Citations

BACKGROUND AND OBJECTIVES: Corpus callosotomy is an effective procedure approach for treating medication-resistant drop seizures, which pose a significant challenge in patients with epilepsy. Laser interstitial thermal therapy offers an alternative to open surgery for performing corpus callosotomy that may limit approach-related comorbidities. Practices vary regarding the number of laser filaments used and staging; outcome data for pediatric patients remain relatively limited. METHODS: We illustrate a set of 4 standardized trajectories for performing MRI-guided stereotactic laser corpus callosotomy (SLCC). For this retrospective cohort study in a pediatric neurosurgery practice, the medical records and imaging were reviewed for 10 consecutive patients who had medication-refractory drop seizures and underwent SLCC. Data collected and analyzed included patient and epilepsy characteristics, procedural details, surgical approaches, and clinical follow-up results. RESULTS: Over 2 years, complete, single-stage SLCC was performed in 8 patients, and posterior completion SLCC was performed in 2 patients who had previously had open anterior corpus callosotomy. Four laser fibers were used in four-eighth complete SLCC, and 3 fibers were used in four-eighth complete SLCC. Seven of 10 patients were discharged from the hospital on postoperative day 1, with only 1 requiring a maximum stay of 6 days. Five of 9 evaluable patients reported no drop seizures at the last clinical follow-up. In the other 4 patients, 1 experienced them only rarely, another experienced less than 25% preoperative frequency, and the remaining 2 had less than a 50% improvement. In addition, improvement in other seizure types exceeded 50% in 8 of 9 patients. Notably, no perioperative or postoperative complications were observed, nor were there any sustained neurological deficits reported. CONCLUSION: Complete SLCC can be safely and effectively performed in pediatric patients. It is comparable in effectiveness with open surgery but has lower complication rates and shorter hospitalization.

OBJECTIVE Stereoelectroencephalography (SEEG) has become the predominant method for intracranial seizure localization. When imaging, semiology, and scalp EEG findings are not in full agreement or definitively localizing, implanted SEEG recordings are used to test candidate seizure onset zones (SOZs). Discovered SOZs may then be targeted for resection, laser ablation, or neurostimulation. If an SOZ is eloquent, resection and ablation are both contraindicated, so identifying functional representation is crucial for therapeutic decision-making. The authors present a novel functional brain mapping technique that utilizes task-based electrophysiological changes in SEEG during behavioral tasks and test this in pediatric and adult patients. METHODS SEEG was recorded in 20 patients with epilepsy who ranged in age from 6 to 39 years (12 female, 18 of 20 patients < 21 years of age) and underwent implanted monitoring to identify seizure onset. Each performed 1) visually cued simple repetitive movements of the hand, foot, or tongue while electromyography was recorded; and 2) simple picture-naming or verb-generation speech tasks while audio was recorded. Broadband changes in the power spectrum of the SEEG recording were compared between behavior and rest. RESULTS Electrophysiological functional mapping of movement and/or speech areas was completed in all 20 patients. Eloquent representation was identified in both cortex and white matter and generally corresponded to classically described functional anatomical organization as well as other clinical mapping results. Robust maps of brain activity were identified in healthy brain, regions of developmental or acquired structural abnormality, and SOZs. CONCLUSIONS Task-based electrophysiological mapping using broadband changes in the SEEG signal reliably identifies movement and speech representation in pediatric and adult epilepsy patients.

Background Atherosclerosis is highly prevalent in people with chronic kidney disease (CKD), including those receiving peritoneal dialysis (PD). Although it is lifesaving, PD induces profound systemic inflammation, which may aggravate atherosclerosis. Therefore, the hypothesis is that this PD‐induced inflammation aggravates atherosclerosis via immune cell activation. Methods and Results ApoE −/− mice were subjected to a 5/6 nephrectomy to induce CKD. Three weeks later, mice were fed a high‐cholesterol diet. Half of the nephrectomized mice then received daily peritoneal infusions of 3.86% Physioneal for 67 further days (CKD+PD) until the end of the experiment, and were compared with mice without CKD. Sham operated and PD‐only mice were additional controls. CKD+PD mice displayed more severe atherosclerotic disease than control mice. Plaque area increased, and plaques were more advanced with a vulnerable phenotype typified by decreased collagen content and decreased fibrous cap thickness. Increased CD3 + T‐cell numbers were present in plaques and perivascular adipose tissue of CKD and CKD+PD mice. Plaques of CKD+PD mice contained more iNOS + immune cells. Spleens of CKD+PD mice showed more CD4 + central memory, terminally differentiated type 1 T‐helper (Th1), Th17, and CX3C motif chemokine receptor 1 + (CX3CR1) CD4 + T‐cells with less regulatory and effector T‐cells. Conclusions PD‐fluid exposure in uremic mice potentiates systemic and vascular T‐cell‐driven inflammation and aggravates atherosclerosis. PD polarized CD4 + T‐cells toward an inflammatory Th1/Th17 phenotype, and increased CX3CR1 + CD4 + T‐cells, which are associated with vascular homing in CKD‐associated atherosclerosis. Targeting CD4 + T‐cell activation and CX3CR1 + polarization has the potential to attenuate atherosclerosis in PD patients.

