Prognostic significance of infarct size and location: The case of insular stroke

The prognostic relevance of strokes in different locations is debated. For example, insular strokes have been associated with increased mortality, but this association could reflect their greater severity. In two independent cohorts of patients with supratentorial ischemic stroke (n = 90 and 105), we studied the prognostic consequences of lesion size and location using voxel-based lesion-symptom mapping before and after volume control, which better accounts for total lesion volume. Strokes affecting the insula were larger than non-insular strokes (28 vs 2cc and 25 vs 3cc, p < 0.001 in both cohorts). A number of supratentorial areas (mainly in the left hemisphere), including the insula, were associated with poor functional outcome in both cohorts before (4014 voxels) and after volume control (1378 voxels), while the associations with death were greatly reduced after volume control (from 8716 to 325 voxels). Exploratory analyses suggested that the method of lesion volume quantification, the National Institutes of Health Stroke Scale hemispheric bias and patient selection can result in false associations between specific brain lesions and outcomes. In conclusion, death in the first months after stroke is mainly explained by large infarct volumes, whereas lesions of specific supratentorial structures, mostly in the left hemisphere, also contribute to poor functional outcomes

Elevated glucose is associated with hemorrhagic transformation after mechanical thrombectomy in acute ischemic stroke patients with severe pretreatment hypoperfusion

Several pretreatment variables such as elevated glucose and hypoperfusion severity are related to brain hemorrhage after endovascular treatment of acute stroke. We evaluated whether elevated glucose and severe hypoperfusion have synergistic effects in the promotion of parenchymal hemorrhage (PH) after mechanical thrombectomy (MT). We included 258 patients MT-treated who had a pretreatment computed tomography perfusion (CTP) and a post-treatment follow-up MRI. Severe hypoperfusion was defined as regions with cerebral blood volume (CBV) values < 2.5% of normal brain [very-low CBV (VLCBV)-regions]. Median baseline glucose levels were 119 (IQR = 105-141) mg/dL. Thirty-nine (15%) patients had pretreatment VLCBV-regions, and 42 (16%) developed a PH after MT. In adjusted models, pretreatment glucose levels interacted significantly with VLCBV on the prediction of PH (p-interaction = 0.011). In patients with VLCBV-regions, higher glucose was significantly associated with PH (adjusted-OR = 3.15; 95% CI = 1.08-9.19, p = 0.036), whereas this association was not significant in patients without VLCBV-regions. CBV values measured at pretreatment CTP in coregistered regions that developed PH or infarct at follow-up were not correlated with pretreatment glucose levels, thus suggesting the existence of alternative deleterious mechanisms other than direct glucose-driven hemodynamic impairments. Overall, these results suggest that both severe hypoperfusion and glucose levels should be considered in the evaluation of adjunctive neuroprotective strategies

ESO Guideline on Covert Cerebral Small Vessel Disease

'Covert' cerebral small vessel disease (ccSVD) is common on neuroimaging in persons without overt neurological manifestations, and increases the risk of future stroke, cognitive impairment, dependency, and death. These European Stroke Organisation (ESO) guidelines provide evidence-based recommendations to assist with clinical decisions about management of ccSVD, specifically white matter hyperintensities and lacunes, to prevent adverse clinical outcomes. The guidelines were developed according to ESO standard operating procedures and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. We prioritised the clinical outcomes of stroke, cognitive decline or dementia, dependency, death, mobility and mood disorders, and interventions of blood pressure lowering, antiplatelet drugs, lipid lowering, lifestyle modifications, glucose lowering and conventional treatments for dementia. We systematically reviewed the literature, assessed the evidence, formulated evidence-based recommendations where feasible, and expert consensus statements. We found little direct evidence, mostly of low quality. We recommend patients with ccSVD and hypertension to have their blood pressure well controlled; lower blood pressure targets may reduce ccSVD progression. We do not recommend antiplatelet drugs such as aspirin in ccSVD. We found little evidence on lipid lowering in ccSVD. Smoking cessation is a health priority. We recommend regular exercise which may benefit cognition, and a healthy diet, good sleep habits, avoiding obesity and stress for general health reasons. In ccSVD, we found no evidence for glucose control in the absence of diabetes or for conventional Alzheimer dementia treatments. Randomised controlled trials with clinical endpoints are a priority for ccSVD.Peer reviewe

