Primary lateral sclerosis (PLS)

Date Updated: 08/21/2021

Overview

Primary lateral sclerosis (PLS) is a type of motor neuron disease that causes the nerve cells in the brain that control movement to fail over time. PLS causes weakness in your voluntary muscles, such as those you use to control your legs, arms and tongue. You may experience movement problems, such as difficulty with balance, slow movements and clumsiness. You may eventually experience problems with chewing, swallowing and speaking.

This rare condition can develop at any age, but it usually occurs between ages 40 and 60 and is more common in males than females. A very rare subtype of PLS, known as juvenile primary lateral sclerosis, begins in early childhood and is caused by an abnormal gene passed from parents to children.

PLS is often mistaken for another, more common motor neuron disease called amyotrophic lateral sclerosis (ALS). While likely related to ALS, PLS progresses more slowly than ALS and in most cases isn't fatal.

Symptoms

Signs and symptoms of primary lateral sclerosis usually take years to progress and generally begin in the legs. Rarely, PLS begins in your tongue or hands and then progresses down your spinal cord to your legs. However, the disease has highly variable effects from person to person. Signs and symptoms may include:

Stiffness, weakness and muscle spasms (spasticity) in your legs, rarely starting in one leg, and eventually progressing to your arms, hands, tongue and jaw
Slowed movement
Tripping, clumsiness and difficulty with balance
Hand clumsiness
Hoarseness, as well as slowed, slurred speech and drooling
Difficulties with chewing and swallowing
Sometimes, frequent, rapid and intense shifts in emotions (mood lability)
Rarely, breathing problems and bladder problems late in the disease

When to see a doctor

Make an appointment to see your doctor if you have persistent problems with stiffness or weakness in your legs or arms, or with swallowing or speaking.

If your child develops involuntary muscle spasms or seems to be losing balance more often than usual, make an appointment with a pediatrician for an evaluation.

Causes

In primary lateral sclerosis, the nerve cells in the brain that control movement (upper motor neurons) slowly break down and fail over time. This makes the nerves unable to activate the motor neurons in the spinal cord, which control voluntary muscles. This loss causes movement problems, such as difficulty with balance, weakness, slowed movement and clumsiness, and problems with speech and swallowing.

Adult-onset primary lateral sclerosis

The cause of PLS that begins in adulthood is unknown. In most cases, it's not an inherited disease, and it's not known why or how it begins.

Juvenile primary lateral sclerosis

Juvenile PLS is caused by mutations in a gene called ALS2.

Although researchers don't understand how this gene causes the disease, they know that the ALS2 gene gives instructions for creating a protein called alsin, which is present in motor neuron cells. When the instructions are changed in someone with juvenile PLS, the protein alsin becomes unstable and doesn't work properly, which in turn impairs normal muscle function.

Juvenile PLS is an autosomal recessive inherited disease, meaning that both parents have to be carriers of the gene to pass it to their child, even though they don't have the disease themselves.

Complications

Average progression of primary lateral sclerosis can take as long as 20 years and has highly variable effects from person to person. Some people continue to walk, but others eventually need to use wheelchairs or other assistive devices.

In most cases, adult-onset PLS isn't thought to shorten life expectancy, but it can gradually affect the quality of your life as more muscles become disabled. Weaker muscles can cause you to fall, which can result in injuries. Problems with chewing and swallowing may result in poor nutrition. Performing activities of daily living, such as bathing and dressing, may become difficult.

Diagnosis

There is no single test that confirms a diagnosis of primary lateral sclerosis (PLS). In fact, because the disease can mimic signs and symptoms of other neurological diseases such as multiple sclerosis and ALS, your doctor is likely to order several tests to rule out other diseases.

After taking a careful record of your medical history and family history and performing a neurological examination, your doctor might order the following tests:

Bloodwork. Blood tests check for infections or other possible causes of muscle weakness.
MRI. An MRI or other imaging tests of your brain or spine might reveal signs of nerve cell degeneration. An MRI can also show other causes of your symptoms, such as structural abnormalities, multiple sclerosis or spinal cord tumors.
Electromyogram (EMG). During an EMG, your doctor inserts a needle electrode through your skin into various muscles. The test evaluates the electrical activity of your muscles when they contract and when they're at rest. This test also measures the involvement of lower motor neurons, which can help to differentiate between PLS — an upper motor neuron disease — and ALS, which affects both upper and lower motor neurons.
Nerve conduction studies. These tests use a low amount of electrical current to measure your nerves' ability to send impulses to muscles in different areas of your body. This test can determine if you have nerve damage.
Spinal tap (lumbar puncture). Your doctor uses a thin, hollow needle inserted into your spinal canal to remove small samples of the fluid that surrounds your brain and spinal cord (cerebrospinal fluid) for laboratory analysis. A spinal tap can help rule out multiple sclerosis, infections and other conditions.

Sometimes doctors wait 3 to 4 years before finalizing a diagnosis because early ALS can look just like PLS until additional symptoms surface a few years later. You might be asked to return for repeat electromyography testing over 3 to 4 years before the PLS diagnosis is confirmed.

Genetic testing may be done when juvenile PLS is suspected. Genetic counseling also may be recommended.

Treatment

There are no treatments to prevent, stop or reverse primary lateral sclerosis. Treatment, which focuses on relieving symptoms and preserving function, can include the following options.

Medication

Your doctor might prescribe medication to relieve symptoms:

Muscle spasms (spasticity). Spasticity may be relieved by medications such as, baclofen, tizanidine (Zanaflex) or clonazepam (Klonopin). These medications are taken by mouth.

If your spasticity isn't controlled with oral medication, your doctor might recommend surgically implanting a medication pump to deliver baclofen directly to your spinal fluid (intrathecal baclofen).
Emotional changes. If you have frequent, rapid and intense shifts in emotions, your doctor might prescribe antidepressants.
Drooling. Drooling may be helped by amitriptyline or other drugs.

Physical and occupational therapies

Stretching and strengthening exercises can help maintain muscle strength, flexibility and range of motion and prevent joint immobility.

Speech and language therapy

If your facial muscles are affected by PLS, speech therapy might help with communication and swallowing.

Nutrition support

If you experience difficulty with chewing and swallowing that make eating difficult, a nutritionist can offer diet tips, nutritional supplements or special feeding methods to help maintain your body weight.

Assistive devices

As PLS progresses, physical or occupational therapists may evaluate you periodically to determine whether you need assistive devices, such as a brace, cane, walker or wheelchair. Assistive technology devices may help with communication.

Coping and support

Periods of feeling down about having primary lateral sclerosis are expected and normal. Dealing with the reality of an incurable, progressive disease can be challenging. To cope with the disease and its effects, consider these tips:

Seek emotional support. Family and friends can be great sources of comfort and support when you're coping with the emotional aspects of long-term disease. Because PLS is an uncommon diagnosis, it might be a challenge to find a local support group for people with your condition. However, some online discussion groups are available. It might help to see how others cope with the disease. Your health care team may have some suggestions.
Get professional help if you need it. When faced with a chronic illness, it's not unusual to become overwhelmed at times. Seek professional counseling for another perspective or if you have depression and need advice on treatment.
Know and use resources available to you. If you reach a point where your disease is restricting your activities significantly, ask your doctor about devices designed to help you stay independent. In addition, there are social services available to people with disabilities of all kinds. Try to learn all you can about the resources available to you. Sometimes relying on your community for help can strengthen ties in new ways.