What is amyotrophic lateral sclerosis (ALS)?
Amyotrophic lateral sclerosis (ALS), formerly known as Lou Gehrig's disease, is a neurological disorder that affects motor neurons, the nerve cells in the brain and spinal cord that control voluntary muscle movement and breathing. As motor neurons degenerate and die, they stop sending messages to the muscles, which causes the muscles to weaken, start to twitch (fasciculations), and waste away (atrophy). Eventually, in people with ALS, the brain loses its ability to initiate and control voluntary movements such as walking, talking, chewing and other functions, as well as breathing. ALS is progressive, meaning the symptoms get worse over time.
The U.S. Food and Drug Administration has approved several drugs for ALS that may prolong survival, reduce the rate of decline, or help manage symptoms. However, there is currently no known treatment that stops or reverses the progression of ALS.
Early symptoms include:
- Muscle twitches in the arm, leg, shoulder, or tongue
- Muscle cramps
- Tight and stiff muscles (spasticity)
- Muscle weakness affecting an arm, a leg, or the neck
- Slurred and nasal speech
- Difficulty chewing or swallowing
As the disease progresses, muscle weakness and atrophy spread to other parts of your body. People with ALS may develop problems with:
- Chewing food and swallowing (dysphagia)
- Drooling (sialorrhea)
- Speaking or forming words (dysarthria)
- Breathing (dyspnea)
- Unintended crying, laughing, or other emotional displays (pseudobulbar symptoms)
- Maintaining weight and getting enough nutrients
Eventually, people with ALS will not be able to stand or walk, get in or out of bed on their own, use their hands and arms, or breathe on their own. Because they usually remain able to reason, remember, and understand, they are aware of their progressive loss of function. This can cause anxiety and depression in the person with ALS and their loved ones. Although not as common, people with ALS also may experience problems with language or decision-making. Some also develop a form of dementia known as FTD-ALS.
Most people with ALS die from being unable to breathe on their own (known as respiratory failure,) usually within three to five years from when the symptoms first appear. However, about 10% survive for a decade or more.
Who is more likely to get amyotrophic lateral sclerosis (ALS)?
A risk factor is a condition or behavior that occurs more frequently in those who have a disease, or who are at greater risk of getting a disease, than in those who don't have the risk factor. Having a risk factor doesn't mean a person will develop a disorder, and not having a risk factor doesn't mean you won’t. Risk factors for ALS include:
- Age—Although the disease can strike at any age, symptoms most commonly develop between the ages of 55 and 75.
- Biological sex—Men are slightly more likely to develop ALS than women. However, at older ages, men and women are equally likely to be diagnosed with ALS.
- Race and ethnicity—Whites and non-Hispanics are most likely to develop the disease, but ALS affects people of all races and ethnic backgrounds.
Some studies suggest military veterans are about one and a half to two 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. Some studies have also shown that head injury can be associated with higher risk for ALS, but more research is needed to understand this connection.
Sporadic and Familial ALS
Nearly all cases of ALS are considered sporadic, meaning 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 ALS are at an increased risk for the disease, the overall risk is very low, and most will not develop ALS.
About 10% of all ALS cases are familial (also called inherited or genetic). Changes in more than a dozen genes have been found to cause familial ALS.
- About 25-40% of all familial cases (and a small percentage of sporadic cases) are caused by a defect in the C9orf72 gene. C9orf72 makes a protein found in motor neurons and nerve cells in the brain.
- Another 12-20% of familial cases result from mutations in the SOD1 gene. SOD1 is involved in production of the enzyme copper-zinc superoxide dismutase 1.
In 2021, a team of scientists led by the NIH and the Uniformed Services University of the Health Sciences announced it had discovered a unique form of genetic ALS that affects children as early as age 4 years. This childhood form is linked to the gene SPTLC1 that is part of the body's fat production system and may be caused by changes in the way the body metabolizes fatty materials (lipids).
How is amyotrophic lateral sclerosis (ALS) diagnosed and treated?
It is important to get an accurate ALS diagnosis as soon as possible. ALS treatments may be most effective early in the course of the disease. A neurologist familiar with ALS can help a person get diagnosed early after symptom onset.
There is no single test that can definitely diagnose ALS. A healthcare provider will conduct a physical exam and review the person’s full medical history. A neurologic examination will test reflexes, muscle strength, and other responses. These tests should be performed at regular intervals to assess whether symptoms are getting worse over time.
