Multimodal mapping of regional brain vulnerability to focal cortical dysplasia.

Focal cortical dysplasia (FCD) type II is a highly epileptogenic developmental malformation and a common cause of surgically treated drug-resistant epilepsy. While clinical observations suggest frequent occurrence in the frontal lobe, mechanisms for such propensity remain unexplored. Here, we hypothesized that cortex-wide spatial associations of FCD distribution with cortical cytoarchitecture, gene expression and organizational axes may offer complementary insights into processes that predispose given cortical regions to harbour FCD. We mapped the cortex-wide MRI distribution of FCDs in 337 patients collected from 13 sites worldwide. We then determined its associations with (i) cytoarchitectural features using histological atlases by Von Economo and Koskinas and BigBrain; (ii) whole-brain gene expression and spatiotemporal dynamics from prenatal to adulthood stages using the Allen Human Brain Atlas and PsychENCODE BrainSpan; and (iii) macroscale developmental axes of cortical organization. FCD lesions were preferentially located in the prefrontal and fronto-limbic cortices typified by low neuron density, large soma and thick grey matter. Transcriptomic associations with FCD distribution uncovered a prenatal component related to neuroglial proliferation and differentiation, likely accounting for the dysplastic makeup, and a postnatal component related to synaptogenesis and circuit organization, possibly contributing to circuit-level hyperexcitability. FCD distribution showed a strong association with the anterior region of the antero-posterior axis derived from heritability analysis of interregional structural covariance of cortical thickness, but not with structural and functional hierarchical axes. Reliability of all results was confirmed through resampling techniques. Multimodal associations with cytoarchitecture, gene expression and axes of cortical organization indicate that prenatal neurogenesis and postnatal synaptogenesis may be key points of developmental vulnerability of the frontal lobe to FCD. Concordant with a causal role of atypical neuroglial proliferation and growth, our results indicate that FCD-vulnerable cortices display properties indicative of earlier termination of neurogenesis and initiation of cell growth. They also suggest a potential contribution of aberrant postnatal synaptogenesis and circuit development to FCD epileptogenicity.

KCNQ2 R144 variants cause neurodevelopmental disability with language impairment and autistic features without neonatal seizures through a gain-of-function mechanism.

BACKGROUND: Prior studies have revealed remarkable phenotypic heterogeneity in KCNQ2-related disorders, correlated with effects on biophysical features of heterologously expressed channels. Here, we assessed phenotypes and functional properties associated with KCNQ2 missense variants R144W, R144Q, and R144G. We also explored in vitro blockade of channels carrying R144Q mutant subunits by amitriptyline. METHODS: Patients were identified using the RIKEE database and through clinical collaborators. Phenotypes were collected by a standardized questionnaire. Functional and pharmacological properties of variant subunits were analyzed by whole-cell patch-clamp recordings. FINDINGS: Detailed clinical information on fifteen patients (14 novel and 1 previously published) was analyzed. All patients had developmental delay with prominent language impairment. R144Q patients were more severely affected than R144W patients. Infantile to childhood onset epilepsy occurred in 40%, while 67% of sleep-EEGs showed sleep-activated epileptiform activity. Ten patients (67%) showed autistic features. Activation gating of homomeric Kv7.2 R144W/Q/G channels was left-shifted, suggesting gain-of-function effects. Amitriptyline blocked channels containing Kv7.2 and Kv7.2 R144Q subunits. INTERPRETATION: Patients carrying KCNQ2 R144 gain-of-function variants have developmental delay with prominent language impairment, autistic features, often accompanied by infantile- to childhood-onset epilepsy and EEG sleep-activated epileptiform activity. The absence of neonatal seizures is a robust and important clinical differentiator between KCNQ2 gain-of-function and loss-of-function variants. The Kv7.2/7.3 channel blocker amitriptyline might represent a targeted treatment. FUNDING: Supported by FWO, GSKE, KCNQ2-Cure, Jack Pribaz Foundation, European Joint Programme on Rare Disease 2020, the Italian Ministry for University and Research, the Italian Ministry of Health, the European Commission, the University of Antwerp, NINDS, and Chalk Family Foundation.

Connectomic profiling and Vagus nerve stimulation Outcomes Study (CONNECTiVOS): a prospective observational protocol to identify biomarkers of seizure response in children and youth.

