High-gamma modulation language mapping and cognitive outcomes after epilepsy surgery.

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.

Antibiotic impregnated catheters and intrathecal antibiotics for CSF shunt infection prevention in children undergoing low-risk CSF shunt surgery.

BACKGROUND: Cerebrospinal fluid (CSF) shunts allow children with hydrocephalus to survive and avoid brain injury (J Neurosurg 107:345-57, 2007; Childs Nerv Syst 12:192-9, 1996). The Hydrocephalus Clinical Research Network implemented non-randomized quality improvement protocols that were shown to decrease infection rates compared to pre-operative prophylactic intravenous antibiotics alone (standard care): initially with intrathecal (IT) antibiotics between 2007-2009 (J Neurosurg Pediatr 8:22-9, 2011), followed by antibiotic impregnated catheters (AIC) in 2012-2013 (J Neurosurg Pediatr 17:391-6, 2016). No large scale studies have compared infection prevention between the techniques in children. Our objectives were to compare the risk of infection following the use of IT antibiotics, AIC, and standard care during low-risk CSF shunt surgery (i.e., initial CSF shunt placement and revisions) in children. METHODS: A retrospective observational cohort study at 6 tertiary care children's hospitals was conducted using Pediatric Health Information System + (PHIS +) data augmented with manual chart review. The study population included children ≤ 18 years who underwent initial shunt placement between 01/2007 and 12/2012. Infection and subsequent CSF shunt surgery data were collected through 12/2015. Propensity score adjustment for regression analysis was developed based on site, procedure type, and year; surgeon was treated as a random effect. RESULTS: A total of 1723 children underwent initial shunt placement between 2007-2012, with 1371 subsequent shunt revisions and 138 shunt infections. Propensity adjusted regression demonstrated no statistically significant difference in odds of shunt infection between IT antibiotics (OR 1.22, 95% CI 0.82-1.81, p = 0.3) and AICs (OR 0.91, 95% CI 0.56-1.49, p = 0.7) compared to standard care. CONCLUSION: In a large, observational multicenter cohort, IT antibiotics and AICs do not confer a statistically significant risk reduction compared to standard care for pediatric patients undergoing low-risk (i.e., initial or revision) shunt surgeries.

The Anti-Inflammatory Agent Bindarit Attenuates the Impairment of Neural Development through Suppression of Microglial Activation in a Neonatal Hydrocephalus Mouse Model.

Neonatal hydrocephalus presents with various degrees of neuroinflammation and long-term neurologic deficits in surgically treated patients, provoking a need for additional medical treatment. We previously reported elevated neuroinflammation and severe periventricular white matter damage in the progressive hydrocephalus (prh) mutant which contains a point mutation in the Ccdc39 gene, causing loss of cilia-mediated unidirectional CSF flow. In this study, we identified cortical neuropil maturation defects such as impaired excitatory synapse maturation and loss of homeostatic microglia, and swimming locomotor defects in early postnatal prh mutant mice. Strikingly, systemic application of the anti-inflammatory small molecule bindarit significantly supports healthy postnatal cerebral cortical development in the prh mutant. While bindarit only mildly reduced the ventricular volume, it significantly improved the edematous appearance and myelination of the corpus callosum. Moreover, the treatment attenuated thinning in cortical Layers II-IV, excitatory synapse formation, and interneuron morphogenesis, by supporting the ramified-shaped homeostatic microglia from excessive cell death. Also, the therapeutic effect led to the alleviation of a spastic locomotor phenotype of the mutant. We found that microglia, but not peripheral monocytes, contribute to amoeboid-shaped activated myeloid cells in prh mutants' corpus callosum and the proinflammatory cytokines expression. Bindarit blocks nuclear factor (NF)-kB activation and its downstream proinflammatory cytokines, including monocyte chemoattractant protein-1, in the prh mutant. Collectively, we revealed that amelioration of neuroinflammation is crucial for white matter and neuronal maturation in neonatal hydrocephalus. Future studies of bindarit treatment combined with CSF diversion surgery may provide long-term benefits supporting neuronal development in neonatal hydrocephalus.SIGNIFICANCE STATEMENT In neonatal hydrocephalus, little is known about the signaling cascades of neuroinflammation or the impact of such inflammatory insults on neural cell development within the perinatal cerebral cortex. Here, we report that proinflammatory activation of myeloid cells, the majority of which are derived from microglia, impairs periventricular myelination and cortical neuronal maturation using the mouse prh genetic model of neonatal hydrocephalus. Administration of bindarit, an anti-inflammatory small molecule that blocks nuclear factor (NF)-kB activation, restored the cortical thinning and synaptic maturation defects in the prh mutant brain through suppression of microglial activation. These data indicate the potential therapeutic use of anti-inflammatory reagents targeting neuroinflammation in the treatment of neonatal hydrocephalus.