Effectiveness of Thrombectomy in Stroke According to Baseline Prognostic Factors: Inverse Probability of Treatment Weighting Analysis of a Population-Based Registry

Background and Purpose In real-world practice, the benefit of mechanical thrombectomy (MT) is uncertain in stroke patients with very favorable or poor prognostic profiles at baseline. We studied the effectiveness of MT versus medical treatment stratifying by different baseline prognostic factors. Methods Retrospective analysis of 2,588 patients with an ischemic stroke due to large vessel occlusion nested in the population-based registry of stroke code activations in Catalonia from January 2017 to June 2019. The effect of MT on good functional outcome (modified Rankin Score 85 years, National Institutes of Health Stroke Scale [NIHSS] >25, time from onset >6 hours, Alberta Stroke Program Early CT Score 3), good (if NIHSS <6 or distal occlusion, in the absence of poor prognostic factors), or reference (not meeting other groups' criteria). Results Patients receiving MT (n=1,996, 77%) were younger, had less pre-stroke disability, and received systemic thrombolysis less frequently. These differences were balanced after the IPTW stratified by prognosis. MT was associated with good functional outcome in the reference (odds ratio [OR], 2.9; 95% confidence interval [CI], 2.0 to 4.4), and especially in the poor baseline prognostic stratum (OR, 3.9; 95% CI, 2.6 to 5.9), but not in the good prognostic stratum. MT was associated with survival only in the poor prognostic stratum (OR, 2.6; 95% CI, 2.0 to 3.3). Conclusions Despite their worse overall outcomes, the impact of thrombectomy over medical management was more substantial in patients with poorer baseline prognostic factors than patients with good prognostic factors

Effectiveness of thrombectomy in stroke according to baseline prognostic factors: inverse probability of treatment weighting analysis of a population-based registry

Background and purpose: in real-world practice, the benefit of mechanical thrombectomy (MT) is uncertain in stroke patients with very favorable or poor prognostic profiles at baseline. We studied the effectiveness of MT versus medical treatment stratifying by different baseline prognostic factors. Methods: retrospective analysis of 2,588 patients with an ischemic stroke due to large vessel occlusion nested in the population-based registry of stroke code activations in Catalonia from January 2017 to June 2019. The effect of MT on good functional outcome (modified Rankin Score ≤2) and survival at 3 months was studied using inverse probability of treatment weighting (IPTW) analysis in three pre-defined baseline prognostic groups: poor (if pre-stroke disability, age >85 years, National Institutes of Health Stroke Scale [NIHSS] >25, time from onset >6 hours, Alberta Stroke Program Early CT Score 3), good (if NIHSS <6 or distal occlusion, in the absence of poor prognostic factors), or reference (not meeting other groups' criteria). Results: patients receiving MT (n=1,996, 77%) were younger, had less pre-stroke disability, and received systemic thrombolysis less frequently. These differences were balanced after the IPTW stratified by prognosis. MT was associated with good functional outcome in the reference (odds ratio [OR], 2.9; 95% confidence interval [CI], 2.0 to 4.4), and especially in the poor baseline prognostic stratum (OR, 3.9; 95% CI, 2.6 to 5.9), but not in the good prognostic stratum. MT was associated with survival only in the poor prognostic stratum (OR, 2.6; 95% CI, 2.0 to 3.3). Conclusions: despite their worse overall outcomes, the impact of thrombectomy over medical management was more substantial in patients with poorer baseline prognostic factors than patients with good prognostic factors

