Primary lateral sclerosis

Primary lateral sclerosis is a rare neuromuscular disease that affects the nerve cells that control the voluntary muscles, with slowly progressive weakness in voluntary muscle movement. Primary lateral sclerosis belongs to a group of disorders known as motor neuron diseases. Primary lateral sclerosis affects the upper motor neurons also called corticospinal neurons in the arms, legs, and face. Primary lateral sclerosis occurs when nerve cells in the motor regions of the cerebral cortex (the thin layer of cells covering the brain which is responsible for most higher level mental functions) gradually degenerate, causing movements to be slow and effortful. Primary lateral sclerosis often affects the legs first, followed by the body, trunk, arms and hands, and, finally the bulbar muscles (muscles that control speech, swallowing, and chewing). Symptoms include weakness, muscle stiffness and spasticity, clumsiness, slowing of movement, and problems with balance and speech. Primary lateral sclerosis is more common in men than in women, with a varied gradual onset that generally occurs between ages 40 and 60. Problems in the legs (such as weakness, stiffness, spasticity, and balance problems) are often observed first, but hand clumsiness and changes in speech can be early symptoms, as well. Primary lateral sclerosis progresses gradually over a number of years, or even decades, becoming worse over time; however, affected people have a normal life expectancy.

The underlying cause of adult primary lateral sclerosis is currently unknown. Scientists do not believe primary lateral sclerosis has a simple hereditary cause. In most cases, it occurs sporadically in people with no family history of the condition. A subtype of primary lateral sclerosis, called juvenile primary lateral sclerosis, is caused by changes (mutations) in the ALS2 gene and is inherited in an autosomal recessive manner.

The diagnosis of primary lateral sclerosis requires extensive testing to exclude other diseases. When symptoms begin, primary lateral sclerosis may be mistaken for amyotrophic lateral sclerosis (ALS) or spastic paraplegia. Most neurologists follow an affected individual’s clinical course for at least 3 to 4 years before making a diagnosis of primary lateral sclerosis.

Primary lateral sclerosis treatment is based on the signs and symptoms present in each person. Muscle relaxants such as baclofen, tizanidine, and the benzodiazepines may reduce spasticity. Other drugs may relieve pain and antidepressants can help treat depression. Physical therapy, occupational therapy, and rehabilitation may prevent joint immobility and slow muscle weakness and atrophy. Assistive devices such as supports or braces, speech synthesizers, and wheelchairs ma help some people retain independence.. Speech therapy may be useful for those with involvement of the facial muscles.

Primary lateral sclerosis vs ALS

Primary lateral sclerosis is often mistaken for another, more common motor neuron disease called amyotrophic lateral sclerosis (ALS). However, primary lateral sclerosis progresses more slowly than ALS (amyotrophic lateral sclerosis) and in most cases isn’t fatal. ALS also called “Lou Gehrig’s disease,” is a progressive motor neuron disease which leads to problems with muscle control and movement. There are various types of ALS that are distinguished by symptoms and, in some cases, genetic cause. Early symptoms may include muscle twitching, cramping, stiffness, or weakness, slurred speech, and/or difficulty chewing or swallowing. As the disease progresses, people become weaker and are eventually wheelchair-dependent. Death often results from respiratory failure within 2 to 10 years after the symptoms begin.

About 90-95% percent of cases of ALS are not inherited and occur in individuals with no history of the disease in their family. The remaining 5-10% of cases are familial, and are thought to be caused by mutations in any one of several genes. The inheritance pattern associated with familial ALS varies depending on the disease-causing gene involved.

Most familial cases are inherited in an autosomal dominant manner. This means that only one altered (mutated) copy of the disease-causing gene in each cell is sufficient to cause the condition. In most of these cases, an affected individual has one parent with the condition. When an individual with an autosomal dominant form of ALS has children, each child has a 50% (1 in 2) risk to inherited the mutated copy of the gene and be affected.

Less frequently, ALS is inherited in an autosomal recessive manner. In autosomal recessive inheritance, both copies of the disease-causing gene (typically one copy inherited from each parent) must have a mutation for the individual to be affected. The parents of an individual with an autosomal recessive condition, who presumably each carry one mutated copy of the gene, are referred to as carriers. Carriers typically do not have any signs or symptoms of the condition. When two carriers for the same condition are having children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each parent, and a 25% risk to not have the condition and not be a carrier. Autosomal recessive forms of ALS may be mistaken for non-inherited (sporadic) forms due to having a negative family history of the condition.

In rare cases, ALS is inherited in an X-linked dominant manner. This occurs when the disease-causing gene is located on the X chromosome (a sex chromosome). Although females have 2 X chromosomes, having a mutation in one X chromosome is still sufficient to cause the condition. Males who have a mutation (and only one X chromosome) will have the condition. Usually, males with an X-linked dominant form of ALS experience more severe symptoms than females with the same form.

Some individuals who do inherit a mutation known to cause ALS never develop signs and symptoms of ALS, although the reason for this is unclear. This phenomenon is referred to as reduced penetrance.

