ABSTRACT
OBJECTIVE: We evaluated changes in cognitive domains after neurosurgical lesioning of cortical sites with significant high-gamma power modulations (HGM) during a visual naming task, although these sites were found language-negative on standard-of-care electrical stimulation mapping (ESM). METHODS: In drug-resistant epilepsy patients who underwent resection/ablation after stereo-electroencephalography (SEEG), we computed reliable change indices (RCIs) from a battery of presurgical and 1-year postsurgical neuropsychological assessments. We modeled RCIs as a function of lesioning even one HGM language site, number of HGM language sites lesioned, and the magnitude of naming-related HGM. The analyses were adjusted for 1-year seizure freedom, operated hemispheres, and the volumes of surgical lesions. RESULTS: In 37 patients with 4455 SEEG electrode contacts (1839 and 2616 contacts in right and left hemispheres, respectively), no ESM language sites were lesioned. Patients with lesioning of even one HGM language site showed significantly lower RCIs for Peabody Picture Vocabulary Test (PPVT), working memory, and verbal learning immediate (VLI) scores. RCI declines with higher number of HGM language sites lesioned were seen in PPVT (slope [ß] = -.10), working memory (ß = -.10), VLI (ß = -.14), and letter-word identification (LWI; ß = -.14). No neuropsychological domains improved after lesioning of HGM language sites. Significant effects of the HGM magnitude at lesioned sites were seen on working memory (ß = -.31), story memory immediate (ß = -.27), verbal learning recognition (ß = -.18), LWI (ß = -.16), spelling (ß = -.49), and passage comprehension (ß = -.33). Because working memory was significantly affected in all three analyses, patients with maximal working memory decline were examined post hoc, revealing that all such patients had HGM naming sites lesioned in the posterior quadrants of either hemisphere. SIGNIFICANCE: HGM language mapping should be used as an adjunct to ESM in clinical practice and may help counsel patients/families about postsurgical cognitive deficits.
ABSTRACT
OBJECTIVE: The postsynaptic density protein of excitatory neurons PSD-95 is encoded by discs large MAGUK scaffold protein 4 (DLG4), de novo pathogenic variants of which lead to DLG4-related synaptopathy. The major clinical features are developmental delay, intellectual disability (ID), hypotonia, sleep disturbances, movement disorders, and epilepsy. Even though epilepsy is present in 50% of the individuals, it has not been investigated in detail. We describe here the phenotypic spectrum of epilepsy and associated comorbidities in patients with DLG4-related synaptopathy. METHODS: We included 35 individuals with a DLG4 variant and epilepsy as part of a multicenter study. The DLG4 variants were detected by the referring laboratories. The degree of ID, hypotonia, developmental delay, and motor disturbances were evaluated by the referring clinician. Data on awake and sleep electroencephalography (EEG) and/or video-polygraphy and brain magnetic resonance imaging were collected. Antiseizure medication response was retrospectively assessed by the referring clinician. RESULTS: A large variety of seizure types was reported, although focal seizures were the most common. Encephalopathy related to status epilepticus during slow-wave sleep (ESES)/developmental epileptic encephalopathy with spike-wave activation during sleep (DEE-SWAS) was diagnosed in >25% of the individuals. All but one individual presented with neurodevelopmental delay. Regression in verbal and/or motor domains was observed in all individuals who suffered from ESES/DEE-SWAS, as well as some who did not. We could not identify a clear genotype-phenotype relationship even between individuals with the same DLG4 variants. SIGNIFICANCE: Our study shows that a subgroup of individuals with DLG4-related synaptopathy have DEE, and approximately one fourth of them have ESES/DEE-SWAS. Our study confirms DEE as part of the DLG4-related phenotypic spectrum. Occurrence of ESES/DEE-SWAS in DLG4-related synaptopathy requires proper investigation with sleep EEG.
