Publications by authors named "Hansel M Greiner"

59 Publications

Fast Automated Stereo-EEG Electrode Contact Identification and Labeling Ensemble.

Stereotact Funct Neurosurg 2021 Apr 13:1-12. Epub 2021 Apr 13.

Division of Neurology, Comprehensive Epilepsy Center, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Introduction: Stereotactic electroencephalography (SEEG) has emerged as the preferred modality for intracranial monitoring in drug-resistant epilepsy (DRE) patients being evaluated for neurosurgery. After implantation of SEEG electrodes, it is important to determine the neuroanatomic locations of electrode contacts (ECs), to localize ictal onset and propagation, and integrate functional information to facilitate surgical decisions. Although there are tools for coregistration of preoperative MRI and postoperative CT scans, identification, sorting, and labeling of SEEG ECs is often performed manually, which is resource intensive. We report development and validation of a software named Fast Automated SEEG Electrode Contact Identification and Labeling Ensemble (FASCILE).

Methods: FASCILE is written in Python 3.8.3 and employs a novel automated method for identifying ECs, assigning them to respected SEEG electrodes, and labeling. We compared FASCILE with our clinical process of identifying, sorting, and labeling ECs, by computing localization error in anteroposterior, superoinferior, and lateral dimensions. We also measured mean Euclidean distances between ECs identified by FASCILE and the clinical method. We compared time taken for EC identification, sorting, and labeling for the software developer using FASCILE, a first-time clinical user using FASCILE, and the conventional clinical process.

Results: Validation in 35 consecutive DRE patients showed a mean overall localization error of 0.73 ± 0.15 mm. FASCILE required 10.7 ± 5.5 min/patient for identifying, sorting, and labeling ECs by a first-time clinical user, compared to 3.3 ± 0.7 h/patient required for the conventional clinical process.

Conclusion: Given the accuracy, speed, and ease of use, we expect FASCILE to be used frequently for SEEG-driven epilepsy surgery. It is freely available for noncommercial use. FASCILE is specifically designed to expedite localization of ECs, assigning them to respective SEEG electrodes (sorting), and labeling them and not for coregistration of CT and MRI data as there are commercial software available for this purpose.
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http://dx.doi.org/10.1159/000515090DOI Listing
April 2021

Early identification of epilepsy surgery candidates: A multicenter, machine learning study.

Acta Neurol Scand 2021 Mar 26. Epub 2021 Mar 26.

Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Objectives: Epilepsy surgery is underutilized. Automating the identification of potential surgical candidates may facilitate earlier intervention. Our objective was to develop site-specific machine learning (ML) algorithms to identify candidates before they undergo surgery.

Materials & Methods: In this multicenter, retrospective, longitudinal cohort study, ML algorithms were trained on n-grams extracted from free-text neurology notes, EEG and MRI reports, visit codes, medications, procedures, laboratories, and demographic information. Site-specific algorithms were developed at two epilepsy centers: one pediatric and one adult. Cases were defined as patients who underwent resective epilepsy surgery, and controls were patients with epilepsy with no history of surgery. The output of the ML algorithms was the estimated likelihood of candidacy for resective epilepsy surgery. Model performance was assessed using 10-fold cross-validation.

Results: There were 5880 children (n = 137 had surgery [2.3%]) and 7604 adults with epilepsy (n = 56 had surgery [0.7%]) included in the study. Pediatric surgical patients could be identified 2.0 years (range: 0-8.6 years) before beginning their presurgical evaluation with AUC =0.76 (95% CI: 0.70-0.82) and PR-AUC =0.13 (95% CI: 0.07-0.18). Adult surgical patients could be identified 1.0 year (range: 0-5.4 years) before beginning their presurgical evaluation with AUC =0.85 (95% CI: 0.78-0.93) and PR-AUC =0.31 (95% CI: 0.14-0.48). By the time patients began their presurgical evaluation, the ML algorithms identified pediatric and adult surgical patients with AUC =0.93 and 0.95, respectively. The mean squared error of the predicted probability of surgical candidacy (Brier scores) was 0.018 in pediatrics and 0.006 in adults.

Conclusions: Site-specific machine learning algorithms can identify candidates for epilepsy surgery early in the disease course in diverse practice settings.
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http://dx.doi.org/10.1111/ane.13418DOI Listing
March 2021

Beta synchrony for expressive language lateralizes to right hemisphere in development.

Sci Rep 2021 Feb 17;11(1):3949. Epub 2021 Feb 17.

Neurosciences and Mental Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON, M5G 0A4, Canada.

A left perisylvian network is known to support language in healthy adults. Low-beta (13-23 Hz) event-related desynchrony (ERD) has been observed during verb generation, at approximately 700-1200 ms post-stimulus presentation in past studies; the signal is known to reflect increased neuronal firing and metabolic demand during language production. In contrast, concurrent beta event-related synchrony (ERS) is thought to reflect neuronal inhibition but has not been well studied in the context of language. Further, while low-beta ERD for expressive language has been found to gradually shift from bilateral in childhood to left hemispheric by early adulthood, developmental lateralization of ERS has not been established. We used magnetoencephalography to study low beta ERS lateralization in a group of children and adolescents (n = 78), aged 4 to less than 19 years, who performed covert verb generation. We found that the youngest children had bilateral ERD and ERS. By adolescence, low-beta ERD was predominantly left lateralized in perisylvian cortex (i.e., Broca's and Wernicke's regions), while beta ERS was predominantly right lateralized. Increasing lateralization was significantly correlated to age for both ERD (Spearman's r = 0.45, p < 0.01) and ERS (Spearman's r =  - 0.44, p < 0.01). Interestingly, while ERD lateralized in a linear manner, ERS lateralization followed a nonlinear trajectory, suggesting distinct developmental trajectories. Implications to early-age neuroplasticity and neuronal inhibition are discussed.
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http://dx.doi.org/10.1038/s41598-021-83373-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889886PMC
February 2021

High-gamma modulation language mapping with stereo-EEG: A novel analytic approach and diagnostic validation.

Clin Neurophysiol 2020 Dec 16;131(12):2851-2860. Epub 2020 Oct 16.

Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA. Electronic address:

Objective: A novel analytic approach for task-related high-gamma modulation (HGM) in stereo-electroencephalography (SEEG) was developed and evaluated for language mapping.

Methods: SEEG signals, acquired from drug-resistant epilepsy patients during a visual naming task, were analyzed to find clusters of 50-150 Hz power modulations in time-frequency domain. Classifier models to identify electrode contacts within the reference neuroanatomy and electrical stimulation mapping (ESM) speech/language sites were developed and validated.

Results: In 21 patients (9 females), aged 4.8-21.2 years, SEEG HGM model predicted electrode locations within Neurosynth language parcels with high diagnostic odds ratio (DOR 10.9, p < 0.0001), high specificity (0.85), and fair sensitivity (0.66). Another SEEG HGM model classified ESM speech/language sites with significant DOR (5.0, p < 0.0001), high specificity (0.74), but insufficient sensitivity. Time to largest power change reliably localized electrodes within Neurosynth language parcels, while, time to center-of-mass power change identified ESM sites.

Conclusions: SEEG HGM mapping can accurately localize neuroanatomic and ESM language sites.

Significance: Predictive modelling incorporating time, frequency, and magnitude of power change is a useful methodology for task-related HGM, which offers insights into discrepancies between HGM language maps and neuroanatomy or ESM.
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http://dx.doi.org/10.1016/j.clinph.2020.09.023DOI Listing
December 2020

Generator replacement with cardiac-based VNS device in children with drug-resistant epilepsy: An observational study.

Epilepsy Res 2020 11 16;167:106431. Epub 2020 Jul 16.

Epilepsy Program, Division of Neurology, Department of Pediatrics, The Hospital for Sick Children (University of Toronto), Toronto, Ontario, M5G 1X8, Canada. Electronic address:

Purpose: This study evaluated the seizure outcomes in children with drug-resistant epilepsy (DRE), having a pre-existing VNS device, after generator replacement with cardiac-based VNS device.

Methods: This retrospective study enrolled 30 children with DRE from 2 centers with an existing VNS device nearing end-of-service who underwent generator replacement with cardiac-based VNS device and had at least 1 year follow up. Seizure outcomes and adverse effects were studied.

Results: The mean age at insertion of cardiac-based VNS device was 15.03 years. 26.7 % patients showed at least one class improvement at last follow up (mean 2.08 years) and half of the patients maintained their McHugh seizure-outcome class. Thirty-six percent of patients had > 50 % seizure reduction at last follow up. Ten patients reported improvement in ictal severity. Most of the patients tolerated the replacement well.

Conclusions: Nearly one-third of patients with DRE showed additional improvement after replacement with cardiac based VNS device. Half of the patients maintained their seizure control.
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http://dx.doi.org/10.1016/j.eplepsyres.2020.106431DOI Listing
November 2020

Neuropsychological outcomes after pediatric epilepsy surgery: Role of electrical stimulation language mapping.

Seizure 2020 Aug 25;80:183-191. Epub 2020 Jun 25.

Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA. Electronic address:

Purpose: We studied the association between electrical stimulation mapping (ESM) with a visual naming task and post-operative neuropsychological outcomes after pediatric epilepsy surgery.

Methods: Children who underwent epilepsy surgery, having pre- and 1-year post-surgery neuropsychological evaluation (NPE) available, were included. NPE scores were transformed using principal components (PC) analysis. The relationship between post-surgical PC scores, adjusted for pre-surgery PC scores, and ESM was analyzed. Clinical variables influencing this relationship were also sought.

Results: One hundred and four children (89 patients >5 years-old, and 15 patients 3-5 years-old) were included. Among children >5 years-of-age, a significant effect of language ESM was observed on all 3 post-surgery PC scores adjusted for respective pre-surgery PC scores. Specifically, only 30 % patients who underwent language ESM had a decrease in PC1 scores ≥1-year after epilepsy surgery, compared to 68 % those who did not undergo language ESM (p = 0.001). Seizure outcomes, age at the time of surgery, predominant seizure type, and family history of epilepsy were other significant determinants of post-surgical PC scores including a change in PC scores from pre-surgery baseline. Combinations of pre-surgical variables were able to predict post-surgical PC scores with high specificity. In children aged 3-5 years, no significant effect of language ESM was seen on post-surgery PC scores adjusted for respective pre-surgery PC scores.

Conclusions: Speech/language ESM should be performed more widely in patients >5 years-of-age undergoing epilepsy surgery. Also, more efficient brain mapping techniques and language paradigms are needed for younger children.
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http://dx.doi.org/10.1016/j.seizure.2020.06.029DOI Listing
August 2020

Electrical stimulation sensorimotor mapping with stereo-EEG.

Clin Neurophysiol 2020 Aug 18;131(8):1691-1701. Epub 2020 May 18.

Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Objective: We evaluated stereo-EEG electrical stimulation mapping (ESM) for localization of anatomic sensorimotor parcels in pediatric patients with drug-resistant epilepsy. We also analyzed sensorimotor and after-discharge thresholds, and the somatotopy of sensorimotor responses.

Methods: ESM was performed with 50 Hz, biphasic, 2-3 s trains, using 1-9 mA current. Pre- and post-implant neuroimaging was co-registered and intersected with Neurosynth reference, to classify each electrode contact as lying within/outside an anatomic sensorimotor parcel. Indices of diagnostic performance were computed. Sensorimotor and after-discharge thresholds were analyzed using multivariable linear mixed models.

Results: In 15 patients (6 females), aged 5.5-21.2 years, ESM showed high accuracy (0.80), high specificity (0.86), and diagnostic odds ratio (11.4, p < 0.0001) for localization of sensorimotor parcels. Mean sensorimotor threshold (3.4 mA) was below mean after-discharge threshold (4.2 mA, p = 0.0004). Sensorimotor and after-discharge thresholds showed a significant decrease with increasing intelligence quotient. Somatotopy of sensorimotor responses was mapped to standardized brain parcels.

Conclusions: We provide evidence for diagnostic validity and safety of stereo-EEG sensorimotor ESM.

