Faculty Bibliography

BACKGROUND:It remains difficult to predict who will succumb to Sudden Unexpected Death in Epilepsy (SUDEP). As the mechanisms for SUDEP remain unknown, there are not adequate strategies to prevent SUDEP. Thus, some providers are reluctant to discuss SUDEP risk with patients. Public health surveillance and prevention efforts are limited. The SUDEP Summit aimed to identify gaps in the field and prioritize recommendations to advance basic science, clinical care, and public health approaches to mitigate SUDEP. METHODS:In 2020, a diverse group of stakeholders formed the four SUDEP Summit workgroups: 1. Clinical Action, 2. Awareness and Behavior Change, 3. Public Health and Epidemiology, and 4. Basic Science. RESULTS:Each workgroup defined priorities for action and necessary resources and partners; outlined challenges and barriers; defined metrics of success; and developed short and long-term goals. Workgroups discussed methods to prioritize SUDEP research and develop educational materials for healthcare professionals to raise awareness about the risks of SUDEP. Since the meeting, progress has been made in alignment with the workgroups' recommendations. These include studies examining the use of wearables, clinical trials reporting SUDEP rates, tools to improve SUDEP education, policies to improve SUDEP reporting, SUDEP risk calculators, new clinically relevant models, and standardization of data collection. SIGNIFICANCE/CONCLUSIONS:Advancements in SUDEP awareness, education, epidemiology, and causal mechanisms require interdisciplinary collaborative approaches between funding agencies, advocacy groups, providers, and researchers; and the development of new partnerships. More work remains to achieve the recommendations from the Summit, which highlight the fundamental importance of coordinating efforts to mitigate and end SUDEP.

OBJECTIVES/OBJECTIVE:To investigate the associations between total and individual potato intake and risk of type 2 diabetes (T2D), estimate the effect on T2D risk of replacing potatoes with whole grains and other major carbohydrate sources, and conduct a dose-response and substitution meta-analysis of prospective cohort studies. DESIGN/METHODS:Prospective cohort study and dose-response meta-analysis of prospective cohort studies. SETTING/METHODS:Individual participant data from Nurses' Health Study (1984-2020), Nurses' Health Study II (1991-2021), and Health Professionals Follow-up Study (1986-2018). PARTICIPANTS/METHODS:205 107 men and women free of diabetes, cardiovascular disease, or cancer at baseline. MAIN OUTCOME MEASURE/METHODS:Incident type 2 diabetes. RESULTS:During 5 175 501 person years of follow-up, T2D was documented in 22 299 participants. After adjustment for updated body mass index and other diabetes related risk factors, higher intakes of total potatoes and French fries were associated with increased risk of T2D. For every increment of three servings weekly of total potato, the rate for T2D increased by 5% (hazard ratio 1.05, 95% confidence interval (CI) 1.02 to 1.08) and for every increment of three servings weekly of French fries the rate increased by 20% (1.20, 1.12 to 1.28). Intake of combined baked, boiled, or mashed potatoes was not significantly associated with T2D risk (pooled hazard ratio 1.01, 95% CI 0.98 to 1.05). In substitution analyses, replacing three servings weekly of potatoes with whole grains was estimated to lower T2D rates by 8% (95% CI 5% to 11%) for total potatoes, 4% (1% to 8%) for baked, boiled, or mashed potatoes, and 19% (14% to 25%) for French fries. In contrast, replacing total potatoes or baked, boiled, or mashed potatoes with white rice was associated with an increased risk of T2D. In a meta-analysis of 13 cohorts (587 081 participants and 43 471 diagnoses of T2D), the pooled hazard ratio for risk of T2D with each increment of three servings weekly of total potato was 1.03 (95% CI 1.02 to 1.05) and of fried potatoes was 1.16 (1.09 to 1.23). In substitution meta-analyses, replacing three servings weekly of total, non-fried, and fried potatoes with whole grains was estimated to lower the risk of T2D by 7% (95% CI 5% to 9%), 5% (3% to 7%), and 17% (12% to 22%), respectively. CONCLUSIONS:Higher intake of French fries, but not combined baked, boiled, or mashed potatoes, was associated with a higher risk of T2D. The T2D risk linked to potato intake seemed to depend on the food being replaced: replacing potato with whole grains was associated with lower risk, whereas replacing with white rice was associated with increased risk.

