# Motor Neuron Diseases

## What are motor neuron diseases?

Motor neuron diseases (MNDs) are a group of progressive neurological disorders that destroy motor neurons, the cells that control skeletal muscle activity such as walking, breathing, speaking, and swallowing. This group includes diseases such as amyotrophic lateral sclerosis, progressive bulbar palsy, primary lateral sclerosis, progressive muscular atrophy, spinal muscular atrophy, Kennedy's disease, and post-polio syndrome.

Messages or signals from nerve cells in the brain (upper motor neurons) are typically transmitted to nerve cells in the brain stem and spinal cord (lower motor neurons) and then to muscles throughout the body. This process is how we move our muscles. 

When signals from the lower motor neurons to the muscles are disrupted, the muscles begin to weaken and shrink in size (muscle atrophy or wasting). They may also start to spontaneously twitch. These twitches, called fasciculations, can sometimes be seen or felt below the surface of the skin.

When lower motor neurons cannot receive signals from upper motor neurons, it can cause muscle stiffness (spasticity) and overactive reflexes. This can make voluntary movements slow and difficult. 

Over time, individuals with MNDs may lose the ability to walk or control other movements.

MNDs are classified according to whether the loss of function is due to a genetic mutation (inherited) or sporadic (no family history); and whether they affect the upper motor neurons, lower motor neurons, or both.

Inherited MNDs are usually caused by changes in a single gene. 

Though there are several types of MNDs, they all cause muscle weakness that gradually worsens over time and can lead to physical disability. In some people, these diseases are fatal. Weakness in muscles that control breathing can lead to respiratory insufficiency, a condition in which the lungs cannot properly take in oxygen or expel carbon dioxide. This is a feature of most MNDs. Symptoms may include breathlessness, shortness of breath that occurs while lying down, recurrent chest infections, disturbed sleep, poor concentration and/or memory, confusion, morning headaches, and fatigue.

### Types of motor neuron diseases

**Amyotrophic lateral sclerosis (ALS)**, formerly known as Lou Gehrig's disease, can affect the upper and/or lower motor neurons. It causes rapid loss of muscle control and eventual paralysis. 

Read more about amyotrophic lateral sclerosis. 

**Spinal muscular atrophy (SMA)** refers to a group of hereditary diseases that affect lower motor neurons. The most common form is caused by a mutated or missing gene known as the survival motor neuron gene 1 (SMN1), which causes the neurons to deteriorate, producing muscle weakness and wasting. 

Read more about spinal muscular atrophy.

**Spinal muscular atrophy with respiratory distress type 1 (SMARD1)** is a very rare form of SMA caused by mutations in the *IGHMBP2* (immunoglobulin helicase μ-binding protein 2) gene. Symptoms appear during infancy, between ages 6 weeks and 6 months. Children with SMARD1 suddenly may be unable to breathe due to diaphragm paralysis and may develop weakness in the muscles of their hands and feet.

**Congenital SMA with arthrogryposis** is a rare disorder that appears at birth. Symptoms include severe joint contractures, making babies unable to extend or flex the affected joints. In most children, both the arms and legs are affected. Other symptoms include scoliosis (curvature of the spine), chest deformity, respiratory problems, unusually small jaw, and drooping eyelids.

**Progressive bulbar palsy (PBP)**, also known as progressive bulbar atrophy, is due to injury of the upper motor neurons in the brainstem or the lower motor neurons connected to the brainstem. The brainstem controls the muscles needed for swallowing, speaking, chewing, and other functions.

PBP symptoms worsen over time and include trouble chewing, speaking, and swallowing. People with progressive bulbar palsy may also have weakness in the tongue and facial muscles, twitches, and a reduced gag reflex. They may also experience weakness in the arms or legs, but it is less noticeable than other symptoms.

Because they have difficulty swallowing, people with PBP are at risk of choking and inhaling food and fluids, including saliva, into the lungs. They may also laugh or cry at inappropriate times, called pseudobulbar affect or pathological laughing and crying. Some symptoms of stroke and myasthenia gravis are similar to those of progressive bulbar palsy (e.g. slurring of the speech and choking) and must be ruled out prior to diagnosis.

Many ALS experts consider PBP to be a form of ALS because the majority of individuals who begin with this form of the disease eventually develop more widespread MND symptoms. Indeed, many clinicians believe that PBP by itself, without evidence of abnormalities in the arms or legs, is extremely rare.

**Primary lateral sclerosis (PLS)**affects only the upper motor neurons, causing difficulty and slowness in the movements of the arms, legs, and face. Symptoms include weakness, muscle stiffness and spasticity, clumsiness, slowing of movement, and problems with balance and speech. The disorder often affects the legs first, followed by the torso, arms and hands, and, finally, the muscles used for swallowing, speaking, and chewing.

