An Initial Experience of Completion Hemispherotomy via Magnetic Resonance-Guided Laser Interstitial Therapy.

INTRODUCTION: In carefully selected patients with medically refractory epilepsy, disconnective hemispherotomy can result in significant seizure freedom; however, incomplete disconnection can result in ongoing seizures and poses a significant challenge. Completion hemispherotomy provides an opportunity to finish the disconnection. We describe the use of magnetic resonance-guided laser interstitial thermal ablation (MRgLITT) for completion hemispherotomy. METHODS: Patients treated with completion hemispherotomy using MRgLITT at our institution were identified. Procedural and seizure outcomes were evaluated retrospectively. RESULTS: Five patients (3 males) underwent six MRgLITT procedures (one child treated twice) for completion hemispherotomy at a median age of 6 years (range 1.8-12.9). Two children had hemimegalencephaly, two had Rasmussen encephalitis, and one had polymicrogyria. All five children had persistent seizures likely secondary to incomplete disconnection after their functional hemispherotomy. The mean time from open hemispherotomy to MRgLITT was 569.5 ± 272.4 days (median 424, range 342-1,095). One patient underwent stereoelectroencephalography before MRgLITT. The mean number of ablation targets was 2.3 ± 0.47 (median 2, range 2-3). The mean length of the procedure was 373 min ± 68.9 (median 374, range 246-475). Four of the five patients were afforded improvement in their neurocognitive functioning and speech performance after ablation, with mean daily seizure frequency at 1 year of 1.03 ± 1.98 (median 0, range 0-5). Two patients achieved Engel Class I outcomes at 1 year after ablation, one was Engel Class III, and two were Engel Class IV. The mean follow-up time was 646.8 ± 179.5 days (median 634, range 384-918). No MRgLITT-related complications occurred. Delayed retreatment (>1 year) occurred in three patients: one child underwent redo ablation and two underwent anatomic hemispherectomy. CONCLUSION: We have demonstrated the feasibility of a minimally invasive approach for completion hemispherotomy using MRgLITT. Delayed retreatment was needed in three patients; thus, further study of this technique with comparison to other surgical techniques is warranted.

Virtual reality-based 3-dimensional localization of stereotactic EEG (SEEG) depth electrodes and related brain anatomy in pediatric epilepsy surgery.

INTRODUCTION: The increasing use of stereoelectroencephalography (SEEG) in the USA and the need for three-dimensional (3D) appreciation of complex spatial relationships between implanted stereotactic EEG depth electrodes and surrounding brain and cerebral vasculature are a challenge to clinicians who are used to two-dimensional (2D) appreciation of cortical anatomy having been traditionally trained on 2D radiologic imaging. Virtual reality and its 3D renderings have grown increasingly common in the multifaceted practice of neurosurgery. However, there exists a paucity in the literature regarding this emerging technology in its utilization of epilepsy surgery. METHODS: An IRB-approved, single-center retrospective study identifying all SEEG pediatric patients in which virtual reality was applied was observed. RESULTS: Of the 46 patients identified who underwent an SEEG procedure, 43.5% (20/46) had a 3D rendering (3DR) of their SEEG depth electrodes. All 3DRs were used during patient-family education and discussion among the Epilepsy multidisciplinary team meetings, while 35% (7/20) were used during neuronavigation in surgery. Three successful representative cases of its application were presented. DISCUSSION: Our institution's experience regarding virtual reality in the 3D representation of SEEG depth electrodes and the application to pre-surgical planning, patient-family education, multidisciplinary communication, and intraoperative neuronavigation demonstrate its applicability in comprehensive epilepsy patient care.

Scalp-HFO indexes are biomarkers for the lateralization and localization of the epileptogenic zone in preoperative assessment.