BACKGROUND:Sturge-Weber syndrome (SWS) is a congenital neurocutaneous disorder characterized by angiomas of the face, choroid, and leptomeninges. Seizures in these children often present within the first 2 years of life. SWS is typically unilateral, but bilateral SWS occurs in approximately 15% of cases. Bilateral SWS is associated with earlier seizure onset and poorer cognitive, developmental, and functional outcomes. More than half of children with SWS develop drug-resistant epilepsy requiring surgical intervention. Hemispherotomy has been established as a successful treatment for unilateral SWS, but resective surgery has traditionally not been considered a treatment option for patients with bilateral disease. OBSERVATIONS/METHODS:In this report, the authors present the cases of 4 children (7 months-2 years of age) with bilateral SWS and drug-resistant epilepsy with a unilateral electroencephalography predominance. After a multidisciplinary conference in each case, all children were successfully treated with unilateral hemispherotomy. These patients achieved prolonged periods of seizure freedom postoperatively, a better quality of life, and demonstrated improved developmental progress at long-term follow-up. LESSONS/CONCLUSIONS:This case series suggests that functional hemispherotomy may be a safe and effective therapeutic option for improving seizure burden in cases of bilateral drug-resistant SWS with asymmetric seizure burden. https://thejns.org/doi/10.3171/CASE25125.

IMPORTANCE/UNASSIGNED:The rise in chatbot health advice (CHA) studies is accompanied by heterogeneity in reporting standards, impacting their interpretability. OBJECTIVE/UNASSIGNED:To provide reporting recommendations for studies evaluating the performance of generative artificial intelligence (AI)-driven chatbots when summarizing clinical evidence and providing health advice. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:CHART was developed in several phases after performing a comprehensive systematic review to identify variation in the conduct, reporting, and methodology in CHA studies. Findings from the review were used to develop a draft checklist that was revised through an international, multidisciplinary modified asynchronous Delphi consensus process of 531 stakeholders, 3 synchronous panel consensus meetings of 48 stakeholders, and subsequent pilot testing of the checklist. RESULTS/UNASSIGNED:CHART includes 12 items and 39 subitems to promote transparent and comprehensive reporting of CHA studies. These include title (subitem 1a), abstract or summary (subitem 1b), background (subitems 2ab), model identifiers (subitem 3ab), model details (subitems 4abc), prompt engineering (subitems 5ab), query strategy (subitems 6abcd), performance evaluation (subitems 7ab), sample size (subitem 8), data analysis (subitem 9a), results (subitems 10abc), discussion (subitems 11abc), disclosures (subitem 12a), funding (subitem 12b), ethics (subitem 12c), protocol (subitem 12d), and data availability (subitem 12e). CONCLUSIONS AND RELEVANCE/UNASSIGNED:The CHART checklist and corresponding methodological diagram were designed to support key stakeholders including clinicians, researchers, editors, peer reviewers, and readers in reporting, understanding, and interpreting the findings of CHA studies.

