Motor neuron diseases (muscle stimulation disorders) are characterized by progressive deterioration of the nerves and other structures involved in muscle movement. These disorders develop when motor nerves (which control muscle movement) do not stimulate muscles normally.

• Amyotrophic lateral sclerosis (Lou Gehrig disease) is the most common form of motor neuron disease.
• Typically, muscles are weak and waste away, and movements become stiff, clumsy, and awkward.
• Doctors base the diagnosis on results of electromyography, magnetic resonance imaging, and blood tests.
• There is no specific treatment or cure, but drugs can help lessen symptoms.

For normal muscle function, muscle tissue and nerve connections between the brain and muscle must be normal. In motor neuron diseases, motor nerves do not stimulate muscles normally. As a result, muscles weaken, waste away (atrophy), and can become completely paralyzed even though the muscles themselves are not the cause of the problem.

Motor neuron diseases have various forms, such as amyotrophic lateral sclerosis (the most common), primary lateral sclerosis, progressive pseudobulbar palsy, progressive muscular atrophy, progressive bulbar palsy, and postpolio syndrome. These disorders are more common among men and usually develop in people who are in their 50s. The cause is usually unknown. About 5 to 7% of people who have a motor neuron disease have a hereditary type and thus have family members who also have the disease.

In all forms of motor neuron disease, the parts of the nervous system involved in muscle movement—including motor nerves in the spinal cord, in other parts of the body, and in parts of the brain—progressively deteriorate, causing muscle weakness that can progress to paralysis. Long-lasting paralysis can lead to permanent shortening of muscles (contractures). However, in each form, a different part of the nervous system is affected. Consequently, each form has different effects. For example, some affect the mouth and throat first, and others affect a hand or foot first or most severely.

Symptoms

Muscles are affected, but people do not have pain or any changes in sensation. Depression is common.

Amyotrophic lateral sclerosis (Lou Gehrig disease): This progressive form begins with weakness, often in the hands and less frequently in the feet or mouth and throat. Weakness may progress more on one side of the body than on the other and usually proceeds up the arm or leg. Cramps are also common and may occur before the weakness, but no changes in sensation occur. People may lose weight and feel unusually tired.

Over time, weakness increases. Muscles twitch, waste away, and become tight, followed by muscle spasms (spasticity). Tremors (shaking) may appear. Controlling facial expressions may become difficult. Weakening of muscles in the throat may lead to difficulty speaking (dysarthria) and swallowing (dysphagia). Because swallowing is difficult, people sometimes drool and are more likely to choke on liquids. As symptoms progress, people may be unable to control emotional responses and may laugh or cry inappropriately.

Eventually, the muscles involved in breathing may weaken, leading to breathing problems. Some people need a ventilator to breathe.

How rapidly amyotrophic lateral sclerosis progresses varies:

• About 50% of people with the disorder die within 3 to 5 years of the first symptoms.
• About 10% live 10 years or more.
• A few people survive as long as 30 years.

Primary lateral sclerosis and progressive pseudobulbar palsy: These forms are rare, slowly progressive variants of amyotrophic lateral sclerosis. Primary lateral sclerosis affects mainly the arms and legs, and progressive pseudobulbar palsy affects mainly the muscles of the face, jaw, and throat. In both disorders, severe stiffness accompanies muscle weakness. Emotions may be changeable: People with progressive pseudobulbar palsy may switch from happiness to sadness quickly and without reason. Inappropriate emotional outbursts are common. Many years later, muscles begin to twitch and waste away. Symptoms usually progress for several years before total disability results.

Progressive muscular atrophy: This form can develop at any age. It is similar to amyotrophic lateral sclerosis, but it progresses more slowly, spasticity does not occur, and muscle weakness is less severe. Involuntary contractions or twitching of muscle fibers may be the earliest symptoms. The hands are usually affected first, followed by the arms, shoulders, and legs. Eventually, the whole body is affected. Many people with this form survive 25 years or longer.

Progressive bulbar palsy: In this form, the nerves controlling the muscles of chewing, swallowing, and talking are affected, making these functions increasingly difficult. The voice may have a nasal tone. In some people, emotions are changeable. Because swallowing is difficult, food or saliva is often inhaled (aspirated) into the lungs, causing choking or gagging and increasing the risk of pneumonia. Death, which is often due to pneumonia, usually occurs 1 to 3 years after symptoms appear.

Postpolio syndrome: In some people who have had polio, muscles may become tired, painful, and weak 15 years or more after recovery from polio. Sometimes muscle tissue also wastes away, suggesting a reactivation of the polio infection. However, in most people who have had polio, such symptoms are not due to postpolio syndrome but to the development of a new disorder, such as diabetes, a ruptured (herniated) disk, or osteoarthritis. Postpolio syndrome, although similar to motor neuron disease, is often considered a separate disorder.

Diagnosis

Doctors suspect motor neuron disease in adults who have progressive muscle weakness without pain or loss of sensation. Doctors ask people which parts of the body are affected, when symptoms started, which symptoms appeared first, and how the symptoms have changed over time. This information gives them clues about the cause of symptoms.

Muscle weakness can have many causes (see Symptoms and Diagnosis of Brain, Spinal Cord, and Nerve Disorders: Causes), so diagnostic tests, such as the following, are needed to help narrow the possibilities:

• Magnetic resonance imaging (MRI) of the brain and sometimes the spinal cord is done to check for abnormalities that may cause similar symptoms.
• Electromyography (see Symptoms and Diagnosis of Brain, Spinal Cord, and Nerve Disorders: Electromyography and Nerve Conduction Studies), which involves stimulating muscles and recording their electrical activity, can help determine whether the problem is in nerves or muscles.
• Nerve conduction studies, which measures how fast nerves transmit impulses, may also be done. The speed of impulses is not affected until late in motor neuron disease, so if impulses are unexpectedly slow, the cause of symptoms may be another disorder.
• Blood tests are done to check for other disorders (such as infections and metabolic disorders) that do not affect the nerves but can cause weakness.

Treatment

Motor neuron diseases have no specific treatment or cure. Care provided by a team of several types of health care practitioners (a multidisciplinary team) helps people cope with progressive disability. Physical therapy helps people maintain muscle strength and helps prevent contractures. Nurses or other caregivers must feed people with swallowing difficulties carefully to prevent choking. Some people must be fed through a tube inserted through the abdominal wall into the stomach (gastrostomy tube).

Certain drugs can help relieve symptoms:

• Baclofen may help make muscles less spastic.
• Phenytoin or quinine may help decrease cramps.
• Drugs with anticholinergic effects, such as amitriptyline (an antidepressant), may be used to reduce drooling because one of its anticholinergic effects is to reduce saliva formation.
• Amitriptyline or fluvoxamine (also an antidepressant) may help people who have changeable emotions or depression. A drug that combines dextromethorphan (a cough suppressant) with quinidine (used to treat malaria) may help control changeable emotions.

In some people with amyotrophic lateral sclerosis, riluzole, a drug that protects nerve cells, can prolong life for a few months. It is taken by mouth.

If pain develops as the disease progresses (for example, if pain occurs when a person has to sit in one position too long), opioids and benzodiazepines, which are mild sedatives, may be used.

In a few people with progressive bulbar palsy, surgery to improve swallowing helps.

Because amyotrophic lateral sclerosis and progressive bulbar palsy are progressive and incurable, people who have one of these diseases are advised to establish advanced directives that specify what kind of care they want at the end of life (see Legal and Ethical Issues: Advance Directives).

Last full review/revision September 2012 by Michael Rubin, MDCM