Subject(s)
Brain Diseases , Epilepsy, Generalized , Epilepsy , Intellectual Disability , Humans , Retrospective Studies , Muscle Hypotonia , Epilepsy/diagnostic imaging , Epilepsy/genetics , Epilepsy/complications , Brain Diseases/genetics , Seizures/complications , Epilepsy, Generalized/complications , Electroencephalography/methods , Intellectual Disability/genetics , Intellectual Disability/complications , Disks Large Homolog 4 Protein/geneticsABSTRACT
OBJECTIVE: To determine whether automated, electronic alerts increased referrals for epilepsy surgery. METHODS: We conducted a prospective, randomized controlled trial of a natural language processing-based clinical decision support system embedded in the electronic health record (EHR) at 14 pediatric neurology outpatient clinic sites. Children with epilepsy and at least two prior neurology visits were screened by the system prior to their scheduled visit. Patients classified as a potential surgical candidate were randomized 2:1 for their provider to receive an alert or standard of care (no alert). The primary outcome was referral for a neurosurgical evaluation. The likelihood of referral was estimated using a Cox proportional hazards regression model. RESULTS: Between April 2017 and April 2019, at total of 4858 children were screened by the system, and 284 (5.8%) were identified as potential surgical candidates. Two hundred four patients received an alert, and 96 patients received standard care. Median follow-up time was 24 months (range: 12-36 months). Compared to the control group, patients whose provider received an alert were more likely to be referred for a presurgical evaluation (3.1% vs 9.8%; adjusted hazard ratio [HR] = 3.21, 95% confidence interval [CI]: 0.95-10.8; one-sided p = .03). Nine patients (4.4%) in the alert group underwent epilepsy surgery, compared to none (0%) in the control group (one-sided p = .03). SIGNIFICANCE: Machine learning-based automated alerts may improve the utilization of referrals for epilepsy surgery evaluations.
Subject(s)
Electronic Health Records , Epilepsy , Humans , Child , Prospective Studies , Machine Learning , Epilepsy/diagnosis , Epilepsy/surgery , Referral and ConsultationABSTRACT
OBJECTIVE: Electrical stimulation mapping (ESM) is the clinical standard for functional localization with subdural electrodes (SDE). As stereoelectroencephalography (SEEG) has emerged as an alternative option, we compared functional responses, afterdischarges (ADs), and unwanted ESM-induced seizures (EISs) between the two electrode types. METHODS: Incidence and current thresholds for functional responses (sensory, motor, speech/language), ADs, and EISs were compared between SDE and SEEG using mixed models incorporating relevant covariates. RESULTS: We identified 67 SEEG ESM and 106 SDE ESM patients (7207 and 4980 stimulated contacts, respectively). We found similar incidence of language and motor responses between electrode types; however, more SEEG patients reported sensory responses. ADs and EISs occurred less commonly with SEEG than SDE. Current thresholds for language, face motor, and upper extremity (UE) motor responses and EIS significantly decreased with age. However, they were not affected by electrode type, premedication, or dominant hemispheric stimulation. AD thresholds were higher with SEEG than with SDE. For SEEG ESM, language thresholds remained below AD thresholds up to 26 years of age, whereas this relationship was inverse for SDE. Also, face and UE motor thresholds fell below AD thresholds at earlier ages for SEEG than SDE. AD and EIS thresholds were not affected by premedication. SIGNIFICANCE: SEEG and SDE have clinically relevant differences for functional brain mapping with electrical stimulation. Although evaluation of language and motor regions is comparable between SEEG and SDE, SEEG offers a higher likelihood of identifying sensory areas. A lower incidence of ADs and EISs, and a favorable relationship between functional and AD thresholds suggest superior safety and neurophysiologic validity for SEEG ESM than SDE ESM.
Subject(s)
Drug Resistant Epilepsy , Electroencephalography , Humans , Electroencephalography/adverse effects , Electrodes, Implanted , Stereotaxic Techniques , Seizures , Brain Mapping , Electric StimulationABSTRACT
BACKGROUND AND PURPOSE: We analyzed the association of neuropsychological outcomes after epilepsy surgery with the intracranial electrode type (stereo electroencephalography [SEEG] and subdural electrodes [SDE]), and electrical stimulation mapping (ESM) of speech/language. METHODS: Drug-resistant epilepsy patients who underwent comprehensive neuropsychological evaluation before and 1 year after epilepsy surgery were included. SEEG and SDE subgroups were matched by age, handedness, operated hemisphere, and seizure freedom. Postsurgical neuropsychological outcomes (adjusted for presurgical scores) and reliable change indices were analyzed as functions of electrode type and ESM. RESULTS: Ninety-nine patients aged 6-29 years were included with similar surgical resection/ablation volumes in the SEEG and SDE subgroups. Most of the neuropsychological outcomes were comparable between SEEG and SDE subgroups; however, Working Memory and Processing Speed were significantly improved in the SEEG subgroup. Undergoing language ESM was associated with significant improvements in Spelling, Letter-Word Identification, Vocabulary, Verbal Comprehension, Verbal Learning, and Story Memory scores, but a decline in Calculation scores. CONCLUSIONS: Intracranial evaluations with SEEG and SDE are comparable in terms of long-term postsurgical neuropsychological outcomes. Our data suggest that SEEG may be associated with improvements in working memory and processing speed, representing cognitive domains served by spatially distributed networks. Our study also supports wider use of language ESM before epilepsy surgery, preferably using other language tasks in addition to visual naming. Rather than the type of electrode, postsurgical neuropsychological outcomes are driven by whether language ESM was performed or not, with beneficial effects of language mapping.
