Faculty Bibliography

OBJECTIVES/OBJECTIVE:The practice of limiting life-sustaining therapy (LST) at end-of-life is widespread globally. The goal of this study was to evaluate whether patient's age influences end-of-life limitations overall and of various LST in ICUs worldwide. DESIGN/METHODS:Multinational, multicenter, prospective observational study. SETTING/METHODS:One hundred ninety-nine ICUs in 36 countries worldwide. PATIENTS/METHODS:Consecutive adult patients admitted to ICUs who died and/or had LST limitations (withholding, withdrawing, or active shortening of the dying process) were included during a 6-month period between September 2015 and September 2016. INTERVENTIONS/METHODS:None. MEASUREMENTS AND MAIN RESULTS/RESULTS:Patients were grouped: younger than 65 years, 65-79 years old, and 80 years old or older. A total of 12,200 patients were included. In multivariate logistic regression analysis, odds ratio (OR) for any LST limitation in the 80 years old or older group was higher than in younger than the 65 years old group (OR 1.47 [95% CI, 1.22-1.76], p < 0.001). When stratified by region, this association was significant in Central and Southern Europe (OR 1.56 [95% CI, 1.11-2.20], p = 0.037 and OR 2.23 [95% CI, 1.58-3.17], p < 0.001, respectively), but not in the other regions. The proportion of withholding therapy of each LST was highest in the group of individuals 80 years or older, whereas the proportion of withdrawing therapy was highest in the group younger than 65 years. The 80-year-old or older group also had a shorter time from ICU admission to first limitation. The predominant reason for any LST limitation in all age groups was unresponsiveness to maximal therapy, followed by neurologic and chronic diseases. Patient age was rarely the primary reason for limitations for all groups. CONCLUSIONS:End-of-life limitations were higher in patients 80 years or older compared to those 65 years old or younger, with regional variations. The main reasons for limitations were comparable across age groups, with age not being the primary reason.

BACKGROUND:The RESCUE-ICAS study (Registry of Emergent Large-Vessel Occlusion due to Intracranial Stenosis) demonstrated that patients undergoing acute stenting of intracranial atherosclerosis with large-vessel occlusion after mechanical thrombectomy had better outcomes than those undergoing mechanical thrombectomy alone. We present 2 secondary analyses of RESCUE-ICAS to evaluate intracranial stenting among patients who achieved successful reperfusion. METHODS:From a prospective observational cohort of 25 stroke centers (2022-2023), patients with acute intracranial occlusion, National Institutes of Health Stroke Scale score ≥6, and 50% to 99% residual stenosis or occlusion after endovascular thrombectomy were included. In the first analysis, we compared patients with stenting versus those without stenting from among those patients with a final modified Thrombolysis in Cerebral Infarction score of 2B-3. In the second analysis, we compared patients who underwent stenting with those who did not from among the patients with a Thrombolysis in Cerebral Infarction (TICI) score of 2B-3 before stenting. The odds of a favorable 90-day mRS (0-2) and 24-hour MRI infarct volume <30 mL were assessed using multivariable logistic regression. We also examined the rates of symptomatic ICH and death at 90 days in these cohorts. RESULTS:=0.480). CONCLUSIONS:Among both the cohort with final successful reperfusion and the cohort with initial successful reperfusion after mechanical thrombectomy alone, intracranial stenting was associated with better long-term clinical and radiographic outcomes, without higher morbidity and mortality. REGISTRATION/BACKGROUND:URL: https://www.clinicaltrials.gov; Unique identifier: NCT05403593.

Metaphors have long played multiple roles in conceptualizing the mind and brain, guiding the development and refinement of theoretical models and empirical questions. Early analogies (comparing the brain to hydraulic systems, telephone exchanges, factories, or libraries) offered shortcuts to understanding aspects of cognition, memory, and brain dynamics. From theoretical frameworks, metaphors like the mind as a computer evolved into central scientific metaphors, shaping core theoretical frameworks, inspiring predictions, and informing research methodologies. As such, metaphors play a key role in guiding scientific inquiries. Building on that premise, we propose music as a scientific metaphor for understanding multiple brain dynamics and cognitive functions. Unlike metaphors focusing on static components or linear flows, music emphasizes continuous adaptation, context-dependence, and cultural embedding, and presents a model for simultaneous engagement with multiple layers of meaning. Integrating analytical techniques from music theory and experiential insights from performance and listening, we can deepen our understanding of mind and brain dynamics and provide fresh epistemological pathways for interdisciplinary research. Music has a hierarchical structure, temporal complexity, and capacity to integrate multiple processes that parallel key features of the brain's architecture and cognitive functions. Drawing from research on neural oscillations, plasticity, predictive coding, and emotional processing, we illustrate how the musical paradigm can capture the rich entanglement of mind and brain, from large-scale brain dynamics and developmental trajectories to the emergence of consciousness and the interplay of affective states.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Severe hypoxemia after generalized convulsive seizures (GCSs) can trigger neural injury and is a potential biomarker for sudden unexpected death in epilepsy (SUDEP). Some degree of variability in interbreath interval is normal, but increased variability may suggest dysfunctional breathing control and may be associated with severe postictal hypoxemia. We evaluated the relationship between interictal breathing variability and severity and duration of hypoxemia after GCS. METHODS:nadir), and secondary outcome: occurrence of combined prolonged and pronounced hypoxemia. Univariable and multivariable models were created for primary outcomes, but only univariable analyses were performed for the secondary outcome. RESULTS:= 0.002) was the only variable significantly associated with hypoxemia severity after controlling for duration of postictal generalized EEG suppression, SD-2 of the awake interbreath interval, and body mass index. Univariable analyses for combined prolonged and pronounced hypoxemia showed SD-2 of the awake interbreath interval, temporal lobe epilepsy, ictal central apnea, and a shorter tonic phase duration were significantly associated. DISCUSSION/CONCLUSIONS:Measures of interictal respiratory variability are associated with severe and prolonged hypoxemia after GCS. Increased interictal respiratory variability suggests baseline respiratory dysregulation in some PWE and may be a surrogate for SUDEP risk.

