Introduction
After minor head injury (MHI), post-concussive symptoms commonly occur. The purpose of this study was to correlate the severity of post-concussive symptoms in MHI patients with MRI ...measures of microstructural brain injury, namely mean diffusivity (MD) and fractional anisotropy (FA), as well as the presence of microhaemorrhages.
Methods
Twenty MHI patients and 12 healthy controls were scanned at 3 T using diffusion tensor imaging (DTI) and high-resolution gradient recalled echo (HRGRE) T2*-weighted sequences. One patient was excluded from the analysis because of bilateral subdural haematomas. DTI data were preprocessed using Tract Based Spatial Statistics. The resulting MD and FA images were correlated with the severity of post-concussive symptoms evaluated with the Rivermead Postconcussion Symptoms Questionnaire. The number and location of microhaemorrhages were assessed on the HRGRE T2*-weighted images.
Results
Comparing patients with controls, there were no differences in MD. FA was decreased in the right temporal subcortical white matter. MD was increased in association with the severity of post-concussive symptoms in the inferior fronto-occipital fasciculus (IFO), the inferior longitudinal fasciculus and the superior longitudinal fasciculus. FA was reduced in association with the severity of post-concussive symptoms in the uncinate fasciculus, the IFO, the internal capsule and the corpus callosum, as well as in the parietal and frontal subcortical white matter. Microhaemorrhages were observed in one patient only.
Conclusions
The severity of post-concussive symptoms after MHI was significantly correlated with a reduction of white matter integrity, providing evidence of microstructural brain injury as a neuropathological substrate of the post-concussion syndrome.
Aphasia has a large impact on the quality of life and adds significantly to the costs of stroke care. Early recognition of aphasia in stroke patients is important for prognostication and well-timed ...treatment planning. We aimed to identify available screening tests for differentiating between aphasic and non-aphasic stroke patients, and to evaluate test accuracy, reliability, and feasibility. We searched PubMed, EMbase, Web of Science, and PsycINFO for published studies on screening tests aimed at assessing aphasia in stroke patients. The reference lists of the selected articles were scanned, and several experts were contacted to detect additional references. Of each screening test, we estimated the sensitivity, specificity, likelihood ratio of a positive test, likelihood ratio of a negative test, and diagnostic odds ratio (DOR), and rated the degree of bias of the validation method. We included ten studies evaluating eight screening tests. There was a large variation across studies regarding sample size, patient characteristics, and reference tests used for validation. Many papers failed to report on the consecutiveness of patient inclusion, time between aphasia onset and administration of the screening test, and blinding. Of the three studies that were rated as having an intermediate or low risk of bias, the DOR was highest for the Language Screening Test and ScreeLing. Several screening tools for aphasia in stroke are available, but many tests have not been verified properly. Methodologically sound validation studies of aphasia screening tests are needed to determine their usefulness in clinical practice.
Revascularization after endovascular therapy for acute ischemic stroke is measured by the Thrombolysis In Cerebral Infarction (TICI) scale, yet variability exists in scale definitions. We examined ...the degree of reperfusion with the expanded TICI (eTICI) scale and association with outcomes in the HERMES collaboration of recent endovascular trials.
The HERMES Imaging Core, blind to all other data, evaluated angiography after endovascular therapy in HERMES. A battery of TICI scores (mTICI, TICI, TICI2C) was used to define reperfusion of the initial target occlusion defined by non-invasive imaging and conventional angiography.
Angiography of 801 subjects was available, including 797 defined by non-invasive imaging (154 internal carotid artery (ICA), 583 M1, 60 M2) and 748 by conventional angiography (195 ICA, 459 M1, 94 M2). Among 729 subjects in whom the reperfusion grade could be established, using eTICI (3=100%, 2C=90-99%, 2b67=67-89%, 2b50=50-66%) of the conventional angiography target occlusion, there were 63 eTICI 3 (9%), 166 eTICI 2c (23%), 218 eTICI 2b67 (30%), 103 eTICI 2b50 (14%), 100 eTICI 2a (14%), 19 eTICI 1 (3%), and 60 eTICI 0 (8%). Modified Rankin Scale shift analyses from baseline to 90 days showed that increasing TICI grades were linked with better outcomes, with significant distinctions between TICI 0/1 versus 2a (p=0.028), 2a versus 2b50 (p=0.017), and 2b50 versus 2b67 (p=0.014).
The benefit of endovascular therapy in HERMES was strongly associated with increasing degrees of reperfusion defined by eTICI. The eTICI metric identified meaningful distinctions in clinical outcomes and may be used in future studies and routine practice.
