Citations

AbstractThe Psychiatric Pediatric Issues Task Force of the International League Against Epilepsy (ILAE) aimed to develop recommendations for the diagnosis and treatment of anxiety and depression in children and adolescents with epilepsy. The Task Force conducted a systematic review and identified two studies that assessed the accuracy of four screening measures for depression and anxiety symptoms compared with a psychiatric interview. Nine studies met the eligibility criteria for treatment of anxiety and depressive disorders or symptoms. The risk of bias and certainty of evidence were assessed. The evidence generated by this review followed by consensus where evidence was missing generated 47 recommendations. Those with a high level of agreement (≥80%) are summarized. Diagnosis: (1) Universal screening for anxiety and depression is recommended. Closer surveillance is recommended for children after 12 years, at higher risk (e.g., suicide‐related behavior), with subthreshold symptoms, and experiencing seizure worsening or therapeutic modifications. (2) Multiple sources of ascertainment and a formal screening are recommended. Clinical interviews are recommended whenever possible. The healthcare provider must always explain that symptom recognition is essential to optimize treatment outcomes and reduce morbidity. (3) Questioning about the relationship between symptoms of anxiety or depression with seizure worsening/control and behavioral adverse effects of antiseizure medications is recommended. Treatment: (1) An individualized treatment plan is recommended. (2) For mild depression, active monitoring must be considered. (3) Referral to a mental health care provider must be considered for moderate to severe depression and anxiety. (4) Clinical care pathways must be developed. (5) Psychosocial interventions must be tailored and age‐appropriate. (6) Healthcare providers must monitor children with epilepsy who are prescribed antidepressants, considering symptoms and functioning that may not improve simultaneously. (7) Caregiver education is essential to ensure treatment adherence. (8) A shared‐care model involving all healthcare providers is recommended for children and adolescents with epilepsy and mental health disorders. We identified clinical decisions in the management of depression and anxiety that lack solid evidence and provide consensus‐based guidance to address the care of children and adolescents with epilepsy.

ImportancePatients with atrial fibrillation (AF) who have ischemic stroke despite taking oral anticoagulation therapy (OAT) have a very high risk of recurrence. Left atrial appendage occlusion (LAAO) is a mechanical stroke prevention strategy that may provide additional protection in patients with thromboembolic events under OAT.ObjectiveTo compare percutaneous LAAO with continuing OAT alone regarding stroke prevention in patients with AF who had a thromboembolic event despite taking OAT.Design, Setting, and ParticipantsThis cohort study was a propensity score–matched comparison of the STR-OAC LAAO cohort, an international collaboration of 21 sites combining patients from multiple prospective registries of patients who underwent LAAO between 2010 and 2022. STR-OAC LAAO cohort patients who had follow-up longer than 3 months were propensity score–matched to a previously published control cohort comprising patients from an established international collaboration of investigator-initiated prospective studies. This control cohort included patients with nonvalvular AF, recent ischemic stroke or transient ischemic attack, and follow-up longer than 3 months who were taking OAT before the index event. Analyses were adjusted for imbalances in gender, age, hypertension, diabetes, and CHA2 DS2-VASc score.ExposureLeft atrial appendage occlusion vs continuation of oral anticoagulation therapy alone (control group).Main Outcomes and MeasuresThe primary outcome was time to first ischemic stroke.ResultsFour hundred thirty-three patients from the STR-OAC LAAO cohort (mean [SD] age, 72 [9] years; 171 [39%] females and 262 [61%] males; mean [SD] CHA2 DS2-VASc score, 5.0 [1.6]) were matched to 433 of 1140 patients (38%) from the control group. During 2-year follow-up, 50 patients experienced ischemic stroke: an annualized event rate of 2.8% per patient-year in the STR-OAC LAAO group vs 8.9% per patient-year in the control group. Left atrial appendage occlusion was associated with a lower risk of ischemic stroke (hazard ratio, 0.33; 95% CI, 0.19-0.58; P < .001) compared with the control group. After LAAO, OAT was discontinued in 290 patients (67%), and the remaining 143 patients (33%) continued OAT after LAAO as an adjunctive therapy.Conclusions and RelevanceIn patients with nonvalvular AF and a prior thromboembolic event despite taking OAT, LAAO was associated with a lower risk of ischemic stroke compared with continued OAT alone. Randomized clinical trial data are needed to confirm that LAAO may be a promising treatment option for this population with a very high risk of stroke.

