Overview
Primary lateral sclerosis, often called PLS, is a rare neurological disease that affects the nerve cells in the brain that control voluntary movement. These nerve cells, called upper motor neurons, gradually stop working properly. Unlike the more well-known ALS (amyotrophic lateral sclerosis), PLS does not typically affect the lower motor neurons — the nerve cells in the spinal cord that directly connect to muscles. This difference is important because it means PLS usually progresses more slowly and does not shorten life expectancy as dramatically as ALS. The main symptoms of PLS include slowly worsening stiffness and weakness in the legs, arms, and sometimes the face and throat. People may notice they have trouble walking, balancing, or speaking clearly. Muscle spasms and cramps are also common. Symptoms usually begin in the legs and gradually spread upward over many years. There is currently no cure for PLS. Treatment focuses on managing symptoms and maintaining quality of life. Physical therapy, occupational therapy, and medications to reduce muscle stiffness are the main tools doctors use. With the right support, many people with PLS live for decades after diagnosis and can maintain meaningful independence for a long time.
Also known as:
Key symptoms:
Stiffness and tightness in the legs (spasticity)Slowly worsening leg weaknessDifficulty walking and problems with balanceMuscle cramps and spasmsWeakness or stiffness spreading to the arms over timeSlurred or slow speechDifficulty swallowingEmotional changes such as sudden laughing or crying (pseudobulbar affect)FatigueDragging one or both feet when walkingStiffness in the hands and fingers
Clinical phenotype terms (26)— hover any for plain English
Sporadic
Usually appears on its own, not inherited from a parent
Adult
Begins in adulthood (age 18 or older)
FDA & Trial Timeline
2 eventsHospital for Special Surgery, New York — PHASE1
Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.
Treatments
No FDA-approved treatments are currently listed for Primary lateral sclerosis.
2 clinical trialsare actively recruiting — trials can provide access to cutting-edge therapies.
View clinical trials →Treatment Centers
8 centersBaylor College of Medicine Rare Disease Center ↗
Baylor College of Medicine
📍 Houston, TX
🏥 NORDStanford Medicine Rare Disease Center ↗
Stanford Medicine
📍 Stanford, CA
🔬 UDNNIH Clinical Center Undiagnosed Diseases Program ↗
National Institutes of Health
📍 Bethesda, MD
🔬 UDNUCLA UDN Clinical Site ↗
UCLA Health
📍 Los Angeles, CA
🔬 UDNBaylor College of Medicine UDN Clinical Site ↗
Baylor College of Medicine
📍 Houston, TX
🔬 UDNHarvard/MGH UDN Clinical Site ↗
Massachusetts General Hospital
📍 Boston, MA
🏥 NORDMayo Clinic Center for Individualized Medicine ↗
Mayo Clinic
📍 Rochester, MN
👤 Mayo Clinic Center for Individualized Medicine
🏥 NORDUCLA Rare Disease Day Program ↗
UCLA Health
📍 Los Angeles, CA
Travel Grants
No travel grants are currently matched to Primary lateral sclerosis.
Community
No community posts yet. Be the first to share your experience with Primary lateral sclerosis.
Start the conversation →Latest news about Primary lateral sclerosis
Disease timeline:
New recruiting trial: Imaging Biomarkers in ALS
A new clinical trial is recruiting patients for Primary lateral sclerosis
Caregiver Resources
NORD Caregiver Resources
Support, advocacy, and financial assistance for caregivers of rare disease patients.
Mental Health Support
Rare disease caregiving can be isolating. Connect with counseling and peer support.
Family & Caregiver Grants
Financial assistance programs specifically for caregivers of rare disease patients.
Social Security Disability
Learn how rare disease patients may qualify for SSDI/SSI benefits.
Questions for your doctor
Bring these to your next appointment
- Q1.How confident are you in the PLS diagnosis, and what would make you reconsider it?,How often should I be monitored, and what signs should prompt me to contact you sooner?,Is there any chance my PLS could develop into ALS, and how would we know?,What medications or therapies do you recommend to manage my muscle stiffness right now?,Should I have genetic testing, and could this condition affect my family members?,What therapists or specialists should be part of my care team?,Are there any clinical trials for PLS that I might be eligible to join?
Common questions about Primary lateral sclerosis
What is Primary lateral sclerosis?
Primary lateral sclerosis, often called PLS, is a rare neurological disease that affects the nerve cells in the brain that control voluntary movement. These nerve cells, called upper motor neurons, gradually stop working properly. Unlike the more well-known ALS (amyotrophic lateral sclerosis), PLS does not typically affect the lower motor neurons — the nerve cells in the spinal cord that directly connect to muscles. This difference is important because it means PLS usually progresses more slowly and does not shorten life expectancy as dramatically as ALS. The main symptoms of PLS include slow
How is Primary lateral sclerosis inherited?
Primary lateral sclerosis follows a sporadic inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.
At what age does Primary lateral sclerosis typically begin?
Typical onset of Primary lateral sclerosis is adult. Age of onset can vary across affected individuals.
Are there clinical trials for Primary lateral sclerosis?
Yes — 2 recruiting clinical trials are currently listed for Primary lateral sclerosis on UniteRare. See the clinical trials section on this page for phase, sponsor, and site details sourced from ClinicalTrials.gov.
Which specialists treat Primary lateral sclerosis?
25 specialists and care centers treating Primary lateral sclerosis are listed on UniteRare, sourced from ClinicalTrials.gov principal investigators, published research, and the NPPES NPI registry.