Drug-resistant Focal Epilepsy Research Articles

C.1 Utility of genetic testing in the pre-surgical evaluation of children with drug-resistant epilepsy

Background: All patients with drug-resistant focal epilepsy, should undergo an evaluation to determine if non-medical options, including surgical intervention, are appropriate. This evaluation involves a thorough work-up, typically including some or all of neuropsychological evaluation, prolonged video EEG monitoring, and advanced neuroimaging. The utility of genetic testing as part of this evaluation has not been thoroughly investigated. Methods: In this retrospective study, we reviewed the charts of pediatric patients referred for epilepsy surgery evaluation over a 5-year period. We extracted and analyzed results of genetic testing as well as clinical, EEG, and neuroimaging data. Results: 125 patients were referred for epilepsy surgical evaluation, 86 of whom had some form of genetic testing. Of these, 18 had a pathogenic or likely pathogenic variant identified. Genes affected included NPRL3, TSC2, KCNH1, CHRNA4, SPTAN1, DEPDC5, SCN2A, ARX, SCN1A, DLG4, and ST5. One patient had ring chromosome 20, one a 7.17p12 duplication, and one a 15q13 deletion. A specific medical therapy choice was allowed due to genetic diagnosis in three patients who did not undergo surgery. Conclusions: Obtaining a molecular diagnosis may dramatically alter management in children with drug-resistant focal epilepsy. Genetic testing should be incorporated as part of standard investigations in the pre-surgical work-up of such patients.

High-precision stereotactic irradiation for focal drug-resistant epilepsy versus standard treatment: a randomized waitlist-controlled trial (the PRECISION trial)

IntroductionThe standard treatment for patients with focal drug-resistant epilepsy (DRE) who are not eligible for open brain surgery is the continuation of anti-seizure medication (ASM) and neuromodulation. This treatment does not cure epilepsy but only decreases severity. The PRECISION trial offers a non-invasive, possibly curative intervention for these patients, which consist of a single stereotactic radiotherapy (SRT) treatment. Previous studies have shown promising results of SRT in this patient population. Nevertheless, this intervention is not yet available and reimbursed in the Netherlands. We hypothesize that: SRT is a superior treatment option compared to palliative standard of care, for patients with focal DRE, not eligible for open surgery, resulting in a higher reduction of seizure frequency (with 50% of the patients reaching a 75% seizure frequency reduction at 2 years follow-up).MethodsIn this waitlist-controlled phase 3 clinical trial, participants are randomly assigned in a 1:1 ratio to either receive SRT as the intervention, while the standard treatments consist of ASM continuation and neuromodulation. After 2-year follow-up, patients randomized for the standard treatment (waitlist-control group) are offered SRT. Patients aged ≥ 18 years with focal DRE and a pretreatment defined epileptogenic zone (EZ) not eligible for open surgery will be included. The intervention is a LINAC-based single fraction (24 Gy) SRT treatment. The target volume is defined as the epileptogenic zone (EZ) on all (non) invasive examinations. The seizure frequency will be monitored on a daily basis using an electronic diary and an automatic seizure detection system during the night. Potential side effects are evaluated using advanced MRI, cognitive evaluation, Common Toxicity Criteria, and patient-reported outcome questionnaires. In addition, the cost-effectiveness of the SRT treatment will be evaluated.DiscussionThis is the first randomized trial comparing SRT with standard of care in patients with DRE, non-eligible for open surgery. The primary objective is to determine whether SRT significantly reduces the seizure frequency 2 years after treatment. The results of this trial can influence the current clinical practice and medical cost reimbursement in the Netherlands for patients with focal DRE who are not eligible for open surgery, providing a non-invasive curative treatment option.Trial registrationClinicaltrials.gov Identifier: NCT05182437. Registered on September 27, 2021.

Stereoelectroencephalography-guided radiofrequency thermocoagulation of the epileptogenic zone: a potential treatment and prognostic indicator for subsequent excision surgery.

