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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. We studied the TSC phenotype of a 13-year-old individual and three family members with a TSC2 c.2714G>A (R905Q) pathogenic variant. 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. 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. [ABSTRACT FROM AUTHOR]

• Graph theory can interpret coherence-based connectivity of iEEG in MRE patients. • Specific local graph metrics are significantly correlated with the ripple rate. • Specific local graph metrics are negatively correlated with the fast ripple rate. • Graph measure-based classifiers can predict epileptogenicity with 82.5 % accuracy. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Open corpus callosotomy (CC) poses a higher risk of perioperative morbidity than does magnetic resonance–guided laser interstitial thermal therapy (MRgLITT) for treatment of drop and generalized seizures without documented superiority. We present a single-institution comparison between open and MRgLITT CC. A 2-year retrospective review was performed of patients who underwent open and MRgLITT CC (January 2019–January 2021). Demographics, surgical outcome data, hospital costs, and interhemispheric connectivity with diffusion tensor imaging were compared. The average age in years was 9.3 and 11.4 for CC (n = 4) and MRgLITT (n = 9), respectively. Preoperative drop seizure frequency was higher in CC (25 vs. 14.5 seizures/day; P = 0.59). At 10 months follow-up, the reduction in drop seizure frequency was better in open CC, but not statistically significant (93.8% vs. 64.3%; P = 0.21). The extent of CC ablation did not correlate with seizure reduction (Pearson coefficient = 0.09). An inverse correlation between interhemispheric connectivity change (diffusion tensor imaging analysis) and drop seizure frequency reduction was noted (Pearson coefficient = –0.97). Total hospital cost was significantly lower in MRgLITT ($67,754 vs. $107,111; P = 0.004), attributed to lower intensive care unit (1.1 vs. 4 days; P = 0.004) and total hospital stay (1.8 vs. 10.5 days; P = 0.0001). Postoperative hydrocephalus was present in 75% of patients in the CC group compared with zero in the MRgLITT group. Our middle-volume single-institution experience shows the safety, efficacy, and cost-effective benefit of MRgLITT compared with the traditional CC with therapeutic equipoise. This study is limited by the number of patients and, hence, further patient enrollment or multicenter study is warranted. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. • Ketogenic diet therapies are safe and effective treatment options for adults and children with medically refractory epilepsy. • Patients desire treatment options which can be tailored to their individual needs. • KDTs may offer greater opportunity for enhancement and personalization than ASMs or VNS, but require more time and workload [ABSTRACT FROM AUTHOR]

Stereoelectroencephalography (SEEG) has gained popularity as an invasive monitoring modality for epileptogenic zone (EZ) localization. The need and indications for SEEG in patients with evident brain lesions or associated abnormalities on imaging is debated. We report our experience with SEEG as a presurgical evaluation tool for patients with lesional epilepsy. A retrospective cohort study was performed of 131 patients with lesional or magnetic resonance imaging abnormality–associated medically refractory focal epilepsy who underwent resections from 2010 to 2017. Seventy-one patients had SEEG followed by resection, and 60 had no invasive recordings. Volumetric analysis of resection cavities from 3T magnetic resonance imaging was performed. Mean lesion and resection volumes for SEEG and non-SEEG were 16.2 (standard deviation [SD] = 29) versus 23.7 cm3 (SD = 38.4) and 28.1 (SD = 23.2) versus 43.6 cm3 (SD = 43.5), respectively (P = 0.009). Comparing patients with seizure recurrence and patients who remained seizure free, significantly associated variables with seizure recurrence included mean number of failed antiseizure medications (6.86 [SD = 0.32] vs. 5.75 [SD = 0.32]; P = 0.01) and in SEEG patients the mean number of electrodes implanted (8.1 [SD = 0.8] vs. 5.0 [SD = 0.8]; P = 0.005). After multivariate analysis, only failed numbers of medication remained significantly associated with seizure recurrence. Seizure outcomes did not correlate with final resection volume after SEEG evaluation. SEEG evaluation presurgically can be used to maintain the efficacy of resection and decrease the volume and subsequent risk of extensive tissue removal. We believe that this technology allows resective surgery to proceed in a subpopulation of patients with lesional epilepsy who may otherwise not have been considered surgical candidates. [ABSTRACT FROM AUTHOR]

