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Introduction: Large vessel occlusion-acute ischemic stroke (LVO-AIS) is infrequent in young adults and exhibits distinct stroke mechanisms compared to older adults. This study sought to evaluate the impact of varying stroke etiologies on treatment-related outcomes in young adults with LVO-AIS, an aspect that remains unclear., Methods: This retrospective cohort study included patients aged 18-50 presenting with AIS from January 2017 to December 2021 within our multi-center stroke network. Patients with LVO on CTA/MRA at presentation were included. We assessed demographics, stroke etiology (TOAST classification), and treatment-related outcomes. Based on intervention received, patients were divided into 5 groups [IV-thrombolysis (IVT) only, Mechanical Thrombectomy (MT) only, IVT+MT, no treatment, unsuccessful MT]., Results: Among 1210 AIS patients, 220 with LVO were included. The median age was 42 (36, 46). 75 (34.1 %) patients underwent successful MT (46.7 % received IVT+MT). 26 (11.8 %) received IVT only, 110 (50 %) received neither intervention, and 9 (4.1 %) underwent unsuccessful MT. Per TOAST, 17.4 % had large artery atherosclerosis (LAA), 19.2 % cardio-embolism, 28.6 % stroke of other etiology, and 34.7 % had undetermined etiology. Favorable thrombectomy outcomes (TICI 2b/2c/3) were observed in 87.2 %. Discharge NIH Stroke Scale (NIHSS) scores improved for patients with IVT+MT in all TOAST categories except LAA., Conclusions: Young adults with LVO-AIS had good outcomes irrespective of stroke etiology, except LAA, which was associated with a higher discharge NIHSS. Moreover, 50 % of young adults in our study received no intervention, a quarter of those owing to delayed presentation. Further studies are needed to identify barriers in seeking acute treatment in young adults with LVO-AIS., Competing Interests: Declaration of competing interest M. Shazam Hussain serves as a Core Lab Principal Investigator for ADVANCE, ELEVATE and INSPIRE trials for which funding is received. He also serves on the following advisory boards for Cerenovus, Stryker Neurovascular, Rapid Medical, and Kaneka. G. Abbas Kharal serves on the advisory board for Bayer. No disclosures for other authors., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Estimating change in health-related quality of life (HRQOL) from pre- to poststroke is challenging because HRQOL is rarely collected prior to stroke. Leveraging HRQOL data collected both before and after stroke, we sought to estimate the change in HRQOL from prestroke to early poststroke., Methods: Stroke survivors completed the Patient-Reported Outcomes Measurement Information System Global Health (PROMIS-GH) scale at both pre- and early poststroke. Patient characteristics were compared for those who did and did not complete the PROMIS-GH. The mean change in PROMIS-GH T-score was estimated using complete case analysis, multiple imputation, and multiple imputation with delta adjustment., Results: A total of 4,473 stroke survivors were included (mean age 63.1 ± 14.1 y, 47.5% female, 82.6% ischemic stroke). A total of 993 (22.2%) patients completed the PROMIS-GH at prestroke while 2,298 (51.4%) completed it early poststroke. Compared with those without PROMIS-GH, patients with PROMIS-GH prestroke had worse comorbidity burden. Patients who completed PROMIS-GH early poststroke had better early poststroke clinician-rated function and shorter hospital length of stay. Complete case analysis and multiple imputation revealed patients' PROMIS-GH T-scores worsened by 2 to 3 points. Multiple imputation with delta adjustment revealed patients' PROMIS-GH T-scores worsened by 4 to 10 points, depending on delta values chosen., Conclusions: Systematic differences in patients who completed the PROMIS-GH at both pre- and early poststroke suggest that missing PROMIS-GH scores may be missing not at random (MNAR). Multiple imputation with delta adjustment, which is better suited for MNAR data, may be a preferable method for analysis of change in HRQOL from pre- to poststroke. Given our study's large proportion of missing HRQOL data, future studies with less missing HRQOL data are necessary to verify our results., Highlights: Estimating the change in health-related quality of life from pre- to poststroke is challenging because health-related quality-of-life data are rarely collected prior to stroke. Previously used methods to assess the burden of stroke on health-related quality of life suffer from recall bias and selection bias.Using health-related quality-of-life