Faculty Bibliography

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.

OBJECTIVE:Central to the development of novel antiseizure medications (ASMs) is testing of antiseizure activity in preclinical models. Although various well-established models exist, their predictive validity across the spectrum of clinical epilepsies has been less clear. We sought to establish the translational concordance of commonly used preclinical models to define models with the highest predictive clinical validity for focal onset seizures (FOS). METHODS:The Praxis Analysis of Concordance (PAC) framework was implemented to assess the translational concordance between preclinical and clinical ASM response for 32 US Food and Drug Administration-approved ASMs. Preclinical ASM responses in historically used seizure models were collected. Protective indices based on reported median tolerability and median efficacy values were calculated for each ASM in each preclinical model. A weighted scale representing relative antiseizure effect was used to grade preclinical ASM response for each seizure model. Data depth was further scored based on the number of evaluated ASMs with publicly available data. Established reports of clinical ASM use in patients with FOS were similarly evaluated, and a weighted scale representing prescribing patterns and perceived efficacy was used to grade clinical ASM response. To assess the predictive validity of preclinical models, a unified translational scoring matrix was developed to assign a concordance score spanning the spectrum from complete discordance (-1) to complete concordance (1) between preclinical and clinical ASM responses. Scores were summed and normalized to generate a global translational concordance score. RESULTS:The preclinical models with the highest translational concordance and greatest data depth for FOS were rodent maximal electroshock seizure (MES), mouse audiogenic seizure, mouse 6 Hz (32 mA), and rat amygdala kindling. SIGNIFICANCE/CONCLUSIONS:The PAC-FOS framework highlights mouse MES, mouse audiogenic, and mouse 6 Hz (32 mA) as three acute seizure models consistently demonstrating high predictive validity for FOS. We provide a pragmatic decision tree approach to support efficient resource utilization for novel ASM discovery for FOS.

[This corrects the article DOI: 10.3389/fimmu.2025.1590165.].

This article reflects on two proposals to classify and stage Parkinson's disease (PD) and related conditions based on the presence of aggregated alpha-synuclein (ASN) detected by alpha-synuclein aggregation assay (SAA). The authors highlight the significant shortcomings of the proposals: detection of ASN by SAA is not specific of PD or other well-established clinical conditions; they do not allow prediction of clinical course and prognosis; and they are not suitable as an endpoint for clinical trials. To move forward with proposals reflecting so many uncertainties and unknowns will just sow confusion and misunderstanding within the PD community.

PURPOSE/OBJECTIVE:To compare the performance of different measures of long-term psychiatric outcomes in patients with post-acute autoimmune encephalitis (AE) who may require comprehensive psychiatric evaluation. METHODS:The sensitivity of three self-reported measures of mood and anxiety symptoms (Patient Health Questionnaire [PHQ-9]; Profiles of Mood States-2 [POMS-2]; Generalized Anxiety Disorder 7-item [GAD7]) was compared with a structured clinician-administered tool (Mini Neuropsychiatric Inventory 7.0.2 [MINI 7.0.2]). New cutoff scores that optimized accuracy were then identified by Youden Index Method. RESULTS:Thirty-five patients with post-acute AE completed testing a median of 3 years after symptomatic onset (range = 1-22 years). The median PHQ9 score was 5 (range = 0-18), median POMS2 Total Mood Disturbance T-Score was 52 (range = 37-93), and median GAD7 score was 3 (range = 0-17). Twenty-five patients (71 %) met criteria for a psychiatric diagnosis on the MINI. When compared with the MINI, the sensitivity and specificity of the self-reported psychiatric symptom tools using standard cutoffs were 25 % and 80 % for the PHQ9, 50 % and 87 % for the POMS-2, 23 % and 91 % for the GAD7. Accuracy was improved when cutoffs of ≥5 for the PHQ9, ≥50 for the POMS2, and ≥ 3 for the GAD7 were used, at the cost of lower specificity. CONCLUSIONS:Patients with post-acute AE with psychiatric sequalae may be underrecognized if self-reported measures of psychiatric symptoms are used instead of clinician-administered structured interviews. If self-reported measures are used in AE, consideration should be given into using tools with higher validity in this patient population, such as the POMS-2.

BACKGROUND/UNASSIGNED:Cognitive impairment is common in multiple sclerosis (MS). Transcranial direct current stimulation (tDCS) combined with adaptive cognitive training (aCT) may improve clinical outcomes. OBJECTIVE/UNASSIGNED:To evaluate the effect of active vs. sham home-based tDCS + aCT on cognitive function. METHODS/UNASSIGNED:-scores. RESULTS/UNASSIGNED: = .411). CONCLUSIONS/UNASSIGNED:Active vs. sham tDCS + aCT resulted in significantly better cognitive outcomes, with the greatest benefit in those with high neurologic disability.CLINICALTRIALS.GOV; https://clinicaltrials.gov/study/NCT03838770; IDENTIFIER: NCT03838770.

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.

