Primary Lateral Sclerosis (PLS): A Targeted Literature Review of Symptoms, Progression, and Outcomes to Inform Evidence Gaps for Rare Neurological Disorders
Author(s)
Iain A. Kaan, MBA, DrPH1, Katharina Buesch, MSc2.
1Managing Director, Aeolian Logic, Singapore, Singapore, 2KJM Büsch Consulting GmbH, Zug, Switzerland.
1Managing Director, Aeolian Logic, Singapore, Singapore, 2KJM Büsch Consulting GmbH, Zug, Switzerland.
OBJECTIVES: While awareness of amyotrophic lateral sclerosis (ALS) has grown, evidence for primary lateral sclerosis (PLS), a distinct upper motor neuron disease, remains limited. The fragmented understanding of PLS symptoms, progression, and outcomes hinders evidence-based clinical and policy decisions. In 2020, updated consensus diagnostic criteria were introduced with the aim of reducing diagnostic delay, optimising therapeutic trial design, and catalysing the development of disease-modifying therapy. This targeted literature review (TLR) aimed to synthesise the recent evidence base for PLS post-2020 to identify gaps in outcomes and inform future research and evaluation frameworks.
METHODS: A TLR was conducted using PubMed (search term: “primary lateral sclerosis pls” [All Fields]) with inclusion criteria: English-language human studies published between 2020 and 2025, full text available, reporting PLS symptoms, progression, or outcomes. Records were screened and data were extracted on symptoms, disease course, outcome measures, and management approaches.
RESULTS: Forty records met the inclusion criteria. Study types included narrative reviews, cohort studies, biomarker and imaging research, and genetic analyses; no randomised controlled trials were found. Symptoms consistently reported, with spasticity, weakness, bulbar dysfunction, and pseudobulbar affect predominant. However, standardised outcomes reporting was sparse. ALS Functional Rating Scale - Revised (ALSFRS-R) was inconsistently used; PLS-specific measures (PLSFRS), quality of life tools, or economic evaluations were rare. Emerging biomarker studies are increasing, but treatment evidence remains lacking.
CONCLUSIONS: Despite clinical descriptions, the outcomes evidence for PLS remains limited and fragmented. The scarcity of validated outcome measures and quality of life data constrains clinical guideline development, health technology assessment, and service planning for PLS. Addressing these evidence gaps is essential to enable equitable and informed care pathways for patients with rare neurodegenerative conditions such as PLS.
METHODS: A TLR was conducted using PubMed (search term: “primary lateral sclerosis pls” [All Fields]) with inclusion criteria: English-language human studies published between 2020 and 2025, full text available, reporting PLS symptoms, progression, or outcomes. Records were screened and data were extracted on symptoms, disease course, outcome measures, and management approaches.
RESULTS: Forty records met the inclusion criteria. Study types included narrative reviews, cohort studies, biomarker and imaging research, and genetic analyses; no randomised controlled trials were found. Symptoms consistently reported, with spasticity, weakness, bulbar dysfunction, and pseudobulbar affect predominant. However, standardised outcomes reporting was sparse. ALS Functional Rating Scale - Revised (ALSFRS-R) was inconsistently used; PLS-specific measures (PLSFRS), quality of life tools, or economic evaluations were rare. Emerging biomarker studies are increasing, but treatment evidence remains lacking.
CONCLUSIONS: Despite clinical descriptions, the outcomes evidence for PLS remains limited and fragmented. The scarcity of validated outcome measures and quality of life data constrains clinical guideline development, health technology assessment, and service planning for PLS. Addressing these evidence gaps is essential to enable equitable and informed care pathways for patients with rare neurodegenerative conditions such as PLS.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO189
Topic
Clinical Outcomes, Epidemiology & Public Health, Patient-Centered Research
Topic Subcategory
Clinician Reported Outcomes
Disease
Neurological Disorders, Rare & Orphan Diseases