data collected both before and after stroke, we sought to estimate the change in health-related quality of life after stroke using statistical methods that account for missing data.Comparisons of patients who did and did not complete health-related quality-of-life scales at both pre- and poststroke suggested that missing data may be missing not at random.Statistical methods that account for data that are missing not at random revealed more worsening in health-related quality of life after stroke than traditional methods such as complete case analysis or multiple imputation., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Seizures are a common clinical occurrence in high-grade glioma (HGG). While many studies have explored seizure incidence and prevalence in HGG, limited studies have examined the prognostic effect of seizures occurring in the post-diagnosis setting. This study aims to assess the impact of seizure presentation on HGG survival outcomes., Methods: Single-center retrospective review identified 950 patients with histologically-confirmed high-grade glioma. Seizure presentation was determined by clinical history and classified as early onset (occurring within 30 days of HGG presentation) or late onset (first seizure occurring after beginning HGG treatment). The primary outcome, hazard ratios for overall survival and progression-free survival, was assessed with multivariable Cox proportional-hazards models. IDH1 mutation status (assessed through immunohistochemistry) was only consistently available beginning in 2015; subgroup analyses were performed in the subset of patients with known IDH1 status., Results: Epileptic activity before (HR = 0.81, 95% CI = 0.68-0.96, P = 0.017) or after (HR = 0.74, 95% CI = 0.60-0.91, P = 0.005) HGG diagnosis associated with improved overall survival. Additionally, late seizure onset significantly associated with lower odds of achieving partial (OR = 0.25, 95% CI = 0.12-0.53, P = < 0.001) or complete (OR = 0.30, 95% CI = 0.18-0.50, P < 0.001) seizure control than patients with early seizure onset., Conclusions: Clinical seizures both at the time of diagnosis and later during the HGG treatment course are associated with improved overall survival. This association potentially persists for both IDH1-wildtype and IDH1-mutant patients, but further study is required., (© 2024. The Author(s).)

Background: Intracranial compliance refers to the relationship between changes in volume and the resultant changes in intracranial pressure (ICP). This study aimed to assess the agreement of a noninvasive ICP waveform device for the estimation of compliance compared with invasive ICP monitoring employing three distinct methods., Methods: We conducted a retrospective analysis of ICP waveform morphology recorded through both invasive (external ventricular drain) and noninvasive (mechanical extensometer) methods in adult patients with acute brain injury admitted to a neurointensive care unit between August 2021 and August 2022. Compliance was calculated as the amplitude of the fundamental component of cerebral arterial blood volume (estimated with concurrent Transcranial Doppler [TCD] recordings), divided by the amplitude of the fundamental component of the invasive and noninvasive ICP waveforms. Subsequently, we assessed the agreement between invasive and noninvasive intracranial compliance by repeated measures correlation coefficient analysis using three methods: TCD-derived, P2/P1 ratio, and time-to-peak (TTP). A linear mixed-effects model was used to compute the concordance correlation coefficient, total deviation index, and coefficient of individual agreement. Coverage probability plot was calculated to estimate the percent of observations within different cut points for each of the three methods., Results: A total of 21 patients were identified for this study. Repeated measures correlation analysis showed a strong correlation (R = 0.982, 95% confidence interval [0.980-0.984], p < 0.0001) between log-transformed noninvasive and invasive compliance. Agreement statistics for TCD, P2/P1 ratio, and TTP indicated that although the concordance correlation coefficient was highest for log(TCD) values, TTP and P2:P1 ratio measures had better agreement with total deviation index and coverage probability plot analyses., Conclusions: Repeated measures correlations suggest that ICP waveform analyses may offer a more accurate estimate of compliance than TCD-derived methods for noninvasive ICP monitoring. Further validations studies are warranted to confidently establish this method as an