Subject(s)
Drug Resistant Epilepsy , Epilepsy , Humans , Stereotaxic Techniques , Electrodes, Implanted , Electroencephalography , Epilepsy/surgery , Drug Resistant Epilepsy/surgeryABSTRACT
OBJECTIVE: Patients with tuberous sclerosis complex (TSC) epilepsy present with unique clinical challenges such as early seizure onset and high rates of intractability and multifocality. Although there are numerous studies about the safety and efficacy of stereoelectroencephalography (SEEG), this topic has not been studied in TSC patients who have distinct epilepsy profiles. The authors investigated subdural grid (SDG) and SEEG monitoring to determine whether these procedures lead to similar seizure and safety outcomes and to identify features unique to this pediatric population. METHODS: TSC patients who underwent SDG or SEEG placement and a second epilepsy surgery during the period from 2007 to 2021 were included in this single-center retrospective cohort analysis. Various patient, hospitalization, and epilepsy characteristics were collected. RESULTS: A total of 50 TSC patients were included in this study: 30 were included in the SDG cohort and 20 in the SEEG cohort. Baseline weekly seizure count did not significantly differ between the 2 groups (p = 0.412). The SEEG group had a greater mean baseline number of antiepileptic drugs (AEDs) (3.0 vs 2.0, p = 0.003), higher rate of previous surgical interventions (25% vs 0%, p = 0.007), and larger proportion of patients who underwent bilateral monitoring (50% vs 13.3%, p = 0.005). Despite this, there was no significant difference in seizure freedom between the SDG and SEEG cohorts. The mean reduction in seizure count was 84.9% and 47.8% of patients were seizure free at last follow-up (mean 79.4 months). SEEG trended toward being a safer procedure than SDG monitoring, with a shorter mean ICU stay (0.7 days vs 3.9 days, p < 0.001), lower blood transfusion rate (0% vs 13.3%, p = 0.140), and lower surgical complication rate (0% vs 10%, p = 0.265). CONCLUSIONS: In the comparison of the SDG and SEEG cohorts, the SEEG group included patients who appeared to receive more aggressive management and have a higher rate of multifocality, more prior surgical interventions, more AEDs at baseline, and a higher rate of bilateral invasive monitoring. Despite this, the SEEG cohort had similar seizure outcomes and a trend toward increased safety. Based on these findings, SEEG appears to allow for monitoring of a wider breadth of TSC patients given its minimally invasive nature and its relative simplicity for monitoring numerous regions of the brain.
Subject(s)
Drug Resistant Epilepsy , Epilepsy , Tuberous Sclerosis , Child , Humans , Anticonvulsants/therapeutic use , Drug Resistant Epilepsy/surgery , Electrodes, Implanted , Electroencephalography/methods , Epilepsy/surgery , Retrospective Studies , Seizures/surgery , Stereotaxic Techniques , Treatment Outcome , Tuberous Sclerosis/complications , Tuberous Sclerosis/surgeryABSTRACT
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.
