Getting the best outcomes from epilepsy surgery.

Neurosurgery is an underutilized treatment that can potentially cure drug-refractory epilepsy. Careful, multidisciplinary presurgical evaluation is vital for selecting patients and to ensure optimal outcomes. Advances in neuroimaging have improved diagnosis and guided surgical intervention. Invasive electroencephalography allows the evaluation of complex patients who would otherwise not be candidates for neurosurgery. We review the current state of the assessment and selection of patients and consider established and novel surgical procedures and associated outcome data. We aim to dispel myths that may inhibit physicians from referring and patients from considering neurosurgical intervention for drug-refractory focal epilepsies. Ann Neurol 2018;83:676-690

Evidence for the role of magnetic source imaging in the presurgical evaluation of refractory epilepsy patients

Magnetoencephalography (MEG) in the field of epilepsy has multiple advantages; just like electroencephalography (EEG), MEG is able to measure the epilepsy specific information (i.e., the brain activity reflecting seizures and/or interictal epileptiform discharges) directly, non-invasively and with a very high temporal resolution (millisecond-range). In addition MEG has a unique sensitivity for tangential sources, resulting in a full picture of the brain activity when combined with EEG. It accurately allows to perform source imaging of focal epileptic activity and functional cortex and shows a specific high sensitivity for a source in the neocortex. In this paper the current evidence and practice for using magnetic source imaging of focal interictal and ictal epileptic activity during the presurgical evaluation of drug resistant patients is being reviewed

Stereo-Encephalographic Presurgical Evaluation of Temporal Lobe Epilepsy: An Evolving Science

Drug-resistant epilepsy is present in nearly 30% of patients. Resection of the epileptogenic zone has been found to be the most effective in achieving seizure freedom. The study of temporal lobe epilepsy for surgical treatment is extensive and complex. It involves a multidisciplinary team in decision-making with initial non-invasive studies (Phase I), providing 70% of the required information to elaborate a hypothesis and treatment plans. Select cases present more complexity involving bilateral clinical or electrographic manifestations, have contradicting information, or may involve deeper structures as a part of the epileptogenic zone. These cases are discussed by a multidisciplinary team of experts with a hypothesis for invasive methods of study. Subdural electrodes were once the mainstay of invasive presurgical evaluation and in later years most Comprehensive Epilepsy Centers have shifted to intracranial recordings. The intracranial recording follows original concepts since its development by Bancaud and Talairach, but great advances have been made in the field. Stereo-electroencephalography is a growing field of study, treatment, and establishment of seizure pattern complexities. In this comprehensive review, we explore the indications, usefulness, discoveries in interictal and ictal findings, pitfalls, and advances in the science of presurgical stereo-encephalography for temporal lobe epilepsy

Interictal magnetoencephalographic findings related with surgical outcomes in lesional and nonlesional neocortical epilepsy

Purpose: To investigate whether interictal magnetoencephalography (MEG) concordant with other techniques can predict surgical outcome in patients with lesional and nonlesional refractory neocortical epilepsy (NE). Methods: 23 Patients with lesional NE and 20 patients with nonlesional NE were studied. MEG was recorded for all patients with a 275 channel whole-head system. Synthetic aperture magnetometry (SAM) with excess kurtosis (g2) and conventional Equivalent Current Dipole (ECD) were used for MEG data analysis. 27 Patients underwent long-term extraoperative intracranial video electroencephalography (iVEEG) monitoring. Surgical outcomes were assessed based on more than 1-year of post-surgical follow-up using Engel classification system. Results: As we expected, both favorable outcomes (Engel class I or II) and seizure freedom outcomes (Engel class IA) were higher for the concordance condition (MEG findings are concordant with MRI or iVEEG findings) versus the discordance condition. Also the seizure free rate was significantly higher (x2 = 5.24, P \u3c 0.05) for the patients with lesional NE than for the patients with nonlesional NE. In 30% of the patients with nonlesional NE, the MEG findings proved to be valuable for intracranial electrode implantation. Conclusions: This study demonstrates that a favorable post-surgical outcome can be obtained in most patients with concordant MEG and MRI results even without extraoperative iVEEG monitoring, which indicates that the concordance among different modalities could indicate a likelihood of better postsurgical outcomes. However, extraoperative iVEEG monitoring remains prerequisite to the patients with discordant MEG and MRI findings. For nonlesional cases, our results showed that MEG could provide critical information in the placement of intracranial electrodes

