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Objective To determine the frequency and accuracy of diffusion restriction (DR) of the retina and/or optic nerve (ON) detection on standard brain magnetic resonance diffusion-weighted imaging (DWI-MRI) in patients presenting with acute non-arteritic central retinal artery occlusion (CRAO). Methods This is a retrospective case-control study that includes all consecutive patients presenting to our tertiary academic center from 2013-2021 with acute non-arteritic CRAO (cases) or acute ischemic stroke syndrome (controls, age and gender-matched) that had brain MRI performed within 14 days from symptom onset. Two neurology residents (junior and senior), a vascular neurologist, and two neuroradiologists, blinded to the site of CRAO, independently reviewed the brain MRIs to assess for the presence of retina and ON DR. The consensus agreement between the two neuroradiologists was used to perform sensitivity and specificity analyses and calculate inter-rater reliability (prevalence-adjusted bias-adjusted kappa coefficient). Results A total of 128 patients with acute non-arteritic CRAO (mean (SD) age 69 (14) years; 50% female; median time from CRAO to DW-MRI 2 days (IQR 1-5)) and 128 age and gender-matched controls with acute cerebral ischemia were included. After the neuroradiologist consensus, DR was correctly identified in the retina or ON in 51/128 (39.8%) CRAO cases, retina alone 27.3%, ON alone 24.2%, and both retina and ON 11.7%, with almost perfect neuroradiologists’ inter-rater reliability for retina (K = 0.91) and ON (K = 0.83). Among controls, the retina DR was identified in 1/128 (0.8%) and ON DR in 5/128 (3.9%). The sensitivity, specificity, positive predictive value, and negative predictive value were 28.1%, 99.2%, 97.3%, and 58.0% for retina DR, and 27.3%, 96.1%, 87.5%, and 56.9% for ON DR. Conclusions Though experienced neuroradiologists identified retina and ON DR with excellent inter-rater reliability, these are infrequent findings in real world CRAO practice, with excellent specificity but limited sensitivity. Prospective studies with larger cohort of patients, optimization of standardized orbit DWI-MRI protocols are needed to facilitate a more accurate and reliable identification of retina and ON DR in acute CRAO.

Background: Although no tests are currently available to predict post-stroke depression (PSD), a risk factor for diminished quality of life and stroke-related death, emerging evidence suggests that ischemic stroke (IS) may induce behavioral changes by damaging connections throughout the brain rather than via localized injury. Hypothesis: We sought to determine if active (surveys) and passive (accelerometer, GPS, and other sensors) smartphone data could quantify exploratory behavioral proxies of PSD. Methods: Thirty-four adults with a recent IS (n = 12) or transient ischemic attack (TIA) (n = 22) diagnosis were followed for 3 months. Participants used the Beiwe app to complete a weekly Patient Health Questionnaire-8 (PHQ-8) survey and were evaluated every 30 days with the Montgomery-Asberg Depression Rating Scale (MADRS). Results: Preliminary analysis of app survey compliance was adequate (86%), and the quantity of data collected was greater for Android than iOS phones. PHQ-8 indicated depression (moderate or severe) in 20% of participants. MADRS highly correlated with the most recent PHQ-8 ( r = 0.92, 95% CI (0.19, 0.99), P = 0.028). Several exploratory passive physical activity and social measures showed statistically significant change over time and/or associations with PHQ-8 and MADRS. Conclusion: Low-burden smartphone data holds promise for developing novel IS and TIA outcome measures as well as identifying patients most at risk of PSD.