To evaluate the safety and efficacy of stereoelectroencephalography (SEEG)-guided radiofrequency thermocoagulation (RFTC) for drug-resistant focal epilepsy and investigate the relationship between post-RFTC remission duration and delayed excision surgery effectiveness. We conducted a retrospective analysis of 43 patients with drug-resistant focal epilepsy who underwent RFTC via SEEGelectrodes. After excluding three, the remaining 40 were classified into subgroups based on procedures and outcomes. Twenty-four patients (60%) underwent a secondary excision surgery. We determined the predictive value of RFTC outcome upon subsequent surgical outcome by categorizing the delayed secondary surgery outcome as success (Engel I/II) versus failure (Engel III/IV). Demographic information, epilepsy characteristics, and the duration of seizure freedom after RFTC were assessed. Among 40 patients, 20% achieved Engel class I with RFTC alone, while 24 underwent delayed secondary excision surgery. Overall, 41.7% attained Engel class I, with a 66.7% success rate combining RFTC with delayed surgery. Seizure freedom duration was significantly longer in the success group (mean 4.9months, SD = 2.7) versus the failure group (mean 1.9months, SD = 1.1; P = 0.007). A higher proportion of RFTC-only and delayed surgical success group patients had preoperative lesional findings (p = 0.01), correlating with a longer time to seizure recurrence (p < 0.05). Transient postoperative complications occurred in 10%, resolving within a year. This study demonstrates that SEEG-guided RFTC is a safe and potential treatment option for patients with drug-resistant focal epilepsy. A prolonged duration of seizure freedom following RFTC may serve as a predictive marker for the success of subsequent excision surgery.

Disrupting the epileptogenic network with stereoelectroencephalography-guided radiofrequency thermocoagulation.

Stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) is a treatment option for focal drug-resistant epilepsy. In previous studies, this technique has shown seizure reduction by ≥50% in 50% of patients at 1 year. However, the relationship between the location of the ablation within the epileptogenic network and clinical outcomes remains poorly understood. Seizure outcomes were analyzed for patients who underwent SEEG-guided RF-TC and across subgroups depending on the location of the ablation within the epileptogenic network, defined as SEEG sites involved in seizure generation and spread. Eighteen patients who had SEEG-guided RF-TC were included. SEEG-guided seizure-onset zone ablation (SEEG-guided SOZA) was performed in 12 patients, and SEEG-guided partial seizure-onset zone ablation (SEEG-guided P-SOZA) in 6 patients. The early spread was ablated in three SEEG-guided SOZA patients. Five patients had ablation of a lesion. The seizure freedom rate in the cohort ranged between 22% and 50%, and the responder rate between 67% and 85%. SEEG-guided SOZA demonstrated superior results for both outcomes compared to SEEG-guided P-SOZA at 6 months (seizure freedom p = .294, responder rate p = .014). Adding the early spread ablation to SEEG-guided SOZA did not increase seizure freedom rates but exhibited comparable effectiveness regarding responder rates, indicating a potential network disruption.

Mapping interictal discharges using intracranial EEG-fMRI to predict postsurgical outcomes.

Various subjective and objective methods have been proposed to identify which interictal epileptiform discharge (IED)-related EEG-fMRI results are more likely to delineate seizure generating tissue in patients with drug-resistant focal epilepsy for the purposes of surgical planning. In this intracranial EEG-fMRI study, we evaluated the utility of these methods to localize clinically relevant regions pre-operatively and compared the extent of resection of these areas to post-operative outcome. Seventy patients admitted for intracranial video-EEG monitoring were recruited for a simultaneous intracranial EEG-fMRI study. For all analyses of blood oxygen level-dependent responses associated with IEDs, an experienced epileptologist identified the most Clinically Relevant brain activation cluster using available clinical information. The Maximum cluster (the cluster with the highest z-score) was also identified for all analyses and assigned to one of three confidence levels (low, medium, or high) based on the difference of the peak z-scores between the Maximum and Second Maximum cluster (the cluster with the second highest peak z-value). The distance was measured and compared between the peak voxel of the aforementioned clusters and the electrode contacts where the interictal discharge and seizure onset were recorded. In patients who subsequently underwent epilepsy surgery, the spatial concordance between the aforementioned clusters and the area of resection was determined and compared to post-operative outcome. We evaluated 106 different IEDs in 70 patients. Both subjective (identification of the Clinically Relevant cluster) and objective (Maximum cluster much more significant than the second maximum cluster) methods of culling non-localizing EEG-fMRI activation maps increased the spatial concordance between these clusters and the corresponding IED or seizure onset zone contacts. However, only the objective methods of identifying medium and high confidence maps resulted in a significant association between resection of the peak voxel of the Maximum cluster and post-operative outcome. Resection of this area was associated with good post-operative outcomes but was not sufficient for seizure freedom. On the other hand, we found that failure to resect the medium and high confidence Maximum clusters was associated with a poor post-surgical outcome (negative predictive value = 1.0, sensitivity = 1.0). Objective methods to identify higher confidence EEG-fMRI results are needed to localize areas necessary for good post-operative outcomes. However, resection of the peak voxel within higher confidence Maximum clusters is not sufficient for good outcomes. Conversely, failure to resect the peak voxel in these clusters is associated with a poor post-surgical outcome.