PLS is more common in men than in women, with an onset that generally occurs between age 40 and 60. PLS progresses slowly over years or even decades.  Extensive testing is required to rule out other disorders before diagnosing PLS. A neurologist may need to track the person’s symptoms for several years before making a diagnosis. 

There is no cure for PLS and the rate of symptom progression varies. Many people can walk without assistance early on, but most will need canes, walkers, wheelchairs, or other assistive devices to prevent falls and injuries as the disorder progresses.

**Progressive muscular atrophy (PMA)**is an uncommon subtype of ALS marked by slow but progressive damage to the lower motor neurons. It affects men more often than women, and usually at symptoms begin later in life than typical ALS. People with PMA usually notice weakness in their hands or feet followed by spreads into other body regions. They may have weakness in the torso muscles and may have trouble breathing. Exposure to cold can worsen the person’s symptoms. Other symptoms may include muscle wasting or shrinking, clumsy hand movements, twitches, and muscle cramps. 

**Kennedy's disease** is an inherited lower motor neuron disorder that affects men. The onset of symptoms varies, but usually begins between the ages of 20 and 40. Kennedy’s disease is also known as spinal and bulbar muscular atrophy (SBMA), bulbo-spinal muscular atrophy, or X-linked spinal and bulbar muscular atrophy. It is caused by mutations in the gene for the androgen (male sex hormone) receptor. Daughters of people with Kennedy's disease have a 50% chance of having a son affected with the disease.

Kennedy's disease is slowly progressive. Early symptoms include tremor of the hands when they are outstretched, muscle cramps with exertion, and fasciculations. Eventually, individuals develop weakness in their arms and legs. Weakness of the facial and tongue muscles may occur later in the disorder and often leads to difficulty swallowing, slurred speech, and repeated cases of pneumonia. Some people develop gynecomastia (excessive enlargement of male breasts) and low sperm count or infertility. Others may develop diabetes.

Currently, there is no known cure for Kennedy's disease. Treatments are available to help alleviate some of the symptoms. Physical and occupational therapy to improve function and prevent injuries is often recommended. Some individuals may use mobility devices such as wheelchairs when the weakness becomes more severe.

**Post-polio syndrome (PPS)**usually occurs 15-40 years after a person has polio, an infectious viral disease. PPS is believed to be the result of deterioration of the motor neurons over many years that leads to loss of muscle strength and dysfunction. It is not contagious and only someone who has had polio can develop PPS. Not everyone who has had polio will develop PPS.

The polio vaccine has essentially eradicated polio from the U.S. However, polio still exists in some countries, where cases of PPS still occur.  

PPS is rarely life-threatening, but the symptoms, which include muscle weakness, fatigue, atrophy, and scoliosis, can significantly interfere with a person's ability to function independently. 

## Who is more likely to have motor neuron diseases?

MNDs occur in both adults and children. In children, MNDs are typically caused by specific gene mutations, as in spinal muscular atrophy. Symptoms may be present at birth or appear in early childhood. In adults, MNDs are more likely to be sporadic, meaning the disease occurs with no family history. Symptoms typically appear after age 50, though onset of disease can occur at any age.

While some MNDs are inherited, the causes of most MNDs are not known. In sporadic or non-inherited MNDs, environmental, viral, and/or other factors may play a role in the development of the disease.

## How are motor neuron diseases diagnosed and treated?

### Diagnosing MNDs

There are no specific tests to diagnose MNDs in most cases. Symptoms vary among individuals and, in the early stages, may be similar to other diseases, making diagnosis difficult. However, there are genetic tests for SMA, Kennedy's disease, and some genetic causes of ALS.

To diagnose MNDs, a doctor will obtain a thorough medical history and perform a physical exam followed by an extensive neurological exam to assess motor and sensory function, hearing and speech, vision, coordination and balance, thinking, and changes in mood or behavior.

The following two tests can identify whether the person may have a nerve or muscle disease, or an MND.
              - Electromyography (EMG) is used to diagnose lower motor neuron disorders, as well as disorders of muscle and peripheral nerves. It assesses electrical activity in the muscles during movement and at rest.
              - A nerve conduction study is usually done in combination with an EMG. Nerve conduction studies measure the speed and size of the signal from the nerves using small electrodes taped to the skin.

Additional tests may include:
              - Laboratory tests of blood, urine, or cerebrospinal fluid can rule out other disorders that may have symptoms similar to MNDs.
              - MRI (magnetic resonance imaging) in MND is typically normal. However, MRI can help exclude other diseases that have symptoms similar to MNDs, such as brain and spinal cord tumors, inflammation, infection, and vascular irregularities that may lead to stroke. MRI can also detect and monitor inflammatory disorders such as multiple sclerosis and can document brain injury from trauma. It is often used to rule out diseases that affect the head, neck, and spinal cord. Magnetic resonance spectroscopy is a type of MRI that measures chemicals in the brain and may be used to evaluate the health of the upper motor neurons.
              - Muscle or nerve biopsy can help diagnose muscle or nerve disease; however, it is an invasive procedure and many experts do not believe it is needed to diagnose MND.