IMPORTANCE/UNASSIGNED:Fluorescence-guided surgery aims to improve intraoperative identification of vital structures. Rizedisben is a myelin-binding fluorophore that fluoresces in the blue light (370-425 nm) spectrum to improve intraoperative nerve identification. OBJECTIVE/UNASSIGNED:To determine the optimal safe and clinically effective dose of rizedisben for sustained intraoperative fluorescence of nerve structures. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:A single-arm, open-label, phase 1 study was conducted in patients undergoing robot-assisted laparoscopic radical prostatectomy (RALP) at an urban academic cancer center in New York City between January 2023 and October 2024. Using a dose escalation design, increasing doses of rizedisben were administered after safety was assessed at each level until a clinically effective dose was determined. The obturator nerve served as the reference nerve for measuring fluorescence intensity. Eligible patients were 18 years old and older, diagnosed with prostate cancer, and scheduled for RALP. Patients were recruited in preoperative clinic visits once deemed eligible for the study. Those with prior pelvic surgery or radiation, known central or peripheral nervous system disease, current use of neurotoxic medications, recent exposure to phototoxic drugs, or serious kidney or liver dysfunction were excluded. INTERVENTIONS/UNASSIGNED:Rizedisben was intravenously administered intraoperatively 30 minutes prior to visualization of the obturator nerve. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Safety was assessed through 45 postoperative days. Fluorescence was measured via subjective intraoperative scoring and by post hoc objective image analysis. Clinically effective dose was defined as achieving sustained fluorescence of the obturator nerve in 3 or more of 5 patients in 2 consecutive cohorts, provided fewer than 20% of patients experienced grade 2 or greater toxicity. Sustained fluorescence was defined as moderate or better fluorescence for 90 minutes or longer. At the clinically effective dose, fluorescence assessments of the neurovascular bundles were included. RESULTS/UNASSIGNED:Thirty-eight patients (median [IQR] age, 61.5 [57.8-66.3] years) enrolled in and completed the trial. Dosing was escalated from 0.25 to 3.0 mg/kg. There was 1 grade 2 adverse event (rash) possibly attributable to rizedisben. Sustained fluorescence of the obturator nerve was achieved in all patients at 3.0 mg/kg. Prostate neurovascular bundles demonstrated evidence of fluorescence in 8 of 9 (89%) patients at 3.0 mg/kg. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this phase 1 trial of rizedisben, the 3.0-mg/kg dose was shown to be generally well tolerated and clinically effective. At this dose, there was excellent sustained fluorescence of the obturator nerves, and the neurovascular bundles were visualized in 8 of 9 patients. Based on these data, we are designing phase 2 studies with rizedisben for additional indications. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04983862.

BACKGROUND:To address financial barriers that limit access to genomic profiling and precision medicine, philanthropy supported clinical genomic testing was offered worldwide at no cost to patients with select rare cancers via the Make-an-IMPACT program. Herein, we report our findings in pediatric patients with solid or central nervous system (CNS) tumors. METHODS:Tumor DNA or CSF-derived circulating tumor DNA (CSF ctDNA) was analyzed using the MSK-IMPACT assay, supplemented by targeted RNA panel sequencing in select cases. Results were returned to the patients/families and treating oncologists. RESULTS:63 patients from 11 countries had successful MSK-IMPACT testing. The results provided clinically relevant new diagnostic or prognostic information in 41% and 38% of solid and CNS tumor patients, respectively. Potentially therapeutically actionable alterations were identified in 44% of pediatric solid tumor and 21% of pediatric CSF ctDNA samples, respectively. Four patients subsequently received molecularly guided therapy, resulting in partial responses in two and prolonged stable disease in one. Serial tumor and CSF sampling identified resistance mutations in two patients, informing additional molecular targeted therapy recommendations. CONCLUSIONS:The Make-an-IMPACT program provided global access to state-of-the-art tumor and CSF genomic profiling across a diverse cohort of pediatric cancer patients, providing clinically relevant and actionable diagnostic, prognostic and therapeutic information reported in real time to patients and local physicians.

BACKGROUND:The Chatbot Assessment Reporting Tool (CHART) is a reporting guideline developed to provide reporting recommendations for studies evaluating the performance of generative artificial intelligence (AI)-driven chatbots when summarizing clinical evidence and providing health advice, referred to as Chatbot Health Advice (CHA) studies. METHODS:CHART was developed in several phases after performing a comprehensive systematic review to identify variation in the conduct, reporting, and methodology in CHA studies. Findings from the review were used to develop a draft checklist that was revised through an international, multidisciplinary modified asynchronous Delphi consensus process of 531 stakeholders, three synchronous panel consensus meetings of 48 stakeholders, and subsequent pilot testing of the checklist. RESULTS:CHART includes 12 items and 39 subitems to promote transparent and comprehensive reporting of CHA studies. These include Title (subitem 1a), Abstract/Summary (subitem 1b), Background (subitems 2ab), Model Identifiers (subitems 3ab), Model Details (subitems 4abc), Prompt Engineering (subitems 5ab), Query Strategy (subitems 6abcd), Performance Evaluation (subitems 7ab), Sample Size (subitem 8), Data Analysis (subitem 9a), Results (subitems 10abc), Discussion (subitems 11abc), Disclosures (subitem 12a), Funding (subitem 12b), Ethics (subitem 12c), Protocol (subitem 12d), and Data Availability (subitem 12e). CONCLUSION/CONCLUSIONS:The CHART checklist and corresponding methodological diagram were designed to support key stakeholders including clinicians, researchers, editors, peer reviewers, and readers in reporting, understanding, and interpreting the findings of CHA studies.

