Isolated Optic Neuritis: Etiology, Characteristics, and Outcomes in a US Mountain West Cohort.

BACKGROUND: The diagnosis and treatment of autoimmune optic neuritis (ON) has improved with the accessibility and reliability of aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibody testing, yet autoantibody-negative ON remains common. This study describes the demographic, clinical, and outcome data in patients with isolated ON across the pediatric and adult cohort. METHODS: A retrospective chart review of University of Utah Health patients with the International Classification of Diseases (ICD) code of ICD-9 377.30 (ON unspecified), ICD-9 377.39 (other ON), or ICD-10 H46 (ON) and at least 2 ophthalmologic evaluations were conducted between February 2011 and July 2023. Only isolated cases of ON without other brain or spinal demyelinating lesions were evaluated. Differences in demographic and clinical characteristics between AQP4, MOG, and Other-ON were determined. RESULTS: Of the 98 patients (15 children and 83 adults), 9 (9.2%) were positive for AQP4-IgG and 35 (35.7%) tested positive for MOG-IgG. Fifty-four were classified into Other-ON, of which 7 (13.0%) had recurrence or new demyelinating lesions during a median follow-up of 12.5 months-2 were ultimately diagnosed with recurrent isolated ON (RION), 1 with chronic relapsing inflammatory ON (CRION), 2 with multiple sclerosis, 1 with collapsin response-mediator protein (CRMP)-5-ON, and 1 with seronegative neuromyelitis optica spectrum disorder. Four patients were treated with long-term immunosuppressive therapy. No patients with RION or CRION had preceding infections; they had first recurrences of ON within 2 months. At presentation, AQP4-ON (75%) and MOG-ON (48.8%) had more severe vision loss (visual acuity <20/200) than Other-ON (23.2%, P = 0.01). At the 1-month follow-up, 93.0% of patients with MOG-ON and 89.3% of patients with Other-ON demonstrated a visual acuity ≥20/40, compared with only 50% of patients with AQP4-ON (P < 0.01). By the last follow-up, 37.5% of the AQP4-ON still exhibited visual acuity <20/40, including 25% who experienced severe vision loss (visual acuity <20/200). By contrast, over 95% of patients with MOG-ON and Other-ON maintained a visual acuity of ≥20/40. In our cohort, over a quarter of pediatric cases presented with simultaneous bilateral ON, 40% had a preceding infection, and 44.4% initially presented with a visual acuity <20/200. Two pediatric cases had recurrence, and both were MOG-ON. By their last follow-up, all pediatric cases had achieved a visual acuity of 20/40 or better. In addition, pediatric cases were more likely to exhibit disc edema compared with adult cases (100% vs 64%, P < 0.01). CONCLUSIONS: Despite recent advances in identification and availability of testing for AQP4-IgG and MOG-IgG, over half of patients who presented with isolated ON remained with an "idiopathic" diagnostic label. As more than 1 in 10 patients with AQP4-IgG and MOG-IgG negative ON experienced recurrence or develop new demyelinating lesions, clinicians should provide anticipatory guidance and closely monitor for potential long-term outcomes. In addition, it is crucial to re-evaluate the diagnosis in cases of poor recovery, ON recurrence, and the emergence of new neurological symptoms, as ON can often be the initial presentation of other conditions.

Post-Stroke Brain Health Monitoring and Optimization: A Narrative Review.

Significant advancements have been made in recent years in the acute treatment and secondary prevention of stroke. However, a large proportion of stroke survivors will go on to have enduring physical, cognitive, and psychological disabilities from suboptimal post-stroke brain health. Impaired brain health following stroke thus warrants increased attention from clinicians and researchers alike. In this narrative review based on an open timeframe search of the PubMed, Scopus, and Web of Science databases, we define post-stroke brain health and appraise the body of research focused on modifiable vascular, lifestyle, and psychosocial factors for optimizing post-stroke brain health. In addition, we make clinical recommendations for the monitoring and management of post-stroke brain health at major post-stroke transition points centered on four key intertwined domains: cognition, psychosocial health, physical functioning, and global vascular health. Finally, we discuss potential future work in the field of post-stroke brain health, including the use of remote monitoring and interventions, neuromodulation, multi-morbidity interventions, enriched environments, and the need to address inequities in post-stroke brain health. As post-stroke brain health is a relatively new, rapidly evolving, and broad clinical and research field, this narrative review aims to identify and summarize the evidence base to help clinicians and researchers tailor their own approach to integrating post-stroke brain health into their practices.

