motor neuron 

degeneration in ALS.

In 2011, another important discovery was 

made when scientists found that a defect 

in the C9ORF72 gene is not only present 

in a significant subset of individuals with 

ALS but also in some people with a type 

of frontotemporal dementia (FTD). This 

observation provides evidence for genetic ties 

between these two neurodegenerative disorders. 

Most researchers now believe ALS and some 

forms of FTD are related disorders.

Environmental factors

In searching for the cause of ALS, researchers 

are also studying the impact of environmental 

factors. Researchers are investigating a number 

of possible causes such as exposure to toxic or 

infectious agents, viruses, physical trauma, diet, 

and behavioral and occupational factors. 

For example, some researcher suggest that 

exposure to toxins during warfare, or strenuous 

physical activity, may increase the risk of ALS 

in some veterans and athletes. 
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Although there has been no consistent 

association between any environmental factor 

and the risk of developing ALS, future research 

may show that some factors are involved in the 

development or progression of the disease.

How is ALS diagnosed?

No one test can provide a definitive diagnosis 

of ALS. ALS is primarily diagnosed 

based on detailed history of the symptoms and 

signs observed by a physician during physical 

examination along with a series of tests to rule 

out other mimicking diseases. However, the 

presence of upper and lower motor neuron 

symptoms strongly suggests the presence 

of the disease. 

Physicians will review an individual’s full 

medical history and conduct a neurologic 

examination at regular intervals to assess 

whether symptoms such as muscle weakness, 

atrophy of muscles, and spasticity are getting 

progressively worse.

ALS symptoms in the early stages of the 

disease can be similar to those of a wide variety 

of other, more treatable diseases or disorders. 

Appropriate tests can exclude the possibility 

of other conditions. 

Muscle and imaging tests

Electromyography (EMG), a special recording 

technique that detects electrical activity of 

muscle fibers, can help diagnose ALS. Another 

common test is a nerve conduction study (NCS), 

which measures electrical activity of the nerves 

and muscles by assessing the nerve’s ability to 

send a signal along the nerve or to the muscle. 
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Specific abnormalities in the NCS and EMG 

may suggest, for example, that the individual 

has a form of peripheral neuropathy (damage 

to peripheral nerves outside of the brain and 

spinal cord) or myopathy (muscle disease) 

rather than ALS. 

A physician may also order a magnetic 

resonance imaging (MRI) test, a noninvasive 

procedure that uses a magnetic field and 

radio waves to produce detailed images of the 

brain and spinal cord. Standard MRI scans 

are generally normal in people with ALS. 

However, they can reveal other problems that 

may be causing the symptoms, such as a spinal 

cord tumor, a herniated disk in the neck that 

compresses the spinal cord, syringomyelia (a 

cyst in the spinal cord), or cervical spondylosis 

(abnormal wear affecting the spine in the neck).

Laboratory tests

Based on the person’s symptoms, test results, 

and findings from the examination, a physician 

may order tests on blood and urine samples to 

eliminate the possibility of other diseases. 

Tests for other diseases and disorders

Infectious diseases such as human 

immunodeficiency virus (HIV), human T-cell 

leukemia virus (HTLV), polio, and West 

Nile virus can, in some cases, cause ALS-like 

symptoms. Neurological disorders such as 

multiple sclerosis, post-polio syndrome, multifocal 

motor neuropathy, and spinal and bulbar 

muscular atrophy (Kennedy’s disease) also can 

mimic certain features of the disease and should 

be considered by physicians attempting to make 
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a diagnosis. Fasciculations and muscle cramps 

also occur in benign conditions.

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, individuals may wish to obtain a second 

neurological opinion. 

How is ALS treated?

No cure has yet been found for ALS. 

However, there are treatments available 

that can help control symptoms, prevent 

unnecessary complications, and make living 

with the disease easier. 

Supportive care is best provided by multidisciplinary teams of health care professionals 

such as physicians; pharmacists; physical, 

occupational, and speech therapists; 

nutritionists; social workers; respiratory 

therapists and clinical psychologists; and 

home care and hospice nurses. These teams 

can design an individualized treatment plan 

and provide special equipment aimed at 

keeping people as mobile, comfortable, and 

independent as possible.