BACKGROUND:Associations of youth sport participation patterns, health, and social-environmental factors with subsequent participation in the National Basketball Association (NBA) have not been investigated systematically. Prior studies suggest that high-performing athletes who achieve the world-class level of adult sport engaged in less organized training in their primary sport, participated in more multisport practice and competition, and incurred fewer injuries as youths compared with lower-performing adult national-class athletes. HYPOTHESIS/OBJECTIVE:Players who sign an NBA player contract engaged in less organized basketball, demonstrated more multisport practice, and incurred fewer injuries as youth athletes compared with non-NBA peers. STUDY DESIGN/METHODS:Cross-sectional study. LEVEL OF EVIDENCE/METHODS:Level 4. METHODS: RESULTS:Youth athletes who later became NBA players reported more organized participation in sports other than basketball until age 14 years (90.0% vs 52.5%), began playing on select teams and focusing exclusively on basketball at older ages (10.7 ± 2.4 vs 9.1 ± 2.5 and 12.9 ± 2.2 vs 9.6 ± 2.5 years), and spent less time in organized and nonorganized basketball than matched non-NBA peers. NBA players also reported fewer severe injuries at ≥14 years (25.0% vs 47.5%) and were less likely to stay back in school, relocate residence, and receive scholarships/funding, respectively. BLR correctly classified 85.0% of NBA and non-NBA players. CONCLUSION/CONCLUSIONS:Participation in approximately 2 other sports, later specialization, less coach-led and nonorganized basketball, fewer injuries, and less disruption to academic and home life were characteristic of top-ranked youth players who later played in the NBA. CLINICAL RELEVANCE/CONCLUSIONS:This is the first study to investigate youth basketball participation patterns associated with reaching the NBA among top-ranked U.S. high school basketball players.

INTRODUCTION/BACKGROUND:It remains unclear whether specific blood pressure components-systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), or mean arterial pressure (MAP)-are similarly associated with white matter hyperintensity (WMH) burden across sexes within racial and ethnic groups. METHODS:= 1307) adults. Linear regression models examined associations between SBP, DBP, PP, and MAP with log-transformed WMH volume normalized to intracranial volume. Analyses were stratified by race and ethnic group and included sex × blood pressure interaction terms. Models adjusted for age, education, neuroimaging scanner, diabetes, dyslipidemia, obesity, and tobacco use. RESULTS:Among NHW participants, higher SBP and PP were more strongly associated with greater WMH volume in females compared to males. Among NHB participants, blood pressure-WMH associations did not differ by sex. Among Hispanic participants, females exhibited greater WMH volume in DBP- and MAP-adjusted models, although blood pressure-WMH associations were stronger in males. DISCUSSION/CONCLUSIONS:Blood pressure-WMH associations differ by sex within racial and ethnic groups. These findings highlight intersectional heterogeneity in cerebrovascular vulnerability and suggest that sex-specific blood pressure-related pathways to small-vessel injury vary across racial and ethnic contexts. HIGHLIGHTS/UNASSIGNED:Non-Hispanic White (NHW) females showed stronger systolic blood pressure (SBP)- and pulse pressure (PP)-white matter hyperintensity (WMH) associations than NHW males.Blood pressure (BP)-WMH associations did not differ by sex among non-Hispanic Black participants.Among Hispanic adults, BP-WMH associations were stronger in males than females.Antihypertensive use was associated with higher WMHs across race and ethnic groups.BP-related WMH vulnerability varies by sex and race and ethnic context.