Modelling anticoagulation and health-related quality of life in those with atrial fibrillation: a secondary analysis of AFFIRM.

Associations of anticoagulation with primary endpoints in longitudinal studies are impacted by selection bias and time-varying covariates (e.g. comorbidities). We demonstrate how time-varying covariates and selection bias influence association estimates between anticoagulation and health-related quality of life (HRQoL) in patients with atrial fibrillation. We performed a secondary analysis of the Atrial Fibrillation Follow-up Investigation of Rhythm Management trial quality of life substudy. Dichotomized warfarin use was ascertained at the study baseline, 2 months later, and annually for up to 6 years. HRQoL was measured at every time point using a self-reported ordinal 5-point Likert-scale (lower score and lower odds ratio represents better health-related quality of life). Static and time-varying covariates were ascertained throughout the study period. Confounder-adjusted generalized mixed model and generalized estimating equation regressions were used to demonstrate traditional association estimates between anticoagulation and HRQoL. Inverse probability of treatment and censorship weights were used to ascertain the influence of time-varying confounding and selection bias. Age-stratified analysis (age ≥ 70 years) evaluated for effect modification. 656 individuals were included in the analysis, 601 on warfarin at baseline. The association of warfarin use with better HRQoL over time strengthened when accounting for time-varying confounding and selection bias (OR 0.30, 95% CI 0.14-0.55) compared to traditional analyses (OR 0.61, 95% CI 0.38-0.97), and was most pronounced in those ≥ 70 years upon stratified analysis. Anticoagulation is associated with higher HRQoL in patients with atrial fibrillation, with time-varying confounding and selection bias likely influencing longitudinal estimates in anticoagulation-HRQoL research.

Association of Blood Pressure Variability With Death and Discharge Destination Among Critically Ill Patients With and Without Stroke.

BACKGROUND AND OBJECTIVES: It is unclear whether blood pressure variability's (BPV) association with worse outcomes is unique to patients with stroke or a risk factor among all critically ill patients. We (1) determined whether BPV differed between patients with stroke and nonstroke patients, (2) examined BPV's associations with in-hospital death and favorable discharge destination in patients with stroke and nonstroke patients, and (3) assessed how minimum mean arterial pressure (MAP)-a correlate of illness severity and cerebral perfusion-affects these associations. METHODS: This is a retrospective analysis of adult intensive care unit patients hospitalized between 2001 and 2012 from the Medical Information Mart for Intensive Care III database. Confounder-adjusted logistic regressions determined associations between BPV, measured as SD and average real variability (ARV), and (1) in-hospital death and (2) favorable discharge, with testing of minimum MAP for effect modification. RESULTS: BPV was higher in patients with stroke (N = 2,248) compared with nonstroke patients (N = 9,085) (SD mean difference 2.3, 95% CI 2.1-2.6, p < 0.01). After adjusting for minimum tertile of MAP and other confounders, higher SD remained significantly associated (p < 0.05) with higher odds of in-hospital death for patients with acute ischemic strokes (AISs, odds ratio [OR] 2.7, 95% CI 1.5-4.8), intracerebral hemorrhage (ICH, OR 2.6, 95% CI 1.6-4.3), subarachnoid hemorrhage (SAH, OR 3.4, 95% CI 1.2-9.3), and pneumonia (OR 1.9, 95% CI 1.1-3.3) and lower odds of favorable discharge destination in patients with ischemic stroke (OR 0.3, 95% CI 0.2-0.6) and ICH (OR 0.4, 95% CI 0.3-0.6). No interaction was found between minimum MAP tertile with SD (p > 0.05). Higher ARV was not significantly associated with increased risk of death in any condition when adjusting for illness severity but portended worse discharge destination in those with AIS (OR favorable discharge 0.4, 95% CI 0.3-0.7), ICH (OR favorable discharge 0.5, 95% CI 0.3-0.7), sepsis (OR favorable discharge 0.8, 95% CI 0.6-1.0), and pneumonia (OR favorable discharge 0.5, 95% CI 0.4-0.8). DISCUSSION: BPV is higher and generally associated with worse outcomes among patients with stroke compared with nonstroke patients. BPV in patients with AIS and patients with ICH may be a marker of central autonomic network injury, although clinician-driven blood pressure goals likely contribute to the association between BPV and outcomes.