Medication

in 1995, the Food and Drug Administration 

(FDA) approved riluzole (Rilutek), the only 

disease-modifying drug to date for ALS. 

Although it is not entirely understood how 

the drug works, riluzole is believed to reduce 

damage to motor neurons by decreasing levels of 

glutamate, which transports messages between 

nerve cells and motor neurons. Clinical trials in 
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people with ALS showed that riluzole prolongs 

survival by a few months, particularly in the 

bulbar form of the disease. 

Riluzole does not reverse the damage already 

done to motor neurons, and people taking 

the drug must be monitored for liver damage 

and other possible side effects. However, this 

therapy offers hope that the progression of ALS 

may one day be slowed by new medications or 

combinations of drugs.

Physicians can also prescribe medications to 

help manage symptoms of ALS, including 

muscle cramps, stiffness, excess saliva 

and phlegm, and the pseudobulbar affect 

(involuntary or uncontrollable episodes of crying 

and/or laughing, or other emotional displays). 

Drugs also are available to help individuals 

with pain, depression, sleep disturbances, 

and constipation. Pharmacists can give 

advice on the proper use of medications and 

monitor a person’s prescriptions to avoid 

risks of drug interactions.

Physical therapy

Physical therapy and special equipment 

can enhance an individual’s 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 people fight 

fatigue and depression. Range of motion 

and stretching exercises can help prevent 

painful spasticity and shortening (contracture) 

of muscles. 
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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 individuals conserve 

energy and remain mobile.

Speech therapy

People with ALS who have difficulty speaking 

may benefit from working with a speech 

therapist, who can teach adaptive strategies 

to speak louder and more clearly. As ALS 

progresses, speech therapists can help people 

maintain the ability to communicate. They can 

recommend aids such as computer-based speech 

synthesizers that use eye-tracking technology 

and can help people develop ways for responding 

to yes-or-no questions with their eyes or by 

other nonverbal means. 

Some people with ALS may choose to use 

voice banking while they are still able to speak 

as a process of storing their own voice for future 

use in computer-based speech synthesizers. 

These methods and devices help people 

communicate when they can no longer 

speak or produce vocal sounds.

Nutritional support

Nutritional support is an important part of the 

care of people with ALS. It has been shown 

that individuals with ALS will get weaker 

if they lose weight. Nutritionists can teach 

individuals and caregivers how to plan and 

prepare small meals throughout the day that 

provide enough calories, fiber, and fluid and 

how to avoid foods that are difficult to swallow. 
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People may begin using suction devices to 

remove excess fluids or saliva and prevent 

choking. When individuals 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. 

Breathing support

As the muscles responsible for breathing start 

to weaken, people may experience shortness of 

breath during physical activity and difficulty 

breathing at night or when lying down. 

Doctors may test an individual’s breathing to 

determine when to recommend a treatment 

called noninvasive ventilation (NIV). NIV refers 

to breathing support that is usually delivered 

through a mask over the nose and/or mouth. 

Initially, NIV may only be necessary at night. 

When muscles are no longer able to maintain 

normal oxygen and carbon dioxide levels, NIV 

may be used full-time. NIV improves the 

quality of life and prolongs survival for many 

people with ALS.

Because the muscles that control breathing 

become weak, individuals with ALS may 

also have trouble generating a strong cough. 

There are several techniques to help people 

increase forceful coughing, including 

mechanical cough assist devices and breath 

stacking. In breath stacking, a person takes a 

series of small breaths without exhaling until 

the lungs are full, briefly holds the breath, 

and then expels the air with a cough. 
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As the disease progresses and muscles weaken 

further, individuals may consider forms of 

mechanical ventilation (respirators) in which 

a machine inflates and deflates the lungs. 

Doctors may place a breathing tube through 

the mouth or may surgically create a hole at 

the front of the neck and insert a tube leading 

to the windpipe (tracheostomy). The tube is 

connected to a respirator. 

