Lou Gehrig’s disease, known medically as amyotrophic lateral sclerosis (ALS), is a progressive neurological disease that destroys the nerve cells responsible for voluntary movement. It affects roughly 33,000 people in the United States at any given time, and without respiratory support, most people survive 3 to 5 years after symptoms begin. The disease is named after the famous New York Yankees first baseman who was diagnosed in 1939.
ALS targets two types of motor neurons: upper motor neurons in the brain and lower motor neurons in the brainstem and spinal cord. As these cells degenerate and die, the muscles they control weaken, shrink, and eventually stop working. The brain itself remains largely intact, meaning most people stay fully aware as their body loses function.
What Happens Inside the Body
Motor neurons are long, specialized nerve cells that carry signals from your brain to your muscles. In ALS, these cells break down through several overlapping processes. One of the most studied involves a protein called TDP-43, which normally helps regulate genetic activity inside cells. In ALS, TDP-43 clumps together abnormally, disrupting the cell’s ability to manage oxidative stress, a form of chemical damage. These protein clumps also impair the cell’s energy-producing structures and its internal waste-disposal systems.
The damage cascades. Defective transport systems inside the nerve cell prevent essential materials from reaching the far ends of long motor neurons. Inflammation around the neurons accelerates the process. Supporting cells that normally insulate nerve fibers and help them communicate also malfunction, further starving motor neurons of the support they need. The result is a steady, irreversible loss of the nerve connections that make muscles move.
Early Symptoms and How They Differ
ALS typically starts in one of two ways, and the pattern of early symptoms depends on which motor neurons are affected first.
In limb-onset ALS, which is more common, the first signs usually appear in the hands, arms, or legs. You might notice trouble gripping objects, frequent tripping, or a sense that one hand or foot feels clumsy or weak. Muscle twitching (fasciculations) and cramping are common early on.
In bulbar-onset ALS, the disease first affects the muscles controlling speech and swallowing. Early signs include slurred speech, difficulty chewing, or a change in voice quality. People with bulbar onset typically develop limb symptoms within the first six months. Bulbar onset generally carries a faster progression.
Regardless of where it starts, ALS eventually spreads to other body regions. Muscles weaken, then waste away visibly. Reflexes may become abnormally brisk in some areas while disappearing in others, reflecting damage to both upper and lower motor neurons. Importantly, ALS usually does not affect thinking, vision, bladder control, or sensation on the skin, though a small percentage of patients develop cognitive changes.
Causes: Genetics and the Unknown
About 90 to 95 percent of ALS cases are sporadic, meaning they occur in people with no family history of the disease. The remaining 5 to 10 percent are familial, linked to inherited gene mutations. More than 30 genes have been associated with ALS, but a few stand out. Mutations in the C9orf72 gene are the most common genetic cause. Mutations in the SOD1 gene, one of the first identified, are the target of the newest approved therapy.
For the vast majority of people with sporadic ALS, no single cause has been pinpointed. The current understanding is that ALS likely results from a combination of genetic susceptibility and environmental factors that together push motor neurons past a tipping point.
How ALS Is Diagnosed
There is no single blood test or scan that confirms ALS. Diagnosis relies on clinical criteria, most recently formalized as the Gold Coast criteria. These require three things: progressive loss of motor function that was previously normal, evidence of both upper and lower motor neuron damage in at least one body region, and tests ruling out other conditions that could explain the symptoms.
Upper motor neuron damage shows up as abnormally brisk reflexes, spasticity, or slow and poorly coordinated movements. Lower motor neuron damage presents as visible muscle weakness and wasting, or specific electrical patterns on electromyography (EMG), a test that measures the electrical activity of muscles. EMG can detect signs of ongoing nerve damage even before weakness is obvious.
The diagnostic process often takes months because doctors must first exclude other conditions, including spinal cord compression, autoimmune disorders, and other neurological diseases. MRI scans, nerve conduction studies, and blood work are commonly part of the workup.
Survival and Prognosis
Median survival from diagnosis is about 2.2 years in large cohort studies, though this number includes people diagnosed late in their disease course. The more commonly cited figure of 3 to 5 years from symptom onset better reflects the typical trajectory when respiratory support is not used. At five years, roughly 21 percent of patients are still alive. At ten years, about 7 percent survive.
A small group of long-term survivors defies the usual timeline. In one large cohort study, 7 percent of patients qualified as long-survivors, with a median survival of 13.4 years. Younger age at onset, limb-onset (rather than bulbar), and slower initial decline are all associated with longer survival. The physicist Stephen Hawking, who lived more than 50 years with a motor neuron disease, remains the most famous example of this rare outcome.
Treatment Options
No treatment cures or reverses ALS, but several approved medications can slow the progression. Riluzole, the first drug approved for ALS, works by reducing the toxic effects of excess glutamate, a chemical messenger that can overstimulate and damage motor neurons. It extends median survival by roughly 2 to 3 months and improves first-year survival by about 9 percent. It does not restore lost muscle strength or improve breathing capacity, but it remains a standard part of treatment.
Edaravone, approved more recently, takes a different approach. It acts as an antioxidant, reducing the oxidative damage that contributes to motor neuron death. Clinical trials showed that patients treated with edaravone lost function more slowly than untreated patients, as measured on a standardized rating scale that tracks abilities like speaking, swallowing, walking, and breathing.
The newest addition is tofersen (brand name Qalsody), approved specifically for adults with ALS caused by a mutation in the SOD1 gene. This is a targeted therapy, meaning it only works for the small subset of patients carrying that particular mutation. It was tested in a 28-week clinical trial in patients aged 23 to 78 with confirmed SOD1 mutations. Genetic testing is required before prescribing it.
Breathing Support and Quality of Life
Respiratory failure is the leading cause of death in ALS, driven by progressive weakening of the muscles that control breathing and the upper airway. As breathing muscles weaken, people first notice shortness of breath during exertion, then while lying down, and eventually at rest.
Noninvasive ventilation (NIV), a mask-based system that assists breathing without requiring a surgical airway, has become one of the most impactful interventions in ALS care. NIV increases survival, reduces hospital admissions, improves sleep quality, and helps manage the fatigue and headaches that come with inadequate breathing. Assisted coughing techniques also play a role, helping clear the airways when cough strength declines.
Beyond breathing support, ALS care typically involves a multidisciplinary team. Speech therapists help with communication strategies as speech deteriorates, including augmentative devices that track eye movement. Occupational therapists adapt the home environment as mobility declines. Nutritional support becomes critical as swallowing difficulties progress, sometimes requiring a feeding tube to maintain adequate calorie intake.
Tracking Disease Progression
Doctors and researchers use a tool called the ALSFRS-R to track how ALS is affecting daily function over time. It scores 12 different activities on a scale from 0 (complete loss of function) to 4 (normal function), covering areas like handwriting, walking, climbing stairs, speaking, swallowing, and breathing. The total score ranges from 0 to 48, with higher scores indicating better function.
This scale serves a dual purpose. In clinical care, it helps doctors and patients monitor the pace of decline and anticipate when new supports will be needed. In research, it is the primary measure used in drug trials to determine whether a treatment is slowing progression. The rate at which someone’s score drops over time is also a useful predictor of survival, helping guide conversations about planning and care goals.