ALS kills primarily by destroying the nerve cells that control breathing muscles. Respiratory failure accounts for about 25% of all ALS deaths, making it the single most common cause. As motor neurons in the spinal cord and brainstem die off, the muscles responsible for inflating the lungs gradually weaken until they can no longer move air in and out of the body. This process unfolds over months to years, with a median survival of about 2.2 years from diagnosis.
How Motor Neurons Break Down
ALS targets two types of nerve cells: the motor neurons in the brain that initiate movement commands, and the motor neurons in the spinal cord that relay those commands to muscles. As these cells die, the muscles they control stop receiving signals. Without nerve input, muscle fibers weaken, shrink, and eventually become paralyzed. The destruction of motor neurons in the spinal cord is particularly devastating because these cells directly connect to every voluntary muscle in the body, from the hands and legs to the tongue and diaphragm.
The exact reason these neurons die is still not fully understood, but researchers have identified several destructive processes happening simultaneously. Some neurons undergo a form of programmed cell death where they essentially shrink and fragment. Others die through an inflammatory process where pores form in the cell membrane, causing the cell to rupture. Still others are destroyed by iron-driven damage to their outer membranes when the cell’s antioxidant defenses fail. These processes don’t happen in a neat sequence. They overlap and accelerate each other, which is part of why ALS progresses relentlessly once it begins.
Respiratory Failure: The Primary Killer
The diaphragm, a dome-shaped muscle beneath the lungs, does most of the work of breathing. It’s controlled by phrenic nerves that originate from motor neurons in the upper spinal cord. Research shows that the diaphragm often suffers more severe nerve damage than other muscles in the body, and the motor neurons in the cervical (neck) region of the spinal cord can be among the earliest and hardest hit.
As the diaphragm weakens, the lungs can’t fully expand. Carbon dioxide, the waste gas your body needs to exhale, starts building up in the blood. At the same time, less oxygen gets in. This imbalance, called hypercapnia, initially causes headaches, daytime drowsiness, and fragmented sleep. Over time, the breathing muscles weaken to the point where they can no longer sustain life. In some patients, respiratory failure is the very first symptom of ALS, appearing before any noticeable limb weakness.
Noninvasive ventilation, a mask-based breathing support device, can extend survival. One clinical trial found it added a median of 205 days of life, and a separate study showed that patients who used it for four or more hours daily survived about 14 months from the time it was prescribed, compared to roughly 3 months for those who didn’t use it at all. But ventilation supports breathing rather than stopping the underlying nerve damage, so it delays rather than prevents the outcome.
Aspiration Pneumonia and Swallowing Loss
Pneumonia and pneumonitis (lung inflammation from inhaled material) together account for about 8.5% of ALS deaths. The root cause is dysphagia, the progressive inability to swallow safely. ALS first disrupts the oral phase of swallowing, making it hard to control food and liquid in the mouth. Then it affects the pharyngeal phase, where the throat muscles coordinate to push food toward the stomach while sealing off the airway.
When these muscles fail, food particles, saliva, and liquids slip into the lungs instead of the stomach. This is called aspiration, and it introduces bacteria directly into the lungs. The resulting infections can be severe and recurrent. In a body already struggling to cough effectively due to weakened chest muscles, clearing those infections becomes increasingly difficult. Each episode of aspiration pneumonia further damages lung tissue and reduces the respiratory reserve a patient has left.
Malnutrition and Metabolic Strain
ALS creates a cruel metabolic contradiction. The disease causes hypermetabolism, meaning the body burns more energy than normal even as muscles waste away. At the same time, swallowing difficulties make it harder and harder to eat. This combination drives rapid weight loss and malnutrition, which in turn accelerates muscle breakdown and weakens the immune system.
Malnourished ALS patients show measurably lower muscle mass, worse functional scores, and changes in their body’s fluid balance. As muscle cells shrink, the water normally held inside those cells shifts outward, causing a type of fluid imbalance that serves as a marker of advancing malnutrition. Feeding tubes can help maintain calorie intake, but they don’t fully compensate for the metabolic overdrive or the continued loss of muscle tissue.
Cardiac and Autonomic Complications
ALS is primarily known as a disease of voluntary muscles, but it also damages the autonomic nervous system, the network that controls involuntary functions like heart rate, blood pressure, and digestion. This damage follows a pattern. Early in the disease, the vagus nerve (which normally slows the heart) loses function, leaving the sympathetic “fight or flight” system unopposed. This causes elevated resting heart rate and exaggerated blood pressure swings.
Later, the sympathetic nerves also degenerate. When that happens, the vagus nerve becomes dominant again, but now in an unregulated way. This can slow the heart excessively, delay the electrical signals that coordinate heartbeats, and prolong the heart’s recovery time between beats. The prevalence of heart block is estimated to be 25% higher in ALS patients than in the general population. These rhythm disturbances can become life-threatening, particularly when combined with the respiratory and nutritional stress the body is already under. Combined, major cardiovascular disease and cardiac arrest account for nearly 24% of ALS deaths.
What the Final Weeks Feel Like
In the last month of life, caregivers report that the most common symptoms are difficulty communicating (62% of patients), shortness of breath (56%), discomfort other than pain (48%), insomnia (42%), and significant pain. The experience varies. Some patients decline gradually as breathing weakens over weeks. Others develop a sudden pneumonia or respiratory crisis that accelerates the timeline.
Most people with ALS are aware of and plan for this trajectory. In one study, 88% of patients had completed an advance directive, and 88% had their end-of-life wishes honored by their medical team. Two-thirds enrolled in hospice care, and those who did were significantly more likely to die in their preferred location, outside a hospital, and with adequate symptom management including medication for air hunger and pain. Most caregivers reported that their loved one was at peace and accepting of death, though a third felt that symptom management still fell short in some way.
The median diagnostic delay for ALS is about 9 months from when symptoms first appear, and median survival from diagnosis is 2.2 years, though the range is wide. About 5-10% of patients survive a decade or longer, with median survival in that long-surviving group reaching 13.4 years. What determines who falls where on that spectrum involves a mix of factors including which motor neurons are affected first, the rate of progression, age at onset, and how early supportive treatments like ventilation and nutritional support begin.