Significance: The somatotopy of sensorimotor responses elicited with electrical stimulation provide new insights into mechanisms of motor control and sensory perception.
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http://dx.doi.org/10.1016/j.clinph.2020.04.159DOI Listing
August 2020

Functional MRI in Children: Current Clinical Applications.

Semin Pediatr Neurol 2020 Apr 22;33:100800. Epub 2020 Jan 22.

Department of Pediatric Radiology and Medical Imaging, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Department of Radiology, Mayo Clinic, Rochester, MN. Electronic address:

Functional magnetic resonance imaging has become a critical research tool for evaluating brain function during active tasks and resting states. This has improved our understanding of developmental trajectories in children as well as the plasticity of neural networks in disease states. In the clinical setting, functional maps of eloquent cortex in patients with brain lesions and/or epilepsy provides crucial information for presurgical planning. Although children are inherently challenging to scan in this setting, preparing them appropriately and providing adequate resources can help achieve useful clinical data. This article will review the basic underlying physiologic aspects of functional magnetic resonance imaging, review clinically relevant research applications, describe known validation data compared to gold standard techniques and detail future directions of this technology.
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http://dx.doi.org/10.1016/j.spen.2020.100800DOI Listing
April 2020

Prospective validation of a machine learning model that uses provider notes to identify candidates for resective epilepsy surgery.

Epilepsia 2020 01 29;61(1):39-48. Epub 2019 Nov 29.

Department of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Objective: Delay to resective epilepsy surgery results in avoidable disease burden and increased risk of mortality. The objective was to prospectively validate a natural language processing (NLP) application that uses provider notes to assign epilepsy surgery candidacy scores.

Methods: The application was trained on notes from (1) patients with a diagnosis of epilepsy and a history of resective epilepsy surgery and (2) patients who were seizure-free without surgery. The testing set included all patients with unknown surgical candidacy status and an upcoming neurology visit. Training and testing sets were updated weekly for 1 year. One- to three-word phrases contained in patients' notes were used as features. Patients prospectively identified by the application as candidates for surgery were manually reviewed by two epileptologists. Performance metrics were defined by comparing NLP-derived surgical candidacy scores with surgical candidacy status from expert chart review.

Results: The training set was updated weekly and included notes from a mean of 519 ± 67 patients. The area under the receiver operating characteristic curve (AUC) from 10-fold cross-validation was 0.90 ± 0.04 (range = 0.83-0.96) and improved by 0.002 per week (P < .001) as new patients were added to the training set. Of the 6395 patients who visited the neurology clinic, 4211 (67%) were evaluated by the model. The prospective AUC on this test set was 0.79 (95% confidence interval [CI] = 0.62-0.96). Using the optimal surgical candidacy score threshold, sensitivity was 0.80 (95% CI = 0.29-0.99), specificity was 0.77 (95% CI = 0.64-0.88), positive predictive value was 0.25 (95% CI = 0.07-0.52), and negative predictive value was 0.98 (95% CI = 0.87-1.00). The number needed to screen was 5.6.

Significance: An electronic health record-integrated NLP application can accurately assign surgical candidacy scores to patients in a clinical setting.
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http://dx.doi.org/10.1111/epi.16398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980264PMC
January 2020

Clinical Letter: A case report of targeted therapy with sirolimus for NPRL3 epilepsy.

Seizure 2019 Dec 31;73:43-45. Epub 2019 Oct 31.

Division of Child Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States. Electronic address:

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http://dx.doi.org/10.1016/j.seizure.2019.10.007DOI Listing
December 2019

Investigation of bias in an epilepsy machine learning algorithm trained on physician notes.

Epilepsia 2019 09 23;60(9):e93-e98. Epub 2019 Aug 23.

Department of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Racial disparities in the utilization of epilepsy surgery are well documented, but it is unknown whether a natural language processing (NLP) algorithm trained on physician notes would produce biased recommendations for epilepsy presurgical evaluations. To assess this, an NLP algorithm was trained to identify potential surgical candidates using 1097 notes from 175 epilepsy patients with a history of resective epilepsy surgery and 268 patients who achieved seizure freedom without surgery (total N = 443 patients). The model was tested on 8340 notes from 3776 patients with epilepsy whose surgical candidacy status was unknown (2029 male, 1747 female, median age = 9 years; age range = 0-60 years). Multiple linear regression using demographic variables as covariates was used to test for correlations between patient race and surgical candidacy scores. After accounting for other demographic and socioeconomic variables, patient race, gender, and primary language did not influence surgical candidacy scores (P > .35 for all). Higher scores were given to patients >18 years old who traveled farther to receive care, and those who had a higher family income and public insurance (P < .001, .001, .001, and .01, respectively). Demographic effects on surgical candidacy scores appeared to reflect patterns in patient referrals.
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http://dx.doi.org/10.1111/epi.16320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731998PMC
September 2019

Electrical stimulation mapping of language with stereo-EEG.

Epilepsy Behav 2019 10 15;99:106395. Epub 2019 Aug 15.

Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Objective: We prospectively validated stereo-electroencephalography (EEG) electrical stimulation mapping (ESM) of language against a reference standard of meta-analytic functional magnetic resonance imaging (fMRI) framework (Neurosynth).

Methods: Language ESM was performed using 50 Hz, biphasic, bipolar, stimulation at 1-8 mA, with a picture naming task. Electrode contacts (ECs) were scored as ESM+ if ESM interfered with speech/language function. For each patient, presurgical MRI was transformed to a standard space and coregistered with computed tomographic (CT) scan to obtain EC locations. After whole-brain parcellation, this fused image data were intersected with three-dimensional language fMRI (Neurosynth), and each EC was classified as lying within/outside the fMRI language parcel. Diagnostic odds ratio (DOR) and other indices were estimated. Current thresholds for language inhibition and after-discharges (ADs) were analyzed using multivariable linear mixed models.

