Language and developmental plasticity after perinatal stroke.

The mature human brain is lateralized for language, with the left hemisphere (LH) primarily responsible for sentence processing and the right hemisphere (RH) primarily responsible for processing suprasegmental aspects of language such as vocal emotion. However, it has long been hypothesized that in early life there is plasticity for language, allowing young children to acquire language in other cortical regions when LH areas are damaged. If true, what are the constraints on functional reorganization? Which areas of the brain can acquire language, and what happens to the functions these regions ordinarily perform? We address these questions by examining long-term outcomes in adolescents and young adults who, as infants, had a perinatal arterial ischemic stroke to the LH areas ordinarily subserving sentence processing. We compared them with their healthy age-matched siblings. All participants were tested on a battery of behavioral and functional imaging tasks. While stroke participants were impaired in some nonlinguistic cognitive abilities, their processing of sentences and of vocal emotion was normal and equal to that of their healthy siblings. In almost all, these abilities have both developed in the healthy RH. Our results provide insights into the remarkable ability of the young brain to reorganize language. Reorganization is highly constrained, with sentence processing almost always in the RH frontotemporal regions homotopic to their location in the healthy brain. This activation is somewhat segregated from RH emotion processing, suggesting that the two functions perform best when each has its own neural territory.

Seizure Control Outcomes following Resection of Cortical Dysplasia in Patients with DEPDC5 Variants: A Systematic Review and Individual Patient Data Analysis.

There is insufficient evidence regarding the efficacy of epilepsy surgery in patients with pharmacoresistant focal epilepsy and coexistent DEPDC5 (dishevelled EGL-10 and pleckstrin domain-containing protein 5) pathogenic (P), likely pathogenic (LP), or variance of unknown significance (VUS) variants. To conduct a systematic review on the literature regarding the use and efficacy of epilepsy surgery as an intervention for patients with DEPDC5 variants who have pharmacoresistant epilepsy. A systematic review of the current literature published regarding the outcomes of epilepsy surgery for patients with DEPDC5 variants was conducted. Demographics and individual patient data were recorded and analyzed. Subsequent statistical analysis was performed to assess significance of the findings. A total of eight articles comprising 44 DEPDC5 patients with genetic variants undergoing surgery were included in this study. The articles primarily originated in high-income countries (5/8, 62.5%). The average age of the subjects was 10.06 ± 9.41 years old at the time of study. The most common form of epilepsy surgery was focal resection (38/44, 86.4%). Thirty-seven of the 40 patients (37/40, 92.5%) with reported seizure frequency results had improvement. Twenty-nine out of 38 patients (29/38, 78.4%) undergoing focal resection achieved Engel Score I postoperatively, and two out of four patients achieved International League Against Epilepsy I (50%). Epilepsy surgery is effective in patients with pharmacoresistant focal epilepsy and coexistent DEPDC5 P, LP, or VUS variants.

One right can make a left: sentence processing in the right hemisphere after perinatal stroke.

When brain regions that are critical for a cognitive function in adulthood are irreversibly damaged at birth, what patterns of plasticity support the successful development of that function in an alternative location? Here we investigate the consistency of language organization in the right hemisphere (RH) after a left hemisphere (LH) perinatal stroke. We analyzed fMRI data collected during an auditory sentence comprehension task on 14 people with large cortical LH perinatal arterial ischemic strokes (left hemisphere perinatal stroke (LHPS) participants) and 11 healthy sibling controls using a "top voxel" approach that allowed us to compare the same number of active voxels across each participant and in each hemisphere for controls. We found (1) LHPS participants consistently recruited the same RH areas that were a mirror-image of typical LH areas, and (2) the RH areas recruited in LHPS participants aligned better with the strongly activated LH areas of the typically developed brains of control participants (when flipped images were compared) than the weakly activated RH areas. Our findings suggest that the successful development of language processing in the RH after a LH perinatal stroke may in part depend on recruiting an arrangement of frontotemporal areas reflective of the typical dominant LH.

Outcomes of stereoelectroencephalography following failed epilepsy surgery in children.

