Abstract: Equine exercise-associated myopathies are prevalent, clinically heterogeneous, generally idiopathic disorders characterised by episodes of myofibre damage that occur in association with exercise. Episodes are intermittent and vary within and between affected horses and across breeds. The aetiopathogenesis is often unclear; there might be multiple causes. Poor phenotypic characterisation hinders genetic and other disease analyses. Objective: The aim of this study was to characterise phenotypic patterns across exercise-associated myopathies in horses. Methods: Historical cross-sectional study, with subsequent masked case-control validation study. Methods: Historical clinical and histological features from muscle samples (n = 109) were used for k-means clustering and validated using principal components analysis and hierarchical clustering. For further validation, a blinded histological study (69 horses) was conducted comparing two phenotypic groups with selected controls and horses with histopathological features characterised by myofibrillar disruption. Results: We identified two distinct broad phenotypes: a non-classic exercise-associated myopathy syndrome (EAMS) subtype was associated with practitioner-described signs of apparent muscle pain (p < 0.001), reluctance to move (10.85, p = 0.001), abnormal gait (p < 0.001), ataxia (p = 0.001) and paresis (p = 0.001); while a non-specific classic RER subtype was not uniquely associated with any particular variables. No histological differences were identified between subtypes in the validation study, and no identifying histopathological features for other equine myopathies identified in either subtype. Conclusions: Lack of an independent validation population; small sample size of smaller identified subtypes; lack of positive control myofibrillar myopathy cases; case descriptions derived from multiple independent and unblinded practitioners. Conclusions: This is the first study using computational clustering methods to identify phenotypic patterns in equine exercise-associated myopathies, and suggests that differences in patterns of presenting clinical signs support multiple disease subtypes, with EAMS a novel subtype not previously described. Routine muscle histopathology was not helpful in sub-categorising the phenotypes in our population. Background: Les myopathies induites à l'exercice demeurent fréquentes, hétérogènes cliniquement et représentent des désordres idiopathiques caractérisés par des épisodes de dommages myofibrillaires en lien avec l'exercice. Les épisodes sont intermittents et varient à la fois chez le même cheval, entre chevaux et entre les différentes races. L'étiopathogénie demeure obscure et pourrait être multifactorielle. La pauvre caractérisation phénotypique des myopathies ne simplifie pas les analyses génétiques ni celles d'autres maladies. Objective: Le but de cette étude est de caractériser les patrons phénotypiques en lien avec les myopathies induites à l'exercice chez le cheval. TYPE D'ÉTUDE: Étude transversale historique et étude subséquente de validation de cas témoins aveugle. MÉTHODES: Les facteurs clés cliniques et histologiques provenant d'échantillons de muscles (n = 109) ont été utilisés pour l'algorithme de K‐moyennes et validés par le biais d'analyse des composantes principales et de classification hiérarchique. Pour validation additionnelle, une étude histologique à l'aveugle (69 chevaux) a été faite comparant les deux groupes phénotypiques avec des contrôles sélectionnés et des chevaux avec éléments histopathologiques caractérisés par de la discontinuité myofibrillaire. RÉSULTATS: Deux phénotypes distincts ont été identifiés: un premier sous‐type de syndrome de myopathie induite à l'exercice non‐classique (EAMS) associé à de la douleur musculaire telle que décrite par le praticien suivant le cheval (χ = 19.33, p < 0.001), difficulté à se déplacer (χ = 10.85, p = 0.001), démarche anormale (χ = 34.61, p < 0.001), ataxie (χ = 10.88, p = 0.001) et parésie (χ = 10.88, p = 0.001); alors qu'un sous‐type RER classique non‐spécifique n'était associé à aucune variable en particulier. Aucune différente histologique n'a été identifié entre les sous‐types dans l'étude de validation et aucune caractéristique histopathologique d'autres myopathies équines n'a été identifiées dans les différents sous‐types. Unassigned: Aucune population indépendante pour validation; petite taille d'échantillon pour les sous‐types peu nombreux identifiés; aucun cas contrôles positifs de myopathie fibrillaire; description des cas provenant de multiples praticiens indépendants et non‐aveugles. Conclusions: Cette étude est la première utilisant des méthodes de regroupement informatique pour identifier des patrons phénotypiques de myopathies équines induites à l'exercice et suggère que des différences existent dans les patrons de signes cliniques en faveur de multiples sous‐types de maladie, incluant EAMS qui représente un nouveau sous‐type non décrit jusqu'à maintenant. L'histopathologie musculaire de routine n'a pas permis de sous‐catégoriser les phénotypes dans cette population.
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The research article explores the different patterns and characteristics found in horses suffering from equine exercise-associated myopathies, a collection of muscle disorders linked with exercise. The article uses computational methods to better identify and understand these disorders, and to reveal that there are potentially multiple different disease subtypes.
Objective and Method of Study
The main goal of this research was to identify phenotypic patterns in equine exercise-associated myopathies, a prevalent and varying collection of muscle disorders in horses associated with exercise.
The researchers performed a historical cross-sectional study using historical clinical and histological features from muscle samples of 109 horses.
These data were used in an algorithm for k-means clustering, this was then validated through a technique called principal components analysis and hierarchical clustering.
To further validate the study’s findings, a blind histological study was conducted using 69 more horses, comparing two identified phenotypic groups with selected controls and horses with characterized myofibrillar disruption.
Key Findings
The study found two distinct phenotypes associated with the myopathies. These are known as the non-classic exercise-associated myopathy syndrome (EAMS) and non-specific classic RER subtype.
Notably, EAMS is associated with muscle pain, reluctance to move, unusual gait, ataxia and paresis. None of these abnormalities were unique to the non-specific classic RER subtype.
No significant histological differences were found between these subtypes in the validation phase of this study.
Furthermore, no identifying histopathological features for other equine myopathies was identified in either suffering groups.
Conclusions
The research, for the first time, applied computational methods to understand phenotypic patterns in equine exercise-associated myopathies. This highlighted the possibility of multiple disease subtypes, with EAMS representing a new subtype that was previously undescribed.
However, the authors noted certain limitations to their study, including the lack of an independent validation population, small sample sizes, the absence of positive control myofibrillar myopathy cases and the fact that their case descriptions derived from multiple independent and unblinded practitioners.
Cite This Article
APA
Lindsay-McGee V, Massey C, Li YT, Clark EL, Psifidi A, Piercy RJ.
(2024).
Characterisation of phenotypic patterns in equine exercise-associated myopathies.
Equine Vet J.
https://doi.org/10.1111/evj.14128
Department of Clinical Sciences and Services, Royal Veterinary College, London, UK.
Massey, Claire
Department of Clinical Sciences and Services, Royal Veterinary College, London, UK.
Li, Ying Ting
Department of Clinical Sciences and Services, Royal Veterinary College, London, UK.
Clark, Emily L
The Roslin Institute, University of Edinburgh, Edinburgh, UK.
Psifidi, Androniki
Department of Clinical Sciences and Services, Royal Veterinary College, London, UK.
The Roslin Institute, University of Edinburgh, Edinburgh, UK.
Piercy, Richard J
Department of Clinical Sciences and Services, Royal Veterinary College, London, UK.
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