INTRODUCTION: Vagus nerve stimulation (VNS) is a neuromodulation therapy that can reduce the seizure burden of children with medically intractable epilepsy. Despite the widespread use of VNS to treat epilepsy, there are currently no means to preoperatively identify patients who will benefit from treatment. The objective of the present study is to determine clinical and neural network-based correlates of treatment outcome to better identify candidates for VNS therapy. METHODS AND ANALYSIS: In this multi-institutional North American study, children undergoing VNS and their caregivers will be prospectively recruited. All patients will have documentation of clinical history, physical and neurological examination and video electroencephalography as part of the standard clinical workup for VNS. Neuroimaging data including resting-state functional MRI, diffusion-tensor imaging and magnetoencephalography will be collected before surgery. MR-based measures will also be repeated 12 months after implantation. Outcomes of VNS, including seizure control and health-related quality of life of both patient and primary caregiver, will be prospectively measured up to 2 years postoperatively. All data will be collected electronically using Research Electronic Data Capture. ETHICS AND DISSEMINATION: This study was approved by the Hospital for Sick Children Research Ethics Board (REB number 1000061744). All participants, or substitute decision-makers, will provide informed consent prior to be enrolled in the study. Institutional Research Ethics Board approval will be obtained from each additional participating site prior to inclusion. This study is funded through a Canadian Institutes of Health Research grant (PJT-159561) and an investigator-initiated funding grant from LivaNova USA (Houston, TX; FF01803B IIR).

ILAE Neuroimaging Task Force Highlight: harnessing optimized imaging protocols for drug-resistant childhood epilepsy.

The ILAE Neuroimaging Task Force aims to publish educational case reports highlighting basic aspects related to neuroimaging in epilepsy consistent with the educational mission of the ILAE. Previous quantitative MRI studies have established important imaging markers of epilepsy-related pathology, including features sensitive to hippocampal cell loss and reactive astrogliosis. Here, we review the case of a female with pediatric drug-resistant epilepsy. Throughout her course of treatment, she had seven MRI investigations at several centers; the first three did not follow optimized epilepsy imaging protocols whereas the remaining four adhered to HARNESS-MRI protocols ( har monized n euroimaging of e pilepsy s tructural s equences). Visual inspection of a set of HARNESS-MR images revealed conspicuous left hippocampal hyperintensity which may have been initially overlooked on non-optimized MR images. Quantitative analysis of these multimodal imaging data along hippocampal subfields provided clear evidence of hippocampal sclerosis, with increased atrophy, increased mean diffusivity, increased T2-FLAIR signal, and lower qT1 values observed in the anterior portions of the left, compared to the right hippocampus. The patient underwent a left anterior temporal lobectomy with amygdalohippocampectomy at age 16 years. Histopathology of the resected specimen also confirmed hippocampal sclerosis with widespread gliosis and focal neuronal loss in the hippocampal subfields overlapping with regions of multimodal quantitative alterations. The patient remains seizure-free one year after surgery. Collectively, this case highlights the need for optimized data acquisition protocols early in the treatment of epilepsy and supports quantitative analysis of MRI contrasts to enhance personalized diagnosis and prognosis of drug-resistant patients with epilepsy.

Multicenter Validation of a Deep Learning Detection Algorithm for Focal Cortical Dysplasia.

BACKGROUND AND OBJECTIVE: To test the hypothesis that a multicenter-validated computer deep learning algorithm detects MRI-negative focal cortical dysplasia (FCD). METHODS: We used clinically acquired 3-dimensional (3D) T1-weighted and 3D fluid-attenuated inversion recovery MRI of 148 patients (median age 23 years [range 2-55 years]; 47% female) with histologically verified FCD at 9 centers to train a deep convolutional neural network (CNN) classifier. Images were initially deemed MRI-negative in 51% of patients, in whom intracranial EEG determined the focus. For risk stratification, the CNN incorporated bayesian uncertainty estimation as a measure of confidence. To evaluate performance, detection maps were compared to expert FCD manual labels. Sensitivity was tested in an independent cohort of 23 cases with FCD (13 ± 10 years). Applying the algorithm to 42 healthy controls and 89 controls with temporal lobe epilepsy disease tested specificity. RESULTS: Overall sensitivity was 93% (137 of 148 FCD detected) using a leave-one-site-out cross-validation, with an average of 6 false positives per patient. Sensitivity in MRI-negative FCD was 85%. In 73% of patients, the FCD was among the clusters with the highest confidence; in half, it ranked the highest. Sensitivity in the independent cohort was 83% (19 of 23; average of 5 false positives per patient). Specificity was 89% in healthy and disease controls. DISCUSSION: This first multicenter-validated deep learning detection algorithm yields the highest sensitivity to date in MRI-negative FCD. By pairing predictions with risk stratification, this classifier may assist clinicians in adjusting hypotheses relative to other tests, increasing diagnostic confidence. Moreover, generalizability across age and MRI hardware makes this approach ideal for presurgical evaluation of MRI-negative epilepsy. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that deep learning on multimodal MRI accurately identifies FCD in patients with epilepsy initially diagnosed as MRI negative.

