Amyotrophic Lateral Sclerosis (ALS)

What happens in ALS

Motor neurons carry signals from the brain to the muscles. Upper motor neurons run from the brain to the spinal cord; lower motor neurons run from the spinal cord and brainstem to the muscles. ALS damages both. As the nerve cells die, muscles weaken, shrink (atrophy) and twitch.

ALS does not usually affect sensation, eye movements, or bladder and bowel control. Up to half of people develop some changes in thinking or behavior, and about 1 in 10 to 15 develop frontotemporal dementia.

Early signs of ALS

Symptoms typically begin in one area:

• Limb-onset ALS (about 2 out of 3 cases): weakness in a hand (dropping things, trouble with buttons or keys), or a foot (tripping, foot drop), often on one side.
• Bulbar-onset ALS (about 1 in 3 cases): slurred speech, a nasal voice, difficulty swallowing, choking on liquids.
• Respiratory-onset ALS (rare): breathlessness as the first symptom.

Other early features:

• muscle twitching (fasciculations) under the skin
• muscle cramps, especially in the legs
• stiffness and slowness of movement (spasticity)
• visible thinning of muscles, often between the thumb and index finger
• uncontrollable laughing or crying (pseudobulbar affect)

Twitching alone, without weakness or wasting, is very common in healthy people and is almost never ALS.

How ALS progresses

Weakness spreads to neighboring regions and then the rest of the body over months to years. Over time, people may lose the ability to walk, use their hands, speak, swallow and breathe without support. Breathing muscle weakness is the usual cause of death. The pace varies widely between individuals.

Causes and risk factors

• Sporadic ALS (90 to 95%): no clear cause. Likely a combination of genetic susceptibility and environmental factors.
• Familial ALS (5 to 10%): inherited, most often through changes in the C9orf72, SOD1, TARDBP or FUS genes. C9orf72 changes also cause frontotemporal dementia in some families.
• Age: most often diagnosed between 40 and 70.
• Sex: slightly more common in men.
• Military service: veterans have a higher risk, and ALS is recognized as a service-connected condition by the US Department of Veterans Affairs.
• Smoking and possibly some environmental toxins.

Diagnosis

There is no single test for ALS. A neurologist makes the diagnosis by finding upper and lower motor neuron signs that are spreading, and by ruling out other conditions. Diagnosis often takes about a year from first symptoms.

• Neurological examination: weakness, wasting, twitching, brisk or reduced reflexes, spasticity.
• Electromyography (EMG) and nerve conduction studies: detect ongoing nerve damage in muscles, including those not yet weak.
• MRI of the brain and spine: to exclude spinal cord compression, tumors or multiple sclerosis.
• Blood and urine tests: thyroid, B12, calcium, creatine kinase, antibodies and others.
• Genetic testing: offered to many people, particularly with a family history, and important now that a gene-targeted treatment exists.

Conditions that can mimic ALS

Treatment

Medicines that slow ALS

• Riluzole: tablets that modestly extend survival, by a few months on average.
• Edaravone: given intravenously or as an oral suspension; may slow functional decline in some people.
• Tofersen: a gene-targeted therapy given by spinal injection, for people with SOD1 gene ALS. It lowers SOD1 protein levels.

Clinical trials are a standard part of ALS care, and many people choose to take part.

Symptom treatment

• Cramps and spasticity: stretching, physical therapy and medicines such as baclofen.
• Excess saliva and drooling: medicines, botulinum toxin injections to the salivary glands.
• Pseudobulbar affect: dextromethorphan with quinidine.
• Depression and anxiety: counseling and medicines.
• Pain and sleep problems.

Breathing support

• Non-invasive ventilation (NIV): a mask machine (BiPAP) used at night and later during the day. It extends survival and improves quality of life.
• Cough assist devices to clear secretions.
• Tracheostomy ventilation: some people choose long-term ventilation through a tube in the neck.

Nutrition

Swallowing problems and high energy use lead to weight loss, which shortens survival. A dietitian helps with calorie-dense foods and texture changes. A feeding tube (gastrostomy) is best placed before breathing becomes too weak.

Communication and mobility

Speech therapy, voice banking (recording your voice early), eye-gaze computers, braces, wheelchairs and home adaptations help maintain independence.

Multidisciplinary clinics

Care in a specialist ALS clinic, with neurologists, nurses, respiratory therapists, dietitians, speech, physical and occupational therapists, social workers and palliative care, is linked to longer survival and better quality of life.

Outlook and planning

Median survival is about 2 to 5 years from first symptoms. About 1 in 5 people live 5 years or more and about 1 in 10 live more than 10 years. Younger age and limb onset are linked to slower progression. Early conversations about advance directives, breathing support choices and end-of-life wishes help people stay in control of their care.

Frequently asked questions

What are the first signs of ALS?

The earliest signs are usually painless weakness in one hand or foot, such as dropping objects or tripping, or slurred speech and difficulty swallowing. Muscle twitching and cramps often accompany the weakness. Symptoms slowly spread to other areas over months.

Is ALS hereditary?

Most ALS is not inherited. About 5 to 10% of cases are familial, caused by gene changes such as C9orf72 or SOD1 that can pass from parent to child. Genetic counseling and testing can help families understand their risk.

What is the life expectancy with ALS?

Median survival is 2 to 5 years from the start of symptoms, but it varies greatly. About 10% of people live more than 10 years. Breathing support, nutrition and specialist clinic care all help extend life.

Does muscle twitching mean ALS?

Almost never on its own. Twitching is very common and usually caused by caffeine, stress, exercise or fatigue (benign fasciculations). ALS twitching comes with progressive weakness and muscle wasting. If you have twitching without weakness, ALS is extremely unlikely.

Is ALS painful?

ALS does not directly damage pain nerves, but many people experience pain from cramps, stiffness, joint strain and immobility. These can be treated with stretching, positioning, physical therapy and medicines. Palliative care specialists help manage discomfort at all stages.