Introduction
Current recommendations for regional stroke destination suggest that patients with severe acute stroke in non‐urban areas should be triaged based on the estimated transport time to a ...referral thrombectomy‐capable center.
Methods
We performed a post hoc analysis to evaluate the association of pre‐hospital workflow times with neurological outcomes in patients included in the RACECAT trial. Workflow times evaluated were known or could be estimated before transport allocation. Primary outcome was the shift analysis on the modified Rankin score at 90 days.
Results
Among the 1,369 patients included, the median time from onset to emergency medical service (EMS) evaluation, the estimated transport time to a thrombectomy‐capable center and local stroke center, and the estimated transfer time between centers were 65 minutes (interquartile ratio IQR = 43–138), 61 minutes (IQR = 36–80), 17 minutes (IQR = 9–27), and 62 minutes (IQR = 36–73), respectively. Longer time intervals from stroke onset to EMS evaluation were associated with higher odds of disability at 90 days in the local stroke center group (adjusted common odds ratio (acOR) for each 30‐minute increment = 1.03, 95% confidence interval CI = 1.01–1.06), with no association in the thrombectomy‐capable center group (acOR for each 30‐minute increment = 1.01, 95% CI = 0.98–1.01, pinteraction = 0.021). No significant interaction was found for other pre‐hospital workflow times. In patients evaluated by EMS later than 120 minutes after stroke onset, direct transport to a thrombectomy‐capable center was associated with better disability outcomes (acOR = 1.49, 95% CI = 1.03–2.17).
Conclusion
We found a significant heterogeneity in the association between initial transport destination and neurological outcomes according to the elapse of time between the stroke onset and the EMS evaluation (ClinicalTrials.gov: NCT02795962). ANN NEUROL 2022;92:931–942
OBJECTIVEWe tested the hypothesis that the risk of intracranial hemorrhage (ICH) in patients with cardioembolic ischemic stroke who are treated with oral anticoagulants (OAs) can be predicted by ...evaluating surrogate markers of hemorrhagic-prone cerebral angiopathies using a baseline MRI.
METHODSPatients were participants in a multicenter and prospective observational study. They were older than 64 years, had a recent cardioembolic ischemic stroke, and were new users of OAs. They underwent a baseline MRI analysis to evaluate microbleeds, white matter hyperintensities, and cortical superficial siderosis. We collected demographic variables, clinical characteristics, risk scores, and therapeutic data. The primary endpoint was ICH that occurred during follow-up. We performed bivariate and multivariate Cox regression analyses.
RESULTSWe recruited 937 patients (aged 77.6 ± 6.5 years; 47.9% were men). Microbleeds were detected in 207 patients (22.5%), moderate/severe white matter hyperintensities in 419 (45.1%), and superficial siderosis in 28 patients (3%). After a mean follow-up of 23.1 ± 6.8 months, 18 patients (1.9%) experienced an ICH. In multivariable analysis, microbleeds (hazard ratio 2.7, 95% confidence interval CI 1.1–7, p = 0.034) and moderate/severe white matter hyperintensities (hazard ratio 5.7, 95% CI 1.6–20, p = 0.006) were associated with ICH (C index 0.76, 95% CI 0.66–0.85). Rate of ICH was highest in patients with both microbleed and moderate/severe WMH (3.76 per 100 patient-years, 95% CI 1.62–7.4).
CONCLUSIONPatients taking OAs who have advanced cerebral small vessel disease, evidenced by microbleeds and moderate to severe white matter hyperintensities, had an increased risk of ICH. Our results should help to determine the risk of prescribing OA for a patient with cardioembolic stroke.
CLINICALTRIALS.GOV IDENTIFIERNCT02238470.
