Prognostic biomarkers of intracerebral hemorrhage identified using targeted proteomics and machine learning algorithms.

Early prognostication of patient outcomes in intracerebral hemorrhage (ICH) is critical for patient care. We aim to investigate protein biomarkers' role in prognosticating outcomes in ICH patients. We assessed 22 protein biomarkers using targeted proteomics in serum samples obtained from the ICH patient dataset (N = 150). We defined poor outcomes as modified Rankin scale score of 3-6. We incorporated clinical variables and protein biomarkers in regression models and random forest-based machine learning algorithms to predict poor outcomes and mortality. We report Odds Ratio (OR) or Hazard Ratio (HR) with 95% Confidence Interval (CI). We used five-fold cross-validation and bootstrapping for internal validation of prediction models. We included 149 patients for 90-day and 144 patients with ICH for 180-day outcome analyses. In multivariable logistic regression, UCH-L1 (adjusted OR 9.23; 95%CI 2.41-35.33), alpha-2-macroglobulin (aOR 5.57; 95%CI 1.26-24.59), and Serpin-A11 (aOR 9.33; 95%CI 1.09-79.94) were independent predictors of 90-day poor outcome; MMP-2 (aOR 6.32; 95%CI 1.82-21.90) was independent predictor of 180-day poor outcome. In multivariable Cox regression models, IGFBP-3 (aHR 2.08; 95%CI 1.24-3.48) predicted 90-day and MMP-9 (aOR 1.98; 95%CI 1.19-3.32) predicted 180-day mortality. Machine learning identified additional predictors, including haptoglobin for poor outcomes and UCH-L1, APO-C1, and MMP-2 for mortality prediction. Overall, random forest models outperformed regression models for predicting 180-day poor outcomes (AUC 0.89), and 90-day (AUC 0.81) and 180-day mortality (AUC 0.81). Serum biomarkers independently predicted short-term poor outcomes and mortality after ICH. Further research utilizing a multi-omics platform and temporal profiling is needed to explore additional biomarkers and refine predictive models for ICH prognosis.

Pathophysiology, Diagnosis, Prognosis, and Prevention of Poststroke Epilepsy: Clinical and Research Implications.

Poststroke epilepsy (PSE) is associated with higher mortality and poor functional and cognitive outcomes in patients with stroke. With the remarkable development of acute stroke treatment, there is a growing number of survivors with PSE. Although approximately 10% of patients with stroke develop PSE, given the significant burden of stroke worldwide, PSE is a significant problem in stroke survivors. Therefore, the attention of health policymakers and significant funding are required to promote PSE prevention research. The current PSE definition includes unprovoked seizures occurring more than 7 days after stroke onset, given the high recurrence risks of seizures. However, the pathologic cascade of stroke is not uniform, indicating the need for a tissue-based approach rather than a time-based one to distinguish early seizures from late seizures. EEG is a commonly used tool in the diagnostic work-up of PSE. EEG findings during the acute phase of stroke can potentially stratify the risk of subsequent seizures and predict the development of poststroke epileptogenesis. Recent reports suggest that cortical superficial siderosis, which may be involved in epileptogenesis, is a promising marker for PSE. By incorporating such markers, future risk-scoring models could guide treatment strategies, particularly for the primary prophylaxis of PSE. To date, drugs that prevent poststroke epileptogenesis are lacking. The primary challenge involves the substantial cost burden due to the difficulty of reliably enrolling patients who develop PSE. There is, therefore, a critical need to determine reliable biomarkers for PSE. The goal is to be able to use them for trial enrichment and as a surrogate outcome measure for epileptogenesis. Moreover, seizure prophylaxis is essential to prevent functional and cognitive decline in stroke survivors. Further elucidation of factors that contribute to poststroke epileptogenesis is eagerly awaited. Meanwhile, the regimen of antiseizure medications should be based on individual cardiovascular risk, psychosomatic comorbidities, and concomitant medications. This review summarizes the current understanding of poststroke epileptogenesis, its risks, prognostic models, prophylaxis, and strategies for secondary prevention of seizures and suggests strategies to advance research on PSE.

Clinical characteristics and outcomes of patients with post-stroke epilepsy: protocol for an individual patient data meta-analysis from the International Post-stroke Epilepsy Research Repository (IPSERR).

