Microstructural brain injury in post-concussion syndrome after minor head injury

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

Prediction of final infarct volume from native CT perfusion and treatment parameters using deep learning

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.Comment: Accepted for publication in Medical Image Analysi

Ordinal outcome analysis improves the detection of between-hospital differences in outcome

Background: There is a growing interest in assessment of the quality of hospital care, based on outcome measures. Many quality of care comparisons rely on binary outcomes, for example mortality rates. Due to low numbers, the observed differences in outcome are partly subject to chance. We aimed to quantify the gain in efficiency by ordinal instead of binary outcome analyses for hospital comparisons. We analyzed patients with traumatic brain injury (TBI) and stroke as examples. Methods: We sampled patients from two trials. We simulated ordinal and dichotomous outcomes based on the modified Rankin Scale (stroke) and Glasgow Outcome Scale (TBI) in scenarios with and without true differences between hospitals in outcome. The potential efficiency gain of ordinal outcomes, analyzed with ordinal logistic regression, compared to dichotomous outcomes, analyzed with binary logistic regression was expressed as the possible reduction in sample size while keeping the same statistical power to detect outliers. Results: In the IMPACT study (9578 patients in 265 hospitals, mean number of patients per hospital = 36), the analysis of the ordinal scale rather than the dichotomized scale (‘unfavorable outcome’), allowed for up to 32% less patients in the analysis without a loss of power. In the PRACTISE trial (1657 patients in 12 hospitals, mean number of patients per hospital = 138), ordinal analysis allowed for 13% less patients. Compared to mortality, ordinal outcome analyses allowed for up to 37 to 63% less patients. Conclusions: Ordinal analyses provide the statistical power of substantially larger studies which have been analyzed with dichotomization of endpoints. We advise to exploit ordinal outcome measures for hospital comparisons, in order to increase efficiency in quality of care measurements. Trial registration: We do not report the results of a health care intervention

Prediction of intracranial findings on CT-scans by alternative modelling techniques

Background: Prediction rules for intracranial traumatic findings in patients with minor head injury are designed to reduce the use of computed tomography (CT) without missing patients at risk for complications. This study investigates whether alternative modelling techniques might improve the applicability and simplicity of such prediction rules. Methods. We included 3181 patients with minor head injury who had received CT scans be

PRECIOUS: PREvention of Complications to Improve OUtcome in elderly patients with acute Stroke: rationale and design of a randomised, open, phase III, clinical trial with blinded outcome assessment

Background: Elderly patients are at high risk of complications after stroke, such as infections and fever. The occurrence of these complications has been associated with an increased risk of death or dependency. Hypothesis: Prevention of aspiration, infections, or fever with metoclopramide, ceftriaxone, paracetamol, or any combination of these in the first four days after stroke onset will improve functional outcome at 90 days in elderly patients with acute stroke. Design: International, 3 × 2-factorial, randomised-controlled, open-label clinical trial with blinded outcome assessment (PROBE) in 3800 patients aged 66 years or older with acute ischaemic stroke or intracerebral haemorrhage and an NIHSS score ≥ 6. Patients will be randomly allocated to any combination of oral, rectal, or intravenous metoclopramide (10 mg thrice daily); intravenous ceftriaxone (2000 mg once daily); oral, rectal, or intravenous paracetamol (1000 mg four times daily); or usual care, started within 24 h after symptom onset and continued for four days or until complete recovery or discharge from hospital, if earlier. Outcome: The primary outcome measure is the score on the modified Rankin Scale at 90 days (± 14 days), as analysed with multiple regression. Summary: This trial will provide evidence for a simple, safe and generally available treatment strategy that may reduce the burden of death or disability in patients with stroke at very low costs. Planning: First patient included in May 2016; final follow-up of the last patient by April 202

Validation of automated Alberta Stroke Program Early CT Score (ASPECTS) software for detection of early ischemic changes on non-contrast brain CT scans