OBJECTIVES/OBJECTIVE:Anti-amyloid-beta immunotherapy requires frequent MRI screening for amyloid-related imaging abnormalities-hemorrhage subtype (ARIA-H), consisting of cerebral microbleeds (CMB) and/or superficial siderosis (SS), using gradient-recalled echo (GRE) or susceptibility-weighted imaging (SWI). Screening MRI sequences for ARIA-H may benefit from acceleration to maximize patient enrollment by increased throughput and reduced motion degradation. This study assessed the diagnostic performance of standard GRE and SWI to echo-planar imaging (EPI) accelerated substitutions for detecting CMB and SS. MATERIALS AND METHODS/METHODS:This retrospective single-center rater study included 50 patients, 25 with CMB and 25 patients without CMB (median age 77 y, IQR: 70 to 82 y; 30 of 50 female) who were imaged with FDG PET-3T MRI from April to July 2023. Standard GRE (90 s) and SWI (192 s) were compared with an EPI-accelerated GRE (aGRE; 13 s, 86% time reduction) and an EPI-accelerated SWI substitution (aSWI; 33 s, 83% time reduction). Three board-certified neuroradiologists independently reported CMB and SS (per ARIA-H monitoring guidelines), perceived image quality and motion for each sequence. There were 240 total assessments per rater (the 4 different sequences for the 50 patients plus 10 duplicated patients). Sensitivity, specificity, positive and negative predictive values, area under the curve (AUC), inter-rater and intrarater agreement were determined for each sequence and rater. RESULTS:The aggregate AUCs for the 4 individual sequences were excellent for detecting CMB (0.84 to 0.94) and SS (0.89 to 1.00) without statistical differences observed between standard and EPI-accelerated substitutions. Both aGRE and aSWI had high negative predictive values (96.5% to 100%). There were modest quantitative correlations between standard and accelerated sequences (0.606 and 0.391 for GRE and SWI, respectively), no differences in CMB count for aGRE (bias 0.01, P=0.895), but reduced CMB count with aSWI (bias -1.12, P=0.014). Inter-rater agreements were mildly reduced for both GRE versus aGRE (eg, 0.757 to 0.622 for CMB detection) and SWI versus aSWI (eg, 0.834 to 0.649 for SS detection). Perceived image quality for accelerated sequences was reduced, but with less motion observed with aSWI. CONCLUSIONS:The aGRE and aSWI sequences shorten scan times 86% and 83%, respectively, with similar diagnostic performance for ARIA-H screening, but reduced rater agreement and perceived image quality.

The convergence of artificial intelligence (AI) and neuroscience represents one of medicine's most profound intellectual partnerships. Neuronal architecture has inspired computational methods, while computational models, evolving from theoretical constructs to transformative clinical tools, are reshaping neurological practice. As AI systems attempt to augment diagnostic accuracy, treatment planning, and patient care, neurologists must develop fluency in these technologies to harness their potential while navigating their limitations and dangers. AI-related publications have exponentially increased in recent years, yet many neurologists lack the foundational computer science background needed to critically evaluate and most safely and effectively implement these tools in clinical practice. This article serves to outline the historical foundations linking neuroscience to computing, examine core concepts of the past and current AI landscape in neurology, and describe methodologies that aim to revolutionize neurological care.

Childhood adversity is increasingly recognized as a critical modifier of neurologic disorder development and disease severity, including in the neuroimmune disorder multiple sclerosis (MS). While previous studies have linked early-life adversity to increased MS susceptibility and more severe disease, the underlying biological mechanisms remain poorly understood. This study investigated associations between childhood adversity and MS clinical features, with a focus on two potential pathogenic mechanisms: allostatic load and epigenetic modifications. We evaluated 60 consecutively enrolled young adults with MS; 30 with paediatric-onset MS (POMS) and 30 with adult-onset MS (AOMS). At time of enrolment in this cross-sectional study, participants had MS disease duration of 6 years on average. POMS participants were mean 22.09 (2.66) years and AOMS participants were mean 32.41 (2.19) years old. 62% of participants were female. Childhood adversity was defined using a composite index of individual, family and socioeconomic measures captured by the adverse childhood experiences questionnaire, parental education level and estimated household income during childhood. Clinical outcomes included patient-reported SymptoMScreen questionnaire regarding MS symptom burden and MS neurologist-assessed disability using the Expanded Disability Status Scale (EDSS) of the participant's neurologic exam at the time of enrolment. Circulating biomarkers of allostatic load and genome-wide epigenetic profiles (DNA methylation via RRBS; reduced representation bisulfite sequencing) were also assessed. A history of high childhood adversity was associated with significantly greater patient-reported MS symptom burden (P = 0.001) and higher neurologist-reported EDSS disability scores (P = 0.028), independent of disease duration or timing of treatment initiation. There were no differences between childhood adversity and circulating biomarkers of allostatic load. While childhood adversity was not associated with global epigenetic changes across the entire cohort, stratified analysis revealed divergent methylation patterns by age of MS onset: POMS participants with childhood adversity had increased DNA methylation, whereas AOMS participants with childhood adversity showed decreased methylation compared to individuals without childhood adversity. None of the observed clinical and biologic differences were explained by differences in disease duration or the interval between symptom onset and treatment initiation. Our findings suggest that childhood adversity is associated with increased MS symptom burden and neurologic disability in young adults with MS. Childhood adversity may differentially shape the epigenome, depending on the age of MS onset, with potential implications for disease trajectory and therapeutic vulnerability. These results support the biological embedding of childhood adversity in MS and highlight the need for age- and exposure-sensitive approaches to understanding MS pathogenesis across the lifespan.