INTRODUCTION: Despite significant advances in managing acute stroke and reducing stroke mortality, preventing complications like post-stroke epilepsy (PSE) has seen limited progress. PSE research has been scattered worldwide with varying methodologies and data reporting. To address this, we established the International Post-stroke Epilepsy Research Consortium (IPSERC) to integrate global PSE research efforts. This protocol outlines an individual patient data meta-analysis (IPD-MA) to determine outcomes in patients with post-stroke seizures (PSS) and develop/validate PSE prediction models, comparing them with existing models. This protocol informs about creating the International Post-stroke Epilepsy Research Repository (IPSERR) to support future collaborative research. METHODS AND ANALYSIS: We utilised a comprehensive search strategy and searched MEDLINE, Embase, PsycInfo, Cochrane, and Web of Science databases until 30 January 2023. We extracted observational studies of stroke patients aged ≥18 years, presenting early or late PSS with data on patient outcome measures, and conducted the risk of bias assessment. We did not apply any restriction based on the date or language of publication. We will invite these study authors and the IPSERC collaborators to contribute IPD to IPSERR. We will review the IPD lodged within IPSERR to identify patients who developed epileptic seizures and those who did not. We will merge the IPD files of individual data and standardise the variables where possible for consistency. We will conduct an IPD-MA to estimate the prognostic value of clinical characteristics in predicting PSE. ETHICS AND DISSEMINATION: Ethics approval is not required for this study. The results will be published in peer-reviewed journals. This study will contribute to IPSERR, which will be available to researchers for future PSE research projects. It will also serve as a platform to anchor future clinical trials. TRIAL REGISTRATION NUMBER: NCT06108102.

Polygenic Risk of Epilepsy and Post-Stroke Epilepsy.

Background and Aims: Epilepsy is highly heritable, with numerous known genetic risk loci. However, the genetic predisposition's role in post-acute brain injury epilepsy remains understudied. This study assesses whether a higher genetic predisposition to epilepsy raises post-stroke or Transient Ischemic Attack (TIA) survivor's risk of Post-Stroke Epilepsy (PSE). Methods: We conducted a three-stage genetic analysis. First, we identified independent epilepsy-associated ( p <5x10 -8 ) genetic variants from public data. Second, we estimated PSE-specific variant weights in stroke/TIA survivors from the UK Biobank. Third, we tested for an association between a polygenic risk score (PRS) and PSE risk in stroke/TIA survivors from the All of Us Research Program. Primary analysis included all ancestries, while a secondary analysis was restricted to European ancestry only. A sensitivity analysis excluded TIA survivors. Association testing was conducted via multivariable logistic regression, adjusting for age, sex, and genetic ancestry. Results: Among 19,708 UK Biobank participants with stroke/TIA, 805 (4.1%) developed PSE. Likewise, among 12,251 All of Us participants with stroke/TIA, 394 (3.2%) developed PSE. After establishing PSE-specific weights for 39 epilepsy-linked genetic variants in the UK Biobank, the resultant PRS was associated with elevated odds of PSE development in All of Us (OR:1.16[1.02-1.32]). A similar result was obtained when restricting to participants of European ancestry (OR:1.23[1.02-1.49]) and when excluding participants with a TIA history (OR:1.18[1.02-1.38]). Conclusions: Our findings suggest that akin to other forms of epilepsy, genetic predisposition plays an essential role in PSE. Because the PSE data were sparse, our results should be interpreted cautiously.

Outcomes in Patients With Poststroke Seizures: A Systematic Review and Meta-Analysis.