Results: In 10 patients (5 females), aged 5.4-21.2 years, speech/language inhibition was noted with ESM on 87/304 (29%) ECs. Stereo-EEG language ESM was a valid classifier of fMRI (Neurosynth) language sites (DOR: 9.02, p < 0.0001), with high specificity (0.87) but poor sensitivity (0.57). Similar diagnostic indices were seen for ECs in frontal or posterior regions, and gray or white matter. Language threshold (3.1 ± 1.5 mA) was lower than AD threshold (4.0 ± 2.0 mA, p = 0.0001). Language and AD thresholds decreased with age and intelligence quotient. Electrical stimulation mapping triggered seizures/auras represented patients' habitual semiology with 1 Hz stimulation.

Conclusions: Stereo-EEG ESM can reliably identify cerebral parcels with/without language function but may under detect all language sites. We suggest a 50-Hz stimulation protocol for language ESM with stereo-EEG.
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http://dx.doi.org/10.1016/j.yebeh.2019.06.038DOI Listing
October 2019

A model for visual naming based on spatiotemporal dynamics of ECoG high-gamma modulation.

Epilepsy Behav 2019 10 13;99:106455. Epub 2019 Aug 13.

Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States of America; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America.

Objective: We studied spatiotemporal dynamics of electrocorticographic (ECoG) high-gamma modulation (HGM) during visual naming.

Methods: In 8 patients, aged 4-19 years, with left hemisphere subdural electrodes, propagation of ECoG HGM during overt visual naming was mapped with trial-averaged time-frequency analysis. Group-level synthesis was performed by transforming all electrodes to a standard space and assigning cortical parcels based on a reference atlas.

Results: After image display following cortical parcels were activated: inferior occipital, caudal angular, fusiform, and middle temporal gyri, and superior temporal sulcus [0-400 ms]; rostral pars triangularis (A45r), inferior frontal sulcus, caudal dorsolateral premotor cortex (A6cdl) [300-600 ms]; caudal ventrolateral premotor cortex (A6cvl), caudal pars triangularis (A45c), pars opercularis (A44) [400-800 ms]; primary sensorimotor cortex [600-1400 ms], with most prominent HGM in glossolaryngeal region (A4tl). Lastly, auditory cortex (A41/A42) and superior temporal gyrus (A22) were activated [900 ms-1.4 s]. After 1.5 s, HGM decreased globally, except in ventrolateral premotor cortex.

Conclusions: During visual naming, ECoG HGM shows a sequential but overlapping spatiotemporal course through cortical regions. We provide neurophysiologic validation for a model of visual naming incorporating both modular and distributed cortical processing. This may explain cognitive deficits seen in some patients after surgery involving HGM naming sites outside perisylvian language cortex.
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http://dx.doi.org/10.1016/j.yebeh.2019.106455DOI Listing
October 2019

Long-term seizure outcomes after pediatric temporal lobectomy: does brain MRI lesion matter?

J Neurosurg Pediatr 2019 May 31;24(2):200-208. Epub 2019 May 31.

1Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center.

Objective: There is emerging data that adults with temporal lobe epilepsy (TLE) without a discrete lesion on brain MRI have surgical outcomes comparable to those with hippocampal sclerosis (HS). However, pediatric TLE is different from its adult counterpart. In this study, the authors investigated if the presence of a potentially epileptogenic lesion on presurgical brain MRI influences the long-term seizure outcomes after pediatric temporal lobectomy.

Methods: Children who underwent temporal lobectomy between 2007 and 2015 and had at least 1 year of seizure outcomes data were identified. These were classified into lesional and MRI-negative groups based on whether an epilepsy-protocol brain MRI showed a lesion sufficiently specific to guide surgical decisions. These patients were also categorized into pure TLE and temporal plus epilepsies based on the neurophysiological localization of the seizure-onset zone. Seizure outcomes at each follow-up visit were incorporated into a repeated-measures generalized linear mixed model (GLMM) with MRI status as a grouping variable. Clinical variables were incorporated into GLMM as covariates.

Results: One hundred nine patients (44 females) were included, aged 5 to 21 years, and were classified as lesional (73%), MRI negative (27%), pure TLE (56%), and temporal plus (44%). After a mean follow-up of 3.2 years (range 1.2-8.8 years), 66% of the patients were seizure free for ≥ 1 year at last follow-up. GLMM analysis revealed that lesional patients were more likely to be seizure free over the long term compared to MRI-negative patients for the overall cohort (OR 2.58, p < 0.0001) and for temporal plus epilepsies (OR 1.85, p = 0.0052). The effect of MRI lesion was not significant for pure TLE (OR 2.64, p = 0.0635). Concordance of ictal electroencephalography (OR 3.46, p < 0.0001), magnetoencephalography (OR 4.26, p < 0.0001), and later age of seizure onset (OR 1.05, p = 0.0091) were associated with a higher likelihood of seizure freedom. The most common histological findings included cortical dysplasia types 1B and 2A, HS (40% with dual pathology), and tuberous sclerosis.

Conclusions: A lesion on presurgical brain MRI is an important determinant of long-term seizure freedom after pediatric temporal lobectomy. Pediatric TLE is heterogeneous regarding etiologies and organization of seizure-onset zones with many patients qualifying for temporal plus nosology. The presence of an MRI lesion determined seizure outcomes in patients with temporal plus epilepsies. However, pure TLE had comparable surgical seizure outcomes for lesional and MRI-negative groups.
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http://dx.doi.org/10.3171/2019.4.PEDS18677DOI Listing
May 2019

Development of information sharing in language neocortex in childhood-onset drug-resistant epilepsy.

Epilepsia 2019 03 11;60(3):393-405. Epub 2019 Feb 11.

Division of Neurology, Comprehensive Epilepsy Center, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Objective: We studied age-related dynamics of information sharing among cortical language regions with electrocorticographic high-gamma modulation during picture-naming and story-listening tasks.

Methods: Seventeen epilepsy patients aged 4-19 years, undergoing extraoperative monitoring with left-hemispheric subdural electrodes, were included. Mutual information (MI), a nondirectional measure of shared information, between 16 pairs of cortical regions of interest, was computed from trial-averaged 70-150 Hz power modulations during language tasks. Impact of age on pairwise MI between language regions and their determinants were ascertained with regression analysis.