INTRODUCTION: Stereoelectroencephalography (SEEG) is valuable for delineating the seizure onset zone (SOZ) in pharmacoresistant epilepsy when non-invasive presurgical techniques are inconclusive. Secondary epilepsy surgery after initial failure is challenging and there is limited research on SEEG following failed epilepsy surgery in children. OBJECTIVE: The objective of this manuscript is to present the outcomes of children who underwent SEEG after failed epilepsy surgery. METHODS: In this single-institution retrospective study, demographics, previous surgery data, SEEG characteristics, management, and follow-up were analyzed for pediatric patients who underwent SEEG after unsuccessful epilepsy surgery between August 2016 and February 2023. RESULTS: Fifty three patients underwent SEEG investigation during this period. Of this, 13 patients were identified who had unsuccessful initial epilepsy surgery (24%). Of these 13 patients, six patients (46%) experienced unsuccessful resective epilepsy surgery that targeted the temporal lobe, six patients (46%) underwent surgery involving the frontal lobe, and one patient (8%) had laser interstitial thermal therapy (LITT) of the right insula. SEEG in two thirds of patients (4/6) with initial failed temporal resections revealed expanded SOZ to include the insula. All 13 patients (100%) had a subsequent surgery after SEEG which was either LITT (54%) or surgical resection (46%). After the subsequent surgery, a favorable outcome (Engel class I/II) was achieved by eight patients (62%), while five patients experienced an unfavorable outcome (Engel class III/IV, 38%). Of the six patients with secondary surgical resection, four patients (67%) had favorable outcomes, while of the seven patients with LITT, two patients (29%) had favorable outcomes (Engel I/II). Average follow-up after the subsequent surgery was 37 months ±23 months. CONCLUSION: SEEG following initial failed resective epilepsy surgery may help guide next steps at identifying residual epileptogenic cortex and is associated with favorable seizure control outcomes.

Networks Underlie Temporal Onset of Dysplasia-Related Epilepsy: A MELD Study.

OBJECTIVE: The purpose of this study was to evaluate if focal cortical dysplasia (FCD) co-localization to cortical functional networks is associated with the temporal distribution of epilepsy onset in FCD. METHODS: International (20 center), retrospective cohort from the Multi-Centre Epilepsy Lesion Detection (MELD) project. Patients included if >3 years old, had 3D pre-operative T1 magnetic resonance imaging (MRI; 1.5 or 3 T) with radiologic or histopathologic FCD after surgery. Images processed using the MELD protocol, masked with 3D regions-of-interest (ROI), and co-registered to fsaverage_sym (symmetric template). FCDs were then co-localized to 1 of 7 distributed functional cortical networks. Negative binomial regression evaluated effect of FCD size, network, histology, and sulcal depth on age of epilepsy onset. From this model, predictive age of epilepsy onset was calculated for each network. RESULTS: Three hundred eighty-eight patients had median age seizure onset 5 years (interquartile range [IQR] = 3-11 years), median age at pre-operative scan 18 years (IQR = 11-28 years). FCDs co-localized to the following networks: limbic (90), default mode (87), somatomotor (65), front parietal control (52), ventral attention (32), dorsal attention (31), and visual (31). Larger lesions were associated with younger age of onset (p = 0.01); age of epilepsy onset was associated with dominant network (p = 0.04) but not sulcal depth or histology. Sensorimotor networks had youngest onset; the limbic network had oldest age of onset (p values <0.05). INTERPRETATION: FCD co-localization to distributed functional cortical networks is associated with age of epilepsy onset: sensory neural networks (somatomotor and visual) with earlier onset, and limbic latest onset. These variations may reflect developmental differences in synaptic/white matter maturation or network activation and may provide a biological basis for age-dependent epilepsy onset expression. ANN NEUROL 2022;92:503-511.

Inequities in Therapy for Infantile Spasms: A Call to Action.