SPECT postprocessing for epileptogenic focus localization: SISCOM versus ISAS.

Ictal SPECT can be used as an estimate for the epileptogenic zone in people with focal epilepsy. Subtraction of ictal and interictal SPECT scans reveals the area with significant ictal hyperperfusion. Some methods use a control database to also correct for physiological variance. This control database is ideally scanner specific, but it is not trivial to obtain such a database because of ethical issues. In this study, we used a publicly available control database to compare ictal-interictal SPECT analyzed by SPM (ISAS) with the most commonly used subtraction ictal SPECT co-registered to MRI (SISCOM). Ictal and interictal SPECTs of 26 patients (age range: 7-50 years, 15 adults, 11 children) with focal drug resistant epilepsy in workup for epilepsy surgery were retrospectively analyzed using both SISCOM and ISAS. The control database for ISAS was obtained from the ISAS website. Two groups of blinded reviewers determined the location of ictal hyperperfusion in all datasets. Results were compared between subtraction algorithms and with the resected area (if available) or the suspected epileptogenic zone. The number of significant clusters and the locations of maximum hyperperfusion were compared between algorithms. The location of ISAS and SISCOM hyperperfusion was the same in 14 patients (54%). ISAS localized in 6 patients where SISCOM did not. Compared to the resected area or suspected epileptogenic zone, SISCOM correctly localized in 55%, while ISAS did in 65% (not significantly different). ISAS shows significantly less clusters than SISCOM. The maximum hyperperfusion was in the reviewer's location in 65% for ISAS and 38% for SISCOM. ISAS using a publicly available control database gives comparable or better results than SISCOM. ISAS results are easier to interpret than SISCOM results. We show that ISAS is a reliable alternative for SISCOM, which could easily be implemented in epilepsy surgery clinics. We explored the effectiveness of ISAS as an alternative to the widely used SISCOM for assessing SPECT scans in epilepsy surgery candidates. Utilizing a publicly available control database, we compared the two methods in 26 patients. The results indicate that ISAS might offer increased accuracy and interpretability, making it a promising option, especially for centers without access to a specific control dataset.

Surgical outcomes in children with drug-resistant epilepsy and hippocampal sclerosis

BackgroundHippocampal sclerosis (HS) is a common surgical substrate in adult epilepsy surgery cohorts but variably reported in various pediatric cohorts. ObjectiveWe aimed to study the epilepsy phenotype, radiological and pathological variability, seizure and neurocognitive outcomes in children with drug-resistant epilepsy and hippocampal sclerosis (HS) with or without additional subtle signal changes in anterior temporal lobe who underwent surgery. MethodsThis retrospective study enrolled children with drug-resistant focal epilepsy and hippocampal sclerosis with or without additional subtle T2-Fluid Attenuated Inversion Recovery (FLAR)/Proton Density (PD) signal changes in anterior temporal lobe who underwent anterior temporal lobectomy with amygdalohippocampectomy. Their clinical, EEG, neuropsychological, radiological and pathological data were reviewed and summarized. ResultsThirty-six eligible patients were identified. The mean age at seizure onset was 3.7 years; 25% had daily seizures at time of surgery. Isolated HS was noted in 22 (61.1%) cases and additional subtle signal changes in ipsilateral temporal lobe in 14 (38.9%) cases. Compared to the normative population, the group mean performance in intellectual functioning and most auditory and visual memory tasks were significantly lower than the normative sample. The mean age at surgery was 12.3 years; 22 patients (61.1%) had left hemispheric surgeries. ILAE class 1 outcomes was seen in 28 (77.8%) patients after a mean follow up duration of 2.3 years. Hippocampal sclerosis was noted pathologically in 32 (88.9%) cases; type 2 (54.5%) was predominant subtype where further classification was possible. Additional pathological abnormalities were seen in 11 cases (30.6%); these had had similar rates of seizure freedom as compared to children with isolated hippocampal sclerosis/gliosis (63.6% vs 84%, p=0.21). Significant reliable changes were observed across auditory and visual memory tasks at an individual level post surgery. ConclusionsFavourable seizure outcomes were seen in most children with isolated radiological hippocampal sclerosis. Patients with additional pathological abnormalities had similar rates of seizure freedom as compared to children with isolated hippocampal sclerosis/gliosis.

