Amyotrophic lateral sclerosis (ALS), is also known as “motor neuron disease” or “Lou Gehrig’s disease,” the latter of which was named after the famous baseball player who was diagnosed with the condition in 1939.

ALS is characterized by the gradual degeneration and death of motor neurons, which are the nerve cells in the brain and spinal cord that control voluntary muscles, such as those involved in walking and talking. The degeneration and death of these cells lead to muscle weakness and muscle wasting that worsen over time.

Over months and years, people with ALS lose the ability to control voluntary muscle movement throughout their body, and are unable to walk, move, and, eventually, breathe. While the disease progresses differently for every patient, most people with ALS die from respiratory failure, typically within three to five years from the onset of symptoms—less than 10% patients survive up to 10 years or more.

Furthermore, in about half of cases, ALS does not impact a person's cognitive abilities, although a subset of individuals may experience problems with memory or decision-making, calculation, and word-finding difficulty, termed as “frontotemporal dementia.”

ALS is a rare disease, affecting around 9 in every 100,000 people in the United States. According to the Centers for Disease Control and Prevention (CDC), around 5,000 new cases of ALS are diagnosed in the U.S. every year. ALS can affect people of any age, but it most commonly begins between ages 50 and 75. It occurs more frequently in men than in women.

While there is no cure for ALS, treatments are available that can help manage symptoms, slow the progression of the disease, and improve quality of life.

ALS may start with limb weakness or difficulty with speaking, chewing, swallowing or breathing, and will progress to involve other parts of body. Progression rates vary, depending on each patient. Symptoms of ALS include:

• Muscle weakness in a foot, arm, and/or leg.
• Muscle wasting
• Muscle twitching
• Muscle tightness and stiffness (spasticity)
• Muscle cramps
• Weight loss
• Difficulty swallowing or chewing
• Slurred or nasal speech
• Difficulty breathing
• Falling episodes and excessive tripping
• Difficulty with fine movements, such as shirt buttoning
• Excessive drooling
• Mood changes with uncontrolled, unexpected crying or laughing spells
• Difficulty holding head up or head drop

ALS typically does not affect a person's senses, such as sight, smell, taste, hearing, and touch. Furthermore, in about half of cases, ALS does not impact a person's cognitive abilities, although a subset of individuals may experience problems with memory or decision-making, and some (around 15%) may develop a form of dementia known as frontotemporal dementia, which can cause a number of symptoms including impulsive and inappropriate behavior, loss of interest in activities and relationships, and loss of empathy. About 50% of people with ALS develop thinking and language problems.

Over time, as the disease progresses and muscle weakness becomes more pronounced, people with ALS have difficulty performing daily activities, such as bathing, eating, using the bathroom, and talking. Eventually, people with ALS become unable to walk, stand, move their limbs, use their hands, and/or breathe without the support of mechanical ventilation.

The exact cause of ALS is unknown. However, it is believed that a combination of genetic and environmental factors contributes to the development of the disease.

In 90% of cases, ALS is sporadic, meaning it occurs without known risk factors or a family history of the condition. Researchers continue to study a number of factors that may cause or contribute to ALS.

In about 10%-15% of cases, ALS is familial. Roughly 70% of familial ALS and 15% of sporadic ALS have mutations in known ALS genes, including SOD1, FUS, TARDBP, C9ORF72, and ATXN2, among others. It is important to note that presence of certain gene mutations doesn’t necessarily mean that someone will develop ALS.

The lifetime risk of ALS is approximately one in 350 men and one in 400 women. Although the exact cause of ALS is not known, certain factors may increase a person’s risk. These include:

• Age. ALS is rare in people under age 40. Over age 40, the risk increases exponentially with increasing age.
• Male sex. ALS is more common in men than women, though this difference disappears after age 70.
• Genetic risk factors
• Lifestyle risk factors, such as smoking
• Occupational risk factors, such as military personnel and welders, among others
• Environmental risk factors, such as exposure to chemicals and heavy metals, such as pesticides and lead

There is no single test for ALS. Diagnosis involves assessing the patient's medical history, conducting a physical examination, and performing various tests to exclude other possible causes of the symptoms. A number of diagnostic tests are helpful in supporting an ALS diagnosis, including electromyography (EMG), magnetic resonance imaging (MRI), blood tests, and genetic tests.

The doctor may ask about a family history of ALS, frontotemporal dementia, or other motor neuron disease. They will ask when symptoms began and whether they have worsened or spread to other parts of the body over time. During the physical exam, the doctor will check for signs of ALS, including muscle loss, respiratory problems, muscle weakness, muscle twitching, and problems with speech and/or swallowing, among others.