The expansion in treatments for medically refractory epilepsy heightens the importance of identifying patients who are likely to benefit from vagus nerve stimulation (VNS). Here, we identify predictors with a positive VNS response. We present a retrospective analysis of 158 patients with medically refractory epilepsy. Patients were categorized as VNS responders or nonresponders. Baseline characteristics and time to VNS response were recorded. Univariate and multivariate Cox regression were used to identify predictors of response. Recursive partitioning analysis was used to identify likely VNS responders. Eighty-nine (56.3%) patients achieved ≥50% seizure frequency reduction. Left-hand dominance (hazard ratio [HR] 1.703, P = 0.038), age at epilepsy onset ≥15 years (HR 2.029, P = 0.005), duration of epilepsy ≥8 years (HR 1.968, P = 0.007) and age at implantation ≥35 years (HR 1.809, P = 0.020), and baseline seizure frequency <5/month (HR 1.569, P = 0.044) were significant univariate predictors of VNS response. Following multivariate Cox regression, left-hand dominance, age at epilepsy onset ≥15 years, and duration of epilepsy ≥8 years remained significant. With recursive partitioning analysis, patients with either age at epilepsy onset ≥15 years, left-hand dominance, or baseline seizure frequency <5/month were stratified into Group A and had a 73.9% responder rate; the remaining patients stratified into Group B had a 43.8% responder rate. Patients with age at epilepsy onset ≥15 years, left-hand dominance, or baseline seizure frequency <5/month are ideal candidates for VNS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Background Hybrid PET/MRI can non-invasively improve localization and delineation of the epileptic focus (EF) prior to surgical resection in medically refractory epilepsy (MRE), especially when MRI is negative or equivocal. In this study, we developed a PET-guided diffusion tractography (PET/DTI) approach combining 18F-fluorodeoxyglucose PET (FDG-PET) and diffusion MRI to investigate white matter (WM) integrity in MRI-negative MRE patients and its potential impact on epilepsy surgical planning. Methods FDG-PET and diffusion MRI of 14 MRI-negative or equivocal MRE patients were used to retrospectively pilot the PET/DTI approach. We used asymmetry index (AI) mapping of FDG-PET to detect the EF as brain areas showing the largest decrease in FDG uptake between hemispheres. Seed-based WM fiber tracking was performed on DTI images with a seed location in WM 3 mm from the EF. Fiber tractography was repeated in the contralateral brain region (opposite to EF), which served as a control for this study. WM fibers were quantified by calculating the fiber count, mean fractional anisotropy (FA), mean fiber length, and mean cross-section of each fiber bundle. WM integrity was assessed through fiber visualization and by normalizing ipsilateral fiber measurements to contralateral fiber measurements. The added value of PET/DTI in clinical decision-making was evaluated by a senior neurologist. Results In over 60% of the patient cohort, AI mapping findings were concordant with clinical reports on seizure-onset localization and lateralization. Mean FA, fiber count, and mean fiber length were decreased in 14/14 (100%), 13/14 (93%), and 12/14 (86%) patients, respectively. PET/DTI improved diagnostic confidence in 10/14 (71%) patients and indicated that surgical candidacy be reassessed in 3/6 (50%) patients who had not undergone surgery. Conclusions We demonstrate here the utility of AI mapping in detecting the EF based on brain regions showing decreased FDG-PET activity and, when coupled with DTI, could be a powerful tool for detecting EF and assessing WM integrity in MRI-negative epilepsy. PET/DTI could be used to further enhance clinical decision-making in epilepsy surgery.