In experimental animals, the presence of brain-derived constituents in cervical lymph nodes has been associated with the activation of local lymphocytes poised to minimize the inflammatory response ...after acute brain injury. In this study, we assessed whether this immune crosstalk also existed in stroke patients. We studied the clinical course, neuroimaging, and immunoreactivity to neuronal derived Ags (microtubule-associated protein-2 and N-methyl d-aspartate receptor subunit NR-2A), and myelin-derived Ags (myelin basic protein and myelin oligodendrocyte glycoprotein) in palatine tonsils and cervical lymph nodes of 28 acute stroke patients and 17 individuals free of neurologic disease. Stroke patients showed greater immunoreactivity to all brain Ags assessed compared with controls, predominantly in T cell zones. Most brain immunoreactive cells were CD68(+) macrophages expressing MHC class II receptors. Increased reactivity to neuronal-derived Ags was correlated with smaller infarctions and better long-term outcome, whereas greater reactivity to myelin basic protein was correlated with stroke severity on admission, larger infarctions, and worse outcome at follow-up. Patients also had more CD69(+) T cells than controls, indicative of T cell activation. Overall, the study showed in patients with acute stroke the presence of myelin and neuronal Ags associated with lymph node macrophages located near activated T cells. Whether the outcome of acute stroke is influenced by Ag-specific activation of immune responses mediated by CD69 lymphocytes deserves further investigation.
The number of circulating monocytes increases after stroke. In this study, we assessed the time course and phenotype of monocyte subsets and their relationship with the clinical course and outcome in ...46 consecutive stroke patients and 13 age-matched controls. The proportion of the most abundant ‘classical’ CD14highCD16 monocytes did not change after stroke, whereas that of CD14highCD16+ monocytes increased and CD14dimCD16+ monocytes decreased. CD14highCD16 + monocytes had the highest expression of TLR2, HLA-DR and the angiogenic marker, Tie-2; CD14dimCD16+ monocytes had the highest expression of costimulatory CD86 and adhesion molecule CD49d. Platelet-monocyte interactions were highest in CD14highCD16 monocytes and lowest in CD14dimCD16+ monocytes. In adjusted models, 1/CD14highCD16 monocytes were associated with poor outcome (OR: 1.38), higher mortality (OR: 1.40) and early clinical worsening (OR: 1.29); 2/CD14highCD16+ monocytes were inversely related to mortality (OR: 0.32); and 3/CD14dimCD16+ monocytes were inversely related to poor outcome (OR: 0.74) and infarction size (r= 0.45; P = 0.02). These results illustrate that the predominant monocyte subtype conveys harmful effects after stroke, which include stronger interaction with platelets. Alternatively, rarer subpopulations of monocytes are beneficial with a phenotype that could promote tissue repair and angiogenesis. Therefore, monitoring of monocyte subtypes may emerge as a useful tool at the bedside for stroke patients.
In-hospital stroke death rate is an important sanitary issue. Despite advances in the acute phase management of stroke patients, mortality and disability rates remain high. In aging populations and ...with different mortality between the sexes in general, the study of sex- and age-related differences becomes increasingly relevant for optimization of post-acute clinical care of stroke patients.
We designed a cohort follow-up study with 13,932 consecutive ischemic stroke (IS) patients from 19 Spanish hospitals. Data was obtained from the Spanish Stroke Registry; transient ischemic attacks and ages <18 years were excluded. Patients were organised by age group and sex. We compared female and male patient cohorts within and across age groups univariately and used multivariable logistic regression to adjust for confounders in differential in-hospital mortality.
The median (percentiles 2.5 and 97.5%) age was 78 (41-92) years old for women and 71 (41-92) for men. IS women were more likely to be older, to exhibit cardio-embolic aetiology, and less likely to have been admitted to a stroke unit or to have had a stroke code activated. Both pre-stroke modified Rankin Scale and National Institute of Health Stroke Scale (NIHSS) scores at admission increased significantly with age and were higher in women than those in men. Differences in distributions of common risk factors for IS and of in-hospital outcomes between women and men actually changed with patient's age. It is to be noted here that although there were no statistically significant differences (p > 0.05) between the sexes within any age group, in-hospital mortality appeared significantly higher in women than that in men when analysed overall, due to confounding. Death was more closely related to stroke in women than in men and occurred earlier. Although there were some age-specific sex differences between the predictors for in-hospital mortality, stroke severity measured by NIHSS was the main predictor of in-hospital mortality for both sexes. Topographic classifications - partial anterior circulatory infarct and total anterior circulatory infarct - were significant prognostic factors for men aged <60 years and for those in the 60-69 years range respectively.