Psychiatric complications following SEEG-guided radiofrequency thermocoagulations in patients with drug-resistant epilepsy

SEEG-guided radiofrequency thermocoagulation (RF-TC) in the epileptogenic regions is a therapeutic option for patients with drug-resistant focal epilepsy who may have or not indication for epilepsy surgery. The most common adverse events of RF-TC are seizures, headaches, somatic pain, and sensory-motor deficits. If RF-TC could lead to psychiatric complications is unknown. In the present study, seven out of 164 patients (4.2 %) experienced psychiatric decompensation with or without memory deterioration after RF-TC of bilateral or unilateral amygdala and hippocampus. The appearance of symptoms was either acute, subacute, or chronic and the symptoms were either transient or lasted for several months. Common features among these patients were female sex, mesial temporal epilepsy, and a pre-existing history of psychological distress and memory dysfunction. Our study highlights the possibility of neuropsychiatric deterioration in specific patients following SEEG-guided RF-TC, despite its rarity.

Stereo-EEG features of temporal and frontal lobe seizures with loss of consciousness.

The loss of consciousness (LOC) during seizures is one of the most striking features that significantly impact the quality of life, even though the neuronal network involved is not fully comprehended. We analyzed the intracerebral patterns in patients with focal drug-resistant epilepsy, both with and without LOC. We assessed the localization, lateralization, stereo electroencephalography (SEEG) patterns, seizure duration, and the quantification of contacts exhibiting electrical discharge. The degree of LOC was quantified using the Consciousness Seizure Scale. Thirteen patients (40 seizures) with focal drug-resistant epilepsy underwent SEEG. In cases of temporal lobe epilepsy (TLE, 6 patients and 15 seizures), LOC occurred more frequently in seizures with mesial rather than lateral temporal lobe onset. On the other hand, in cases of frontal lobe epilepsy (7 patients; 25 seizures), LOC was associated with pre-frontal onset, a higher number of contacts with epileptic discharge compared to the onset count and longer seizure durations. Our study revealed distinct characteristics during LOC depending on the epileptogenic zone. For temporal lobe seizures, LOC was associated with mesial seizure onset, whereas in frontal lobe epilepsy, seizure with LOC has a significant increase in contact showing epileptiform discharge and a pre-frontal onset. This phenomenon may be correlated with the broad neural network required to maintain consciousness, which can be affected in different ways, resulting in LOC.

Management of Anti-seizure Medication in Patients with Drug-resistant Focal Epilepsy Secondary to Focal Cortical Dysplasia Undergoing Epilepsy Surgery in Argentina (P10-1.016)

Management of Anti-seizure Medication in Patients with Drug-resistant Focal Epilepsy Secondary to Focal Cortical Dysplasia Undergoing Epilepsy Surgery in Argentina (P10-1.016)

Enhancement of Subjective Quality of Life Following Surgical Intervention in Patients With Drug-Resistant Epilepsy: A Depressive Symptom-Independent Outcome.

To evaluate the impact of depressive symptoms on the subjective perception of quality of life in patients with drug-resistant epilepsy (DRE) after surgical treatment for seizures. Methods: A case-control study with DRE patients who received surgical treatment (n=19) and matched non-operated patients (n=23). We assessed the quality of life using the Subjective Handicap of Epilepsy (SHE) scale, alongside measuring depressive symptoms using the Beck Depression Inventory (BDI). The mean age of the participants was 45 years, with females constituting 52.4% of the patients. A majority (73.8%) had been diagnosed with temporal lobe epilepsy. Those who had undergone surgical intervention showed significantly enhanced performance across all quality-of-life domains on the SHE scale independently of depressive symptoms. The domains of "Work and Activity,""Physical Health,"and "Self-Perception" displayed the greatest improvements, with the surgical group's averages outperforming the control group by factors of 1.87, 2.53, and 2.81, respectively. Influential differences impacting the quality-of-life scores included seizure frequency, the quantity of antiepileptic drugs utilized, and the incidence of convulsive seizures. The findings suggest that surgical control of seizures in drug-resistant focal epilepsy is associated with improvement in quality of life across various domains, independently of the depressive symptoms of the patients.