A healthcare provider may conduct muscle and imaging tests to rule out other diseases. This can help support an ALS diagnosis. These tests include:
- Electromyography (EMG)—evaluates how well nerves and muscles are functioning. This test can include:
- A nerve conduction study (NCS) — measures the electrical activity of nerves and muscles by assessing the nerve's ability to send a signal along the nerve or to the muscle.
- A needle exam — a recording technique that detects electrical activity in muscle fibers using a needle electrode.
- Magnetic resonance imaging (MRI) — uses a magnetic field and radio waves to produce detailed images of the brain and spinal cord.
Blood and urine tests may be performed based on the person’s symptoms, test results, and findings from a neurological exam. In some cases, a spinal tap (lumbar puncture) may be performed to obtain the fluid that surrounds the brain and spinal cord called cerebrospinal fluid (CSF) for additional testing. A physician may order these tests to eliminate the possibility of other diseases. A muscle biopsy may be performed to help determine whether the person may have a muscle disease other than ALS.
There is no treatment to reverse damage to motor neurons or cure ALS at this time. However, some treatments may slow progression of the disease, improve quality of life, and extend survival. New treatments have become available in the past several years, and researchers continue to explore diverse avenues to slow or stop progression of ALS.
Supportive health care is best provided by integrated, multi-disciplinary teams of professionals that may include physicians, pharmacists, physical, occupational, speech, and respiratory therapists, nutritionists, social workers, 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.
Doctors may use the following medications approved by the U.S. Food and Drug Administration (FDA) to support a treatment plan for ALS:
- Riluzole (Rilutek) is an oral medication believed to reduce damage to motor neurons by decreasing levels of glutamate, which transports messages between nerve cells and motor neurons. Clinical trials in people with ALS showed that riluzole may prolong survival by a few months. The thickened liquid form (Tiglutik) or the tablet (Exservan) that dissolves on the tongue may be preferred if the person has swallowing difficulties.
- Edaravone (Radicava) is an antioxidant given either orally or intravenously and has been shown to slow functional decline in some people with ALS. RADICAVA ORS is a form of edaravone that can be taken orally or via feeding tube.
- Sodium phenylbutyrate/taurursodiol (Relyvrio) is an oral medication that is believed to prevent nerve cell death by blocking stress signals in cells. It has been shown to slow functional decline and extend survival in some individuals with ALS.
- Tofersen (Qalsody) is given through a spinal injection to ALS patients who have been determined to have a mutation in the SOD1 gene. While the benefits of this drug are still under study, it may work by decreasing one of the markers of damage to neurons.
A doctor may prescribe other medications or treatments to help manage symptoms, including muscle cramps and stiffness, excessive saliva and phlegm, and unwanted episodes of crying and/or laughing, or other emotional displays. Medications may also help with any pain, depression, sleep disturbances, or constipation.
Rehabilitation, therapy, and other support
A treatment plan for ALS usually includes rehabilitation, which should be tailored to the person’s individual needs and may include physical, occupational, and speech therapy.
Support for physical function and daily life
Physical therapy can help the person with ALS maintain function, including lowering their risk of falls and joint pain and maximizing their independence at different stages of the disease. Low-impact exercises such as walking, swimming, or using a stationary exercise bike along with range of motion exercises can help maintain muscle strength and function. Occupational therapists can help with activities of daily living and self-care. They can also suggest assistive devices for feeding, bathing, and grooming so that the person can be as independent as possible.
Speech and communication support
Speech therapists can help people with ALS learn strategies to speak louder and more clearly and help maintain the ability to communicate. Computer-based speech synthesizers use eye-tracking devices that allow a person to navigate the web and to type on custom screens to communicate. Voice banking is a process sometimes used by people with ALS to store their own voice for future use in computer-based speech synthesizers.
A brain-computer interface (BCI) is a system that allows individuals to communicate or control equipment such as a wheelchair using only brain activity. Researchers are developing more efficient, mobile BCIs for people with severe paralysis and/or visual impairments.
Support for nutrition, breathing, and feeding
People with ALS may have trouble chewing and swallowing their food, and getting the nutrients they need. Nutritionists and registered dieticians can help plan small, nutritious meals throughout the day and identify foods to avoid. When the person can no longer eat with help, a feeding tube can reduce the person’s risk of choking and pneumonia.
As the muscles responsible for breathing start to weaken, individuals with ALS may have shortness of breath during physical activity and difficulty breathing at night or when lying down. Noninvasive ventilation (NIV) is a type of breathing support that is usually delivered through a mask over the nose and/or mouth. It may help decrease the discomfort of breathing in some individuals with ALS. Initially, NIV may only be necessary at night, but may eventually be used full time. As the disease progresses, the person may need the support of respirators (mechanical ventilators) to inflate and deflate the lungs.