OBJECTIVE: The aim of this study was to determine whether selection of treatment for children with infantile spasms (IS) varies by race/ethnicity. METHODS: The prospective US National Infantile Spasms Consortium database includes children with IS treated from 2012 to 2018. We examined the relationship between race/ethnicity and receipt of standard IS therapy (prednisolone, adrenocorticotropic hormone, vigabatrin), adjusting for demographic and clinical variables using logistic regression. Our primary outcome was treatment course, which considered therapy prescribed for the first and, when needed, the second IS treatment together. RESULTS: Of 555 children, 324 (58%) were non-Hispanic white, 55 (10%) non-Hispanic Black, 24 (4%) non-Hispanic Asian, 80 (14%) Hispanic, and 72 (13%) other/unknown. Most (398, 72%) received a standard treatment course. Insurance type, geographic location, history of prematurity, prior seizures, developmental delay or regression, abnormal head circumference, hypsarrhythmia, and IS etiologies were associated with standard therapy. In adjusted models, non-Hispanic Black children had lower odds of receiving a standard treatment course compared with non-Hispanic white children (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.20-0.89; p = 0.02). Adjusted models also showed that children with public (vs. private) insurance had lower odds of receiving standard therapy for treatment 1 (OR, 0.42; CI, 0.21-0.84; p = 0.01). INTERPRETATION: Non-Hispanic Black children were more often treated with non-standard IS therapies than non-Hispanic white children. Likewise, children with public (vs. private) insurance were less likely to receive standard therapies. Investigating drivers of inequities, and understanding the impact of racism on treatment decisions, are critical next steps to improve care for patients with IS. ANN NEUROL 2022;92:32-44.

A scoping review of the functional magnetic resonance imaging-based functional connectivity of focal cortical dysplasia-related epilepsy.

Focal cortical dysplasia (FCD) is the most frequent etiology of operable pharmacoresistant epilepsy in children. There is burgeoning evidence that FCD-related epilepsy is a disorder that involves distributed brain networks. Functional magnetic resonance imaging (fMRI) is a tool that allows one to infer neuronal activity and to noninvasively map whole-brain functional networks. Despite its relatively widespread availability at most epilepsy centers, the clinical application of fMRI remains mostly task-based in epilepsy. Another approach is to map and characterize cortical functional networks of individuals using resting state fMRI (rsfMRI). The focus of this scoping review is to summarize the evidence to date of investigations of the network basis of FCD-related epilepsy, and to highlight numerous potential future applications of rsfMRI in the exploration of diagnostic and therapeutic strategies for FCD-related epilepsy. There are numerous studies demonstrating a global disruption of cortical functional networks in FCD-related epilepsy. The underlying pathological subtypes of FCD influence overall functional network patterns. There is evidence that cortical functional network mapping may help to predict postsurgical seizure outcomes, highlighting the translational potential of these findings. Additionally, several studies emphasize the important effect of FCD interaction with cortical networks and the expression of epilepsy and its comorbidities.

Focal to bilateral tonic-clonic seizures predict pharmacoresistance in focal cortical dysplasia-related epilepsy.

