CONTROL OF SYNCHRONIZATION OF BRAIN DYNAMICS LEADS TO CONTROL OF EPILEPTIC SEIZURES IN RODENTS

We have designed and implemented an automated, just-in-time stimulation, seizure control method using a seizure prediction method from nonlinear dynamics coupled with deep brain stimulation in the centromedial thalamic nuclei in epileptic rats. A comparison to periodic stimulation, with identical stimulation parameters, was also performed. The two schemes were compared in terms of their efficacy in control of seizures, as well as their effect on synchronization of brain dynamics. The automated just-in-time (JIT) stimulation showed reduction of seizure frequency and duration in 5 of the 6 rats, with significant reduction of seizure frequency (>50%) in 33% of the rats. This constituted a significant improvement over the efficacy of the periodic control scheme in the same animals. Actually, periodic stimulation showed an increase of seizure frequency in 50% of the rats, reduction of seizure frequency in 3 rats and significant reduction in 1 rat. Importantly, successful seizure control was highly correlated with desynchronization of brain dynamics. This study provides initial evidence for the use of closed-loop feedback control systems in epileptic seizures combining methods from seizure prediction and deep brain stimulation.

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Deep Brain Stimulation in Epilepsy: A Role for Modulation of the Mammillothalamic Tract in Seizure Control?

Neurosurgery ◽

10.1093/neuros/nyaa141 ◽

2020 ◽

Vol 87 (3) ◽

pp. 602-610 ◽

Cited By ~ 4

Author(s):

Frédéric L W V J Schaper ◽

Birgit R Plantinga ◽

Albert J Colon ◽

G Louis Wagner ◽

Paul Boon ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Seizure Frequency ◽

Brain Stimulation ◽

Euclidean Distance ◽

Seizure Control ◽

Hot Spot ◽

Stimulation Site ◽

Heat Maps ◽

Mammillothalamic Tract ◽

Deep Brain

Abstract BACKGROUND Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) can improve seizure control for patients with drug-resistant epilepsy (DRE). Yet, one cannot overlook the high discrepancy in efficacy among patients, possibly resulting from differences in stimulation site. OBJECTIVE To test the hypothesis that stimulation at the junction of the ANT and mammillothalamic tract (ANT-MTT junction) increases seizure control. METHODS The relationship between seizure control and the location of the active contacts to the ANT-MTT junction was investigated in 20 patients treated with ANT-DBS for DRE. Coordinates and Euclidean distance of the active contacts relative to the ANT-MTT junction were calculated and related to seizure control. Stimulation sites were mapped by modelling the volume of tissue activation (VTA) and generating stimulation heat maps. RESULTS After 1 yr of stimulation, patients had a median 46% reduction in total seizure frequency, 50% were responders, and 20% of patients were seizure-free. The Euclidean distance of the active contacts to the ANT-MTT junction correlates to change in seizure frequency (r2 = 0.24, P = .01) and is ∼30% smaller (P = .015) in responders than in non-responders. VTA models and stimulation heat maps indicate a hot-spot at the ANT-MTT junction for responders, whereas non-responders had no evident hot-spot. CONCLUSION Stimulation at the ANT-MTT junction correlates to increased seizure control. Our findings suggest a relationship between the stimulation site and therapy response in ANT-DBS for epilepsy with a potential role for the MTT. DBS directed at white matter merits further exploration for the treatment of epilepsy.

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Uncovering the underlying mechanisms and whole-brain dynamics of deep brain stimulation for Parkinson’s disease

Scientific Reports ◽

10.1038/s41598-017-10003-y ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 30

Author(s):

Victor M. Saenger ◽

Joshua Kahan ◽

Tom Foltynie ◽

Karl Friston ◽

Tipu Z. Aziz ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Brain Dynamics ◽

Whole Brain ◽

Underlying Mechanisms ◽

Deep Brain

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Linking brain dynamics, neural mechanisms, and deep brain stimulation in Parkinson's disease: An integrated perspective