A number of diagnostic tests are helpful in supporting an ALS diagnosis and ruling out other possible causes of symptoms such as myasthenia gravis, primary lateral sclerosis, infections such as HIV or Lyme disease, hyperthyroidism, and compression of the cervical (neck region) spinal cord, among many others. Diagnostic tests may include:

• Electromyography (EMG) to measure the electrical activity of a muscle. For this test, a needle electrode is inserted through the skin into various muscles. The needle records the electrical activity of the muscles when they contract and when they're at rest. People may feel some pain or discomfort during the test.
• Magnetic resonance imaging (MRI) of the brain or spinal cord can help rule out other conditions such as structural problems or inflammatory disorders of the neck that can cause symptoms similar to those of ALS.
• Blood and urine tests help rule out thyroid problems, Lyme disease, HIV, and other conditions and detect any issues related to ALS.
• Genetic testing may be recommended for patients with a family history of ALS to determine if they carry a gene that causes ALS.

Although there is currently no cure for ALS, treatments are available that can help manage symptoms, prevent unnecessary complications, and improve quality of life. There are FDA-approved drugs available to slow the progression of ALS (more on that below).

A multidisciplinary approach is used to treat ALS because of the disease's complexity, which affects various aspects of a patient's physical function and quality of life. This approach includes a team of health care professionals, each addressing different aspects of care, that typically includes a neurologist, nurses, physical and occupational therapists, a speech-language pathologist, a dietitian, a respiratory therapist, mental health professionals, social workers, and palliative care specialists.

Treatment for ALS may include:

• Medications:
• Riluzole, which is believed to reduce damage to motor neurons by decreasing levels of glutamate, a chemical messenger in the brain that delivers signals between nerve cells. Elevated levels of glutamate are associated with ALS and can cause nerve cell damage. This treatment may slow disease progression.
• Edaravone may also slow the progression of ALS. It is believed to work by relieving the effects of oxidative stress, which has been linked to cell damage in patients with ALS.
• Tofersen is a drug designed to treat ALS associated with a specific mutation in the SOD1 gene (SOD1-ALS). In SOD1-ALS, the harmful SOD1 protein builds up in the brain and spinal cord. Tofersen reduces the production of this harmful protein.

Other medications may be used to manage various symptoms of ALS, including muscle cramps and spasticity, uncontrollable laughter and crying, drooling, pain, and depression.

• Physical Therapy:
• Physical therapy can help people maintain mobility and ease the discomfort of muscle stiffness, cramps, and weakness. Physical therapy might involve walking, swimming, or using a stationary bike and range-of-motion exercises to help maintain muscle strength, flexibility, and function.
• Occupational Therapy:
• Mobility aids such as walkers, wheelchairs, ramps, and braces help people remain mobile.
• Speech Therapy:
• As ALS progresses, it can affect muscles involved in speech. Speech therapists can teach adaptive techniques, including voice banking, to make speaking easier and more understandable. They can also help patients explore alternative methods of communication, such as computer-based speech synthesizers or alphabet, word, or picture boards.
• Nutritional Support:
• Individuals with ALS often have trouble swallowing, which can make eating difficult. A dietitian can provide guidance on maintaining a balanced diet, planning meals, and managing weight.
• In advanced stages of ALS, a feeding tube may be recommended to ensure proper nutrition and hydration.
• Breathing Support:
• As the disease advances, breathing may become difficult. Non-invasive ventilation (NIV) can help. It includes the use of non-invasive equipment to assist breathing, such as a face or nose mask attached to a mechanical ventilator.
• In later stages of the disease, patients may choose to have a tracheostomy, a surgically created hole in the neck leading to the windpipe. A tube attached to a mechanical ventilator is placed in the hole to provide full-time breathing support.
• People with ALS may not be able to cough with enough force to clear their airways. Treatment may involve learning coughing techniques or using devices to assist in coughing.
• Emotional and Social Support:
• Support groups, mental health professionals, social workers, and home care and hospice services can provide emotional support and advice for patients and their families.
• Palliative Care:
  • Palliative care aims to improve quality of life by alleviating symptoms, helping with decision-making, and providing emotional support. It is an essential aspect of ALS treatment and can be provided in combination with the above-mentioned treatments.

There is currently no cure for ALS. Symptoms usually begin gradually and worsen over time. The rate of progression, however, can vary greatly from person to person. Most people with the condition eventually die of respiratory failure. On average, people with ALS live 3 to 5 years after symptoms begin. However, about 30% of people with ALS live five years, 13% will survive 10 years, and some will live 20 years or more.

The outlook also depends on several factors, such as the person's age and general health, the extent of muscle weakness at diagnosis, and the muscles affected. For example, people with ALS who have difficulty swallowing and breathing at the time of diagnosis typically have a worse prognosis than those without these symptoms.

“We offer a comprehensive, multidisciplinary approach in one location,” says Uzma Usman, MBBS, director of the Yale ALS/Motor Neuron Disease Clinic and director of the ALS Association at Yale. “In addition, our ALS team staff, including our social worker, ALS nurse, and ALS association representative, also reaches out to patients virtually on an ‘as needed’ basis to provide the best care without any delay. We are not only focusing on current treatments but our physicians and research-scientists are working closely with our patients to provide access to ALS clinical trials.”