OBJECTIVE: Focal cortical dysplasia (FCD) is the most common etiology of surgically-remediable epilepsy in children. Eighty-seven percent of patients with FCD develop epilepsy (75% is pharmacoresistant epilepsy [PRE]). Focal to bilateral tonic-clonic (FTBTC) seizures are associated with worse surgical outcomes. We hypothesized that children with FCD-related epilepsy with FTBTC seizures are more likely to develop PRE due to lesion interaction with restricted cortical neural networks. METHODS: Patients were selected retrospectively from radiology and surgical databases from Children's National Hospital. INCLUSION CRITERIA: 3T magnetic resonance imaging (MRI)-confirmed FCD from January 2011 to January 2020; ages 0 days to 22 years at MRI; and 18 months of documented follow-up. FCD dominant network (Yeo 7-network parcellation) was determined. Association of FTBTC seizures with epilepsy severity, surgical outcome, and dominant network was tested. Binomial regression was used to evaluate predictors (FTBTC seizures, age at seizure onset, pathology, hemisphere, lobe) of pharmacoresistance and Engel outcome. Regression was used to evaluate predictors (age at seizure onset, pathology, lobe, percentage default mode network [DMN] overlap) of FTBTC seizures. RESULTS: One hundred seventeen patients had a median age at seizure onset of 3.00 years (interquartile range [IQR] .42-5.59 years). Eighty-three patients had PRE (71%); 34 had pharmacosensitive epilepsy (PSE) (29%). Twenty patients (17%) had FTBTC seizures. Seventy-three patients underwent epilepsy surgery. Multivariate regression showed that FTBTC seizures are associated with an increased risk of PRE (odds ratio [OR] 6.41, 95% confidence interval [CI] 1.21-33.98, p = .02). FCD hemisphere/lobe was not associated with PRE. Percentage DMN overlap predicts FTBTC seizures. Seventy-two percent (n = 52) overall and 53% (n = 9) of patients with FTBTC seizures achieved Engel class I outcome. SIGNIFICANCE: In a heterogeneous population of surgical and non-operated patients with FCD-related epilepsy, the presence of FTBTC seizures is associated with a tremendous risk of PRE. This finding is a recognizable marker to help neurologists identify those children with FCD-related epilepsy at high risk of PRE and can flag patients for earlier consideration of potentially curative surgery. The FCD-dominant network also contributes to FTBTC seizure clinical expression.

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.

Comparison of psychosocial screeners in an epilepsy clinic.

Screenings are recommended for co-occurring conditions in pediatric epilepsy. However, there is limited research regarding which screener to implement in the clinic. This study aimed to compare different screening measures for attention-deficit/hyperactivity disorder (ADHD) and emotional concerns in a pediatric epilepsy population during a routine neurology clinic visit. Fifty (22%) of 226 contacted parents of children with epilepsy ages 5-17 years old agreed to participate. Screening measures included the Strengths and Difficulties Questionnaire (SDQ; Hyperactivity/Inattention (ADHD), Emotional Problems (E) subscales), the Pediatric Quality of Life Inventory Epilepsy Module (PedsQL-EM; Executive Functioning (EF), Mood/Behavior (M/B) subscales), and the ADHD Rating Scale (ADHD-RS). Analyses comparing measures included Chi Square, Pearson's correlation, and agreement statistics (Cohen's kappa, overall agreement). Consistent with prior literature, positive screening rates ranged from 40% to 72% for ADHD concerns and 38% to 46% for emotional concerns. Agreement between measures ranged from fair to substantial, with the highest agreement (85%; κ = 0.70) between the SDQ-E and PedsQL-EM-M/B. Although all measures rendered positive screens within expected rates, there are differences among the measures that inform screening measure selection.

The neural basis of language development: Changes in lateralization over age.

We have long known that language is lateralized to the left hemisphere (LH) in most neurologically healthy adults. In contrast, findings on lateralization of function during development are more complex. As in adults, anatomical, electrophysiological, and neuroimaging studies in infants and children indicate LH lateralization for language. However, in very young children, lesions to either hemisphere are equally likely to result in language deficits, suggesting that language is distributed symmetrically early in life. We address this apparent contradiction by examining patterns of functional MRI (fMRI) language activation in children (ages 4 through 13) and adults (ages 18 through 29). In contrast to previous studies, we focus not on lateralization per se but rather on patterns of left-hemisphere (LH) and right-hemisphere (RH) activation across individual participants over age. Our analyses show significant activation not only in the LH language network but also in their RH homologs in all of the youngest children (ages 4 through 6). The proportion of participants showing significant RH activation decreases over age, with over 60% of adults lacking any significant RH activation. A whole-brain correlation analysis revealed an age-related decrease in language activation only in the RH homolog of Broca's area. This correlation was independent of task difficulty. We conclude that, while language is left-lateralized throughout life, the RH contribution to language processing is also strong early in life and decreases through childhood. Importantly, this early RH language activation may represent a developmental mechanism for recovery following early LH injury.

Impact of development and recent-onset epilepsy on language dominance.