Abstract BACKGROUND Leptomeningeal disease (LMD) carries poor prognosis with an average survival of 3-6 months after diagnosis. Ommaya reservoirs (OR) are an accessible alternative to serial lumbar punctures for delivery of intrathecal chemotherapy (IC) and disease monitoring but are not widely used. Intraventricular administration of chemotherapy may be associated with superior efficacy and improved patient comfort. The purpose of this study was to assess safety and efficacy of IC and disease monitoring via OR in routine clinical practice. MATERIAL AND METHODS Patients who received at least one administration of IC via OR for LMD between 2017 and 2022 were included. Demographics, treatment type, complications and outcomes were recorded. RESULTS We identified 22 patients (17 females, 5 males) with mean age 50.9 ± 14.8 years. The primary tumors were: breast (12), leukemia (3), ovarian carcinoma (3), CNS lymphoma (1), urothelial carcinoma (1), spinal melanocytoma (1), and high-grade glioma (1). A total of 208 OR injections were performed [median was 9 OR injections per patient, interquartile range (IQR) (5, 13)]. Five patients (23%) experienced mild adverse events of grade 2 or lower by Common Terminology Criteria for Adverse Events. Overall risk of adverse event from injection was 3.4% (7/208). Eight patients (36.3%) converted into negative CSF cytology (median 1 month following first injection), and 18 patients (82%) had clinical or radiological progression of their LMD (median 2 months following first injection). Eleven patients (50%) died of their LMD during follow-up. Median OS and PFS from the first injection were 5.3 months [95% CI 4.8-NE (not estimable)] and 4.3 months [95% CI 1.8-16.0], respectively. CONCLUSION Use of OR in routine clinical practice is a safe and feasible option and should be strongly considered for treatment and frequent disease monitoring of patients with LMD, especially in the era of circulating tumor cells analysis. The median OS in our cohort is comparable to prior published series.

Background Patients with atrial fibrillation (AF) are at increased risk of ischemic cerebrovascular events despite anticoagulants (AC). We aim to evaluate whether changing AC or adding antiplatelet therapy to anticoagulants (AP + AC) in patients with AF presenting with acute ischemic stroke (AIS) or transient ischemic attack (TIA) despite AC, decreases the risk of recurrent AIS/TIA compared to patients continued on same AC regimen. Methods Patients with AF on AC presenting with AIS or TIA at our center between 2011- 2021 were included. Data on Demographics, index event, antithrombotic therapy before and after index event, recurrent AIS/TIA, or major bleeding events (MBE) were extracted. Cox proportional hazards models were used to compare outcomes between AC unchange vs AC change, and AP + AC vs AC only groups. Results One hundred eighty-five patients were included (mean age 78.3 years; 62% males, median follow-up 9 months (IQR 1-34)). Seventeen patients (9%) had AC change, 100 (54%) received AP + AC, 39 (21%) had recurrent AIS/TIA, and 27 (15%) had MBE following index event. No difference was observed between AC unchange vs AC change and AP + AC vs AC only groups regarding recurrent AIS/TIA (HR 1.72 [.65-4.57], P = .27 and HR 1.02 [.53- 1.98], P = .95, respectively) or MBE (HR .85 [.19-3.67], P = .83 and HR 1.49 [.67-3.33)], P = .33, respectively). Fourteen vascular neurologists treated this cohort and 9(64%) implemented AC changes. Conclusion In this single center retrospective study of 185 patients with AF and AIS/TIA despite AC, changing AC or adding AP agents did not decrease the risk of ischemic cerebrovascular events.