During the noninvasive evaluation phase for refractory epilepsy, the localization of the epileptogenic zone (EZ) is essential for the surgical protocols. Confirmation of laterality is required when the preoperative evaluation limits the EZ to bilateral anterior temporal lobes or bilateral frontal lobes. High-frequency oscillations (HFOs) are considered to be promising biological markers for the EZ. However, a large number of studies on HFOs stem from intracranial research. There were few quantitative measures for scalp HFOs, so we proposed a new method to quantify and analyze scalp HFOs. This method was called the "scalp-HFO index" (HI) and calculated in both the EZ and non-EZ. The calculation was based on the numbers and spectral power of scalp HFOs automatically detected. We labeled the brain lobes involved in the EZ as regions of interest (ROIs). The HIs based on the ripple numbers (n-HI) and spectral power (s-HI) were significantly higher in the ROI than in the contra-ROI (P = 0.012, P = 0.003), indicating that HIs contributed to the lateralization of EZ. The sensitivity and specificity of n-HI for the localization of the EZ were 90% and 79.58%, respectively, suggesting that n-HI was valuable in localizing the EZ. HI may contribute to the implantation strategy of invasive electrodes. However, few scalp HFOs were recorded when the EZ was located in the medial cortex region.NEW & NOTEWORTHY We proposed the scalp-high-frequency oscillation (HFO) index (HI) as a quantitative assessment method for scalp HFOs to locate the epileptogenic zone (EZ). Our results showed that the HI in regions of interest (ROIs) was significantly higher than in contra-ROIs. Sensitivity and specificity of HI based on ripple rates (n-HI) for EZ localization were 90% and 79.58%, respectively. If the n-HI of the brain region was >1.35, it was more likely to be an epileptogenic region. Clinical application of HIs as an indicator may facilitate localization of the EZ.

Individualized stereoelectroencephalography evaluation and navigated resection in medically refractory pediatric epilepsy.

Pediatric patients frequently require invasive exploration with intracranial electrodes to achieve high-resolution delineation of the epileptogenic zones (EZ). We intend to discuss the efficacy and safety of stereoelectroencephalophraphy (SEEG) monitoring in pediatric patients with difficulty to localize the EZ. We retrospectively analyzed presurgical findings, SEEG data, resections, and outcomes of a series of 72 consecutive pediatric patients (<18 yrs) who had medically refractory epilepsy and received SEEG recording between January 2015 and September 2019. There were 20 girls and 52 boys with a mean age of 10.13 ±â€¯4.11 years old (range: 1.8-18 years). Twenty-seven patients (37.5%) had nonlesional magnetic resonance imagings (MRIs). In total, 744 electrodes were implanted for an average of 10.33 ±â€¯2.53 (range: 3-18) electrodes per patient. Twenty-eight explorations were unilateral (17 left and 11 right), and 44 explorations were bilateral (12 of which was predominately one side). The average monitoring period in days for the SEEG was 8.99 ±â€¯5.79 (range: 3-25) days. The EZ could be located in 67 (94.4%) patients for the initial implantation according to SEEG monitoring. Lobectomy was performed in 12 patients (17.9%), of those anterior temporal lobectomy (ATL) was performed in 8 cases (11.9%) and insular plus was 2 cases (3.0%), multilobectomy resections in 15 cases (22.4%), tailored cortical resections in 37 cases (55.2%), and corpus callosotomy plus in 2 cases (3.0%). The average follow-up was 18.1 ±â€¯7.53 months (range: 6-54). Forty-three of 67 patients (64.2%) were Engel class I, 12 patients (17.9%) were Engel class II, 10 patients (14.9%) were Engel class III, and an additional 2 patients (3.0%) were Engel class IV. In the SEEG implantation series, no child experienced serious or permanent morbidity. One patient (1.4%) experienced symptomatic intracranial hemorrhage (ICH), and 3 patients (4.2%) experienced asymptomatic ICH. There were no postimplantation infections or other postoperative complications associated with the SEEG. Several common complications related to resection surgery were included in this series with zero mortality. Of the 6 patients in whom we performed a second surgery, 4 of them subsequently became seizure-free (66.7%) after undergoing the second resection with SEEG evaluation. Stereoelectroencephalophraphy is a safe and efficient methodology to identify the EZ in particularly complex cases of focal medically refractory epilepsy for pediatric patients, even in infancy and early childhood. Seizure outcomes of SEEG-guided resection surgery are desirable. We recommend SEEG evaluations and even a more aggressive resection in certain pediatric patients who failed initial resection with realistic chances to benefit from reoperation.

