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

• Amyotrophic lateral sclerosis is the most common of these disorders.
• 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 muscle stimulation disorders (motor neuron disorders), 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.

Muscle stimulation disorders include 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 10% of people who have a muscle stimulation disorder have a hereditary type and thus have family members who also have the disorder.

In all of these disorders, the parts of the nervous system involved in muscle movement—including motor nerves in the spinal cord and in other parts of the body and parts of the brain—progressively deteriorate, causing muscle weakness that can progress to paralysis. However, in each disorder, a different part of the nervous system is affected. Consequently, each disorder 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's Disease): This progressive disorder is 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 and become tight, followed by muscle spasms (spasticity). Tremors may appear. Controlling facial expressions may become difficult. Weakening of muscles in the throat may lead to difficulty speaking (dysarthria) and swallowing (dysphagia). Excess saliva is produced, sometimes causing drooling. As the disorder progresses, 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 years of the first symptoms, 10% live 10 years or more, and a few people survive as long as 30 years.

Primary Lateral Sclerosis and Progressive Pseudobulbar Palsy: These disorders 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. The disorders usually progress for several years before total disability results.

Progressive Muscular Atrophy: This disorder 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 disorder survive 25 years or longer.

Progressive Bulbar Palsy: In this disorder, 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 the disorder begins.

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 slipped (herniated) disk, or osteoarthritis.

Diagnosis

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

Muscle weakness can have many causes (see Classifying Weakness ), 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 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 these disorders, 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

Muscle stimulation disorders have no specific treatment or cure. Care provided by a team of several types of health care practitioners (multidisciplinary team) helps people cope with progressive disability. Physical therapy helps people maintain muscle strength and helps prevent shortening of muscles (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).

Baclofen may help make muscles less spastic, and phenytoin or quinine may help decrease cramps. Drugs with anticholinergic effects, such as amitriptyline (an antidepressant), may be used because of one of its anticholinergic effects—reducing saliva formation. Amitriptyline or fluvoxamine (also an antidepressant) may help people who have changeable emotions or depression.

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

If pain develops as the disorder progresses (for example, it may become painful to sit in one spot without being able to shift position), 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 with one of these disorders 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 February 2008 by Michael Rubin, MD