Uric acid therapy prevents early ischemic stroke progression: A tertiary analysis of the URICO-ICTUS trial (Efficacy Study of Combined Treatment With Uric Acid and r-tPA in Acute Ischemic Stroke)

[Background and Purpose] Identification of neuroprotective therapies in acute ischemic stroke is imperative. We report a predefined analysis of the URICO-ICTUS trial (Efficacy Study of Combined Treatment With Uric Acid and r-tPA in Acute Ischemic Stroke) assessing the efficacy of uric acid (UA) compared with placebo to prevent early ischemic worsening (EIW) and the relevance of collateral circulation. [Methods] URICO-ICTUS was a double-blind, placebo-controlled, phase 2b trial where a total of 411 patients treated with alteplase within 4.5 hours of stroke onset were randomized (1:1) to receive UA 1000 mg (n=211) or placebo (n=200) before the end of alteplase infusion. EIW defined an increment ≥4 points in the National Institutes of Health Stroke Scale score within 72 hours of treatment in the absence of hemorrhage or recurrent stroke. Logistic regression models assessed the interaction between therapy and the collateral circulation in 112 patients who had a pretreatment computed tomographic angiography. [Results] EIW occurred in 2 of 149 (1%) patients with good outcome and 23 of 262 (9%) patients with poor outcome (χ2; P=0.002). EIW occurred in 7 of 204 (3%) patients treated with UA and in 18 of 200 (9%) patients treated with placebo (χ2; P=0.01). There was a significant interaction between the efficacy of UA to prevent EIW and collaterals (P=0.029), with lower incidence in patients with good collaterals treated with UA compared with placebo (2% versus 15%, respectively; P=0.048). [Conclusions] UA therapy may prevent EIW after acute stroke in thrombolysed patients. Optimal access of UA to its molecular targets through appropriate collaterals may modify the magnitude of the neuroprotective effect.Peer Reviewe

Neuroanatomical correlates of stroke-associated infection and stroke-induced immunodepression

[Background] Infections represent the most frequent medical complications in stroke patients. Their main determinants are dysphagia and a transient state of immunodepression. We analyzed whether distinct anatomical brain regions were associated with the occurrence of stroke-associated infections or immunodepression.[Materials and methods] In 106 patients with acute ischemic stroke, we evaluated the incidence of pneumonia, urinary tract infection, or other infections together with the characterization of biomarkers of immunodepression. Twenty control subjects served to provide reference values. Using voxel-based lesion-symptom mapping, the involvement of gray and white matter structures was correlated with clinical and laboratory findings in crude analyses and in volume adjusted models to rule out associations reflecting differences in the size of the infarction.[Results] Stroke-associated infection occurred in 22 (21%) patients and prevailed in patients with larger infarcts. Volume adjusted voxel-based lesion-symptom mapping revealed the involvement of the superior and middle temporal gyri, the orbitofrontal cortex, the superior longitudinal fasciculus and the inferior fronto-occipital fasciculus amongst infected patients. These associations were similar for pneumonia but not for urinary tract infections. Lymphopenia was associated with lesions of the superior and middle temporal gyri. Laterality did not influence stroke-associated infections or the presence of immunodepressive traits after volume control. The greatest overlap in the neuroanatomical correlates occurred between pneumonia and dysphagia.[Conclusion] Infarct volume plays a relevant role in the occurrence of stroke-associated infections, but lesions in specific brain locations such as the superior and lateral temporal lobe and the orbitofrontal cortex are also associated with increased infectious risk, especially pneumonia.This study was funded by grants from the Spanish Ministry of Economy and Competitiveness to Dr. Chamorro [grant numbers PS09/01313 and PI12/01437], funded as part of the Plan Nacional Investigación, Desarrollo e Innovación and cofinanced by Instituto Salud Carlos III–Subdirección General de Evaluación and by Fondo Europeo de Desarrollo Regional. Yashu Zhao has a scholarship of the State Scholarship Fund of China.Peer reviewe