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. ALS is a progressive disease, causing the motor neurons to deteriorate over time, leading to muscle weakness and wasting throughout the body.

The exact cause of ALS is unknown, but there are certain risk factors such as age, family history and exposure to toxins or heavy metals. There is no known way to prevent the disease, but avoiding smoking and engaging in regular physical activity may help reduce the risk.

In cases of familial ALS (inherited or genetic), changes in more than a dozen genes have been found to cause the disease.

• About 25–40% of all familial cases (and a small percentage of sporadic cases) are caused by a defect in the C9orf72 gene. This gene 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. This gene is involved in producing the copper-zinc superoxide dismutase 1 enzyme.

A risk factor is a condition or behavior that occurs more frequently in those who have a disease or are at greater risk of getting a disease than in those who don’t. Having a risk factor doesn’t mean a person will develop a disorder, and not having a risk factor doesn’t mean they won’t. Risk factors for ALS include:

• Age: Although ALS 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, older men and women are equally likely to be diagnosed with ALS.
• Race and ethnicity: White people and non-Hispanic people 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 a higher risk for ALS, but more research is needed to understand this connection.

It is essential to get screened for and diagnosed with ALS at the onset of symptoms, as ALS treatments may be most effective early in the course of the disease. For diagnosis and treatment, find a neurologist familiar with ALS. While research is ongoing to identify risk factors and methods of prevention, there is no known way to prevent the disease of ALS. 

The care team may perform blood and urine tests and a neurological exam based on the presentation of symptoms. A spinal tap (lumbar puncture) may sometimes be performed to obtain the fluid surrounding 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 help determine whether the person has a muscle disease other than ALS.

The most common symptom of ALS is muscle weakness, particularly in the hands and feet. Other symptoms may include twitching and cramping muscles, difficulty speaking or swallowing, fatigue and weight loss. As the disease progresses, patients may experience breathing difficulties due to weakened chest muscles and paralysis of the arms, legs and diaphragm.

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 the 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)
• Constipation
• 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, patients are aware of their progressive loss of function. These changes 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 (respiratory failure), usually within three to five years of symptoms appearing. However, about 10% survive for a decade or more.

There is no single test that can diagnose ALS. A healthcare provider will conduct a physical exam and review the patient’s complete 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 neurologist usually diagnoses ALS based on the patient’s symptoms after a thorough physical examination and medical history. Various tests, including electromyography (EMG), nerve conduction studies (NCS) and magnetic resonance imaging (MRI), can help confirm the diagnosis.

• 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 brain and spinal cord images

There is no treatment to reverse damage to motor neurons or cure ALS at this time. However, some treatments may slow the progression of the disease, improve quality of life and extend survival. New therapies have become available in the past several years, and researchers continue to explore different avenues to slow or stop the progression of ALS.

Supportive healthcare is best provided by integrated, multidisciplinary teams of professionals, including physicians, pharmacists, physical therapists, occupational therapists, speech therapists, 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 to keep patients as mobile, comfortable and independent as possible.

Doctors may use the following medications to support a treatment plan for ALS:

• Riluzole (Rilutek®) is an oral medication believed to reduce damage to motor neurons by decreasing glutamate levels, which transport messages between nerve cells and motor neurons. Clinical trials in people with ALS showed that riluzole may prolong survival by a few months. If the person has swallowing difficulties, the thickened liquid form (Tiglutik®) or the tablet (Exservan) that dissolves on the tongue may be preferred.
• Edaravone (RADICAVA IV® and RADICAVA ORS®) is an antioxidant given orally or intravenously. It 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 a feeding tube.
• Tofersen (Qalsody®) is given through a spinal injection to people with ALS with 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, unwanted crying and/or laughing episodes and other emotional displays. Medications may also help with pain, depression, sleep disturbances and constipation.

A treatment plan for ALS usually includes rehabilitation, which should be tailored to the person’s individual needs and may consist of physical, occupational and speech therapy.

• Physical therapy can help people 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. Physical therapists can also suggest assistive devices for feeding, bathing and grooming so that the person can be as independent as possible.
• Speech therapists can help people with ALS learn strategies to speak more loudly and more clearly and maintain their communication ability. Computer-based speech synthesizers use eye-tracking devices that allow a person to navigate the web and type on custom screens to communicate. People with ALS sometimes use voice banking to store their 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.
• People with ALS may have trouble chewing and swallowing food and getting the necessary nutrients. 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 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 be necessary only at night, but it 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. Several techniques increase forceful coughing, including mechanical cough assistive devices.

As individuals with ALS progress 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 vital for caregivers to take care of themselves and to seek support when needed. Free and paid resources are available to provide home healthcare services and support.

To further your understanding of your diagnosis and to contribute to cutting-edge research, consider participating in a clinical trial so clinicians and scientists can learn more about the causes, symptoms, treatment and prevention of 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 participants at Clinicaltrials.gov.