Hippocampal Depth Electrodes in Epilepsy Surgery: Diagnostic or Damaging?
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ABSTRACT:
SUBMITTER: Drane DL
PROVIDER: S-EPMC5887612 | biostudies-literature | 2018 Mar-Apr
REPOSITORIES: biostudies-literature
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Hippocampal Depth Electrodes in Epilepsy Surgery: Diagnostic or Damaging?
Drane Daniel L DL Gross Robert E RE
Epilepsy currents 20180301 2
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Project description:Samples used in the study originated from three UK sites: the Walton Centre for Neurology and Neurosurgery in Liverpool, the Salford Royal Hospital in Salford and the Southern General Hospital in Glasgow. We recruited patients with pharmacoresistant mesial temporal lobe epilepsy for whom a therapeutic temporal lobectomy was being undertaken. After surgery, the hippocampus was divided into two portions: (1) one portion was preserved for RNA isolation, and (2) the other portion underwent histological analysis by an experienced neuropathologist. Frozen post-mortem histologically-normal hippocampal samples from donors with no known brain diseases were obtained from the MRC Edinburgh Brain Bank (Edinburgh, UK) and the Queen Square Brain Bank (London, UK). Brain samples were disrupted and homogenized in an appropriate volume of QIAzol lysis reagent (Qiagen, Crawley, United Kingdom) by using a TissueRuptor handheld rotor-stator homogenizer (Qiagen, Crawley, United Kingdom). Total RNA was extracted from the homogenates using the RNeasy Lipid Tissue Mini Kit (Qiagen, Crawley, United Kingdom), according to the manufacturer’s instructions. RNA quality was examined by capillary electrophoresis on an Agilent Bioanalyzer 2100 (Agilent, Palo Alto, CA) and Agilent 2100 Expert software was used to calculate the RNA Integrity number (RIN) of each sample. Purity of the RNA sample was assessed using a NanoDrop1000 Spectrophotometer. Capillary electrophoresis traces were also examined. Samples with RNA integrity number scores (RIN) below 6, obvious RNA degradation, significant 18S or 28S ribosomal RNA degradation, ratio of absorbance at 260nm and 280nm <1.95, or with noticeable DNA or background contaminants did not pass QC, and were withheld from microarray analysis. The microarrays were processed at the Centre for Genomics Research in the University of Liverpool (http://www.liv.ac.uk/genomic-research/). 50ng of total RNA was amplified and labelled using the Agilent Low Input Quick Amp One-Colour Labeling Kit and labelled RNA was hybridized to Agilent SurePrint G3 Custom Exon 8x60K Microarrays designed to contain probes for each exon of 936 selected genes, including all known SLC genes. Standard Agilent protocols were followed. One array failed on five of the QC criteria and, hence, was excluded. Intensity data were extracted from the remaining arrays using the Feature Extraction Software, in line with the manufacturer’s recommendations. The uploaded files contain data both for a custom exon array designed to contain probes for each exon of 936 selected genes and for a custom gene expression array designed to contain gene expression probes for genes across the whole genome.
2015-08-01 | E-MTAB-3123 | biostudies-arrayexpress
Project description:Depth intracranial electrodes (IEs) placement is one of the most used procedures to identify the epileptogenic zone (EZ) in surgical treatment of drug resistant epilepsy patients, about 20-30% of this population. IEs localization is therefore a critical issue defining the EZ and its relation with eloquent functional areas. That information is then used to target the resective surgery and has great potential to affect outcome. We designed a methodological procedure intended to avoid the need for highly specialized medical resources and reduce time to identify the anatomical location of IEs, during the first instances of intracranial EEG recordings. This workflow is based on established open source software; 3D Slicer and Freesurfer that uses MRI and Post-implant CT fusion for the localization of IEs and its relation with automatic labeled surrounding cortex. To test this hypothesis we assessed the time elapsed between the surgical implantation process and the final anatomical localization of IEs by means of our proposed method compared against traditional visual analysis of raw post-implant imaging in two groups of patients. All IEs were identified in the first 24 H (6-24 H) of implantation using our method in 4 patients of the first group. For the control group; all IEs were identified by experts with an overall time range of 36 h to 3 days using traditional visual analysis. It included (7 patients), 3 patients implanted with IEs and the same 4 patients from the first group. Time to localization was restrained in this group by the specialized personnel and the image quality available. To validate our method; we trained two inexperienced operators to assess the position of IEs contacts on four patients (5 IEs) using the proposed method. We quantified the discrepancies between operators and we also assessed the efficiency of our method to define the EZ comparing the findings against the results of traditional analysis.
