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@ARTICLE{Faber:155578,
author = {Faber, Jennifer and Schaprian, Tamara and Berkan, Koyak and
Reetz, Kathrin and França, Marcondes Cavalcante and de
Rezende, Thiago Junqueira Ribeiro and Hong, Jiang and Liao,
Weihua and van de Warrenburg, Bart and van Gaalen, Judith
and Dürr, Alexandra and Mochel, Fanny and Giunti, Paola and
Garcia-Moreno, Hector and Schoels, Ludger and Hengel, Holger
and Synofzik, Matthis and Bender, Benjamin and Oz, Gulin and
Joers, James and de Vries, Jereon J and Kang, Jun-Suk and
Timmann-Braun, Dagmar and Jacobi, Heike and Infante, Jon and
Joules, Richard and Romanzetti, Sandro and Diedrichsen, Jorn
and Schmid, Matthias and Wolz, Robin and Klockgether,
Thomas},
title = {{R}egional {B}rain and {S}pinal {C}ord {V}olume {L}oss in
{S}pinocerebellar {A}taxia {T}ype 3.},
journal = {Movement disorders},
volume = {36},
number = {10},
issn = {1531-8257},
address = {New York, NY},
publisher = {Wiley},
reportid = {DZNE-2021-00756},
pages = {2273-2281},
year = {2021},
abstract = {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.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.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.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.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. ©
2021 The Authors. Movement Disorders published by Wiley
Periodicals LLC on behalf of International Parkinson and
Movement Disorder Society.},
keywords = {Brain: diagnostic imaging / Cerebellum / Humans /
Machado-Joseph Disease / Spinocerebellar Ataxias: diagnostic
imaging / Spinocerebellar Ataxias: genetics / MRI (Other) /
biomarker (Other) / spinocerebellar ataxia (Other) /
volumetry (Other)},
cin = {AG Klockgether / AG Gasser 1},
ddc = {610},
cid = {I:(DE-2719)1011001 / I:(DE-2719)1210000},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
experiment = {EXP:(DE-2719)ESMI-20140101},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC9521507},
pubmed = {pmid:33951232},
doi = {10.1002/mds.28610},
url = {https://pub.dzne.de/record/155578},
}