What is Primary Lateral Sclerosis (PLS)?

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Last updated: May 15, 2025View editorial policy

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From the Guidelines

Primary lateral sclerosis (PLS) is a rare neurodegenerative disorder characterized by the progressive degeneration of upper motor neurons, leading to muscle weakness, stiffness, and spasticity, with a slower progression compared to amyotrophic lateral sclerosis (ALS) 1.

Key Characteristics of PLS

  • Affects the upper motor neurons in the brain
  • Causes progressive muscle weakness and stiffness
  • Slower progression compared to ALS
  • Involvement of only upper motor neurons
  • Patients typically experience gradually worsening spasticity and weakness, particularly in the legs

Symptoms and Diagnosis

  • Symptoms usually begin after age 40
  • Include muscle stiffness, balance problems, slurred speech, and difficulty with fine motor tasks
  • Diagnosis involves ruling out other conditions through clinical examination, MRI scans, electromyography, and sometimes spinal fluid analysis
  • Symptoms typically present for at least 3-4 years before a definitive diagnosis

Treatment and Management

  • Treatment focuses on symptom management
  • Medications like baclofen or tizanidine for spasticity
  • Physical therapy to maintain mobility
  • Occupational therapy for daily activities
  • Speech therapy as needed

Prognosis

  • The disease progresses slowly over years or decades
  • While it causes disability, it is not typically life-threatening like ALS
  • Most patients having a normal life expectancy, as the focus is on improving quality of life, similar to the goals outlined for ALS in the 2024 National Academies of Sciences, Engineering, and Medicine report 1.

From the Research

Definition and Characteristics

  • Primary lateral sclerosis (PLS) is a rare neurodegenerative disorder characterized by the selective deterioration of the upper motor neurons (UMNs), sparing the lower motor neuron (LMN) system 2.
  • It is defined by a slowly progressive upper motor neuron syndrome, with a clinical diagnosis made after exclusion of structural, neurodegenerative, and metabolic mimics 3.
  • PLS often presents with gradual-onset, progressive lower extremity stiffness and pain due to muscle spasticity 4.

Clinical Features

  • Patients with PLS experience stiffness, decreased balance and coordination, mild weakness, and difficulty speaking and swallowing if the bulbar region is affected 5.
  • Emotionality and emotional lability are also common features of PLS, particularly with corticobulbar involvement 6.
  • Cognitive dysfunction is recognized, but dementia is rarely a prominent management issue 6.

Diagnosis and Diagnostic Criteria

  • The diagnosis of PLS is clinical, based on characteristic features and the absence of lower motor neuron involvement 5, 3.
  • Diagnostic criteria for PLS have been updated to reduce diagnostic delay and optimize therapeutic trial design 3.
  • Differentiation of PLS from upper motor neuron-predominant forms of amyotrophic lateral sclerosis remains a significant challenge in the early symptomatic phase of both disorders 2, 3.

Treatment and Management

  • Treatment for PLS is largely supportive, with a focus on managing symptoms such as spasticity 5.
  • Intrathecal baclofen pumps (ITB) have been used to effectively treat spasticity in PLS patients 4.
  • Specialized multidisciplinary care is recommended for PLS patients, with increasing international research cooperation needed to achieve dedicated therapeutic trials 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Primary Lateral Sclerosis: An Overview.

Journal of clinical medicine, 2024

Research

Primary lateral sclerosis: consensus diagnostic criteria.

Journal of neurology, neurosurgery, and psychiatry, 2020

Research

Utility of intrathecal baclofen pump in primary lateral sclerosis.

Journal of the neurological sciences, 2021

Research

Primary Lateral Sclerosis.

Neurologic clinics, 2015

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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