•Prediction of the final infarct volume in acute ischemic stroke patients.•Takes into account the baseline CTP images and the time and treatment parameters.•Convolutional neural network trained and ...validated on a multicenter dataset.•Operates on the native CTP measurements without explicit deconvolution.•Improved performance over classical approach.
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CT Perfusion (CTP) imaging has gained importance in the diagnosis of acute stroke. Conventional perfusion analysis performs a deconvolution of the measurements and thresholds the perfusion parameters to determine the tissue status. We pursue a data-driven and deconvolution-free approach, where a deep neural network learns to predict the final infarct volume directly from the native CTP images and metadata such as the time parameters and treatment. This would allow clinicians to simulate various treatments and gain insight into predicted tissue status over time. We demonstrate on a multicenter dataset that our approach is able to predict the final infarct and effectively uses the metadata. An ablation study shows that using the native CTP measurements instead of the deconvolved measurements improves the prediction.
IMPORTANCE: It is uncertain whether therapeutic reperfusion with endovascular treatment yields more or less brain edema. OBJECTIVE: To elucidate the association between reperfusion and brain edema. ...The secondary objectives were to evaluate whether brain edema could partially be responsible for worse outcomes in patients with later reperfusion or lower Alberta Stroke Program Early Computed Tomography Score. DESIGN, SETTING, AND PARTICIPANTS: This was a post hoc analysis of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), which was a prospective, randomized, multicenter clinical trial of endovascular treatment compared with conventional care of patients with acute anterior circulation ischemic stroke. Of 502 patients enrolled from December 2010 to June 2014, 2 patients declined to participate. Additionally, exclusion criteria were absence of follow-up imaging or presence of parenchymal hematoma, resulting in 462 patients included in this study. Brain edema was assessed retrospectively, from December 10, 2016, to July 24, 2017, by measuring midline shift (MLS) in all available follow-up scans. Observers were blinded to clinical data. MAIN OUTCOMES AND MEASURES: Midline shift was assessed as present or absent and as a continuous variable. Reperfusion status was assessed by the modified thrombolysis in cerebral infarction score in the endovascular treatment arm. The modified arterial occlusive lesion score was used to evaluate the recanalization status in both arms. The modified Rankin scale score at 90 days was used for functional outcome. RESULTS: Of 462 patients, the mean (SD) age was 65 (11) years, and 41.8% (n = 193) were women. Successful reperfusion and recanalization were associated with a reduced likelihood of having MLS (adjusted common odds ratio, 0.25; 95% CI, 0.12-0.53; P < .001 and adjusted common odds ratio, 0.34; 95% CI, 0.21-0.55; P < .001, respectively). Midline shift was partially responsible for worse modified Rankin scale scores in patients without reperfusion or recanalization (MLS changed the logistic regression coefficients by 30.3% and 12.6%, respectively). In patients with delayed reperfusion or lower Alberta Stroke Program Early Computed Tomography Score, MLS mediated part of the worse modified Rankin scale scores, corresponding to a change in the regression coefficient of 33.3% and 64.2%, respectively. CONCLUSIONS AND RELEVANCE: Successful reperfusion was associated with reduced MLS. This study identifies an additional benefit of reperfusion in relation to edema, as well as rescuing ischemic brain tissue at risk for infarction. TRIAL REGISTRATION: Netherlands Trial Registry number: NTR1804 and Current Controlled Trials number: ISRCTN10888758.