Abstract Background: Medium vessel occlusion (MeVO) strokes, particularly affecting the M2 segment of the middle cerebral artery, represent a critical proportion of acute ischemic strokes, posing significant challenges in management and outcome prediction. The efficacy of mechanical thrombectomy (MT) in MeVO stroke may warrant reliable predictors of functional outcomes. This study aimed to investigate the prognostic value of follow-up infarct volume (FIV) for predicting 90-day functional outcomes in MeVO stroke patients undergoing MT. Methods: This multicenter, retrospective cohort study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, covering patients with acute ischemic stroke due to M2 segment occlusion treated with MT. We examined the relationship between 90-day functional outcomes, measured by the modified Rankin Scale (mRS), and follow-up infarct volume (FIV), assessed through CT or MRI within 12–36 h post-MT. Results: Among 130 participants, specific FIV thresholds were identified with high specificity and sensitivity for predicting outcomes. A FIV ⩽5 ml was highly specific for predicting favorable and excellent outcomes. The optimal cut-off for both prognostications was identified at ⩽15 ml by the Youden Index, with significant reductions in the likelihood of favorable outcomes observed above a 40 ml threshold. Receiver Operator Curve (ROC) analyses confirmed FIV as a superior predictor of functional outcomes compared to traditional recanalization scores, such as final modified thrombolysis in cerebral infarction score (mTICI). Multivariable analysis further highlighted the inverse relationship between FIV and positive functional outcomes. Conclusions: FIV within 36 h post-MT serves as a potent predictor of 90-day functional outcomes in patients with M2 segment MeVO strokes. Establishing FIV thresholds may aid in the prognostication of stroke outcomes, suggesting a role for FIV in guiding post intervention treatment decisions and informing clinical practice. Future research should focus on validating these findings across diverse patient populations and exploring the integration of FIV measurements with other clinical and imaging markers to enhance outcome prediction accuracy.

Background: Bipolar disorder (BD) involves significant mood and energy shifts reflected in speech patterns. Detecting these patterns is crucial for diagnosis and monitoring, currently assessed subjectively. Advances in natural language processing offer opportunities to objectively analyze them. Aims: To (i) correlate speech features with manic-depressive symptom severity in BD, (ii) develop predictive models for diagnostic and treatment outcomes, and (iii) determine the most relevant speech features and tasks for these analyses. Methods: This naturalistic, observational study involved longitudinal audio recordings of BD patients at euthymia, during acute manic/depressive phases, and after-response. Patients participated in clinical evaluations, cognitive tasks, standard text readings, and storytelling. After automatic diarization and transcription, speech features, including acoustics, content, formal aspects, and emotionality, will be extracted. Statistical analyses will (i) correlate speech features with clinical scales, (ii) use lasso logistic regression to develop predictive models, and (iii) identify relevant speech features. Results: Audio recordings from 76 patients (24 manic, 21 depressed, 31 euthymic) were collected. The mean age was 46.0 ± 14.4 years, with 63.2% female. The mean YMRS score for manic patients was 22.9 ± 7.1, reducing to 5.3 ± 5.3 post-response. Depressed patients had a mean HDRS-17 score of 17.1 ± 4.4, decreasing to 3.3 ± 2.8 post-response. Euthymic patients had mean YMRS and HDRS-17 scores of 0.97 ± 1.4 and 3.9 ± 2.9, respectively. Following data pre-processing, including noise reduction and feature extraction, comprehensive statistical analyses will be conducted to explore correlations and develop predictive models. Conclusions: Automated speech analysis in BD could provide objective markers for psychopathological alterations, improving diagnosis, monitoring, and response prediction. This technology could identify subtle alterations, signaling early signs of relapse. Establishing standardized protocols is crucial for creating a global speech cohort, fostering collaboration, and advancing BD understanding.