Importance: Published data about the impact of poststroke seizures (PSSs) on the outcomes of patients with stroke are inconsistent and have not been systematically evaluated, to the authors' knowledge. Objective: To investigate outcomes in people with PSS compared with people without PSS. Data Sources: MEDLINE, Embase, PsycInfo, Cochrane, LILACS, LIPECS, and Web of Science, with years searched from 1951 to January 30, 2023. Study Selection: Observational studies that reported PSS outcomes. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was used for abstracting data, and the Joanna Briggs Institute tool was used for risk-of-bias assessment. Data were reported as odds ratio (OR) and standardized mean difference (SMD) with a 95% CI using a random-effects meta-analysis. Publication bias was assessed using funnel plots and the Egger test. Outlier and meta-regression analyses were performed to explore the source of heterogeneity. Data were analyzed from November 2022 to January 2023. Main Outcomes and Measures: Measured outcomes were mortality, poor functional outcome (modified Rankin scale [mRS] score 3-6), disability (mean mRS score), recurrent stroke, and dementia at patient follow-up. Results: The search yielded 71 eligible articles, including 20 110 patients with PSS and 1 166 085 patients without PSS. Of the participants with PSS, 1967 (9.8%) had early seizures, and 10 605 (52.7%) had late seizures. The risk of bias was high in 5 studies (7.0%), moderate in 35 (49.3%), and low in 31 (43.7%). PSSs were associated with mortality risk (OR, 2.1; 95% CI, 1.8-2.4), poor functional outcome (OR, 2.2; 95% CI, 1.8-2.8), greater disability (SMD, 0.6; 95% CI, 0.4-0.7), and increased dementia risk (OR, 3.1; 95% CI, 1.3-7.7) compared with patients without PSS. In subgroup analyses, early seizures but not late seizures were associated with mortality (OR, 2.4; 95% CI, 1.9-2.9 vs OR, 1.2; 95% CI, 0.8-2.0) and both ischemic and hemorrhagic stroke subtypes were associated with mortality (OR, 2.2; 95% CI, 1.8-2.7 vs OR, 1.4; 95% CI, 1.0-1.8). In addition, early and late seizures (OR, 2.4; 95% CI, 1.6-3.4 vs OR, 2.7; 95% CI, 1.8-4.1) and stroke subtypes were associated with poor outcomes (OR, 2.6; 95% CI, 1.9-3.7 vs OR, 1.9; 95% CI, 1.0-3.6). Conclusions and Relevance: Results of this systematic review and meta-analysis suggest that PSSs were associated with significantly increased mortality and severe disability in patients with history of stroke. Unraveling these associations is a high clinical and research priority. Trials of interventions to prevent seizures may be warranted.

Common Pathways of Epileptogenesis in Patients With Epilepsy Post-Brain Injury: Findings From a Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: Epilepsy may result from various brain injuries, including stroke (ischemic and hemorrhagic), traumatic brain injury, and infections. Identifying shared common biological pathways and biomarkers of the epileptogenic process initiated by the different injuries may lead to novel targets for preventing the development of epilepsy. We systematically reviewed biofluid biomarkers to test their association with the risk of post-brain injury epilepsy. METHODS: We searched articles until January 25, 2022, in MEDLINE, Embase, PsycInfo, Web of Science, and Cochrane. The primary outcome was the difference in mean biomarker levels in patients with and without post-brain injury epilepsy. We used the modified quality score on prognostic studies for risk of bias assessment. We calculated each biomarker's pooled standardized mean difference (SMD) and 95% CI. Molecular interaction network and enrichment analyses were conducted in Cytoscape (PROSPERO CRD42021297110). RESULTS: We included 22 studies with 1,499 cases with post-brain injury epilepsy and 7,929 controls without post-brain injury epilepsy. Forty-five biomarkers in the blood or CSF were investigated with samples collected at disparate time points. Of 22 studies, 21 had a moderate-to-high risk of bias. Most of the biomarkers (28/45) were investigated in single studies; only 9 provided validation data, and studies used variable definitions for early-onset and late-onset seizures. A meta-analysis was possible for 19 biomarkers. Blood glucose levels in 4 studies were significantly higher in patients with poststroke epilepsy (PSE) than those without PSE (SMD 0.44; CI 0.19-0.69). From individual studies, 15 biomarkers in the blood and 7 in the CSF were significantly associated with post-brain injury epilepsy. Enrichment analysis identified that the significant biomarkers (interleukin [IL]-6, IL-1ß]) were predominantly inflammation related. DISCUSSION: We cannot yet recommend using the reported biomarkers for designing antiepileptogenesis trials or use in the clinical setting because of methodological heterogeneity, bias in the included studies, and insufficient validation studies. Although our analyses indicate the plausible role of inflammation in epileptogenesis, this is likely not the only mechanism. For example, an individual's genetic susceptibilities might contribute to his/her risk of epileptogenesis after brain injury. Rigorously designed biomarker studies with methods acceptable to the regulatory bodies should be conducted.

Comparison of Sex-Based In-Hospital Procedural Outcomes and Hospital Readmission Frequency After Patent Foramen Ovale Occluder Device Placement: A Propensity Matched National Cohort.