Individuals with ALS and their families often 

consider several factors when deciding whether 

and when to use ventilation support. These 

devices differ in their effect on a person’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. People may choose to be fully informed 

about these considerations and the long-term 

effects of life without movement before they 

make decisions about ventilation support.

What research is being done?

T he mission of the National Institute of 

Neurological Disorders and Stroke (NINDS) 

is to seek fundamental knowledge about the 

brain and nervous system and to use that 

knowledge to reduce the burden of neurological 

disease. The NINDS is a component of the 

National Institutes of Health (NIH), the leading 

supporter of biomedical research in the world. 

The goals of NINDS research on ALS are to 

understand the cellular mechanisms involved in 

the development and progression of the disease, 

investigate the influence of genetics and other 

potential risk factors, identify biomarkers, and 

develop new and more effective treatments. 
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Cellular defects

Scientists are seeking to understand the 

mechanisms that selectively trigger motor neurons 

to degenerate in ALS, and to find effective 

approaches to halt the processes leading to 

cell death. Using both animal models and cell 

culture systems, scientists are trying to determine 

how and why ALS-causing gene mutations lead 

to the destruction of neurons. These animal 

models include fruit flies, zebrafish, and rodents. 

Initially, genetically modified animal models 

focused on mutations in the SOD1 gene but more 

recently, models have been developed for defects 

in the C9ORF72, TARDP, FUS, PFN1, TUBA4A, 

and UBQLN2 genes. Research in these models 

suggests that, depending on the gene mutation, 

motor neuron death is caused by a variety of 

cellular defects, including in the processing 

of RNA molecules and recycling of proteins, 

and structural impairments of motor neurons. 

Increasing evidence also suggests that various 

types of glial support cells and inflammation 

cells of the nervous system may play an 

important role in the disease.

Stem Cells

In addition to animal models, scientists are 

also using innovative stem cells models to study 

ALS. Scientists have developed ways to take 

skin or blood cells from individuals with ALS 

and turn them into stem cells, which are capable 

of becoming any cell type in the body, including 

motor neurons and other cell types that may be 

involved in the disease. NINDS is supporting 

research on the development of stem cell lines 

for a number of neurodegenerative diseases, 

including ALS.
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Familial versus sporadic ALS 

Overall, the work in familial ALS is already 

leading to a greater understanding of the more 

common sporadic form of the disease. Because 

familial ALS and sporadic ALS show many of 

the same signs and symptoms, some researchers 

believe that some familial ALS genes may also 

be involved in sporadic ALS. 

Clinical research studies supported by NINDS 

are looking into how ALS symptoms change 

over time in people with C9ORF72 mutations. 

Other NINDS-supported research studies are 

working to identify additional genes that may 

cause or put a person at risk for either familial 

or sporadic ALS.

Additionally, researchers are looking at the 

potential role of epigenetics in the development 

of ALS. Epigenetic changes can switch genes 

on and off, and thus can profoundly affect the 

human condition in both health and disease. 

These changes can occur in response to multiple 

factors, including external or environmental 

conditions and events. Although this research is 

still at a very exploratory stage, scientists hope 

that understanding epigenetics can offer new 

information about how ALS develops. 

Biomarkers

Biomarkers are biological measures that help 

to identify the presence or rate of progression 

of a disease or the effectiveness of a therapeutic 

intervention. Since ALS is difficult to diagnose, 

biomarkers could potentially help clinicians 

diagnose ALS earlier and faster. 
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Additionally, biomarkers are needed to 

help predict and accurately measure disease 

progression and enhance clinical studies 

aimed at developing more effective treatments. 

Biomarkers can be molecules derived from a 

bodily fluid (such as those in the blood and 

cerebrospinal fluid), an image of the brain or 

spinal cord, or a measure of the ability of a 

nerve or muscle to process electrical signals. 

The NINDS is supporting research on the 

development biomarkers for ALS.

New treatment options

Potential therapies for ALS are being investigated 

in a range of disease models. This work involves 

tests of drug-like compounds, gene therapy 

approaches, antibodies, and cell-based therapies. 

For example, NINDS-supported scientists are 

currently investigating whether lowering levels 

of the SOD1 enzyme in the brain and spinal 

cord of individuals with SOD1 gene mutations 

would slow the rate of disease progression. 