Background Endovascular treatment with the woven endobridge (WEB) device has been widely utilized for managing intracranial aneurysms. However, predicting the probability of achieving adequate occlusion (Raymond–Roy classification 1 or 2) remains challenging. Objective Our study sought to develop and validate a predictive calculator for adequate occlusion using the WEB device via data from a large multi-institutional retrospective cohort. Methods We used data from the WorldWide WEB Consortium, encompassing 356 patients from 30 centers across North America, South America, and Europe. Bivariate and multivariate regression analyses were performed on a variety of demographic and clinical factors, from which predictive factors were selected. Calibration and validation were conducted, with variance inflation factor (VIF) parameters checked for collinearity. Results A total of 356 patients were included: 124 (34.8%) were male, 108 (30.3%) were elderly (≥65 years), and 118 (33.1%) were current smokers. Mean maximum aneurysm diameter was 7.09 mm (SD 2.71), with 112 (31.5%) having a daughter sac. In the multivariate regression, increasing aneurysm neck size (OR 0.706 [95% CI: 0.535–0.929], p = 0.13) and partial aneurysm thrombosis (OR 0.135 [95% CI: 0.024–0.681], p = 0.016) were found to be the only statistically significant variables associated with poorer likelihood of achieving occlusion. The predictive calculator shows a c-statistic of 0.744. Hosmer–Lemeshow goodness-of-fit test indicated a satisfactory model fit with a p-value of 0.431. The calculator is available at: https://neurodx.shinyapps.io/WEBDEVICE/ . Conclusion The predictive calculator offers a substantial contribution to the clinical toolkit for estimating the likelihood of adequate intracranial aneurysm occlusion by WEB device embolization.

Background: Acute ischemic stroke (AIS) from primary medium vessel occlusions (MeVO) is a prevalent condition associated with substantial morbidity and mortality. Despite the common use of mechanical thrombectomy (MT) in AIS, predictors of poor outcomes in MeVO remain poorly characterized. Methods: In this prospectively collected, retrospectively reviewed, multicenter, multinational study, data from the MAD-MT (Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy) registry were analyzed. The study included 1568 patients from 37 academic centers across North America, Asia, and Europe, treated with MT, with or without intravenous tissue plasminogen activator (IVtPA), between September 2017 and July 2021. Results: Among the 1568 patients, 347 (22.2%) experienced very poor outcomes (modified Rankin score (mRS), 5–6). Key predictors of poor outcomes were advanced age (odds ratio (OR): 1.03; 95% confidence interval (CI): 1.02 to 1.04; p < 0.001), higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (OR: 1.07; 95% CI: 1.05 to 1.10; p < 0.001), pre-operative glucose levels (OR: 1.01; 95% CI: 1.00 to 1.02; p < 0.001), and a baseline mRS of 4 (OR: 2.69; 95% CI: 1.25 to 5.82; p = 0.011). The multivariable model demonstrated good predictive accuracy with an area under the receiver-operating characteristic (ROC) curve of 0.76. Conclusions: This study demonstrates that advanced age, higher NIHSS scores, elevated pre-stroke mRS, and pre-operative glucose levels significantly predict very poor outcomes in AIS-MeVO patients who received MT. These findings highlight the importance of a comprehensive risk assessment in primary MeVO patients for personalized treatment strategies. However, they also suggest a need for cautious patient selection for endovascular thrombectomy. Further prospective studies are needed to confirm these findings and explore targeted therapeutic interventions.