Vagus nerve stimulation with tachycardia detection provides additional seizure reduction compared to traditional vagus nerve stimulation.

PURPOSE: This study investigates the clinical and cost effectiveness of switching from traditional vagus nerve stimulation (VNS) to responsive VNS (rVNS), which has an additional ictal tachycardia detection and stimulation (AutoStim) mode. METHODS: Retrospective chart review was used to collect data from patients with medically refractory epilepsy who underwent generator replacements. Patients with confounding factors such as medication changes were excluded. Vagus nerve stimulation parameters, seizure frequency, and healthcare costs were collected for the 1-year period following generator replacement with the rVNS device. RESULTS: Documented seizure frequency was available for twenty-five patients. After implant with rVNS, 28% of patients had an additional ≥50% seizure reduction. There was a significant decrease in the average monthly seizure count (p = 0.039). In patients who were not already free of disabling seizures (n = 17), 41.2% had ≥50% additional seizure reduction. There was no difference in healthcare costs during the 1-year follow-up after the rVNS implant compared with one year prior. CONCLUSIONS: Ictal tachycardia detection and stimulation provided a significant clinical benefit in patients who were not free of disabling seizures with treatment from traditional VNS. There was no additional increase in healthcare costs during the first year after device replacement.

Complications after Anterior Temporal Lobectomy for Medically Intractable Epilepsy: A Systematic Review and Meta-Analysis.

BACKGROUND: The efficacy of surgery in the management of patients with longstanding temporal lobe epilepsy has been established. Anterior temporal lobectomy (ATL) is the most frequently implemented procedure. However, there is an obvious need to assess its perioperative safety. OBJECTIVE: We conducted a meta-analysis to estimate the postoperative mortality (Q1) and morbidity (Q2) associated with ATL for medically intractable epilepsy. In addition, we tried to identify the most frequent complications after ATL and assess their relative frequency (Q3) in children and adults. METHODS: Fixed- and random-effects model meta-analysis was conducted to assess the proportion estimate for each outcome individually. RESULTS: The postoperative mortality and cumulative morbidity were estimated to be as high as 0.01 (95% CI: 0.01, 0.02) and 0.17 (95% CI: 0.12, 0.24), respectively. Psychiatric disorders were the most common postoperative complications after ATL, with an estimated frequency as high as 0.07 (95% CI: 0.04, 0.10), followed by visual field defects (0.06; 0.03, 0.11), and cognitive disorders (0.05; 0.02, 0.10). Less frequent complications included hemiparesis and language disorders (0.03; 0.01, 0.06), infections (0.03; 0.02, 0.04), hemorrhage (0.02; 0.01, 0.05), cranial nerve deficits (0.03; 0.02, 0.05), extra-axial fluid collections (0.02; 0.01, 0.03), and medical complications (0.02; 0.01, 0.03). CONCLUSIONS: Even though the mortality after ATL is minimal, the overall morbidity cannot be ignored. Psychiatric disturbances, visual field defects, and cognitive disorders are the most common postoperative complications, and should be considered during the preoperative planning and consultation.

Laser ablation is effective for temporal lobe epilepsy with and without mesial temporal sclerosis if hippocampal seizure onsets are localized by stereoelectroencephalography.