Results: During picture naming, significant increase in MI with age was seen between pairwise combinations of Broca's area, inferior precentral gyrus (iPreC), and frontal association cortex (FAC); Wernicke's area and posterior association cortex (PAC); and Broca's and Wernicke's areas. During story listening, significant age-related increase in MI was seen between Wernicke's area and either Broca's area, FAC, or PAC; and between Broca's area and FAC. Significant impact of baseline intelligence quotient was seen on the relationship between age and MI for all pairs, except between Broca's area and iPreC. The mean MI was higher during naming compared to listening for pairs including iPreC with Broca's area, FAC, or PAC and was lower for pairs of Wernicke's area or PAC with anterior language regions.

Significance: Information sharing matures with age "within" frontal and temporoparietal language cortices, and "between" Broca's and Wernicke's areas. This study provides evidence for distinct patterns of developmental plasticity within perisylvian language cortex and has implications for planning epilepsy surgery.
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http://dx.doi.org/10.1111/epi.14661DOI Listing
March 2019

Neuropsychological outcomes after resection of cortical sites with visual naming associated electrocorticographic high-gamma modulation.

Epilepsy Res 2019 03 29;151:17-23. Epub 2019 Jan 29.

Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Background: Language mapping with high-gamma modulation (HGM) has compared well with electrical cortical stimulation mapping (ESM). However, there is limited prospective data about its functional validity. We compared changes in neuropsychological evaluation (NPE) performed before and 1-year after epilepsy surgery, between patients with/without resection of cortical sites showing HGM during a visual naming task.

Methods: Pediatric drug-resistant epilepsy (DRE) patients underwent pre-surgical language localization with ESM and HGM using a visual naming task. Surgical decisions were based solely on ESM results. NPE difference scores were compared between patients with/without resection of HGM naming sites using principal component (PC) analysis. Follow-up NPE scores were modeled with resection group as main effect and respective pre-surgical score as a covariate, using analysis of covariance.

Results: Seventeen native English speakers (12 females), aged 6.5-20.2 years, were included. One year after epilepsy surgery, first PC score increased by (mean ± standard deviation) 14.4 ± 16.5 points in patients without resection, whereas it decreased by 7.6 ± 24.6 points in those with resection of HGM naming sites (p = 0.040). This PC score represented verbal comprehension, working memory, perceptual reasoning (Wechsler subscales); Woodcock-Johnson Tests of Achievement; and Peabody Picture Vocabulary Test. Subsequent analysis showed significant difference in working memory score between patients with/without resection of HGM naming sites (-15.2 points, 95% confidence limits -29.7 to -0.7, p = 0.041).

Conclusion: We highlight the functional consequences of resecting HGM language sites, and suggest that NPE of DRE patients should include comprehensive assessment of multiple linguistic and cognitive domains besides naming ability.
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http://dx.doi.org/10.1016/j.eplepsyres.2019.01.011DOI Listing
March 2019

Impact of radiotracer injection latency and seizure duration on subtraction ictal SPECT co-registered to MRI (SISCOM) performance in children.

Clin Neurophysiol 2018 09 23;129(9):1842-1848. Epub 2018 Jun 23.

Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Objective: We evaluated the impact of radiotracer injection latency and post-injection seizure duration on subtraction ictal SPECT co-registered to MRI (SISCOM) test performance in identifying the epileptogenic zone (EZ) in children with drug-resistant epilepsy who had undergone a resective epilepsy surgery.

Methods: SISCOM concordance with the EZ was retrospectively reviewed to evaluate its performance in 113 children. The impact of radiotracer injection latency and post-injection seizure duration was evaluated for their predictive value of SISCOM localization accuracy.

Results: The overall sensitivity and specificity of SISCOM in identifying an EZ was 64.8% (95%CI = 50.6-77.3) and 40.7% (95%CI = 28.1-54.3). The positive likelihood ratio and diagnostic odd ratio was 1.09 (95%CI = 0.80-1.48) and 1.26 (95%CI = 0.59-2.71), respectively. Logistic regression showed that injection latency and post-injection seizure duration did not significantly predict the probability of true positive SISCOM (p-value = 0.45 and 0.29, respectively).

Conclusion: Radiotracer injection latency and post-injection seizure duration were not shown to have a statistical significant impact on SISCOM performance in identifying the EZ.

Significance: This study demonstrates that further study of factors contributing to the performance of SISCOM in EZ identification in children is needed.
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http://dx.doi.org/10.1016/j.clinph.2018.06.010DOI Listing
September 2018

Electrocorticographic high-gamma modulation with passive listening paradigm for pediatric extraoperative language mapping.

Epilepsia 2018 04 20;59(4):792-801. Epub 2018 Feb 20.

Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Objective: This prospective study compared the topography of high-gamma modulation (HGM) during a story-listening task requiring negligible patient cooperation, with the conventional electrical stimulation mapping (ESM) using a picture-naming task, for presurgical language localization in pediatric drug-resistant epilepsy.

Methods: Patients undergoing extraoperative monitoring with subdural electrodes were included. Electrocorticographic signals were recorded during quiet baseline and a story-listening task. The likelihood of 70- to 150-Hz power modulation during the listening task relative to the baseline was estimated for each electrode and plotted on a cortical surface model. Sensitivity, specificity, accuracy, and diagnostic odds ratio (DOR) were estimated compared to ESM, using a meta-analytic framework.

Results: Nineteen patients (10 with left hemisphere electrodes) aged 4-19 years were analyzed. HGM during story listening was observed in bilateral posterior superior temporal, angular, supramarginal, and inferior frontal gyri, along with anatomically defined language association areas. Compared to either cognitive or both cognitive and orofacial sensorimotor interference with naming during ESM, left hemisphere HGM showed high specificity (0.82-0.84), good accuracy (0.66-0.70), and DOR of 2.23 and 3.24, respectively. HGM was a better classifier of ESM language sites in the left temporoparietal cortex compared to the frontal lobe. Incorporating visual naming with the story-listening task substantially improved the accuracy (0.80) and DOR (13.61) of HGM mapping, while the high specificity (0.85) was retained. In the right hemisphere, no ESM sites for aphasia were seen, and the results of HGM and ESM comparisons were not significant.