Evidence for Age Bias Contributing to Therapeutic Inertia in Blood Pressure Management: A Secondary Analysis of SPRINT.

BACKGROUND: Despite evidence supporting the cardiovascular and cognitive benefits of intensive blood pressure management, older adults have the lowest rates of blood pressure control. We determined the association between age and therapeutic inertia (TI) in SPRINT (Systolic Blood Pressure Intervention Trial), and whether frailty, cognitive function, or gait speed moderate or mediate these associations. METHODS: We performed a secondary analysis of SPRINT of participant visits with blood pressure above randomized treatment goal. We categorized baseline age as <60, 60 to <70, 70 to <80, and ≥80 years and TI as no antihypertensive medication intensification per participant visit. Generalized estimating equations generated odds ratios for TI associated with age, stratified by treatment group based on nested models adjusted for baseline frailty index score (fit [frailty index, ≤0.10], less fit [0.100.10). CONCLUSIONS: Older age is associated with greater TI independent of physical or cognitive function, implying age bias in hypertension management.

Acute Ischemic Stroke Interventions in the United States and Racial, Socioeconomic, and Geographic Disparities.

BACKGROUND AND OBJECTIVES: In patients with ischemic stroke (IS), IV alteplase (tissue plasminogen activator [tPA]) and endovascular thrombectomy (EVT) reduce long-term disability, but their utilization has not been fully optimized. Prior research has also demonstrated disparities in the use of tPA and EVT specific to sex, race/ethnicity, socioeconomic status, and geographic location. We sought to determine the utilization of tPA and EVT in the United States from 2016-2018 and if disparities in utilization persist. METHODS: This is a retrospective, longitudinal analysis of the 2016-2018 National Inpatient Sample. We included adult patients who had a primary discharge diagnosis of IS. The primary study outcomes were the proportions who received tPA or EVT. We fit a multivariate logistic regression model to our outcomes in the full cohort and also in the subset of patients who had an available baseline National Institutes of Health Stroke Scale (NIHSS) score. RESULTS: The full cohort after weighting included 1,439,295 patients with IS. The proportion who received tPA increased from 8.8% in 2016 to 10.2% in 2018 (p < 0.001) and who had EVT from 2.8% in 2016 to 4.9% in 2018 (p < 0.001). Comparing Black to White patients, the odds ratio (OR) of receiving tPA was 0.82 (95% confidence interval [CI] 0.79-0.86) and for having EVT was 0.75 (95% CI 0.70-0.81). Comparing patients with a median income in their zip code of ≤$37,999 to >$64,000, the OR of receiving tPA was 0.81 (95% CI 0.78-0.85) and for having EVT was 0.84 (95% CI 0.77-0.91). Comparing patients living in a rural area to a large metro area, the OR of receiving tPA was 0.48 (95% CI 0.44-0.52) and for having EVT was 0.92 (95% CI 0.81-1.05). These associations were largely maintained after adjustment for NIHSS, although the effect size changed for many of them. Contrary to prior reports with older datasets, sex was not consistently associated with tPA or EVT. DISCUSSION: Utilization of tPA and EVT for IS in the United States increased from 2016 to 2018. There are racial, socioeconomic, and geographic disparities in the accessibility of tPA and EVT for patients with IS, with important public health implications that require further study.

Biopsy-proven PML in an HIV-negative patient with discoid lupus: Failure to detect JC virus in CSF.