New stimulation procedures for language mapping in stereo-EEG.

Cortical intracerebral electrical stimulation is an important tool for language mapping in the presurgical work-up of patients with drug-resistant focal epilepsy. Language mapping with stereo-electroencephalography (EEG) is usually performed by high-frequency stimulations (HFS: 50 Hz), whereas low-frequency stimulations (LFS: 1 Hz) are usually considered useful for primary cortices mapping. Little is known in literature about "intermediate" frequencies (IFS: 6-15 Hz). Our objective is to explore the clinical usefulness of IFS in language mapping and identify factors, beyond the electrical parameters, that impact the mapping. We studied 23 patients submitted to stereo-EEG for presurgical evaluation. Language mapping was performed in the anterior, posterior and/or basal language region of the dominant hemisphere for language. We included all contact positions within these regions stimulated by HFS (50 Hz, 5 s, 1-3 mA) and IFS (6-15 Hz, 15 s, 5 mA). We compared the capability of both stimulation methods to induce a language deficit without afterdischarges (ADs), and we analyzed factors related to clinical examination, region, and stimulation technique by multivariate analysis. A total of 211 stimulations (98 HFS, 113 IFS) in 70 cortical sites within the anterior (84 stimulations), posterior (137), and basal language region (60) were included. IFS induced more frequently language deficits not associated to AD compared to HFS (37.1% vs 25.7%, p = .0043), whereas HFS provoked more diffuse AD (34.7% vs 15.0%, p = .001). Investigating multiple language functions increased the probability of revealing a deficit (odds ratio [OR] 3.16, p = .0016), independently of the stimulation method. IFS are valuable for language mapping, thereby improving the probability of inducing a clinical deficit not accompanied by an AD. The completeness of the clinical examination independently affects the sensitivity of the mapping. IFS are a new tool with potential usefulness for the cortical mapping of other associative cortical regions.

Development and prospective clinical validation of a convolutional neural network for automated detection and segmentation of focal cortical dysplasias

PurposeFocal cortical dysplasias (FCDs) are a leading cause of drug-resistant epilepsy. Early detection and resection of FCDs have favorable prognostic implications for postoperative seizure freedom. Despite advancements in imaging methods, FCD detection remains challenging. House et al. (2021) introduced a convolutional neural network (CNN) for automated FCD detection and segmentation, achieving a sensitivity of 77.8%. However, its clinical applicability was limited due to a low specificity of 5.5%. The objective of this study was to improve the CNN’s performance through data-driven training and algorithm optimization, followed by a prospective validation on daily-routine MRIs. Material and methodsA dataset of 300 3 T MRIs from daily clinical practice, including 3D T1 and FLAIR sequences, was prospectively compiled. The MRIs were visually evaluated by two neuroradiologists and underwent morphometric assessment by two epileptologists. The dataset included 30 FCD cases (11 female, mean age: 28.1 ± 10.1 years) and a control group of 150 normal cases (97 female, mean age: 32.8 ± 14.9 years), along with 120 non-FCD pathological cases (64 female, mean age: 38.4 ± 18.4 years). The dataset was divided into three subsets, each analyzed by the CNN. Subsequently, the CNN underwent a two-phase-training process, incorporating subset MRIs and expert-labeled FCD maps. This training employed both classical and continual learning techniques. The CNN’s performance was validated by comparing the baseline model with the trained models at two training levels. ResultsIn prospective validation, the best model trained using continual learning achieved a sensitivity of 90.0%, specificity of 70.0%, and accuracy of 72.0%, with an average of 0.41 false positive clusters detected per MRI. For FCD segmentation, an average Dice coefficient of 0.56 was attained. The model’s performance improved in each training phase while maintaining a high level of sensitivity. Continual learning outperformed classical learning in this regard. ConclusionsOur study presents a promising CNN for FCD detection and segmentation, exhibiting both high sensitivity and specificity. Furthermore, the model demonstrates continuous improvement with the inclusion of more clinical MRI data. We consider our CNN a valuable tool for automated, examiner-independent FCD detection in daily clinical practice, potentially addressing the underutilization of epilepsy surgery in drug-resistant focal epilepsy and thereby improving patient outcomes.

Monopolar stereoelectroencephalography-guided radiofrequency thermocoagulation.