Computer-Assisted Planning and Robotics in Epilepsy Surgery

Epilepsy is a severe and devastating condition that affects ~1% of the population. Around 30% of these patients are drug-refractory. Epilepsy surgery may provide a cure in selected individuals with drug-resistant focal epilepsy if the epileptogenic zone can be identified and safely resected or ablated. Stereoelectroencephalography (SEEG) is a diagnostic procedure that is performed to aid in the delineation of the seizure onset zone when non-invasive investigations are not sufficiently informative or discordant. Utilizing a multi-modal imaging platform, a novel computer-assisted planning (CAP) algorithm was adapted, applied and clinically validated for optimizing safe SEEG trajectory planning. In an initial retrospective validation study, 13 patients with 116 electrodes were enrolled and safety parameters between automated CAP trajectories and expert manual plans were compared. The automated CAP trajectories returned statistically significant improvements in all of the compared clinical metrics including overall risk score (CAP 0.57 +/- 0.39 (mean +/- SD) and manual 1.00 +/- 0.60, p < 0.001). Assessment of the inter-rater variability revealed there was no difference in external expert surgeon ratings. Both manual and CAP electrodes were rated as feasible in 42.8% (42/98) of cases. CAP was able to provide feasible electrodes in 19.4% (19/98), whereas manual planning was able to generate a feasible electrode in 26.5% (26/98) when the alternative generation method was not feasible. Based on the encouraging results from the retrospective analysis a prospective validation study including an additional 125 electrodes in 13 patients was then undertaken to compare CAP to expert manual plans from two neurosurgeons. The manual plans were performed separately and blindly from the CAP. Computer-generated trajectories were found to carry lower risks scores (absolute difference of 0.04 mm (95% CI = -0.42-0.01), p = 0.04) and were subsequently implanted in all cases without complication. The pipeline has been fully integrated into the clinical service and has now replaced manual SEEG planning at our institution. Further efforts were then focused on the distillation of optimal entry and target points for common SEEG trajectories and applying machine learning methods to develop an active learning algorithm to adapt to individual surgeon preferences. Thirty-two patients were prospectively enrolled in the study. The first 12 patients underwent prospective CAP planning and implantation following the pipeline outlined in the previous study. These patients were used as a training set and all of the 108 electrodes after successful implantation were normalized to atlas space to generate ‘spatial priors’, using a K-Nearest Neighbour (K-NN) classifier. A subsequent test set of 20 patients (210 electrodes) were then used to prospectively validate the spatial priors. From the test set, 78% (123/157) of the implanted trajectories passed through both the entry and target spatial priors defined from the training set. To improve the generalizability of the spatial priors to other neurosurgical centres undertaking SEEG and to take into account the potential for changing institutional practices, an active learning algorithm was implemented. The K-NN classifier was shown to dynamically learn and refine the spatial priors. The progressive refinement of CAP SEEG planning outlined in this and previous studies has culminated in an algorithm that not only optimizes the surgical heuristics and risk scores related to SEEG planning but can also learn from previous experience. Overall, safe and feasible trajectory schema were returning in 30% of the time required for manual SEEG planning. Computer-assisted planning was then applied to optimize laser interstitial thermal therapy (LITT) trajectory planning, which is a minimally invasive alternative to open mesial temporal resections, focal lesion ablation and anterior 2/3 corpus callosotomy. We describe and validate the first CAP algorithm for mesial temporal LITT ablations for epilepsy treatment. Twenty-five patients that had previously undergone LITT ablations at a single institution and with a median follow up of 2 years were included. Trajectory parameters for the CAP algorithm were derived from expert consensus to maximize distance from vasculature and ablation of the amygdalohippocampal complex, minimize collateral damage to adjacent brain structures whilst avoiding transgression of the ventricles and sulci. Trajectory parameters were also optimized to reduce the drilling angle to the skull and overall catheter length. Simulated cavities attributable to the CAP trajectories were calculated using a 5-15 mm ablation diameter. In comparison to manually planned and implemented LITT trajectories,CAP resulted in a significant increase in the percentage ablation of the amygdalohippocampal complex (manual 57.82 +/- 15.05% (mean +/- S.D.) and unablated medial hippocampal head depth (manual 4.45 +/- 1.58 mm (mean +/- S.D.), CAP 1.19 +/- 1.37 (mean +/- S.D.), p = 0.0001). As LITT ablation of the mesial temporal structures is a novel procedure there are no established standards for trajectory planning. A data-driven machine learning approach was, therefore, applied to identify hitherto unknown CAP trajectory parameter combinations. All possible combinations of planning parameters were calculated culminating in 720 unique combinations per patient. Linear regression and random forest machine learning algorithms were trained on half of the data set (3800 trajectories) and tested on the remaining unseen trajectories (3800 trajectories). The linear regression and random forest methods returned good predictive accuracies with both returning Pearson correlations of ρ = 0.7 and root mean squared errors of 0.13 and 0.12 respectively. The machine learning algorithm revealed that the optimal entry points were centred over the junction of the inferior occipital, middle temporal and middle occipital gyri. The optimal target points were anterior and medial translations of the centre of the amygdala. A large multicenter external validation study of 95 patients was then undertaken comparing the manually planned and implemented trajectories, CAP trajectories targeting the centre of the amygdala, the CAP parameters derived from expert consensus and the CAP trajectories utilizing the machine learning derived parameters. Three external blinded expert surgeons