What is Primary Lateral Sclerosis?
Primary lateral sclerosis (PLS) is a neurological disorder in which nerve cells in the brain progressively deteriorate over time. The disease affects upper motor neurons, nerve cells responsible for communicating signals involved in voluntary muscle movement from the brain to the rest of the body. As these cells degrade and become dysfunctional, movement-related symptoms emerge.
Early PLS symptoms are similar to those of amyotrophic lateral sclerosis (ALS). However, ALS typically affects more of the nervous system and is fatal. PLS can cause significant disabilities, but it is not fatal.
Symptoms of PLS
PLS symptoms typically progress slowly over a period of years. The disorder most often occurs in adults between the ages of 40 and 60, but a juvenile-onset type of the disorder begins in early childhood.
Common symptoms of PLS include:
- Weakness, stiffness, or muscle spasms in one or both legs
- Problems with balance and coordination
- Muscle weakness that progresses to the arms, trunk, jaw, and tongue
- Slurred speech
- Difficulty swallowing
What Causes Primary Lateral Sclerosis?
The cause of PLS is unknown. Most cases occur in people with no family history of the disease, suggesting that even if there is a genetic cause, it happens randomly or because of some external environmental trigger. However, scientists do not yet know what those triggers might be.
Is Primary Lateral Sclerosis Hereditary?
In most cases, PLS is not an inherited disorder. The exception is juvenile PLS, which is usually caused by abnormal changes (mutations) in the ALS2 gene. The disorder-causing gene mutations are inherited in an autosomal recessive pattern. This means that a child must inherit two copies of the gene mutation, one from each parent, to develop the disorder. People who have only one copy of the mutated gene will not develop PLS but will be carriers who can pass the mutation on to their children. Two carrier parents have a 25 percent chance of having a child with PLS with each pregnancy. Half of their pregnancies will produce a carrier, and a quarter of the pregnancies will produce a child with no mutated genes.
How Is Primary Lateral Sclerosis Detected?
The earliest and most common signs of PLS are weakness and stiffness in the legs. The disorder usually first affects one leg and then progresses to affect the other.
Early signs of PLS can include:
- Involuntary muscle spasms in the legs
- Leg stiffness
- Slow movements of leg muscles
- Leg cramps
- Balance difficulties
- Problems walking
- Falls or clumsiness
How Is Primary Lateral Sclerosis Diagnosed?
To diagnose PLS, a doctor will look for the symptoms and features of the disorder while working to rule out other potential causes of the symptoms, such as ALS or multiple sclerosis (MS). The diagnostic process may include:
- Physical exams and assessment of the patient’s medical history
- Neurological exams
- Blood tests
- Magnetic resonance imaging (MRI) to look for deterioration of nerve cells in the brain or spinal cord
- Electromyogram (EMG) or nerve conduction studies to measure muscle function and the communication between muscles and nerve cells
- Spinal tap (lumbar puncture) to rule out MS, infections, or other potential causes of the symptoms
PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.
How Is Primary Lateral Sclerosis Treated?
PLS has no cure, and no treatment will stop or reverse the disorder’s progression. However, treatment options aim to prevent complications and improve quality of life. Common treatments include:
- Muscle-relaxant drugs such as baclofen, tizanidine, and benzodiazepines
- Antidepressant medications to treat depression, a common complication of PLS
- Physical therapy
- Occupational therapy
- Speech therapy
- Assistive devices such as wheelchairs or speech-assistive technologies
How Does Primary Lateral Sclerosis Progress?
The progression of PLS varies from case to case. Symptoms typically worsen over 20 years but may progress more quickly in some cases. In some cases, physical impairments remain relatively mild, and some people with PLS may retain the ability to walk. However, symptoms can significantly impair mobility and speech in other cases and cause a reduced quality of life.
Progressive symptoms of PLS can include:
- Injuries from falls
- Muscle weakness in the hands
- Speech impairment
- Difficulty swallowing
- Difficulty breathing
- Loss of the ability to walk
- Loss of bladder control
PLS is not fatal, and adults with the disorder have an average life expectancy.
How Is Primary Lateral Sclerosis Prevented?
There is no known way to prevent PLS. However, parents with a family history of the disorder or who have had another child with juvenile PLS are advised to consult a genetic counselor to assess their risk if they plan to have another child.
Primary Lateral Sclerosis Caregiver Tips
- Learn as much as you can about PLS. The disorder usually progresses slowly, and living with its challenges is easier if you know what to expect.
- Find a community. Online support groups can be helpful sources of information and encouragement from other families living with PLS and other motor neuron diseases.
- Take care of yourself. People responsible for caring for someone with a progressive disease such as PLS are in danger of sacrificing their own mental and physical health. Understand that taking time away from caregiving when you can is an essential part of keeping yourself healthy. You shouldn’t feel guilty about taking time for yourself, and you’ll be a better caregiver when you do.
Primary Lateral Sclerosis Brain Science
Scientists don’t know what causes adult-onset PLS, but mutations in the ALS2 gene cause most cases of juvenile PLS. This gene carries instructions for creating a protein called alsin. The disorder-causing ALS2 mutations result in the production of a dysfunctional form of alsin.
Researchers know that motor neurons contain a significant amount of alsin, and the protein is likely essential for the cells’ health and function. However, it is still unclear how a deficiency of functional alsin causes the deterioration of neurons.
Primary Lateral Sclerosis Research
Title: Use of Dalfampridine in Primary Lateral Sclerosis
Principal investigator: Jim Wymer, MD
University of Florida Gainesville
This study will comprise an 18-week open-label safety and tolerability trial. In this study, a total of 35 subjects with primary lateral sclerosis PLS or upper motor neuron predominant ALS will be enrolled. At the initial screening evaluation, a baseline T25FW will be obtained. This baseline test will be repeated at weeks 2, 4, 6, 10, 14, and 18. The validity of this measure was shown in MS studies when compared to the MSWS-12 (12-item walking scale) and CGI (clinical global impression) scales (35-37). A consistent responder will be defined as improvement in three of four Timed 25Foot Walk while on medication, compared with the baseline results while off medication.
Title: Phenotype, Genotype and Biomarkers 2 (PGB2)
Principal investigator: Michael Benatar, MD, PhD
University of Miami
The purpose of this study is to learn more about amyotrophic lateral sclerosis (ALS) and other related neurodegenerative diseases, including frontotemporal dementia (FTD), primary lateral sclerosis (PLS), hereditary spastic paraplegia (HSP), progressive muscular atrophy (PMA), and multisystem proteinopathy (MSP). More precisely, the investigator wants to identify the links between the disease phenotype (phenotype refers to observable signs and symptoms) and the disease genotype (genotype refers to your genetic information). The investigator also wants to identify biomarkers of ALS and related diseases.
Title: Clinical Procedures to Support Research in ALS (CAPTURE-ALS)
Principal investigator: Yuen T. So, MD
Palo Alto, CA
The purpose of the Clinical Procedures To Support Research (CAPTURE) study is to utilize information collected in the medical record to learn more about a disease called amyotrophic lateral sclerosis (ALS) and related disorders.
The study will involve patients with ALS or related disorders receiving care at a clinical center in the CReATe consortium that uses Epic as its electronic health record (EHR) system. The study aims to systematically gather a clinical dataset through the EHR using a standardized approach to characterize the natural history of ALS and related diseases.