Stereoelectroencephalography (SEEG)-guided radiofrequency thermocoagulation (RFTC) has the advantage of producing a lesion in the epileptogenic zone (EZ) at the end of SEEG. The majority of published SEEG-guided RFTCs have been bipolar and usually performed between contiguous contacts of the same electrode. In the present study, the authors evaluate the safety, efficacy, and benefits of monopolar RFTC at the end of SEEG. This study included a series of 31 consecutive patients who had undergone RFTC at the end of SEEG for drug-resistant focal epilepsy in the period of January 2013-December 2019. Post-RFTC seizure control was assessed after 2 months and at the last follow-up visit. Twenty-one patients underwent resective epilepsy surgery after the SEEG-guided RFTC, and the postoperative seizure outcome among these patients was compared with the post-RFTC seizure outcome. Four hundred forty-six monopolar RFTCs were done in the 31 patients. Monopolar RFTCs were performed in all cortical areas, including the insular cortex in 11 patients (56 insular RFTCs). There were 31 noncontiguous lesions (7.0%) because of vascular constraints. The volume of one monopolar RFTC, as measured on T2-weighted MRI immediately after the procedure, was between 44 and 56 mm3 (mean 50 mm3). The 2-month post-RFTC seizure outcomes were as follows: seizure freedom in 13 patients (41.9%), ≥ 50% reduced seizure frequency in 11 (35.5%), and no significant change in 7 (22.6%). Seizure outcome at the last follow-up visit (mean 18 months, range 2-54 months) showed seizure freedom in 2 patients (6.5%) and ≥ 50% reduced seizure frequency in 20 patients (64.5%). Seizure freedom after monopolar RFTC was not significantly associated with the number or location of coagulated contacts. Seizure response after monopolar RFTC had a high positive predictive value (93.8%) but a low negative predictive value (40%) for seizure outcome after subsequent resective surgery. In this series, the only complication (3.2%) was a limited intraventricular hematoma following RFTC performed in the hippocampal head, with spontaneous resolution and no sequelae. The use of monopolar SEEG-guided RFTC provides more freedom in terms of choosing the SEEG contacts for thermocoagulation and a larger thermolesion volume. Monopolar thermocoagulation seems particularly beneficial in cases with an insular EZ, in which vascular constraints could be partially avoided by making noncontiguous lesions within the EZ.

486 Responsive Neurostimulation of the Centromedian Nucleus of the Thalamus in Adult Epilepsy: Multi-center Case Series

INTRODUCTION: Responsive neurostimulation (RNS) is an FDA-approved therapy for focal drug-resistant epilepsy (DRE). Emerging evidence supports a role for RNS in DRE with regional, multifocal, or non-resectable seizure onset zones. The centromedian nucleus of the thalamus (CMT) is a promising target, although descriptions of predictors of longer-term response are lacking. METHODS: We retrospectively reviewed patients who underwent RNS implantation with at least one CMT electrode at Baylor College of Medicine (BCM) and the University of Utah (UoU) from 2019-2023. Patients with = 6 months of follow-up were assessed for changes in clinical seizure frequency following surgery, as well as changes in seizure severity and subjective quality-of-life (QoL). RESULTS: Sixteen patients underwent CMT RNS (n = 12 BCM, n = 4 UoU) at a median age of 30 years [range 20-51] with a median 19-year history of epilepsy. All patients were evaluated by a multidisciplinary team that recommended thalamic RNS. Thirteen underwent bilateral CMT implantation and 7 had a documented lesional effect (&gt;50% reduction in seizures in the months following implantation). Thirteen patients had = 6-month follow-up with which to do subsequent seizure outcome analysis. In these patients, with a median follow-up of 18 months [6-40], median clinical seizure reduction was 80% [0-100%], 2 patients were seizure free for 6 months, and 1 was seizure free for 40 months. Patients with a lesional effect had a median 87% seizure reduction at last follow-up while those without a lesional effect had a 51% seizure reduction (two-tailed, two-sample t-test, p = 0.04). Subjective reduced seizure severity and increased QoL was documented in 92% of patients. CONCLUSIONS: RNS of the CMT can result in robust seizure frequency, severity, and QoL improvements in patients with DRE. Post-implantation lesional effect may be associated with longer-term improved response.

Safety of Concomitant Cortical and Thalamic Stereoencephalography Explorations in Patients With Drug-Resistant Epilepsies.

