ALS, or amyotrophic lateral sclerosis, is a progressive disease that destroys the nerve cells controlling voluntary movement. It affects both the upper motor neurons in the brain and the lower motor neurons in the brainstem and spinal cord, gradually cutting off the signals that tell muscles to move. As those neurons die, muscles weaken, shrink, and eventually stop working. Most people survive 2 to 5 years from the onset of symptoms, though survival varies widely depending on the type of onset and the care a person receives.
How ALS Damages the Nervous System
Motor neurons are long, cable-like cells that carry movement signals from the brain down through the spinal cord and out to muscles. In ALS, the internal transport system of these neurons breaks down. Tiny structures called mitochondria, which supply energy to the cell, stop being delivered where they’re needed along the nerve fiber. This disrupts the cell’s ability to manage calcium and maintain its internal scaffolding, creating a destructive cycle: the transport problems get worse, proteins pile up inside the cell, and the neuron eventually dies.
Four genes are most commonly linked to this breakdown. Mutations in these genes can cause proteins to misfold, triggering the cascade of transport failure and cell death. Once neurons die, the muscles they controlled begin to waste away. The degeneration tends to spread outward from wherever it starts, moving toward the lower parts of the body over time.
Early Symptoms and Types of Onset
ALS typically begins in one of two ways. Limb-onset ALS, which is about 2.3 times more common than the other form, starts with weakness or fatigue in an arm or leg. You might notice trouble gripping objects, loss of hand dexterity, or a foot that drags when you walk. Because it often appears as a focal, one-sided weakness, it’s frequently mistaken for a spinal or orthopedic problem at first.
Bulbar-onset ALS starts with the muscles of the mouth and throat. Early signs include slurred speech, difficulty swallowing, drooling, or trouble chewing. This form tends to be diagnosed faster because its symptoms are harder to attribute to something routine like a back problem. The median age at symptom onset is around 57 to 61, with bulbar-onset patients skewing slightly older.
Regardless of where it starts, ALS eventually spreads to affect muscles throughout the body. The disease does not typically affect thinking or memory in most patients, though a subset develops cognitive changes.
How ALS Is Diagnosed
There is no single blood test or scan that confirms ALS. Diagnosis relies on a combination of clinical examination and electrical testing of the nerves and muscles, along with ruling out other conditions that can mimic it.
The most important diagnostic tool is needle electromyography (EMG), which involves inserting a thin needle into muscles to record their electrical activity. Doctors look for two specific patterns: signs that nerve connections to the muscle have recently been lost (acute denervation) and signs that surviving neurons have been compensating for dead ones over time (chronic neurogenic change). Nerve conduction studies are also performed to measure how well the motor and sensory nerves transmit signals, typically testing nerves in at least one arm and one leg.
To confirm the diagnosis, doctors use a standardized framework that divides the body into four regions: bulbar (face and throat), cervical (arms), thoracic (trunk), and lumbosacral (legs). The diagnostic certainty increases with the number of regions showing evidence of both upper and lower motor neuron damage. A “clinically definite” diagnosis requires signs in multiple regions, while fewer affected areas may result in a “clinically possible” label that warrants continued monitoring.
What Causes ALS
In 90 to 95 percent of cases, ALS appears without any family history. This is called sporadic ALS, and its cause remains poorly understood, though it likely involves a combination of genetic susceptibility and environmental factors. The remaining 5 to 10 percent of cases are familial, meaning the person has a known family history of the disease.
Two genes account for the largest share of familial cases. One produces an antioxidant enzyme that, when mutated, misfolds and becomes toxic to motor neurons. The other involves a repeated DNA sequence that expands far beyond its normal length, producing abnormal proteins that accumulate in nerve cells. Researchers have identified dozens of other genes involved in rarer cases, but these two remain the most clinically significant because targeted treatments now exist for one of them.
How the Disease Progresses
ALS progression is measured by tracking a person’s ability to perform everyday tasks: speaking, swallowing, writing, dressing, walking, and breathing. Clinicians use a 12-item rating scale that scores each of these functions, and the pattern of decline helps predict what support a person will need next.
Staging systems group patients based on how many functional domains they’ve lost. Someone who has weakness in one limb but can still speak, swallow, and breathe independently is at an earlier stage than someone who has lost function in multiple areas. The progression rate varies enormously from person to person. Median survival from diagnosis was about 18 to 20 months in large studies, though survival from symptom onset (which precedes diagnosis) averages 2 to 5 years. A recent analysis of patients treated between 1995 and 2018 found a modest but statistically significant improvement in survival over time, with median survival rising from about 18.5 months to 20 months in the most recent period studied.
Breathing and Nutrition Support
Respiratory failure is the most common cause of death in ALS, which makes breathing support one of the most consequential interventions. Non-invasive ventilation, a mask-based system that assists breathing, is recommended as soon as any respiratory abnormality is detected, even before obvious symptoms like shortness of breath appear. Starting it early, before lung capacity drops below 80 percent of normal, has been shown to slow the subsequent decline in breathing function compared to waiting until symptoms are severe.
Nighttime breathing problems often appear first. Overnight monitoring can detect drops in oxygen or rises in carbon dioxide that a person may not notice while awake. These subtle changes are an early signal that ventilation support should begin.
As swallowing becomes more difficult, maintaining adequate nutrition becomes a challenge. A feeding tube placed directly into the stomach helps ensure consistent calorie intake and reduces the risk of choking. This procedure can be performed safely even in patients with significantly reduced lung capacity, as long as breathing support is established first and used during the procedure itself.
Available Treatments
Three FDA-approved medications are currently available for ALS, though none is a cure. The oldest, riluzole, works by reducing levels of a chemical messenger called glutamate, which in excess can be toxic to nerve cells. It was the first drug approved for the disease and remains a standard part of treatment.
A second medication, approved in 2017 as an intravenous infusion and later as an oral suspension, acts as an antioxidant. It neutralizes unstable molecules that damage cells when they build up, a process thought to contribute to the nerve degeneration in ALS.
The newest treatment, approved in 2023, is the first genetically targeted therapy for ALS. It is designed specifically for the roughly 2 percent of ALS patients whose disease is caused by a mutation in a specific antioxidant enzyme gene. The drug blocks the production of the toxic protein produced by the mutated gene, helping slow progression in this subset of patients. It is not effective for other forms of ALS.
The Role of Multidisciplinary Care
Beyond medication, the single biggest factor in ALS outcomes is the care model. Multidisciplinary clinics that bring together neurologists, pulmonologists, nutritionists, physical therapists, speech therapists, psychologists, and social workers in a coordinated team have been shown to meaningfully extend survival. One study at a Spanish ALS center found that patients treated under this model had a median survival of 40 months, compared to 34 months for a historical group that received standard care. That six-month difference was even more pronounced in patients with bulbar-onset ALS, where multidisciplinary care added 10 months of survival.
The benefits go beyond survival. Coordinated care improves quality of life by anticipating needs before they become crises: fitting breathing support before respiratory muscles fail, placing feeding tubes before malnutrition sets in, and adapting communication tools before speech is fully lost. Each specialist addresses a different aspect of the disease at the right time, rather than reacting after function has already been lost.