Low frequency centromedian thalamic nuclei deep brain stimulation for the treatment of super refractory status epilepticus: A case report and a review of the literature

Stavropoulos, Ioannis; Selway, Richard; Hasegawa, Harutomo; Hughes, Elaine; Rittey, Chris; Jiménez‐Jiménez, Diego; Valentin, Antonio

doi:10.1016/j.brs.2020.12.013

Cited by 17 publications

(19 citation statements)

References 9 publications

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“…The study is of a single canine, which limits the statistical conclusions, but primarily serves as pilot validation of the implant technology. Although our results are consistent with recent human case studies (Valentín et al, 2012;Sa et al, 2019;Stavropoulos et al, 2021) where the benefit of CMN thalamic stimulation at LF relative to HF was observed providing further support for the clinical value of thalamic LF stimulation, additional tests are needed. We adapted the stimulation based on physiological measurements and chose a higher frequency stimulation for entrainment.…”

Section: Case Limitationssupporting

confidence: 91%

“…For human generalized seizures, the CMN is involved early or late in the seizure and when involved, appears to lead the cortex (Martín-López et al, 2017). Probably for this reason, this nucleus appears to be particularly useful for the treatment of super refractory SE in human patients (Valentín et al, 2012;Sa et al, 2019;Stavropoulos et al, 2021). SE is a serious ictal condition that is considered an emergent situation and can be fatal if these self-sustaining seizures cannot be interrupted.…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2021

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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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Section: Case Limitationssupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…15,17,[20][21][22] DBS has been utilized safely in children specifically for drug-resistant epilepsy, including at least 40 pediatric patients (ages 4-18 years) who have received DBS treatment for epilepsy (see review 23 ). There are a total of eight cases published that report the use of DBS for SRSE, in which seizure frequency decreased following implantation to the CMTN 8,13,24,25 or anterior thalamic nucleus (ATN). [26][27][28] This suggests that DBS may be employed as a rescue therapy to reduce overall morbidity and neurologic insult related to prolonged epileptic activity and sedation.…”

Section: Discussionmentioning

confidence: 99%

“…Most studies report seizure improvement when using frequencies of 130 Hz and 90-120 µsec pulse width. 8,13,24,25 Stavropoulos and colleagues most recently reported patient responsiveness to low-frequency stimulation to the CMTN (6Hz/300 µsec pulse width). 25 Sa and colleagues report using high-frequency (130 Hz) stimulation to mitigate generalized seizures and later low-frequency stimulation (6 Hz) for bifrontal focal seizures, which resulted in a transient reduction.…”

Section: Discussionmentioning

confidence: 99%

Deep brain stimulation of the centromedian thalamic nucleus for the treatment of FIRES

et al. 2021

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Febrile infection-related epilepsy syndrome (FIRES) is a rare, life-threatening complication of febrile illness in previously healthy individuals, who present with a nonspecific febrile illness followed by prolonged, refractory status epilepticus, with a mortality of 12% in children and 16%-27% in adults. 1,2 The consensus definition for FIRES includes the onset of refractory status epilepticus within 24 hours to 2 weeks of a febrile illness and is characteristically nonresponsive to traditional antiseizure medications, anesthetics, and immunotherapy. [1][2][3]

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“…For example, both RNS ( 18 ) and DBS of the thalamus ( 19 ) were initially tested in animal models including pilocarpine-treated rats prior to clinical translation. In addition, direct stimulation of the hippocampus ( 20 ) and the centromedian thalamic nuclei ( 21 ) also reduced seizures in the absence of additional cognitive impairments. Critically, the majority of these studies focused on high frequency stimulation parameters to desynchronize neuronal output and reduce epileptiform activity.…”

Section: Introductionmentioning

confidence: 99%

Early Intervention via Stimulation of the Medial Septal Nucleus Improves Cognition and Alters Markers of Epileptogenesis in Pilocarpine-Induced Epilepsy

et al. 2021

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Over one-third of patients with temporal lobe epilepsy are refractory to medication. In addition, anti-epileptic drugs often exacerbate cognitive comorbidities. Neuromodulation is an FDA treatment for refractory epilepsy, but patients often wait >20 years for a surgical referral for resection or neuromodulation. Using a rodent model, we test the hypothesis that 2 weeks of theta stimulation of the medial septum acutely following exposure to pilocarpine will alter the course of epileptogenesis resulting in persistent behavioral improvements. Electrodes were implanted in the medial septum, dorsal and ventral hippocampus, and the pre-frontal cortex of pilocarpine-treated rats. Rats received 30 min/day of 7.7 Hz or theta burst frequency on days 4–16 post-pilocarpine, prior to the development of spontaneous seizures. Seizure threshold, spikes, and oscillatory activity, as well as spatial and object-based learning, were assessed in the weeks following stimulation. Non-stimulated pilocarpine animals exhibited significantly decreased seizure threshold, increased spikes, and cognitive impairments as compared to vehicle controls. Furthermore, decreased ventral hippocampal power (6–10 Hz) correlated with both the development of spikes and impaired cognition. Measures of spikes, seizure threshold, and cognitive performance in both acute 7.7 Hz and theta burst stimulated animals were statistically similar to vehicle controls when tested during the chronic phase of epilepsy, weeks after stimulation was terminated. These data indicate that modulation of the septohippocampal circuit early after pilocarpine treatment alters the progression of epileptic activity, resulting in elevated seizure thresholds, fewer spikes, and improved cognitive outcome. Results from this study support that septal theta stimulation has the potential to serve in combination or as an alternative to high frequency thalamic stimulation in refractory cases and that further research into early intervention is critical.

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Low frequency centromedian thalamic nuclei deep brain stimulation for the treatment of super refractory status epilepticus: A case report and a review of the literature

Cited by 17 publications

References 9 publications

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

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

Deep brain stimulation of the centromedian thalamic nucleus for the treatment of FIRES

Early Intervention via Stimulation of the Medial Septal Nucleus Improves Cognition and Alters Markers of Epileptogenesis in Pilocarpine-Induced Epilepsy

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