Rationale: Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder characterized by multiple multi-organ hamartomas. Medically refractory epilepsy (MRE) occurs in up to 60% of TSC patients. The results of the EXIST-3 study have shown the efficacy of MRE treatment with an mTOR inhibitor everolimus. In the Russian Federation, the drug has been approved since 2017 for the treatment of TSC-associated MRE in patients above 2 years of age. Aim: To assess the efficacy of everolimus for treatment of medically refractory seizures associated with TSC. Materials and methods: We retrospectively analyzed medical files from 89 patients with TSC who had been admitted with MRE to the Department of Psychoneurology and Epileptology, Research and Clinical Institute for Pediatrics (Moscow, Russia) from November 2016 to December 2018. The patients were divided into three groups depending on their indications for everolimus: 1) 17 patients received with MRE; 2) 64 patients with MRE and subependymal giant cell astrocytoma (SEGA) of > 1 cm in diameter; 3) 8 patients with MRE and renal angiomyolipoma (AML) of > 3 cm in diameter. Their median age was 7.9 year (range, from 2 to 34 years). There were 45 (50.6%) male and 44 (49.4%) female patients. Their treatment lasted from 6 months to 5 years; the dose of everolimus was 8 mg/m2 . Focal seizures were more prevalent than epileptic spasms: 60 (67.4%) and 29 (32.6%) patients, respectively. Results: There were 9/17 (52.9%) responders in the MRE group, 16/64 (25%) in the MRE + SEGA group, and 4/8 (50%) in the MRE + AML group. Mild to moderate stomatitis was the most frequent side effect (40.5%). Conclusion: Everolimus is a new important agent for MRE in TSC patients. Treatment with everolimus is safe and well tolerated.

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. [ABSTRACT FROM AUTHOR]

This article is co-authored by a parent of a 32-year-old male patient with Lennox–Gastaut syndrome (LGS) and his epileptologist. It discusses the parent's experience of having a child with LGS from diagnosis through living day-to-day with the disease and the physician's perspective when treating this devastating epilepsy syndrome. The patient's mother, who is his legal representative, provided written consent for publication of this article. [ABSTRACT FROM AUTHOR]

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.

Background: Hybrid PET/MRI can non-invasively improve localization and delineation of the epileptic focus (EF) prior to surgical resection in medically refractory epilepsy (MRE), especially when MRI is negative or equivocal. In this study, we developed a PET-guided diffusion tractography (PET/DTI) approach combining 18F-fluorodeoxyglucose PET (FDG-PET) and diffusion MRI to investigate white matter (WM) integrity in MRI-negative MRE patients and its potential impact on epilepsy surgical planning. Methods: FDG-PET and diffusion MRI of 14 MRI-negative or equivocal MRE patients were used to retrospectively pilot the PET/DTI approach. We used asymmetry index (AI) mapping of FDG-PET to detect the EF as brain areas showing the largest decrease in FDG uptake between hemispheres. Seed-based WM fiber tracking was performed on DTI images with a seed location in WM 3 mm from the EF. Fiber tractography was repeated in the contralateral brain region (opposite to EF), which served as a control for this study. WM fibers were quantified by calculating the fiber count, mean fractional anisotropy (FA), mean fiber length, and mean cross-section of each fiber bundle. WM integrity was assessed through fiber visualization and by normalizing ipsilateral fiber measurements to contralateral fiber measurements. The added value of PET/DTI in clinical decision-making was evaluated by a senior neurologist. Results: In over 60% of the patient cohort, AI mapping findings were concordant with clinical reports on seizure-onset localization and lateralization. Mean FA, fiber count, and mean fiber length were decreased in 14/14 (100%), 13/14 (93%), and 12/14 (86%) patients, respectively. PET/DTI improved diagnostic confidence in 10/14 (71%) patients and indicated that surgical candidacy be reassessed in 3/6 (50%) patients who had not undergone surgery. Conclusions: We demonstrate here the utility of AI mapping in detecting the EF based on brain regions showing decreased FDG-PET activity and, when coupled with DTI, could be a powerful tool for detecting EF and assessing WM integrity in MRI-negative epilepsy. PET/DTI could be used to further enhance clinical decision-making in epilepsy surgery. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the expression of somatostatin receptors (SSTRs) and markers of mTOR pathway in paediatric glioneuronal tumours and correlate these findings with tumour type, BRAFV600E mutational status and clinical characteristics such as tumour location, seizure frequency and duration, and age.Method: 37 children and adolescents with a neuropathological diagnosis of glioneuronal tumour were identified over a 22-year period. Immunohistochemical analyses for SSTRs type 1, 2A, 3, 5 and ezrin-radixin-moesin (ERM) and phosphorylated S6 (pS6), which are indicators of mTOR pathway activation, were performed in tumour specimens from 33 patients and evaluated using the immunoreactive score (IRS). The IRS were compared to tumour type, BRAFV600E status and clinical characteristics.Results: Ganglioglioma (GG) was the most frequently encountered subgroup (n = 27), followed by dysembryoplastic neuroepithelial tumour (DNET; n = 4). GGs expressed SSTR2A and SSTR3 to a high extent, 56 % and 44 % respectively. Expression of SSTR2A was also found in DNETs. Signs of mTOR pathway activation were abundant in GGs, but only present in one DNET. No correlations with BRAFV600E presence or clinical characteristics were found.Conclusions: Expression of SSTRs and activation of mTOR pathway in paediatric glioneuronal tumour suggest that somatostatin analogues and mTOR inhibitors may have potential therapeutic implications in a subset of inoperable childhood glioneuronal tumours causing medically refractory epilepsy and/or tumour growth. Further clinical studies are warranted to validate these findings. [ABSTRACT FROM AUTHOR]

