Regional Brain and Spinal Cord Volume Loss in Spinocerebellar Ataxia Type 3

被引：40

作者：

Faber, Jennifer ^{[1
,2
]}

Schaprian, Tamara ^{[1
]}

Berkan, Koyak ^{[1
]}

Reetz, Kathrin ^{[3
,4
]}

Franca, Marcondes Cavalcante ^{[5
,6
]}

Rezende, Thiago Junqueira Ribeiro ^{[5
,6
]}

Hong, Jiang ^{[7
]}

Liao, Weihua ^{[8
]}

Warrenburg, Bart ^{[9
]}

Gaalen, Judith ^{[9
]}

Durr, Alexandra ^{[10
]}

Mochel, Fanny ^{[10
]}

Giunti, Paola ^{[11
,12
]}

Garcia-Moreno, Hector ^{[11
,12
]}

Schoels, Ludger ^{[13
,14
,15
]}

Hengel, Holger ^{[13
,14
,15
]}

Synofzik, Matthis ^{[13
,14
,15
]}

Bender, Benjamin ^{[16
]}

Oz, Gulin ^{[17
]}

Joers, James ^{[17
]}

Vries, Jereon J. ^{[18
]}

Kang, Jun-Suk ^{[19
]}

Timmann-Braun, Dagmar ^{[20
]}

Jacobi, Heike ^{[21
]}

Infante, Jon ^{[22
]}

Joules, Richard ^{[23
]}

Romanzetti, Sandro ^{[4
]}

Diedrichsen, Jorn ^{[24
]}

Schmid, Matthias ^{[1
,25
]}

Wolz, Robin ^{[23
]}

Klockgether, Thomas ^{[1
,2
]}

机构：

[1] DZNE, German Ctr Neurodegenerat Dis, Bonn, Germany

[2] Univ Hosp Bonn, Dept Neurol, Bonn, Germany

[3] RVVTH Aachen Univ, Dept Neurol, Bonn, Germany

[4] Forschungszentrum Julich, JARA Brain Inst Mol Neurosci & Neuroimaging, Julich, Germany

[5] Brazilian Inst Neurosci & Neurotechnol BRAINN, Campinas, Brazil

[6] Univ Estadual Campinas, Dept Neurol, Campinas, Brazil

[7] Cent South Univ, Xiangya Hosp, Dept Neurol, Changsha, Peoples R China

[8] Cent South Univ, Xiangya Hosp, Dept Radiol, Changsha, Peoples R China

[9] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Dept Neurol, Med Ctr, Nijmegen, Netherlands

[10] Sorbonne Univ, Pitie Salpetriere Univ Hosp, AP HP, Paris Brain Inst,INSERM,CNRS, Paris, France

[11] UCL Queen Sq Inst Neurol, Dept Clin & Movement Neurosci, Ataxia Ctr, London, England

[12] Univ Coll London Hosp NHS Fdn Trust, Natl Hosp Neurol & Neurosurg, London, England

[13] Univ Tubingen, Dept Neurodegenerat Dis, Tubingen, Germany

[14] Univ Tubingen, Hertie Inst Clin Brain Res, Tubingen, Germany

[15] German Ctr Neurodegenerat Dis DZNE, Tubingen, Germany

[16] Univ Hosp Tubingen, Dept Diagnost & Intervent Neuroradiol, Tubingen, Germany

[17] Univ Minnesota, Dept Radiol, Ctr Magnet Resonance Res, Minneapolis, MN 55455 USA

[18] Univ Groningen, Univ Med Ctr Groningen, Dept Neurol, Groningen, Netherlands

[19] Goethe Univ, Dept Neurol, Frankfurt, Germany

[20] Essen Univ Hosp, Dept Neurol, Essen, Germany

[21] Univ Hosp Heidelberg, Dept Neurol, Heidelberg, Germany

[22] Univ Cantabria, Univ Hosp Marques de Valdecilla IDIVAL, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Neurol Serv, Santander, Spain

[23] IXICO Plc, London, England

[24] Univ Western Ontario, Brain Mind Inst, Dept Comp Sci, Dept Stat, London, ON, Canada

[25] Univ Hosp Bonn, Inst Med Biometry Informat & Epidemiol, Bonn, Germany

来源：

MOVEMENT DISORDERS | 2021年 / 36卷 / 10期

基金：

英国医学研究理事会;

关键词：

spinocerebellar ataxia; MRI; volumetry; biomarker;

D O I：

10.1002/mds.28610

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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. (c) 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

引用

页码：2273 / 2281

页数：9

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