Primary lateral sclerosis (PLS)

Primary lateral sclerosis (PLS) is a rare condition that affects the nerve cells in the brain that control movement. PLS slowly breaks down nerve cells and causes weakness in the leg, arm and tongue muscles. It is a motor neuron disease that makes it harder to control voluntary muscle activity such as speaking, walking, breathing, and swallowing.

Symptoms typically begin with balance trouble. People with PLS may move slowly and bump into or drop things. Over time, symptoms may include trouble with the hands and arms, followed by issues with chewing, swallowing and speaking. Less commonly, issues with speaking and swallowing may be the first symptoms.

This condition can develop at any age, but usually happens between the ages of 40 and 60. PLS also can begin in early childhood, although this is not common. PLS in children is known as juvenile primary lateral sclerosis. Juvenile PLS is caused by changes in a gene passed from both parents to a child. PLS is more common in people who are assigned male at birth.

PLS is often mistaken for another, more common motor neuron disease called amyotrophic lateral sclerosis (ALS). While PLS is likely related to ALS, PLS gets worse more slowly than ALS. In most people, PLS isn't fatal.

Symptoms of primary lateral sclerosis usually take years to develop and get worse. Symptoms generally begin in the legs. It is not common, but PLS symptoms can begin with weakness in the tongue or hands, then slowly move down the spinal cord to the legs. Symptoms may be different for everyone. These are common symptoms.

• Stiffness, weakness and muscle spasms in the legs. This is known as spasticity. Spasticity may start in only one leg and move to the arms, hands, tongue and jaw.
• Slow movement.
• Tripping and having trouble with balance.
• Bumping into or dropping things.
• Slow or slurred speech, a hoarse voice, and drooling.
• Trouble chewing and swallowing.
• In some people, frequent, rapid and intense shifts in emotions.
• Rarely, breathing and bladder issues late in the disease.

When to see a doctor

Make an appointment to see a healthcare professional if you have lasting stiffness or weakness in your legs or arms. Also see a healthcare professional if you have trouble swallowing or speaking.

Take your child to a healthcare professional if your child develops muscle spasms or seems to be losing balance more often than usual.

In primary lateral sclerosis, the nerve cells in the brain that control movement slowly break down and stop working. These nerve cells are called upper motor neurons.

As a result, the nerves are not able to activate the motor neurons in the spinal cord, which control voluntary muscles. This loss causes issues with movement. People with PLS may have trouble with balance, weakness, slowed movement and clumsiness. PLS also may affect speech and swallowing.

Adult-onset primary lateral sclerosis

The cause of PLS that begins in adulthood is not known. In most people, the disease is not inherited. It's not known why or how it begins.

Juvenile primary lateral sclerosis

Juvenile PLS is linked to changes in a gene called ALS2. The condition also has been linked to ERLIN2.

Researchers don't understand how these genes may cause the disease. But they know that the ALS2 gene instructs cells to create a protein called alsin. Alsin is present in motor neuron cells. These instructions are changed in someone with juvenile PLS, which causes the protein alsin to become unstable and not work as it should. This affects the function of the muscle.

Juvenile PLS is an autosomal recessive inherited disease. This means both parents have to be carriers of the gene to pass it to their child. Parents may not have symptoms of the condition, but if they both have the gene for the condition, they can pass it down to their child.

There are no known environmental or gene risk factors for adult primary lateral sclerosis. Genes may play a role in juvenile PLS, but researchers are still working to understand exactly how.

It can take as long as 20 years for primary lateral sclerosis to become worse. Symptoms vary from person to person. Some people continue to walk, but others eventually need wheelchairs or other assistive devices.

For most people, 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. Trouble with chewing and swallowing may result in poor nutrition. Performing activities of daily living, such as bathing and dressing, may become hard.

People with PLS may develop trouble with their thinking, known as cognitive decline. Or they may have changes in their behavior. In some people, symptoms overlap with symptoms of frontotemporal dementia. Frontotemporal dementia is a form of dementia that also leads to changes in behavior and language skills.