Patent foramen ovale (PFO) occluder device has been shown to reduce the chance of recurrent stroke. Per guidelines, stroke is higher in females but procedural efficacy and complications based on sex difference is understudied. The nationwide readmission database (NRD) was used to create sex cohorts using ICD-10 Procedural code for elective PFO occluder device placement performed during the years 2016-2019. The 2 groups were compared using propensity score matching (PSM) and multivariate regression models that matched for confounders to report multivariate odds ratio (mOR) for primary and secondary cardiovascular outcomes. Outcomes included in-hospital mortality, acute kidney injury (AKI), acute ischemic stroke, postprocedure bleeding, and cardiac tamponade. Statistical analysis was performed using STATA v. 17. A total of 5818 patients who underwent PFO occluder device placement were identified, of which 3144 (54.0%) were females, and 2673 (46.0%) were males. There was no difference in periprocedural in-hospital mortality, new onset acute ischemic stroke, postprocedural bleeding, or cardiac tamponade between both sexes undergoing occluder device placement. AKI incidence was higher in males compared to females after matching for CKD (mOR = 0.66; 95% CI [0.48-0.92]; P = 0.016) this can be procedural or can be secondary to volume status or nephrotoxins. Males also had a higher length of stay (LOS) at their index hospitalization (2 days vs 1 day) which led to slightly higher total hospitalization cost ($26,585 vs $24,265). Our data did not show a statistically significant difference in the readmission LOS trends between the 2 groups at 30, 90, and 180 days. This national retrospective cohort study of PFO occluder outcomes shows similar efficacy and complication rates between sexes, with the exception of AKI incidence which was higher in males. AKI occurrence was high in males that can be limited due to unavailability of data about hydration status and nephrotoxic medications.

Impact of genetic polymorphisms on the risk of epilepsy amongst patients with acute brain injury: A systematic review.

BACKGROUND AND PURPOSE: The genetics of late seizure or epilepsy secondary to traumatic brain injury (TBI) or stroke are poorly understood. We undertook a systematic review to test the association of single-nucleotide polymorphisms (SNPs) with the risk of post-traumatic epilepsy (PTE) and post-stroke epilepsy (PSE). METHODS: We followed methods from our prespecified protocol on PROSPERO to identify indexed articles for this systematic review. We collated the association statistics from the included articles to assess the association of SNPs with the risk of epilepsy amongst TBI or stroke patients. We assessed study quality using the Q-Genie tool. We report odds ratios (OR) and hazard ratios with 95% confidence intervals (CIs). RESULTS: The literature search yielded 420 articles. We included 16 studies in our systematic review, of which seven were of poor quality. We examined published data on 127 SNPs from 32 genes identified in PTE and PSE patients. Eleven SNPs were associated with a significantly increased risk of PTE. Three SNPs, TRMP6 rs2274924, ALDH2 rs671, and CD40 -1C/T, were significantly associated with an increased risk of PSE, while two, AT1R rs12721273 and rs55707609, were significantly associated with reduced risk. The meta-analysis for the association of the APOE ɛ4 with PTE was nonsignificant (OR 1.8, CI 0.6-5.6). CONCLUSIONS: The current evidence on the association of genetic polymorphisms in epilepsy secondary to TBI or stroke is of low quality and lacks validation. A collaborative effort to pool genetic data linked to epileptogenesis in stroke and TBI patients is warranted.