Background: To control brain tumor-related epilepsy (BTRE), both epileptological and neuro-oncological approaches are required. We hypothesized that using depth electrodes (DEs) as fence post catheters, we could detect the area of epileptic seizure onset and achieve both brain tumor removal and epileptic seizure control. Methods: Between August 2009 and April 2018, we performed brain tumor removal for 27 patients with BTRE. Patients who underwent lesionectomy without DEs were classified into Group 1 (13 patients) and patients who underwent the fence post DE technique were classified into Group 2 (14 patients). Results: The patients were 15 women and 12 men (mean age, 28.1 years; median age 21 years; range, 5-68 years). The brain tumor was resected to a greater extent in Group 2 than Group 1 (P < 0.001). Shallower contacts showed more epileptogenicity than deeper contacts (P < 0.001). Group 2 showed better epilepsy surgical outcomes than Group 1 (P = 0.041). Conclusion: Using DEs as fence post catheters, we detected the area of epileptic seizure onset and controlled epileptic seizures. Simultaneously, we removed the brain tumor to a greater extent with fence post DEs than without. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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. Highlights • Responsive neurostimulation (RNS) is approved for refractory focal epilepsy. • Candidates for RNS have two seizure foci or a single unresectable seizure focus. • RNS intracranial leads can be flexibly configured based on the clinical scenario. • The efficacy of RNS relative to other neurostimulation modalities is unknown. • RNS provides chronic electrocorticography that has powerful diagnostic potential. [ABSTRACT FROM AUTHOR]

Focal cortical dysplasia (FCD) is the most common cause of intractable focal epilepsy in children, in whom seizures are most commonly pharmacoresistant from onset. This review summarizes the current understandings of the epidemiology, natural history, and the proposed mechanisms of epileptogenisis in FCD. Advances in neuroimaging techniques have enhanced the recognition of this pathology, which can be subtle. Illustrative neurophysiology and imaging examples are provided to help the clinicians identify diagnostic evidence of suspected FCD. Given the refractory course to pharmacologic management, alternative options such as ketogenic diet, resective surgery or neuromodulation can be considered. Recognition of FCD pathology in children with early onset epilepsy should prompt timely evaluations for resective surgery, which may render a significant number of patients seizure-free and improve neurocognitive outcome. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this trial was to investigate the efficacy and safety of transcutaneous vagal nerve stimulation (t-VNS) in the palliative treatment of drug resistant epileptic patients ineligible for surgery.Methods: Twenty adult patients received four hours of t-VNS per day for six months (T1), followed by a two-month washout period (T2). The frequency and type of seizures recorded at T1 and T2 were compared with those occurring in the three months preceding study entry (T0). Responders (>30% reduction in the total number of seizures) subsequently received two hours of t-VNS per day for further six months (T3). All patients underwent electroencephalography (EEG) and completed the Quality of Life in Epilepsy questionnaire at baseline and T1.Results: At T1 six patients were considered responders. In these patients, at T3 the average reduction in seizure frequency was 60% compared to T0 (p = 0.043), and 51% compared to T2 (p = 0.043). Responders had more often seizures with falls (5 of 6; 83.3%) compared with non-responders (3 of 14; 21.4%) (p = 0,010) and t-VNS reduced their frequency by a percentage ranging from 47.5 to 100%. There was no change in responders' EEG findings after stimulation. At the end of the trial, three responders continued t-VNS, one implanted VNS.Conclusions: t-VNS had no or minimal side effects and significantly reduced seizures in about one third of the enrolled patients. Further studies should be planned to assess whether t-VNS is a suitable tool to predict the efficacy of implanted VNS. [ABSTRACT FROM AUTHOR]

