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Case Report: Embedding “Digital Chronotherapy” Into Medical Devices—A Canine Validation for Controlling Status Epilepticus Through Multi-Scale Rhythmic Brain Stimulation

Circadian and other physiological rhythms play a key role in both normal homeostasis and disease processes. Such is the case of circadian and infradian seizure patterns observed in epilepsy. However, these rhythms are not fully exploited in the design of active implantable medical devices. In this p...

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Autores principales: Zamora, Mayela, Meller, Sebastian, Kajin, Filip, Sermon, James J., Toth, Robert, Benjaber, Moaad, Dijk, Derk-Jan, Bogacz, Rafal, Worrell, Gregory A., Valentin, Antonio, Duchet, Benoit, Volk, Holger A., Denison, Timothy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498587/
https://www.ncbi.nlm.nih.gov/pubmed/34630021
http://dx.doi.org/10.3389/fnins.2021.734265
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author Zamora, Mayela
Meller, Sebastian
Kajin, Filip
Sermon, James J.
Toth, Robert
Benjaber, Moaad
Dijk, Derk-Jan
Bogacz, Rafal
Worrell, Gregory A.
Valentin, Antonio
Duchet, Benoit
Volk, Holger A.
Denison, Timothy
author_facet Zamora, Mayela
Meller, Sebastian
Kajin, Filip
Sermon, James J.
Toth, Robert
Benjaber, Moaad
Dijk, Derk-Jan
Bogacz, Rafal
Worrell, Gregory A.
Valentin, Antonio
Duchet, Benoit
Volk, Holger A.
Denison, Timothy
author_sort Zamora, Mayela
collection PubMed
description Circadian and other physiological rhythms play a key role in both normal homeostasis and disease processes. Such is the case of circadian and infradian seizure patterns observed in epilepsy. However, these rhythms are not fully exploited in the design of active implantable medical devices. In this paper we explore a new implantable stimulator that implements chronotherapy as a feedforward input to supplement both open-loop and closed-loop methods. This integrated algorithm allows for stimulation to be adjusted to the ultradian, circadian and infradian patterns observed in patients through slowly-varying temporal adjustments of stimulation and algorithm sub-components, while also enabling adaption of stimulation based on immediate physiological needs such as a breakthrough seizure or change of posture. Embedded physiological sensors in the stimulator can be used to refine the baseline stimulation circadian pattern as a “digital zeitgeber,” i.e., a source of stimulus that entrains or synchronizes the subject's natural rhythms. This algorithmic approach is tested on a canine with severe drug-resistant idiopathic generalized epilepsy exhibiting a characteristic diurnal pattern correlated with sleep-wake cycles. Prior to implantation, the canine's cluster seizures evolved to status epilepticus (SE) and required emergency pharmacological intervention. The cranially-mounted system was fully-implanted bilaterally into the centromedian nucleus of the thalamus. Using combinations of time-based modulation, thalamocortical rhythm-specific tuning of frequency parameters as well as fast-adaptive modes based on activity, the canine experienced no further SE events post-implant as of the time of writing (7 months). Importantly, no significant cluster seizures have been observed either, allowing the reduction of rescue medication. The use of digitally-enabled chronotherapy as a feedforward signal to augment adaptive neurostimulators could prove a useful algorithmic method in conditions where sensitivity to temporal patterns are characteristics of the disease state, providing a novel mechanism for tailoring a more patient-specific therapy approach.