Key Points Morphometry allows for a more prognostic multidimensional quantification of interstitial fibrosis and tubular atrophy (IFTA) in kidneys than does visual inspection. The density of IFTA foci is determined by dividing the number of contiguous IFTA patches in the kidney cortex by the area of cortex. Higher density of IFTA foci significantly predicted renal allograft failure beyond %IFTA and other biopsy and clinical characteristics. Background Contraction of interstitial fibrosis and tubular atrophy (IFTA) may cause %IFTA to under-represent the severity of nephron loss. Higher density of IFTA foci is an important predictor of progressive CKD in native kidneys independent of %IFTA. Methods We studied kidney transplant recipients transplanted between 2000 and 2013 who had a 5-year surveillance kidney biopsy and subsequent follow-up. Banff ci score (interstitial fibrosis) was obtained from the pathology reports. After digitizing the biopsies, we traced cortex area and each distinct IFTA focus on a single trichrome-stained section. Percent IFTA area and IFTA foci density (count of IFTA foci/cortex area) were calculated. Cox models assessed the risk of death-censored graft failure after the 5-year biopsy with Banff ci score, morphometric %IFTA, and IFTA foci density. Results There were 58 death-censored allograft failures among 835 kidney recipients during the 5 years of follow-up. Biopsies from grafts that failed had higher mean Banff ci score (1.5 versus 0.7, P < 0.0001), %IFTA (22.6% versus 7.0%, P < 0.0001), and IFTA foci density (1.3/mm 2 versus 0.4/mm 2 , P < 0.0001). After adjusting for other Banff scores or clinical variables, Banff ci did not correlate with allograft failure, but both higher %IFTA (hazard ratio = 1.56, P < 0.0001) and higher IFTA foci density (hazard ratio = 2.34, P < 0.0001) did. All but four allograft failures by 10 years had biopsies in the top quartile of either %IFTA or IFTA foci density at 5 years. A model using just these two morphometric measures without clinical characteristics resulted in a c-statistic of 0.891 with respect to allograft failure. Conclusions Morphometric characterization of IFTA foci density is a strong predictor of death-censored allograft failure not captured in current Banff classification for grading of kidney fibrosis.

Background Acute ischemic stroke (AIS) caused by distal medium vessel occlusions (DMVOs) represents a significant proportion of overall stroke cases. While intravenous thrombolysis (IVT) has been a primary treatment, advancements in endovascular procedures have led to increased use of mechanical thrombectomy (MT) in DMVO stroke patients. However, symptomatic intracerebral hemorrhage (sICH) remains a critical complication of AIS, particularly after undergoing intervention. This study aims to identify factors associated with sICH in DMVO stroke patients undergoing MT. Methods This retrospective analysis utilized data from the Multicenter Analysis of Distal Medium Vessel Occlusions: Effect of Mechanical Thrombectomy (MAD-MT) registry, involving 37 centers across North America, Asia, and Europe. Middle cerebral artery (MCA) DMVO stroke patients were included. The primary outcome measured was sICH, as defined per the Heidelberg Bleeding Classification. Univariable and multivariable logistic regression were used to identify factors independently associated with sICH. Results Among 1708 DMVO stroke patients, 148 (8.7%) developed sICH. Factors associated with sICH in DMVO patients treated with MT included older age (adjusted odds ratio (aOR) 1.01, 95% confidence interval (95% CI) 1.00 to 1.03, P=0.048), distal occlusion site (M3, M4) compared with medium occlusions (M2) (aOR 1.71, 95% CI 1.07 to 2.74, P=0.026), prior use of antiplatelet drugs (aOR 2.06, 95% CI 1.41 to 2.99, P<0.001), lower Alberta Stroke Program Early CT Scores (ASPECTS) (aOR 0.75, 95% CI 0.66 to 0.84, P<0.001), higher preoperative blood glucose level (aOR 1.00, 95% CI 1.00 to 1.01, P=0.012), number of passes (aOR 1.27, 95% CI 1.15 to 1.39, P<0.001), and successful recanalization (Thrombolysis In Cerebral Infarction (TICI) 2b-3) (aOR 0.43, 95% CI 0.28 to 0.66, P<0.001). Conclusion This study provides novel insight into factors associated with sICH in patients undergoing MT for DMVO, emphasizing the importance of age, distal occlusion site, prior use of antiplatelet drugs, lower ASPECTS, higher preoperative blood glucose level, and procedural factors such as the number of passes and successful recanalization. Pending confirmation, consideration of these factors may improve personalized treatment strategies.

