The important evidence for diagnosing ALS is obtained by neurological examination. A doctor trained in neurology is able to make a clinical diagnosis of ALS by finding characteristic symptoms. The clinical symptoms of ALS are characterised by progressive paralysis (paresis) and muscle wasting (atrophy). The reflexes are also usually increased in the muscle groups affected by paresis and atrophy (hyperreflexia). There can also be an increase in muscle tension, which is apparent as muscle cramps or in the form of stiffness of the limbs (spasticity). This combination of symptoms where paresis, atrophy, hyperreflexia and spasticity are present side by side is typical of ALS and is the basis for the clinical diagnosis.

Fine muscle movements (fasciculations) are a typical though nonspecific feature of ALS. Fasciculations can occur in very different neurological disorders and in healthy people so that diagnosis of ALS on the basis of fasciculations is not justified. The feeling of touch, pain and temperature (sensation) is undisturbed. The presence of disorders of sensation may be evidence of a different diagnosis or of an additional disease (e.g. diabetes mellitus with polyneuropathy).