Importance West Nile virus (WNV) is the leading cause of human arboviral disease in the US, peaking during summer. The incidence of WNV, including its neuroinvasive form (NWNV), is increasing, largely due to the expanding distribution of its vector, the Culex mosquito, and climatic changes causing heavy monsoon rains. However, the distinct characteristics and outcomes of NWNV in individuals who are immunosuppressed (IS) and individuals who are not IS remain underexplored. Objective To describe and compare clinical and radiographic features, treatment responses, and outcomes of NWNV infection in individuals who are IS and those who are not IS. Design, Setting, and Participants This retrospective cohort study used data from the Mayo Clinic Hospital system collected from July 2006 to December 2021. Participants were adult patients (age ≥18 years) with established diagnosis of NWNV infection. Data were analyzed from May 12, 2020, to July 20, 2023. Exposure Immunosuppresion. Main Outcomes and Measures Outcomes of interest were clinical and radiographic features and 90-day mortality among patients with and without IS. Results Of 115 participants with NWNV infection (mean [SD] age, 64 [16] years; 75 [66%] male) enrolled, 72 (63%) were not IS and 43 (37%) were IS. Neurologic manifestations were meningoencephalitis (98 patients [85%]), encephalitis (10 patients [9%]), and myeloradiculitis (7 patients [6%]). Patients without IS, compared with those with IS, more frequently reported headache (45 patients [63%] vs 18 patients [42%]) and myalgias (32 patients [44%] vs 9 patients [21%]). In contrast, patients with IS, compared with those without, had higher rates of altered mental status (33 patients [77%] vs 41 patients [57%]) and myoclonus (8 patients [19%] vs 8 patients [4%]). Magnetic resonance imaging revealed more frequent thalamic T2 fluid-attenuated inversion recovery hyperintensities in individuals with IS than those without (4 patients [11%] vs 0 patients). Individuals with IS had more severe disease requiring higher rates of intensive care unit admission (26 patients [61%] vs 24 patients [33%]) and mechanical ventilation (24 patients [56%] vs 22 patients [31%]). The 90-day all-cause mortality rate was higher in the patients with IS compared with patients without IS (12 patients [28%] vs 5 patients [7%]), and this difference in mortality persisted after adjusting for Glasgow Coma Scale score (adjusted hazard ratio, 2.22; 95% CI, 1.07-4.27; P = .03). Individuals with IS were more likely to receive intravenous immunoglobulin than individuals without IS (12 individuals [17%] vs 24 individuals [56%]), but its use was not associated with survival (hazard ratio, 1.24; 95% CI, 0.50-3.09; P = .64). Conclusions and Relevance In this cohort study of individuals with NWNV infection, individuals with IS had a higher risk of disease complications and poor outcomes than individuals without IS, highlighting the need for innovative and effective therapies to improve outcomes in this high-risk population.

Objective: To assess whether diffusion restriction (DR) of the retina and optic nerve (ON) can be accurately and reliably identified on standard stroke protocol brain magnetic resonance diffusion-weighted imaging (DWI-MRI) in patients presenting with acute non-arteritic central retinal artery occlusion (CRAO). Background: Retinal DR (RDR) and ONDR in patients with acute non-arteritic CRAO have been described with various diagnostic accuracies and often identified by experienced neuroradiologists with fair inter-rater agreement. Methods: This retrospective case-control study included patients that presented to our academic center from 2013-2021 with acute non-arteritic CRAO or acute cerebral ischemia (controls, age and gender-matched) and had brain MRI performed within 14 days from symptom onset. Two neuroradiologists, blinded to the site of CRAO and diagnosis, independently reviewed MRI of CRAO cases and controls to assess for the presence of RDR and ONDR. Their inter-rater agreement was calculated (prevalence and bias- adjusted kappa coefficient) and their final consensus was used to perform sensitivity and specificity analyses. Results: We included 128 patients with CRAO (mean age 69 years; 50% males; median time from CRAO to MRI 2 days (IQR 1-5)) and 128 matched controls with acute cerebral ischemia (mean age 68 years; 51% males). After neuroradiologists’ consensus, DR was correctly identified in the retina or ON in 51/128 (39.8%), retina alone 35/128 (27.3%), ON alone 31/128 (24.2%), both retina and ON 15/128 (11.7%), with excellent inter-rater agreement for retina (K=0.91) and ON (K=0.83). There were no cases of RDR or ONDR in the control group. After neuroradiologists’ consensus, sensitivity, specificity, PPV and NPV were 28.1%, 100%, 100%, and 58.2% for RDR and 27.3%, 100%, 100%, and 57.9% for ONDR. Conclusion: Though RDR and ONDR can be identified with excellent interrater reliability, they are infrequent findings and their role in diagnosing acute CRAO is unclear. Observational prospective studies with large cohort of patients, optimization of dedicated and standardized orbit DWI-MRI protocols, and education of neurology and neuroradiology providers are needed to facilitate more accurate identification of RDR and ONDR in hyperacute CRAO.