indicator of intracranial compliance., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background and Objectives: Adult neurology clinical trainees in Accreditation Council for Graduate Medical Education (ACGME)-accredited residency programs spend their postgraduate year (PGY)-1 within the internal medicine department, potentially causing a perceived disconnect with their neurology program. Our Adult Neurology Clinical Competency Committee found this disconnect may decrease resident well-being. We hypothesized implementing a novel PGY-1 Director role focusing on unique aspects of this first year would improve resident well-being and connection to the neurology program., Methods: The PGY-1 Director was established as an associate program director in the adult neurology residency program with goals to improve wellness, advocacy, compliance with ACGME requirements, education, and communication. Anonymous surveys compared preintervention (before the PGY-1 Director role) with postintervention resident opinions on PGY-1 experience, assessing wellness, burnout, and perception of advocacy., Results: A total of 15 (75%) preintervention residents and 23 (96%) postintervention residents completed the study surveys. 53.7% of preintervention residents agreed or strongly agreed to feeling burned out, while only 17.4% of postintervention residents agreed they felt burned out and none strongly agreed. Significant improvement occurred in feeling supported clinically and emotionally and feeling validated. Most postintervention residents felt the PGY-1 Director was valuable and directly led to positive change. The relationship between the neurology and internal medicine departments was improved., Discussion: A dedicated PGY-1 Director position can improve trainee wellness outcomes and relationships between preliminary and matched departments. This mutually benefits both programs but requires substantial resources. We propose this as a best practice when feasible for ACGME programs with the following suggestions: (1) provide dedicated full-time equivalent time, (2) meet with preliminary program leadership regularly, (3) meet with PGY-1 trainees during orientation and at least quarterly, (4) serve as an advocate, and (5) facilitate mentorship in areas of interest., Competing Interests: The authors report no relevant disclosures. Go to Neurology.org/N for full disclosures., (© 2024 American Academy of Neurology.)

Background: While sleep disorders are implicated in atrial fibrillation (AF), the interplay of physiologic alterations and symptoms remains unclear. Sleep-based phenotypes can account for this complexity and translate to actionable approaches to identify at-risk patients and therapeutic interventions., Objectives: This study hypothesized discrete phenotypes of symptoms and polysomnography (PSG)-based data differ in relation to incident AF., Methods: Data from the STARLIT (sleep Signals, Testing, And Reports LInked to patient Traits) registry on Cleveland Clinic patients (≥18 years of age) who underwent PSG from November 27, 2004, to December 30,2015, were retrospectively examined. Phenotypes were identified using latent class analysis of symptoms and PSG-based measures of sleep-disordered breathing and sleep architecture. Phenotypes were included as the primary predictor in a multivariable-adjusted Cox proportional hazard models for incident AF., Results: In our cohort (N = 43,433, age 51.8 ± 14.5 years, 51.9% male, 74.9% White), 7.3% (n = 3,166) had baseline AF. Over a 7.6- ± 3.4-year follow-up period, 8.9% (n = 3,595) developed incident AF. Five phenotypes were identified. The hypoxia subtype (n = 3,245) had 48% increased incident AF (HR: 1.48; 95% CI: 1.34-1.64), the apneas + arousals subtype (n = 4,592) had 22% increased incident AF (HR: 1.22; 95% CI: 1.10-1.35), and the short sleep + nonrapid eye movement subtype (n = 6,126) had 11% increased incident AF (HR: 1.11; 95% CI: 1.01-1.22) compared with long sleep + rapid eye movement (n = 26,809), the reference group. The hypopneas subtype (n = 2,661) did not differ from reference (HR: 0.89; 95% CI: 0.77-1.03)., Conclusions: Consistent with prior evidence supporting hypoxia as an AF driver and cardiac risk of the sleepy phenotype, this constellation of symptoms and physiologic alterations illustrates vulnerability for AF development, providing potential value in enhancing our understanding of integrated sleep-specific symptoms and physiologic risk of atrial arrhythmogenesis., Competing Interests: Funding Support and Author Disclosures This work was supported by a Transformative Neuroscience Research Resource Development Award funded by the Cleveland Clinic Foundation; a Neurological Institute Center for Outcomes Research and Evaluation Pilot Grant funded by the Cleveland Clinic Foundation; SMARRT (Supporting Multidisciplinary Achievement in Respiratory Research Training) grant T32HL155005 funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health; and Physician Scientist Training Grant 302-PA-23 funded by the American Academy of Sleep Medicine Foundation. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

