Faculty Bibliography

Amid the dismantling of state structures in Haiti, the first Black republic faces significant health disparities compared to its former colonial power, France. These disparities include lower life expectancy (64.8 vs. 82.3 years) and higher infant and maternal mortality rates. The situation is further exacerbated by widespread mental health issues, severe food insecurity (50% acute vs. 37% moderate), and elevated homicide rates (13.35 vs. 1.35 per 100,000 inhabitants). As calls grow for France to return the independence ransoms extracted from Haiti, there remains limited data on how reparations could impact the country's public health, community well-being, or effective implementation of healing programs. Between Spring and Fall 2023, we conducted 4 focus groups: 1st with Haitian men and women residing in the United States, a 2nd-with men in Haiti, a 3rd with women in Cap-Haïtien and Les Cayes, and a 4th with women in Cité Soleil. We conducted focus groups structured interview protocol, comprised of open-ended questions categorized into 4 thematic sections. These questions provided insights into participants' perceptions on mental health, the daily challenges and barriers to access care, and community-based healing. Participants emphasized need for policies that address the social determinants of health, ensure safety and justice, and promote healthier workplace environments. They also advocated for mental health education aimed at reducing stigma, cultivating trust, and strengthening community support systems; with an emphasis on developing professional training, ethics, and sustainable long-term mental health services accessible for individuals of all ages. Haitian participants underscore the critical need to restore security, address the social determinants of health, and implement community-based mental health initiatives. We propose a biopsychosocial-ecological approach to guide reparations efforts. A targeted investment of $30 billion could yield substantial improvements in healthcare, mental health services, and public safety-contributing to increased life expectancy, reduced mortality rates, and decreased violence.

BACKGROUND/UNASSIGNED:Time-to-treatment goals for acute ischemic stroke (AIS) have substantially improved outcomes, yet similar metrics have not been studied in patients with intracerebral hemorrhage (ICH), where mortality rates are much higher. METHODS/UNASSIGNED:Multicenter, observational retrospective study of patients with ICH and AIS between January 1, 2017, and December 31, 2022, in 11 comprehensive stroke centers across the United States participating in Get With The Guidelines. We included patients with ICH who received antihypertensive therapy and anticoagulation reversal, and patients with AIS requiring intravenous thrombolytic and mechanical thrombectomy. The coprimary outcomes included (1) time-to-treatment and (2) the percentage of patients meeting current national time interval goals. Multivariable logistic regression models controlling for age, sex, race and ethnicity, time to arrival, National Institutes of Health Stroke Scale score, arrival systolic blood pressure, and admission international normalized ratio were constructed to assess the likelihood of patients with ICH being treated within goal compared with patients with AIS. Multivariable logistic regression models were constructed to assess the impact of treatment time on mortality or discharge disposition in patients with ICH. RESULTS/UNASSIGNED:<0.01) compared with those treated in >60 minutes. CONCLUSIONS/UNASSIGNED:Time-to-treatment for patients with ICH is significantly longer than for patients with AIS. Faster antihypertensive treatment times are associated with better discharge outcomes in patients with ICH.

BACKGROUND AND IMPORTANCE/BACKGROUND:Marfan syndrome's association with intracranial aneurysms, though controversial, poses unique challenges for surgical intervention because of the inherent vascular fragility. Open surgical approaches carry considerable risk. Endovascular flow diversion with the Pipeline embolization device (PED) offers a less invasive alternative, and adjunctive coiling can decrease occlusion time for complex aneurysms. We report the first combined use of PED and coiling to treat a Marfan-associated intracranial aneurysm, detailing our operative approach and reviewing the literature. CLINICAL PRESENTATION/METHODS:mutation was incidentally found to have an unruptured paraophthalmic aneurysm during stroke workup. Diagnostic angiography revealed an irregular superior hypophyseal aneurysm along with tortuous and irregular internal carotid arteries suggesting previous dissections. The aneurysm was successfully treated with a PED and adjunctive coil embolization. The patient was discharged on aspirin and clopidogrel. Six-month follow-up angiography confirmed aneurysm occlusion. Although there was no residual or recurrent aneurysm at 2-year follow-up, imaging revealed 2 de novo intracranial aneurysms. The patient remains asymptomatic and under observation. CONCLUSION/CONCLUSIONS:mutations and cerebrovascular pathology.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Epilepsy is a common neurologic disorder. Although antiseizure medications (ASMs) are the first-line treatment, identifying the most effective ASM for each individual remains a trial-and-error process. Genetic variation may influence treatment response. We aimed to develop and validate a multimodal deep learning model that integrates clinical and genomic features to predict response to the initial ASM in people with newly diagnosed epilepsy. METHODS:We used data from individuals with newly diagnosed epilepsy in Australia as the development cohort and participants from the Human Epilepsy Project 1 (recruited in the United States, Europe, and Australia) as the external validation cohort. All participants initiated ASM treatment and were followed prospectively for at least 1 year. We included 16 clinical factors and constructed 4 genomic feature types related to epilepsy and ASM pharmacogenomics, with and without functional impact annotations. We evaluated various machine learning architectures and multimodal fusion strategies to predict seizure freedom while taking the initial ASM at 1 year. RESULTS:< 0.05). Applying this model to the development cohort, if all participants took the highest ranked ASMs, the mean predicted seizure-free probability would be 68.05% (95% CI 65.79%-70.35%) compared with the observed seizure-free rate of 47.2% (95% CI 41.3%-53.2%). DISCUSSION/CONCLUSIONS:Integrating genomic data with clinical features enhances the ability of deep learning models in predicting ASM response in newly diagnosed epilepsy. This approach may support personalized treatment selection and improve clinical outcomes.