Significance: HGM associated with story listening is a specific determinant of left hemisphere ESM language sites. It can be used for presurgical language mapping in children who cannot cooperate with conventional language tasks requiring active engagement. Incorporation of additional language tasks, if feasible, can further improve the diagnostic accuracy of language localization with HGM.
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http://dx.doi.org/10.1111/epi.14029DOI Listing
April 2018

Fosphenytoin pre-medication for pediatric extra-operative electrical stimulation brain mapping.

Epilepsy Res 2018 02 3;140:171-176. Epub 2018 Feb 3.

Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Purpose: We studied the effect of fosphenytoin (FOS) pre-medication on the incidence and thresholds of after-discharges (ADs), seizures, and functional responses during electrical stimulation mapping (ESM).

Methods: As individualized by the attending epileptologist, FOS was given intravenously at 2 mg-phenytoin-equivalents (PE)/kg/min or 150 mg-PE/min (whichever slower). Patients who received and did not receive FOS were compared for the incidence and thresholds of ADs, seizures, and functional responses.

Results: Before ESM, 40 and 82 patients respectively were pre-medicated/not pre-medicated with FOS. The incidence of ESM-induced seizures was significantly lower in FOS pre-medicated patients (22.5% vs. 42.7%, p = 0.044), whereas temporal language threshold was higher (9.2 vs. 6.5 mA, p = 0.032). FOS was more efficacious in preventing ESM-induced seizures in patients with symptomatogenic zone ipsilateral to the side of ESM. Although FOS dose had no significant effect on minimum language, minimum motor, or AD thresholds; seizure and temporal language thresholds showed trends approaching significance, intersecting at 12.2 mg-PE/kg. The incidence of ESM-induced seizures was significantly lower in those who received FOS at a dose of ≤12 mg/kg (9.1%) compared to those who did not receive any FOS (42.7%, p = 0.046), while the temporal language thresholds were not significantly different (6.3 vs. 6.5 mA, p = 0.897).

Conclusions: This study provides class III evidence that FOS pre-medication before ESM decreases the incidence of ESM-induced seizures, but increases temporal language threshold. FOS pre-medication may thus be considered before ESM. Future studies should prospectively verify these observations and characterize dose-response relationships.
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http://dx.doi.org/10.1016/j.eplepsyres.2018.01.017DOI Listing
February 2018

After-discharges and seizures during pediatric extra-operative electrical cortical stimulation functional brain mapping: Incidence, thresholds, and determinants.

Clin Neurophysiol 2017 10 18;128(10):2078-2086. Epub 2017 Jul 18.

Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. Electronic address:

Objective: This study examined the incidence, thresholds, and determinants of electrical cortical stimulation (ECS)-induced after-discharges (ADs) and seizures.

Methods: Electrocorticograph recordings were reviewed to determine incidence of ECS-induced ADs and seizures. Multivariable analyses for predictors of AD/seizure occurrence and their thresholds were performed.

Results: In 122 patients, the incidence of ADs and seizures was 77% (94/122) and 35% (43/122) respectively. Males (odds ratio [OR] 2.92, 95% CI 1.21-7.38, p=0.02) and MRI-negative patients (OR 3.69, 95% CI 1.24-13.7, p=0.03) were found to have higher odds of ECS-induced ADs. A significant trend for decreasing AD thresholds with age was seen (regression co-efficient -0.151, 95% CI -0.267 to -0.035, p=0.011). ECS-induced seizures were more likely in patients with lateralized functional imaging (OR 6.62, 95% CI 1.36-55.56, p=0.036, for positron emission tomography) and presence of ADs (OR 3.50, 95% CI 1.12-13.36, p=0.043).

Conclusions: ECS is associated with a high incidence of ADs and seizures. With age, current thresholds decrease and the probability for AD/seizure occurrence increases.

Significance: ADs and seizures during ECS brain mapping are potentially hazardous and affect its functional validity. Thus, safer method(s) for brain mapping with improved neurophysiologic validity are desirable.
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http://dx.doi.org/10.1016/j.clinph.2017.06.259DOI Listing
October 2017

Language and motor function thresholds during pediatric extra-operative electrical cortical stimulation brain mapping.

Clin Neurophysiol 2017 10 18;128(10):2087-2093. Epub 2017 Jul 18.

Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. Electronic address:

Objective: To examine current thresholds and their determinants for language and motor mapping with extra-operative electrical cortical stimulation (ECS).

Methods: ECS electrocorticograph recordings were reviewed to determine functional thresholds. Predictors of functional thresholds were found with multivariable analyses.

Results: In 122 patients (age 11.9±5.4years), average minimum, frontal, and temporal language thresholds were 7.4 (± 3.0), 7.8 (± 3.0), and 7.4 (± 3.1) mA respectively. Average minimum, face, upper and lower extremity motor thresholds were 5.4 (± 2.8), 6.1 (± 2.8), 4.9 (± 2.3), and 5.3 (± 3.3) mA respectively. Functional and after-discharge (AD)/seizure thresholds were significantly related. Minimum, frontal, and temporal language thresholds were higher than AD thresholds at all ages. Minimum motor threshold was higher than minimum AD threshold up to 8.0years of age, face motor threshold was higher than frontal AD threshold up to 11.8years age, and lower subsequently. UE motor thresholds remained below frontal AD thresholds throughout the age range.

Conclusions: Functional thresholds are frequently above AD thresholds in younger children.

Significance: These findings raise concerns about safety and neurophysiologic validity of ECS mapping. Functional and AD/seizure thresholds relationships suggest individual differences in cortical excitability which cannot be explained by clinical variables.
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http://dx.doi.org/10.1016/j.clinph.2017.07.006DOI Listing
October 2017

Subdural grid and depth electrode monitoring in pediatric patients.

Epilepsia 2017 04;58 Suppl 1:56-65

Division of Pediatric Neurosurgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, U.S.A.

Invasive electroencephalographic monitoring with implantable subdural electrodes and intraparenchymal depth electrodes has become a basic tenet of epilepsy surgery. Improved localization of epileptic foci justifies the secondary procedure and monitoring period in many patients. Informed use of invasive monitoring in conjunction with imaging and functional studies makes epilepsy surgery a smaller, safer, and more effective endeavor. Herein we review the history, indications, implementation, and foreseeable future of grid, strip, and depth electrode use.
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http://dx.doi.org/10.1111/epi.13685DOI Listing
April 2017

Epilepsy prevalence and severity predictors in MRI-identified focal cortical dysplasia.