Medical Engineering & Physics ◽

10.1016/j.medengphy.2009.01.005 ◽

2009 ◽

Vol 31 (6) ◽

pp. 615-623 ◽

Cited By ~ 20

Author(s):

Julien Modolo ◽

Anne Beuter

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Neural Mechanisms ◽

Brain Dynamics ◽

Deep Brain

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Anterior Nucleus Deep Brain Stimulation for Refractory Epilepsy

Neurosurgery ◽

10.1227/neu.0000000000001197 ◽

2016 ◽

Vol 78 (6) ◽

pp. 802-811 ◽

Cited By ~ 45

Author(s):

Vibhor Krishna ◽

Nicolas Kon Kam King ◽

Francesco Sammartino ◽

Ido Strauss ◽

Danielle M. Andrade ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Seizure Frequency ◽

Brain Stimulation ◽

Refractory Epilepsy ◽

Term Outcome ◽

Long Term Outcome ◽

Anterior Nucleus ◽

Term Efficacy ◽

Deep Brain

Abstract BACKGROUND: Anterior nucleus (AN) deep brain stimulation (DBS) is a palliative treatment for medically refractory epilepsy. The long-term efficacy and the optimal target localization for AN DBS are not well understood. OBJECTIVE: To analyze the long-term efficacy of AN DBS and its predictors. METHODS: We performed a retrospective review of 16 patients who underwent AN DBS. We selected only patients with reliable seizure frequency data and at least a 1-year follow-up. We studied the duration of the seizure reduction after DBS insertion and before stimulation (the insertional effect) and its association with long-term outcome. We modeled the volume of activation using the active contacts, stimulation parameters, and postoperative imaging. The overlap of this volume was plotted in Montreal Neurological Institute 152 space in 7 patients with significant clinical efficacy. RESULTS: Nine patients reported a decrease in seizure frequency immediately after electrode insertion (insertional or microthalamotomy effect). The duration of insertional effect varied from 2 to 4 months. However, 1 patient had a long-term insertional effect of 36 months. Altogether, 11 patients reported >50% decrease in seizure frequency with long-term stimulation. The most common pattern of seizure control was immediate and sustained stimulation benefit (n = 8). In patients with long-term stimulation benefit, the efficacious target was localized in the anteroventral AN in close proximity to the mammillothalamic tract. CONCLUSION: AN DBS is efficacious in the control of seizure frequency in selected patients. An insertional effect is commonly observed (56%). The most efficacious site of stimulation appears to be the anteroventral AN.

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Deep brain stimulation for seizure control in drug-resistant epilepsy

Neurosurgical FOCUS ◽

10.3171/2018.4.focus1872 ◽

2018 ◽

Vol 45 (2) ◽

pp. E4 ◽

Cited By ~ 13

Author(s):

Neil Klinger ◽

Sandeep Mittal

Keyword(s):

Deep Brain Stimulation ◽

Brain Stimulation ◽

Seizure Control ◽

Effective Means ◽

Drug Resistant ◽

Thalamic Nuclei ◽

Stimulation Parameters ◽

Number Of Patients ◽

Drug Resistant Epilepsy ◽

Deep Brain

Antiepileptic drugs prevent morbidity and death in a large number of patients suffering from epilepsy. However, it is estimated that approximately 30% of epileptic patients will not have adequate seizure control with medication alone. Resection of epileptogenic cortex may be indicated in medically refractory cases with a discrete seizure focus in noneloquent cortex. For patients in whom resection is not an option, deep brain stimulation (DBS) may be an effective means of seizure control. Deep brain stimulation targets for treating seizures primarily include the thalamic nuclei, hippocampus, subthalamic nucleus, and cerebellum. A variety of stimulation parameters have been studied, and more recent advances in electrical stimulation to treat epilepsy include responsive neurostimulation. Data suggest that DBS is effective for treating drug-resistant epilepsy.

