Amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's Disease, is a rare neurological disease that affects motor neurons—those nerve cells in the brain and spinal cord that control voluntary muscle movement. Voluntary muscles are those we choose to move to produce movements like chewing, walking, and talking. The disease is progressive, meaning the symptoms get worse over time. ALS has no cure and there is no effective treatment to reverse its progression.

ALS is a type of motor neuron disease. 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, the brain loses its ability to initiate and control voluntary movements.

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, the neck, or diaphragm
• Slurred and nasal speech
• Difficulty chewing or swallowing

As the disease progresses, muscle weakness and atrophy spread to other parts of your body. You may develop problems with:

• People with ALS eventually will not be able to stand or walk, get in or out of bed on their own, or use their hands and arms
• Chewing food and swallowing (dysphagia)
• Speaking or forming words (dysarthria)
• Breathing (dyspnea); individuals with ALS eventually lose the ability to breathe on their own and must depend on a ventilator
• Maintaining weight and malnourishment
• Muscle cramps and neuropathy (nerve damage or disease)
• Anxiety and depression, because people with ALS usually remain able to reason, remember, understand, and are aware of their progressive loss of function

Although not as common, people with ALS may also:

• Experience problems with language or decision-making
• Develop a form of dementia over time

ALS doesn't affect your ability to taste, touch, or smell, or hear. Most people with ALS die from respiratory failure, usually within three to five years from when the symptoms first appear. However, about 10 percent of people with ALS survive for a decade or more.

Who is more likely to get amyotrophic lateral sclerosis (ALS)?

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—Males are slightly more likely to develop ALS. However, as people age the difference between the sexes disappears.
• Race and ethnicity—Caucasians and non-Hispanics are most likely to develop the disease, but ALS affects people of all races and ethnic backgrounds.

Some studies suggest that military veterans are about one and 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.

Sporadic and Familial ALS

Nearly all cases of ALS 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.

About five to 10 percent of all ALS cases are familial (also called inherited or genetic). 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 the C9ORF72 gene, which makes a protein that is found in motor neurons and nerve cells in the brain. Some people with this gene also develop a type of frontotemporal degeneration (FTD, a form of dementia) caused by atrophy of the brain's temporal and frontal lobes.
• Another 12 to 20 percent of familial cases result from mutations in the SOD1 gene that 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 of ALS 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 called lipids.

How is amyotrophic lateral sclerosis (ALS) diagnosed and treated?

Diagnosing ALS. There is no single test that can definitely diagnose ALS. Your healthcare provider will conduct a physical exam and review your full medical history. A neurologic examination will test your reflexes, muscle strength, and other responses and will be held at regular intervals to assess whether symptoms such as muscle weakness, muscle wasting, and spasticity are progressively getting worse.

Muscle and imaging tests to rule out other diseases and confirm the diagnosis include:

• Electromyography (EMG) is a recording technique that detects electrical activity of muscle fibers and can help diagnose ALS.
• A nerve conduction study (NCS) measures the electrical activity of your nerves and muscles by assessing the nerve's ability to send a signal along the nerve or to the muscle.
• Magnetic resonance imaging (MRI) is a noninvasive procedure that 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 your symptoms, test results, and findings from the examination by a doctor. A physician may order these tests to eliminate the possibility of other diseases.
• A muscle biopsy may be performed if your doctor believes you may have a muscle disease other than ALS. Under local anesthesia, a small sample of muscle is removed and sent to the lab for analysis.

Treating ALS. There is no treatment to reverse damage to motor neurons or cure ALS. However, treatments can make living with the disease easier.

Supportive health care is best provided by multidisciplinary teams of professionals such as 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 prolongs survival by a few months. The thickened liquid form (Tiglutik) or the tablet (Exservan) that dissolves on the tongue may be preferred if you have swallowing difficulties.
• Edaravone (Radicava) is given intravenously and has been shown to slow the decline in clinical assessment of daily functioning in people with ALS.

Other medications may be prescribed to help you manage symptoms including muscle cramps, stiffness, excess saliva and phlegm, and the unwanted episodes of crying and/or laughing, or other emotional displays. Medications may also help you with any pain, depression, sleep disturbances, and constipation.