This position statement provides updated member guidance from the American Academy of Neurology (AAN) regarding (1) communication with surrogate decision makers about brain death/death by neurologic criteria (BD/DNC), (2) management of surrogate decision-maker objections to BD/DNC, (3) the ethical considerations associated with BD/DNC determination in a pregnant person, and (4) enhancing public trust in BD/DNC. This position statement is intended to complement recommendations in the 2023 "Pediatric and Adult Brain Death/Death by Neurologic Criteria Consensus Guideline" published by the AAN, American Academy of Pediatrics, Child Neurology Society, and Society of Critical Care Medicine, as well as the 2021 AAN Code of Professional Conduct. It replaces the 2019 AAN position statement, "Brain death, the determination of brain death, and member guidance for brain death accommodation requests."

Breast cancer screening recommendations have been established historically for women, but, have been less clearly outlined for men. For average-risk men and younger men less than 25 year of age, imaging is not usually appropriate as a screening test for breast cancer. For men of higher-than-average risk, screening with mammography as annual surveillance imaging is usually appropriate. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Vascular dysfunction contributes to Alzheimer disease (AD) and related dementias (ADRDs), but the underlying mechanisms remain unclear. Previous studies link midlife hemostasis and platelet aggregation measures to late-life dementia risk. We aimed to determine whether platelet aggregation in midlife is associated with imaging markers of AD pathology. METHODS:F-flortaucipir) PET uptake in dementia-free, middle-aged adults from the Framingham Heart Study. Co-primary outcomes included amyloid and tau uptake in AD-vulnerable regions. We also examined an MRI-based cortical thickness signature of AD risk as a secondary outcome. We used multivariable regression models adjusted for demographic and clinical factors, considering potential nonlinear associations. RESULTS:< 0.035), consistent with a neurodegenerative pattern. DISCUSSION/CONCLUSIONS:Our findings indicate that platelet aggregation is linked to PET and MRI markers of AD pathology as early as midlife. These findings support further investigation of platelet-mediated mechanisms in AD pathogenesis.

BACKGROUND:Age is the strongest factor determining disease expression in multiple sclerosis (MS). We previously demonstrated biological age acceleration in pediatric-onset MS (POMS) compared to controls with both epigenetic clocks (DNAm) and telomere length (TL). It is unknown whether these markers report overlapping or distinct aging-related processes. OBJECTIVES/OBJECTIVE:To determine the correlation between DNAm and TL aging markers. METHODS:We conducted a cross-sectional case-control study within the US Network of Pediatric MS Centers. We calculated age acceleration residuals for the Horvath, Hannum, PhenoAge, and GrimAge epigenetic clocks and measured TL from whole blood samples to estimate telomere to somatic DNA ratios (T/S ratio). We employed multivariable analysis of covariance to assess the correlation between DNAm estimates and TL. RESULTS: = 0.06). CONCLUSIONS:DNAm did not correlate with TL in this sample of POMS and controls, suggesting that these biomarkers may capture complementary and non-overlapping elements of aging-related biology.

BACKGROUND:There is paucity of data on long-term functional and cognitive outcomes after COVID-19 compared to COVID-negative controls. METHODS:We conducted an observational cohort study of patients ≥ 1 year after COVID-19 compared to contemporaneous COVID-19 negative controls (SARS-CoV-2 nucleocapsid IgG negative with no history of COVID-19). Functional (modified Rankin Scale [mRS], Barthel Index), cognitive (telephone MoCA [t-MoCA]), and patient-reported neuropsychiatric symptoms were compared between groups using multivariable logistic regression analysis. In a subgroup of COVID-19 patients who were followed longitudinally, trajectories of recovery were assessed using the paired samples Sign test. RESULTS:Of 145 participants, N = 115 COVID-19 patients (median age 62, 51 % female, 33 % hospitalized for COVID-19, median 2.9 years from index infection), and N = 30 non-COVID-19 controls (median age 75, 70 % female) were enrolled. Neuropsychiatric symptoms were reported in 76 % of COVID-19 patients versus 7 % of controls (aOR 15.0, 95 %CI 3.09-72.47, P < 0.001). Abnormal mRS> 0 occurred in 42 % of COVID-19 patients compared to 11 % of controls (P = 0.002). However, this difference was not significant after adjusting for age, sex, COVID-19 hospitalization and history of mood disorder (aOR 2.10, 95 %CI 0.52-8.51). Rates of abnormal t-MoCA≤ 18 (40 % of COVID-19 versus 41 % of controls, P = 1.00) and Barthel scores< 100 (19 % of COVID-19 versus 14 % in controls, P = 0.785) were similar. Among N = 26 COVID-19 patients with repeated measures, mRS significantly improved between 6-months to 3-years post-COVID (+1.3 points, p = 0.004), while no changes were observed in t-MoCA or Barthel. CONCLUSIONS:Three years after COVID-19, neuropsychiatric symptoms were significantly more frequent compared to controls, however no differences in functional or cognitive status were detected.