Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States and Canada—Lou Gehrig's disease (LGD), is a rare, terminal neurodegenerative disorder that results in the progressive loss of both upper and lower motor neurons that normally control voluntary muscle contraction. ALS is the most common form of the broader group of motor neuron diseases. ALS often presents in its early stages with gradual muscle stiffness, twitches, weakness, and wasting. Motor neuron loss typically continues until the abilities to eat, speak, move, and breathe without mechanical support are lost. While only 15% of people with ALS also develop full-blown frontotemporal dementia, an estimated 50% face at least minor changes in thinking and behavior, and a loss of energy, possibly secondary to metabolic dysfunction, is thought to drive a characteristic loss of empathy. Depending on which of the aforementioned symptoms develops first, ALS is classified as limb-onset (begins with weakness in the arms or legs) or bulbar-onset (begins with difficulty in speaking and/or swallowing). Respiratory onset occurs in approximately 1%–3% of cases.
Most cases of ALS (about 90–95%) have no known cause, and are known as sporadic ALS. However, both genetic and environmental factors are believed to be involved. The remaining 5–10% of cases have a genetic cause, often linked to a family history of the disease, and these are known as familial ALS (hereditary). About half of these genetic cases are due to disease-causing variants in one of four specific genes. The diagnosis is based on a person's signs and symptoms, with testing conducted to rule out other potential causes.