Because the muscles that control breathing become weak, people with ALS also may have trouble generating a strong cough. There are several techniques to increase forceful coughing, including mechanical cough assistive devices.
Caring for a person living with ALS
As the person with ALS progresses in their disease, they will need more and more help with daily activities. Being a caregiver for a person with ALS, while rewarding, can be challenging for the person’s loved ones and caregivers. It is important for caregivers take care of themselves and to seek support when needed. Free and paid resources are available to provide home health care services and support. Visit the organizations listed at the end of this article to find support in your area.
What are the latest updates on amyotrophic lateral sclerosis (ALS)?
NINDS is the primary federal funder of research on the brain and nervous system, including disorders such as ALS. NINDS is a component of the NIH, the leading supporter of biomedical research in the world. In 2023, NINDS published strategic priorities for ALS research(pdf, 1818 KB) to accelerate the development of effective interventions for the diagnosis, treatment, management, prevention, or cure of ALS. These strategic priorities were developed with input from scientists, clinicians, advocates, people affected by ALS, and the public. Under the Accelerating Access to Critical Therapies for ALS Act, NINDS also funds research on expanded access for investigational new drugs to people living with ALS who are not eligible for clinical trials.
Scientific discoveries have resulted in the identification of multiple therapeutic targets for ALS, and four disease-modifying, plus one symptom-managing, ALS therapies have been approved by the FDA. However, the impact of these disease-modifying therapies is modest. To develop truly effective ALS treatments, we must address numerous challenges. The goals of NINDS’s ALS research 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 treatments.
Ongoing studies seek to understand the mechanisms that selectively trigger motor neurons to degenerate in ALS, which may lead to effective approaches to stop this process. Research using cellular culture systems and animal models suggests that motor neuron death is caused by a variety of cellular defects, including those involved in protein recycling and gene regulation, as well as structural impairments of motor neurons. Increasing evidence also suggests that glial support cells and inflammation cells of the nervous system may play an important role in ALS.
Scientists are turning adult skin and blood cells into stem cells that are capable of becoming any cell type, including motor neurons and other cells which may be involved in ALS. NINDS-funded scientists are using stem cells to grow human spinal cord sections on tissue chips to help better understand the function of neurons involved in ALS.
Genetics and epigenetics
Clinical research studies supported by NINDS are looking into how ALS symptoms change over time in people with C9orf72 mutations. Other studies are working to identify additional genes that may cause or put a person at risk for either familial or sporadic ALS.
A large-scale collaborative research effort supported by NINDS, other NIH institutes, and several public and private organizations is analyzing genetic data from thousands of individuals with ALS to discover new genes involved in the disease. By using novel gene sequencing tools, researchers are now able to rapidly identify new genes in the human genome involved in ALS and other neurodegenerative diseases. People who carry genes associated with ALS may be able to participate in long-term, observational studies to help researchers understand how the disease progresses over time in diverse populations.
Additionally, researchers are looking at the potential role of epigenetics in ALS development. Epigenetic changes can switch genes on and off during a person’s lifetime, which can greatly impact both health and disease. Although this research is exploratory, scientists hope that understanding epigenetics can offer new information about how ALS develops.
NINDS supports research on the development of biomarkers—biological measures of a disease. Biomarkers can be molecules derived from a bodily fluid (blood or 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. ALS biomarkers can help identify the rate of progression and the effectiveness of current and future therapies.
For research articles and summaries on ALS, search PubMed, which contains citations from medical journals and other sites.
How can I or my loved one help improve care for people with amyotrophic lateral sclerosis (ALS)?
The National ALS Registry collects, manages, and analyzes de-identified 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 and sign up to receive for more information.
Consider participating in a clinical trial so clinicians and scientists can learn more about ALS. Clinical research uses human study participants to help researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.
All types of study participants are needed—those who are healthy or may have an illness or disease—of all different ages, sexes, races, and ethnicities to ensure that study results apply to as many people as possible, and that treatments will be safe and effective for everyone who will use them.
NINDS also supports the NIH NeuroBioBank, 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 help advance critical research on the disease. A single donated brain can make a huge impact on ALS research, potentially providing information for hundreds of studies. 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 Learn How to Become a Brain Donor.
Where can I find more information about amyotrophic lateral sclerosis (ALS)?
The following organizations and resources help individuals, families, friends, and caregivers of people living with ALS:
ALS Therapy Development Institute
I AM ALS
Les Turner ALS Foundation