We sought to quantify benzodiazepine prescribing by primary care providers from 2019 to 2020 and identify correlates of prescribing. We hypothesized prescribing would increase post-COVID-19 lockdown. We conducted a retrospective cohort study of adult patients with primary care visits in 2019 or 2020 in a large Ohio healthcare system. Demographics, diagnosis codes, and receipt of benzodiazepine prescriptions were collected. Using multivariable logistic regression, we examined factors associated with benzodiazepine prescription receipt during the whole study period and post-lockdown. 455,537 adult patients had 1,643,473 visits. Benzodiazepines were prescribed in 3.2% (53,049/1,643,473) of visits. Effect sizes for positive associations with benzodiazepine prescription were largest for anxiety disorders. For negative associations, they were largest for Black patients and patients with cocaine use disorder. Benzodiazepine prescribing was positively associated with multiple groups having contraindications, though effect sizes were small. Contrary to our hypothesis, odds of receiving a prescription were 8.8% lower post-lockdown. Benzodiazepine prescribing rates in our system compared favorably to national rates. Year over year odds of receiving a prescription were slightly lower post-lockdown. Racial disparities were present and deserve further study. Strategies to reduce benzodiazepine prescribing to patients with anxiety may yield the largest reductions for benzodiazepine prescribing in primary care settings.

Background: We aimed to investigate the prognostic factors associated with clinical outcomes in CV2/Collapsin response-mediator protein 5 (CRMP5)-IgG paraneoplastic neurologic disorders (PND)., Methods: This is a retrospective study of patients with CV2/CRMP5-IgG PND evaluated between 2002-2022. We examined the association of clinical variables (including age, clinical phenotype [autoimmune encephalopathy, myelopathy, polyneuropathy/radiculopathy, MG, cerebellar ataxia, chorea, optic neuropathy], cancer) with three clinical outcomes (wheelchair dependence, modified Rankin Scale [mRS], mortality) using univariate logistic regression and Cox proportional hazards modeling. Kaplan-Meier estimates were used to determine the probability of survival., Results: Twenty-seven patients (56% female) with CV2/CRMP5-IgG PND were identified with a median follow-up of 54 months (IQR = 11-102). An underlying tumor was identified in 15 patients (56%) including small cell lung cancer (SCLC) (8, [53%]), thymoma (4, [27%]), and other histologies (3, [20%]). At last follow-up, 10 patients (37%) needed a wheelchair for mobility and this outcome was associated with myelopathy (HR = 7.57, 95% CI = 1.87-30.64, P = 0.005). Moderate-severe mRS = 3-5 was associated with CNS involvement (encephalopathy, myelopathy, or cerebellar ataxia) (OR = 7.00, 95% CI = 1.18-41.36, P = 0.032). The probability of survival 4 years after symptom onset was 66%. Among cancer subtypes, SCLC (HR = 18.18, 95% CI = 3.55-93.04, P < 0.001) was significantly associated with mortality, while thymoma was not., Interpretation: In this retrospective longitudinal study of CV2/CRMP5-IgG PND, patients with CNS involvement, particularly myelopathy, had higher probability of disability. SCLC was the main determinant of survival in this population., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background and Objectives: Longitudinal outcomes in anti-NMDA receptor encephalitis (anti-NMDARe) are still not fully understood and may not be adequately captured with the modified Rankin Scale (mRS), often the sole reported outcome. We aim to characterize longitudinal outcomes in anti-NMDARe using multiple outcome measures., Methods: This single-center, retrospective, observational study examined outcome measures (mRS and Clinical Assessment Scale in Autoimmune Encephalitis [CASE]) in adults with NMDA receptor-IgG in CSF at short- and long-term follow-ups using linear and logistic regression modeling. Patients with evaluations for