Objective The aim of the study was to evaluate the parameters for localizing the seizure onset zone in refractory epilepsy patients using cortico-cortical evoked potentials (CCEP). Methods Fifteen patients (nine females) with medically refractory partial epilepsy underwent stereo electro encephalography (SEEG) in Tsinghua University Yu-Quan Hospital from 2015 to 2016. Clinical semiology and, scalp electroencephalography (EEG) findings were analyzed during phase I preoperative evaluation. During phase II evaluation, localization of seizure onset zone (SOZ) was analyzed using SEEG by experienced epileptologists. Meanwhile, the cortico-cortical evoked potential (CCEP) paradigm was tested in all patients in phase II. The value of root-mean-square (RMS) of CCEPs amplitude from 7 ms to 300 ms after stimulation was analyzed to quantify the response. Results RMS of CCEPs amplitude in SOZ was higher than in seizure propagation zone (SPZ) (P < 0.05) and non-seizure onset zone (NSOZ) (P < 0.05). RMS of CCEPs amplitude in SOZ was higher than in NSOZ in epilepsy patients with secondary generalized tonic-clonic seizures (SGTCS) (N = 6, P < 0.05); The RMS of CCEPs amplitude in SOZ was strikingly higher than SPZ in the repetitive spiking (RS) onset pattern, and the difference was significant (N = 5, P < 0.01). Conclusions This data indicated that CCEP response is enhanced in SOZ despite different seizure types (with or without SGTCS). CCEP may be an effective method to locate SOZ. [ABSTRACT FROM AUTHOR]

A procedure called laser interstitial thermal ablation has been utilized to treat drug resistant epilepsy. With this technique, a probe is stereotactically inserted into a target structure responsible for seizures, such as mesial temporal lobe, hypothalamic hamartoma, or a small malformation of cortical development, and the tip is then heated by application of laser energy to ablate structures adjacent to the probe tip. This procedure has the advantage of selectively targeting small lesions responsible for seizures, and is far less invasive than open surgery with shorter hospitalization, less pain, and rapid return to normal activities. Initial results in mesial temporal lobe epilepsy are promising, with perhaps half of patients becoming free of seizures after the procedure. Neuropsychological deficits appear to be reduced because of the smaller volume of ablated cortex in contrast to large resections. More research must be done to establish optimal targeting of structures for ablation and selection of candidates for surgery, and more patients must be studied to better establish efficacy and adverse effect rates. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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, = .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. [ABSTRACT FROM AUTHOR]

For some patients with medically refractory epilepsy (MRE), surgery is a safe and effective treatment for controlling epilepsy. However, the functional consequences of such surgery on brain activity and connectivity in children remain unknown. In the present study, we carried out a longitudinal study using resting-state functional magnetic resonance imaging in 10 children with MRE before and again at a mean of 79 days after surgery, as well as in a group of 28 healthy controls. Compared with the controls, children with epilepsy exhibited abnormalities in intrinsic activity in the thalamus, putamen, pallidum, insula, hippocampus, cerebellum, and cingulate gyrus both before and after surgery. Longitudinal analyses showed that the amplitude of low frequency fluctuations (ALFF) increased in the parietal–frontal cortex and decreased in the deep nuclei from pre- to post-surgery. The percentage changes in ALFF values in the deep nuclei were positively correlated with the age of epilepsy onset. Functional connectivity (FC) analyses demonstrated a reorganization of FC architecture after surgery. These changes in brain activity and FC after surgery might indicate that the previously disrupted functional interactions were reorganized after surgery. All these results provide preliminary evidence that the age of epilepsy onset may have some potential to predict the outcome of brain functional reorganization after surgery in children with MRE.