No single test confirms a diagnosis of primary lateral sclerosis (PLS). PLS can have symptoms similar to those of other neurological diseases, such as multiple sclerosis and ALS. For this reason, you may need to have several tests to rule out other diseases.

A healthcare professional carefully reviews your medical and family history and performs a neurological exam. Then you may have one or more of the following tests:

• Blood work. Blood tests are done to check for infections or other possible causes of muscle weakness.
• MRI. An MRI or other imaging tests of your brain or spine might show signs that nerve cells have broken down. An MRI also can show other causes of symptoms, such as structural changes, multiple sclerosis or spinal cord tumors.

• Electromyogram (EMG). The test evaluates the electrical activity of muscles when they contract and are at rest. This test also measures the involvement of lower motor neurons. This can help tell the difference between PLS, an upper motor neuron disease, and ALS, which affects both upper and lower motor neurons.

  During an EMG, your healthcare professional inserts a needle electrode through your skin into different muscles.

• Nerve conduction study. This test can determine whether you have nerve damage. Low electrical current measures how well your nerves can send impulses to muscles in different areas of your body.
• Lumbar puncture, also known as a spinal tap. A spinal tap can help rule out multiple sclerosis, infections and other conditions. A thin, hollow needle inserted into your spinal canal removes small samples of cerebrospinal fluid. This is the fluid that surrounds your brain and spinal cord. The samples are then studied in a lab.

Sometimes it takes 3 to 4 years to get a diagnosis. This is because early ALS can look like PLS until other symptoms surface a few years later. You might have to return for repeat EMGs during those 3 to 4 years.

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

There are no treatments to prevent, stop or reverse primary lateral sclerosis. Treatment focuses on relieving symptoms and preserving function.

Medicine

You might take medicine to relieve these symptoms:

• Muscle spasms, known as spasticity. Muscle spasms may be relieved by several medicines that can be taken by mouth, such as:
  • Baclofen (Fleqsuvy, Ozobax, Lyvispah).
  • Tizanidine (Zanaflex).
  • Benzodiazepines:
    • Clonazepam (Klonopin).
    • Diazepam (Valium).
  • Gabapentin (Neurontin).
  • Pregabalin (Lyrica).
  • Dantrolene (Dantrium).

  If muscle spasms aren't controlled with medicine you take by mouth, your healthcare professional might recommend surgery to implant a medicine pump. The pump delivers baclofen directly to the spinal fluid.

• Emotional changes. You may be prescribed an antidepressant if you have frequent, rapid and intense shifts in emotions.
• Drooling. Drooling may be helped by the medicine onabotulinumtoxinA (Botox) or muscle relaxers. Medicines such as amitriptyline, glycopyrrolate and atropine also may be helpful.

Physical and occupational therapies

Stretching and strengthening exercises can help maintain muscle strength, flexibility and range of motion. The exercises also may help keep joints from becoming less mobile.

Speech and language therapy

Speech therapy might help with communication and swallowing if your facial muscles are affected by PLS.

Nutrition support

If you have trouble chewing and swallowing, a dietitian can offer diet tips, nutritional supplements or special feeding methods. These can help you maintain your body weight when symptoms make it hard to eat.

Assistive devices

As PLS symptoms get worse, you may need assistive devices. Physical or occupational therapists may evaluate you regularly to determine whether you need a brace, cane, walker or wheelchair. Assistive technology devices also may help with communication.

It's common to have a range of emotions when you have primary lateral sclerosis. 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. By joining a support group, you might learn how others cope with the condition. Because PLS is not common, it might be a challenge to find a local support group. But online discussion groups are available. Your healthcare team may have suggestions.
• Get help from a mental health professional if you need it. Living with a chronic illness can feel overwhelming at times. Seek counseling from a mental health professional for another point of view or if you have depression and need advice on treatment.
• Know and use resources available to you. If PLS limits your activities, ask a healthcare professional about devices designed to help you stay independent. Social services also help people with disabilities of all kinds. Try to learn all you can about the resources available to you. Sometimes, leaning on your community for help can strengthen ties in new ways.