cognitive impairment (Montreal Cognitive Assessment/Mini-Mental State Examination), depression (Patient Health Questionnaire-9), and anxiety (General Anxiety Disorder-7) >6 months from symptom onset were correlated with final CASE scores., Results: Thirty-eight patients (76% female, median disease onset age = 28 years, range = 1-75 years) were included. The majority received first-line immunosuppressants (97%) at a median of 3.9 weeks (interquartile range [IQR] = 2.1-9.7) from symptom onset and 68% received second-line therapies. At baseline, median/mean mRS and CASE were 4 (IQR = 3-5) and 12.9 (SD = 7.2), respectively. At short-term follow-up (median = 10 weeks, IQR = 6-17), factors associated with higher CASE and mRS included dysautonomia, coma/lethargy, seizures/status epilepticus, and intensive care unit admission ( p < 0.05). At long-term follow-up (median = 70 weeks, IQR = 51-174), median/mean mRS and CASE were 2 (IQR = 1-3) and 4.4 (SD = 4.2), respectively. Only weakness at symptom onset predicted higher mRS scores (odds ratio = 5.6, 95% confidence interval 1.02-30.9, p = 0.047). Despite both mRS and CASE improving from baseline ( p < 0.001), only 9 patients (31%) returned to their premorbid function. Among patients with cognitive and mood evaluations >6 months from onset, moderate-severe cognitive impairment (42%), depression (28%), and anxiety (30%) were frequent. Cognitive and depression measures were associated with final CASE subscores (including memory, language, weakness, and psychiatric)., Discussion: Multiple clinical factors influenced short-term outcomes, but only onset weakness influenced long-term mRS, highlighting that mRS is predominantly affected by global motor function. Although mRS and CASE improved over time for most patients, these outcome measures did not capture the full extent of long-term functional impairment in terms of mood, cognition, and the ability to return to premorbid function. This emphasizes the need for increased utilization of more nuanced cognitive and mood outcome measures.

Background and Objectives: Most acute symptomatic seizure (ASyS) patients stay on antiseizure medications (ASM) long-term, despite low epilepsy development risk. The Post-Acute Symptomatic Seizure (PASS) clinic is a transition of care model for ASyS patients who individualize ASM management with the goal of a safe deprescription. We evaluated patients discharged on ASMs after a witnessed or suspected ASyS to analyze their PASS clinic visit attendance and its predictors., Methods: A single-center, retrospective cohort study of adults without epilepsy who were discharged from January 1, 2019, to September 30, 2019, on first-time ASMs due to witnessed or suspected ASyS (PASS clinic-eligible). We fit a cause-specific Cox proportional hazards model to analyze factors associated with PASS clinic attendance, which depends on survival in this patient population that has a high early postdischarge mortality (a competing risk). We checked for multicollinearity and the assumption of proportional hazards., Results: Among 307 PASS clinic-eligible patients, 95 (30.9%) attended the clinic and 136 (44.3%) died during a median follow-up of 14 months (interquartile range = 2-34). ASyS occurred in 60.2% (convulsive 47%; electrographic 26.7%) of patients. ASMs were continued in the absence of ASyS or epileptiform abnormalities (EAs) in 27% of patients. Multivariable analysis revealed that the presence of EAs (HR = 1.69, 95% CI 1.10-2.59), PASS clinic appointments provided before discharge (HR = 3.39, 95% CI 2.15-5.33), and less frequently noted ASyS etiologies such as autoimmune encephalitis (HR = 2.03, 95% CI 1.07-3.86) were associated with an increased clinic attendance rate. Medicare/Medicaid insurance (HR = 0.43, 95% CI 0.24-0.78, p = 0.005) and the presence of progressive brain injury (i.e., tumors; HR = 0.55, 95% CI 0.32-0.95, p = 0.032) were associated with reduced rate of PASS clinic attendance., Discussion: Our real-world data highlight the need for appropriate postdischarge follow-up of ASyS patients, which can be fulfilled by the PASS clinic model. Modest PASS clinic attendance can be significantly improved by adhering to a structured discharge planning process whereby appointments are provided before discharge. Future research comparing patient outcomes, specifically safe ASM discontinuation in a PASS clinic model to routine clinical care, is needed., Competing Interests: The authors report no relevant disclosures. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (© 2024 American Academy of Neurology.)