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Cerebellar stimulation in the management of medically intractable epilepsy: a systematic and critical review

Neurosurgical FOCUS ◽

10.3171/2010.5.focus10111 ◽

2010 ◽

Vol 29 (2) ◽

pp. E8 ◽

Cited By ~ 28

Author(s):

Kostas N. Fountas ◽

Eftychia Kapsalaki ◽

Georgios Hadjigeorgiou

Keyword(s):

Deep Brain Stimulation ◽

Seizure Frequency ◽

Brain Stimulation ◽

Clinical Studies ◽

Intractable Epilepsy ◽

Implantation Technique ◽

Seizure Outcome ◽

Double Blind ◽

Deep Brain ◽

Cerebellar Stimulation

Object The wide application of deep brain stimulation in the management of movement as well as other degenerative neurological and psychiatric disorders has renewed the interest in using deep brain stimulation in the management of medically intractable epilepsy. Various stimulation targets have been used with significantly varying results in aborting seizure activity. Electrical cerebellar stimulation (CS) has been used for more than 50 years in the management of epilepsy, with conflicting results. In the current study, the authors review the pertinent literature to outline the role of CS in the management of medically refractory epilepsy. Methods The PubMed medical database was systematically searched for the following terms: “cerebellar,” “epilepsy,” “stimulation,” and “treatment,” and all their combinations. Case reports were excluded from this study. Results The pertinent articles were categorized into 2 large groups: animal experimental and human clinical studies. Particular emphasis on the following aspects was given when reviewing the human clinical studies: their methodological characteristics, the number of participants, their seizure types, the implantation technique and its associated complications, the exact stimulation target, the stimulation technique, the seizure outcome, and the patients' psychological and social poststimulation status. Three clinical double-blind studies were found, with similar implantation surgical technique, stimulation target, and stimulation parameters, but quite contradictory results. Two of these studies failed to demonstrate any significant seizure reduction, whereas the third one showed a significant poststimulation decrease in seizure frequency. All possible factors responsible for these differences in the findings are analyzed in the present study. Conclusions Cerebellar stimulation seems to remain a stimulation target worth exploring for defining its potential in the treatment of medically intractable epilepsy, although the data from the double-blind clinical studies that were performed failed to establish a clear benefit in regard to seizure frequency. A large-scale, double-blind clinical study is required for accurately defining the efficacy of CS in epilepsy treatment.

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P.026 Focal DBS of Posterior Cingulate Cortex for Refractory Nonlesional Epilepsy: A Case Report

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2016.131 ◽

2016 ◽

Vol 43 (S2) ◽

pp. S27-S28

Author(s):

AW Wong ◽

F Moien-Afshari

Keyword(s):

Deep Brain Stimulation ◽

Seizure Frequency ◽

Brain Stimulation ◽

Posterior Cingulate Cortex ◽

Focal Lesion ◽

Depth Electrodes ◽

Pet Ct ◽

The Right ◽

Video Eeg ◽

Deep Brain

Background: Deep brain stimulation for epilepsy is becoming an effective option for the treatment of refractory epilepsy. This is the case of a 19-year-old male patient who has had refractory seizures since 2.5 years old. Seizures occur up to 100 times per day, including gelastic, complex partial, and generalized tonic-clonic types. Methods: Continuous video-EEG monitoring, technetium 99 m ECD SPECT, PET-CT and 3T MRI are used for localization. Depth electrodes are implanted in right frontal orbital, cingulate and lateral frontal regions. Results: Video-EEG records 79 seizures arising from the right frontocentral region. Clinically, patient assumes a fencing posture, with left arm extension. Some seizures undergo secondary generalization. SPECT reveals subtle asymmetric hyperperfusion in right mesial frontal area, while PET-CT and MRI do not show focal lesion(s).Stereo-EEG recording and stimulation confirm seizure onset and trigger zone in the premotor cingulate posterior region. Treatment with stimulation in this region at 130-150 Hz, 4-5 mA, and pulse duration 0.1 ms reduces seizure frequency from 100/day to 3/week. Seizures last only 2-3 seconds, without postictal confusion leading to improvements in neuropsychological function. AED dosages are not reduced. Conclusions: Successful intracranial EEG localization of otherwise non-lesional non-resectable seizure focus permits the use of deep brain stimulation that effectively reduces refractory seizure frequency.

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