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OBJECTIVES: Delirium is common among patients with acute stroke and associated with worse outcomes. However, it is unclear which stroke locations or types are most associated with delirium. MATERIALS AND METHODS: We systematically reviewed studies of patients with acute stroke that reported stroke locations and types by delirium status. We included papers in any language, through a combined search from January 2010 to June 2021. Case studies with less than 20 patients, case-control studies, and randomized controlled trials were excluded. MEDLINE, EMBASE, PsycINFO, CINAHL, and Alois databases were searched. Pooled relative risks were calculated using bivariate random effects models or network metaanalysis. Methodological quality was assessed across 8 factors. RESULTS: 31 patient samples representing 8,329 patients were included. Delirium was more common in patients with supratentorial lesions than infratentorial (RR [Relative Risk] 2.01, CI [Confidence Interval] 1.49-2.72); anterior circulation lesions than posterior (RR 1.41, CI 1.13-1.78); and cortical lesions than subcortical (RR 1.54, CI 1.25-1.89). Stroke side was not associated with delirium (right vs. left: RR 0.99, CI 0.77-1.28). Delirium was more common in patients with hemorrhagic strokes than ischemic (RR 1.74, CI 1.42-2.11) and patients with preexisting qualitative atrophy (RR 1.66, CI 1.21-2.27). CONCLUSION: Several brain localizations and types of strokes were associated with delirium. Conclusions were in part limited by the heterogeneity of studies and broad or qualitative lesion descriptions. These results may assist in anticipating the risk of delirium in acute stroke and highlight brain networks and pathologies that may be involved in the pathophysiology of delirium.

BACKGROUND: The Systolic Blood Pressure Intervention Trial (SPRINT) randomized patients to a goal systolic blood pressure (SBP)

Aspirin is known to reduce stroke risk; however, its role in reducing severity of ischemic syndrome is not clear. We sought to investigate the relationship between antecedent aspirin use and stroke severity in patients presenting with acute ischemic stroke (AIS).We retrospectively analyzed a prospectively collected database of consecutive AIS patients presenting to our center. Clinical characteristics (including antecedent aspirin use), imaging findings, and laboratory data were assessed in association with presenting stroke severity, as measured by the National Institutes of Health Stroke Scale (NIHSS). Logistic regression models were used to determine univariate and multivariate predictors of baseline NIHSS.Of the 610 AIS patients with admission brain magnetic resonance imaging available for volumetric analysis of acute infarct size, 241 (39.5%) used aspirin prior to stroke onset. Antecedent aspirin use (P = .0005), history of atrial fibrillation (P .0001), acute infarct volume (P .0001), initial systolic blood pressure (P = .041), admission glucose level (P = .0027), and stroke subtype (P .0001) were associated with presenting stroke severity in univariate analysis. Antecedent aspirin use (P .0001), history of atrial fibrillation (P .0002), acute infarct volume (P .0001), systolic blood pressure (P = .038), and glucose level (P = .0095) remained independent predictors of NIHSS in multivariable analysis.Antecedent aspirin use was independently associated with milder presenting stroke severity, even after accounting for acute infarct volume. While the underlying biology of this apparent protective relationship requires further study, patients at high risk of stroke may benefit from routine aspirin use.