### Treating MNDs

There is no cure for most MNDs, although new treatments are under development. The outlook for individuals with MNDs varies depending on the type and the age the person’s symptoms begin. Some MNDs, such as PLS or Kennedy's disease, are usually not fatal and progress slowly. The symptoms in people with SMA type III may be stable for long periods. Some forms of MND, such as the severe form of SMA and ALS, are fatal.

Treatments are available to help with some symptoms and supportive treatment can help people maintain their independence and quality of life. Multidisciplinary clinics, with specialists from neurology, physical and occupational therapy, respiratory therapy, speech therapy, and social work are particularly important in the care of individuals with MNDs.

#### Medications for treating MNDs

Several medications have been approved to treat MNDs. Some of these medications can slow progression of ALS and others target the gene mutations in SMA and genetic forms of ALS . People with MND may be prescribed muscle relaxers to reduce muscle stiffness and help with muscle spasms. They may also receive botulinum toxin injections to treat muscle stiffness by weakening overactive muscles or decrease drooling. Excessive saliva also can be treated with medications such as amitriptyline, glycopyrrolate, and atropine.

#### Supportive therapies for MNDs

People with MNDs may also benefit from supportive therapies and assistive devices to help them adapt to changes brought on by the disorders and maintain strength and function for as long as possible. 

Physical and occupational therapy and rehabilitation may help the person improve their posture, prevent joint immobility, and slow muscle weakness and atrophy. Stretching and strengthening exercises can help reduce stiffness and increase range of motion and circulation. Some individuals may benefit from speech therapy to improve speech, chewing, and swallowing. 

Heating pads can help relieve muscle pain. Mobility and communication devices may help some people maintain their independence.

People with MNDs should eat a balanced diet that provides the proper nutrients to help them maintain their weight and strength as much as possible. 

In later stages of the disorders, people who cannot chew or swallow may require a feeding tube. Others may need ventilators to improve breathing at night. Some individuals also may need to use a breathing machine during the day due to weakness in the breathing muscles.

## What are the latest updates on motor neuron diseases?

NINDS, a component of NIH, conducts and supports a wide range of research aimed at discovering the cause of MNDs, finding better treatments, and, ultimately, preventing and curing the disorders.

Research is focused on creating new and better medicines, identifying genetic mutations and other factors that may influence the development of these diseases, and establishing biomarkers (biological measures of a disease) that can be used in research studies.

In 2023, NINDS published strategic priorities for ALS research**(pdf, 1818 KB) to speed up the development of effective interventions to diagnose, treat, manage, prevent, or cure ALS. The priorities were created with input from scientists, clinicians, advocates, people living with ALS and their families caregivers, and the public.

In a broader effort, NINDS researchers are studying inherited neurological disorders, including MNDs, to learn about their natural history and the role that genes play in their development. Other NINDS scientists are studying the use of ultrasound to observe nerves and muscles and learn more about how they function. In another study, NINDS researchers are exploring a new technique, called electrical impedance myography, for evaluating muscle and nerve disorders, including MNDs.

NINDS-supported researchers also are using gene mutation-targeting strategies, including antisense oligonucleotides and gene-editing tools to develop strategies to correct MND gene mutations, with the goal of developing treatments for ALS, SMA and other genetic causes of MNDs.

More information about MND research supported by NINDS and other NIH Institutes and Centers can be found using NIH RePORTER, a searchable database of current and past research projects supported by NIH and other federal agencies. RePORTER also includes links to publications and resources from these projects.

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## How can I or my loved one help improve care for people with motor neuron diseases?

Consider participating in a clinical trial so clinicians and scientists can learn more about MNDs and related disorders. Clinical research with human study participants to help researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.

All types of participants are needed—those who are healthy or may have an illness or disease—of all different ages, sexes, races, and ethnicities to ensure that study results apply to as many people as possible, and that treatments will be safe and effective for everyone who will use them.

For information about participating in clinical research visit NIH Clinical Research Trials and You. Learn about clinical trials currently looking for people with MNDs at Clinicaltrials.gov.
> Where can I find more information about motor neuron diseases?
Information may be available from the following organizations and resources:

ALS Association202-407-8580

ALS Therapy Development Institute617-441-7200

Cure SMA800-886-1762

Kennedy's Disease Association559-658-5950

Les Turner ALS Foundation847-679-3311

Muscular Dystrophy Association800-572-1717

Post-Polio Health International314-534-0475

Project ALS212-420-7382

Spastic Paraplegia Foundation877-773-4483

Spinal Muscular Atrophy Foundation646-253-7100 or 877-386-3762

## Learn about related topics

              - Amyotrophic Lateral Sclerosis (ALS)
              - Spinal Muscular Atrophy

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