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Abstract Weak macromolecular interactions assume a dominant role in the behavior of highly concentrated solutions, and are at the center of a variety of fields ranging from colloidal chemistry to cell biology, neurodegenerative diseases, and manufacturing of protein drugs. They are frequently measured in different biophysical techniques in the form of second virial coefficients, and nonideality coefficients of sedimentation and diffusion, which may be related mechanistically to macromolecular distance distributions in solution and interparticle potentials. A problem arises for proteins where reversible self-association often complicates the concentration-dependent behavior, such that grossly inconsistent coefficients are measured in experiments based on different techniques, confounding quantitative conclusions. Here we present a global multi-method analysis that synergistically bridges gaps in resolution and sensitivity of orthogonal techniques. We demonstrate the method with a panel of monoclonal antibodies exhibiting different degrees of self-association. We show how their concentration-dependent behavior, examined by static and dynamic light scattering and sedimentation velocity, can be jointly described in a self-consistent framework that separates nonideality coefficients from self-association properties, and thereby extends the quantitative interpretation of nonideality coefficients to probe dynamics in highly concentrated protein solutions.

Complex assembly pathways often involve transient, partly-formed intermediates that are challenging to characterize. Here, the authors present a simple and rapid spectroscopic thermal hysteresis method for mapping the energy landscapes of supramolecular assembly.

Background: The expanding field of global neurosurgery calls for a committed neurosurgical community to advocate for universal access to timely, safe, and affordable neurosurgical care for everyone, everywhere. The aim of this study was to assess the current state of global neurosurgery activity amongst European neurosurgeons and to identify barriers to involvement in global neurosurgery initiatives., Methods: Cross-sectional study through dissemination of a web-based survey, from September 2019 to January 2020, to collect data from European neurosurgeons at various career stages. Descriptive analysis was conducted on respondent data., Results: Three hundred and ten neurosurgeons from 40 European countries responded: 53.5% regularly follow global neurosurgery developments, and 29.4% had travelled abroad with a global neurosurgery collaborative, with 23.2% planning a future trip. Respondents from high income European countries predominantly travelled to Africa (41.6%) or Asia (34.4%), whereas respondents from middle income European countries frequently traversed Europe (63.2%) and North America (47.4%). Cost implications (66.5%) were the most common barrier to global neurosurgery activity, followed by interference with current practice (45.8%), family duties (35.2%), difficulties obtaining humanitarian leave (27.7%) and lack of international partners (27.4%). 86.8% would incorporate a global neurosurgery period within training programmes., Conclusions: European neurosurgeons are interested in engaging in global neurosurgery partnerships, and several sustainable programs focused on local capacity building, education and research have been established over the last decade. However, individual and system barriers to engagement persist. We provided insight into these to allow development of tailored mechanisms to overcome such barriers, enabling European neurosurgeons to advocate for the Global Surgery 2030 goals.

Background: Recent guidelines suggest that, for venous thromboembolism (VTE), standard doses of apixaban are appropriate in patients with body mass index (BMI) >40 kg/m2 or >120 kg. Atrial fibrillation (AF) is excluded from this recommendation., Objective: The goals of our study were to measure and describe anti-Xa levels of patients with a BMI ≥40 kg/m2 and/or a weight ≥120 kg with a clinical indication of AF or VTE who were treated with apixaban, and to determine whether BMI or weight are associated with anti-Xa levels in this population., Methods: We conducted an observational cohort study at a single health care system in Oregon, USA. Patients meeting enrollment criteria were recruited and had peak and trough apixaban anti-Xa levels drawn., Results: Of 55 patients enrolled, 5 (9%) had peak anti-Xa levels below the reference range and 3 (6%) had trough anti-Xa levels below the reference range. BMI did not significantly correlate with peak or trough anti-Xa levels (r = -0.10, p = 0.45 and r = -0.14, p = 0.31). Weight had a moderate, negative correlation with peak anti-Xa levels (r = -0.42, p = 0.002) and a weak, negative correlation with trough anti-Xa levels (r = -0.32, p = 0.02)., Conclusions and Relevance: This study provides evidence that anti-Xa levels among obese patients are not substantially different from patients with nomral BMI and weight. This supports recent ISTH guidance for standard dosing of apixaban for VTE patients with BMI >40 kg/m2 or weight >120 kg and provides additional evidence that the standard dosing may also be appropriate in patients with AF.