AbstractObjectivesThe main goal of presurgical evaluation in drug‐resistant focal epilepsy is to identify a seizure onset zone (SOZ). Of the noninvasive, yet resource‐intensive tests available, ictal single‐photon emission computed tomography (SPECT) aids SOZ localization by measuring focal increases in blood flow within the SOZ via intravenous peri‐ictal radionuclide administration. Recent studies indicate that geographic and center‐specific factors impact utilization of these diagnostic procedures. Our study analyzed successful ictal SPECT acquisition (defined as peri‐ictal injection during inpatient admission) using surgery‐related data from the Pediatric Epilepsy Research Consortium (PERC) surgery database. We hypothesized that a high seizure burden, longer duration of video EEG monitoring (VEEG), and more center‐specific hours of SPECT availability would increase the likelihood of successful ictal SPECT.MethodsWe identified study participants (≤18 years of age) who underwent SPECT as part of their phase 1 VEEG from January 2018 to June 2022. We assessed association between ictal SPECT outcomes (success vs. failure) and variables including patient demographics, epilepsy history, and center‐specific SPECT practices.ResultsPhase 1 VEEG monitoring with ictal SPECT injection was planned in 297 participants and successful in 255 participants (85.86%). On multivariable analysis, the likelihood of a successful SPECT injection was higher in patients of non‐Hispanic ethnicity (p = 0.040), shorter duration VEEG (p = 0.004), and higher hours of available SPECT services (p < 0.001). Higher seizure frequency (p = 0.033) was significant only in bivariate analysis. Patients treated at centers with more operational hours were more likely to experience pre‐admission protocols prior to VEEG (p = 0.002).SignificanceThere is inter‐center variability in protocols and SPECT acquisition capabilities. Shorter duration of EEG monitoring, non‐Hispanic ethnicity (when on private insurance), extended operational hours of nuclear medicine as noted on multivariate analysis and higher seizure frequency in bivariate analysis are strongly associated with successful ictal SPECT injection.Plain Language SummaryIn pediatric patients with drug‐resistant epilepsy, single‐photon emission computed tomography (SPECT) scans can be helpful in localizing seizure onset zone. However, due to many logistical challenges described below, which include not only the half‐life of the technetium isotope used to inject intravenously during a seizure (called the ictal SPECT scan) but also available nuclear scanner time in addition to the unpredictability of seizures, obtaining an ictal SPECT during a planned elective inpatient hospital stay is not guaranteed. Thus, as healthcare costs increase, planning a prolonged hospital stay during which an ictal SPECT scan is not feasible is not optimal. We leveraged our prospective surgery database to look at center‐specific factors and patient‐specific factors associated with an ictal SPECT injection in the first, pediatric‐focussed, large‐scale, multicenter, prospective, SPECT feasibility study. We found that longer availability of the scanner is the most important center‐specific factor in assuring ictal SPECT injection. Although seizure frequency is an important patient‐specific factor on bivariate analysis, this factor lost statistical significance when other factors like patient insurance status and video EEG duration were also considered in our multivariable logistical model.

Objective Previous studies indicate that eosinophils are recruited into the allograft following orthotopic liver transplantation and protect from ischaemia reperfusion (IR) injury. In the current studies, we aim to explore whether their protective function could outlast during liver repair. Design Eosinophil-deficient mice and adoptive transfer of bone marrow-derived eosinophils (bmEos) were employed to investigate the effects of eosinophils on tissue repair and regeneration after hepatic IR injury. Aside from exogenous cytokine or neutralising antibody treatments, mechanistic studies made use of a panel of mouse models of eosinophil-specific IL-4/IL-13-deletion, cell-specific IL-4rα-deletion in liver macrophages and hepatocytes and macrophage-specific deletion of heparin-binding epidermal growth factor-like growth factor (hb-egf). Result We observed that eosinophils persisted over a week following hepatic IR injury. Their peak accumulation coincided with that of hepatocyte proliferation. Functional studies showed that eosinophil deficiency was associated with a dramatic delay in liver repair, which was normalised by the adoptive transfer of bmEos. Mechanistic studies demonstrated that eosinophil-derived IL-4, but not IL-13, was critically involved in the reparative function of these cells. The data further revealed a selective role of macrophage-dependent IL-4 signalling in liver regeneration. Eosinophil-derived IL-4 stimulated macrophages to produce HB-EGF. Moreover, macrophage-specific hb-egf deletion impaired hepatocyte regeneration after IR injury. Conclusion Together, these studies uncovered an indispensable role of eosinophils in liver repair after acute injury and identified a novel crosstalk between eosinophils and macrophages through the IL-4/HB-EGF axis.

