Postural Body Sway as Surrogate Outcome for Myelopathy in Adrenoleukodystrophy

Abstract

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.

Molecular Biomarkers for Adrenoleukodystrophy: An Unmet Need

“…For example, the Expanded Disability Status Scale (EDSS) is the most commonly used measure to assess disability in studies concerning myelopathy in ALD patients [ 10 ], however, it is subject to high variability in inter-rater and intra-rater reliability [ 25 ]. Additionally, recent developments in monitoring disease progression in ALD using optical coherence tomography and body sway are promising, but still require trials of several years duration and a large number of participants [ 26 , 27 ]. The increasing amount of biological sample repositories (‘biobanking’) creates a unique opportunity for rapid evaluation of new or existing biomarkers.…”

Gait Difficulties and Postural Instability in Adrenoleukodystrophy

“…It is clear that myelopathy affects these males with stable brain lesions as well (8). Patients suffer from gait and balance difficulties across the phenotypic spectrum in adulthood (9)(10)(11), but little is known about the relative contributions of sensory loss, motor dysfunction, and postural control to gait dysfunction and fall risk. Multidimensional quantitative performance measures are needed to better characterize and define the association between sensory deficits and balance issues in both males and females with ALD.…”