OBJECTIVE: Reorganization of the language network from typically left-lateralized frontotemporal regions to bilaterally distributed or right-lateralized networks occurs in anywhere from 25%-30% of patients with focal epilepsy. In patients who have been recently diagnosed with epilepsy, an important question remains as to whether it is the presence of seizures or the underlying epilepsy etiology that leads to atypical language representations. This question becomes even more interesting in pediatric samples, where the typical developmental processes of the language network may confer more variability and plasticity in the language network. We assessed a carefully selected cohort of children with recent-onset epilepsy to examine whether it is the effects of seizures or their underlying cause that leads to atypical language lateralization. METHODS: We used functional magnetic resonance imaging (fMRI) to compare language laterality in children with recently diagnosed focal unaware epilepsy and age-matched controls. Age at epilepsy onset (age 4 to 6 years vs age 7 to 12 years) was also examined to determine if age at onset influenced laterality. RESULTS: The majority of recent-onset patients and controls exhibited left-lateralized language. There was a significant interaction such that the relationship between epilepsy duration and laterality differed by age at onset. In children with onset after age 6, a longer duration of epilepsy was associated with less left-lateralized language dominance. In contrast, in children with onset between 4 and 6 years of age, a longer duration of epilepsy was not associated with less left language dominance. SIGNIFICANCE: Our results demonstrate that although language remained largely left-lateralized in children recently diagnosed with epilepsy, the impact of seizure duration depended on age at onset, indicating that the timing of developmental and disease factors are important in determining language dominance.

Common functional connectivity alterations in focal epilepsies identified by machine learning.

OBJECTIVE: This study was undertaken to identify shared functional network characteristics among focal epilepsies of different etiologies, to distinguish epilepsy patients from controls, and to lateralize seizure focus using functional connectivity (FC) measures derived from resting state functional magnetic resonance imaging (MRI). METHODS: Data were taken from 103 adult and 65 pediatric focal epilepsy patients (with or without lesion on MRI) and 109 controls across four epilepsy centers. We used three whole-brain FC measures: parcelwise connectivity matrix, mean FC, and degree of FC. We trained support vector machine models with fivefold cross-validation (1) to distinguish patients from controls and (2) to lateralize the hemisphere of seizure onset in patients. We reported the regions and connections with the highest importance from each model as the common FC differences between the compared groups. RESULTS: FC measures related to the default mode and limbic networks had higher importance relative to other networks for distinguishing epilepsy patients from controls. In lateralization models, regions related to somatosensory, visual, default mode, and basal ganglia showed higher importance. The epilepsy versus control classification model trained using a 400-parcel connectivity matrix achieved a median testing accuracy of 75.6% (median area under the curve [AUC] = .83) in repeated independent testing. Lateralization accuracy using the 400-parcel connectivity matrix reached a median accuracy of 64.0% (median AUC = .69). SIGNIFICANCE: Machine learning models revealed common FC alterations in a heterogeneous group of patients with focal epilepsies. The distribution of the most altered regions supports the hypothesis that shared functional alteration exists beyond the seizure onset zone and its epileptic network. We showed that FC measures can distinguish patients from controls, and further lateralize focal epilepsies. Future studies are needed to confirm these findings by using larger numbers of epilepsy patients.

Atlas of lesion locations and postsurgical seizure freedom in focal cortical dysplasia: A MELD study.