Other NINDS scientists are studying the use 

of glial-restricted progenitor cells (which have 

the ability to develop into other support cells) to 

slow disease progression and improve respiratory 

function. Additionally, a number of exploratory 

treatments are being tested in people with ALS. 

Investigators are optimistic that these and other 

basic, translational, and clinical research studies 

will eventually lead to new and more effective 

treatments for ALS.

More information about ALS research supported 

by NINDS and other NIH Institutes and 

Centers can be found using NIH RePORTER 

(projectreporter.nih.gov), a searchable database 
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of current and past research projects supported 

by NIH and other federal agencies. RePORTER 

also includes links to publications and resources 

from these projects.

How can I help research?

National ALS Registry

T he National ALS Registry is a program 

to collect, manage, and analyze data 

about people with ALS in the United States. 

Developed by the Center for Disease Control 

and Prevention’s Agency for Toxic Substances 

and Disease Registry (ATSDR), this registry 

establishes information about the number of 

ALS cases, collects demographic, occupational 

and environmental exposure data from people 

with ALS to learn about potential risk factors 

for the disease, and notifies participants about 

research opportunities. The Registry includes data 

from national databases as well as de-identified 

information provided by individuals with ALS. 

All information is kept confidential. People with 

ALS can add their information to the Registry 

by visiting www.cdc.gov/als. 

Clinical trials

Many neurological disorders do not have 

effective treatment options. Clinical trials offer 

hope for many people and an opportunity to 

help researchers find better ways to safely detect, 

treat, or prevent disease. For information about 

finding and participating in a clinical trial, visit 

NIH Clinical Research Trials and You at www.

nih.gov/health/clinicaltrials. Use the search 

terms “amyotrophic lateral sclerosis” or “ALS 

AND (your state)” to locate trials in your area.
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NIH NeuroBioBank

The NINDS supports the NIH NeuroBioBank 

(www.neurobiobank.nih.gov), a collaborative 

effort involving several brain banks across the 

U.S, that supply investigators with tissue from 

people with neurological and other disorders. 

Tissue from individuals with ALS is needed 

to enable scientists to study this disorder more 

intensely. The goal is to increase the availability 

of, and access to, high quality specimens for 

research to understand the neurological basis 

of the disease. Prospective donors can begin 

the enrollment process by visiting www.

neurobiobank.nih.gov/pages/donor.

Where can I get more information? 

For more information on neurological 

disorders or research programs funded by the 

National Institute of Neurological Disorders and 

Stroke, contact the Institute’s Brain Resources 

and Information Network (BRAIN) at: 

BRAIN

P.O. Box 5801

Bethesda, MD 20824

800-352-9424

www.ninds.nih.gov

Information also is available from the following 

organizations:

The ALS Association 

275 K Street N.W., Suite 250

Washington, DC 20005

202-407-8580

www.alsa.org
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ALS Therapy Development Institute

300 Technology Square, Suite 400

Cambridge, MA 02139

617-441-7200

www.als.net

Les Turner ALS Foundation

5550 West Touhy Avenue, Suite 302

Skokie, IL 60077-3254

847-679-3311

www.lesturnerals.org

Prize4Life

P.O. Box 5755

Berkeley, CA 94705

617-545-4882 

www.prize4life.org

Project ALS

801 Riverside Drive, Suite 6G

New York, NY 10032

212-420-7382

855-900-2257

www.projectals.org

Muscular Dystrophy Association

222 S. Riverside Plaza, Suite 1500

Chicago, IL 60606

800-572-1717

www.mda.org

U.S. National Library of Medicine 

National Institutes of Health/DHHS

8600 Rockville Pike

Bethesda, MD 20894

301-594-5983

888-346-3656

www.nlm.nih.gov

NIH . . . Turning Discovery Into Health

Prepared by:

Office of Communications and Public Liaison

National Institute of Neurological 

Disorders and Stroke

National Institutes of Health

Department of Health and Human Services

Bethesda, Maryland 20892-2540

NIH Publication No. 17-916 January 2017