Subject(s)
Algorithms , Epilepsy/diagnostic imaging , Epilepsy/surgery , Machine Learning , Adolescent , Adult , Child , Child, Preschool , Cohort Studies , Early Diagnosis , Electroencephalography/methods , Epilepsy/physiopathology , Female , Humans , Longitudinal Studies , Magnetic Resonance Imaging/methods , Male , Middle Aged , Retrospective Studies , Young AdultABSTRACT
OBJECTIVE: We evaluated SISCOM patterns and their relationship with surgical outcome in children with temporal lobe epilepsy (TLE) who had undergone a temporal lobe surgery. METHODS: This was an observational study evaluating SISCOM patterns in 40 children with TLE. We classified SISCOM patterns into 4 categories; (i) unilateral anteromesial and/or anterolateral temporal pattern; (ii) unilateral anteromesial and/or anterolateral temporal plus posterior extension pattern; (iii) bilateral anteromesial and/or anterolateral temporal pattern; and (iv) atypical pattern. Determinants of SISCOM pattern and correlation between postoperative outcomes and SISCOM patterns were evaluated. RESULTS: Pattern (i), (ii), (iii), and (iv) were identified in 10 (25%), 14 (35%), 0 (0%), and 16 (40%) patients, respectively. There was no significant correlation between patterns and postoperative outcomes. SISCOM patterns significantly associated with the presence of hippocampal sclerosis and type of focal cortical dysplasia (p-value = 0.048 and 0.036, respectively). Patients with HS had 5 times the odds of having unilateral temporal pattern, compared to patients with other neuropathology (OR = 5, 95% CI 0.92 to 27.08). Patients with FCD type 2 had 9.71 times the odds of having atypical pattern, compared to patients with other types of FCD (OR = 9.71, 95% CI 0.92 to 103.04). Lobar concordance of SISCOM and ictal and interictal scalp EEG significantly correlated with postoperative outcomes (p-value = 0.018 and 0.013, respectively). CONCLUSION: Three SISCOM patterns were seen. Patients with HS had increased odds of having unilateral temporal pattern while patients with FCD type 2 had increased odds of having atypical pattern. However, there was no significant correlation between SISCOM patterns and postoperative outcomes. Lobar concordance of SISCOM and ictal and interictal scalp EEG significantly correlated with postoperative outcome. SIGNIFICANCE: This study shows that the distribution of SISCOM patterns and their relationship with postoperative outcomes in children with TLE are different from adult population. Besides, SISCOM may add only limited diagnostic and prognostic information in children with drug-resistant TLE undergoing epilepsy surgery. Further evaluation to identify patient populations that may benefit from SISCOM is desirable.
Subject(s)
Drug Resistant Epilepsy , Epilepsy, Temporal Lobe , Adult , Child , Electroencephalography , Epilepsy, Temporal Lobe/complications , Epilepsy, Temporal Lobe/diagnostic imaging , Epilepsy, Temporal Lobe/surgery , Humans , Magnetic Resonance Imaging , Retrospective Studies , Tomography, Emission-Computed, Single-PhotonABSTRACT
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.
Subject(s)
Drug Resistant Epilepsy , Epilepsy , Drug Resistant Epilepsy/diagnostic imaging , Drug Resistant Epilepsy/surgery , Electrodes , Electroencephalography , Epilepsy/diagnostic imaging , Epilepsy/surgery , Humans , Magnetic Resonance ImagingABSTRACT
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.
Subject(s)
Electronic Health Records , Epilepsy/surgery , Machine Learning , Natural Language Processing , Patient Selection , Adolescent , Adult , Child , Child, Preschool , Decision Support Systems, Clinical , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Prospective Studies , Young AdultABSTRACT
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.
Subject(s)
Epilepsy/surgery , Healthcare Disparities , Machine Learning , Patient Selection , Prejudice , Adolescent , Adult , Age Factors , Algorithms , Child , Child, Preschool , Electroencephalography , Humans , Infant , Middle Aged , Referral and Consultation , Young AdultABSTRACT
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.
Subject(s)
Drug Resistant Epilepsy/physiopathology , Language , Neocortex/physiopathology , Adolescent , Age Factors , Brain Mapping , Broca Area/physiopathology , Child , Child, Preschool , Electrocardiography , Female , Frontal Lobe/physiopathology , Humans , Male , Wernicke Area/physiopathology , Young AdultABSTRACT
OBJECTIVE: We studied spatiotemporal dynamics of electrocorticographic (ECoG) high-gamma modulation (HGM) during visual naming. METHODS: In 8 patients, aged 4-19â¯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 [0-400â¯ms]; rostral pars triangularis (A45r), inferior frontal sulcus, caudal dorsolateral premotor cortex (A6cdl) [300-600â¯ms]; caudal ventrolateral premotor cortex (A6cvl), caudal pars triangularis (A45c), pars opercularis (A44) [400-800â¯ms]; primary sensorimotor cortex [600-1400â¯ms], with most prominent HGM in glossolaryngeal region (A4tl). Lastly, auditory cortex (A41/A42) and superior temporal gyrus (A22) were activated [900â¯ms-1.4â¯s]. After 1.5â¯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.