Seizure action plans in the pediatric population with epilepsy: Uptake, determinants, and parental interest in a mobile application.

BACKGROUND: Status epilepticus (SE) is a common pediatric neurological emergency that requires timely treatment to minimize morbidity and mortality, yet administration of rescue medications is often delayed and underdosed. Seizure action plans (SAPs) outline the steps that should be taken by parents and caregivers in case of SE in order to optimize patient outcomes. Our study determined the uptake of SAPs in a pediatric population with epilepsy and assessed parental interest in a SAP mobile application. METHODS: A survey was distributed to parents of patients with epilepsy aged 1 month to 19 years at British Columbia Children's Hospital. Following chart review, univariate and multivariate analyses were performed to identify variables that predict whether patients have SAPs. A systematic search of available mobile applications for epilepsy management was conducted. RESULTS: Of 192 participants, 62% have SAPs. On univariate analysis, history of prior SE and male gender increased likelihood of SAP. On logistic regression, Nagelkerke R2 was 0.204 and our model correctly predicted 82% of patients with SAPs. 83% of parents were interested in a SAP mobile application. There are currently 40 mobile applications available for epilepsy management, but only 15% of respondents reported using them. CONCLUSIONS: There is a need to increase the percentage of patients with epilepsy with SAPs, particularly in those at greater risk of SE. Most parents would find a SAP mobile application valuable in their child's epilepsy management. There is a gap between the high parental interest in mobile applications for epilepsy management and their current use of such applications.

Rapid Implementation of Virtual Health in a Pediatric Neurology Practice During COVID-19.

During the COVID-19 pandemic, the Division of Neurology at BC Children's Hospital rapidly transitioned to almost exclusively virtual health. In April 2020, 96% of outpatient visits were done virtually (64%) or by telephone, and only 4.2% were in-person. Total clinic visit numbers were unchanged compared to previous months. Neurologists reported high satisfaction with the virtual history and overall assessment, while the physical examination was less reliable. Additional in-person visits were rarely required. Rapid, sustained adoption of virtual health is possible in a pediatric neurology setting, providing reliable care that is comparable to in-person consultations when physical distancing is necessary.

Functional connectome contractions in temporal lobe epilepsy: Microstructural underpinnings and predictors of surgical outcome.

OBJECTIVE: Temporal lobe epilepsy (TLE) is the most common drug-resistant epilepsy in adults. Although it is commonly related to hippocampal pathology, increasing evidence suggests structural changes beyond the mesiotemporal lobe. Functional anomalies and their link to underlying structural alterations, however, remain incompletely understood. METHODS: We studied 30 drug-resistant TLE patients and 57 healthy controls using multimodal magnetic resonance imaging (MRI) analyses. All patients had histologically verified hippocampal sclerosis and underwent postoperative imaging to outline the extent of their surgical resection. Our analysis leveraged a novel resting-state functional MRI framework that parameterizes functional connectivity distance, consolidating topological and physical properties of macroscale brain networks. Functional findings were integrated with morphological and microstructural metrics, and utility for surgical outcome prediction was assessed using machine learning techniques. RESULTS: Compared to controls, TLE patients showed connectivity distance reductions in temporoinsular and prefrontal networks, indicating topological segregation of functional networks. Testing for morphological and microstructural associations, we observed that functional connectivity contractions occurred independently from TLE-related cortical atrophy but were mediated by microstructural changes in the underlying white matter. Following our imaging study, all patients underwent an anterior temporal lobectomy as a treatment of their seizures, and postsurgical seizure outcome was determined at a follow-up at least 1 year after surgery. Using a regularized supervised machine learning paradigm with fivefold cross-validation, we demonstrated that patient-specific functional anomalies predicted postsurgical seizure outcome with 76 ± 4% accuracy, outperforming classifiers operating on clinical and structural imaging features. SIGNIFICANCE: Our findings suggest connectivity distance contractions as a macroscale substrate of TLE. Functional topological isolation may represent a microstructurally mediated network mechanism that tilts the balance toward epileptogenesis in affected networks and that may assist in patient-specific surgical prognostication.