Aims: We understand little of the pathogenesis of developmental cortical lesions, because we understand little of the diversity of the cell types that contribute to the diseases or how those cells interact. We tested the hypothesis that cellular diversity and cell-cell interactions play an important role in these disorders by investigating the signalling molecules in the commonest cortical malformations that lead to childhood epilepsy, focal cortical dysplasia (FCD) and tuberous sclerosis (TS)., Methods: Transcriptional profiling clustered cases into molecularly distinct groups. Using gene expression data, we identified the secretory signalling molecules in FCD/TS and characterised the cell types expressing these molecules. We developed a functional model using organotypic cultures., Results: We identified 113 up-regulated secretory molecules in FCDIIB/TS. The top 12 differentially expressed genes (DEGs) were validated by immunohistochemistry. This highlighted two molecules, Chitinase 3-like protein 1 (CHI3L1) and C-C motif chemokine ligand 2 (CCL2) (MCP1) that were expressed in a unique population of small cells in close proximity to balloon cells (BC). We then characterised these cells and developed a functional model in organotypic slice cultures. We found that the number of CHI3L1 and CCL2 expressing cells decreased following inhibition of mTOR, the main aberrant signalling pathway in TS and FCD., Conclusions: Our findings highlight previously uncharacterised small cell populations in FCD and TS which express specific signalling molecules. These findings indicate a new level of diversity and cellular interactions in cortical malformations and provide a generalisable approach to understanding cell-cell interactions and cellular heterogeneity in developmental neuropathology., (© 2021 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.)

Study Objective: Rivaroxaban, enoxaparin, and aspirin are commonly used medications for thromboprophylaxis following lower extremity joint arthroplasty or revision. Previous research has demonstrated efficacy in preventing venous thromboembolism with each medication, however, the comparative risk of bleeding between them remains poorly understood. The aim of this study was to compare the odds of bleeding between rivaroxaban, enoxaparin, and aspirin following lower extremity joint arthroplasty or revision., Design: This is a 3-year retrospective cohort study., Setting: Data were obtained from 148 facilities across 55 states and territories of the United States., Patients: This study included 85,938 patients who underwent hip or knee arthroplasty or revision., Intervention: Patients received enoxaparin, rivaroxaban, or aspirin as monotherapy for thromboprophylaxis., Measurements: The primary outcome was all bleeding, classified as major or minor bleeding, occurring in the 40 days following surgery. The secondary outcome was venous thromboembolism., Main Results: Among 85,938 patients, 10,465 received rivaroxaban, 14,047 received enoxaparin, and 61,426 received aspirin. Bleeding occurred in 126 (1.20%) patients with rivaroxaban, 253 (1.80%) with enoxaparin, and 611 (0.99%) with aspirin. There was a significant increase in odds of bleeding in the enoxaparin compared to aspirin group odds ratio (OR) 1.18, 95% confidence interval (CI) 1.01-1.38, p = 0.042), and a trend toward increased odds of bleeding in rivaroxaban compared to aspirin group (OR 1.21, 95% CI 0.99-1.47, p = 0.058) and rivaroxaban compared to enoxaparin (OR 1.03, 95% CI 0.82-1.28, p = 0.827). Odds of venous thromboembolism were not statistically significant between all three study medications., Conclusions: Among rivaroxaban, enoxaparin, and aspirin used for thromboprophylaxis in knee and hip arthroplasty or revision, aspirin had significantly decreased odds of bleeding complications compared to enoxaparin. Although not statistically significant, aspirin also had a trend toward decreased odds of bleeding complications compared to rivaroxaban. Our study results suggest that aspirin is a safer alternative for use in postoperative thromboprophylaxis following lower extremity joint arthroplasty or revision., (© 2021 Pharmacotherapy Publications, Inc.)