Most people with ALS have a sporadic (not inherited) form of ALS. It is believed that these cases are caused by an interaction between genetic and environmental factors. This means that a person may have inherited genetic changes (variants) that increase their risk to develop ALS, but the person will only develop ALS if exposed to certain environmental triggers. About 10% of the people with ALS have at least one relative with the disease and are said to have have a familial (inherited) form of the disease. Familial ALS may be caused by changes (pathogenic variants, also known as mutations) in any one of several genes and the pattern of inheritance varies depending on the gene involved. The distinction between sporadic and familial cases is not always clear. The average age at which symptoms begin is 56 years old in the sporadic cases and 46 years old in the familial cases.

Diagnosis of ALS is based on symptoms and a variety of tests to rule out other possible medical diseases that can cause similar symptoms. The goal of treatment is to improve the quality of life for people with ALS, by assisting with breathing, nutrition, mobility, and communication. Medications specifically approved for the treatment of ALS in the United States include riluzole and edaravone.

What cause primary lateral sclerosis

The cause of sporadic primary lateral sclerosis is currently unknown. In primary lateral sclerosis, the nerve cells in the brain that control movement fail over time. This loss causes movement problems, such as slow movements, balance problems and clumsiness.

Adult primary lateral sclerosis

The cause of adult primary lateral sclerosis 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 primary lateral sclerosis 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 primary lateral sclerosis, the protein alsin becomes unstable and doesn’t work properly, which in turn impairs normal muscle function.

Juvenile primary lateral sclerosis is an autosomal recessive 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.

Primary lateral sclerosis symptoms

The signs and symptoms of primary lateral sclerosis often develop between the ages of 40 and 60 and progress (become worse) over time. The voluntary muscles of the legs are often involved first, with symptoms beginning in one leg and then progressing to the other. In general, people with primary lateral sclerosis may experience ¹:

• Muscle weakness and stiffness progressing to your trunk, then your arms, hands, tongue and jaw
• Muscle stiffness, weakness and muscle spasms (spasticity) in your legs, often starting in one leg
• Difficulty with balance and clumsiness. Tripping, difficulty with balance and clumsiness as the leg muscles weaken
• Slowed movement
• Problems with speech. Hoarseness, as well as slowed, slurred speech and drooling as the facial muscles weaken
• Difficulties with swallowing and occasionally breathing late in the disease

Less commonly, primary lateral sclerosis begins in your tongue or hands and then progresses down your spinal cord to your legs.

Primary lateral sclerosis complications

Although the average progression of primary lateral sclerosis (primary lateral sclerosis) lasts around 20 years, the disease has highly variable effects from person to person. Some people continue to walk, but others eventually need to use wheelchairs or other assistive devices.

Adult primary lateral sclerosis 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.

Primary lateral sclerosis diagnosis

There is no single test that confirms a diagnosis of primary lateral sclerosis (primary lateral sclerosis). 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.
• Magnetic resonance imaging (MRI) of the brain and spine. An MRI or other imaging tests of your brain or spine might reveal signs of nerve cell degeneration. An MRI can 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 can measure the involvement of lower motor neurons, which can help to differentiate between primary lateral sclerosis and ALS.
• Nerve conduction studies. Motor and sensory nerve conduction studies 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) for cerebrospinal fluid (CSF) analysis. Your doctor uses a thin, hollow needle to remove from your spinal canal 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 three to four years before finalizing a diagnosis because early ALS can look just like primary lateral sclerosis until additional symptoms surface a few years later. You might be asked to return for repeat electromyography testing over three to four years before the primary lateral sclerosis diagnosis is confirmed.

Primary lateral sclerosis treatment

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

• Medication. Your doctor might prescribe medication such as baclofen, tizanidine (Zanaflex) or clonazepam (Klonopin) to relieve muscle spasms (spasticity). 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).
  • If you have depression, your doctor might prescribe antidepressants. Amitriptyline and other drugs also can help drooling problems.
• Physical therapy. Stretching and strengthening exercises can help maintain muscle strength, flexibility and range of motion, and prevent joint immobility. Heating pads can help relieve muscle pain.
• Speech therapy. If your facial muscles are affected by primary lateral sclerosis, speech therapy might help.
• Assistive devices. Physical or occupational therapists might evaluate you periodically to determine whether you need assistive devices, such as a cane, walker or wheelchair, as primary lateral sclerosis progresses.

Living with primary lateral sclerosis

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 wrestling with the emotional aspects of long-term disease. Because primary lateral sclerosis 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.
• 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’re struggling with 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.

Primary lateral sclerosis life expectancy

Primary lateral sclerosis is progressive gradually becomes worse over time, affected people have a normal life expectancy. However, inspection of reported survival data from 36 patients with primary lateral sclerosis now suggests that the median survival is approximately 20 years ² . Primary lateral sclerosis is not fatal. There is no cure and the progression of symptoms varies. Some people may retain the ability to walk without assistance, but others eventually require wheelchairs, canes, or other assistive devices.

1. Primary lateral sclerosis (PLS). https://www.mayoclinic.org/diseases-conditions/primary-lateral-sclerosis/symptoms-causes/syc-20353968
2. Tartaglia MC, Rowe A, Findlater K, Orange JB, Grace G, Strong MJ. Differentiation between primary lateral sclerosis and amyotrophic lateral sclerosis: examination of symptoms and signs at disease onset and during follow-up. Arch Neurol. 2007 Feb. 64(2):232-6.