Background: African-Americans (AA) are 3 times more likely to have small-vessel-type ischemic strokes (SVS) than Whites. Small vessel strokes are associated with cognitive impairment, a relationship incompletely explained by white matter hyperintensity (WMH) burden. We examined whether inflammatory/endothelial dysfunction biomarkers are associated with cognition after SVS in AAs. Methods: Biomarkers were obtained in 24 subjects (median age 56.5 years, 54% women, median 12 years education). Cognition was assessed more than 6 weeks poststroke using the memory composite score (MCS), which was generated using recall from the Hopkins Verbal Learning Test-II and Brief Visuospatial Memory Test-Revised. A semi-automated, volumetric protocol was used to quantify WMH volume (WMHv) on clinical MRI scans. Potential biomarkers including vascular cell adhesion molecule-1 (VCAM-1), interleukin-1 receptor antagonist, interleukin-6, interleukin-8, interleukin-10, interferon gamma, and thrombin-antithrombin (TAT) were log-transformed and correlated with MCS with adjustment for potential confounders. Results: Among serum biomarkers, only VCAM-1-correlated with poorer memory based on the MCS (r = −.659; P = .0006). VCAM-1 (r = .554; P = .005) and age (r = .479; P = .018) correlated with WMHv; VCAM-1 was independently associated with MCS after adjustment for WMHv, age, and education (P = .023). Conclusions: The findings of this exploratory analysis suggest that endothelial dysfunction and inflammation as reflected by VCAM-1 levels may play a role in poststroke cognitive impairment. Additional studies are needed to validate this observation and to evaluate this relationship in non-AAs and with other stroke types and compare this finding to cognitive impairment in nonstroke populations.

Background: To investigate the effect of COX-2 polymorphism and its product, prostaglandin E2 (PGE2), on stroke risk in an endemic area for Chagas disease. In a separate cohort, to investigate the effect of COX-2 polymorphisms on the total burden of cerebral white matter disease. Methods: Cases were outpatients with ischemic stroke; controls were stroke-free subjects from 2 outpatient clinics (heart failure and caregivers of a movement disorders clinic). We extracted DNA from total blood to investigate the rs20417 COX-2 polymorphism. Serologic tests (Enzime-linked immunosorbent assay) were performed to confirm Trypanosoma cruzi infection and to quantify PGE2 levels. In the Boston cohort, white matter hyperintensity volume (WMHv) was quantified on the admission brain magnetic resonance images of subjects with ischemic stroke, who also donated DNA for the COX-2 gene region analysis. Results: We studied 44 patients with stroke and 96 controls (46 with heart failure and 50 caregivers) in the Brazilian cohort; and 788 stroke patients (302 cardioembolic and 486 noncardioembolic) in the Boston cohort. In the Brazilian cohort, rs20417 polymorphism was associated with both stroke (P 5 5 3 1026 ) and decreased PGE2 levels (P 5 4 3 1025 ); similarly, Chagas was associated with stroke (P 5 4 3 1023 ) and decreased PGE2 levels (P 5 7 3 1023 ). In the Boston cohort, rs20417 polymorphism was associated with increased WMHv among noncardioembolic (P 5.037), but not among cardioembolic stroke patients. Conclusions: Variation in COX-2 gene is associated with both symptomatic and silent brain cerebrovascular disease. This candidate gene region should be tested in population-based samples

Background Proximal artery occlusions (PAO) recanalize in only a small percentage of acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (IV tPA) alone, yet the benefits of adjunctive or substitutive intra-arterial therapy (IAT) in this patient subgroup are not well established. We evaluated early poststroke outcomes in a cohort of AIS patients with PAO categorized as "likely to benefit" (LTB) from IAT using prespecified criteria. Methods Using a prespecified protocol, 193 patients from our institutional stroke database admitted between January 1, 2007, and December 31, 2011, were prospectively deemed LTB from IAT. Logistic regression was used to determine independent predictors of favorable (discharge to home or acute rehabilitation) versus unfavorable (discharge to skilled nursing facility, hospice, or in-hospital mortality) outcome. Results Of the patients included, 29.5% received IV tPA only, 11.4% underwent IAT only, and 37.8% had both. Overall in-hospital mortality was 19.2%. In a univariate analysis, age (odds ratio [OR], .95; 95% confidence interval [CI], .93-.98), IV tPA (OR, 2.3; 95% CI, 1.2-4.3), and history of atrial fibrillation (OR, .5; 95% CI, .28-.97) were associated with outcome. Effect of IAT was not statistically significant (OR, 1.3; 95% CI, .7-2.3; P = .4). In multivariate analysis, the only independent predictor of favorable outcome was IV tPA administration (OR, 2.4; 95% CI, 1.2-5.0). The odds of favorable poststroke outcome were significantly lowered (OR, .3; 95% CI, .1-.6; P = .0006) in those receiving neither IV tPA nor IAT. Conclusions In AIS patients with PAO thought most likely to benefit from IAT, IV tPA independently predicted favorable outcomes. These data reinforce the recommendation to provide early IV tPA to all eligible patients.