Multiscale Structure-Function Gradients in the Neonatal Connectome.

The adult functional connectome is well characterized by a macroscale spatial gradient of connectivity traversing from unimodal toward higher-order transmodal cortices that recapitulates known principles of hierarchical organization and myelination patterns. Despite an emerging literature assessing connectome properties in neonates, the presence of connectome gradients and particularly their correspondence to microstructure remains largely unknown. We derived connectome gradients using unsupervised techniques applied to functional connectivity data from 40 term-born neonates. A series of cortex-wide analysis examined associations to magnetic resonance imaging-derived morphological parameters (cortical thickness, sulcal depth, curvature), measures of tissue microstructure (intracortical T1w/T2w intensity, superficial white matter diffusion parameters), and subcortico-cortical functional connectivity. Our findings indicate that the primary neonatal connectome gradient runs between sensorimotor and visual anchors and captures specific associations to cortical and superficial white matter microstructure as well as thalamo-cortical connectivity. A second gradient indicated an anterior-to-posterior asymmetry in macroscale connectivity alongside an immature differentiation between unimodal and transmodal areas, indicating a connectome-level circuitry en route to an adult-like organization. Our findings reveal an important coordination of structural and functional interactions in the neonatal connectome across spatial scales. Observed associations were replicable across individual neonates, suggesting consistency and generalizability.

Targeting age-related differences in brain and cognition with multimodal imaging and connectome topography profiling.

Aging is characterized by accumulation of structural and metabolic changes in the brain. Recent studies suggest transmodal brain networks are especially sensitive to aging, which, we hypothesize, may be due to their apical position in the cortical hierarchy. Studying an open-access healthy cohort (n = 102, age range = 30-89 years) with MRI and Aß PET data, we estimated age-related cortical thinning, hippocampal atrophy and Aß deposition. In addition to carrying out surface-based morphological and metabolic mapping experiments, we stratified effects along neocortical and hippocampal resting-state functional connectome gradients derived from independent datasets. The cortical gradient depicts an axis of functional differentiation from sensory-motor regions to transmodal regions, whereas the hippocampal gradient recapitulates its long-axis. While age-related thinning and increased Aß deposition occurred across the entire cortical topography, increased Aß deposition was especially pronounced toward higher-order transmodal regions. Age-related atrophy was greater toward the posterior end of the hippocampal long-axis. No significant effect of age on Aß deposition in the hippocampus was observed. Imaging markers correlated with behavioral measures of fluid intelligence and episodic memory in a topography-specific manner, confirmed using both univariate as well as multivariate analyses. Our results strengthen existing evidence of structural and metabolic change in the aging brain and support the use of connectivity gradients as a compact framework to analyze and conceptualize brain-based biomarkers of aging.

Multimodal MRI profiling of focal cortical dysplasia type II.

OBJECTIVE: To characterize in vivo MRI signatures of focal cortical dysplasia (FCD) type IIA and type IIB through combined analysis of morphology, intensity, microstructure, and function. METHODS: We carried out a multimodal 3T MRI profiling of 33 histologically proven FCD type IIA (9) and IIB (24) lesions. A multisurface approach operating on manual consensus labels systematically sampled intracortical and subcortical lesional features. Geodesic distance mapping quantified the same features in the lesion perimeter. Logistic regression assessed the relationship between MRI and histology, while supervised pattern learning was used for individualized subtype prediction. RESULTS: FCD type IIB was characterized by abnormal morphology, intensity, diffusivity, and function across all surfaces, while type IIA lesions presented only with increased fluid-attenuated inversion recovery signal and reduced diffusion anisotropy close to the gray-white matter interface. Similar to lesional patterns, perilesional anomalies were more marked in type IIB extending up to 16 mm. Structural MRI markers correlated with categorical histologic characteristics. A profile-based classifier predicted FCD subtypes with equal sensitivity of 85%, while maintaining a high specificity of 94% against healthy and disease controls. CONCLUSIONS: Image processing applied to widely available MRI contrasts has the ability to dissociate FCD subtypes at a mesoscopic level. Integrating in vivo staging of pathologic traits with automated lesion detection is likely to provide an objective definition of lesional boundary and assist emerging approaches, such as minimally invasive thermal ablation, which do not supply tissue specimen.

