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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2021.734265/full |
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| author | Mayela Zamora Sebastian Meller Filip Kajin James J. Sermon James J. Sermon Robert Toth Moaad Benjaber Moaad Benjaber Derk-Jan Dijk Derk-Jan Dijk Rafal Bogacz Gregory A. Worrell Antonio Valentin Benoit Duchet Holger A. Volk Timothy Denison Timothy Denison |
| author_facet | Mayela Zamora Sebastian Meller Filip Kajin James J. Sermon James J. Sermon Robert Toth Moaad Benjaber Moaad Benjaber Derk-Jan Dijk Derk-Jan Dijk Rafal Bogacz Gregory A. Worrell Antonio Valentin Benoit Duchet Holger A. Volk Timothy Denison Timothy Denison |
| author_sort | Mayela Zamora |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-17T19:44:20Z |
| format | Article |
| id | doaj.art-01ceac76eff94354a975da09d35b3704 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-17T19:44:20Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-01ceac76eff94354a975da09d35b37042022-12-21T21:34:55ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2021-09-011510.3389/fnins.2021.734265734265Case Report: Embedding “Digital Chronotherapy” Into Medical Devices—A Canine Validation for Controlling Status Epilepticus Through Multi-Scale Rhythmic Brain StimulationMayela Zamora0Sebastian Meller1Filip Kajin2James J. Sermon3James J. Sermon4Robert Toth5Moaad Benjaber6Moaad Benjaber7Derk-Jan Dijk8Derk-Jan Dijk9Rafal Bogacz10Gregory A. Worrell11Antonio Valentin12Benoit Duchet13Holger A. Volk14Timothy Denison15Timothy Denison16Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, United KingdomDepartment of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover, Hanover, GermanyDepartment of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover, Hanover, GermanyInstitute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, United KingdomMRC Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United KingdomMRC Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United KingdomInstitute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, United KingdomMRC Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United KingdomSurrey Sleep Research Centre, University of Surrey, Guildford, United KingdomUK Dementia Research Institute, Care Research and Technology Centre, Imperial College London and The University of Surrey, Guildford, United KingdomMRC Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United KingdomDepartment of Neurology, Mayo Clinic, Rochester, MN, United StatesDepartment of Clinical Neurophysiology, King's College Hospital NHS Trust, London, United KingdomMRC Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United KingdomDepartment of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover, Hanover, GermanyInstitute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, United KingdomMRC Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United KingdomCircadian 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.https://www.frontiersin.org/articles/10.3389/fnins.2021.734265/fulldeep brain stimulationcentromedian thalamuscircadianentrainmentepilepsychronotherapy |
| spellingShingle | Mayela Zamora Sebastian Meller Filip Kajin James J. Sermon James J. Sermon Robert Toth Moaad Benjaber Moaad Benjaber Derk-Jan Dijk Derk-Jan Dijk Rafal Bogacz Gregory A. Worrell Antonio Valentin Benoit Duchet Holger A. Volk Timothy Denison Timothy Denison Case Report: Embedding “Digital Chronotherapy” Into Medical Devices—A Canine Validation for Controlling Status Epilepticus Through Multi-Scale Rhythmic Brain Stimulation Frontiers in Neuroscience deep brain stimulation centromedian thalamus circadian entrainment epilepsy chronotherapy |
| 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 | deep brain stimulation centromedian thalamus circadian entrainment epilepsy chronotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2021.734265/full |
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