White matter hyperintensity (WMH), a common radiographic finding associated with stroke risk and outcome, has been linked to matrix metalloproteinase (MMP) activity and increased levels of oxidative stress in nonstroke populations. We sought to determine whether WMH severity is associated with plasma levels of MMPs and oxidative stress (F2-isoprostane) in subjects with acute ischemic stroke (AIS).We measured plasma biomarker levels at baseline and 48 hours in consecutive AIS subjects. White matter hyperintensity volume (WMHv) was quantified on admission magnetic resonance imaging using a validated semiautomated protocol, and Spearman correlation coefficients were derived for all measured biomarkers.We enrolled 405 AIS subjects (mean age 70±15 years; 58% male; median WMHv 3.4 cm3, interquartile range 1.4-9.5). WMHv and age were strongly correlated (ρ=.57, P.0001). WMHv and MMP-2 levels were correlated at baseline (ρ=.23, P.0001) and at 48 hours poststroke (ρ=.19, P=.002). In multivariate analysis, 48-hour MMP-2 levels were independently associated with WMHv (β=.12, P=.04). MMP-9 and F2-isioprostane levels did not correlate with WMHv.In AIS patients, MMP-2 levels are associated with the pre-existing burden of WMH. If validated, these findings may further elucidate the role of MMP-2 in pathophysiology of chronic cerebrovascular injury, such as WMH, and in brain susceptibility to acute ischemia.

Background In elderly acute stroke patients, reperfusion therapy is often withheld. We sought to determine whether prestroke dementia contributed to poor outcomes after reperfusion therapy in these patients. Methods All consecutive patients ≥80 years of age who received intravenous (IV) or intra-arterial reperfusion therapy (IAT) were identified in our Get With the Guidelines Stroke (GWTG-S) database. Vascular risk factors, presence of dementia, and outcomes were abstracted from the medical record. Dementia was recorded when listed in the medical history or when under medical treatment. Primary outcome was in-hospital mortality. Secondary outcome was discharge destination, “favorable” (home or rehabilitation facility) versus “unfavorable” (skilled nursing facility, hospice, or death). Multivariate logistic regression models were used to assess outcomes. Results Of 153 patients, 72% received IV tissue plasminogen activator (tPA), 35% IAT, and 7% both. The mean age was 85.8 ± 4.6 years; 13.6% had prestroke dementia. The in-hospital mortality rate was 35%. The likelihood of death increased with National Institutes of Health Stroke Scale (NIHSS; odds ratio [OR] 1.14; 95% confidence interval [CI] 1.07-1.21), IAT (OR 3.43; 95% CI 1.70-6.92), and dementia (OR 3.61; 95% CI 1.39-9.37), and decreased with IV tPA (OR 0.34; 95% CI 0.17-0.71). Increasing NIHSS (OR 0.90; 95% CI 0.85-0.95), symptomatic intracranial hemorrhage (OR 0.08; 95% CI 0.01-0.67), IAT (OR 0.43; 95% CI 0.22-0.84), and dementia (OR 0.37; 95% CI 0.14-0.97) decreased the likelihood of favorable discharge. In multivariate analysis, only NIHSS (OR 1.13; 95% CI 1.06-1.22) and dementia (OR 5.64; 95% CI 1.88-16.89) independently predicted death and unfavorable discharge destination. Conclusions Among the elderly, prestroke dementia is a powerful independent predictor of in-hospital mortality after acute reperfusion therapy for stroke. Future investigations of thrombolysis outcomes in the elderly are warranted.