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Updated: May 5, 2026

Utility of Dissociated Intrinsic Hand Muscle Atrophy in the Diagnosis of Amyotrophic Lateral Sclerosis

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Published on: March 4, 2014

Slower Progression Rates in Lower Limb-Onset ALS.

Yehuda Shovman^1,2, Yossef Lerner¹, Marc Gotkine¹

¹Department of Neurology, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel.

Journal of Clinical Medicine

|May 4, 2026

Summary

This summary is machine-generated.

People with Amyotrophic Lateral Sclerosis (ALS) show variations in diagnostic delay and disease progression based on onset site. Lower limb onset (LLO) ALS patients experienced longer delays and slower functional decline, particularly in motor function.

Keywords:

ALS ALSFRS-R mixed-effects models

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Area of Science:

Neurology
Clinical Research
Amyotrophic Lateral Sclerosis (ALS) Studies

Background:

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease.
The site of initial symptom onset can influence disease trajectory and diagnosis.
Understanding these differences is crucial for patient stratification and clinical trial design.

Purpose of the Study:

To investigate differences in diagnostic delay and disease progression among people with ALS (PALS) based on their site of onset.
To analyze the impact of upper limb onset (ULO), lower limb onset (LLO), and bulbar onset (BO) on ALS progression.
To correlate diagnostic delay with functional decline rates in PALS.

Main Methods:

Retrospective analysis of prospectively collected data from 281 PALS.
Classification of PALS into ULO, LLO, and BO groups.
Application of a linear mixed-effects model to assess diagnostic delay and ALSFRS-R score changes over time.

Main Results:

PALS with LLO exhibited longer diagnostic delays compared to those with BO.
Younger PALS and those with LLO showed slower rates of functional decline (ALSFRS-R) than PALS with BO or ULO.
Slower motor subscale decline contributed to the slower overall ALSFRS-R decline in LLO patients.
Longer diagnostic delays correlated with lower initial ALSFRS-R scores and slower progression rates.

Conclusions:

Significant differences exist in diagnostic delay and functional decline rates among PALS based on onset site (ULO, LLO, BO).
Differentiating between ULO and LLO ALS may enhance patient stratification for clinical trials.
Early diagnosis and understanding onset-specific progression are vital for effective ALS management.