TY - JOUR
T1 - Regional Brain and Spinal Cord Volume Loss in Spinocerebellar Ataxia Type 3
AU - Faber, Jennifer
AU - Schaprian, Tamara
AU - Berkan, Koyak
AU - Reetz, Kathrin
AU - França, Marcondes Cavalcante
AU - de Rezende, Thiago Junqueira Ribeiro
AU - Hong, Jiang
AU - Liao, Weihua
AU - van de Warrenburg, Bart
AU - van Gaalen, Judith
AU - Durr, Alexandra
AU - Mochel, Fanny
AU - Giunti, Paola
AU - Garcia-Moreno, Hector
AU - Schoels, Ludger
AU - Hengel, Holger
AU - Synofzik, Matthis
AU - Bender, Benjamin
AU - Oz, Gulin
AU - Joers, James
AU - de Vries, Jereon J.
AU - Kang, Jun Suk
AU - Timmann-Braun, Dagmar
AU - Jacobi, Heike
AU - Infante, Jon
AU - Joules, Richard
AU - Romanzetti, Sandro
AU - Diedrichsen, Jorn
AU - Schmid, Matthias
AU - Wolz, Robin
AU - Klockgether, Thomas
N1 - Publisher Copyright:
© 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
PY - 2021/10
Y1 - 2021/10
N2 - Background: Given that new therapeutic options for spinocerebellar ataxias are on the horizon, there is a need for markers that reflect disease-related alterations, in particular, in the preataxic stage, in which clinical scales are lacking sensitivity. Objective: The objective of this study was to quantify regional brain volumes and upper cervical spinal cord areas in spinocerebellar ataxia type 3 in vivo across the entire time course of the disease. Methods: We applied a brain segmentation approach that included a lobular subsegmentation of the cerebellum to magnetic resonance images of 210 ataxic and 48 preataxic spinocerebellar ataxia type 3 mutation carriers and 63 healthy controls. In addition, cervical cord cross-sectional areas were determined at 2 levels. Results: The metrics of cervical spinal cord segments C3 and C2, medulla oblongata, pons, and pallidum, and the cerebellar anterior lobe were reduced in preataxic mutation carriers compared with controls. Those of cervical spinal cord segments C2 and C3, medulla oblongata, pons, midbrain, cerebellar lobules crus II and X, cerebellar white matter, and pallidum were reduced in ataxic compared with nonataxic carriers. Of all metrics studied, pontine volume showed the steepest decline across the disease course. It covaried with ataxia severity, CAG repeat length, and age. The multivariate model derived from this analysis explained 46.33% of the variance of pontine volume. Conclusion: Regional brain and spinal cord tissue loss in spinocerebellar ataxia type 3 starts before ataxia onset. Pontine volume appears to be the most promising imaging biomarker candidate for interventional trials that aim at slowing the progression of spinocerebellar ataxia type 3.
AB - Background: Given that new therapeutic options for spinocerebellar ataxias are on the horizon, there is a need for markers that reflect disease-related alterations, in particular, in the preataxic stage, in which clinical scales are lacking sensitivity. Objective: The objective of this study was to quantify regional brain volumes and upper cervical spinal cord areas in spinocerebellar ataxia type 3 in vivo across the entire time course of the disease. Methods: We applied a brain segmentation approach that included a lobular subsegmentation of the cerebellum to magnetic resonance images of 210 ataxic and 48 preataxic spinocerebellar ataxia type 3 mutation carriers and 63 healthy controls. In addition, cervical cord cross-sectional areas were determined at 2 levels. Results: The metrics of cervical spinal cord segments C3 and C2, medulla oblongata, pons, and pallidum, and the cerebellar anterior lobe were reduced in preataxic mutation carriers compared with controls. Those of cervical spinal cord segments C2 and C3, medulla oblongata, pons, midbrain, cerebellar lobules crus II and X, cerebellar white matter, and pallidum were reduced in ataxic compared with nonataxic carriers. Of all metrics studied, pontine volume showed the steepest decline across the disease course. It covaried with ataxia severity, CAG repeat length, and age. The multivariate model derived from this analysis explained 46.33% of the variance of pontine volume. Conclusion: Regional brain and spinal cord tissue loss in spinocerebellar ataxia type 3 starts before ataxia onset. Pontine volume appears to be the most promising imaging biomarker candidate for interventional trials that aim at slowing the progression of spinocerebellar ataxia type 3.
KW - MRI
KW - biomarker
KW - spinocerebellar ataxia
KW - volumetry
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U2 - 10.1002/mds.28610
DO - 10.1002/mds.28610
M3 - Article
C2 - 33951232
AN - SCOPUS:85105064214
SN - 0885-3185
VL - 36
SP - 2273
EP - 2281
JO - Movement Disorders
JF - Movement Disorders
IS - 10
ER -