Study Objective: Previous studies have shown that aspirin is noninferior to other anticoagulation therapies in preventing postoperative venous thromboembolism following lower extremity arthroplasty or revision; however, its optimal dosing for this indication is less clear. This study aims to compare the odds of bleeding between different aspirin dosages following lower extremity joint arthroplasty or revision., Design: This is a 3-year retrospective multi-center cohort study across the United States and its territories., Setting: This study included patients admitted for total hip or knee arthroplasty or revision and were treated with prophylactic aspirin., Patients, Intervention, Measurements: Patients were assigned to groups based on a total daily aspirin dose of 81, 162, 325, or 650 mg. Data were analyzed for postsurgical bleeding and thromboembolism events occurring during the initial admission and up to 40 days following surgery. Other exploratory variables included type of surgery, hip or knee arthroplasty, length of stay, and patient demographic data., Main Results: Among 53,848 patients receiving aspirin, 3922 received a total daily dose of 81 mg, 19,341 received a total daily dose of 162 mg, 5256 received a total daily dose of 325 mg, and 25,329 received a total daily dose of 650 mg. Bleeding occurred in 466 (0.87%) patients and venous thromboembolism (VTE) in 209 patients (0.39%). The odds of bleeding were compared using logistic regression, with the 650-mg dose as the reference group. None were statistically significant for bleeding between all studied aspirin doses: 81 mg (OR 1.12, 95% CI 0.83-1.51, p = 0.451), 162 mg (OR 0.83, 95% CI 0.67-1.03, p = 0.097), and 325 mg (OR 0.83, 95% CI 0.59-1.13, p = 0.245). The odds of VTE were also not statistically significant: 81 mg (OR 0.71, 95% CI 0.40-1.17, p = 0.181), 162 mg (OR 0.75 95% CI 0.54-1.03, p = 0.072), and 325 mg (OR 1.00, 95% CI 0.64-1.53, p = 0.989)., Conclusions: There were no significant differences in the odds of bleeding or venous thromboembolism among all studied aspirin dosages in patients receiving aspirin for thromboprophylaxis following lower extremity joint arthroplasty or revision., (© 2021 Pharmacotherapy Publications, Inc.)

Objective: To evaluate the presence, extent, and temporality of transnational neurosurgical partnerships, to understand and inform measures to address neurosurgical deficiencies in low- and middle-income countries (LMICs)., Methods: A Web search was conducted to identify actors from high-income countries (HICs) participating in neurosurgical delivery and/or capacity-building with LMICs from 2010 to 2018. Descriptive data on current neurosurgical partnerships were collected from published case reports, literature reviews, reports from academic institutions, and information on stakeholder Web pages. The level of training and engagement of each partnership was separately graded based on prespecified criteria, in which grade 3 represented partnerships that have most extensive training and engagement, and grade 1, the least extent. Data were analyzed using descriptive statistics and geospatially depicted on ArcMap GIS software., Results: A total of 123 unique HIC-LMIC partnerships were described. Of these partnerships, 85 (69%) are derived from HICs in North America, followed by Europe, with 23 (19%). The most common LMIC partners were from Africa (n = 56, 45%) and Latin America (n = 32, 26%). In addition, most partnerships provided services in pediatric neurosurgery (88%). The most frequent engagement classifications were grade 2 (35%) or 1 (36%). Similarly, for training, the most common classifications were grade 1 (40%) or 2 (30%)., Conclusions: A robust network of HIC-LMIC partnerships exists with varying degrees of engagement and training activities. Several regions are particularly suitable for growth and development. Systematic consolidation and indexing of transnational neurosurgical partnerships aim to enhance resource allocation and present opportunities for future partnership., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Despite general enthusiasm for international collaboration within the organized neurosurgical community, establishing international partnerships remains challenging. The current study analyzes the initial experience of the InterSurgeon website in partnering surgeons from across the world to increase surgical collaboration., Methods: One year after the launch of the InterSurgeon website, data were collected to quantify the number of website visits, average session duration, total numbers of matches, and number of offers and requests added to the website each month. Additionally, a 15-question survey was designed and distributed to all registered members of the website., Results: There are currently 321 surgeon and institutional members of InterSurgeon representing 69 different countries and all global regions. At the time of the survey there were 277 members, of whom 76 responded to the survey, yielding a response rate of 27.4% (76/277). Twenty-five participants (32.9%) confirmed having either received a match email (12/76, 15.8%) or initiated contact with another user via the website (13/76, 17.1%). As expected, the majority of the collaborations were either between a high-income country (HIC) and a low-income country (LIC) (5/18, 27.8%) or between an HIC and a middle-income country (MIC) (9/18, 50%). Interestingly, there were 2 MIC-to-MIC collaborations (2/18, 11.1%) as well as 1 MIC-to-LIC (1/18, 5.6%) and 1 LIC-to-LIC partnership. At the time of response, 6 (33.3%) of the matches had at least resulted in initial contact via email or telephone. One of the partnerships had involved face-to-face interaction via video conference. A total of 4 respondents had traveled internationally to visit their partner's institution., Conclusions: Within its first year of launch, the InterSurgeon membership has grown significantly. The partnerships that have already been formed involve not only international visits between HICs and low- to middle-income countries (LMICs), but also telecollaboration and inter-LMIC connections that allow for greater exchange of knowledge and expertise. As membership and site features grow to include other surgical and anesthesia specialties, membership growth and utilization is expected to increase rapidly over time according to social network dynamics.

