A rare variant is respiratory-onset ALS that accounts for about 3% of all cases of ALS, in which the initial symptoms are difficulty breathing (dyspnea) with exertion, at rest, or while lying down (orthopnea). Spinal and bulbar symptoms tend to be mild or absent at the beginning. It is more common in males. Respiratory-onset ALS has the worst prognosis of any ALS variant; in a population-based study, those with respiratory-onset had a median survival of 1.4 years and 0% survival at 10 years.Primary lateral sclerosis (PLS) accounts for about 5% of all cases of ALS and affects upper motor neurons in the arms and legs. However, more than 75% of people with apparent PLS develop lower motor neuron signs within four years of symptom onset, meaning that a definite diagnosis of PLS cannot be made until then. PLS has a better prognosis than classic ALS, as it progresses slower, results in less functional decline, does not affect the ability to breathe, and causes less severe weight loss.Progressive muscular atrophy (PMA) accounts for about 5% of all cases of ALS and affects lower motor neurons in the arms and legs. While PMA is associated with longer survival on average than classic ALS, it still progresses to other spinal cord regions over time, eventually leading to respiratory failure and death. Upper motor neuron signs can develop late in the course of PMA, in which case the diagnosis might be changed to classic ALS.
Initial symptoms
The start of ALS may be so subtle that the symptoms are overlooked. The earliest symptoms of ALS are muscle weakness or muscle atrophy. 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. An abnormal reflex commonly called Babinskis sign also indicates upper motor neuron damage.