Background Mechanical thrombectomy has become the standard of care for treatment of acute ischemic stroke secondary to large‐vessel occlusion up to 24 hours from last known normal time. Multiple different techniques for mechanical thrombectomy have been described, including a direct aspiration first‐pass technique and stent retriever thrombectomy. With a direct aspiration first‐pass technique, classically, a large‐bore aspiration catheter is delivered over a microcatheter and microwire to the clot. Recently, a novel macrowire has been introduced as a potential alternative to the use of microwire–microcatheter to allow the delivery of the aspiration catheter. The aim of this study is to develop a multicenter registry comparing delivery of an aspiration catheter for intracranial thrombectomy for acute ischemic stroke secondary to emergent large‐vessel occlusion over a macrowire in comparison with traditional use of microcatheter and microwire. Methods MINT (Macrowire for Intracranial Thrombectomy) is a multicenter, observational study currently enrolling patients with large‐vessel occlusion who underwent mechanical thrombectomy using a macrowire to deliver the aspiration catheter to the intracranial occlusion. All the participating sites will screen and report cases on a monthly basis. The decision to use the macrowire and various aspiration catheters is at the discretion of the interventionalist. Results We will collect patient's clinical, demographic, and radiographic data. In addition, we plan to collect procedure variables and postprocedure clinical and imaging data. Outcomes include successful delivery of the reperfusion catheter to the clot interface, time taken from groin access to first pass, and a bailout strategy for thrombectomy in cases where this is not feasible. Conclusion The MINT registry will add to our understanding of safety and efficacy of this novel macrowire in intracranial thrombectomy. This registry will also highlight and allow for understanding in workflow improvements from simplifying setup and possibly cost effectiveness of this technique.

e16301 Background: Outcomes for patients with Stage 3 pancreatic ductal adenocarcinoma (PDAC) remain poor with a mean overall survival (OS) of 11 months. Irreversible electroporation (IRE) is a method of local tumor ablation that causes cell death by disrupting homeostasis in the cell membrane. Previous research suggests IRE can be useful in the multi-disciplinary treatment of Stage 3 PDAC. The present study was designed to assess the effectiveness and safety of IRE for Stage 3 PDAC in a real-world setting after induction chemotherapy. Methods: Patients with Stage 3 PDAC treated with IRE were prospectively enrolled in a multicenter registry study. Enrollment required 3 months of active multi-agent chemotherapy, with no progression before IRE treatment. Endpoints were 30- and 90-day mortality from enrollment and the new onset of an adverse event (AE). Results: 87 patients were enrolled in the registry between May 2019 and May 2023. Mean age was 64.0 ± 8.4 years, 57.5% were female and mean tumor diameter was 2.2 ± 0.7 cm. Mean time from diagnosis to IRE treatment was 8.9 ± 4.9 months. All subjects underwent induction chemotherapy with the most common being FOLFIRINOX alone, gemcitabine with albumin-bound paclitaxel, or a combination of both in 47 (54.0%) patients. Thirty-seven (42.5%) patients had prior radiation therapy. All procedures were performed using an open approach with 50 (57.5%) for in-situ tumor ablation and 37 (42.5%) with the intent of margin accentuation in combination with resection. Major adjunctive procedures were performed for 70 (80.5%) patients. Common adjunctive surgeries were cholecystectomy (33.3%), Whipple procedure (28.7%) and either distal or subtotal pancreatectomy (11.4%). Mean IRE delivery time was 55.7 ± 54.5 minutes with an average of 3.1 probes (range 2 to 6) used per procedure. There was a mean of 1031.1 ± 882.1 pulses delivered per procedure. The 30- and 90-day mortality was 3/87 (3.4%) and 4/82 (4.9%) respectively. There were 21 (24.1%) patients who developed AEs related to IRE treatment during the 90-day post-procedure period (9 patients had AEs that were definitely related to IRE, 5 probably and 7 possibly). Of these related events, only three were Grade 4 or higher (arterial hemorrhage, cardiac arrest, and septic shock). Overall, gastrointestinal related AEs were the most common representing 16 of the 28 (57.1%) of all AEs associated with the IRE procedure. One patient died within 30 days of the procedure due to an intraperitoneal arterial hemorrhage that was deemed to be definitely related to the IRE treatment. Conclusions: The use of IRE for curative intent tumor ablation alone or in combination with resection following induction chemotherapy in patients with locally advanced Stage 3 PDAC has acceptable safety and is associated with acceptable morbidity and mortality rates in appropriately selected patients. Clinical trial information: NCT03899649 .