A structural brain lesion in patients with drug-resistant epilepsy (DRE) greatly increases the likelihood of identification of the seizure focus and ultimately seizure-free outcome following resective epilepsy surgery. In contrast, surgical outcomes of true non-lesional DRE are less favorable. Therefore, discovery of an underlying lesion is paramount in the pre-surgical work-up of patients with DRE. Over the years, the surgical treatment of pharmacoresistant epilepsy has evolved from straightforward lesional cases to include cases with hippocampal sclerosis. With the advent of magnetic resonance imaging (MRI), most cases of mesial temporal sclerosis became more easily identifiable on pre-operative neuroimaging. With the widespread use of high-resolution MRI with epilepsy protocols over the last two decades, our ability to visualize subtle structural changes has been greatly enhanced. However, there are some cases of lesional epilepsy, which remain unidentified on these routine MRIs. In such "non-lesional" refractory epilepsies, further investigation with advanced neuroimaging techniques, including metabolic imaging, as well as electrophysiological studies may help to identify the previously non-visualized focal brain abnormalities. In this review, we outline the current status for evaluation of MRI-negative DRE.

There is a new focus on minimally invasive treatments for medically refractory mesial temporal lobe epilepsy (MTLE). MRI-guided laser interstitial thermal therapy (MRgLITT) is one such minimally invasive procedure, which utilizes MRI guidance and real-time feedback to ablate an epileptogenic focus. A total of 38 patients presenting exclusively with MTLE and no other lesions (including neoplasia), who underwent MRgLITT were reviewed. We evaluated a number of outcome measures, including seizure freedom, neuropsychological performance, complications, and other considerations. Eighteen (53%) had an Engel class I outcome, 10 patients had repeat procedures/operations, and 12 post-procedural complications occurred. Follow-up time ranged from 6 to 38.5 months. There was a decreased length of procedure time, hospitalization time, and analgesic requirement when compared to open surgery. In cases of well-localized MTLE this procedure may offer similar (albeit slightly lower) rates of seizure freedom versus traditional surgery. MRgLITT may be an alternative treatment option for high risk surgical patients and, more importantly, could increase referrals for surgery in patients with medically refractory MTLE. However, data is limited and long-term outcomes have not been evaluated. Further investigation is required to understand the potential of this minimally invasive technique for MTLE. [ABSTRACT FROM AUTHOR]

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-1β and IL-1α were lowest in the hippocampus, compared to cortical regions. In the temporal cortex, IL-1β, 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-1β, 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. [ABSTRACT FROM AUTHOR]

Objective Epilepsy surgery is largely underused in developing counties as a result of many misconceptions. The current study evaluates complications of epilepsy surgery performed by a single surgeon from South India. Methods A retrospective analysis was performed of 697 consecutive patients who underwent epilepsy surgery. Complications were classified as minor and major medical, neurologic, and psychiatric complications. The study population was divided into groups of surgery for temporal lobe epilepsy (TLE), extratemporal lobe epilepsy (ETLE), and other procedures. Incidence of complications was compared in children aged ≤12 years and those aged >12 years. Engel class I and IIA was classified as favorable outcomes. Results The average age of the cohort was 21.9 ± 11.15 years, with 300 (42.8%) females. The mortality was 0.14%. Medical complications were observed in 2%: minor in 10 patients (1.43%) and major in 4 patients (0.57%). In patients with TLE ( n = 467), minor and major neurologic complications were observed in 18 patients (3.9%) and 4 patients (0.9%), respectively, and 14 patients (2.9%) had psychiatric complications. In 175 patients with ETLE, the lesion was in noneloquent area in 108; no patients had major and 20 patients (18.5%) had minor neurologic complications. In the remaining 67 patients with ETLE with eloquent area surgery, 29 patients (43.2%) had neurologic deficits as expected, and 12 (17.9%) had major neurologic deficit. Age did not influence complications. Engel favorable outcome was reported in 400 patients with TLE (85.7%) and 116 patients with ETLE (65.2%). Conclusions In the current study, risk of mortality was 0.1% and rate of overall major complications was 1.4%. Epilepsy surgery should be increasingly used in developing countries. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Patients with medically refractory epilepsy have historically had few effective treatment options. Electrical brain stimulation for seizures has been studied for decades and ongoing technological refinements have made possible the development of an implantable electrical brain stimulator. The NeuroPace responsive neurostimulator was recently approved by the FDA for clinical use and the initial reports are encouraging. This device continually monitors brain activity and delivers an electric stimulus when abnormal activity is detected. Early reports of efficacy suggest that the device is well tolerated and offers a reduction in seizure frequency by approximately half at 2 years. [ABSTRACT FROM AUTHOR]