Summary Background In 2015, five randomised trials showed efficacy of endovascular thrombectomy over standard medical care in patients with acute ischaemic stroke caused by occlusion of arteries of ...the proximal anterior circulation. In this meta-analysis we, the trial investigators, aimed to pool individual patient data from these trials to address remaining questions about whether the therapy is efficacious across the diverse populations included. Methods We formed the HERMES collaboration to pool patient-level data from five trials (MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA) done between December, 2010, and December, 2014. In these trials, patients with acute ischaemic stroke caused by occlusion of the proximal anterior artery circulation were randomly assigned to receive either endovascular thrombectomy within 12 h of symptom onset or standard care (control), with a primary outcome of reduced disability on the modified Rankin Scale (mRS) at 90 days. By direct access to the study databases, we extracted individual patient data that we used to assess the primary outcome of reduced disability on mRS at 90 days in the pooled population and examine heterogeneity of this treatment effect across prespecified subgroups. To account for between-trial variance we used mixed-effects modelling with random effects for parameters of interest. We then used mixed-effects ordinal logistic regression models to calculate common odds ratios (cOR) for the primary outcome in the whole population (shift analysis) and in subgroups after adjustment for age, sex, baseline stroke severity (National Institutes of Health Stroke Scale score), site of occlusion (internal carotid artery vs M1 segment of middle cerebral artery vs M2 segment of middle cerebral artery), intravenous alteplase (yes vs no), baseline Alberta Stroke Program Early CT score, and time from stroke onset to randomisation. Findings We analysed individual data for 1287 patients (634 assigned to endovascular thrombectomy, 653 assigned to control). Endovascular thrombectomy led to significantly reduced disability at 90 days compared with control (adjusted cOR 2·49, 95% CI 1·76–3·53; p<0·0001). The number needed to treat with endovascular thrombectomy to reduce disability by at least one level on mRS for one patient was 2·6. Subgroup analysis of the primary endpoint showed no heterogeneity of treatment effect across prespecified subgroups for reduced disability (pinteraction =0·43). Effect sizes favouring endovascular thrombectomy over control were present in several strata of special interest, including in patients aged 80 years or older (cOR 3·68, 95% CI 1·95–6·92), those randomised more than 300 min after symptom onset (1·76, 1·05–2·97), and those not eligible for intravenous alteplase (2·43, 1·30–4·55). Mortality at 90 days and risk of parenchymal haematoma and symptomatic intracranial haemorrhage did not differ between populations. Interpretation Endovascular thrombectomy is of benefit to most patients with acute ischaemic stroke caused by occlusion of the proximal anterior circulation, irrespective of patient characteristics or geographical location. These findings will have global implications on structuring systems of care to provide timely treatment to patients with acute ischaemic stroke due to large vessel occlusion. Funding Medtronic.
Background
Stroke is the main cause of disability in high‐income countries and ranks second as a cause of death worldwide. Infections occur frequently after stroke and may adversely affect outcome. ...Preventive antibiotic therapy in the acute phase of stroke may reduce the incidence of infections and improve outcome. In the previous version of this Cochrane Review, published in 2012, we found that antibiotics did reduce the risk of infection but did not reduce the number of dependent or deceased patients. However, included studies were small and heterogeneous. In 2015, two large clinical trials were published, warranting an update of this Review.
Objectives
To assess the effectiveness and safety of preventive antibiotic therapy in people with ischaemic or haemorrhagic stroke. We wished to determine whether preventive antibiotic therapy in people with acute stroke:
• reduces the risk of a poor functional outcome (dependency and/or death) at follow‐up;
• reduces the occurrence of infections in the acute phase of stroke;
• reduces the occurrence of elevated body temperature (temperature ≥ 38° C) in the acute phase of stroke;
• reduces length of hospital stay; or
• leads to an increased rate of serious adverse events, such as anaphylactic shock, skin rash, or colonisation with antibiotic‐resistant micro‐organisms.
Search methods
We searched the Cochrane Stroke Group Trials Register (25 June 2017); the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 5; 25 June 2017) in the Cochrane Library; MEDLINE Ovid (1950 to 11 May 2017), and Embase Ovid (1980 to 11 May 2017). In an effort to identify further published, unpublished, and ongoing trials, we searched trials and research registers, scanned reference lists, and contacted trial authors, colleagues, and researchers in the field.
Selection criteria
Randomised controlled trials (RCTs) of preventive antibiotic therapy versus control (placebo or open control) in people with acute ischaemic or haemorrhagic stroke.
Data collection and analysis
Two review authors independently selected articles and extracted data; we discussed and resolved discrepancies at a consensus meeting with a third review author. We contacted study authors to obtain missing data when required. An independent review author assessed risk of bias using the Cochrane 'Risk of bias' tool. We calculated risk ratios (RRs) for dichotomous outcomes, assessed heterogeneity amongst included studies, and performed subgroup analyses on study quality.
