Progression and life expectancy in primary lateral sclerosis

Objectives To characterise the clinical characteristics and longitudinal outcomes in primary lateral sclerosis (PLS), including median survival from symptom onset and age at death. Methods The authors retrospectively reviewed electronic health records of patients diagnosed with PLS referred to a specialised motor neuron disorders clinic from 2002 to 2024, analysed longitudinal Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) assessments using joint models and used Kaplan-Meier methods and life tables to calculate median survival and age at death compared with population-based values. Results Of 52 patients, 34 (65%) were male, 41 (79%) first noted symptoms in the lower limbs and 10 (19%) in corticobulbar function. Median age of symptom onset was 53 years. The mean annual rate of functional decline was -1.92 ALSFRS-R points (95% CI -3.03 to -0.78), with equal highest rates of decline in fine and gross motor subscores. Five patients (10%) received gastrostomy and three (6%) non-invasive ventilation. Median survival from symptom onset was 23.1 years (22.7 to not reached), and median age at death was 79.5 years (77.8 to not reached) compared with a population-based reference mean of 81.9 years (81.1 to 82.8). Discussion PLS may be commensurate with near-normal life expectancy. Significant disability arises from limb motor dysfunction, with a minority of patients requiring nutritional or respiratory support. This has important implications for counselling and trial design.