This study explored predictors of response to vagus nerve stimulation in childhood-onset epilepsy. This retrospective chart review included all patients with new vagus nerve stimulator insertion between January 1, 2006, and December 31, 2011. Primary outcome was change in seizure frequency classified on the International League Against Epilepsy scale. Overall, 67.4% (95% confidence limits 53.3%-81.6%) of the patients had outcome of class 4 or better, and 4 patients (9.3%, 95% confidence interval 0.5%-18.1%) achieved complete seizure freedom (mean follow-up 3.5 y). Absence of magnetic resonance imaging (MRI) lesion (odds ratio 6.068, 95% confidence interval 1.214-30.329, P = .028) and duration of epilepsy before implantation (odds ratio 1.291, 95% confidence interval 1.015-1.642, P = .038) were found to be statistically significant predictors of good outcome and provided a sufficient fit to the data (area under the receiver operating characteristic curve .80, Hosmer-Lemeshow goodness of fit P = .92). This study provides preliminary evidence that nonlesional patients are significantly more likely to have better outcome with vagus nerve stimulation. [ABSTRACT FROM PUBLISHER]

Since its introduction to neurosurgery in 2008, laser ablative techniques have been largely confined to the management of unresectable tumors. Application of this technology for the management of focal epilepsy in the adult population has not been fully explored. Given that nearly 1,000,000 Americans live with medically refractory epilepsy and current surgical techniques only address a fraction of epileptic pathologies, additional therapeutic options are needed. We report the successful treatment of dominant insular epilepsy in a 53-year-old male with minimally invasive laser ablation complicated by mild verbal and memory deficits. We also report neuropsychological test data on this patient before surgery and at 8 months after the ablation procedure. This account represents the first reported successful patient outcome of laser ablation as an effective treatment option for medically refractory post-stroke epilepsy in an adult. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Charlotte, a little girl with SCN1 A-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/Δ9-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. [ABSTRACT FROM AUTHOR]

A structural brain lesion in patients with drug-resistant epilepsy (DRE) greatly increases the likelihood of identification of the seizure focus and ultimately seizure-free outcome following resective epilepsy surgery. In contrast, surgical outcomes of true non-lesional DRE are less favorable. Therefore, discovery of an underlying lesion is paramount in the pre-surgical work-up of patients with DRE. Over the years, the surgical treatment of pharmacoresistant epilepsy has evolved from straightforward lesional cases to include cases with hippocampal sclerosis. With the advent of magnetic resonance imaging (MRI), most cases of mesial temporal sclerosis became more easily identifiable on pre-operative neuroimaging. With the widespread use of high-resolution MRI with epilepsy protocols over the last two decades, our ability to visualize subtle structural changes has been greatly enhanced. However, there are some cases of lesional epilepsy, which remain unidentified on these routine MRIs. In such "non-lesional" refractory epilepsies, further investigation with advanced neuroimaging techniques, including metabolic imaging, as well as electrophysiological studies may help to identify the previously non-visualized focal brain abnormalities. In this review, we outline the current status for evaluation of MRI-negative DRE. [ABSTRACT FROM AUTHOR]

Highlights: [•] Periventricular nodular heterotopias (PVNH) causing medically refractory epilepsy. [•] Surgical resection of PVNH is limited by their deep location. [•] Stereotactic MR guided laser interstitial thermal therapy (MRgLITT) done for PVNH. [•] Accomplished focal ablation of PVNH with lower risk of neurological deficits. [Copyright &y& Elsevier]