OBJECTIVE: Selective laser amygdalohippocampotomy (SLAH) using magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is emerging as a treatment option for drug-resistant mesial temporal lobe epilepsy (MTLE). SLAH is less invasive than open resection, but there are limited series reporting its safety and efficacy, particularly in patients without clear evidence of mesial temporal sclerosis (MTS). METHODS: We report seizure outcomes and complications in our first 30 patients who underwent SLAH for drug-resistant MTLE between January 2013 and December 2016. We compare patients who required stereoelectroencephalography (SEEG) to confirm mesial temporal onset with those treated based on imaging evidence of MTS. RESULTS: Twelve patients with SEEG-confirmed, non-MTS MTLE and 18 patients with MRI-confirmed MTS underwent SLAH. MTS patients were older (median age 50 vs 30 years) and had longer standing epilepsy (median 40.5 vs 5.5 years) than non-MTS patients. Engel class I seizure freedom was achieved in 7 of 12 non-MTS patients (58%, 95% confidence interval [CI] 30%-86%) and 10 of 18 MTS patients (56%, 95% CI 33%-79%), with no significant difference between groups (odds ratio [OR] 1.12, 95% CI 0.26-4.91, P = .88). Length of stay was 1 day for most patients (range 0-3 days). Procedural complications were rare and without long-term sequelae. SIGNIFICANCE: We report similar rates of seizure freedom following SLAH in patients with MTS and SEEG-confirmed, non-MTS MTLE. Consistent with early literature, these rates are slightly lower than typically observed with surgical resection (60%-80%). However, SLAH is less invasive than open surgery, with shorter hospital stays and recovery, and severe procedural complications are rare. SLAH may be a reasonable first-line surgical option for patients with both MTS and SEEG confirmed, non-MTS MTLE.

Responsive neurostimulation: Candidates and considerations.

Responsive neurostimulation (RNS) has recently emerged as a safe and effective treatment for some patients with medically refractory focal epilepsy who are not candidates for surgical resection. Responsive neurostimulation involves an implanted neurostimulator and intracranial leads that detect incipient seizures and respond with electrical counterstimulation. Over 1800 patients have been treated with RNS since its FDA approval in 2013. Despite its widespread use, however, RNS presents distinct challenges for clinicians. What types of patients are most well-suited for treatment with RNS? Given the availability of two other neurostimulation modalities, vagus nerve stimulation (VNS) and thalamic deep brain stimulation (DBS), what patient characteristics favor or disfavor RNS? Once RNS candidates are identified, lead placement presents another challenge. Unlike VNS and thalamic DBS, which both involve prespecified electrode locations, RNS involves intracranial strip and/or depth electrodes that can be flexibly configured based on knowledge of the seizure onset zone. The efficacy of RNS may depend on optimal lead configuration, but there are few resources to guide clinicians in formulating lead placement strategies. Here, we address these challenges, first by reviewing clinical trial data supporting the safety and efficacy of RNS. Then, through a series of clinical vignettes from our center, we provide a framework for RNS patient selection. For each clinical scenario, we illustrate typical strategies for RNS lead placement. We outline considerations for choosing among available neurostimulation devices based on their intrinsic features. For example, a unique feature of RNS is that the neurostimulator provides chronic electrocorticography (ECoG), which has powerful diagnostic potential. We highlight emerging applications of chronic ECoG, and we discuss how the limitations of RNS will inform development of next-generation devices.

Vagal nerve stimulation for medically refractory epilepsy in Angelman syndrome: a series of three cases.

BACKGROUND: We describe three children with Angelman syndrome and medically refractory epilepsy. METHODS: Case series of three pediatric patients with Angelman syndrome and medically refractory epilepsy. All three patients failed medical treatment and were recommended for vagal nerve stimulator (VNS) implantation. RESULTS: Following VNS implantation, all three patients experienced reduction in seizure frequency greater than that afforded by medication alone. CONCLUSION: We present vagal nerve stimulator implantation as a viable treatment option for medically refractory epilepsy associated with Angelman syndrome.