Automated, machine learning-based alerts increase epilepsy surgery referrals: A randomized controlled trial.

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.

Comparing electrical stimulation functional mapping with subdural electrodes and stereoelectroencephalography.

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.

Added value of corpus callosotomy following vagus nerve stimulation in children with Lennox-Gastaut syndrome: A multicenter, multinational study.

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe form of epileptic encephalopathy, presenting during the first years of life, and is very resistant to treatment. Once medical therapy has failed, palliative surgeries such as vagus nerve stimulation (VNS) or corpus callosotomy (CC) are considered. Although CC is more effective than VNS as the primary neurosurgical treatment for LGS-associated drop attacks, there are limited data regarding the added value of CC following VNS. This study aimed to assess the effectiveness of CC preceded by VNS. METHODS: This multinational, multicenter retrospective study focuses on LGS children who underwent CC before the age of 18 years, following prior VNS, which failed to achieve satisfactory seizure control. Collected data included epilepsy characteristics, surgical details, epilepsy outcomes, and complications. The primary outcome of this study was a 50% reduction in drop attacks. RESULTS: A total of 127 cases were reviewed (80 males). The median age at epilepsy onset was 6 months (interquartile range [IQR] = 3.12-22.75). The median age at VNS surgery was 7 years (IQR = 4-10), and CC was performed at a median age of 11 years (IQR = 8.76-15). The dominant seizure type was drop attacks (tonic or atonic) in 102 patients. Eighty-six patients underwent a single-stage complete CC, and 41 an anterior callosotomy. Ten patients who did not initially have a complete CC underwent a second surgery for completion of CC due to seizure persistence. Overall, there was at least a 50% reduction in drop attacks and other seizures in 83% and 60%, respectively. Permanent morbidity occurred in 1.5%, with no mortality. SIGNIFICANCE: CC is vital in seizure control in children with LGS in whom VNS has failed. Surgical risks are low. A complete CC has a tendency toward better effectiveness than anterior CC for some seizure types.

Neuropsychological outcomes after epilepsy surgery: A comparison of stereo electroencephalography and subdural electrodes.

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.

Utility of the material community deprivation index as a metric to identify at-risk children for severe traumatic brain injury.

OBJECTIVE: Pediatric traumatic brain injury (TBI) is a significant cause of morbidity and mortality with lasting effects including neurological deficits and psychological comorbidities. Recent studies have shown that social determinants of health are key factors that impact clinical outcomes in other pediatric traumatic injuries, suggesting that these health disparities may have a significant impact on patients sustaining TBI as well. The purpose of this study was to retrospectively review a cohort of pediatric patients diagnosed with TBI and elucidate the relationships among socioeconomic deprivation, patient-specific demographics, and morbidity and mortality. METHODS: The authors conducted a retrospective cross-sectional analysis of pediatric patients (≤ 18 years of age) treated for TBI at a level I pediatric trauma center between 2016 and 2020. Patients with concussion-related injuries without intracranial findings and those with nonaccidental trauma were excluded from the study. In addition to evaluating basic patient demographics, the authors geocoded patient addresses to allow identification of the patient's home census tract using the material community deprivation index (MCDI). The MCDI is a unique composite index score created by the combination of six census variables and ranges from 0 to 1 in severity. RESULTS: Of the 513 patients included in this study, 71 (13.8%) were diagnosed with severe TBI, 28 (5.5%) with moderate TBI, and 414 (80.7%) with mild TBI. Patients in quartile 4 (MCDI ≥ 0.45) were at a significantly higher risk of having a severe TBI than patients in quartile 1 (OR 2.29, 95% CI 1.1-4.71; p = 0.02). Black patients were more likely to have a firearm-related TBI (OR 3.74, 95% CI 2.01-8.7; p = 0.018) than non-Black patients. Patients who lived in a neighborhood with a lower MCDI were significantly more likely to be discharged home than those who lived in an area with a higher MCDI (OR 2.78, 95% CI 7.90-32.93; p < 0.001). CONCLUSIONS: This study demonstrated that inequities continue to exist within the pediatric TBI population and that the MCDI is a valuable tool to identify at-risk subpopulations. More specifically, patients who lived in a neighborhood with a higher MCDI were at higher risk of sustaining a severe TBI. By partnering with communities, families, and policymakers, healthcare providers could serve as advocates for these patients and work to minimize the social disparities that continue to exist.

International Pediatric Multidisciplinary Management Using Telemedicine to Promote Equitable Care.