Subject(s)
Brain Mapping/methods , Cerebral Cortex/physiology , Drug Resistant Epilepsy/physiopathology , Electrocorticography/methods , Language , Models, Neurological , Visual Perception/physiology , Adolescent , Child , Child, Preschool , Drug Resistant Epilepsy/surgery , Female , Humans , Male , Spatio-Temporal Analysis , Young AdultABSTRACT
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 50â¯Hz, biphasic, bipolar, stimulation at 1-8â¯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 5.4-21.2â¯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, pâ¯<â¯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⯱â¯1.5â¯mA) was lower than AD threshold (4.0⯱â¯2.0â¯mA, pâ¯=â¯0.0001). Language and AD thresholds decreased with age and intelligence quotient. Electrical stimulation mapping triggered seizures/auras represented patients' habitual semiology with 1â¯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.
Subject(s)
Brain Mapping/methods , Brain/physiology , Electroencephalography/methods , Language , Magnetic Resonance Imaging/methods , Stereotaxic Techniques , Adolescent , Brain/diagnostic imaging , Brain/physiopathology , Child , Child, Preschool , Electric Stimulation/methods , Female , Humans , Male , Prospective Studies , Seizures/diagnostic imaging , Seizures/physiopathology , Seizures/surgery , Speech/physiology , Young AdultABSTRACT
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.
Subject(s)
Auditory Perception/physiology , Brain Mapping/methods , Electrocorticography/methods , Gamma Rhythm/physiology , Language , Preoperative Care/methods , Adolescent , Child , Child, Preschool , Drug Resistant Epilepsy/diagnosis , Drug Resistant Epilepsy/physiopathology , Drug Resistant Epilepsy/surgery , Female , Humans , Male , Prospective Studies , Young AdultABSTRACT
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.
Subject(s)
Brain Diseases/physiopathology , Brain Diseases/surgery , Brain Mapping , Electrodes, Implanted , Monitoring, Physiologic/methods , Subdural Space/physiopathology , Brain/diagnostic imaging , Brain/physiopathology , Brain/surgery , Brain Diseases/diagnostic imaging , Electroencephalography , Humans , Magnetic Resonance Imaging , Pediatrics , Subdural Space/diagnostic imagingABSTRACT
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.
Subject(s)
Brain Mapping , Drug Resistant Epilepsy/physiopathology , Gamma Rhythm/physiology , Language , Names , Adolescent , Brain/diagnostic imaging , Brain/physiopathology , Child , Child, Preschool , Drug Resistant Epilepsy/surgery , Electric Stimulation , Electrodes, Implanted , Electroencephalography , Female , Functional Laterality , Humans , Imaging, Three-Dimensional , Magnetic Resonance Imaging , Male , Photic Stimulation , Tomography Scanners, X-Ray Computed , Young AdultABSTRACT
OBJECTIVE: The predictive value of intraoperative electrocorticography (ECoG) in pediatric epilepsy surgery is unknown. In a population of children undergoing ECoG followed typically by invasive extraoperative monitoring (IEM) and resection, we aimed to determine the relationship between frequent ECoG abnormalities and the seizure onset zone and outcome after resection. METHODS: We retrospectively identified 103 children with preresection ECoG of sufficient technical quality. ECoG records were scored based on electrode location and frequency, blinded to the seizure-onset zone and outcome. Electrographic seizure and spike locations were identified. Locations of seizures and spike populations were then compared to the location of seizure-onset zone defined by IEM using subdural electrodes and resection margin. RESULTS: Electrographic seizures were identified in 11 (11%) of 103 patients. A spike population of one or more was noted in 79 (77%) of 103 patients. In 50 (63%) of 79 patients, spike populations correlated with seizure-onset zone location. The overall surgical outcome was good (ILAE 1 to 3) in 53 (52%) of 101 patients. Outcome was good in seven (78%) of nine patients when electrographic seizure location was resected. The best outcomes were obtained with resection of both the seizure-onset zone and ECoG abnormalities to include seizures and spike locations (22/33 good outcome, 67%, p = 0.008). There was a significantly better outcome in children with complete resection of ECoG-identified spike populations (14/26, 62% good outcome) compared to when none were resected (4/14, 29%, p = 0.043). SIGNIFICANCE: Electrographic seizures and frequent spikes are frequently seen on pre-resection ECoG in children. The brain locations corresponding to these discharges are highly concordant with the seizure-onset zone; resection of these regions is correlated with good seizure outcome. Further research is needed to design interventions that increase the reliability of ECoG prediction of the epileptogenic zone and obviate the need for IEM.