Early outcomes of stereoelectroencephalography followed by MR-guided laser interstitial thermal therapy: a paradigm for minimally invasive epilepsy surgery.

OBJECTIVE Stereoelectroencephalography (sEEG) and MR-guided laser interstitial thermal therapy (MRgLITT) have both emerged as minimally invasive alternatives to open surgery for the localization and treatment of medically refractory lesional epilepsy. Although some data are available about the use of these procedures individually, reports are almost nonexistent on their use in conjunction. The authors' aim was to report early outcomes regarding efficacy and safety of sEEG followed by MRgLITT for localization and ablation of seizure foci in the pediatric population with medically refractory lesional epilepsy. METHODS A single-center retrospective review of pediatric patients who underwent sEEG followed by MRgLITT procedures was performed. Demographic, intraoperative, and outcome data were compiled and analyzed. RESULTS Four pediatric patients with 9 total lesions underwent sEEG followed by MRgLITT procedures between January and September 2017. The mean age at surgery was 10.75 (range 2-21) years. Two patients had tuberous sclerosis and 2 had focal cortical dysplasia. Methods of stereotaxy consisted of BrainLab VarioGuide and ROSA robotic guidance, with successful localization of seizure foci in all cases. The sEEG procedure length averaged 153 (range 67-235) minutes, with a mean of 6 (range 4-8) electrodes and 56 (range 18-84) contacts per patient. The MRgLITT procedure length averaged 223 (range 179-252) minutes. The mean duration of monitoring was 6 (range 4-8) days, and the mean total hospital stay was 8 (range 5-11) days. Over a mean follow-up duration of 9.3 (range 5.1-16) months, 3 patients were seizure free (Engel class I, 75%), and 1 patient saw significant improvement in seizure frequency (Engel class II, 25%). There were no complications. CONCLUSIONS These early data demonstrate that sEEG followed by MRgLITT can be used safely and effectively to localize and ablate epileptogenic foci in a minimally invasive paradigm for treatment of medically refractory lesional epilepsy in pediatric populations. Continued collection of data with extended follow-up is needed.

Deep brain stimulation for seizure control in drug-resistant epilepsy.

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.

Brain region and epilepsy-associated differences in inflammatory mediator levels in medically refractory mesial temporal lobe epilepsy.

BACKGROUND: Epilepsy patients have distinct immune/inflammatory cell profiles and inflammatory mediator levels in the blood. Although the neural origin of inflammatory cells and mediators has been implied, few studies have measured these inflammatory components in the human brain itself. This study examines the brain levels of chemokines (8), cytokines (14), and vascular injury mediators (3) suspected of being altered in epilepsy. METHODS: Soluble protein extracts of fresh frozen resected hippocampus, entorhinal cortex, and temporal cortex from 58 medically refractory mesial temporal lobe epilepsy subjects and 4 nonepileptic neurosurgical subjects were assayed for 25 inflammation-related mediators using ultrasensitive low-density arrays. RESULTS: Brain mediator levels were compared between regions and between epileptic and nonepileptic cases, showing a number of regional and possible epilepsy-associated differences. Eotaxin, interferon-γ, interleukin (IL)-2, IL-4, IL-12 p70, IL-17A, tumor necrosis factor-α, and intercellular adhesion molecule (ICAM)-1 levels were highest in the hippocampus, the presumptive site of epileptogenesis. Surprisingly, IL-1ß and IL-1α were lowest in the hippocampus, compared to cortical regions. In the temporal cortex, IL-1ß, IL-8, and MIP-1α levels were highest, compared to the entorhinal cortex and the hippocampus. The most pronounced epilepsy-associated differences were decreased levels of eotaxin, IL-1ß, C-reactive protein, and vascular cell adhesion molecule (VCAM)-1 and increased IL-12 p70 levels. Caution must be used in interpreting these results, however, because nonepileptic subjects were emergent neurosurgical cases, not a control group. Correlation analyses of each mediator in each brain region yielded valuable insights into the regulation of these mediator levels in the brain. Over 70 % of the associations identified were between different mediators in a single brain region, providing support for local control of mediator levels. Correlations of different mediators in different brain regions suggested more distributed control mechanisms, particularly in the hippocampus. Interestingly, only four mediators showed robust correlations between the brain regions, yet levels in three of these were significantly different between regions, indicating both global and local controls for these mediators. CONCLUSIONS: Both brain region-specific and epilepsy-associated changes in inflammation-related mediators were detected. Correlations in mediator levels within and between brain regions indicated local and global regulation, respectively. The hippocampus showed the majority of interregional associations, suggesting a focus of inflammatory control between these regions.