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spelling pubmed-84985872021-10-09 Case Report: Embedding “Digital Chronotherapy” Into Medical Devices—A Canine Validation for Controlling Status Epilepticus Through Multi-Scale Rhythmic Brain Stimulation Zamora, Mayela Meller, Sebastian Kajin, Filip Sermon, James J. Toth, Robert Benjaber, Moaad Dijk, Derk-Jan Bogacz, Rafal Worrell, Gregory A. Valentin, Antonio Duchet, Benoit Volk, Holger A. Denison, Timothy Front Neurosci Neuroscience Circadian and other physiological rhythms play a key role in both normal homeostasis and disease processes. Such is the case of circadian and infradian seizure patterns observed in epilepsy. However, these rhythms are not fully exploited in the design of active implantable medical devices. In this paper we explore a new implantable stimulator that implements chronotherapy as a feedforward input to supplement both open-loop and closed-loop methods. This integrated algorithm allows for stimulation to be adjusted to the ultradian, circadian and infradian patterns observed in patients through slowly-varying temporal adjustments of stimulation and algorithm sub-components, while also enabling adaption of stimulation based on immediate physiological needs such as a breakthrough seizure or change of posture. Embedded physiological sensors in the stimulator can be used to refine the baseline stimulation circadian pattern as a “digital zeitgeber,” i.e., a source of stimulus that entrains or synchronizes the subject's natural rhythms. This algorithmic approach is tested on a canine with severe drug-resistant idiopathic generalized epilepsy exhibiting a characteristic diurnal pattern correlated with sleep-wake cycles. Prior to implantation, the canine's cluster seizures evolved to status epilepticus (SE) and required emergency pharmacological intervention. The cranially-mounted system was fully-implanted bilaterally into the centromedian nucleus of the thalamus. Using combinations of time-based modulation, thalamocortical rhythm-specific tuning of frequency parameters as well as fast-adaptive modes based on activity, the canine experienced no further SE events post-implant as of the time of writing (7 months). Importantly, no significant cluster seizures have been observed either, allowing the reduction of rescue medication. The use of digitally-enabled chronotherapy as a feedforward signal to augment adaptive neurostimulators could prove a useful algorithmic method in conditions where sensitivity to temporal patterns are characteristics of the disease state, providing a novel mechanism for tailoring a more patient-specific therapy approach. Frontiers Media S.A. 2021-09-24 /pmc/articles/PMC8498587/ /pubmed/34630021 http://dx.doi.org/10.3389/fnins.2021.734265 Text en Copyright © 2021 Zamora, Meller, Kajin, Sermon, Toth, Benjaber, Dijk, Bogacz, Worrell, Valentin, Duchet, Volk and Denison. 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
Zamora, Mayela
Meller, Sebastian
Kajin, Filip
Sermon, James J.
Toth, Robert
Benjaber, Moaad
Dijk, Derk-Jan
Bogacz, Rafal
Worrell, Gregory A.
Valentin, Antonio
Duchet, Benoit
Volk, Holger A.
Denison, Timothy
Case Report: Embedding “Digital Chronotherapy” Into Medical Devices—A Canine Validation for Controlling Status Epilepticus Through Multi-Scale Rhythmic Brain Stimulation
title Case Report: Embedding “Digital Chronotherapy” Into Medical Devices—A Canine Validation for Controlling Status Epilepticus Through Multi-Scale Rhythmic Brain Stimulation
title_full Case Report: Embedding “Digital Chronotherapy” Into Medical Devices—A Canine Validation for Controlling Status Epilepticus Through Multi-Scale Rhythmic Brain Stimulation
title_fullStr Case Report: Embedding “Digital Chronotherapy” Into Medical Devices—A Canine Validation for Controlling Status Epilepticus Through Multi-Scale Rhythmic Brain Stimulation
title_full_unstemmed Case Report: Embedding “Digital Chronotherapy” Into Medical Devices—A Canine Validation for Controlling Status Epilepticus Through Multi-Scale Rhythmic Brain Stimulation
title_short Case Report: Embedding “Digital Chronotherapy” Into Medical Devices—A Canine Validation for Controlling Status Epilepticus Through Multi-Scale Rhythmic Brain Stimulation
title_sort case report: embedding “digital chronotherapy” into medical devices—a canine validation for controlling status epilepticus through multi-scale rhythmic brain stimulation
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498587/
https://www.ncbi.nlm.nih.gov/pubmed/34630021
http://dx.doi.org/10.3389/fnins.2021.734265
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