We present a case of a 58-year-old man with a history of severe discoid lupus erythematosus and acute encephalopathy and incoordination. Antinuclear antibody testing was weakly positive but all other laboratory tests for systemic lupus erythematosus were negative and serum quantitative immunoglobulins and lymphocytes were normal. MRI brain showed T2/FLAIR hyperintensities within the bilateral parietal and temporal lobes with involvement of subcortical U fibers. CSF PCR was negative for varicella-zoster virus, herpes simplex, JCV and BK virus. However, JCV antibody index was elevated (3.88; reference: < 0.2). Right parietal brain biopsy was consistent with JCV infection and diagnostic of progressive multifocal leukoencephalopathy (PML). To the best of our knowledge, this is the first reported case of PML in a patient with discoid lupus without other traditional risk factors for the disease and highlights the need for clinical vigilance in this patient population.

Midlife Blood Pressure Variability and Risk of All-Cause Mortality and Cardiovascular Events During Extended Follow-up.

BACKGROUND: Studies demonstrate an association between visit-to-visit blood pressure variability (BPV) and cardiovascular events and death. We aimed to determine the long-term cardiovascular and mortality effects of BPV in midlife in participants with and without cardiovascular risk factors. METHODS: This is a post-hoc analysis of the Atherosclerosis Risk in the Community study. Long-term BPV was derived utilizing mean systolic blood pressure at Visits 1-4 (Visit 1: 1987-1989, Visit 2: 1990-1992, Visit 3: 1993-1995, Visit 4: 1996-1998). The primary outcome was mortality from Visit 4 to 2016 and secondary outcome was cardiovascular events (fatal coronary heart disease, myocardial infarction, cardiac procedure, or stroke). We fit Cox proportional hazards models and also performed the analysis in a subgroup of cardiovascular disease-free patients without prior stroke, myocardial infarction, congestive heart failure, hypertension, or diabetes. RESULTS: We included 9,578 participants. The mean age at the beginning of follow-up was 62.9 ± 5.7 years, and mean follow-up was 14.2 ± 4.5 years. During follow-up, 3,712 (38.8%) participants died and 1,721 (n = 8,771, 19.6%) had cardiovascular events. For every SD higher in systolic residual SD (range 0-60.5 mm Hg, SD = 5.6 mm Hg), the hazard ratio for death was 1.09 (95% confidence interval [CI] 1.05-1.12) and for cardiovascular events was 1.00 (95% CI 0.95-1.05). In cardiovascular disease-free participants (n = 4,452), the corresponding hazard ratio for death was 1.12 (95% CI 1.03-1.21) and for cardiovascular events was 1.01 (95% CI 0.89-1.14). CONCLUSION: Long-term BPV during midlife is an independent predictor of later life mortality but not cardiovascular events.

Association of Neighborhood Socioeconomic Status With Outcomes in Patients Surviving Stroke.

OBJECTIVE: To examine associations between neighborhood socioeconomic status (nSES) and 90-day poststroke outcomes. METHODS: The Brain Attack Surveillance in Corpus Christi Project is a population-based surveillance study in Nueces County, Texas. Patients with strokes were identified between 2010 and 2016 via active and passive surveillance and enrolled in the study. nSES index is a standardized composite of 2010 Census tract-level income, wealth, education, and employment (median -4.56, interquartile range -7.48 to -0.46). The 90-day outcomes were ascertained via interview: functional status measured by the average of 22 activities of daily living/instrumental activities of daily living (range 1-4), biopsychosocial health by the Stroke-Specific Quality of Life scale (range 0-5), and depressive symptoms by the 8-item Patient Health Questionnaire (range 0-24). Associations between nSES and outcomes were estimated using confounder-adjusted generalized estimating equations with an nSES × NIH Stroke Scale score interaction term. RESULTS: Seven hundred seventy-six survivors made up the analytical sample (52.96% male, 62.24% Mexican American, 52.96% ≥64 years old). Higher compared to lower nSES (mean difference comparing 75th to 25th percentile of nSES) was associated with better function (-0.27, 95% confidence interval [CI] -0.49 to -0.05), better biopsychosocial health (0.26, 95% CI 0.06-0.47), and fewer depressive symptoms (-1.77, 95% CI -3.306 to -0.48) among those with moderate to severe strokes. Among those with minor strokes, higher nSES was associated with better function (-0.13, 95% CI -0.24 to -0.02). CONCLUSIONS: nSES may influence poststroke recovery. Studies should identify neighborhood characteristics that contribute to poststroke outcomes, particularly in moderate to severe stroke survivors.

