Symptoms develop slowly and can be confused with symptoms of some other unrelated neurological conditions.

Early symptoms depend upon which body system is affected first. Typical symptoms begin in one of three areas: the arms and legs, the mouth (bulbar), or the respiratory system.

They include:

• a weakening grip, making it hard to pick up and hold things
• fatigue
• muscle pains, cramps, and twitches
• slurred and sometimes confused or jumbled speech
• weakness in the arms and legs
• increased clumsiness and stumbling
• difficulty swallowing
• trouble breathing or shortness of breath

As the disease progresses motor neuron diseases can leave those with the disease severely restricted in mobility. As the condition progresses, symptoms become more severe.

Physical therapy, occupational therapy, speech therapy and rehabilitation may help to improve posture, prevent joint immobility, and manage muscle weakness and atrophy. Stretching and strengthening exercises may help reduce spasticity, increase range of motion, and keep circulation flowing. Some individuals require additional therapy for speech, chewing, and swallowing difficulties. Applying heat may relieve muscle pain. Assistive devices such as supports or braces, orthotics, speech synthesizers, and wheelchairs may help some people retain independence.

Proper nutrition and a balanced diet are essential to maintaining weight and strength. People who cannot chew or swallow may require insertion of a feeding tube. In ALS, insertion of a percutaneous gastronomy (PEG) tube (to help with feeding) is frequently carried out even before it is needed, when the individual is strong enough to undergo this minor surgery. Non-invasive ventilation at night can prevent apnoea (the temporary stopping of breathing) in sleep, and some individuals may also require assisted ventilation due to muscle weakness in the neck, throat, and chest during daytime.