Related Experiment Video
Updated: Jun 5, 2026
15:48
ALS - Motor Neuron Disease: Mechanism and Development of New Therapies
Published on: July 29, 2007
Progression and life expectancy in primary lateral sclerosis.
David G Lester1, Alexander G Thompson1, Kevin Talbot1
1Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Journal of Neurology, Neurosurgery, and Psychiatry
|May 16, 2025
Summary
Primary Lateral Sclerosis (PLS) patients show near-normal life expectancy, with limb motor dysfunction causing significant disability. This finding impacts patient counseling and clinical trial design for this rare motor neuron disease.
Area of Science:
- Neurology
- Neuroscience
- Clinical Medicine
Background:
- Primary Lateral Sclerosis (PLS) is a rare, adult-onset upper motor neuron disorder.
- Characterizing its clinical trajectory and long-term outcomes is crucial for patient management.
Purpose of the Study:
- To define the clinical features of PLS.
- To determine longitudinal outcomes, including survival and age at death.
- To inform patient counseling and clinical trial design.
Main Methods:
- Retrospective review of electronic health records for 52 PLS patients (2002-2024).
- Analysis of functional decline using Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) scores.
- Calculation of median survival and age at death using Kaplan-Meier methods and life tables.
Main Results:
- Median age of symptom onset was 53 years; 65% were male.
- Annual functional decline averaged -1.92 ALSFRS-R points, with limb motor scores most affected.
- Median survival from symptom onset was 23.1 years; median age at death was 79.5 years.
Conclusions:
- PLS is associated with near-normal life expectancy.
- Limb motor dysfunction is a primary driver of disability.
- Findings have significant implications for patient counseling and future research, including clinical trial design.
More Related Videos
Related Concept Videos
02:07Tumor Progression
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
01:15Parkinson's Disease: Overview
Neurodegenerative disorders are progressive diseases that cause irreversible damage and loss to neurons in specific brain areas. Examples of these disorders include Parkinson's disease, Alzheimer's disease, Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). These disorders share characteristics such as proteinopathies, selective neuronal vulnerability, and a complex interplay between genetic and environmental factors. The primary therapeutic goal for these conditions is to...
01:19Multiple Sclerosis l: Introduction
Multiple sclerosis is a chronic autoimmune disease of the central nervous system (CNS) that affects the brain, spinal cord, and optic nerves. It is an inflammatory demyelinating disorder and a leading cause of neurological disability in young adults.EpidemiologyMS commonly begins between 20 and 40 years of age and is twice as common in women. Its exact cause remains unclear, but genetic susceptibility contributes, with higher risk in first-degree relatives and identical twins. A greater...
01:24Parkinson Disease l: Introduction
Parkinson’s disease is a chronic, progressive neurodegenerative disorder that primarily affects movement. It is characterized by motor symptoms such as resting tremors, muscle rigidity, bradykinesia (slowness of movement), and postural instability. Patients may notice hand tremors at rest, stiffness during movement, or a shuffling gait. In addition to motor features, non-motor symptoms include sleep disturbances, mood and behavioral changes, constipation, and cognitive impairment, all of which...
01:24Parkinson Disease ll: Pathophysiology
Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...
01:25Secondary Spinal Cord Injury llI: Pathophysiology
Early Ischemia and Ionic ImbalanceWithin minutes of spinal cord injury, a secondary cascade begins, progressing over hours to weeks. Vascular damage reduces blood flow, causing ischemia and mitochondrial dysfunction. ATP depletion leads to ion pump failure, membrane depolarization, sodium influx, potassium efflux, and water accumulation, resulting in cellular swelling. Increased intracellular calcium further disrupts mitochondria and accelerates cellular injury.Excitotoxicity and Neuronal...