New Techniques and Progress in Epilepsy Surgery.

While open surgical resection for medically refractory epilepsy remains the gold standard in current neurosurgical practice, modern techniques have targeted areas for improvement over open surgical resection. This review focuses on how a variety of these new techniques are attempting to address these various limitations. Stereotactic electroencephalography offers the possibility of localizing deep epileptic foci, improving upon subdural grid placement which limits localization to neocortical regions. Laser interstitial thermal therapy (LITT) and stereotactic radiosurgery can minimally or non-invasively ablate specific regions of interest, with near real-time feedback for laser interstitial thermal therapy. Finally, neurostimulation offers the possibility of seizure reduction without needing to ablate or resect any tissue. However, because these techniques are still being evaluated in current practice, there are no evidence-based guidelines for their use, and more research is required to fully evaluate their proper role in the current management of medically refractory epilepsy.

The case for medical marijuana in epilepsy.

Charlotte, a little girl with SCN1A-confirmed Dravet syndrome, was recently featured in a special that aired on CNN. Through exhaustive personal research and assistance from a Colorado-based medical marijuana group (Realm of Caring), Charlotte's mother started adjunctive therapy with a high concentration cannabidiol/Δ(9) -tetrahydrocannabinol (CBD:THC) strain of cannabis, now known as Charlotte's Web. This extract, slowly titrated over weeks and given in conjunction with her existing antiepileptic drug regimen, reduced Charlotte's seizure frequency from nearly 50 convulsive seizures per day to now 2-3 nocturnal convulsions per month. This effect has persisted for the last 20 months, and Charlotte has been successfully weaned from her other antiepileptic drugs. We briefly review some of the history, preclinical and clinical data, and controversies surrounding the use of medical marijuana for the treatment of epilepsy, and make a case that the desire to isolate and treat with pharmaceutical grade compounds from cannabis (specifically CBD) may be inferior to therapy with whole plant extracts. Much more needs to be learned about the mechanisms of antiepileptic activity of the phytocannabinoids and other constituents of Cannabis sativa.

A side-by-side comparison of fine-tuning options for treatment of medically refractory epilepsy: Antiseizure medications, vagus nerve stimulation and ketogenic diet therapies.

There are many treatment options available for patients with medically refractory epilepsy including antiseizure medications, surgery, devices and ketogenic diet therapy. Ketogenic diet therapy has been shown to be a safe and effective treatment option in adult and pediatric patients. In order to obtain maximal clinical effectiveness and tolerability of any treatment option, adjustments are often necessary. This article outlines the "fine-tuning" options available for antiseizure medications, vagus nerve stimulation and ketogenic diet therapies and demonstrates that ketogenic diet therapies offer a wider array of personalizing and fine-tuning options.

Epileptic tissue localization using graph-based networks in the high frequency oscillation range of intracranial electroencephalography.