Epilepsy Res 2017 05 6;132:41-49. Epub 2017 Mar 6.

Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States; University of Cincinnati, Cincinnati, OH 45220, United States. Electronic address:

Objectives: To determine the prevalence of epilepsy and drug-resistant epilepsy in pediatric patients with focal cortical dysplasia (FCD) identified by magnetic resonance imaging (MRI). To determine clinical and imaging differences between those with drug-resistant epilepsy, drug-responsive epilepsy, and no epilepsy among children with MRI-identified FCD.

Methods: A keyword search of a hospital radiology database identified 97 study participants for inclusion in this retrospective study. Participants were included if they were under 18 years of age at time of database query and had an MRI between 2004 and 2013 showing FCD. Exclusion was based on imaging and clinical characteristics. Data was gathered using a chart review and supplemental questionnaire.

Results: In this cohort of patients with imaging findings compatible with FCD, 29% had not developed epilepsy. The prevalence of epilepsy and drug-resistant epilepsy was 71.13% (95% C.I.=61.05-79.89%) and 32.99% (95% C.I.=23.78-43.27%), respectively. Patients with epilepsy were more likely to have temporal (p=0.029) or frontal (p=0.044) lobe lesions and a family history of seizures (p=0.003) than those without epilepsy. Age of seizure onset was later in those with drug-responsive epilepsy than those with drug-resistant epilepsy (p=0.0002). A later age of seizure onset (OR=1.22, p=0.0441, 95% C.I.=1.00-1.486) and absence of developmental delay (OR=3.624, p=0.0497, 95% C.I.=1.002-13.110) predicted a less severe epilepsy phenotype.

Conclusions: Previous studies have only assessed patient cohorts with FCD and epilepsy, limiting the data on "asymptomatic" or "atypically presenting" FCD. Identifying a surprisingly large, novel cohort of children with FCD that had not developed epilepsy helps define prognosis and inform clinical management of children with FCD on imaging.
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http://dx.doi.org/10.1016/j.eplepsyres.2017.03.001DOI Listing
May 2017

Presurgical language localization with visual naming associated ECoG high- gamma modulation in pediatric drug-resistant epilepsy.

Epilepsia 2017 04 22;58(4):663-673. Epub 2017 Feb 22.

Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, U.S.A.

Objective: This prospective study compared presurgical language localization with visual naming-associated high-γ modulation (HGM) and conventional electrical cortical stimulation (ECS) in children with intracranial electrodes.

Methods: Patients with drug-resistant epilepsy who were undergoing intracranial monitoring were included if able to name pictures. Electrocorticography (ECoG) signals were recorded during picture naming (overt and covert) and quiet baseline. For each electrode the likelihood of high-γ (70-116 Hz) power modulation during naming task relative to the baseline was estimated. Electrodes with significant HGM were plotted on a three-dimensional (3D) cortical surface model. Sensitivity, specificity, and accuracy were calculated compared to clinical ECS.

Results: Seventeen patients with mean age of 11.3 years (range 4-19) were included. In patients with left hemisphere electrodes (n = 10), HGM during overt naming showed high specificity (0.81, 95% confidence interval [CI] 0.78-0.85), and accuracy (0.71, 95% CI 0.66-0.75, p < 0.001), but modest sensitivity (0.47) when ECS interference with naming (aphasia or paraphasic errors) and/or oral motor function was regarded as the gold standard. Similar results were reproduced by comparing covert naming-associated HGM with ECS naming sites. With right hemisphere electrodes (n = 7), no ECS-naming deficits were seen without interference with oral-motor function. HGM mapping showed a high specificity (0.81, 95% CI 0.78-0.84), and accuracy (0.76, 95% CI 0.71-0.81, p = 0.006), but modest sensitivity (0.44) compared to ECS interference with oral-motor function. Naming-associated ECoG HGM was consistently observed over Broca's area (left posterior inferior-frontal gyrus), bilateral oral/facial motor cortex, and sometimes over the temporal pole.

Significance: This study supports the use of ECoG HGM mapping in children in whom adverse events preclude ECS, or as a screening method to prioritize electrodes for ECS testing.
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http://dx.doi.org/10.1111/epi.13708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651677PMC
April 2017

Pediatric Epilepsy Surgery: The Prognostic Value of Central Nervous System Comorbidities in Patients and their Families

J Child Neurol 2017 04 6;32(5):467-474. Epub 2017 Jan 6.

2 Division of Pediatric Neurology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Central nervous system comorbidities have been identified in patients with epilepsy. Several of these comorbidities have been correlated with poor surgery outcomes in patient cohorts. The authors sought to determine if prevalence of comorbidities in pediatric epilepsy surgery patients and their families correlate with long-term seizure outcome in a cross-sectional analysis. Three-generation pedigrees were elicited to compare family history of epilepsy, ADHD, anxiety, autism, bipolar disorder, cognitive disability, depression, migraine, and motor disability to surgery outcomes in 52 patients. Proportions of affected patients and relatives were compared to general population comorbidity rates and the patients' most recent seizure outcome classification. Patients and families had significantly higher rates of comorbidities than the general population. Poorer long-term seizure outcomes following resective surgery were associated with autism or cognitive disability in patients. Together these data support evidence for a common pathophysiological mechanism between epilepsy and central nervous system comorbidities.
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http://dx.doi.org/10.1177/0883073816685653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290252PMC
April 2017

Acute postoperative seizures as predictors of seizure outcomes after epilepsy surgery.

Epilepsy Res 2016 11 24;127:119-125. Epub 2016 Aug 24.

Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. Electronic address:

Objectives: This meta-analysis was performed to determine if acute postoperative seizures (APOS) predict epilepsy surgery outcomes. Additionally, we estimated pooled prevalence for APOS and explored if certain APOS characteristics predict surgical outcomes.