| S-EPMC3876273 | biostudies-literature
Project description:Epilepsy is potentially curable with resective surgery if the epileptogenic zone (EZ) can be identified. If non-invasive imaging is unable to elucidate the EZ, intracranial electrodes may be implanted to identify the EZ as well as map cortical function. In current clinical practice, each electrode trajectory is determined by time-consuming manual inspection of preoperative imaging to find a path that avoids blood vessels while traversing appropriate deep and superficial regions of interest (ROIs). We present anatomy-driven multiple trajectory planning (ADMTP) to find safe trajectories from a list of user-defined ROIs within minutes rather than the hours required for manual planning.Electrode trajectories are automatically computed in three steps: (1) Target Point Selection to identify appropriate target points within each ROI; (2) Trajectory Risk Scoring to quantify the cumulative distance to critical structures (blood vessels) along each trajectory, defined as the skull entry point to target point. (3) Implantation Plan Computation: to determine a feasible combination of low-risk trajectories for all electrodes.ADMTP was evaluated on 20 patients (190 electrodes). ADMTP lowered the quantitative risk score in 83% of electrodes. Qualitative results show ADMTP found suitable trajectories for 70% of electrodes; a similar portion of manual trajectories were considered suitable. Trajectory suitability for ADMTP was 95% if traversing sulci was not included in the safety criteria. ADMTP is computationally efficient, computing between 7 and 12 trajectories in 54.5 (17.3-191.9) s.ADMTP efficiently compute safe and surgically feasible electrode trajectories.
| S-EPMC5541140 | biostudies-other
Project description:In patients with drug-resistant epilepsy who are considering surgery, intracranial EEG (iEEG) helps delineate the putative epileptogenic zone. In a minority of patients, iEEG fails to identify seizure onsets. In such cases, it might be worthwhile to reimplant more iEEG electrodes. The consequences of such a strategy for the patient are unknown. We matched 12 patients in whom the initially implanted iEEG electrodes did not delineate the seizure onset zone precisely enough to offer resective surgery, and in whom additional iEEG electrodes were implanted during the same inpatient stay, to controls who did not undergo reimplantation. Seven cases and eight controls proceeded to resective surgery. No intracranial infection occurred. One control suffered an intracranial hemorrhage. Three cases and two controls suffered from a post-operative neurological or neuropsychological deficit. We found no difference in post-operative seizure control between cases and controls. Compared to an ILAE score of 5 (ie, stable seizure frequency in the absence of resective surgery), cases showed significant improvement. Reimplantation of iEEG electrodes can offer the possibility of resective epilepsy surgery to patients in whom the initial iEEG investigation was inconclusive, without compromising on the risk of complications or seizure control.
| S-EPMC10690689 | biostudies-literature
Project description:In this study, we quantified the coverage of gray and white matter during intracranial electroencephalography in a cohort of epilepsy patients with surface and depth electrodes. We included 65 patients with strip electrodes (n = 12), strip and grid electrodes (n = 24), strip, grid, and depth electrodes (n = 7), or depth electrodes only (n = 22). Patient-specific imaging was used to generate probabilistic gray and white matter maps and atlas segmentations. Gray and white matter coverage was quantified using spherical volumes centered on electrode centroids, with radii ranging from 1 to 15 mm, along with detailed finite element models of local electric fields. Gray matter coverage was highly dependent on the chosen radius of influence (RoI). Using a 2.5 mm RoI, depth electrodes covered more gray matter than surface electrodes; however, surface electrodes covered more gray matter at RoI larger than 4 mm. White matter coverage and amygdala and hippocampal coverage was greatest for depth electrodes at all RoIs. This study provides the first probabilistic analysis to quantify coverage for different intracranial recording configurations. Depth electrodes offer increased coverage of gray matter over other recording strategies if the desired signals are local, while subdural grids and strips sample more gray matter if the desired signals are diffuse.
| S-EPMC8683494 | biostudies-literature
Project description:Background and purposeWe analyzed the association of neuropsychological outcomes after epilepsy surgery with the intracranial electrode type (stereo electroencephalography [SEEG] and subdural electrodes [SDE]), and electrical stimulation mapping (ESM) of speech/language.MethodsDrug-resistant epilepsy patients who underwent comprehensive neuropsychological evaluation before and 1 year after epilepsy surgery were included. SEEG and SDE subgroups were matched by age, handedness, operated hemisphere, and seizure freedom. Postsurgical neuropsychological outcomes (adjusted for presurgical scores) and reliable change indices were analyzed as functions of electrode type and ESM.ResultsNinety-nine patients aged 6-29 years were included with similar surgical resection/ablation volumes in the SEEG and SDE subgroups. Most of the neuropsychological outcomes were comparable between SEEG and SDE subgroups; however, Working Memory and Processing Speed were significantly improved in the SEEG subgroup. Undergoing language ESM was associated with significant improvements in Spelling, Letter-Word Identification, Vocabulary, Verbal Comprehension, Verbal Learning, and Story Memory scores, but a decline in Calculation scores.ConclusionsIntracranial evaluations with SEEG and SDE are comparable in terms of long-term postsurgical neuropsychological outcomes. Our data suggest that SEEG may be associated with improvements in working memory and processing speed, representing cognitive domains served by spatially distributed networks. Our study also supports wider use of language ESM before epilepsy surgery, preferably using other language tasks in addition to visual naming. Rather than the type of electrode, postsurgical neuropsychological outcomes are driven by whether language ESM was performed or not, with beneficial effects of language mapping.
