kb/data/en.wikipedia.org/wiki/ALS-1.md

title	chunk	source	category	tags	date_saved	instance
ALS	2/11	https://en.wikipedia.org/wiki/ALS	reference	science, encyclopedia	2026-05-05T11:04:10.701513+00:00	kb-cron

Classical ALS accounts for about 70% of all cases of ALS and can be subdivided into cases where symptoms first appear, as these are usually focused on one region of the body at initial presentation before later spread. Limb-onset ALS (also known as spinal-onset) and bulbar-onset ALS. Limb-onset ALS begins with weakness in the hands, arms, feet, and/or legs and accounts for about two-thirds of all classical ALS cases. Bulbar-onset ALS begins with weakness in the muscles of speech, chewing, and swallowing and accounts for about 25% of classical ALS cases. A rarer type of classical ALS affecting about 3% of patients is respiratory-onset, in which the initial symptoms are difficulty breathing (dyspnea) upon exertion, at rest, or while lying flat (orthopnea). Primary lateral sclerosis (PLS) accounts for about 5% of all ALS cases and only affects the upper motor neurons in the arms, legs, and bulbar region. However, more than 75% of people with apparent PLS go on to later develop lower motor neuron signs within four years of symptom onset, meaning that a definitive diagnosis of PLS cannot be made until several years have passed. PLS has a better prognosis than classical ALS, as it progresses more slowly, results in less functional decline, does not affect the ability to breathe, and causes less severe weight loss than classical ALS. Progressive muscular atrophy (PMA) accounts for about 5% of all ALS cases and affects lower motor neurons in the arms, legs, and bulbar region. While PMA is associated with longer survival on average than classical ALS, it is still progressive over time, eventually leading to respiratory failure and death. As with PLS, PMA can also develop into classical ALS over time if the lower motor neuron involvement progresses to include upper motor neurons, in which case the diagnosis might be changed to classic ALS.

=== Regionally isolated variants === Rarely, ALS symptoms may be limited to a single region of the body for an extended period of time. The disease typically progresses more slowly than classical ALS and is associated with longer survival. These regional variants of ALS can only be considered as a diagnosis should the initial symptoms fail to spread to other spinal cord regions for at least 12 months. Flail arm syndrome is characterized by lower motor neuron damage affecting the arm muscles, typically starting with the upper arms symmetrically and progressing downwards to the hands. Flail leg syndrome is characterized by lower motor neuron damage leading to asymmetrical weakness and wasting in the legs starting around the feet. Isolated bulbar palsy is characterized by upper or lower motor neuron damage in the bulbar region (in the absence of limb symptoms for at least 20 months), leading to gradual onset of difficulty with speech (dysarthria) and swallowing (dysphagia).

=== Age of onset === ALS can also be classified based on the age of onset. People with familial ALS have an age of onset about 5 years younger than those with apparently sporadic ALS. About 10% of all cases of ALS begin before age 45 ("young-onset" ALS), and about 1% of all cases begin before age 25 ("juvenile" ALS). People who develop young-onset ALS are more likely to be male, less likely to have bulbar onset of symptoms, and more likely to have a slower progression of the disease. Juvenile ALS is more likely to be genetic in origin than adult-onset ALS; the most common genes associated with juvenile ALS are FUS, ALS2, and SETX. Although most people with juvenile ALS live longer than those with adult-onset ALS, some of them have specific mutations in FUS and SOD1 that are associated with a poor prognosis. Late onset (after age 65) is generally associated with a more rapid functional decline and shorter survival.

== Signs and symptoms == The disorder causes muscle weakness, atrophy, and muscle spasms throughout the body due to the degeneration of the upper motor and lower motor neurons. Sensory nerves and the autonomic nervous system are generally unaffected, meaning the majority of people with ALS maintain hearing, sight, touch, smell, and taste.

=== Initial symptoms === Early signs of ALS may be so subtle that the symptoms are overlooked. The earliest symptoms of ALS are muscle weakness or muscle atrophy, typically on one side of the body. Other presenting symptoms include trouble swallowing or breathing, cramping, or stiffness of affected muscles; muscle weakness affecting an arm or a leg; or slurred and nasal speech. The parts of the body affected by early symptoms of ALS depend on which motor neurons in the body are damaged first. In limb-onset ALS, the first symptoms are in the arms or the legs. If the legs are affected first, people may experience awkwardness, tripping, or stumbling when walking or running; this is often marked by walking with a "dropped foot" that drags gently on the ground. If the arms are affected first, they may experience difficulty with tasks requiring manual dexterity, such as buttoning a shirt, writing, or turning a key in a lock. In bulbar-onset ALS, the first symptoms are difficulty speaking or swallowing. Speech may become slurred, nasal in character, or quieter. There may be difficulty with swallowing and loss of tongue mobility. A smaller proportion of people experience "respiratory-onset" ALS, where the intercostal muscles that support breathing are affected first. Over time, people experience increasing difficulty moving, swallowing (dysphagia), and speaking or forming words (dysarthria). Symptoms of upper motor neuron involvement include tight and stiff muscles (spasticity) and exaggerated reflexes (hyperreflexia), including an overactive gag reflex. While the disease does not cause pain directly, pain is a symptom experienced by most people with ALS, caused by reduced mobility, and possibly also some sensory nerve dysfunction. Symptoms of lower motor neuron degeneration include muscle weakness and atrophy, muscle cramps, and fleeting twitches of muscles that can be seen under the skin (fasciculations).