Intracranial electrophysiology of thalamic nuclei has demonstrated involvement of thalamic areas in the propagation of seizures in focal drug-resistant epilepsy. Recent studies have argued that thalamus stereoencephalography (sEEG) may aid in understanding the epileptogenic zone and treatment options. However, the study of thalamic sEEG-associated hemorrhage incidence has not been investigated in a cohort study design. In this article, we present the largest retrospective cohort study of sEEG patients and compare hemorrhage rates between those with and without thalamic sEEG monitoring. Retrospective chart review of clinical and epilepsy history, electrode implantation, rationale, and outcomes was performed for 76 patients (age 20-69 years) with drug-resistant epilepsy who underwent sEEG monitoring at our institution (2019-2022). A subset of 38% of patients (n = 30) underwent thalamic monitoring of the anterior thalamic nucleus (n = 14), pulvinar nucleus (n = 25), or both (n = 10). Planned perisylvian orthogonal sEEG trajectories were extended to 2- to 3-cm intraparenchymally access thalamic area(s).The decision to incorporate thalamic monitoring was made by the multidisciplinary epilepsy team. Statistical comparison of hemorrhage rate, type, and severity between patients with and without thalamic sEEG monitoring was made. Our approach for thalamic monitoring was not associated with local intraparenchymal hemorrhage of thalamic areas or found along extended cortical trajectories, and symptomatic hemorrhage rates were greater for patients with thalamic coverage (10% vs 0%, P = .056), although this was not found to be significant. Importantly, patients with perisylvian electrode trajectories, with or without thalamic coverage, did not experience a higher incidence of hemorrhage (P = .34). sEEG of the thalamus is a safe and valuable tool that can be used to interrogate the efficacy of thalamic neuromodulation for drug-resistant epilepsy. While patients with thalamic sEEG did have higher incidence of hemorrhage at any monitoring site, this finding was apparently not related to the method of perisylvian implantation and did not involve any trajectories targeting the thalamus.

Racial disparities in the utilization of invasive neuromodulation devices for the treatment of drug-resistant focal epilepsy.

Racial disparities affect multiple dimensions of epilepsy care including epilepsy surgery. This study aims to further explore these disparities by determining the utilization of invasive neuromodulation devices according to race and ethnicity in a multicenter study of patients living with focal drug-resistant epilepsy (DRE). We performed a post hoc analysis of the Human Epilepsy Project 2 (HEP2) data. HEP2 is a prospective study of patients living with focal DRE involving 10 sites distributed across the United States. There were no statistical differences in the racial distribution of the study population compared to the US population using census data except for patients reporting more than one race. Of 154 patients enrolled in HEP2, 55 (36%) underwent invasive neuromodulation for DRE management at some point in the course of their epilepsy. Of those, 36 (71%) were patients who identified as White. Patients were significantly less likely to have a device if they identified solely as Black/African American than if they did not (odds ratio = .21, 95% confidence interval = .05-.96, p = .03). Invasive neuromodulation for management of DRE is underutilized in the Black/African American population, indicating a new facet of racial disparities in epilepsy care.

Modification of brain conductivity in human focal epilepsy: A model-based estimation from stereoelectroencephalography.

We have developed a novel method for estimating brain tissue electrical conductivity using low-intensity pulse stereoelectroencephalography (SEEG) stimulation coupled with biophysical modeling. We evaluated the hypothesis that brain conductivity is correlated with the degree of epileptogenicity in patients with drug-resistant focal epilepsy. We used bipolar low-intensity biphasic pulse stimulation (.2 mA) followed by a postprocessing pipeline for estimating brain conductivity. This processing is based on biophysical modeling of the electrical potential induced in brain tissue between the stimulated contacts in response to pulse stimulation. We estimated the degree of epileptogenicity using a semi-automatic method quantifying the dynamic of fast discharge at seizure onset: the epileptogenicity index (EI). We also investigated how the location of stimulation within specific anatomical brain regions or within lesional tissue impacts brain conductivity. We performed 1034 stimulations of 511 bipolar channels in 16 patients. We found that brain conductivity was lower in the epileptogenic zone (EZ; unpaired median difference = .064, p < .001) and inversely correlated with the epileptogenic index value (p < .001, Spearman rho = -.32). Conductivity values were also influenced by anatomical site, location within lesion, and delay between SEEG electrode implantation and stimulation, and had significant interpatient variability. Mixed model multivariate analysis showed that conductivity is significantly associated with EI (F = 13.45, p < .001), anatomical regions (F = 5.586, p < .001), delay since implantation (F = 14.71, p = .003), and age at SEEG (F = 6.591, p = .027), but not with the type of lesion (F = .372, p = .773) or the delay since last seizure (F = 1.592, p = .235). We provide a novel model-based method for estimating brain conductivity from SEEG low-intensity pulse stimulations. The brain tissue conductivity is lower in EZ as compared to non-EZ. Conductivity also varies significantly across anatomical brain regions. Involved pathophysiological processes may include changes in the extracellular space (especially volume or tortuosity) in epileptic tissue.