| S-EPMC10529267 | biostudies-literature
Project description:Resected hippocampal tissue from patients with drug-resistant epilepsy presents a unique possibility to test novel treatment strategies directly in target tissue. The post-resection time for testing and analysis however is normally limited. Acute tissue slices allow for electrophysiological recordings typically up to 12 hours. To enable longer time to test novel treatment strategies such as, e.g., gene-therapy, we developed a method for keeping acute human brain slices viable over a longer period. Our protocol keeps neurons viable well up to 48 hours. Using a dual-flow chamber, which allows for microscopic visualisation of individual neurons with a submerged objective for whole-cell patch-clamp recordings, we report stable electrophysiological properties, such as action potential amplitude and threshold during this time. We also demonstrate that epileptiform activity, monitored by individual dentate granule whole-cell recordings, can be consistently induced in these slices, underlying the usefulness of this methodology for testing and/or validating novel treatment strategies for epilepsy.
| S-EPMC5841387 | biostudies-literature
Project description:Understanding neurological disorders necessitates systems-level approaches that integrate multimodal data, but progress has been hindered by limited sample availability, and the absence of combined electrophysiological and molecular data from live patients. Here, we demonstrate that stereo electroencephalography (sEEG)—stereologically-implanted electrodes routinely used for monitoring epilepsy—enables the integration of RNA sequencing and epigenome maps with in vivo recordings and brain imaging. Here we report a method MoPEDE (Molecular Profiling of Epileptic Brain Activity via Explanted Depth Electrodes) that enables this by recovering extensive protein-coding transcripts and DNA methylation profiles from explanted depth electrodes containing matched electrophysical and radiological data, hence allowing for high-resolution reconstructions of brain structure and function in patients. Our proof-of-concept study shows that epilepsies of different etiologies have distinct molecular landscapes and identifies transcripts correlating with neurophysiological signals, including immediate early genes, inflammation markers, and axon guidance molecules. Additionally, we identify DNA methylation profiles indicative of transcriptionally permissive or restrictive chromatin states. While gene expression gradients corresponded with the assigned epileptogenicity index, we found outlier molecular fingerprints in some electrodes, potentially indicating seizure spread or generation zones not detected during clinical assessments. These findings validate that RNA profiles and genome-wide epigenetic data from explanted sEEGs offer high-resolution surrogate molecular landscapes of brain activity. This revolutionary approach has the potential to enhance diagnostic decisions and deepen our understanding of epileptogenic processes.
2025-01-15 | GSE268715 | GEO
Project description:Understanding neurological disorders necessitates systems-level approaches that integrate multimodal data, but progress has been hindered by limited sample availability, and the absence of combined electrophysiological and molecular data from live patients. Here, we demonstrate that stereo electroencephalography (sEEG)—stereologically-implanted electrodes routinely used for monitoring epilepsy—enables the integration of RNA sequencing and epigenome maps with in vivo recordings and brain imaging. Here we report a method MoPEDE (Molecular Profiling of Epileptic Brain Activity via Explanted Depth Electrodes) that enables this by recovering extensive protein-coding transcripts and DNA methylation profiles from explanted depth electrodes containing matched electrophysical and radiological data, hence allowing for high-resolution reconstructions of brain structure and function in patients. Our proof-of-concept study shows that epilepsies of different etiologies have distinct molecular landscapes and identifies transcripts correlating with neurophysiological signals, including immediate early genes, inflammation markers, and axon guidance molecules. Additionally, we identify DNA methylation profiles indicative of transcriptionally permissive or restrictive chromatin states. While gene expression gradients corresponded with the assigned epileptogenicity index, we found outlier molecular fingerprints in some electrodes, potentially indicating seizure spread or generation zones not detected during clinical assessments. These findings validate that RNA profiles and genome-wide epigenetic data from explanted sEEGs offer high-resolution surrogate molecular landscapes of brain activity. This revolutionary approach has the potential to enhance diagnostic decisions and deepen our understanding of epileptogenic processes.
2025-01-15 | GSE268714 | GEO
Project description:The costs, benefits and risks associated with diagnostic imaging investigations for epilepsy surgery necessitate the identification of an optimal pathway in the pre-surgical workup. In order to assess the added value of additional investigations a full cost-effectiveness evaluation should be conducted, taking into account all of the life-time costs and benefits associated with undertaking additional investigations. This paper considers and applies the appropriate framework against which a full evaluation should be assessed. We conducted a systematic review to evaluate the progression of the literature through this framework, finding that only isolated elements of added value have been appropriately evaluated. The results from applying the full added value framework are also presented, identifying an optimal strategy for pre-surgical evaluation for temporal lobe epilepsy surgery. Our results suggest that additional FDG-PET and invasive EEG investigations after an initially discordant MRI and video-EEG appears cost-effective, and that the value of subsequent invasive-EEGs is closely linked to the maintenance of longer-term benefits after surgery. It is integral to the evaluation of imaging technologies in the work-up for epilepsy surgery that the impact of the use of these technologies on clinical decision-making, and on further treatment decisions, is considered fully when informing cost-effectiveness.
| S-EPMC4000270 | biostudies-literature