Background: It is currently standard practice to correct hypokalemia for the purpose of preventing cardiac arrhythmias in all hospitalized patients. However, the efficacy of this intervention has never been previously studied., Objective: The objective of our study was to evaluate whether patients without acute coronary syndrome or history of arrhythmias were at increased risk of clinically significant cardiac arrhythmias if their potassium level was not corrected to ≥3.5 mEq/L., Design: A retrospective case control study., Setting: A community hospital., Participants: We enrolled selected patients who had episodes of hypokalemia during their hospital stay and were monitored on telemetry. Patients were split into groups based on success of replacing serum potassium to ≥3.5 mEq/L after 24 hours., Measurements: The primary outcome was the development of an arrhythmia. Arrhythmias included supraventricular tachycardia, atrial fibrillation, atrial flutter, Mobitz type II second-degree or third-degree AV block, ventricular tachycardia, or ventricular fibrillation. A one-tailed Fisher's exact test and logistic regression were used for analysis., Results: A total of 1338 hypokalemic patient days were recorded. Out of these days, 22 arrhythmia events (1.6% of patient days) were observed, 8 in the uncorrected group (1% patient days) and 14 in the corrected group (2.6% patient days). We found no statistically significant relationship between successfully correcting potassium to ≥3.5 mEq/L and number of arrhythmic events ( p =0.037, OR = 2.38 (95% CI: 0.99, 6.03)). Logistic regression revealed that correction of potassium does not seem to be significantly related to arrhythmias ( β  = 0.869, p =0.0517)., Conclusions: In the acute care setting, we found that patients with hypokalemia whose potassium level did not correct to ≥3.5 mEq/L were not at increased odds of having an arrhythmia. This study suggests that the common practice of checking and replacing potassium is likely inconsequential., Competing Interests: The authors have no conflicts of interest to report., (Copyright © 2019 Weston Harkness et al.)

Objective: Intelligence quotient (IQ) outcomes after pediatric epilepsy surgery show significant individual variation. Clinical factors such as seizure cessation or antiepileptic medication discontinuation have been implicated, but do not fully account for the heterogeneity seen. Less is known about the impact of neurobiological factors, such as brain development and resection location. This study examines clinical and neuroimaging factors associated with cognitive outcome after epilepsy surgery in childhood., Methods: Fifty-two children (28 boys, 24 girls) were evaluated for epilepsy surgery and reassessed on average 7.7 years later. In the intervening time, 13 were treated pharmacologically and 39 underwent focal surgery (17 temporal, 16 extratemporal, six multilobar; mean age at surgery = 14.0 years). Pre- and postsurgical assessments included IQ tests and T1-weighted brain images. Predictors of IQ change were investigated, including voxel-based analyses of resection location, and gray and white matter volume change., Results: Overall modest IQ improvement was seen in children treated surgically, but not in those treated pharmacologically only. Applying a ≥10-point change threshold, 39% of the surgically treated children improved, whereas 10% declined. Clinical factors associated with IQ increases were lower preoperative IQ and longer follow-up duration, whereas seizure and antiepileptic medication cessation were not predictive. Among neuroimaging factors, we observed that left anterior temporal resections impacted negatively on verbal reasoning, linked to full-scale IQ decline. In contrast, gray matter volume change in ipsi- and contralesional hemispheres was positively correlated with IQ change. Voxel-based morphometry identified the gray matter volume change in the contralesional dorsolateral frontal cortex as most strongly associated with IQ improvement., Significance: We show that a variety of factors are likely to contribute to patterns of postsurgical change in IQ. Neuroimaging results indicate that left anterior temporal resections constrain development of verbal cognition, whereas simultaneously cortical growth after surgical treatment can support improvements in IQ., (Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)

