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An Argument in Favor of Deep Brain Stimulation for Uncommon Movement Disorders: The Case for N-of-1 Trials in Holmes Tremor

Deep brain stimulation (DBS) is part of state-of-the-art treatment for medically refractory Parkinson’s disease, essential tremor or primary dystonia. However, there are multiple movement disorders that present after a static brain lesion and that are frequently refractory to medical treatment. Usin...

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Autores principales: Mendonça, Marcelo, Cotovio, Gonçalo, Barbosa, Raquel, Grunho, Miguel, Oliveira-Maia, Albino J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247189/
https://www.ncbi.nlm.nih.gov/pubmed/35782038
http://dx.doi.org/10.3389/fnhum.2022.921523
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author Mendonça, Marcelo
Cotovio, Gonçalo
Barbosa, Raquel
Grunho, Miguel
Oliveira-Maia, Albino J.
author_facet Mendonça, Marcelo
Cotovio, Gonçalo
Barbosa, Raquel
Grunho, Miguel
Oliveira-Maia, Albino J.
author_sort Mendonça, Marcelo
collection PubMed
description Deep brain stimulation (DBS) is part of state-of-the-art treatment for medically refractory Parkinson’s disease, essential tremor or primary dystonia. However, there are multiple movement disorders that present after a static brain lesion and that are frequently refractory to medical treatment. Using Holmes tremor (HT) as an example, we discuss the effectiveness of currently available treatments and, performing simulations using a Markov Chain approach, propose that DBS with iterative parameter optimization is expected to be more effective than an approach based on sequential trials of pharmacological agents. Since, in DBS studies for HT, the thalamus is a frequently chosen target, using data from previous studies of lesion connectivity mapping in HT, we compared the connectivity of thalamic and non-thalamic targets with a proxy of the HT network, and found a significantly higher connectivity of thalamic DBS targets in HT. The understanding of brain networks provided by analysis of functional connectivity may thus provide an informed framework for proper surgical targeting of individual patients. Based on these findings, we argue that there is an ethical imperative to at least consider surgical options in patients with uncommon movement disorders, while simultaneously providing consistent information regarding the expected effectiveness and risks, even in a scenario of surgical-risk aversion. An approach based on n-of-1 DBS trials may ultimately significantly improve outcomes while informing on optimal therapeutic targets and parameter settings for HT and other disabling and rare movement disorders.
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spelling pubmed-92471892022-07-02 An Argument in Favor of Deep Brain Stimulation for Uncommon Movement Disorders: The Case for N-of-1 Trials in Holmes Tremor Mendonça, Marcelo Cotovio, Gonçalo Barbosa, Raquel Grunho, Miguel Oliveira-Maia, Albino J. Front Hum Neurosci Neuroscience Deep brain stimulation (DBS) is part of state-of-the-art treatment for medically refractory Parkinson’s disease, essential tremor or primary dystonia. However, there are multiple movement disorders that present after a static brain lesion and that are frequently refractory to medical treatment. Using Holmes tremor (HT) as an example, we discuss the effectiveness of currently available treatments and, performing simulations using a Markov Chain approach, propose that DBS with iterative parameter optimization is expected to be more effective than an approach based on sequential trials of pharmacological agents. Since, in DBS studies for HT, the thalamus is a frequently chosen target, using data from previous studies of lesion connectivity mapping in HT, we compared the connectivity of thalamic and non-thalamic targets with a proxy of the HT network, and found a significantly higher connectivity of thalamic DBS targets in HT. The understanding of brain networks provided by analysis of functional connectivity may thus provide an informed framework for proper surgical targeting of individual patients. Based on these findings, we argue that there is an ethical imperative to at least consider surgical options in patients with uncommon movement disorders, while simultaneously providing consistent information regarding the expected effectiveness and risks, even in a scenario of surgical-risk aversion. An approach based on n-of-1 DBS trials may ultimately significantly improve outcomes while informing on optimal therapeutic targets and parameter settings for HT and other disabling and rare movement disorders. Frontiers Media S.A. 2022-06-17 /pmc/articles/PMC9247189/ /pubmed/35782038 http://dx.doi.org/10.3389/fnhum.2022.921523 Text en Copyright © 2022 Mendonça, Cotovio, Barbosa, Grunho and Oliveira-Maia. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Mendonça, Marcelo
Cotovio, Gonçalo
Barbosa, Raquel
Grunho, Miguel
Oliveira-Maia, Albino J.
An Argument in Favor of Deep Brain Stimulation for Uncommon Movement Disorders: The Case for N-of-1 Trials in Holmes Tremor
title An Argument in Favor of Deep Brain Stimulation for Uncommon Movement Disorders: The Case for N-of-1 Trials in Holmes Tremor
title_full An Argument in Favor of Deep Brain Stimulation for Uncommon Movement Disorders: The Case for N-of-1 Trials in Holmes Tremor
title_fullStr An Argument in Favor of Deep Brain Stimulation for Uncommon Movement Disorders: The Case for N-of-1 Trials in Holmes Tremor
title_full_unstemmed An Argument in Favor of Deep Brain Stimulation for Uncommon Movement Disorders: The Case for N-of-1 Trials in Holmes Tremor
title_short An Argument in Favor of Deep Brain Stimulation for Uncommon Movement Disorders: The Case for N-of-1 Trials in Holmes Tremor
title_sort argument in favor of deep brain stimulation for uncommon movement disorders: the case for n-of-1 trials in holmes tremor
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247189/
https://www.ncbi.nlm.nih.gov/pubmed/35782038
http://dx.doi.org/10.3389/fnhum.2022.921523
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