OBJECTIVE: Drug-resistant focal epilepsy is often caused by focal cortical dysplasias (FCDs). The distribution of these lesions across the cerebral cortex and the impact of lesion location on clinical presentation and surgical outcome are largely unknown. We created a neuroimaging cohort of patients with individually mapped FCDs to determine factors associated with lesion location and predictors of postsurgical outcome. METHODS: The MELD (Multi-centre Epilepsy Lesion Detection) project collated a retrospective cohort of 580 patients with epilepsy attributed to FCD from 20 epilepsy centers worldwide. Magnetic resonance imaging-based maps of individual FCDs with accompanying demographic, clinical, and surgical information were collected. We mapped the distribution of FCDs, examined for associations between clinical factors and lesion location, and developed a predictive model of postsurgical seizure freedom. RESULTS: FCDs were nonuniformly distributed, concentrating in the superior frontal sulcus, frontal pole, and temporal pole. Epilepsy onset was typically before the age of 10 years. Earlier epilepsy onset was associated with lesions in primary sensory areas, whereas later epilepsy onset was associated with lesions in association cortices. Lesions in temporal and occipital lobes tended to be larger than frontal lobe lesions. Seizure freedom rates varied with FCD location, from around 30% in visual, motor, and premotor areas to 75% in superior temporal and frontal gyri. The predictive model of postsurgical seizure freedom had a positive predictive value of 70% and negative predictive value of 61%. SIGNIFICANCE: FCD location is an important determinant of its size, the age at epilepsy onset, and the likelihood of seizure freedom postsurgery. Our atlas of lesion locations can be used to guide the radiological search for subtle lesions in individual patients. Our atlas of regional seizure freedom rates and associated predictive model can be used to estimate individual likelihoods of postsurgical seizure freedom. Data-driven atlases and predictive models are essential for evidence-based, precision medicine and risk counseling in epilepsy.

Low-frequency stimulation of a fiber tract in bilateral temporal lobe epilepsy.

OBJECTIVE: Pharmacoresistant bilateral mesial temporal lobe epilepsy often implies poor resective surgical candidacy. Low-frequency stimulation of a fiber tract connected to bilateral hippocampi, the fornicodorsocommissural tract, has been shown to be safe and efficacious in reducing seizures in a previous short-term study. Here, we report a single-blinded, within-subject control, long-term deep-brain stimulation trial of low-frequency stimulation of the fornicodorsocommissural tract in bilateral mesial temporal lobe epilepsy. Outcomes of interest included safety with respect to verbal memory scores and reduction of seizure frequency. METHODS: Our enrollment goal was 16 adult subjects to be randomized to 2-Hz or 5-Hz low-frequency stimulation of the fornicodorsocommissural tract starting at 2 mA. The study design consisted of four two-month blocks of stimulation with a 50%-duty cycle, alternating with two-month blocks of no stimulation. RESULTS: We terminated the study after enrollment of five subjects due to slow accrual. Fornicodorsocommissural tract stimulation elicited bilateral hippocampal evoked responses in all subjects. Three subjects underwent implantation of pulse generators and long-term low-frequency stimulation with mean monthly seizures of 3.14 ±â€¯2.67 (median 3.0 [IQR 1-4.0]) during stimulation-off blocks, compared with 0.96 ±â€¯1.23 (median 1.0 [IQR 0-1.0]) during stimulation-on blocks (p = 0.0005) during the blinded phase. Generalized Estimating Equations showed that low-frequency stimulation reduced monthly seizure-frequency by 0.71 per mA (p < 0.001). Verbal memory scores were stable with no psychiatric complications or other adverse events. SIGNIFICANCE: The results demonstrate feasibility of stimulating both hippocampi using a single deep-brain stimulation electrode in the fornicodorsocommissural tract, efficacy of low-frequency stimulation in reducing seizures, and safety as regards verbal memory.

Migration of High Cardiac Risk Patients from Open to Endovascular Procedures is Evident within the Society for Vascular Surgery Vascular Quality Initiative.