Effectiveness analysis of three-drug combination therapies for refractory focal epilepsy

Selecting appropriate antiseizure medications (ASMs) for combination therapy in patients with drug-resistant epilepsy (DRE) is a complex task that requires an empirical approach, especially in patients receiving polytherapy. We aimed to analyze the effectiveness of various three-drug combinations in a group of patients with DRE under real-world conditions. This single-center, longitudinal observational study investigated patients with drug-resistant focal epilepsy who received three-drug regimens in the outpatient clinic of Tongji Hospital from September 2019 to December 2022. The effectiveness of each triple regimen was evaluated by the seizure-free rate and within-patient ratio of the seizure frequency (a seizure frequency ratio [SFR]<1 indicated superior efficacy). The independent t-test or Mann–Whitney U test was used for effectiveness analysis, and P values were adjusted by the Benjamini–Hochberg method for multiple comparisons. A total of 511 triple trials comprising 76 different regimens were conducted among 323 enrolled patients. Among these triple regimens, lamotrigine (LTG)/valproic acid (VPA)/topiramate (TPM) was the most frequently prescribed (29.4%, n ​= ​95). At the last clinical visit, 14.9% (n ​= ​48) of patients achieved seizure freedom after receiving triple therapy. LTG/VPA/TPM and LTG/VPA/levetiracetam (LEV) exhibited the highest seizure-free rates at 17.9% and 12.8%, respectively. These two regimens also had significantly lower median SFRs of 0.48 (interquartile range [IQR], 0.17–0.85; adjusted P ​< ​0.001) and 0.63 (IQR, 0.21–1.04; adjusted P ​< ​0.01), respectively. LTG/VPA/perampanel (PER) was another promising regimen that showed marginal effectiveness (median SFR ​= ​0.67; adjusted P ​= ​0.053). LTG/VPA/phenobarbital had the highest incidence of regimen-specific side effects (40.0%, 4/10), while the incidence of side effects from LTG/VPA/LEV was minimal (5.1%, 2/39). In conclusion, LTG/VPA/TPM and LTG/VPA/LEV exhibited superior efficacy and good tolerability in treating patients with DRE. Our results provide preliminary insights into the selection of ASMs for three-drug combination therapies in this clinically challenging population.

Neuropsychological characteristics of drug resistant epilepsy patients with and without comorbid functional seizures

IntroductionNeuropsychological testing is a mandatory component in the evaluation of drug resistant epilepsy. The results of testing may assist with both the localization of an epilepsy as well as assessment of surgical risk. Previous studies have demonstrated differences in the neuropsychological performance of patients with epilepsy and functional seizures. We hypothesized that comorbid functional seizures could potentially influence neuropsychological test performance. Therefore, we evaluated whether there is a difference in the neuropsychological test results between drug resistant epilepsy patients with and without comorbid functional seizures. MethodNeuropsychological test results were compared between 25 patients with drug resistant focal epilepsy and 25 patients that also had documented functional seizures. Univariate analyses and multiple logistic regression models were used to both assess performance differences between the groups and to assess whether test results could be used to accurately identify which patients had comorbid functional seizures. ResultsEpilepsy patients with comorbid functional seizures performed significantly worse on the FAS Verbal Fluency Test compared to ES patients (p = 0.047). Digit Span Backwards (p = 0.10), Digit Span Forwards (p = 0.14) and Working Memory Index (p = 0.10) tended to be lower in the epilepsy and functional seizures group but was not statistically significant. A multiple logistic regression model using the results of four neuropsychological tests was able to identify patients with comorbid functional seizures with 83.33% accuracy. ConclusionsThere are appeared to be some differences in the neuropsychological performance among drug resistant epilepsy patients based on whether they have comorbid functional seizures. These findings may have relevant implications for the interpretation of neuropsychological test results.