Association of Preeclampsia With Incident Stroke in Later Life Among Women in the Framingham Heart Study.

Importance: Contemporary research suggests an association between preeclampsia and later-life stroke among women. To our knowledge, no research to date has accounted for the time-varying nature of shared risk factors for preeclampsia and later-life stroke incidence. Objective: To assess the relative risk of incident stroke in later life among women with and without a history of preeclampsia after accounting for time-varying covariates. Design, Setting, and Participants: This population-based cohort study was a secondary analysis of data from the Framingham Heart Study, which was conducted from 1948 to 2016. Women were included in the analysis if they were stroke free at enrollment and had a minimum of 3 study visits and 1 pregnancy before menopause, hysterectomy, or age 45 years. Data on vascular risk factors, history of preeclampsia, and stroke incidence were collected biannually. Participants were followed up until incident stroke or censorship from the study. Marginal structural models were used to evaluate the relative risk of incident stroke among participants with and without a history of preeclampsia after accounting for time-varying covariates. Data were analyzed from May 2019 to December 2020. Exposures: Presence or absence of preeclampsia among women with 1 or more pregnancies. Main Outcomes and Measures: Incident stroke in later life. Results: A total of 1435 women (mean [SD] age, 44.4 [7.7] years at the beginning of the study; 100% White) with 41 422 person-years of follow-up were included in the analytic sample. Of those, 169 women had a history of preeclampsia, and 231 women experienced strokes during follow-up. At baseline, women with preeclampsia were more likely to be younger, to be receiving cholesterol-lowering medications, to have lower cholesterol and higher diastolic blood pressure, and to currently smoke. The association between preeclampsia and stroke in the marginal structural model was only evident when adjustment was made for all vascular risk factors over the life course, which indicated that women with a history of preeclampsia had a higher risk of stroke in later life compared with women without a history of preeclampsia (relative risk, 3.79; 95% CI, 1.24-11.60). Conclusions and Relevance: The findings of this cohort study suggest that preeclampsia may be a risk factor for later-life stroke among women after adjustment for time-varying vascular and demographic factors. Future research is warranted to fully explore the mediation of this association by midlife vascular risk factors.

Impact of COVID-19 on Outcomes in Ischemic Stroke Patients in the United States.

BACKGROUND: Studies have shown worse outcomes in patients with comorbid ischemic stroke (IS) and coronavirus disease 2019 (COVID-19), but have had small sample sizes. METHODS: We retrospectively identified patients in the Vizient Clinical Data Base® with IS as a discharge diagnosis. The study outcomes were in-hospital death and favorable discharge (home or acute rehabilitation). In the primary analysis, we compared IS patients with laboratory-confirmed COVID-19 (IS-COVID) discharged April 1-July 31, 2020 to pre-COVID IS patients discharged in 2019 (IS controls). In a secondary analysis, we compared a matched cohort of IS-COVID patients to patients within the IS controls who had pneumonia (IS-PNA), created with inverse-probability-weighting (IPW). RESULTS: In the primary analysis, we included 166,586 IS controls and 2086 IS-COVID from 312 hospitals in 46 states. Compared to IS controls, IS-COVID were less likely to have hypertension, dyslipidemia, or be smokers, but more likely to be male, younger, have diabetes, obesity, acute renal failure, acute coronary syndrome, venous thromboembolism, intubation, and comorbid intracerebral or subarachnoid hemorrhage (all p<0.05). Black and Hispanic patients accounted for 21.7% and 7.4% of IS controls, respectively, but 33.7% and 18.5% of IS-COVID (p<0.001). IS-COVID, versus IS controls, were less likely to receive alteplase (1.8% vs 5.6%, p<0.001), mechanical thrombectomy (4.4% vs. 6.7%, p<0.001), to have favorable discharge (33.9% vs. 66.4%, p<0.001), but more likely to die (30.4% vs. 6.5%, p<0.001). In the matched cohort of patients with IS-COVID and IS-PNA, IS-COVID had a higher risk of death (IPW-weighted OR 1.56, 95% CI 1.33-1.82) and lower odds of favorable discharge (IPW-weighted OR 0.63, 95% CI 0.54-0.73). CONCLUSIONS: Ischemic stroke patients with COVID-19 are more likely to be male, younger, and Black or Hispanic, with significant increases in morbidity and mortality compared to both ischemic stroke controls from 2019 and to patients with ischemic stroke and pneumonia.