Self-care or lifestyle changes. Nutritionists can teach you 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. Suction devices can remove excess fluids or saliva and prevent choking. When you can no longer eat with help, doctors may advise inserting a feeding tube, which reduces your risk of choking and pneumonia that can result from inhaling liquids into your lungs.

Rehabilitation. A treatment plan for ALS usually includes rehabilitation. Rehabilitation is different for everyone and a very important part of management.

Physical and occupational therapy. Physical therapy can help keep you safe and maintain your independence. Physical therapists can recommend low-impact exercises such as walking, swimming, or using a stationary exercise bike along with range of motion exercises to strengthen muscles. Occupational therapists can suggest devices such as ramps, braces, walkers, and wheelchairs that help you conserve energy and remain mobile.

Communications support . A speech therapist can teach you strategies to speak louder and more clearly and help you maintain the ability to communicate

• Devices such as computer-based speech synthesizers use eye-tracking technology and can help you develop ways to respond to yes-or-no questions with your 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.
• A brain-computer interface (BCI) is a system that allows individuals with ALS to communicate or control equipment such as a wheelchair using only brain activity. Researchers are developing more efficient, mobile, and even some auditory-based BCIs for those with severe paralysis and/or visual impairments.

Breathing support. As your muscles responsible for breathing start to weaken, you may have shortness of breath during physical activity and difficulty breathing at night or when lying down. Noninvasive ventilation (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 but may eventually be used full time.

Because the muscles that control breathing become weak, you also may have trouble generating a strong cough. There are several techniques to increase forceful coughing, including mechanical cough assistive devices.

As the disease progresses, you might need mechanical ventilation (respirators) to inflate and deflate your lungs. Doctors may place a breathing tube through your mouth or may surgically create a hole at the front of your neck and insert a tube leading to the windpipe (tracheostomy).

What are the latest updates on amyotrophic lateral sclerosis (ALS)?

The National Institute of Neurological Disorders and Stroke (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 National Institutes of Health (NIH), the leading supporter of biomedical research in the world.

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.

Cellular defects. Ongoing studies seek to understand the mechanisms that selectively trigger motor neurons to degenerate in ALS, which may lead to effective approaches to halt 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.

Stem cells. Scientists are turning skin cells of people 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 editing tools, researchers are now able to rapidly identify new genes in the human genome involved in ALS and other neurodegenerative diseases.

Additionally, researchers are looking at the potential role of epigenetics in ALS development. Epigenetic changes can switch genes on and off, 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.

Biomarkers. NINDS supports research on the development of biomarkers—biological measures that help identify the presence or rate of progression of a disease or the effectiveness of a therapeutic intervention. 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.

New treatment options. This work involves tests of drug-like compounds, gene therapy approaches, antibodies, and cell-based therapies in a range of disease models. Additionally, a number of exploratory treatments are being tested in people with ALS.

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 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 and sign up for more information.

Learn About Clinical TrialsClinical trials are studies that allow us to learn more about disorders and improve care. They can help connect patients with new and upcoming treatment options.

Consider participating in a clinical trial so clinicians and scientists can learn more about ALS. Clinical research uses human volunteers to help researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.

All types of volunteers 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.

For information about participating in clinical research visit NIH Clinical Research Trials and You. Learn about clinical trials currently looking for people with ALS at Clinicaltrial.gov.

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 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 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
Phone: 617-441-7200

Genetic and Rare Diseases (GARD) Information Center

Les Turner ALS Foundation
Phone: 847-679-3311

MedlinePlus

Muscular Dystrophy Association
Phone: 800-572-1717

Project ALS
Phone: 212-420-7382

The ALS Association
Phone: 800-782-4747

National Institute of Neurological Disorders and Stroke. NINDS Amyotrophic Lateral Sclerosis Information Page. Available at: https://www.ninds.nih.gov/health-information/disorders/amyotrophic-lateral-sclerosis-als. Accessed July 7, 2023.

The information in this document is for general educational purposes only. It is not intended to substitute for personalized professional advice. Although the information was obtained from sources believed to be reliable, MedLink LLC, its representatives, and the providers of the information do not guarantee its accuracy and disclaim responsibility for adverse consequences resulting from its use. For further information, consult a physician and the organization referred to herein.