were then selected to undertake feasibility ratings and preference rankings of the trajectories. CAP generated trajectories result in a significant improvement in many of the planning metrics, notably the risk score (manual 1.3 +/- 0.1 (mean +/- S.D.), CAP 1.1 +/- 0.2 (mean +/- S.D.), p<0.000) and overall ablation of the amygdala (manual 45.3 +/- 22.2 % (mean +/- S.D.), CAP 64.2 +/- 20 % (mean +/- S.D.), p<0.000). Blinded external feasibility ratings revealed that manual trajectories were less preferable than CAP planned trajectories with an estimated probability of being ranked 4th (lowest) of 0.62. Traditional open corpus callosotomy requires a midline craniotomy, interhemispheric dissection and disconnection of the rostrum, genu and body of the corpus callosum. In cases where drop attacks persist a completion corpus callosotomy to disrupt the remaining fibres in the splenium is then performed. The emergence of LITT technology has raised the possibility of being able to undertake this procedure in a minimally invasive fashion and without the need for a craniotomy using two or three individual trajectories. Early case series have shown LITT anterior two-thirds corpus callosotomy to be safe and efficacious. Whole-brain probabilistic tractography connectomes were generated utilizing 3-Tesla multi-shell imaging data and constrained spherical deconvolution (CSD). Two independent blinded expert neurosurgeons with experience of performing the procedure using LITT then planned the trajectories in each patient following their current clinical practice. Automated trajectories returned a significant reduction in the risk score (manual 1.3 +/- 0.1 (mean +/- S.D.), CAP 1.1 +/- 0.1 (mean +/- S.D.), p<0.000). Finally, we investigate the different methods of surgical implantation for SEEG electrodes. As an initial study, a systematic review and meta-analysis of the literature to date were performed. This revealed a wide variety of implantation methods including traditional frame-based, frameless, robotic and custom-3D printed jigs were being used in clinical practice. Of concern, all comparative reports from institutions that had changed from one implantation method to another, such as following the introduction of robotic systems, did not undertake parallel-group comparisons. This suggests that patients may have been exposed to risks associated with learning curves and potential harms related to the new device until the efficacy was known. A pragmatic randomized control trial of a novel non-CE marked robotic trajectory guidance system (iSYS1) was then devised. Before clinical implantations began a series of pre-clinical investigations utilizing 3D printed phantom heads from previously implanted patients was performed to provide pilot data and also assess the surgical learning curve. The surgeons had comparatively little clinical experience with the new robotic device which replicates the introduction of such novel technologies to clinical practice. The study confirmed that the learning curve with the iSYS1 devices was minimal and the accuracies and workflow were similar to the conventional manual method. The randomized control trial represents the first of its kind for stereotactic neurosurgical procedures. Thirty-two patients were enrolled with 16 patients randomized to the iSYS1 intervention arm and 16 patients to the manual implantation arm. The intervention allocation was concealed from the patients. The surgical and research team could be not blinded. Trial management, independent data monitoring and trial steering committees were convened at four points doing the trial (after every 8 patients implanted). Based on the high level of accuracy required for both methods, the main distinguishing factor would be the time to achieve the alignment to the prespecified trajectory. The primary outcome for comparison, therefore, was the time for individual SEEG electrode implantation. Secondary outcomes included the implantation accuracy derived from the post-operative CT scan, infection, intracranial haemorrhage and neurological deficit rates. Overall, 32 patients (328 electrodes) completed the trial (16 in each intervention arm) and the baseline demographics were broadly similar between the two groups. The time for individual electrode implantation was significantly less with the iSYS1 device (median of 3.36 (95% CI 5.72 to 7.07) than for the PAD group (median of 9.06 minutes (95% CI 8.16 to 10.06), p=0.0001). Target point accuracy was significantly greater with the PAD (median of 1.58 mm (95% CI 1.38 to 1.82) compared to the iSYS1 (median of 1.16 mm (95% CI 1.01 to 1.33), p=0.004). The difference between the target point accuracies are not clinically significant for SEEG but may have implications for procedures such as deep brain stimulation that require higher placement accuracy. All of the electrodes achieved their respective intended anatomical targets. In 12 of 16 patients following robotic implantations, and 10 of 16 following manual PAD implantations a seizure onset zone was identified and resection recommended. The aforementioned systematic review and meta-analysis were updated to include additional studies published during the trial duration. In this context, the iSYS1 device entry and target point accuracies were similar to those reported in other published studies of robotic devices including the ROSA, Neuromate and iSYS1. The PAD accuracies, however, outperformed the previously published results for other frameless stereotaxy methods. In conclusion, the presented studies report the integration and validation of a complex clinical decision support software into the clinical neurosurgical workflow for SEEG planning. The stereotactic planning platform was further refined by integrating machine learning techniques and also extended towards optimisation of LITT trajectories for ablation of mesial temporal structures and corpus callosotomy. The platform was then used to seamlessly integrate with a novel trajectory planning software to effectively and safely guide the implantation of the SEEG electrodes. Through a single-blinded randomised control trial, the ISYS1 device was shown to reduce the time taken for individual electrode insertion. Taken together, this work presents and validates the first fully integrated stereotactic trajectory planning platform that can be used for both SEEG and LITT trajectory planning followed by surgical implantation through the use of a novel trajectory guidance system

