Faculty Bibliography

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:Many survivors of hemorrhagic stroke have impaired communication. We aimed to identify preadmission, admission, and post-discharge factors associated with self-reported impaired communication after hemorrhagic stroke. DESIGN/METHODS:Patients with intracerebral or subarachnoid hemorrhage (ICH or SAH) admitted at an urban academic medical center were assessed 3-months post-bleed using the communication Quality of Life in Neurological Disorders (Neuro-QoL) short form inventory. Multivariate analysis was performed to evaluate the relationship between impaired communication (Neuro-QoL scaled score < 100) and preadmission, admission, and post-discharge factors. RESULTS:Of 108 patients (68 ICH and 40 SAH), 59 (54.6%) had impaired communication 3-months post-bleed. On multivariate analysis of the full cohort, when controlling for NIHSS score on admission, impaired communication was associated with: retirement prior to admission (OR: 8.18, 95% CI 1.95-40.5, p = 0.005), hospital length-of-stay (OR: 1.11, 95% CI 1.03-1.22, p = 0.012), and cognitive impairment post-bleed (OR: 32.1, 95% CI 8.93-146, p < 0.001). There were 43 (63.2%) ICH patients with impaired communication 3-months post-bleed. On multivariate analysis, impaired communication was associated with: retirement prior to admission (OR: 9.46, 95% CI 1.76-71.8, p = 0.014), supratentorial location (OR: 8.93, 95% CI 1.22-93.6, p = 0.043), hospital length-of-stay (OR: 1.21, 95% CI 1.01-1.45, p = 0.018), and cognitive impairment post-bleed (OR: 16.3, 95% CI 3.58-102, p < 0.001). CONCLUSIONS:Impaired communication after hemorrhagic stroke is more common in patients who were retired prior to admission and who have post-bleed comorbid cognitive impairment. Increased surveillance is recommended for retired and cognitively impaired patients. Additional investigation into the relationship between communication and both retirement status and cognitive impairment is needed.

IMPORTANCE/UNASSIGNED:Differentiating multiple sclerosis (MS) from myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD), especially in seronegative cases, remains challenging due to overlapping clinical and imaging features. High-level Epstein-Barr virus (EBV)-derived Epstein-Barr nuclear antigen 1 (EBNA-1) peptide antibody titers may be an MS-specific biomarker that could the improve differential diagnosis. OBJECTIVE/UNASSIGNED:To determine whether longitudinal EBNA-1 peptide antibodies can distinguish MS from MOGAD and NMOSD. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This was a retrospective, multicenter, longitudinal, case-control study with patients from Austria, Germany, and the US. This study assessed samples from 2 independent retrospective cohorts. A test cohort and a validation cohort assessed longitudinal plasma samples from patients with MS, MOGAD, or NMOSD. Patients were recruited between 2001 and 2023 and followed up for 2 years. A combined analysis of both cohorts was conducted in January 2025. EXPOSURES/UNASSIGNED:Plasma EBNA-1 peptide immunoglobulin G (IgG) titers measured by enzyme-linked immunosorbent assay after diagnosis and in 3 follow-up samples. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Diagnostic utility of persistent EBNA-1 peptide antibody levels across 4 time points in patients with MS compared with patients with MOGAD and NMOSD. RESULTS/UNASSIGNED:This study included the plasma samples of 2091 patients (mean [SD] age, 31.0 [16.9] years; 1137 female [54.4%]) with neuroinflammatory disease and 1976 healthy controls (mean [SD] age, 39.8 [16.2] years; 1120 male [56.7%]) recruited between 2001 and 2023. The test cohort (310 patients; 54.8% female) included 184 patients with MS, 65 with MOGAD, and 61 with NMOSD (including 12 who were seronegative for aquaporin 4 [AQP4] IgG). The validation cohort (183 patients; 126 female [68.8%]) included 142 patients with MS, 24 with MOGAD, and 17 with NMOSD. In the test cohort, 177 patients with MS (96.2%) had high-level titers in 2 or more of 4 follow-up samples compared with 5 patients (7.7%) with MOGAD (odds ratio [OR], 303.4; 95% CI, 94.4-908.6) and 11 patients (18.0%) with NMOSD (OR, 114.9; 95% CI, 43.0-280.0). Among patients with NMOSD who were seronegative for AQP4-IgG, only 1 (11.1%) had persistent high-level EBNA-1 peptide antibody titers compared with 61 matched patients (96.7%) with MS (OR, 236.0; 95% CI, 18.6-2588.0). In the validation cohort, 135 patients (95.1%) with MS had high-level titers in 2 or more of 4 follow-up samples compared with 4 patients (16.7%) with MOGAD (OR, 96.4; 95% CI, 26.6-293.0) and 3 patients (17.6%) with NMOSD (OR, 90.0; 95% CI, 19.7-319.7). CONCLUSIONS AND RELEVANCE/UNASSIGNED:Results of this case-control study reveal that persistent high-level EBNA-1 peptide antibody titers may serve as a reliable biomarker for differentiating MS from MOGAD, and NMOSD.

