Functional neuroplasticity in response to cerebello-thalamic injury underpins the clinical presentation of tremor in multiple sclerosis

Frederique M.C. Boonstra, Gustavo Noffs, Thushara Perera, Vilija G. Jokubaitis, Adam P. Vogel, Bradford A. Moffat, Helmut Butzkueven, Andrew Evans, Anneke van der Walt, Scott C. Kolbe

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Tremor is present in almost half of multiple sclerosis (MS) patients. The lack of understanding of its pathophysiology is hampering progress in development of treatments. Objectives: To clarify the structural and functional brain changes associated with the clinical phenotype of upper limb tremor in people with MS. Methods: Fifteen healthy controls (46.1 ± 15.4 years), 27 MS participants without tremor (46.7 ± 11.6 years) and 42 with tremor (46.6 ± 11.5 years) were included. Tremor was quantified using the Bain score (0–10) for overall severity, handwriting and Archimedes spiral drawing. Functional magnetic resonance imaging activations were compared between participants groups during performance of a joystick task designed to isolate tremulous movement. Inflammation and atrophy of cerebello-thalamo-cortical brain structures were quantified. Results: Tremor participants were found to have atrophy of the cerebellum and thalamus, and higher ipsilateral cerebellar lesion load compared to participants without tremor (p < 0.020). We found higher ipsilateral activation in the inferior parietal lobule, the premotor cortex and supplementary motor area in MS tremor participants compared to MS participants without tremor during the joystick task. Finally, stronger activation in those areas was associated with lower tremor severity. Conclusion: Subcortical neurodegeneration and inflammation along the cerebello-thalamo-cortical and cortical functional neuroplasticity contribute to the severity of tremor in MS.

Original languageEnglish
Number of pages10
JournalMultiple Sclerosis Journal
DOIs
Publication statusAccepted/In press - 1 Jan 2019

Keywords

  • functional magnetic resonance imaging
  • magnetic resonance imaging
  • Multiple sclerosis

Cite this

@article{b9da600c8d7140bb8ea543db892a1477,
title = "Functional neuroplasticity in response to cerebello-thalamic injury underpins the clinical presentation of tremor in multiple sclerosis",
abstract = "Background: Tremor is present in almost half of multiple sclerosis (MS) patients. The lack of understanding of its pathophysiology is hampering progress in development of treatments. Objectives: To clarify the structural and functional brain changes associated with the clinical phenotype of upper limb tremor in people with MS. Methods: Fifteen healthy controls (46.1 ± 15.4 years), 27 MS participants without tremor (46.7 ± 11.6 years) and 42 with tremor (46.6 ± 11.5 years) were included. Tremor was quantified using the Bain score (0–10) for overall severity, handwriting and Archimedes spiral drawing. Functional magnetic resonance imaging activations were compared between participants groups during performance of a joystick task designed to isolate tremulous movement. Inflammation and atrophy of cerebello-thalamo-cortical brain structures were quantified. Results: Tremor participants were found to have atrophy of the cerebellum and thalamus, and higher ipsilateral cerebellar lesion load compared to participants without tremor (p < 0.020). We found higher ipsilateral activation in the inferior parietal lobule, the premotor cortex and supplementary motor area in MS tremor participants compared to MS participants without tremor during the joystick task. Finally, stronger activation in those areas was associated with lower tremor severity. Conclusion: Subcortical neurodegeneration and inflammation along the cerebello-thalamo-cortical and cortical functional neuroplasticity contribute to the severity of tremor in MS.",
keywords = "functional magnetic resonance imaging, magnetic resonance imaging, Multiple sclerosis",
author = "Boonstra, {Frederique M.C.} and Gustavo Noffs and Thushara Perera and Jokubaitis, {Vilija G.} and Vogel, {Adam P.} and Moffat, {Bradford A.} and Helmut Butzkueven and Andrew Evans and {van der Walt}, Anneke and Kolbe, {Scott C.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1177/1352458519837706",
language = "English",
journal = "Multiple Sclerosis Journal",
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Functional neuroplasticity in response to cerebello-thalamic injury underpins the clinical presentation of tremor in multiple sclerosis. / Boonstra, Frederique M.C.; Noffs, Gustavo; Perera, Thushara; Jokubaitis, Vilija G.; Vogel, Adam P.; Moffat, Bradford A.; Butzkueven, Helmut; Evans, Andrew; van der Walt, Anneke; Kolbe, Scott C.