Objective: To evaluate the use of telemedicine as a collaboration tool between a pediatrician and subspecialists looking to address challenges, such as the lack of health care specialists, which are present in the Dominican Republic. Study design: During this 6-year study, 65 patients were evaluated by a medical team consisting of a local pediatrician and 17 subspecialists from a leading academic medical center in the Unites States. Patient's age ranged from 2 months to 16 years of age (mean 8 years old). The most common reasons for referral were masses or malignancies, vascular malformations, urogenital anomalies, stuttering, and cochlear implant programming. Results: A total of 39 out of 65 cases (60%) carried an initial diagnosis. Of the 65 cases, a change in medical management occurred in 92.31% of cases (60 cases). There was no change in medical diagnosis or treatment in 5 of 65 cases (8%). Conclusion: This protocol exhibited high patient satisfaction with the technology and platform and direct patient savings from transportation costs. It also demonstrated the importance of thorough diagnosis in providing appropriate treatment and solutions. Telemedicine use in comparable practices should be studied further to aid in the development of policies for the diagnosis and management of chronic illnesses that require referrals to subspecialists.

An iPad-based intervention to improve visual-motor, visual-attention, and visual-perceptual skills in children with surgically treated hydrocephalus: A pilot study.

PURPOSE: Develop and pilot an iPad-based intervention for improving visual-motor coordination, visual-spatial processing/reasoning, and visual attention in children with surgically treated hydrocephalus (HCP). METHODS: We developed an intervention protocol targeting visual-motor coordination, visual-spatial processing/reasoning, and visual attention. Fourteen participants with HCP completed 30 h of training over 6 weeks. The primary outcome measure was the Perceptual Reasoning Index from the Wechsler Abbreviated Scale of Intelligence, Second Edition. Secondary measures included subtests from the Wechsler Intelligence Scale for Children, Fourth Edition, Developmental NEuroPSYchological Assessment, Second Edition (NEPSY-II), and Purdue Pegboard. RESULTS: Children with HCP demonstrated gains with statistical significance on the Perceptual Reasoning Index. We also observed significant improvement on a timed test of visuo-motor coordination (Wechsler Intelligence Scale for Children, Fourth Edition, Coding). CONCLUSION: Our iPad-application-based intervention may promote visual-motor coordination, visual-spatial processing/reasoning, and visual attention skills in children with HCP, offering an engaging and economical supplement to more conventional therapies.

Comparison of outcomes after stereoelectroencephalography and subdural grid monitoring in pediatric tuberous sclerosis complex.

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.

A mutation in Ccdc39 causes neonatal hydrocephalus with abnormal motile cilia development in mice.

Pediatric hydrocephalus is characterized by an abnormal accumulation of cerebrospinal fluid (CSF) and is one of the most common congenital brain abnormalities. However, little is known about the molecular and cellular mechanisms regulating CSF flow in the developing brain. Through whole-genome sequencing analysis, we report that a homozygous splice site mutation in coiled-coil domain containing 39 (Ccdc39) is responsible for early postnatal hydrocephalus in the progressive hydrocephalus (prh) mouse mutant. Ccdc39 is selectively expressed in embryonic choroid plexus and ependymal cells on the medial wall of the forebrain ventricle, and the protein is localized to the axoneme of motile cilia. The Ccdc39prh/prh ependymal cells develop shorter cilia with disorganized microtubules lacking the axonemal inner arm dynein. Using high-speed video microscopy, we show that an orchestrated ependymal ciliary beating pattern controls unidirectional CSF flow on the ventricular surface, which generates bulk CSF flow in the developing brain. Collectively, our data provide the first evidence for involvement of Ccdc39 in hydrocephalus and suggest that the proper development of medial wall ependymal cilia is crucial for normal mouse brain development.

Epilepsy surgery in infants up to 3 months of age: Safety, feasibility, and outcomes: A multicenter, multinational study.

OBJECTIVE: Drug-resistant epilepsy (DRE) during the first few months of life is challenging and necessitates aggressive treatment, including surgery. Because the most common causes of DRE in infancy are related to extensive developmental anomalies, surgery often entails extensive tissue resections or disconnection. The literature on "ultra-early" epilepsy surgery is sparse, with limited data concerning efficacy controlling the seizures, and safety. The current study's goal is to review the safety and efficacy of ultra-early epilepsy surgery performed before the age of 3 months. METHODS: To achieve a large sample size and external validity, a multinational, multicenter retrospective study was performed, focusing on epilepsy surgery for infants younger than 3 months of age. Collected data included epilepsy characteristics, surgical details, epilepsy outcome, and complications. RESULTS: Sixty-four patients underwent 69 surgeries before the age of 3 months. The most common pathologies were cortical dysplasia (28), hemimegalencephaly (17), and tubers (5). The most common procedures were hemispheric surgeries (48 procedures). Two cases were intentionally staged, and one was unexpectedly aborted. Nearly all patients received blood products. There were no perioperative deaths and no major unexpected permanent morbidities. Twenty-five percent of patients undergoing hemispheric surgeries developed hydrocephalus. Excellent epilepsy outcome (International League Against Epilepsy [ILAE] grade I) was achieved in 66% of cases over a median follow-up of 41 months (19-104 interquartile range [IQR]). The number of antiseizure medications was significantly reduced (median 2 drugs, 1-3 IQR, p < .0001). Outcome was not significantly associated with the type of surgery (hemispheric or more limited resections). SIGNIFICANCE: Epilepsy surgery during the first few months of life is associated with excellent seizure control, and when performed by highly experienced teams, is not associated with more permanent morbidity than surgery in older infants. Thus surgical treatment should not be postponed to treat DRE in very young infants based on their age.