Sex-Specific Outcomes After Transcatheter Aortic Valve Replacement: FDA Patient-Level Meta-Analysis of Premarket Clinical Trials.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a less invasive alternative approach to surgery. Individual randomized clinical trials evaluating the safety and efficacy of TAVR were mostly underpowered for conducting separate analyses for women and men. We pooled data from premarket TAVR clinical trials comparing short (30 days)- and long-term (∼2 years) outcomes by sex. METHODS: Patient-level data from the TAVR arms of six clinical trials were pooled (2515 patients). Random-effects models for time-to-event outcomes (odds ratios [ORs] for 30-day outcomes and hazard ratios [HRs] for complete follow-up for mortality, ischemic stroke, kidney injury, major bleeding, myocardial infarction, and device migration) and dichotomous outcomes (ORs for reintervention, rehospitalization, and pacemaker implantation) were then fit to directly compare outcomes between women and men. RESULTS: Overall, the pattern of individual comorbidities was more severe in men. There was no difference in mortality risk at 30 days (female-to-male OR = 1.00 [0.69-1.46]); however, at follow-up completion (∼2 years post-TAVR), women had a 24% lower mortality risk than men (HR = 0.76 [95% CI: 0.65-0.89]). Women also had a 30% lower risk of kidney injury at 30 days (OR = 0.70 [0.49-0.98]), which increased to 33% over the complete follow-up period (HR = 0.67 [0.51-0.87]). Major bleeding was more common in women compared to men at both 30 days (OR = 1.44 [1.19-1.76]) and long-term follow-up (HR = 1.22 [1.04-1.43]). For dichotomous outcomes, women had a 68% lower risk for reinterventions (OR = 0.32 [0.18-0.58]). We did not observe any difference in the risk of ischemic stroke, myocardial infarction, device migration, rehospitalizations, or pacemaker implantations between sexes. CONCLUSIONS: This patient-level data meta-analysis of six premarket clinical trials found that women who received TAVR had fewer comorbidities at baseline. Acute outcomes (30 day) with respect to mortality were similar. Women were observed to have a lower risk of kidney injury, but higher risk of major bleeding compared to men receiving TAVR at 30 days. At complete follow-up, statistically significant advantages for women emerged in improved survival and lower reintervention risk. No differences in ischemic stroke, pacemaker implantation, or rehospitalization were observed. That women are healthier at baseline and develop fewer postprocedural complications than men may explain their higher survival.

Time From Imaging to Endovascular Reperfusion Predicts Outcome in Acute Stroke.

BACKGROUND AND PURPOSE: This study aims to describe the relationship between computed tomographic (CT) perfusion (CTP)-to-reperfusion time and clinical and radiological outcomes, in a cohort of patients who achieve successful reperfusion for acute ischemic stroke. METHODS: We included data from the CRISP (Computed Tomographic Perfusion to Predict Response in Ischemic Stroke Project) in which all patients underwent a baseline CTP scan before endovascular therapy. Patients were included if they had a mismatch on their baseline CTP scan and achieved successful endovascular reperfusion. Patients with mismatch were categorized into target mismatch and malignant mismatch profiles, according to the volume of their Tmax >10s lesion volume (target mismatch, <100 mL; malignant mismatch, >100 mL). We investigated the impact of CTP-to-reperfusion times on probability of achieving functional independence (modified Rankin Scale, 0-2) at day 90 and radiographic outcomes at day 5. RESULTS: Of 156 included patients, 108 (59%) had the target mismatch profile, and 48 (26%) had the malignant mismatch profile. In patients with the target mismatch profile, CTP-to-reperfusion time showed no association with functional independence (P=0.84), whereas in patients with malignant mismatch profile, CTP-to-reperfusion time was strongly associated with lower probability of functional independence (odds ratio, 0.08; P=0.003). Compared with patients with target mismatch, those with the malignant mismatch profile had significantly more infarct growth (90 [49-166] versus 43 [18-81] mL; P=0.006) and larger final infarct volumes (110 [61-155] versus 48 [21-99] mL; P=0.001). CONCLUSIONS: Compared with target mismatch patients, those with the malignant profile experience faster infarct growth and a steeper decline in the odds of functional independence, with longer delays between baseline imaging and reperfusion. However, this does not exclude the possibility of treatment benefit in patients with a malignant profile.

Comorbid Parkinson's disease, falls and fractures in the 2010 National Emergency Department Sample.