In: Multiple Sclerosis Journal, 01.01.2019.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Functional neuroplasticity in response to cerebello-thalamic injury underpins the clinical presentation of tremor in multiple sclerosis

AU - Boonstra, Frederique M.C.

AU - Noffs, Gustavo

AU - Perera, Thushara

AU - Jokubaitis, Vilija G.

AU - Vogel, Adam P.

AU - Moffat, Bradford A.

AU - Butzkueven, Helmut

AU - Evans, Andrew

AU - van der Walt, Anneke

AU - Kolbe, Scott C.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Tremor is present in almost half of multiple sclerosis (MS) patients. The lack of understanding of its pathophysiology is hampering progress in development of treatments. Objectives: To clarify the structural and functional brain changes associated with the clinical phenotype of upper limb tremor in people with MS. Methods: Fifteen healthy controls (46.1 ± 15.4 years), 27 MS participants without tremor (46.7 ± 11.6 years) and 42 with tremor (46.6 ± 11.5 years) were included. Tremor was quantified using the Bain score (0–10) for overall severity, handwriting and Archimedes spiral drawing. Functional magnetic resonance imaging activations were compared between participants groups during performance of a joystick task designed to isolate tremulous movement. Inflammation and atrophy of cerebello-thalamo-cortical brain structures were quantified. Results: Tremor participants were found to have atrophy of the cerebellum and thalamus, and higher ipsilateral cerebellar lesion load compared to participants without tremor (p < 0.020). We found higher ipsilateral activation in the inferior parietal lobule, the premotor cortex and supplementary motor area in MS tremor participants compared to MS participants without tremor during the joystick task. Finally, stronger activation in those areas was associated with lower tremor severity. Conclusion: Subcortical neurodegeneration and inflammation along the cerebello-thalamo-cortical and cortical functional neuroplasticity contribute to the severity of tremor in MS.

AB - Background: Tremor is present in almost half of multiple sclerosis (MS) patients. The lack of understanding of its pathophysiology is hampering progress in development of treatments. Objectives: To clarify the structural and functional brain changes associated with the clinical phenotype of upper limb tremor in people with MS. Methods: Fifteen healthy controls (46.1 ± 15.4 years), 27 MS participants without tremor (46.7 ± 11.6 years) and 42 with tremor (46.6 ± 11.5 years) were included. Tremor was quantified using the Bain score (0–10) for overall severity, handwriting and Archimedes spiral drawing. Functional magnetic resonance imaging activations were compared between participants groups during performance of a joystick task designed to isolate tremulous movement. Inflammation and atrophy of cerebello-thalamo-cortical brain structures were quantified. Results: Tremor participants were found to have atrophy of the cerebellum and thalamus, and higher ipsilateral cerebellar lesion load compared to participants without tremor (p < 0.020). We found higher ipsilateral activation in the inferior parietal lobule, the premotor cortex and supplementary motor area in MS tremor participants compared to MS participants without tremor during the joystick task. Finally, stronger activation in those areas was associated with lower tremor severity. Conclusion: Subcortical neurodegeneration and inflammation along the cerebello-thalamo-cortical and cortical functional neuroplasticity contribute to the severity of tremor in MS.

KW - functional magnetic resonance imaging

KW - magnetic resonance imaging

KW - Multiple sclerosis

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U2 - 10.1177/1352458519837706

DO - 10.1177/1352458519837706

M3 - Article

JO - Multiple Sclerosis Journal

JF - Multiple Sclerosis Journal

SN - 1352-4585

ER -