Abstract Background: Breast cancer (BC) patients are at significant risk of therapy-related cardiotoxicity, but prediction of which patients will experience cardiotoxicity and the severity of the outcome are lacking. We hypothesized that germline genetic variants are potential risk factors for cancer treatment-related cardiomyopathy (CTRC) and in this study, we focused on rare non-synonymous variants within 57 genes deemed causative of familial and sporadic forms of idiopathic cardiomyopathies. Methods: We developed a clinical database and biorepository for patients receiving any potentially cardiotoxic cancer therapy at Mayo Clinic Florida. Enrollment is ongoing and includes consent to access external records. Patient data is extracted from records at baseline, completion of treatment and then once per year. The clinical database includes the following datasets: demographics, pathology, chemotherapy, radiation, echocardiography, cardiac MRI, PET/CT scan, blood pressure, BMI, labs, treatment complications. Treatment complications includes pre-existing conditions (smoking, alcohol and drug use history, hypertension, diabetes, coronary artery disease, hyperlipidemia, prior stroke or myocardial infarction, peripheral vascular disease, renal failure); cardiac medications at baseline; cardiac side-effects; time to cardiotoxicity; cardiotoxicity interventions and outcomes. Exome sequencing was performed by the Mayo Clinic NGS core on the first 86 patients in the registry, average of ~120x read depth following Illumina’s standard protocol for the NovaSeq 6000 and S4 flow cell. Genomic variants were extracted for 57 genes known to be causative of dilated, hypertrophic and arrhythmogenic right ventricular cardiomyopathies and channelopathies. Putative risk variants in known cardiomyopathy genes were defined as non-synonymous variants with a frequency of &lt; 0.0004 in the GnomAD database. We compared the number of patients with putative risk variants in those groups with and without CTRC. Results: 84/86 patients had BC diagnosis. Key characteristics are described in the table below. 60/86 (70%) patients had at least one putative risk variant in one of 31 genes (there were no risk variants identified in 27/57 genes). The average number of putative risk variants per patient within the CTRC group was higher than that observed in patients without CTRC (2.06 vs 1.62). Post-hoc analysis suggested this difference is largely from patients with &gt;2 risk variants in the group who experienced CTRC (N=7/17, 41%) compared to those who did not (N=14/69, 20%), p=0.023. Conclusions: Rare missense variants in the causative genes of idiopathic cardiomyopathies are potential risk factors for CTRC and risk may be increased in patients with a higher burden of variants. Analysis of the genetic data from patients that continue to be accrued in this study, including effects of additional clinical risk factors will be undertaken to improve prediction of cardiotoxicity. Table 1 Distribution of putative cardiomyopathy genetic variants in 86 cancer patients with and without treatment-related cardiomyopathy, separated by treatment regimen Citation Format: Nadine Norton, Thien Nguyen, Joseph Reddy, Jinky Harvey, Morgan Weidner, Amanda Arnold, Lily Evans, Laura Vallow, Pooja Advani. Increased burden of genetic variants in idiopathic cardiomyopathy genes is associated with cancer therapy-related cardiomyopathy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-12-08.

Abstract Context Transgender and gender diverse (TGD) individuals have greater access to genital surgery (GS) with improved insurance coverage and access to trained surgeons and interdisciplinary gender-affirming providers. Objective To determine perioperative medical and behavioral health outcomes in transfeminine (TF) individuals undergoing GS, with use of a specific gender-affirming hormone therapy (GAHT) algorithm based on individualized risk factor assessment. Methods In this retrospective observational cohort study, we collected preoperative and postoperative data from 183 TF individuals at a single tertiary referral center from 2017 to 2022, grouping patients by those who continued estradiol (Group 1) vs those who had temporarily discontinued estradiol for 2 to 6 weeks preoperatively (Group 2). Data included clinical and biochemical assessment, GAHT regimens, validated behavioral health measures, and postoperative complications. Main outcomes included venous thromboembolism (VTE) incidence, non-VTE postoperative complication incidence, and change in behavioral health assessments. Results The majority of individuals continued estradiol perioperatively (Group 1; 138 [75.4%]). Individuals who temporarily held estradiol preoperatively (Group 2; 45 [24.6%]) were statistically older (P &lt; .01), had higher incidence of cardiometabolic comorbidities (P &lt; .01), and higher Caprini scores (P &lt; .01). Group 1 was statistically more likely to use oral estradiol (P &lt; .01). One episode (0.05%) of VTE occurred (Group 1). There was no significant difference in postoperative complications or behavioral health measures between groups. Conclusion An individualized algorithm for preoperative hormone management for TF GS resulted in perioperative continuation of GAHT for the majority of individuals without significantly increasing the risk for postoperative surgical complications, while maintaining stable behavioral health measures perioperatively.