Whole-brain MRI phenotyping in dysplasia-related frontal lobe epilepsy.

OBJECTIVE: To perform whole-brain morphometry in patients with frontal lobe epilepsy and evaluate the utility of group-level patterns for individualized diagnosis and prognosis. METHODS: We compared MRI-based cortical thickness and folding complexity between 2 frontal lobe epilepsy cohorts with histologically verified focal cortical dysplasia (FCD) (13 type I; 28 type II) and 41 closely matched controls. Pattern learning algorithms evaluated the utility of group-level findings to predict histologic FCD subtype, the side of the seizure focus, and postsurgical seizure outcome in single individuals. RESULTS: Relative to controls, FCD type I displayed multilobar cortical thinning that was most marked in ipsilateral frontal cortices. Conversely, type II showed thickening in temporal and postcentral cortices. Cortical folding also diverged, with increased complexity in prefrontal cortices in type I and decreases in type II. Group-level findings successfully guided automated FCD subtype classification (type I: 100%; type II: 96%), seizure focus lateralization (type I: 92%; type II: 86%), and outcome prediction (type I: 92%; type II: 82%). CONCLUSION: FCD subtypes relate to diverse whole-brain structural phenotypes. While cortical thickening in type II may indicate delayed pruning, a thin cortex in type I likely results from combined effects of seizure excitotoxicity and the primary malformation. Group-level patterns have a high translational value in guiding individualized diagnostics.

Automated detection of cortical dysplasia type II in MRI-negative epilepsy.

OBJECTIVE: To detect automatically focal cortical dysplasia (FCD) type II in patients with extratemporal epilepsy initially diagnosed as MRI-negative on routine inspection of 1.5 and 3.0T scans. METHODS: We implemented an automated classifier relying on surface-based features of FCD morphology and intensity, taking advantage of their covariance. The method was tested on 19 patients (15 with histologically confirmed FCD) scanned at 3.0T, and cross-validated using a leave-one-out strategy. We assessed specificity in 24 healthy controls and 11 disease controls with temporal lobe epilepsy. Cross-dataset classification performance was evaluated in 20 healthy controls and 14 patients with histologically verified FCD examined at 1.5T. RESULTS: Sensitivity was 74%, with 100% specificity (i.e., no lesions detected in healthy or disease controls). In 50% of cases, a single cluster colocalized with the FCD lesion, while in the remaining cases a median of 1 extralesional cluster was found. Applying the classifier (trained on 3.0T data) to the 1.5T dataset yielded comparable performance (sensitivity 71%, specificity 95%). CONCLUSION: In patients initially diagnosed as MRI-negative, our fully automated multivariate approach offered a substantial gain in sensitivity over standard radiologic assessment. The proposed method showed generalizability across cohorts, scanners, and field strengths. Machine learning may assist presurgical decision-making by facilitating hypothesis formulation about the epileptogenic zone. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that automated machine learning of MRI patterns accurately identifies FCD among patients with extratemporal epilepsy initially diagnosed as MRI-negative.

Advances in MRI for 'cryptogenic' epilepsies.

Nearly one-third of patients with focal epilepsy experience disabling seizures that are refractory to pharmacotherapy. Drug-resistant focal epilepsy is, however, potentially curable by surgery. Although lesions associated with the epileptic focus can often be accurately detected by MRI, in many patients conventional imaging based on visual evaluation is unable to pinpoint the surgical target. Patients with so-called cryptogenic epilepsy represent one of the greatest clinical challenges in many tertiary epilepsy centers. In recent years, it has become increasingly clear that epilepsies that are considered cryptogenic are not necessarily nonlesional, the primary histopathological substrate being subtle cortical dysplasia. This Review considers the application of new advances in brain imaging, such as MRI morphometry, computational modeling and diffusion tensor imaging. By revealing dysplastic lesions that previously eluded visual assessments, quantitative structural MRI methods such as these have clearly demonstrated an increased diagnostic yield of epileptic lesions, and have provided successful surgical options to an increasing number of patients with 'cryptogenic' epilepsy.