PURPOSE: High frequency oscillations (HFOs) are an emerging biomarker of epilepsy. However, very few studies have investigated the functional connectivity of interictal iEEG signals in the frequency range of HFOs. Here, we study the corresponding functional networks using graph theory, and we assess their predictive value for automatic electrode classification in a cohort of 20 drug resistant patients. METHODS: Coherence-based connectivity analysis was performed on the iEEG recordings, and six different local graph measures were computed in both sub-bands of the HFO frequency range (80-250 Hz and 250-500 Hz). Correlation analysis was implemented between the local graph measures and the ripple and fast ripple rates. Finally, the WEKA software was employed for training and testing different predictive models on the aforementioned local graph measures. RESULTS: The ripple rate was significantly correlated with five out of six local graph measures in the functional network. For fast ripples, their rate was also significantly (but negatively) correlated with most of the local metrics. The results from WEKA showed that the Logistic Regression algorithm was able to classify highly HFO-contaminated electrodes with an accuracy of 82.5 % for ripples and 75.4 % for fast ripples. CONCLUSION: Functional connectivity networks in the HFO band could represent an alternative to the direct use of distinct HFO events, while also providing important insights about hub epileptic areas that can represent possible surgical targets. Automatic electrode classification through FC-based classifiers can help bypass the burden of manual HFO annotation, providing at the same time similar amount of information about the epileptic tissue.

The impact of social determinants of health on utilization of pediatric epilepsy surgery: a systematic review.

OBJECTIVE: A minority of pediatric patients who may benefit from epilepsy surgery receive it. The reasons for this utilization gap are complex and not completely understood. Patient and caregiver social determinants of health (SDOH) may impact which patients undergo surgery and when. The authors conducted a systematic review examining SDOH and surgical intervention in children with drug-resistant epilepsy (DRE). They aimed to understand which factors influenced time to surgical program referral or receipt of epilepsy surgery among children with DRE, as well as identify areas to characterize the SDOH impacting epilepsy surgery in children and guide efforts aimed to promote health equity in epilepsy. METHODS: A systematic review was conducted using the PubMed, Embase, and Scopus databases in January 2022. Studies were analyzed by title and abstract, then full text, to identify all studies examining the impact of SDOH on utilization of epilepsy surgery. Studies meeting inclusion criteria were analyzed for SDOH examined, outcomes, and key findings. Quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: Of 4545 resultant articles, 18 were included. Studies examined social, cultural, and environmental factors that contributed to SDOH impacting epilepsy surgery. Patients who underwent surgical evaluation were found to be most commonly White and privately insured and have college-educated caregivers. Five studies found differences in time to referral/surgery or rates of surgery by racial group, with most finding an increased time to referral/surgery or lower rates of surgery for those who were Hispanic and/or non-White. Four studies found that private insurance was associated with higher surgical utilization. Three studies found higher household income was related to surgical utilization. No studies examined biological, psychological, or behavioral factors that contributed to SDOH impacting epilepsy surgery. CONCLUSIONS: The authors conducted a systematic review exploring the impact of SDOH in DRE surgery utilization. They found that race, ethnicity, insurance type, caregiver educational attainment, and household income demonstrate relationships with pediatric epilepsy surgery. Further study is necessary to understand how these factors, and others not identified in this study, contribute to the low rates of utilization of epilepsy surgery and potential target areas for interventions aiming to increase equity in access to epilepsy surgery in children.

Severe Epilepsy in an Individual With a TSC2 R905Q Variant Prompting Late Diagnosis in Affected Family Members.