Although most of our findings were consistent with previous studies, it is important to take into account and highlight differences in in-hospital mortality between the sex and age group. Not to account for age-related differences between the sexes can give false results that may mislead management decisions. As most deaths in women were related to stroke, it is important to improve their early management, stroke code activation, access to stroke units and/or revascularisation therapies, especially in the older age groups.
There is scarce evidence of the role of clinic and ambulatory BP indices, as well as blood pressure phenotypes in the prognosis of stroke survivors. We aimed to evaluate the association between ...ambulatory BP indices and mortality in patients with a previous stroke. Our study was an observational cohort study from individuals included in the Spanish Ambulatory Blood Pressure Registry from March 2004 to December 2014. The Cox model was used to estimate associations between usual clinic and ambulatory BP and mortality, adjusted for confounders and additionally for alternative measures of BP. Two thousand one hundred and eighty-three patients with a previous stroke were included. During a median of 9.2 years, 632 (28.9%) patients died: 236 (10.8%) from cardiovascular causes. In the confounder-adjusted model, clinic systolic BP was not associated with the risk of all-cause or cardiovascular mortality. In contrast, systolic BP indices obtained through ABPM (24 h, day and night) were all associated with all-cause and cardiovascular death. In the simultaneous adjustment of daytime and night-time systolic BP, only night-time systolic BP remained significantly associated with all-cause and cardiovascular death: HR 1.35 (95% CI 01.21-1.51) and 1.44 (1.20-1.72), respectively. For diastolic BP, only night-time BP was associated with all-cause and cardiovascular mortality: HR 1.32 (1.18-1.48) and 1.57 (1.31-1.88), respectively. According to the circadian pattern, a riser pattern was associated with all-cause and cardiovascular mortality: HR 1.49 (1.18-1.87) and 1.70 (1.14-2.52), respectively. In conclusion, in patients who have suffered a stroke, night-time BP is the BP estimate most closely associated with all-cause and cardiovascular mortality.There is scarce evidence of the role of clinic and ambulatory BP indices, as well as blood pressure phenotypes in the prognosis of stroke survivors. We aimed to evaluate the association between ambulatory BP indices and mortality in patients with a previous stroke. Our study was an observational cohort study from individuals included in the Spanish Ambulatory Blood Pressure Registry from March 2004 to December 2014. The Cox model was used to estimate associations between usual clinic and ambulatory BP and mortality, adjusted for confounders and additionally for alternative measures of BP. Two thousand one hundred and eighty-three patients with a previous stroke were included. During a median of 9.2 years, 632 (28.9%) patients died: 236 (10.8%) from cardiovascular causes. In the confounder-adjusted model, clinic systolic BP was not associated with the risk of all-cause or cardiovascular mortality. In contrast, systolic BP indices obtained through ABPM (24 h, day and night) were all associated with all-cause and cardiovascular death. In the simultaneous adjustment of daytime and night-time systolic BP, only night-time systolic BP remained significantly associated with all-cause and cardiovascular death: HR 1.35 (95% CI 01.21-1.51) and 1.44 (1.20-1.72), respectively. For diastolic BP, only night-time BP was associated with all-cause and cardiovascular mortality: HR 1.32 (1.18-1.48) and 1.57 (1.31-1.88), respectively. According to the circadian pattern, a riser pattern was associated with all-cause and cardiovascular mortality: HR 1.49 (1.18-1.87) and 1.70 (1.14-2.52), respectively. In conclusion, in patients who have suffered a stroke, night-time BP is the BP estimate most closely associated with all-cause and cardiovascular mortality.
