Onset is usually midlife, with most cases progressing to death in 3–5 years. In most societies there is an incidence of 1–3 per 100,000 and a prevalence of 3–5 per 100,000. Presentation is variable depending on whether upper motor or lower motor neurons are more prominently involved initially.
Common initial symptoms are weakness, muscle wasting, stiffness and cramping, and twitching in muscles of hands and arms, often first in the intrinsic hand muscles. Legs are less severely involved than arms, with complaints of leg stiffness, cramping, and weakness common. Symptoms of brainstem involvement include dysphagia, which may lead to aspiration pneumonia and compromised energy intake; there may be prominent wasting of the tongue leading to difficulty in articulation (dysarthria), phonation, and deglutition. Weakness of ventilatory muscles leads to respiratory insufficiency. Additional features that characterize ALS are lack of sensory abnormalities, pseudobulbar palsy (e.g., involuntary laughter, crying), and absence of bowel or bladder dysfunction. Dementia is not a component of sporadic ALS; in some families ALS is co-inherited with frontotemporal dementia characterized by behavioral abnormalities due to frontal lobe dysfunction (Chap. 182).