ALS stands for amyotrophic lateral sclerosis, a progressive neurological disease that destroys the nerve cells responsible for voluntary movement. Each word in the name describes what happens in the body: “amyotrophic” comes from Greek words meaning “no muscle nourishment,” referring to muscles that waste away when they stop receiving nerve signals. “Lateral” points to the areas of the spinal cord where these motor nerve cells are located. “Sclerosis” means scarring or hardening, which develops as those nerve pathways break down. You may also hear it called Lou Gehrig’s disease, after the baseball player diagnosed in 1939.
How ALS Damages the Nervous System
Your body has two types of motor neurons that work together to produce movement. Upper motor neurons live in the brain and send signals down the spinal cord. Lower motor neurons pick up those signals in the spinal cord and carry them out to your muscles. ALS attacks both types simultaneously, which is what sets it apart from other motor neuron diseases that affect only one or the other.
As upper motor neurons degenerate, muscles become stiff and reflexes become exaggerated. As lower motor neurons die, muscles weaken, twitch involuntarily (fasciculations), and eventually shrink. The entire segmental motor neuron structure breaks down over time, and the disease appears to spread from one region of the body to the next. One leading explanation for this pattern is a prion-like propagation model, where misfolded proteins trigger neighboring healthy neurons to malfunction in a chain reaction.
Early Symptoms and How They Differ
ALS doesn’t look the same in everyone. About two-thirds of people develop limb-onset ALS, where the first signs appear in the arms or legs. This often starts with weakness in a hand, making it hard to grip things or button a shirt, or with a foot that drags or trips you unexpectedly. The weakness tends to start in distal muscles (hands, feet) before moving to larger muscle groups.
The remaining third develop bulbar-onset ALS, which begins in the muscles controlling speech and swallowing. Early signs include slurred speech, difficulty chewing, or a voice that sounds nasal or strained. Bulbar-onset disease tends to progress faster, with electrical testing showing significantly more nerve damage in the tongue and neck muscles compared to limb-onset cases. In bulbar-onset patients, about 78% show active nerve breakdown in the tongue, compared to roughly 19% of limb-onset patients at similar stages.
Regardless of where it starts, ALS eventually spreads to affect muscles throughout the body. Importantly, it does not affect the senses. Sight, hearing, taste, smell, and touch remain intact, and bladder and bowel control are typically preserved until very late stages.
What Causes ALS
About 5% of ALS cases are inherited, following a clear genetic pattern passed from parent to child. The most common genetic culprit is a mutation in the C9orf72 gene, which accounts for roughly 40% of familial cases. Mutations in three other genes (SOD1, FUS, and TDP-43) are also linked to familial ALS but each appear in less than 1% of sporadic cases.
The remaining 95% of cases are classified as sporadic, meaning they arise without a family history. The triggers behind sporadic ALS remain poorly understood, though researchers suspect a combination of genetic susceptibility, environmental exposures, and cellular stress plays a role. One consistent finding is that excess glutamate, a chemical messenger in the brain, may overstimulate and damage motor neurons. Another is that unstable molecules called reactive oxygen species accumulate and injure nerve cells from the inside out.
How ALS Is Diagnosed
There is no single blood test or scan that confirms ALS. Diagnosis relies on a combination of clinical examination, electrical nerve testing, and ruling out conditions that look similar. The process often takes months, partly because early symptoms like muscle weakness and twitching are common to many conditions.
The most important diagnostic tool is electromyography (EMG), which measures electrical activity in muscles. In ALS, EMG reveals two hallmark patterns at the same time: evidence of ongoing nerve breakdown (seen as abnormal electrical signals called fibrillation potentials) and signs that surviving neurons are trying to compensate (seen as unusually large motor unit potentials). To meet diagnostic criteria, these abnormalities must appear across multiple body regions innervated by different nerves and spinal roots, confirming the disease is widespread rather than localized.
Nerve conduction studies are typically performed alongside EMG to rule out other explanations for the symptoms. Blood tests, MRI scans, and sometimes genetic testing help exclude conditions that can mimic ALS.
Conditions That Mimic ALS
Several diseases cause symptoms strikingly similar to ALS, and distinguishing them matters because some are treatable or progress much more slowly.
- Kennedy’s disease affects men and causes progressive muscle weakness, but it also produces breast enlargement, reduced fertility, and sensory loss in the hands and feet. A genetic test confirms the diagnosis.
- Primary lateral sclerosis (PLS) affects only upper motor neurons, causing stiffness and slowness without the muscle wasting seen in ALS. PLS is typically not diagnosed until someone has had isolated upper motor neuron symptoms for at least three years, and EMG shows little or no lower motor neuron involvement.
- Progressive muscular atrophy (PMA) affects only lower motor neurons and progresses much more slowly. Patients with PMA survive an average of 77 months longer than those with ALS from the time symptoms begin.
- Postpolio syndrome causes new muscle weakness decades after recovery from polio, typically appearing at least 15 years after the original infection.
Treatment Options
No cure exists for ALS, but several FDA-approved medications can slow progression or manage symptoms. Riluzole, the oldest approved treatment, works by reducing glutamate activity to protect motor neurons from overstimulation. It modestly extends survival and has been available since the mid-1990s in both tablet and liquid forms.
Edaravone (brand name Radicava), approved in 2017 with an oral version following in 2022, works differently. It acts as an antioxidant, neutralizing the reactive oxygen species that damage nerve cells. A newer treatment called tofersen (Qalsody), approved in 2023, is the first genetically targeted ALS therapy. It specifically blocks the production of toxic proteins caused by SOD1 gene mutations, making it relevant only to the small percentage of patients who carry that mutation.
For the episodes of involuntary laughing or crying that some ALS patients experience (a condition called pseudobulbar affect), a combination medication called Nuedexta can help regulate these emotional responses. Beyond medications, much of ALS care involves physical therapy, speech therapy, breathing support, and nutritional management tailored to each stage of the disease.
Prognosis and Survival
The average life expectancy after an ALS diagnosis is three to five years. However, this number masks a wide range of outcomes. An estimated 30% of people live five years or more, and 10% to 20% survive at least 10 years. Factors that influence survival include the site of onset (limb-onset generally progresses more slowly than bulbar-onset), age at diagnosis (younger patients tend to live longer), and how quickly the disease was spreading before treatment began.
The rate of progression varies enormously from person to person, which is one reason ALS remains difficult to study and treat. Some people lose function in one region and remain relatively stable for months before the disease advances, while others experience a more rapid, steady decline across multiple body regions simultaneously.