7T Magnetic Resonance Spectroscopy of Non-Lesional Temporal Lobe Epilepsy

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy, and one that is generally amenable to surgical treatment when surgery is necessary. Unfortunately, roughly 25-30% of the patient population have no visible lesions on clinical MRI scans. Without anatomical abnormalities to help guide surgical resection, the success of surgical treatment decreases substantially. However, metabolic abnormalities may exist that could allow for accurate localization of epileptic tissue in this cohort. Magnetic resonance spectroscopy (MRS) is a technique that can detect and measure the concentration of metabolically important molecules within tissue, giving insight into the underlying cellular metabolism. In this thesis, non-lesional TLE patients were studied and compared with control subjects using single voxel MRS at a magnetic field strength of 7T for the first time. We hypothesized that metabolite changes in the hippocampus would be associated with seizure lateralization. Non-lesional patients showed altered levels of creatine and choline when compared to healthy controls. These results were in agreement with prior work in the literature showing non-lesional TLE is primarily a result of glial cell proliferation without neuronal atrophy. However, in the patient cohort studied, these metabolites did not effectively lateralize seizure origin, potentially due to the varied underlying pathologies within the patient group

Presurgical evaluation and surgical treatment of medically refractory epilepsy

Thanks to today's modern imaging examination techniques and especially to the common use of intracranial electrodes for localizing seizure foci, more and more patients with partial epilepsy can be treated microsurgically. The results of such neurosurgical therapies are very good, particularly in mesial temporal lobe epilepsy. In recent years, good results (60-70% seizure freedom) have also been achieved in extratemporal epilepsy surgery, so that such procedures can now be recommended for carefully selected patients. In this review, presurgical evaluations and the different surgical approaches are presente

Software for Stereotactic Navigation System in Epileptosurgery

Tato práce je zaměřena na návrh a implementaci poloautomatického nástroje pro plánování implantace hloubkových elektrod v oboru epileptochirurgie. Navržené řešení je implementováno jako rozšíření do platformy 3D Slicer. Volumetrická data znázorňující omezující podmínky a seznam cílů navigace jsou použity jako vstupy pro automatické zpracování. Systém navrhuje seznam kandidátů na řešení, která mohou být interaktivně ohodnoceny. Toto je první iterace implementace, která obsahuje základní funkcionalitu zahrnující dávkové zpracování vstupních dat, automatické ohodnocení navigační trajektorie a uživatelské rozhraní pro interaktivní ohodnocení navrhovaných řešení.The thesis is focused on the design and implementation of semi-automatic navigation planner for implantation of deep brain electrodes in epileptosurgery. The solution is implemented as an extension into 3D Slicer platform. It uses volumetric data model of restricted areas and list of navigation targets as inputs to automatic processing. The system suggests the list of solution candidates which can be interactively evaluated. This is the first iteration of the implementation which incorporates basic functionality including batch processing of the input data, automatic evaluation of navigation paths and user interface for interactive evaluation