Objective: The presence and capability of existing pediatric neurosurgical care worldwide is unknown. The objective of this study was to solicit the expertise of specialists to quantify the geographic representation of pediatric neurosurgeons, access to specialist care, and equipment and training needs globally., Methods: A mixed-question survey was sent to surgeon members of several international neurosurgical and general pediatric surgical societies via a web-based platform. Respondents answered questions on 5 categories: surgeon demographics and training, hospital and practice details, surgical workforce and access to neurosurgical care, training and equipment needs, and desire for international collaboration. Responses were anonymized and analyzed using Stata software., Results: A total of 459 surgeons from 76 countries responded. Pediatric neurosurgeons in high-income and upper-middle-income countries underwent formal pediatric training at a greater rate than surgeons in low- and lower-middle-income countries (89.5% vs 54.4%). There are an estimated 2297 pediatric neurosurgeons in practice globally, with 85.6% operating in high-income and upper-middle-income countries. In low- and lower-middle-income countries, roughly 330 pediatric neurosurgeons care for a total child population of 1.2 billion. In low-income countries in Africa, the density of pediatric neurosurgeons is roughly 1 per 30 million children. A higher proportion of patients in low- and lower-middle-income countries must travel > 2 hours to seek emergency neurosurgical care, relative to high-income countries (75.6% vs 33.6%, p < 0.001). Vast basic and essential training and equipment needs exist, particularly low- and lower-middle-income countries within Africa, South America, the Eastern Mediterranean, and South-East Asia. Eighty-nine percent of respondents demonstrated an interest in international collaboration for the purposes of pediatric neurosurgical capacity building., Conclusions: Wide disparity in the access to pediatric neurosurgical care exists globally. In low- and lower-middle-income countries, wherein there exists the greatest burden of pediatric neurosurgical disease, there is a grossly insufficient presence of capable providers and equipped facilities. Neurosurgeons across income groups and geographic regions share a desire for collaboration and partnership.

Purpose: Quantifying the global burden of pediatric neurosurgical disease-and current efforts addressing it-is challenging, particularly in the absence of uniform terminology. We sought to establish bellwether procedures for pediatric neurosurgery, in order to standardize terminology, establish priorities, and facilitate goal-oriented capacity building., Methods: Members of international pediatric neurosurgical and pediatric surgical societies were surveyed via the Research Electronic Data Capture (REDCap) platform. Among 15 proposed neurosurgical procedures, respondents assigned numerical grades of surgical necessity and selected hospital-level designation within a three-tiered system. A procedure was considered a bellwether if (a) the majority of respondents deemed it necessary for either a primary- or secondary-level hospital and (b) the procedure was graded at or above the 90th percentile on a continuous scale of essentiality. Data were compiled and analyzed using Stata software., Results: Complete responses were obtained from 459 surgeons from 76 countries, the majority of whom practiced in a tertiary referral hospital (88%), with a primarily public patient population (64%). Six bellwether procedures were identified for pediatric neurosurgery: shunt for hydrocephalus, myelomeningocele closure, burr holes, trauma craniotomy, external ventricular drain (EVD) insertion, and cerebral abscess evacuation. Few differences in bellwether criteria designations were observed among respondents from different World Health Organization regions and World Bank income groups., Conclusions: The six bellwether procedures identified can be used as markers of infrastructure capacity at various hospital levels, hence allowing targeted neurosurgical capacity-building in low-resource settings in order to avert disability and death from childhood neurosurgical disease.

