Henry M Skelton, David M Brandman, Katie Bullinger, Faical Isbaine, Robert E Gross
{"title":"Distinct Biomarkers of ANT Stimulation and Seizure Freedom in an Epilepsy Patient with Ambulatory Hippocampal Electrocorticography.","authors":"Henry M Skelton, David M Brandman, Katie Bullinger, Faical Isbaine, Robert E Gross","doi":"10.1159/000533680","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) and responsive neurostimulation (RNS) of the hippocampus are the predominant approaches to brain stimulation for treating mesial temporal lobe epilepsy (MTLE). Both are similarly effective at reducing seizures in drug-resistant patients, but the underlying mechanisms are poorly understood. In rare cases where it is clinically indicated to use RNS and DBS simultaneously, ambulatory electrophysiology from RNS may provide the opportunity to measure the effects of ANT DBS in the putative seizure onset zone and identify biomarkers associated with clinical improvement. Here, one such patient became seizure free, allowing us to identify and compare the changes in hippocampal electrophysiology associated with ANT stimulation and seizure freedom.</p><p><strong>Methods: </strong>Ambulatory electrocorticography and clinical history were retrospectively analyzed for a patient treated with RNS and DBS for MTLE. DBS artifacts were used to identify ANT stimulation periods on RNS recordings and measure peri-stimulus electrographic changes. Clinical history was used to determine the chronic electrographic changes associated with seizure freedom.</p><p><strong>Results: </strong>ANT stimulation acutely suppressed hippocampal gamma (25-90Hz) power, with minimal theta (4-8Hz) suppression and without clear effects on seizure frequency. Eventually, the patient became seizure free alongside the emergence of chronic gamma increase and theta suppression, which started at the same time as clobazam was introduced. Both seizure freedom and the associated electrophysiology persisted after inadvertent DBS discontinuation, further implicating the clobazam relationship. Unexpectedly, RNS detections and long episodes increased, although they were not considered to be electrographic seizures, and the patient remained clinically seizure free.</p><p><strong>Conclusion: </strong>ANT stimulation and seizure freedom were associated with distinct, dissimilar spectral changes in RNS-derived electrophysiology. The time course of these changes supported a new medication as the most likely cause of clinical improvement. Broadly, this work showcases the use of RNS recordings to interpret the effects of multimodal therapy. Specifically, it lends additional credence to hippocampal theta suppression as a biomarker previously associated with seizure reduction in RNS patients.</p>","PeriodicalId":22078,"journal":{"name":"Stereotactic and Functional Neurosurgery","volume":" ","pages":"349-358"},"PeriodicalIF":1.9000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Stereotactic and Functional Neurosurgery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000533680","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/9/22 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"NEUROIMAGING","Score":null,"Total":0}
引用次数: 1
Abstract
Introduction: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) and responsive neurostimulation (RNS) of the hippocampus are the predominant approaches to brain stimulation for treating mesial temporal lobe epilepsy (MTLE). Both are similarly effective at reducing seizures in drug-resistant patients, but the underlying mechanisms are poorly understood. In rare cases where it is clinically indicated to use RNS and DBS simultaneously, ambulatory electrophysiology from RNS may provide the opportunity to measure the effects of ANT DBS in the putative seizure onset zone and identify biomarkers associated with clinical improvement. Here, one such patient became seizure free, allowing us to identify and compare the changes in hippocampal electrophysiology associated with ANT stimulation and seizure freedom.
Methods: Ambulatory electrocorticography and clinical history were retrospectively analyzed for a patient treated with RNS and DBS for MTLE. DBS artifacts were used to identify ANT stimulation periods on RNS recordings and measure peri-stimulus electrographic changes. Clinical history was used to determine the chronic electrographic changes associated with seizure freedom.
Results: ANT stimulation acutely suppressed hippocampal gamma (25-90Hz) power, with minimal theta (4-8Hz) suppression and without clear effects on seizure frequency. Eventually, the patient became seizure free alongside the emergence of chronic gamma increase and theta suppression, which started at the same time as clobazam was introduced. Both seizure freedom and the associated electrophysiology persisted after inadvertent DBS discontinuation, further implicating the clobazam relationship. Unexpectedly, RNS detections and long episodes increased, although they were not considered to be electrographic seizures, and the patient remained clinically seizure free.
Conclusion: ANT stimulation and seizure freedom were associated with distinct, dissimilar spectral changes in RNS-derived electrophysiology. The time course of these changes supported a new medication as the most likely cause of clinical improvement. Broadly, this work showcases the use of RNS recordings to interpret the effects of multimodal therapy. Specifically, it lends additional credence to hippocampal theta suppression as a biomarker previously associated with seizure reduction in RNS patients.
期刊介绍：
''Stereotactic and Functional Neurosurgery'' provides a single source for the reader to keep abreast of developments in the most rapidly advancing subspecialty within neurosurgery. Technological advances in computer-assisted surgery, robotics, imaging and neurophysiology are being applied to clinical problems with ever-increasing rapidity in stereotaxis more than any other field, providing opportunities for new approaches to surgical and radiotherapeutic management of diseases of the brain, spinal cord, and spine. Issues feature advances in the use of deep-brain stimulation, imaging-guided techniques in stereotactic biopsy and craniotomy, stereotactic radiosurgery, and stereotactically implanted and guided radiotherapeutics and biologicals in the treatment of functional and movement disorders, brain tumors, and other diseases of the brain. Background information from basic science laboratories related to such clinical advances provides the reader with an overall perspective of this field. Proceedings and abstracts from many of the key international meetings furnish an overview of this specialty available nowhere else. ''Stereotactic and Functional Neurosurgery'' meets the information needs of both investigators and clinicians in this rapidly advancing field.
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