BACKGROUND: In this study, pre-operative medical complexity is estimated by the independently validated Vascular Quality Initiative VQI Cardiac Risk Index (CRI). This study aims to identify and correlate trends of CRI for open abdominal aortic aneurysm (OAR) with trends in the CRI for corresponding endovascular aortic repair (EVAR). This assessment of differences in estimated procedural risks will be used to support the theory that, patient migration is an important factor contributing to decreased POMI following open vascular procedures. METHODS: A retrospective review of VQI data from 2003 to 2020 for all patients undergoing elective aortic repairs (OAR and EVAR) was conducted. The CRI scoring developed for the open repair (oCRI) was applied to both the OAR and EVAR cohorts, with variables specific to EVAR translated from similar open repair factors in the model where feasible. To evaluate for changes across time, patients were grouped into Eras based on year of procedure, subsequently, univariate analysis of post-operative myocardial infarction (POMI) rates and CRI scores were perfomed between each era. RESULTS: A total of 56,067 elective aortic repairs were identified (83% EVAR, 17% OAR). Within the OAR cohort, the average oCRI estimate was 7.1% with significant decrease across the studied timeframe (8% ± 4.6%→6.9% ± 4.4%, P < 0.001), which corresponded to a significant decrease in observed clinical myocardial infarction (MI) rate (4.1%→1.4%, P < 0.001). Over that same time period, the open CRI was applied to the EVAR cohort, and the average oCRI estimate was 7.2% and showed a significant increase (6.6% ± 2.8%→7.2% ± 4.4%, P < 0.001). Within the EVAR cohort, the eCRI estimate did not show any significant changes over time (average 0.48%), while the actual rate of clinical MI showed a significant decrease (1.1%→0.3%, P = 0.002). Gap analysis was conducted within the EVAR cohort between CRI estimates of procedural risks from an open operation versus an EVAR, which demonstrated that patients within the EVAR cohort would, on an average, has had 6.7% higher risk of POMI had they undergone an open procedure. CONCLUSIONS: Paradigm shifts with regard to patient selection for aortic repair is evident within this large national cohort. Over time, OAR patients had fewer preoperative estimated cardiac comorbidities and there is a corresponding decrease in POMI rates. As high-risk patients migrate from OAR to EVAR, there has been a subsequent increase in EVAR estimated pre-operative risks as the patients become more medically high-risk. Despite increasing complexity, rates of POMI in EVAR significantly decreased, potentially explained by improved operative technique and peri-operative care.

Intravascular Ultrasound for the Evaluation and Management of Retroperitoneal, Genitourinary Malignancies.

PURPOSE OF REVIEW: Herein we provide a review of intravascular ultrasound (IVUS) and its ability to assist in the evaluation and surgical management of advanced retroperitoneal, genitourinary tumors. RECENT FINDINGS: Advanced retroperitoneal tumors such as advanced renal cell carcinoma, bulky retroperitoneal lymphadenopathy associated with advanced testicular carcinoma, large adrenal tumors, and retroperitoneal sarcomas can invade, compress, or distort vascular anatomy making surgical resection challenging and high risk. Intravascular ultrasonography is commonly used by vascular and cardiothoracic surgery to provide a real time assessment of vascular invasion, compression, and aberrant anatomy to assist with pre-operative and/or intraoperative decision-making. However, the application of this technology to assist with cancer surgery has been limited. The use of intravascular ultrasound prior to radical, extirpative, retroperitoneal surgery involving large vessels can aid in the planning and execution of such challenging operations.

Virtual reality-based 3-dimensional localization of stereotactic EEG (SEEG) depth electrodes and related brain anatomy in pediatric epilepsy surgery.

INTRODUCTION: The increasing use of stereoelectroencephalography (SEEG) in the USA and the need for three-dimensional (3D) appreciation of complex spatial relationships between implanted stereotactic EEG depth electrodes and surrounding brain and cerebral vasculature are a challenge to clinicians who are used to two-dimensional (2D) appreciation of cortical anatomy having been traditionally trained on 2D radiologic imaging. Virtual reality and its 3D renderings have grown increasingly common in the multifaceted practice of neurosurgery. However, there exists a paucity in the literature regarding this emerging technology in its utilization of epilepsy surgery. METHODS: An IRB-approved, single-center retrospective study identifying all SEEG pediatric patients in which virtual reality was applied was observed. RESULTS: Of the 46 patients identified who underwent an SEEG procedure, 43.5% (20/46) had a 3D rendering (3DR) of their SEEG depth electrodes. All 3DRs were used during patient-family education and discussion among the Epilepsy multidisciplinary team meetings, while 35% (7/20) were used during neuronavigation in surgery. Three successful representative cases of its application were presented. DISCUSSION: Our institution's experience regarding virtual reality in the 3D representation of SEEG depth electrodes and the application to pre-surgical planning, patient-family education, multidisciplinary communication, and intraoperative neuronavigation demonstrate its applicability in comprehensive epilepsy patient care.

