Medulla oblongata volume as a promising predictor of survival in amyotrophic lateral sclerosis.
ALS
Brainstem
MRI
Medulla oblongata
Survival
Journal
NeuroImage. Clinical
ISSN: 2213-1582
Titre abrégé: Neuroimage Clin
Pays: Netherlands
ID NLM: 101597070
Informations de publication
Date de publication:
2022
2022
Historique:
received:
11
10
2021
revised:
29
03
2022
accepted:
19
04
2022
pubmed:
14
5
2022
medline:
20
5
2022
entrez:
13
5
2022
Statut:
ppublish
Résumé
Unconventional magnetic resonance imaging studies of the brainstem have recently acquired a growing interest in amyotrophic lateral sclerosis (ALS) pathology since they provide a unique opportunity to evaluate motor tract degeneration and bulbar lower motor neuron involvement. The aim of this study was to investigate the role of brainstem structures as accurate biomarkers of disease severity and predictors of survival. A total of 60 ALS patients and 30 healthy controls subjects (CS) were recruited in this study. Patients were divided in two subgroups according to the onset of the disease: 42 spinal (S-ALS) and 18 bulbar (B-ALS). All subjects underwent 3D-structural MRI. Brainstem volume both of the entire cohort of ALS patients and S-ALS and B-ALS onset were compared with those of CS. In addition the two ALS subgroups were tested for differences in brainstem volumes. Volumetric, vertex-wise, and voxel-based approaches were implemented to assess correlations between MR structural features and clinical characteristics expressed as ALSFRS-r and its bulbar (ALSFSR-r-B) and spinal subscores (ALSFSR-r-S). ROC curves were performed to test the accuracy of midbrain, pons, and medulla oblongata volumes able to discriminate patients dichotomized into long and short survivors by using Two-Steps cluster analysis. Univariate and multivariate survival analyses were carried out to test the prognostic role of brainstem structures' volume, trichotomized by applying a k-means clustering algorithm. Both the entire cohort of ALS patients and B-ALS and S-ALS showed significant lower volumes of both medulla oblongata and pons compared to CS. Furthermore, B-ALS showed a significant lower volume of medulla oblongata, compared to S-ALS. Lower score of ALSFRS-r correlated to atrophy in the anterior compartment of midbrain, pons, and medulla oblongata, as well as in the posterior portion of only this latter region. ALSFSR-r-S positively correlated with shape deformation and density reduction of the anterior portion of the entire brainstem, along the corticospinal tracts. ALSFSR-r-B instead showed a positive correlation with shape deformation of the floor of the fourth ventricle in the medulla oblongata and the crus cerebri in the midbrain. Only medulla oblongata volume demonstrated a significant accuracy to discriminate long and short survivors ALS patients (ROC AUC 0.76, p < 0.001). Univariate and multivariate analysis confirmed the survival predictive role of the medulla oblongata (log rank test p: 0.003). Our findings suggest that brainstem volume may reflect the impairment of corticospinal and corticobulbar tracts as well as lower bulbar motor neurons. Furthermore, medulla oblongata could be used as an early predictor of survival in ALS patients.
Sections du résumé
BACKGROUND
Unconventional magnetic resonance imaging studies of the brainstem have recently acquired a growing interest in amyotrophic lateral sclerosis (ALS) pathology since they provide a unique opportunity to evaluate motor tract degeneration and bulbar lower motor neuron involvement. The aim of this study was to investigate the role of brainstem structures as accurate biomarkers of disease severity and predictors of survival.
MATERIALS AND METHODS
A total of 60 ALS patients and 30 healthy controls subjects (CS) were recruited in this study. Patients were divided in two subgroups according to the onset of the disease: 42 spinal (S-ALS) and 18 bulbar (B-ALS). All subjects underwent 3D-structural MRI. Brainstem volume both of the entire cohort of ALS patients and S-ALS and B-ALS onset were compared with those of CS. In addition the two ALS subgroups were tested for differences in brainstem volumes. Volumetric, vertex-wise, and voxel-based approaches were implemented to assess correlations between MR structural features and clinical characteristics expressed as ALSFRS-r and its bulbar (ALSFSR-r-B) and spinal subscores (ALSFSR-r-S). ROC curves were performed to test the accuracy of midbrain, pons, and medulla oblongata volumes able to discriminate patients dichotomized into long and short survivors by using Two-Steps cluster analysis. Univariate and multivariate survival analyses were carried out to test the prognostic role of brainstem structures' volume, trichotomized by applying a k-means clustering algorithm.
RESULTS
Both the entire cohort of ALS patients and B-ALS and S-ALS showed significant lower volumes of both medulla oblongata and pons compared to CS. Furthermore, B-ALS showed a significant lower volume of medulla oblongata, compared to S-ALS. Lower score of ALSFRS-r correlated to atrophy in the anterior compartment of midbrain, pons, and medulla oblongata, as well as in the posterior portion of only this latter region. ALSFSR-r-S positively correlated with shape deformation and density reduction of the anterior portion of the entire brainstem, along the corticospinal tracts. ALSFSR-r-B instead showed a positive correlation with shape deformation of the floor of the fourth ventricle in the medulla oblongata and the crus cerebri in the midbrain. Only medulla oblongata volume demonstrated a significant accuracy to discriminate long and short survivors ALS patients (ROC AUC 0.76, p < 0.001). Univariate and multivariate analysis confirmed the survival predictive role of the medulla oblongata (log rank test p: 0.003).
DISCUSSIONS
Our findings suggest that brainstem volume may reflect the impairment of corticospinal and corticobulbar tracts as well as lower bulbar motor neurons. Furthermore, medulla oblongata could be used as an early predictor of survival in ALS patients.
Identifiants
pubmed: 35561555
pii: S2213-1582(22)00080-8
doi: 10.1016/j.nicl.2022.103015
pmc: PMC9111981
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
103015Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
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