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

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.

Subtraction ictal SPECT co-registered to MRI (SISCOM) patterns in children with temporal lobe epilepsy.

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.

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

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.

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

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.

Reading in children with drug-resistant epilepsy was related to functional connectivity in cognitive control regions.

AIM: This study aimed to define whether individuals with drug-resistant focal epilepsy also used regions related to cognitive control to facilitate reading. METHODS: We focused on patients with drug-resistant focal epilepsy in 2011-2014, who were aged 8-20 years and were being treated at the Cincinnati Children's Hospital, USA. They performed a verb generation functional magnetic resonance imaging task known to involve language and cognitive control, as well as a formal reading assessment. The reading scores were correlated with functional connectivity of the anterior cingulate cortex (ACC) using seed-to-voxel analysis. RESULTS: There were 81 potential patients and 13 (seven females) met the inclusion criteria. Their age at seizure onset was 0-13 years, and they had a mean age of 12.66 ± 3.17 years at the time of the study. Individuals with epilepsy demonstrated average intelligence and word reading ability. Their reading scores were positively correlated with functional connectivity between the ACC and regions related to emotional processing (right amygdala), learning and language processing (left cerebellum) and visual processing. CONCLUSION: Our results support the role that the ACC plays in proficient reading among children with drug-resistant epilepsy, even in those with epileptogenic foci in areas related to language.

Abnormal anisotropic diffusion properties in pediatric myelomeningocele patients treated with fetal surgery: an initial DTI study.

PURPOSE: To investigate white matter microstructural abnormality based on diffusion tensor imaging (DTI) in pediatric patients with fetal repair for myelomeningocele (MMC). METHODS: This was a retrospective analysis of DTI data from 8 pediatric patients with prenatal MMC repair (age range 1.64-33.70 months; sex 3F/5M) and 8 age-matched controls (age 2.24-31.20 months; sex 5F/2M). All participants were scanned on 1.5T GE Signa MR scanner (GE Healthcare, Milwaukee, WI) with the same sequence specifications. Two DTI measures, including fractional anisotropy (FA) and mean diffusivity (MD), were calculated from the genu of corpus callosum (gCC) and the posterior limb of internal capsule (PLIC). DTI values and fronto-occipital horn ratio (FOHR) were tested for group difference based on two-tailed paired t test. RESULTS: The ventricle size based on FOHR in patients with prenatal MMC repair was significantly larger than that in the age-matched control group (p < 0.001). Statistically significant group difference in DTI (lower FA and higher MD in patient group) was found in gCC (p = 0.007 and 0.003, respectively). A trend level increase in MD was also found (p = 0.065) in PLIC in patients when compared with the age-matched controls. CONCLUSION: Our data showed white matter abnormality based on DTI in pediatric patient with fetal repair for MMC. The sensitivity of DTI in detecting white matter abnormality, as shown in the present study, may help to serve as an imaging biomarker for assessing hydrocephalus and improve and optimize decision making for the treatment of hydrocephalus in this patient population.

Not all ventriculomegaly is created equal: diagnostic overview of fetal, neonatal and pediatric ventriculomegaly.

Fetal ventriculomegaly refers to a condition in which there is enlargement of the ventricular spaces, typically on prenatal ultrasound. It can be associated with other CNS or extra-CNS abnormalities, and this relationship is crucial to understand as it affects overall neonatal outcome. Isolated ventriculomegaly has been described in the literature with variable clinical outcome. Typically, outcome is based on the etiology and degree of ventriculomegaly. When associated with a pathologic condition, ventriculomegaly can be a result of hydrocephalus. While initial diagnosis is usually made on prenatal ultrasound, fetal magnetic resonance imaging is preferred to further elucidate any associated CNS malformations. In this paper, the authors aim to provide a comprehensive review of the diagnosis, associated etiologies, prognosis, and treatment options related to fetal, neonatal, and pediatric ventriculomegaly and hydrocephalus. In addition, preliminary data is provided from our institutional cohort of patients with a prenatal diagnosis of ventriculomegaly followed through the perinatal period.