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Postural Body Sway as Surrogate Outcome for Myelopathy in Adrenoleukodystrophy

BACKGROUND: Myelopathy is the core clinical manifestation of adrenoleukodystrophy (ALD), which is the most common peroxisomal disorder. Development of therapies requires sensitive and clinically relevant outcome measures. Together with spastic paraparesis, balance disturbance is the main cause of di...

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Autores principales: van Ballegoij, Wouter J. C., van de Stadt, Stephanie I. W., Huffnagel, Irene C., Kemp, Stephan, van der Knaap, Marjo S., Engelen, Marc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379508/
https://www.ncbi.nlm.nih.gov/pubmed/32765293
http://dx.doi.org/10.3389/fphys.2020.00786
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author van Ballegoij, Wouter J. C.
van de Stadt, Stephanie I. W.
Huffnagel, Irene C.
Kemp, Stephan
van der Knaap, Marjo S.
Engelen, Marc
author_facet van Ballegoij, Wouter J. C.
van de Stadt, Stephanie I. W.
Huffnagel, Irene C.
Kemp, Stephan
van der Knaap, Marjo S.
Engelen, Marc
author_sort van Ballegoij, Wouter J. C.
collection PubMed
description BACKGROUND: Myelopathy is the core clinical manifestation of adrenoleukodystrophy (ALD), which is the most common peroxisomal disorder. Development of therapies requires sensitive and clinically relevant outcome measures. Together with spastic paraparesis, balance disturbance is the main cause of disability from myelopathy in ALD. In this cross-sectional study, we evaluated whether postural body sway – a measure of balance – could serve as a surrogate outcome in clinical trials. METHODS: Forty-eight male ALD patients and 49 age-matched healthy male controls were included in this study. We compared sway amplitude and sway path of ALD patients to controls. We then correlated the body sway parameters showing the largest between-group differences with clinical measures of severity of myelopathy. To correct for age, we performed multiple linear regression analysis with age and severity of myelopathy as independent variables. RESULTS: All body sway parameters were significantly higher in patients than in controls, with medium to large effect sizes (r = 0.43–0.66, p < 0.001). In the subgroup of asymptomatic patients, body sway amplitude was also higher, but the difference with controls was smaller than for symptomatic patients (effect size r = 0.38–0.46). We found moderate to strong correlations between body sway amplitude and clinical severity of myelopathy (r = 0.40–0.79, p < 0.005). After correction for age, severity of myelopathy was a significant predictor of body sway amplitude in all regression models. CONCLUSIONS: These results indicate that postural body sway may serve as a surrogate outcome for myelopathy in ALD. Such outcomes are important to evaluate new therapies in clinical trials. Further longitudinal studies are needed and ongoing in this cohort.
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spelling pubmed-73795082020-08-05 Postural Body Sway as Surrogate Outcome for Myelopathy in Adrenoleukodystrophy van Ballegoij, Wouter J. C. van de Stadt, Stephanie I. W. Huffnagel, Irene C. Kemp, Stephan van der Knaap, Marjo S. Engelen, Marc Front Physiol Physiology BACKGROUND: Myelopathy is the core clinical manifestation of adrenoleukodystrophy (ALD), which is the most common peroxisomal disorder. Development of therapies requires sensitive and clinically relevant outcome measures. Together with spastic paraparesis, balance disturbance is the main cause of disability from myelopathy in ALD. In this cross-sectional study, we evaluated whether postural body sway – a measure of balance – could serve as a surrogate outcome in clinical trials. METHODS: Forty-eight male ALD patients and 49 age-matched healthy male controls were included in this study. We compared sway amplitude and sway path of ALD patients to controls. We then correlated the body sway parameters showing the largest between-group differences with clinical measures of severity of myelopathy. To correct for age, we performed multiple linear regression analysis with age and severity of myelopathy as independent variables. RESULTS: All body sway parameters were significantly higher in patients than in controls, with medium to large effect sizes (r = 0.43–0.66, p < 0.001). In the subgroup of asymptomatic patients, body sway amplitude was also higher, but the difference with controls was smaller than for symptomatic patients (effect size r = 0.38–0.46). We found moderate to strong correlations between body sway amplitude and clinical severity of myelopathy (r = 0.40–0.79, p < 0.005). After correction for age, severity of myelopathy was a significant predictor of body sway amplitude in all regression models. CONCLUSIONS: These results indicate that postural body sway may serve as a surrogate outcome for myelopathy in ALD. Such outcomes are important to evaluate new therapies in clinical trials. Further longitudinal studies are needed and ongoing in this cohort. Frontiers Media S.A. 2020-07-17 /pmc/articles/PMC7379508/ /pubmed/32765293 http://dx.doi.org/10.3389/fphys.2020.00786 Text en Copyright © 2020 van Ballegoij, van de Stadt, Huffnagel, Kemp, van der Knaap and Engelen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
van Ballegoij, Wouter J. C.
van de Stadt, Stephanie I. W.
Huffnagel, Irene C.
Kemp, Stephan
van der Knaap, Marjo S.
Engelen, Marc
Postural Body Sway as Surrogate Outcome for Myelopathy in Adrenoleukodystrophy
title Postural Body Sway as Surrogate Outcome for Myelopathy in Adrenoleukodystrophy
title_full Postural Body Sway as Surrogate Outcome for Myelopathy in Adrenoleukodystrophy
title_fullStr Postural Body Sway as Surrogate Outcome for Myelopathy in Adrenoleukodystrophy
title_full_unstemmed Postural Body Sway as Surrogate Outcome for Myelopathy in Adrenoleukodystrophy
title_short Postural Body Sway as Surrogate Outcome for Myelopathy in Adrenoleukodystrophy
title_sort postural body sway as surrogate outcome for myelopathy in adrenoleukodystrophy
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379508/
https://www.ncbi.nlm.nih.gov/pubmed/32765293
http://dx.doi.org/10.3389/fphys.2020.00786
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