Glioneuronal tumours are an important cause of treatment-resistant epilepsy. Subtypes of tumour are often poorly discriminated by histological features and may be difficult to diagnose due to a lack of robust diagnostic tools. This is illustrated by marked variability in the reported frequencies across different epilepsy surgical series. To address this, we used DNA methylation arrays and RNA sequencing to assay the methylation and expression profiles within a large cohort of glioneuronal tumours. By adopting a class discovery approach, we were able to identify two distinct groups of glioneuronal tumour, which only partially corresponded to the existing histological classification. Furthermore, by additional molecular analyses, we were able to identify pathogenic mutations in BRAF and FGFR1, specific to each group, in a high proportion of cases. Finally, by interrogating our expression data, we were able to show that each molecular group possessed expression phenotypes suggesting different cellular differentiation: astrocytic in one group and oligodendroglial in the second. Informed by this, we were able to identify CCND1, CSPG4, and PDGFRA as immunohistochemical targets which could distinguish between molecular groups. Our data suggest that the current histological classification of glioneuronal tumours does not adequately represent their underlying biology. Instead, we show that there are two molecular groups within glioneuronal tumours. The first of these displays astrocytic differentiation and is driven by BRAF mutations, while the second displays oligodendroglial differentiation and is driven by FGFR1 mutations.

Objective: Glioneuronal tumors (GNTs) are well-recognized causes of chronic drug-resistant focal epilepsy in children. Our practice involves an initial period of radiological surveillance and antiepileptic medications, with surgery being reserved for those with radiological progression or refractory seizures. We planned to analyze the group of patients with low-grade GNTs, aiming to identify factors affecting seizure and cognitive outcomes., Methods: We retrospectively reviewed the medical records of 150 children presenting to Great Ormond Street Hospital with seizures secondary to GNTs. Analysis of clinical, neuroimaging, neuropsychological, and surgical factors was performed to determine predictors of outcome. Seizure outcome at final follow-up was classified as either seizure-free (group A) or not seizure-free (group B) for patients with at least 12-months follow-up postsurgery. Full-scale intelligence quotient (FSIQ) was used as a measure of cognitive outcome., Results: Eighty-six males and 64 females were identified. Median presurgical FSIQ was 81. One hundred twenty-one patients (80.5%) underwent surgery. Median follow-up after surgery was 2 years, with 92 patients (76%) having at least 12 months of follow-up after surgery. Seventy-four patients (80%) were seizure-free, and 18 (20%) continued to have seizures. Radiologically demonstrated complete tumor resection was associated with higher rates of seizure freedom (P = .026). Higher presurgical FSIQ was related to shorter epilepsy duration until surgery (P = .012) and to older age at seizure onset (P = .043)., Significance: A high proportion of children who present with epilepsy and GNTs go on to have surgical tumor resection with excellent postoperative seizure control. Complete resection is associated with a higher chance of seizure freedom. Higher presurgical cognitive functioning is associated with shorter duration of epilepsy prior to surgery and with older age at seizure onset. Given the high rate of eventual surgery, early surgical intervention should be considered in children with continuing seizures associated with GNTs., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

Objective: To determine whether multiple subpial transection in the posterior temporal lobe has an impact on long-term outcome in children who have drug-resistant Landau-Kleffner syndrome (LKS) or other "electrical status epilepticus during sleep" (ESES)-related regression. Given the wide variability in outcomes reported in the literature, a secondary aim was to explore predictors of outcome., Methods: The current study includes a surgery group (n = 14) comprising patients who underwent multiple subpial transection of the posterior temporal lobe and a nonsurgery comparison group (n = 21) comprising patients who underwent presurgical investigations for the procedure, but who did not undergo surgery. Outcomes were assessed utilizing clinical note review as well as direct assessment and questionnaires., Results: The distribution of nonclassical cases was comparable between groups. There were some differences between the surgery and nonsurgery groups at presurgical investigation including laterality of discharges, level of language impairment, and age; therefore, follow-up analyses focused on change over time and predictors of outcome. There were no statistically significant differences between the groups in language, nonverbal ability, adaptive behavior, or quality of life at follow-up. There was no difference in the proportion of patients showing improvement or deterioration in language category over time for either group. Continuing seizures and an earlier age of onset were most predictive of poorer quality of life at long-term follow-up (F2,23 = 26.2, p = <0.001, R(2) = 0.714)., Significance: Both surgery and nonsurgery groups had similar proportions of classic LKS and ESES-related regression. Because no significant differences were found in the changes observed from baseline to follow-up between the two groups, it is argued that there is insufficient evidence to suggest that multiple subpial transection provides additional benefits over and above the mixed recovery often seen in LKS and related regressive epilepsies., (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)