Cerebral small vessel disease (cSVD) is associated with increased blood-brain barrier (BBB) permeability. We sought to evaluate whether arterial stiffness might be associated with BBB permeability in ...patients with cSVD. We assessed BBB permeability using Dynamic Contrast-Enhanced MRI (DCE-MRI) in 29 patients that had suffered a recent small subcortical infarct (RSSI). BBB permeability in the whole brain (WB), gray matter (GM) and white matter (WM) was assessed with the parameter Ktrans. We used ambulatory blood pressure monitoring to measure 24-h systolic blood pressure (24-h SBP), diastolic blood pressure (24-h DBP), and pulse wave velocity (24-h PWV) both after stroke and following a 2-year follow-up. The differences between both measurements were calculated as Δ24-h SBP, Δ24-h DBP and Δ24-h PWV. DCE-MRI was acquired at a median (IQR) of 24 (19-27) months after stroke. Median age was 66.7 (9.7) years, and 24 (83%) patients were men. Median (IQR) Δ24-h PWV was 0.3 (-0.1, 0.5) m/s. WB-Ktrans, GM-Ktrans, and WM-Ktrans were associated with Δ24-h PWV (Spearman's, r 95% CI, WB 0.651 0.363-0.839; GM 0.657 0.373-0.845, WM 0.5300.197-0.777) but not with Δ24-h SBP or Δ24-h DBP. These associations remained significant after adjustment with linear regression models, controlling for age, sex, body mass index, and Δ24-h SBP (b95% CI, WB 0.7250.384-1.127, GM 0.629 0.316-1.369, WM 0.865 0.455-0.892) or Δ24-h DBP (b95% CI, WM 0.707 0.370-1.103, GM 0.643 0.352-1.371, WM 0.772 0.367-0.834). Our results suggest that an increment on arterial stiffness in the months following a RSSI might increase BBB permeability.Cerebral small vessel disease (cSVD) is associated with increased blood-brain barrier (BBB) permeability. We sought to evaluate whether arterial stiffness might be associated with BBB permeability in patients with cSVD. We assessed BBB permeability using Dynamic Contrast-Enhanced MRI (DCE-MRI) in 29 patients that had suffered a recent small subcortical infarct (RSSI). BBB permeability in the whole brain (WB), gray matter (GM) and white matter (WM) was assessed with the parameter Ktrans. We used ambulatory blood pressure monitoring to measure 24-h systolic blood pressure (24-h SBP), diastolic blood pressure (24-h DBP), and pulse wave velocity (24-h PWV) both after stroke and following a 2-year follow-up. The differences between both measurements were calculated as Δ24-h SBP, Δ24-h DBP and Δ24-h PWV. DCE-MRI was acquired at a median (IQR) of 24 (19-27) months after stroke. Median age was 66.7 (9.7) years, and 24 (83%) patients were men. Median (IQR) Δ24-h PWV was 0.3 (-0.1, 0.5) m/s. WB-Ktrans, GM-Ktrans, and WM-Ktrans were associated with Δ24-h PWV (Spearman's, r 95% CI, WB 0.651 0.363-0.839; GM 0.657 0.373-0.845, WM 0.5300.197-0.777) but not with Δ24-h SBP or Δ24-h DBP. These associations remained significant after adjustment with linear regression models, controlling for age, sex, body mass index, and Δ24-h SBP (b95% CI, WB 0.7250.384-1.127, GM 0.629 0.316-1.369, WM 0.865 0.455-0.892) or Δ24-h DBP (b95% CI, WM 0.707 0.370-1.103, GM 0.643 0.352-1.371, WM 0.772 0.367-0.834). Our results suggest that an increment on arterial stiffness in the months following a RSSI might increase BBB permeability.
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