Methods: A systematic literature search was performed for studies reporting seizure outcomes after epilepsy surgery in patients with and without APOS. APOS were defined as seizure(s) occurring within 30days of surgery. After data extraction, pooled Mantel-Haenszel odds ratio (OR) with 95% confidence intervals (CI) was calculated for 1-year seizure-free outcome in patients with and without APOS using random-effects meta-analysis. Sub-group meta-analysis for pediatric studies, time of occurrence, and APOS semiology were also performed. A meta-regression was performed to explore source(s) of heterogeneity.

Results: Seventeen studies were included in the final synthesis. Pooled prevalence of APOS was found to be 22.58%. A significantly higher proportion of patients without APOS within 30days of surgery (73.49%) were seizure-free at ≥1-year (OR 4.20, 95% CI 2.97-5.93, p<0.0001) compared to those with APOS (38.96%). Among the pediatric studies (n=6) 77.14% of patients without APOS were seizure-free at ≥1-year, compared to 35.94% of those with APOS (OR 5.71, 95% CI 3.32-9.80, p<0.0001). Patients having APOS within 24h of surgery and APOS semiology different from habitual pre-surgical seizures were more likely to achieve seizure-free outcomes, but these results failed to achieve statistical significance.

Conclusions: APOS reliably predict 1-year seizure outcomes after epilepsy surgery. This information should help counsel patients and families.
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http://dx.doi.org/10.1016/j.eplepsyres.2016.08.026DOI Listing
November 2016

Clinical factors predict surgical outcomes in pediatric MRI-negative drug-resistant epilepsy.

Seizure 2016 Oct 20;41:56-61. Epub 2016 Jul 20.

Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Purpose: Lack of a potentially epileptogenic lesion on brain magnetic resonance imaging (MRI) is a poor prognostic marker for epilepsy surgery. We present a single-center series of childhood-onset MRI-negative drug-resistant epilepsy (DRE) and analyze surgical outcomes and predictors.

Methods: Children with MRI-negative DRE who had resective surgery from January 2007 to December 2013 were identified using an institutional database. Relevant clinical, neurophysiological, imaging, and surgical data was extracted. The primary outcome measure was seizure freedom. Predictors of seizure freedom were obtained using multivariate logistic regression.

Results: Out of 47 children with MRI-negative DRE, 12 (25.5%) were seizure free (International League Against Epilepsy [ILAE] outcome class I), after mean follow-up of 2.75 (±1.72) years. Seizure-free proportion was significantly higher in patients with single seizure semiology and concordant ictal EEG (50.0% vs. 15.2%, p=0.025). Multivariate analysis using only non-invasive pre-surgical data showed that children with daily seizures (OR 0.02, 95% CI<0.001-0.55), and earlier onset of seizures (OR 0.72, 95% CI 0.52-0.99) were less likely to be seizure-free. Also, each additional anti-epileptic drug (AED) tried before surgery decreased the probability of seizure-free outcome (OR 0.16, 95% CI 0.04-0.63). Repeat multivariate analysis after including surgical variables found no additional significant predictors of seizure-freedom. Cortical dysplasia (ILAE type IB) was the commonest histopathology.

Conclusion: Surgical outcomes in children with MRI-negative DRE are determined by clinical factors including seizure frequency, age of onset of seizures, and number of failed AEDs.
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http://dx.doi.org/10.1016/j.seizure.2016.07.004DOI Listing
October 2016

Resection of ictal high frequency oscillations is associated with favorable surgical outcome in pediatric drug resistant epilepsy secondary to tuberous sclerosis complex.

Epilepsy Res 2016 10 16;126:90-7. Epub 2016 Jul 16.

Division of Pediatric Neurosurgery, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA. Electronic address:

Resective epilepsy surgery can improve seizures when the epileptogenic zone (EZ) is limited to a well-defined region. High frequency oscillations (HFO) have been recognized as having a high association with the seizure onset zone. Therefore, we retrospectively identified ictal HFOs and determined their relationship to specific intracranial features of cortical tubers in children with TSC who underwent resective surgery. We identified 14 patients with drug resistant epilepsy secondary to TSC who underwent subdural grid and strip implantation for presurgical evaluation and subsequent resection with adequate post-surgical follow-up. We aimed to determine the relationship between ictal HFOs, post-resection outcome and neuroimaging features in this population. The largest tuber was identified in all 14 patients (100%). Four patients (29%) had unusual tubers. HFOs were observed at ictal onset in all 14 patients. Seven of 10 patients with complete resection of HFOs were seizure free. The better seizure outcome (ILAE=1-3) was achieved with complete HFO resection regardless of the unique TSC structural features (p=0.0140). Our study demonstrates the presence of ripple and fast ripple range HFOs at ictal onset in children with TSC. Our study showed that complete HFO resection led to the better surgical outcome, independent of MR imaging findings.
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http://dx.doi.org/10.1016/j.eplepsyres.2016.07.005DOI Listing
October 2016

Methodological Issues in Predicting Pediatric Epilepsy Surgery Candidates Through Natural Language Processing and Machine Learning.

Biomed Inform Insights 2016 22;8:11-8. Epub 2016 May 22.

Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.

Objective: We describe the development and evaluation of a system that uses machine learning and natural language processing techniques to identify potential candidates for surgical intervention for drug-resistant pediatric epilepsy. The data are comprised of free-text clinical notes extracted from the electronic health record (EHR). Both known clinical outcomes from the EHR and manual chart annotations provide gold standards for the patient's status. The following hypotheses are then tested: 1) machine learning methods can identify epilepsy surgery candidates as well as physicians do and 2) machine learning methods can identify candidates earlier than physicians do. These hypotheses are tested by systematically evaluating the effects of the data source, amount of training data, class balance, classification algorithm, and feature set on classifier performance. The results support both hypotheses, with F-measures ranging from 0.71 to 0.82. The feature set, classification algorithm, amount of training data, class balance, and gold standard all significantly affected classification performance. It was further observed that classification performance was better than the highest agreement between two annotators, even at one year before documented surgery referral. The results demonstrate that such machine learning methods can contribute to predicting pediatric epilepsy surgery candidates and reducing lag time to surgery referral.
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http://dx.doi.org/10.4137/BII.S38308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876984PMC
June 2016