INTRODUCTION: Parkinson's disease (PD) is a progressive, neurodegenerative disorder of multifactorial etiology affecting ∼1% of older adults. Research focused on linking PD to falls and bone fractures has been limited in Emergency Department (ED) settings, where most injuries are identified. We assessed whether injured U.S. ED admissions with PD diagnoses were more likely to exhibit comorbid fall- or non-fall related bone fractures and whether a PD diagnosis with a concomitant fall or bone fracture is linked to worse prognosis. METHODS: We performed secondary analyses of 2010 Healthcare Utilization Project National ED Sample from 4,253,987 admissions to U.S. EDs linked to injured elderly patients. ED discharges with ICD-9-CM code (332.0) were identified as PD and those with ICD-9-CM code (800.0-829.0) were used to define bone fracture location. Linear and logistic regression models were constructed to estimate slopes (B) and odds ratios (OR) with 95% confidence intervals (CI). RESULTS: PD admissions had 28% increased adjusted prevalence of bone fracture. Non-fall injuries showed stronger relationship between PD and bone fracture (ORadj = 1.33, 95% CI: 1.22-1.45) than fall injuries (ORadj = 1.06, 95% CI: 1.01-1.10). PD had the strongest impact on hospitalization length when bone fracture and fall co-occurred, and total charges were directly associated with PD only for fall injuries. Finally, PD status was not related to in-hospital death in this population. CONCLUSION: Among injured U.S. ED elderly patient visits, those with PD had higher bone fracture prevalence and more resource utilization especially among fall-related injuries. No association of PD with in-hospital death was noted.

Comparison of stroke volume evolution on diffusion-weighted imaging and fluid-attenuated inversion recovery following endovascular thrombectomy.

Background To compare the evolution of the infarct lesion volume on both diffusion-weighted imaging and fluid-attenuated inversion recovery in the first five days after endovascular thrombectomy. Methods We included 109 patients from the CRISP and DEFUSE 2 studies. Stroke lesion volumes obtained on diffusion-weighted imaging and fluid-attenuated inversion recovery images both early post-procedure (median 18 h after symptom onset) and day 5, were compared using median, interquartile range, and correlation plots. Patients were dichotomized based on the time after symptom onset of their post procedure images (≥18 h vs. <18 h), and the degree of reperfusion (on Tmax>6 s; ≥ 90% vs. < 90%). Results Early post-procedure, median infarct lesion volume was 19 ml [(IQR) 7-43] on fluid-attenuated inversion recovery, and 23 ml [11-64] on diffusion-weighted imaging. On day 5, median infarct lesion volume was 52 ml [20-118] on fluid-attenuated inversion recovery, and 37 ml [16-91] on diffusion-weighted imaging. Infarct lesion volume on early post-procedure diffusion-weighted imaging, compared to fluid-attenuated inversion recovery, correlated better with day 5 diffusion-weighted imaging and fluid-attenuated inversion recovery lesions (r = 0.88 and 0.88 vs. 0.78 and 0.77; p < 0.0001). Median lesion growth was significantly smaller on diffusion-weighted imaging when the early post-procedure scan was obtained ≥18 h post stroke onset (5 ml [-1-13]), compared to <18 h (13 ml [2-47]; p = 0.03), but was not significantly different on fluid-attenuated inversion recovery (≥18 h: 26 ml [12-57]; <18 h: 21 ml [5-57]; p = 0.65). In the <90% reperfused group, the median infarct growth was significantly larger for diffusion-weighted imaging and fluid-attenuated inversion recovery (diffusion-weighted imaging: 23 ml [8-57], fluid-attenuated inversion recovery: 41 ml [13-104]) compared to ≥90% (diffusion-weighted imaging: 6 ml [2-24]; p = 0.003, fluid-attenuated inversion recovery: 19 ml [8-46]; p = 0.001). Conclusions Early post-procedure lesion volume on diffusion-weighted imaging is a better estimate of day 5 infarct volume than fluid-attenuated inversion recovery. However, both early post-procedure diffusion-weighted imaging and fluid-attenuated inversion recovery underestimate day 5 diffusion-weighted imaging and fluid-attenuated inversion recovery lesion volumes, especially in patients who do not reperfuse.

Blood Pressure Management in Acute Stroke.

Raised blood pressure is common in ischaemic stroke and intracerebral haemorrhage and is an independent risk factor for unfavourable outcome. Yet, the approach to blood pressure management represents an unresolved issue in acute stroke treatment. The aim of this review is to present the current knowledge regarding the management of raised blood pressure in patients with acute ischaemic stroke or intracerebral haemorrhage. In ischaemic stroke, several large clinical trials have tested the efficacy of several strategies that lower blood pressure. Overall, blood pressure lowering in the acute phase has no beneficial effect and should not be included in routine clinical practice apart from when treating patients with very raised blood pressure or those who are eligible for thrombolytic treatment. These findings in patients with acute ischaemic stroke are in contrast with those in intracerebral haemorrhage. A recent clinical trial has strongly suggested a clinical benefit of blood pressure lowering during the first few hours in intracerebral haemorrhage, which have led to changes in international guidelines. An important unanswered question in blood pressure management in the acute phase of ischaemic stroke involves the first few hours, when there is still penumbral tissue at risk. Forthcoming trials may help to answer this remaining issue.