IMPORTANCE/UNASSIGNED:Psychiatric disturbances are common in epilepsy and are associated with increased risk of premature mortality, lower quality of life, and poor response to antiseizure medications (ASMs). OBJECTIVE/UNASSIGNED:To evaluate the role of psychiatric disturbances at the time of epilepsy diagnosis in predicting risk of future treatment resistance in focal epilepsy. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:The Human Epilepsy Project (HEP) is a prospective, observational, international, and multicenter cohort study with follow-up for up to 6 years. Participants with newly diagnosed focal epilepsy, enrolled within 4 months of initiating ASM treatment, between the ages 18 and 60 years, and without significant other comorbidities were recruited during the open period of 2012 to 2020. Data analysis was performed from January to September 2025. EXPOSURE/UNASSIGNED:Presence of a psychiatric diagnosis. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Presence of psychiatric diagnosis (mood/anxiety disorders) measured by Mini International Neuropsychiatric Interview (MINI) and/or suicidality measured by Columbia-Suicide Severity Rating Scale (C-SSRS) at enrollment. Treatment response included the following outcomes: treatment resistant (TR), defined as failure of first 2 adequate ASM trials (ongoing seizures at/above therapeutic doses); treatment sensitive (TS), defined by a minimum period of seizure freedom on first 2 adequate ASM trials (12 months/3-fold greatest pretreatment seizure-free interval, whichever is longer); and indeterminate (neither TR/TS). RESULTS/UNASSIGNED:Of 376 enrolled adults, 347 (median [IQR] age at seizure onset, 33 [23-44] years; 209 female [60.2%]) completed the MINI and C-SSRS at enrollment. Of these individuals, 191 (55%) were TS, 83 (24%) TR, and 73 (21%) indeterminate. The rate of psychiatric disturbance (mood/anxiety disorder; suicidality) at epilepsy diagnosis was 38% (n = 133). Fifty-seven (16%) had mood/anxiety disorder(s) without suicidality, and 75 (22%) expressed suicidality with or without a psychiatric disorder. Suicidality at epilepsy diagnosis was associated with greater than 2-fold risk of developing TR (relative risk [RR], 2.02; 95% CI, 1.32-3.09; P = .001). There were no significant overall associations between mood/anxiety disorders and TR. Suicidality alone significantly increased TR probability from 16.3% (95% CI, 11.3%-21.3%) in those with no psychiatric disturbance to 47.1% (RR, 2.89; 95% CI, 1.65-5.05; P < .001). Anxiety disorder alone increased TR probability to 32.9% (RR, 2.02; 95% CI, 1.10-3.71; P = .02), although this was not statistically significant after correcting for multiple comparisons. There was no significant change in TR probability when mood disorder alone was present; however, presence of mood disorder with suicidality increased TR probability to 39.6% (RR, 2.43; 95% CI, 1.26-4.68; P = .008). CONCLUSIONS AND RELEVANCE/UNASSIGNED:Results of this cohort study reveal that suicidality at the time of focal epilepsy diagnosis was associated with future drug resistance and may be a marker of more severe neuropathology. Psychiatric screening at time of diagnosis may facilitate early identification of patients at risk for treatment refractory epilepsy syndromes.

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: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.

Consumer wearable devices are commonly used by patients and consumers for several reasons with increasing application as new technologies are developed. Use of these devices is an emerging issue in Neurology because of increased adoption and the additional data reported to providers by patients. Understanding of possible functions, limitations, and effect on patients of non-US Food and Drug Administration (FDA)-cleared wearable technology to inform neurologic care is needed. A common theme in people with neurologic conditions regarding consumer wearables and associated tracking applications is that there is significant promise in these tools, but adherence (days per use/per week), continued engagement (attrition), and unintended consequences such as heightened anxiety remain important issues. Further understanding and validation of these devices is needed within the field of Neurology before full use and confidence can be achieved. Below, we provide examples of non-FDA-cleared wearable devices used in Neurology in the areas of epilepsy, headache, cardiac monitoring, and sleep.

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.