The Chatbot Assessment Reporting Tool (CHART) is a reporting guideline developed to provide reporting recommendations for studies evaluating the performance of generative artificial intelligence (AI)-driven chatbots when summarizing clinical evidence and providing health advice, referred to as Chatbot Health Advice (CHA) studies. CHART was developed in several phases after performing a comprehensive systematic review to identify variation in the conduct, reporting and methodology in CHA studies. Findings from the review were used to develop a draft checklist that was revised through an international, multidisciplinary modified asynchronous Delphi consensus process of 531 stakeholders, three synchronous panel consensus meetings of 48 stakeholders, and subsequent pilot testing of the checklist. CHART includes 12 items and 39 subitems to promote transparent and comprehensive reporting of CHA studies. These include Title (subitem 1a), Abstract/Summary (subitem 1b), Background (subitems 2ab), Model Identifiers (subitem 3ab), Model Details (subitems 4abc), Prompt Engineering (subitems 5ab), Query Strategy (subitems 6abcd), Performance Evaluation (subitems 7ab), Sample Size (subitem 8), Data Analysis (subitem 9a), Results (subitems 10abc), Discussion (subitems 11abc), Disclosures (subitem 12a), Funding (subitem 12b), Ethics (subitem 12c), Protocol (subitem 12d), and Data Availability (subitem 12e). The CHART checklist and corresponding methodological diagram were designed to support key stakeholders including clinicians, researchers, editors, peer reviewers, and readers in reporting, understanding, and interpreting the findings of CHA studies.

The loss of maternal UBE3A causes Angelman syndrome whereas its duplication is associated with a heterogeneous neurodevelopmental disorder. Here, we describe two affected brothers who possess a novel UBE3A^L734S variant that is not present in two neurotypical siblings. The UBE3A^L734S variant was confirmed to be maternally inherited, and the affected individuals exhibited early global developmental delay, ongoing learning difficulties, and autistic features. Their phenotypes were inconsistent with Angelman syndrome. Biochemical characterization showed the UBE3A^L734S variant causes a dramatic increase in the activity of the UBE3A enzyme, suggesting that a gain in UBE3A activity is the driver of neurodevelopmental disease. Our observations document an emerging class of neurodevelopmental disorders caused by gain-of-function mutations in UBE3A.

Brain death/death by neurologic criteria (BD/DNC) is accepted as legal death throughout much of the world. The World Brain Death Project and a subsequent review of the literature through 2023 highlighted several medicolegal controversies related to BD/DNC in Canada, the United Kingdom, and the United States but did not discuss medicolegal controversies related to BD/DNC in low- and middle-income countries, such as India. Although the Transplantation of Human Organs Act of 1994 acknowledged BD/DNC as death in India, BD/DNC evaluations are not always completed when BD/DNC is suspected. This has been attributed to lack of awareness/acceptance by medical professionals, lack of public awareness/acceptance of BD/DNC, communication challenges, fear, time limitations, and the inclusion of BD/DNC in organ donation law (but not general law). There has been a gradual rise in the number of donations after BD/DNC (a correlate for the number of BD/DNC determinations) in southern and western states, but the number of donations after BD/DNC has decreased in the southwestern state of Kerala in the setting of recent medicolegal controversies. This article reviews the history of BD/DNC determination in India as a whole, then describes the recent medicolegal controversies related to BD/DNC in the state of Kerala. Finally, these controversies are contextualized relative to the aforementioned controversies in high-income countries. Three key international themes of medicolegal controversies related to BD/DNC are regulation, religion, and resource allocation. The global neurocritical care community must advocate for consistency and accuracy in BD/DNC determination and collaborate with legal and policy experts to develop means to mitigate these challenges through revisions to the law, standardization of practice and policies, education, and communication.