BACKGROUND: Tuberous sclerosis complex (TSC) is a multisystemic disorder caused by inactivating variants in the mTOR pathway inhibitor genes TSC1 and TSC2. Individuals with TSC are predisposed to benign tumors in multiple organs as well as TSC-associated neuropsychiatric disorders (TAND) and epilepsy. Pathogenic variants in TSC2 are typically associated with a more severe phenotype compared with TSC1; the TSC2 R905Q variant has been shown to be an exception, where patients have been reported to present with unusually mild TSC features that may be undetected. METHODS: We studied the TSC phenotype of a 13-year-old individual and three family members with a TSC2 c.2714G>A (R905Q) pathogenic variant. RESULTS: Patient 1 presented with severe medically refractory epilepsy without tubers or subependymal nodules and only mild dermatologic features of TSC missed on virtual examinations. Her mother and maternal aunt (Patients 2 and 3-diagnosed after age 50 years) presented with a mild phenotype, with dermatologic features and TAND. Her maternal uncle (Patient 4-diagnosed at age 47 years) displayed the most severe phenotype, presenting with intellectual disability, medically refractory epilepsy, obsessive-compulsive disorder, post-traumatic stress disorder, and psychosis. CONCLUSIONS: This study expands the possible phenotypic spectrum of TSC2 R905Q variant, demonstrating an association with severe epilepsy without associated neuroradiological stigmata. This presentation highlights the possibility of occult focal cortical dysplasia in TSC and emphasizes the importance of genetic testing in individuals with severe epilepsy. Moreover, a late adult diagnosis was subsequently made in other family members allowing for appropriate TSC surveillance to occur.

Posterior Reversible Encephalopathy Syndrome (PRES) and the Uncommon Sequela: Mesial Temporal Sclerosis.

Posterior reversible encephalopathy syndrome is often linked to conditions like hypertension and is characterized by reversible brain edema. The development of mesial temporal sclerosis as a consequence of posterior reversible encephalopathy syndrome is an uncommon clinical outcome.  We report a 48-year-old female who initially presented with severe iron deficiency anemia, hypertension, and septic tenosynovitis requiring surgical drainage with subsequent development of posterior reversible encephalopathy syndrome accompanied by endocarditis. Although there was a question of one seizure episode during one of her hospital days, the patient experienced multiple seizure episodes three months after she left the hospital. Subsequent MRI demonstrated atrophy of the left mesial temporal lobe suggesting mesial temporal sclerosis.  The temporal development of mesial temporal sclerosis in a patient with posterior reversible encephalopathy syndrome highlights mesial temporal sclerosis as a potential long-term consequence of posterior reversible encephalopathy syndrome, and the need for imaging surveillance in patients diagnosed with posterior reversible encephalopathy syndrome.

Readability and content gaps in online epilepsy surgery materials as potential health literacy and shared-decision-making barriers.

OBJECTIVE: Epilepsy surgery is an effective albeit underused treatment for refractory epilepsy, and online materials are vital to patient understanding of the complex process. Our goal is to analyze the readability and content inclusion of online patient health education materials designed for epilepsy surgery. METHODS: A private browser setting was used on Google and Bing to identify the top 100 search results for the terms "epilepsy+surgery". Scientific papers, insurance pages, pay-wall access sites, and non-text content were excluded. The website text was reformatted to exclude graphics, contact information, links, and headers. Readability metrics were calculated using an online tool. Text content was analyzed for inclusion of important concepts (pre-surgical evaluation, complications, risks of continued seizures, types of surgery, complimentary diagrams/audiovisual material). Comparison of readability and content inclusion was performed as a function of organization types (epilepsy center, community health organization, pediatric-specific) and location (region, country). RESULTS: Browser search yielded 82 distinct websites with information regarding epilepsy surgery, with 98.7% of websites exceeding the recommended 6th-grade reading level for health information. Epilepsy centers had significantly worse readability (Flesch-Kincaid Grade Level (FKGL) P < 0.01 and Flesch Reading Ease (FRE) P < 0.05). Content analysis showed that only 37% of websites discuss surgical side effects and only 23% mention the risks of continued seizures. Epilepsy centers were less likely to report information on surgical side effects (P < 0.001). UK-based websites had better readability (FKGL P < 0.01 and FRE P < 0.01) and were more likely to discuss side effects (P = 0.01) compared to US-based websites. SIGNIFICANCE: The majority of online health content is overly complex and relatively incomplete in multiple key areas important to health literacy and understanding of surgical candidacy. Our findings suggest academic organizations, including level 4 epilepsy centers, need to simplify and broaden online education resources. More comprehensive, publicly accessible, and readable information may lead to better-shared decision-making.