IMPORTANCE/UNASSIGNED:Acute necrotizing encephalopathy (ANE) is a rare, but severe, neurologic condition for which epidemiologic and management data remain limited. During the 2024-2025 US influenza season, clinicians at large pediatric centers anecdotally reported an increased number of children with influenza-associated ANE, prompting this national investigation. OBJECTIVE/UNASSIGNED:To understand the clinical presentation, interventions, and outcomes among US children diagnosed with influenza-associated ANE. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This study was a multicenter case series of children diagnosed with ANE with longitudinal follow-up. A call for cases was issued via academic societies, public health agencies, and by directly contacting pediatric specialists at 76 US academic centers, requesting cases between October 1, 2023, and May 30, 2025. Inclusion criteria required acute encephalopathy with radiologic evidence of acute thalamic injury and laboratory confirmation of influenza infection in individuals aged 21 years or younger. EXPOSURE/UNASSIGNED:Influenza-associated ANE. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Presenting symptoms, vaccination history, laboratory and genetic findings, interventions, and clinical outcomes, including modified Rankin Scale score (0: no symptoms; 1-2: mild disability; 3-5: moderate to severe disability; 6: death), length of stay, and functional outcomes. RESULTS/UNASSIGNED:Of 58 submitted cases, 41 cases (23 females; median age, 5 years [IQR, 2-8]) from 23 US hospitals met inclusion criteria. Thirty-one cases (76%) had no significant medical history; 5 (12%) were medically complex. Clinical presentation included fever in 38 patients (93%), encephalopathy in 41 (100%), and seizures in 28 (68%). Thirty-nine patients (95%) had influenza A (14 with A/H1pdm/2009, 7 with A/H3N2, and 18 with no subtype) and 2 had influenza B. Laboratory deviations included elevated liver enzymes (78%), thrombocytopenia (63%), and elevated cerebrospinal fluid protein (63%). Among 32 patients (78%) with genetic testing, 15 (47%) had genetic risk alleles potentially related to risk of ANE including 11 (34%) with RANBP2 variants. Among 38 patients with available vaccination history, only 6 (16%) had received age-appropriate seasonal influenza vaccination. Most patients received multiple immunomodulatory treatments, including methylprednisolone (95%), intravenous immunoglobulin (66%), tocilizumab (51%), plasmapheresis (32%), anakinra (5%), and intrathecal methylprednisolone (5%). Median intensive care unit and hospital lengths of stay were 11 days (IQR, 4-19) and 22 days (IQR, 7-36), respectively. Eleven patients (27%) died a median of 3 days (IQR, 2-4) from symptom onset, primarily from cerebral herniation (91%). Among the 27 survivors with 90-day follow-up, 63% had at least moderate disability (modified Rankin Scale score ≥3). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this case series of children with influenza-associated ANE from the 2 most recent influenza seasons in the US, the condition was associated with high morbidity and mortality in this cohort of predominantly young and previously healthy children. The findings emphasize the need for prevention, early recognition, intensive treatment, and standardized management protocols.

BACKGROUND:Sudden Unexpected Death in Epilepsy (SUDEP) is a rare and tragic outcome in epilepsy, identified by those with the condition as their most serious concern. Although several clinical factors are associated with elevated SUDEP risk, mechanisms underlying SUDEP are poorly understood, making individual risk prediction challenging, especially early in the disease course. We hypothesised that common genetic variation contributes to SUDEP risk. METHODS:Genetic data from people who had succumbed to SUDEP was compared to data from people with epilepsy who had not succumbed to SUDEP and from healthy controls. Polygenic risk scores (PRSs) for longevity, intelligence and epilepsy were compared across cohorts. Reactome pathways and gene ontology terms implicated by the contributing single nucleotide polymorphisms (SNPs) were explored. In the subset of SUDEP cases with the necessary data available, a risk score was calculated using an existing risk prediction tool (SUDEP-3); the added value to this prediction of SNP-based genomic information was evaluated. FINDINGS/RESULTS:Only European-ancestry participants were included. 161 SUDEP cases were compared to 768 cases with epilepsy and 1153 healthy controls. PRS for longevity was significantly reduced in SUDEP cases compared to disease (P = 0·0096) and healthy controls (P = 0·0016), as was PRS for intelligence (SUDEP cases compared to disease (P = 0·0073) and healthy controls (P = 0·00024)). The PRS for epilepsy did not differ between SUDEP cases and disease controls (P = 0·76). SNP-determined pathway and gene ontology analysis highlighted those related to inter-neuronal communication as amongst the most enriched in SUDEP. Addition of PRS for longevity and intelligence to SUDEP-3 scores improved risk prediction in a subset of cases (38) and controls (703), raising the area-under-the-curve in a receiver-operator characteristic from 0·699 using SUDEP-3 alone to 0·913 when PRSs were added. INTERPRETATION/CONCLUSIONS:Common genetic variation contributes to SUDEP risk, offering new approaches to improve risk prediction and to understand underlying mechanisms. FUNDING/BACKGROUND:The Amelia Roberts Fund; CURE Epilepsy; Epilepsy Society, UK; Finding A Cure for Epilepsy and Seizures (FACES).