Main results
We included eight studies involving 4488 participants. Regarding quality of evidence, trials showed differences in study population, study design, type of antibiotic, and definition of infection; however, primary outcomes among the included studies were consistent. Mortality rate in the preventive antibiotic group was not significantly different from that in the control group (373/2208 (17%) vs 360/2214 (16%); RR 1.03, 95% confidence interval (CI) 0.87 to 1.21; high‐quality evidence). The number of participants with a poor functional outcome (death or dependency) in the preventive antibiotic therapy group was also not significantly different from that in the control group (1158/2168 (53%) vs 1182/2164 (55%); RR 0.99, 95% CI 0.89 to 1.10; moderate‐quality evidence). However, preventive antibiotic therapy did significantly reduce the incidence of 'overall' infections in participants with acute stroke from 26% to 19% (408/2161 (19%) vs 558/2156 (26%); RR 0.71, 95% CI 0.58 to 0.88; high‐quality evidence). This finding was highly significant for urinary tract infections (81/2131 (4%) vs 204/2126 (10%); RR 0.40, 95% CI 0.32 to 0.51; high‐quality evidence), whereas no preventive effect for pneumonia was found (222/2131 (10%) vs 235/2126 (11%); RR 0.95, 95% CI 0.80 to 1.13; high‐quality evidence). No major side effects of preventive antibiotic therapy were reported. Only two studies qualitatively assessed the occurrence of elevated body temperature; therefore, these results could not be pooled. Only one study reported length of hospital stay.
Authors' conclusions
Preventive antibiotics had no effect on functional outcome or mortality, but significantly reduced the risk of 'overall' infections. This reduction was driven mainly by prevention of urinary tract infection; no effect for pneumonia was found.
IMPORTANCE: The positive treatment effect of endovascular therapy (EVT) is assumed to be caused by the preservation of brain tissue. It remains unclear to what extent the treatment-related reduction ...in follow-up infarct volume (FIV) explains the improved functional outcome after EVT in patients with acute ischemic stroke. OBJECTIVE: To study whether FIV mediates the relationship between EVT and functional outcome in patients with acute ischemic stroke. DESIGN, SETTING, AND PARTICIPANTS: Patient data from 7 randomized multicenter trials were pooled. These trials were conducted between December 2010 and April 2015 and included 1764 patients randomly assigned to receive either EVT or standard care (control). Follow-up infarct volume was assessed on computed tomography or magnetic resonance imaging after stroke onset. Mediation analysis was performed to examine the potential causal chain in which FIV may mediate the relationship between EVT and functional outcome. A total of 1690 patients met the inclusion criteria. Twenty-five additional patients were excluded, resulting in a total of 1665 patients, including 821 (49.3%) in the EVT group and 844 (50.7%) in the control group. Data were analyzed from January to June 2017. MAIN OUTCOME AND MEASURE: The 90-day functional outcome via the modified Rankin Scale (mRS). RESULTS: Among 1665 patients, the median (interquartile range IQR) age was 68 (57-76) years, and 781 (46.9%) were female. The median (IQR) time to FIV measurement was 30 (24-237) hours. The median (IQR) FIV was 41 (14-120) mL. Patients in the EVT group had significantly smaller FIVs compared with patients in the control group (median IQR FIV, 33 11-99 vs 51 18-134 mL; P = .007) and lower mRS scores at 90 days (median IQR score, 3 1-4 vs 4 2-5). Follow-up infarct volume was a predictor of functional outcome (adjusted common odds ratio, 0.46; 95% CI, 0.39-0.54; P < .001). Follow-up infarct volume partially mediated the relationship between treatment type with mRS score, as EVT was still significantly associated with functional outcome after adjustment for FIV (adjusted common odds ratio, 2.22; 95% CI, 1.52-3.21; P < .001). Treatment-reduced FIV explained 12% (95% CI, 1-19) of the relationship between EVT and functional outcome. CONCLUSIONS AND RELEVANCE: In this analysis, follow-up infarct volume predicted functional outcome; however, a reduced infarct volume after treatment with EVT only explained 12% of the treatment benefit. Follow-up infarct volume as measured on computed tomography and magnetic resonance imaging is not a valid proxy for estimating treatment effect in phase II and III trials of acute ischemic stroke.
Clinical outcomes of patients with acute ischemic stroke depend in part on the extent of their collateral circulation. A good collateral circulation has also been associated with greater benefit of ...intravenous thrombolysis and endovascular treatment. Treatment decisions for these reperfusion therapies are increasingly guided by a combination of clinical and imaging parameters, particularly in later time windows. Computed tomography and magnetic resonance imaging enable a rapid assessment of both the collateral extent and cerebral perfusion. Yet, the role of the collateral circulation in clinical decision-making is currently limited and may be underappreciated due to the use of rather coarse and rater-dependent grading methods. In this review, we discuss determinants of the collateral circulation in patients with acute ischemic stroke, report on commonly used and emerging neuroimaging techniques for assessing the collateral circulation, and discuss the therapeutic and prognostic implications of the collateral circulation in relation to reperfusion therapies for acute ischemic stroke.
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