Epilepsy with occipital features in children: factors predicting seizure outcome and neuroimaging abnormalities.

PURPOSE: The objective of this retrospective study was to identify clinical and EEG features in children with occipital epilepsy that predict MR imaging abnormalities and seizure outcome. METHODS: Patients with clinical and/or EEG features indicating occipital lobe involvement were identified from the epilepsy database at a tertiary children's hospital. The clinical and EEG features were analyzed to identify the most important predictors of abnormal MR imaging and seizure outcome. RESULTS: Sixty-six patients were identified: 21 had symptomatic epilepsy with abnormal MR imaging; 12 patients had probable symptomatic epilepsy based on an abnormal neurological exam; 33 patients had normal neurological development, normal neurological examination and normal neuroimaging. Twenty-two of these 33 patients satisfied criteria for idiopathic occipital syndromes: Panayiotopoulos syndrome (9 patients), Gastaut type idiopathic childhood occipital epilepsy (12 patients) and idiopathic photosensitive occipital epilepsy (1 patient). Eleven patients could not be classified. Early age of seizure onset and an abnormal neurological examination were significant predictors of abnormal MR imaging. None of the variables examined were strong predictors of seizure outcome. CONCLUSION: Early age of seizure onset and an abnormal neurological examination are the best predictors of abnormal MR imaging in children with epilepsy with occipital features.

Cingulate lesions presenting with epileptic spasms.

PURPOSE: To describe the novel finding of epileptic spasms arising from a cingulate lesion. METHODS: We describe two children presenting with epileptic spasms who had lesions of the cingulate gyrus on MRI. RESULTS: In both patients, the lesions involved the midcingulate cortex. Seizures were characterized by prominent motor manifestations and resembled spasms. Both patients had a complete resolution of seizures after resection of their cingulate lesions. DISCUSSION: Cingulate seizures can present with a variety of behaviors including complex motor manifestations, vocalizations, and autonomic changes. Lesions in the midcingulate cortex can also produce epileptic spasms.

Urgent, resective surgery for medically refractory, convulsive status epilepticus.

Refractory, convulsive status epilepticus has significant mortality and morbidity. Urgent resective surgery may be of benefit in selected cases where medical therapies have failed. At our institution, from January 1992 until December 2005, urgent resective surgery was performed in three children with medically refractory convulsive status epilepticus. The etiologies were microdysgenesis, focal cortical dysplasia, and bilateral Rasmussen's syndrome and cortical dysplasia. In two cases, surgery resulted in termination of status epilepticus. In all three cases, surgery permitted discontinuation of high-dose suppression therapy and allowed the patient to leave the intensive care unit, either by terminating status epilepticus or by providing important histopathological information about the nature of the underlying disease and prognosis.

The role of neurosurgery in status epilepticus.

INTRODUCTION: Status epilepticus remains a life-threatening condition that afflicts both adults and children which although occurs in patients with epilepsy, often presents as new-onset seizure activity also. Refractory status epilepticus poses a management challenge for neurological and neurosurgical teams. CASE REPORT AND METHODS: Subdural grid electrodes were used to record cortical discharges and guide tumor resection involving eloquent cortex and multiple subpial transections in a 48-year-old man with left hemiparesis in status epilepticus. He had been refractory to multiple medical therapies in persistent epilepsia partialis continua for a prolonged period. As an alternative to higher-dose suppressive medical therapy, the patient elected to proceed with subdural grid mapping after seizure semiology ("negative" scalp electroencephalogram) localized the seizure focus to the right hemisphere, motor cortex. Following tumor removal, multiple subpial transections were subsequently performed over large areas of the motor and sensory strips and successfully resolved the status epilepticus. RESULTS: The patient made an excellent recovery, became seizure free, had improved left-sided strength and was discharged home shortly after. CONCLUSION: This case illustrates a potentially life-saving technique for the treatment of refractory status epilepticus. Multiple subpial transections and other neurosurgical intervention should be considered for patients with status epilepticus. When localization with surface electrodes is poor, especially in eloquent cortex, subdural grid recording can be used to direct focal resection and/or multiple subpial transections to minimize neurological deficits. A review and summary of previously published neurosurgery cases for status epilepticus is discussed.