Delineating cerebellar mechanisms in DYT11 myoclonus-dystonia

Anna Sadnicka; Joseph M Galea; Jui-Cheng Chen; Thomas T Warner; Kailash P Bhatia; John C Rothwell; Mark J Edwards

doi:10.1002/mds.27517

Delineating cerebellar mechanisms in DYT11 myoclonus-dystonia

Anna Sadnicka, Joseph M Galea, Jui-Cheng Chen, Thomas T Warner, Kailash P Bhatia, John C Rothwell, Mark J Edwards

Psychology

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

135 Downloads (Pure)

Abstract

BACKGROUND: Recent research has highlighted the role of the cerebellum in the pathophysiology of myoclonus-dystonia syndrome as a result of mutations in the ɛ-sarcoglycan gene (DYT11). Specifically, a cerebellar-dependent saccadic adaptation task is dramatically impaired in this patient group.

OBJECTIVES: The objective of this study was to investigate whether saccadic deficits coexist with impairments of limb adaptation to provide a potential mechanism linking cerebellar dysfunction to the movement disorder within symptomatic body regions.

METHODS: Limb adaptation to visuomotor (visual feedback rotated by 30°) and forcefield (force applied by robot to deviate arm) perturbations were examined in 5 patients with DYT11 and 10 aged-matched controls.

RESULTS: Patients with DYT11 successfully adapted to both types of perturbation. Modelled and averaged summary metrics that captured adaptation behaviors were equivalent to the control group across conditions.

CONCLUSIONS: DYT11 is not characterized by a uniform deficit in adaptation. The previously observed large deficit in saccadic adaption is not reflected in an equivalent deficit in limb adaptation in symptomatic body regions. We suggest potential mechanisms at the root of this discordance and identify key research questions that need future study.

Original language	English
Number of pages	6
Journal	Movement Disorders
Early online date	17 Oct 2018
DOIs	https://doi.org/10.1002/mds.27517
Publication status	E-pub ahead of print - 17 Oct 2018

Keywords

Dystonia
DYT11
cerebellum
adaptation
ɛ‐sarcoglycan

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Anna_Sadnicka_et_al_Delineating_cerebellar_mechanisms_in_DYT11_myoclonus-dystonia_Movement_Disorders_2018
Checked for eligibility: 24/10/2018 This is the peer reviewed version of the following article: Sadnicka, A., Galea, J.M., Chen, J.C., Warner, T.T., Bhatia, K.P., Rothwell, J.C. and Edwards, M.J., 2018. Delineating cerebellar mechanisms in DYT11 myoclonus‐dystonia. Movement Disorders., which has been published in final form at https://doi.org/10.1002/mds.27517. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Accepted author manuscript, 1.5 MBLicence: Other (please specify with Rights Statement)

https://onlinelibrary.wiley.com/doi/abs/10.1002/mds.27517Licence: None: All rights reserved

Cite this

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title = "Delineating cerebellar mechanisms in DYT11 myoclonus-dystonia",

abstract = "BACKGROUND: Recent research has highlighted the role of the cerebellum in the pathophysiology of myoclonus-dystonia syndrome as a result of mutations in the ɛ-sarcoglycan gene (DYT11). Specifically, a cerebellar-dependent saccadic adaptation task is dramatically impaired in this patient group.OBJECTIVES: The objective of this study was to investigate whether saccadic deficits coexist with impairments of limb adaptation to provide a potential mechanism linking cerebellar dysfunction to the movement disorder within symptomatic body regions.METHODS: Limb adaptation to visuomotor (visual feedback rotated by 30°) and forcefield (force applied by robot to deviate arm) perturbations were examined in 5 patients with DYT11 and 10 aged-matched controls.RESULTS: Patients with DYT11 successfully adapted to both types of perturbation. Modelled and averaged summary metrics that captured adaptation behaviors were equivalent to the control group across conditions.CONCLUSIONS: DYT11 is not characterized by a uniform deficit in adaptation. The previously observed large deficit in saccadic adaption is not reflected in an equivalent deficit in limb adaptation in symptomatic body regions. We suggest potential mechanisms at the root of this discordance and identify key research questions that need future study.",

keywords = "Dystonia, DYT11, cerebellum, adaptation, ɛ‐sarcoglycan",

author = "Anna Sadnicka and Galea, {Joseph M} and Jui-Cheng Chen and Warner, {Thomas T} and Bhatia, {Kailash P} and Rothwell, {John C} and Edwards, {Mark J}",

note = "{\textcopyright} 2018 International Parkinson and Movement Disorder Society.",

year = "2018",

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doi = "10.1002/mds.27517",

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AU - Sadnicka, Anna

AU - Galea, Joseph M

AU - Chen, Jui-Cheng

AU - Warner, Thomas T

AU - Bhatia, Kailash P

AU - Rothwell, John C

AU - Edwards, Mark J

PY - 2018/10/17

Y1 - 2018/10/17

N2 - BACKGROUND: Recent research has highlighted the role of the cerebellum in the pathophysiology of myoclonus-dystonia syndrome as a result of mutations in the ɛ-sarcoglycan gene (DYT11). Specifically, a cerebellar-dependent saccadic adaptation task is dramatically impaired in this patient group.OBJECTIVES: The objective of this study was to investigate whether saccadic deficits coexist with impairments of limb adaptation to provide a potential mechanism linking cerebellar dysfunction to the movement disorder within symptomatic body regions.METHODS: Limb adaptation to visuomotor (visual feedback rotated by 30°) and forcefield (force applied by robot to deviate arm) perturbations were examined in 5 patients with DYT11 and 10 aged-matched controls.RESULTS: Patients with DYT11 successfully adapted to both types of perturbation. Modelled and averaged summary metrics that captured adaptation behaviors were equivalent to the control group across conditions.CONCLUSIONS: DYT11 is not characterized by a uniform deficit in adaptation. The previously observed large deficit in saccadic adaption is not reflected in an equivalent deficit in limb adaptation in symptomatic body regions. We suggest potential mechanisms at the root of this discordance and identify key research questions that need future study.

AB - BACKGROUND: Recent research has highlighted the role of the cerebellum in the pathophysiology of myoclonus-dystonia syndrome as a result of mutations in the ɛ-sarcoglycan gene (DYT11). Specifically, a cerebellar-dependent saccadic adaptation task is dramatically impaired in this patient group.OBJECTIVES: The objective of this study was to investigate whether saccadic deficits coexist with impairments of limb adaptation to provide a potential mechanism linking cerebellar dysfunction to the movement disorder within symptomatic body regions.METHODS: Limb adaptation to visuomotor (visual feedback rotated by 30°) and forcefield (force applied by robot to deviate arm) perturbations were examined in 5 patients with DYT11 and 10 aged-matched controls.RESULTS: Patients with DYT11 successfully adapted to both types of perturbation. Modelled and averaged summary metrics that captured adaptation behaviors were equivalent to the control group across conditions.CONCLUSIONS: DYT11 is not characterized by a uniform deficit in adaptation. The previously observed large deficit in saccadic adaption is not reflected in an equivalent deficit in limb adaptation in symptomatic body regions. We suggest potential mechanisms at the root of this discordance and identify key research questions that need future study.

KW - Dystonia

KW - DYT11

KW - cerebellum

KW - adaptation

KW - ɛ‐sarcoglycan

U2 - 10.1002/mds.27517

DO - 10.1002/mds.27517

M3 - Article

C2 - 30334277

SN - 0885-3185

JO - Movement Disorders

JF - Movement Disorders

ER -

Delineating cerebellar mechanisms in DYT11 myoclonus-dystonia

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Keywords

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