Abstract: Objective: To evaluate the efficacy of vagus nerve stimulation (VNS) in pediatric patients with medically refractory epilepsy. Method: We reviewed the medical records of 252 consecutive patients who underwent VNS implantation at a single center over a 5-year period. Patients with complete 6- and 12-month follow-up data were included. Analysis was also done across various subgroups including gender, age at implantation, seizure type, abnormal MRI findings pre-implantation, number of medications at baseline, history of SE, and duration of epilepsy. Results: Complete follow-up data were available for 69 patients. Median seizure reduction for these patients was 50% (Q1: 0%; Q3: 73%) at 6 months and 40% (Q1: −25%; Q3: 75%) at 12 months. When stratified by baseline seizure frequency, there was a significant reduction from baseline of 61% at 6 months and 69% at 12 months for patients in the high-baseline frequency group. There were no significant reductions at month 6 or 12 months for the lower-baseline frequency group. Adverse events were reported in 40.6% (28 out of 69 patients). Six patients had the VNS removed for reasons including lack of efficacy and side effects and were excluded from the study group. Conclusion: VNS provides significant seizure reduction, in particular in pediatric patients with a higher baseline seizure frequency. [Copyright &y& Elsevier]

Highlights: [•] Patients with refractory seizures were assessed with diffusion tensor tractography. [•] We evaluated 33 patients of, lesional and non-lesional, refractory epilepsy. [•] Diffusion changes were detected both ipsilateral and contralateral to the lesion. [•] Microstructural changes were also observed in patients with normal imaging. [•] Our findings may help in epilepsy surgery planning and prognostication. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: A proportion of patients with childhood and juvenile absence epilepsies (CAE, JAE) are likely to be classified as medically refractory. In view of evidence gap for the treatment of such patients, this series is reported to generate estimate for efficacy of vagus nerve stimulation (VNS) in this patient population. Methods: Patients were identified by a chart review of all VNS recipients between January 1, 2006 and December 31, 2011. The diagnosis of CAE and JAE was based on conventional criteria. Details of demography, epilepsy phenomenology, management and outcomes were extracted. The outcome measures included reduction in daily seizure frequency measured as a percentage of pre-VNS seizure frequency and classified on International League Against Epilepsy (ILAE) outcome scale. Results: Nine patients (7 CAE, 2 JAE) with a mean age of seizure onset of 5.4 years (±3.9) were identified. Mean duration of epilepsy prior to VNS implant was found to be 3.9 years (±1.4). These patients had failed a median of 5 anti-epileptic drugs before being referred for consideration of surgical treatment. After a mean follow-up of 33.9 months (±25.5, minimum 4 months), 1 patient attained complete seizure freedom (ILAE class 1), 6 had ILAE class 4 and 2 had ILAE class 5 outcomes, respectively. Mean reduction in daily seizure frequency was found to be 53.5±60.3% (1-sided p-value for paired t-test=0.04), with a 50% responder rate of 55.6%. Conclusion: VNS may be considered as a therapeutic option in patients with medically refractory absence epilepsy. [Copyright &y& Elsevier]

Abstract: Objective: To evaluate the effect of surgery on subjective and objective measures of sleep quality among patients with medically refractory focal epilepsy. Methods: In a prospective cohort study, patients with medically refractory epilepsy undergoing epilepsy surgery were recruited. All patients were assessed seven days pre- and three months post-surgery in terms of history pertaining to epilepsy and sleep, Epworth sleepiness score (ESS), one week sleep log and over night polysomnography (PSG). Results: Among 17 patients (mean age 18, 11 males), seizure frequency had reduced (p =0.04) and self reported sleep parameters had significantly improved (reduced total duration of night time sleep, regularity on one week sleep log and ESS (p <0.05)) three months following epilepsy surgery. Patients with good surgical outcome (n =12) showed reduced seizure frequency (p =0.01) and reduced ESS with corresponding reduction in arousal index (AI) (p =0.02) and increase in total sleep time (p =0.03), postoperatively. Three patients in the good surgical outcome group showed reduction in apnea–hypopnea index (AHI) from more than five to less than five. There was no significant change either in seizure frequency, self reported clinical parameters or PSG parameters among patients with poor surgical outcome. Conclusion: Epilepsy surgery improves subjective sleep parameters in patients with medically refractory epilepsy during the early post operative period. Successful epilepsy surgery may improve objective (PSG documented) sleep quality, sleep architecture and obstructive sleep apnea with resultant reduction in excessive daytime sleepiness. [Copyright &y& Elsevier]