A benchmarking tool to evaluate computer tomography perfusion infarct core predictions against a DWI standard.

Differences in research methodology have hampered the optimization of Computer Tomography Perfusion (CTP) for identification of the ischemic core. We aim to optimize CTP core identification using a novel benchmarking tool. The benchmarking tool consists of an imaging library and a statistical analysis algorithm to evaluate the performance of CTP. The tool was used to optimize and evaluate an in-house developed CTP-software algorithm. Imaging data of 103 acute stroke patients were included in the benchmarking tool. Median time from stroke onset to CT was 185 min (IQR 180-238), and the median time between completion of CT and start of MRI was 36 min (IQR 25-79). Volumetric accuracy of the CTP-ROIs was optimal at an rCBF threshold of <38%; at this threshold, the mean difference was 0.3 ml (SD 19.8 ml), the mean absolute difference was 14.3 (SD 13.7) ml, and CTP was 67% sensitive and 87% specific for identification of DWI positive tissue voxels. The benchmarking tool can play an important role in optimizing CTP software as it provides investigators with a novel method to directly compare the performance of alternative CTP software packages.

Test Accuracy of Informant-Based Cognitive Screening Tests for Diagnosis of Dementia and Multidomain Cognitive Impairment in Stroke.

BACKGROUND AND PURPOSE: Poststroke cognitive assessment can be performed using standardized questionnaires designed for family or care givers. We sought to describe the test accuracy of such informant-based assessments for diagnosis of dementia/multidomain cognitive impairment in stroke. METHODS: We performed a systematic review using a sensitive search strategy across multidisciplinary electronic databases. We created summary test accuracy metrics and described reporting and quality using STARDdem and Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tools, respectively. RESULTS: From 1432 titles, we included 11 studies. Ten papers used the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Four studies described IQCODE for diagnosis of poststroke dementia (n=1197); summary sensitivity: 0.81 (95% confidence interval, 0.60-0.93); summary specificty: 0.83 (95% confidence interval, 0.64-0.93). Five studies described IQCODE as tool for predicting future dementia (n=837); summary sensitivity: 0.60 (95% confidence interval, 0.32-0.83); summary specificity: 0.97 (95% confidence interval, 0.70-1.00). All papers had issues with at least 1 aspect of study reporting or quality. CONCLUSIONS: There is a limited literature on informant cognitive assessments in stroke. IQCODE as a diagnostic tool has test properties similar to other screening tools, IQCODE as a prognostic tool is specific but insensitive. We found no papers describing test accuracy of informant tests for diagnosis of prestroke cognitive decline, few papers on poststroke dementia and all included papers had issues with potential bias.

Response to endovascular reperfusion is not time-dependent in patients with salvageable tissue.

OBJECTIVE: To evaluate whether time to treatment modifies the effect of endovascular reperfusion in stroke patients with evidence of salvageable tissue on MRI. METHODS: Patients from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 (DEFUSE 2) cohort study with a perfusion-diffusion target mismatch were included. Reperfusion was defined as a decrease in the perfusion lesion volume of at least 50% between baseline and early follow-up. Good functional outcome was defined as a modified Rankin Scale score ≤2 at day 90. Lesion growth was defined as the difference between the baseline and the early follow-up diffusion-weighted imaging lesion volumes. RESULTS: Among 78 patients with the target mismatch profile (mean age 66 ± 16 years, 54% women), reperfusion was associated with increased odds of good functional outcome (adjusted odds ratio 3.7, 95% confidence interval 1.2-12, p = 0.03) and attenuation of lesion growth (p = 0.02). Time to treatment did not modify these effects (p value for the time × reperfusion interaction is 0.6 for good functional outcome and 0.3 for lesion growth). Similarly, in the subgroup of patients with reperfusion (n = 46), time to treatment was not associated with good functional outcome (p = 0.2). CONCLUSION: The association between endovascular reperfusion and improved functional and radiologic outcomes is not time-dependent in patients with a perfusion-diffusion mismatch. Proof that patients with mismatch benefit from endovascular therapy in the late time window should come from a randomized placebo-controlled trial.