Subject(s)
Electrocorticography/methods , Epilepsy/diagnosis , Epilepsy/surgery , Monitoring, Intraoperative/methods , Seizures/diagnosis , Seizures/surgery , Adolescent , Child , Electrodes, Implanted , Epilepsy/physiopathology , Female , Follow-Up Studies , Humans , Male , Predictive Value of Tests , Preoperative Care/methods , Retrospective Studies , Seizures/physiopathology , Treatment OutcomeABSTRACT
BACKGROUND: Cortical dysplasia is the most common cause of pediatric refractory epilepsy. MRI detection of epileptogenic lesion is associated with good postsurgical outcome. Additional electrophysiological information is suggested to be helpful in localization of cortical dysplasia. Educational measures were taken to increase the awareness of cortical dysplasia at our institution in the context of a recent International League Against Epilepsy (ILAE 2011) classification of cortical dysplasia. OBJECTIVE: To determine changes in the rate of prospective identification of cortical dysplasia on an initial radiology report and also evaluate the benefit of MRI review as part of a multidisciplinary epilepsy conference in identifying previously overlooked MRI findings. MATERIALS AND METHODS: We retrospectively evaluated surgically treated children with refractory epilepsy from 2007 to 2014 with cortical dysplasia on histopathology. We analyzed the initial radiology report, preoperative MRI interpretation at multidisciplinary epilepsy conference and subsequent retrospective MRI review with knowledge of the resection site. We recorded additional electrophysiological data and the presence of lobar concordance with the MRI findings. RESULTS: Of 78 children (44 MRI lesional) evaluated, 18 had initially overlooked MRI findings. Comparing 2007-2010 to 2011-2014, there was improvement in the rate of overlooked findings on the initial radiology report (54% vs. 13% of lesional cases, respectively; P = 0.008). The majority (72%) were identified at a multidisciplinary conference with lobar concordance of findings with at least one additional electrophysiological investigation in 89%. CONCLUSION: Awareness of current classification schemes of cortical dysplasia and image review in the context of a multidisciplinary conference can lead to improved MRI detection of cortical dysplasia in children.
Subject(s)
Drug Resistant Epilepsy/diagnostic imaging , Drug Resistant Epilepsy/pathology , Magnetic Resonance Imaging/methods , Malformations of Cortical Development/diagnostic imaging , Malformations of Cortical Development/pathology , Adolescent , Child , Child, Preschool , Drug Resistant Epilepsy/surgery , Electroencephalography , Female , Humans , Infant , Male , Prospective Studies , Retrospective Studies , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray Computed , Young AdultABSTRACT
It has been postulated that mitochondrial dysfunction may be an important factor in epileptogenesis of intractable epilepsy. The current study tests the hypothesis that mitochondrial Complex IV (CIV) or cytochrome c oxidase dysfunction is associated with the seizure onset zone (SOZ) in patients with focal cortical dysplasia (FCD). Subjects were selected based on: age <19y; epilepsy surgery between May, 2010 and October, 2011; pathological diagnosis of isolated focal cortical dysplasia Type I (FCDI) or Type II (FCDII); and sufficient residual cortical tissue to conduct analysis of electron transport chain complex (ETC) activity in SOZ and adjacent cortical regions. In this retrospective study, patients were identified who had sufficient unfixed, frozen brain tissue for biochemical analysis in tissue homogenates. Specimens were subtyped using ILAE classification for FCD, and excluded if diagnosed with FCD Type III or dual pathology. Analysis of ETC activity in resected tissues was conducted independently and without knowledge of the identity, diagnosis, or clinical status of individual subjects. Seventeen patients met the inclusion criteria, including 6 FCDI and 11 FCDII. Comparison of adjacent cortical resections showed decreased CIV activity in the SOZ of the FCDII group (P = 0.003), but no significant CIV difference in adjacent tissues of the FCDI group. Because of the importance of CIV as the terminal and rate-limiting complex in the mitochondrial electron transport chain, these authors conclude that 1) a deficit of CIV is associated with the SOZ of patients with FCDII; 2) CIV deficiency may contribute to the spectrum of FCD neuropathology; and 3) further investigation of CIV in FCD may lead to the discovery of new targets for neuroprotective therapies for patients with intractable epilepsy.