Inverse associations between cerebellar inhibition and motor impairment in spinocerebellar ataxia type 3
Background: Cerebellar ataxia generally results from a lesion disrupting the corticopontocerebellar or cerebellothalamocortical tract. The cerebellar inhibition (CBI) paradigm represents a dual-coil transcranial magnetic stimulation protocol that interrogates the integrity of the latter pathway. Whe...
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doaj-b145e6e08f32493b94e22544fa7b3d4d2021-03-19T07:23:37ZengElsevierBrain Stimulation1935-861X2021-03-01142351357Inverse associations between cerebellar inhibition and motor impairment in spinocerebellar ataxia type 3Roderick P.P.W.M. Maas0Bart P.C. van de Warrenburg1Dennis J.L.G. Schutter2Department of Neurology, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands; Corresponding author. Department of Neurology, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Reinier Postlaan 4, 6525 GC, Nijmegen, the Netherlands.Department of Neurology, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the NetherlandsExperimental Psychology, Helmholtz Institute, Utrecht University, Utrecht, the NetherlandsBackground: Cerebellar ataxia generally results from a lesion disrupting the corticopontocerebellar or cerebellothalamocortical tract. The cerebellar inhibition (CBI) paradigm represents a dual-coil transcranial magnetic stimulation protocol that interrogates the integrity of the latter pathway. Whether CBI has clinical relevance in ataxia patients remains largely unknown because associations with pertinent disease severity measures in etiologically homogeneous cohorts have not been previously examined. Objective: To investigate if CBI correlates with clinical and functional indices of disease severity in individuals with spinocerebellar ataxia type 3 (SCA3). Methods: CBI was assessed in fourteen SCA3 patients by paired-pulse cerebellar-motor cortex (M1) stimulation using interstimulus intervals of 3, 5, and 10 ms. Correlation coefficients were determined between CBI and ataxia severity, manual dexterity, and walking speed. Results: Suppression of M1 excitability occurred 5 ms following a contralateral cerebellar conditioning stimulus in SCA3 patients, but, on average, CBI was significantly reduced as compared to a healthy control group from the literature (p < 0.001). A significant association was found between decreased CBI levels and higher Scale for the Assessment and Rating of Ataxia (SARA) scores (r = −0.62, p = 0.019). CBI was negatively correlated with axial, appendicular, and speech subscores, as well as with nine-hole peg test performance (r = −0.69, p = 0.006). No association was observed between CBI and walking speed. As expected, there were no significant clinical-neurophysiological correlations at 3 and 10 ms interstimulus intervals. Conclusion: Our results provide the first neurophysiological evidence for an inverse association between cerebellothalamocortical tract integrity, as reflected by reduced levels of CBI, and ataxia severity in SCA3 patients. Longitudinal studies are required to evaluate if CBI could serve as a marker of disease progression.http://www.sciencedirect.com/science/article/pii/S1935861X21000255TMSCerebellar inhibitionSpinocerebellar ataxia type 3Cerebellothalamocortical tractScale for the Assessment and Rating of Ataxia |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Roderick P.P.W.M. Maas Bart P.C. van de Warrenburg Dennis J.L.G. Schutter |
spellingShingle |
Roderick P.P.W.M. Maas Bart P.C. van de Warrenburg Dennis J.L.G. Schutter Inverse associations between cerebellar inhibition and motor impairment in spinocerebellar ataxia type 3 Brain Stimulation TMS Cerebellar inhibition Spinocerebellar ataxia type 3 Cerebellothalamocortical tract Scale for the Assessment and Rating of Ataxia |
author_facet |
Roderick P.P.W.M. Maas Bart P.C. van de Warrenburg Dennis J.L.G. Schutter |
author_sort |
Roderick P.P.W.M. Maas |
title |
Inverse associations between cerebellar inhibition and motor impairment in spinocerebellar ataxia type 3 |
title_short |
Inverse associations between cerebellar inhibition and motor impairment in spinocerebellar ataxia type 3 |
title_full |
Inverse associations between cerebellar inhibition and motor impairment in spinocerebellar ataxia type 3 |
title_fullStr |
Inverse associations between cerebellar inhibition and motor impairment in spinocerebellar ataxia type 3 |
title_full_unstemmed |
Inverse associations between cerebellar inhibition and motor impairment in spinocerebellar ataxia type 3 |
title_sort |
inverse associations between cerebellar inhibition and motor impairment in spinocerebellar ataxia type 3 |
publisher |
Elsevier |
series |
Brain Stimulation |
issn |
1935-861X |
publishDate |
2021-03-01 |
description |
Background: Cerebellar ataxia generally results from a lesion disrupting the corticopontocerebellar or cerebellothalamocortical tract. The cerebellar inhibition (CBI) paradigm represents a dual-coil transcranial magnetic stimulation protocol that interrogates the integrity of the latter pathway. Whether CBI has clinical relevance in ataxia patients remains largely unknown because associations with pertinent disease severity measures in etiologically homogeneous cohorts have not been previously examined. Objective: To investigate if CBI correlates with clinical and functional indices of disease severity in individuals with spinocerebellar ataxia type 3 (SCA3). Methods: CBI was assessed in fourteen SCA3 patients by paired-pulse cerebellar-motor cortex (M1) stimulation using interstimulus intervals of 3, 5, and 10 ms. Correlation coefficients were determined between CBI and ataxia severity, manual dexterity, and walking speed. Results: Suppression of M1 excitability occurred 5 ms following a contralateral cerebellar conditioning stimulus in SCA3 patients, but, on average, CBI was significantly reduced as compared to a healthy control group from the literature (p < 0.001). A significant association was found between decreased CBI levels and higher Scale for the Assessment and Rating of Ataxia (SARA) scores (r = −0.62, p = 0.019). CBI was negatively correlated with axial, appendicular, and speech subscores, as well as with nine-hole peg test performance (r = −0.69, p = 0.006). No association was observed between CBI and walking speed. As expected, there were no significant clinical-neurophysiological correlations at 3 and 10 ms interstimulus intervals. Conclusion: Our results provide the first neurophysiological evidence for an inverse association between cerebellothalamocortical tract integrity, as reflected by reduced levels of CBI, and ataxia severity in SCA3 patients. Longitudinal studies are required to evaluate if CBI could serve as a marker of disease progression. |
topic |
TMS Cerebellar inhibition Spinocerebellar ataxia type 3 Cerebellothalamocortical tract Scale for the Assessment and Rating of Ataxia |
url |
http://www.sciencedirect.com/science/article/pii/S1935861X21000255 |
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