Endovascular thrombectomy in acute ischemic stroke patients with COVID-19: prevalence, demographics, and outcomes.

BACKGROUND: We aimed to compare the outcome of acute ischemic stroke (AIS) patients who received endovascular thrombectomy (EVT) with confirmed COVID-19 to those without. METHODS: We performed a retrospective analysis using the Vizient Clinical Data Base and included hospital discharges from April 1 to July 31 2020 with ICD-10 codes for AIS and EVT. The primary outcome was in-hospital death and the secondary outcome was favorable discharge, defined as discharge home or to acute rehabilitation. We compared patients with laboratory-confirmed COVID-19 to those without. As a sensitivity analysis, we compared COVID-19 AIS patients who did not undergo EVT to those who did, to balance potential adverse events inherent to COVID-19 infection. RESULTS: We identified 3165 AIS patients who received EVT during April to July 2020, in which COVID-19 was confirmed in 104 (3.3%). Comorbid COVID-19 infection was associated with younger age, male sex, diabetes, black race, Hispanic ethnicity, intubation, acute coronary syndrome, acute renal failure, and longer hospital and intensive care unit length of stay. The rate of in-hospital death was 12.4% without COVID-19 vs 29.8% with COVID-19 (P<0.001). In mixed-effects logistic regression that accounted for patient clustering by hospital, comorbid COVID-19 increased the odds of in-hospital death over four-fold (OR 4.48, 95% CI 3.02 to 6.165). Comorbid COVID-19 was also associated with lower odds of a favorable discharge (OR 0.43, 95% CI 0.30 to 0.61). In the sensitivity analysis, comparing AIS patients with COVID-19 who did not undergo EVT (n=2139) to the AIS EVT patients with COVID-19, there was no difference in the rate of in-hospital death (30.6% vs 29.8%, P=0.868), and AIS EVT patients had a higher rate of favorable discharge (32.4% vs 47.1%, P=0.002). CONCLUSION: In AIS patients treated with EVT, comorbid COVID-19 infection was associated with in-hospital death and a lower odds of favorable discharge compared with patients without COVID-19, but not compared with AIS patients with COVID-19 who did not undergo EVT. AIS EVT patients with COVID-19 were younger, more likely to be male, have systemic complications, and almost twice as likely to be black and over three times as likely to be Hispanic.

Sex difference in prevalence of depression after stroke.

OBJECTIVE: This study investigated the sex difference in prevalence of depression at 90 days after first-ever stroke. METHODS: Patients with first-ever stroke (n = 786) were identified from the population-based Brain Attack Surveillance in Corpus Christi project (2011-2016). Poststroke depressive symptoms were assessed by the 8-item Patient Health Questionnaire, and prestroke depression status (history and medication use) was self-reported. Logistic regression was used to examine the association between sex and depression after stroke, and effect modification by prestroke depression status, accounting for missing data. RESULTS: Women were more likely to have a history of and be on medication for depression at the time of stroke than men (p < 0.001). Prevalence of depression at 90 days was 28.2% for men (95% confidence interval [CI], 23.7%-32.8%) and 32.7% for women (95% CI, 27.8%-37.5%). The age-adjusted odds ratio (OR) of depression after stroke comparing women and men was 1.34 (95% CI, 0.97-1.85), and fully attenuated after adjustment for sociodemographic, stroke, and prestroke characteristics. Effect modification by prestroke depression status was present (p = 0.038). Among participants on medication for depression at the time of stroke, women were significantly less likely to have depression at 90 days compared with men (OR, 0.39; 95% CI, 0.16-0.96), whereas significant sex differences were not noted among those with and without a depression history. CONCLUSION: The sex difference in prevalence of depression at 90 days after first-ever stroke was not significant overall, but varied by prestroke depression status. Interventions to address and prevent poststroke depression are needed, particularly among those with prestroke depression but not undergoing treatment for depression at stroke onset.