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.

Aug. 21, 2021
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  4. Primary lateral sclerosis. Genetic and Rare Diseases Information Center. https://rarediseases.info.nih.gov/diseases/10684/primary-lateral-sclerosis. Accessed May 19, 2021.
  5. Juvenile primary lateral sclerosis. Genetic and Rare Diseases Information Center. https://rarediseases.info.nih.gov/diseases/4485/juvenile-primary-lateral-sclerosis. Accessed May 19, 2021.
  6. Jankovic J, et al., eds. Disorders of upper and lower motor neurons. In: Bradley and Daroff's Neurology in Clinical Practice. 8th ed. Elsevier; 2021. https://www.clinicalkey.com. Accessed May 19, 2021.
  7. Cifu DX, et al., eds. Motor neuron diseases. In: Braddom's Physical Medicine & Rehabilitation. 6th ed. Elsevier; 2021. https://www.clinicalkey.com. Accessed May 19, 2021.
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  9. Sorenson, EJ (expert opinion). Mayo Clinic. May 26, 2021.

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