Treatment Practices and Outcomes in Continuous Spike and Wave during Slow Wave Sleep: A Multicenter Collaboration.

OBJECTIVES: To determine how continuous spike and wave during slow wave sleep (CSWS) is currently managed and to compare the effectiveness of current treatment strategies using a database from 11 pediatric epilepsy centers in the US. STUDY DESIGN: This retrospective study gathered information on baseline clinical characteristics, CSWS etiology, and treatment(s) in consecutive patients seen between 2014 and 2016 at 11 epilepsy referral centers. Treatments were categorized as benzodiazepines, steroids, other antiseizure medications (ASMs), or other therapies. Two measures of treatment response (clinical improvement as noted by the treating physician; and electroencephalography improvement) were compared across therapies, controlling for baseline variables. RESULTS: Eighty-one children underwent 153 treatment trials during the study period (68 trials of benzodiazepines, 25 of steroids, 45 of ASMs, 14 of other therapies). Children most frequently received benzodiazepines (62%) or ASMs (27%) as first line therapy. Treatment choice did not differ based on baseline clinical variables, nor did these variables correlate with outcome. After adjusting for baseline variables, children had a greater odds of clinical improvement with benzodiazepines (OR 3.32, 95%CI 1.57-7.04, P = .002) or steroids (OR 4.04, 95%CI 1.41-11.59, P = .01) than with ASMs and a greater odds of electroencephalography improvement after steroids (OR 3.36, 95% CI 1.09-10.33, P = .03) than after ASMs. CONCLUSIONS: Benzodiazepines and ASMs are the most frequent initial therapy prescribed for CSWS in the US. Our data suggests that ASMs are inferior to benzodiazepines and steroids and support earlier use of these therapies. Multicenter prospective studies that rigorously assess treatment protocols and outcomes are needed.

Design and implementation of electronic health record common data elements for pediatric epilepsy: Foundations for a learning health care system.

OBJECTIVE: Common data elements (CDEs) are standardized questions and answer choices that allow aggregation, analysis, and comparison of observations from multiple sources. Clinical CDEs are foundational for learning health care systems, a data-driven approach to health care focused on continuous improvement of outcomes. We aimed to create clinical CDEs for pediatric epilepsy. METHODS: A multiple stakeholder group (clinicians, researchers, parents, caregivers, advocates, and electronic health record [EHR] vendors) developed clinical CDEs for routine care of children with epilepsy. Initial drafts drew from clinical epilepsy note templates, CDEs created for clinical research, items in existing registries, consensus documents and guidelines, quality metrics, and outcomes needed for demonstration projects. The CDEs were refined through discussion and field testing. We describe the development process, rationale for CDE selection, findings from piloting, and the CDEs themselves. We also describe early implementation, including experience with EHR systems and compatibility with the International League Against Epilepsy classification of seizure types. RESULTS: Common data elements were drafted in August 2017 and finalized in January 2020. Prioritized outcomes included seizure control, seizure freedom, American Academy of Neurology quality measures, presence of common comorbidities, and quality of life. The CDEs were piloted at 224 visits at 10 centers. The final CDEs included 36 questions in nine sections (number of questions): diagnosis (1), seizure frequency (9), quality of life (2), epilepsy history (6), etiology (8), comorbidities (2), treatment (2), process measures (5), and longitudinal history notes (1). Seizures are categorized as generalized tonic-clonic (regardless of onset), motor, nonmotor, and epileptic spasms. Focality is collected as epilepsy type rather than seizure type. Seizure frequency is measured in nine levels (all used during piloting). The CDEs were implemented in three vendor systems. Early clinical adoption included 1294 encounters at one center. SIGNIFICANCE: We created, piloted, refined, finalized, and implemented a novel set of clinical CDEs for pediatric epilepsy.