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20-06-2023 | Amyotrophic Lateral Sclerosis | Original Communication

The impact of upper and lower motor neuron burden on diagnostic certainty, and clinical course of spinal-onset amyotrophic lateral sclerosis: a cluster-based approach

Authors: Giammarco Milella, Stefano Zoccolella, Alessia Giugno, Marco Filardi, Daniele Urso, Salvatore Nigro, Benedetta Tafuri, Ludovica Tamburrino, Valentina Gnoni, Giancarlo Logroscino

Published in: Journal of Neurology | Issue 10/2023

Abstract

Background

Upper motor neuron (UMN) and lower motor neuron (LMN) involvement represent the core clinical features of amyotrophic lateral sclerosis (ALS). Several studies divided patients into prevalent UMN and LMN impairment phenotypes to investigate the association between motor systems impairments and ALS clinical course. However, this distinction was somehow heterogeneous and significantly affected the comparability across studies.

Aims

This study aimed to investigate whether patients spontaneously segregate based on the extent of UMN and LMN involvement without a-priori categorization and to identify potential clinical and prognostic features of different clusters.

Methods

Eighty-eight consecutive spinal-onset ALS patients were referred to an ALS tertiary center between 2015 and 2022. UMN and LMN burden was assessed with the Penn Upper Motor Neuron scale (PUMNS) and the Devine score, respectively. PUMNS and LMN scores were normalized into 0–1 and analyzed using a two-step cluster analysis and the Euclidean distance measure. The Bayesian Information Criterion was used to determine the cluster number. Demographic and clinical variables were tested for differences among the clusters.

Results

Three distinct clusters emerged at cluster analysis. Patients in “cluster-1” showed moderate UMN and severe LMN involvement, corresponding to the typical ALS phenotype. Patients in “cluster-2” showed mild LMN and severe UMN damage, corresponding to a predominant UMN phenotype, while “cluster-3” patients showed mild UMN and moderate LMN damage, corresponding to a predominant LMN phenotype. Patients in “cluster-1” and “cluster-2” showed a higher prevalence of definite ALS than those in “cluster-3” (61% and 46 vs 9%, p < 0.001). “Cluster-1” patients had a lower median ALSFRS-r score compared to both “cluster-2” and 3 patients (27 vs 40 and 35, < 0.001). “Cluster-1” (HR: 8.5; 95% CI 2.1–35.1 and p = 0.003) and 3 (HR: 3.2; 95% CI 1.1–9.1; p = 0.03) were associated with shorter survival than those in “cluster-2”.

Conclusions

Spinal-onset ALS can be categorized into three groups according to LMN and UMN burden. The UMN burden is related to higher diagnostic certainty and broader disease spread, while LMN involvement is associated with higher disease severity and shorter survival.

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Title: The impact of upper and lower motor neuron burden on diagnostic certainty, and clinical course of spinal-onset amyotrophic lateral sclerosis: a cluster-based approach
Authors: Giammarco Milella
Stefano Zoccolella
Alessia Giugno
Marco Filardi
Daniele Urso
Salvatore Nigro
Benedetta Tafuri
Ludovica Tamburrino
Valentina Gnoni
Giancarlo Logroscino
Publication date: 20-06-2023
Publisher: Springer Berlin Heidelberg
Keyword: Amyotrophic Lateral Sclerosis
Published in: Journal of Neurology / Issue 10/2023
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-023-11827-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The impact of upper and lower motor neuron burden on diagnostic certainty, and clinical course of spinal-onset amyotrophic lateral sclerosis: a cluster-based approach

Abstract

Background

Aims

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Aims

Methods

Results

Conclusions

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