Purpose: In ASPECTS, 10 brain regions are scored visually for presence of acute ischemic stroke damage. We evaluated automated ASPECTS in comparison to expert readers. Methods: Consecutive, baseline non-contrast CT-scans (5-mm slice thickness) from the prospective MR CLEAN trial (n = 459, MR CLEAN Netherlands Trial Registry number: NTR1804) were evaluated. A two-observer consensus for ASPECTS regions (normal/abnormal) was used as reference standard for training and testing (0.2/0.8 division). Two other observers provided individual ASPECTS-region scores. The Automated ASPECTS software was applied. A region score specificity of ≥ 90% was used to determine the software threshold for detection of an affected region based on relative density difference between affected and contralateral region. Sensitivity, specificity, and receiver-operating characteristic curves were calculated. Additionally, we assessed intraclass correlation coefficients (ICCs) for automated ASPECTS and observers in comparison to the reference standard in the test set. Results: In the training set (n = 104), with software thresholds for a specificity of ≥ 90%, we found a sensitivity of 33–49% and an area under the curve (AUC) of 0.741–0.785 for detection of an affected ASPECTS region. In the test set (n = 355), the results for the found software thresholds were 89–89% (specificity), 41–57% (sensitivity), and 0.750–0.795 (AUC). Comparison of automated ASPECTS with the reference standard resulted in an ICC of 0.526. Comparison of observers with the reference standard resulted in an ICC of 0.383–0.464. Conclusion: The performance of automated ASPECTS is comparable to expert readers and could support readers in the detection of early ischemic changes

Management of Mild Traumatic Brain Injury at the Emergency Department and Hospital Admission in Europe: A Survey of 71 Neurotrauma Centers Participating in the CENTER-TBI Study.

Previous studies have indicated that there is no consensus about management of mild traumatic brain injury (mTBI) at the emergency department (ED) and during hospital admission. We aim to study variability between management policies for TBI patients at the ED and at the hospital ward across Europe. Centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study received questionnaires about different phases of TBI care. These questionnaires included 71 questions about TBI management at the ED and at the hospital ward. We found differences in how centers defined mTBI. For example, 40 centers (59%) defined mTBI as a Glasgow Coma Scale (GCS) score between 13 and 15 and 26 (38%) defined it as a GCS score between 14 and 15. At the ED various guidelines for the use of head computed tomography (CT) in mTBI patients were used; 32 centers (49%) used national guidelines, 10 centers (15%) local guidelines, and 14 centers (21%) used no guidelines at all. Also, differences in indication for admission between centers were found. After ED discharge, 7 centers (10%) scheduled a routine follow-up appointment, whereas 38 (54%) did so only after ward admission. In conclusion, large between-center variation exists in policies for diagnostics, admission, and discharge decisions in patients with mTBI at the ED and in the hospital. Guidelines are not always operational in centers, and reported policies systematically diverge from what is recommended in those guidelines. The results of this study may be useful in the understanding of mTBI care in Europe and show the need for further studies on the effectiveness of different policies on outcome

Hospital Variation in Time to Endovascular Treatment for Ischemic Stroke:What Is the Optimal Target for Improvement?

Background Time to reperfusion in patients with ischemic stroke is strongly associated with functional outcome and may differ between hospitals and between patients within hospitals. Improvement in time to reperfusion can be guided by between-hospital and within-hospital comparisons and requires insight in specific targets for improvement. We aimed to quantify the variation in door-to-reperfusion time between and within Dutch intervention hospitals and to assess the contribution of different time intervals to this variation. Methods and Results We used data from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry. The door-to-reperfusion time was subdivided into time intervals, separately for direct patients (door-to-computed tomography, computed tomography-to-computed tomography angiography [CTA], CTA-to-groin, and groin-to-reperfusion times) and for transferred patients (door-to-groin and groin-to-reperfusion times). We used linear mixed models to distinguish the variation in door-to-reperfusion time between hospitals and between patients. The proportional change in variance was used to estimate the amount of variance explained by each time interval. We included 2855 patients of 17 hospitals providing endovascular treatment. Of these patients, 44% arrived directly at an endovascular treatment hospital. The between-hospital variation in door-to-reperfusion time was 9%, and the within-hospital variation was 91%. The contribution of case-mix variables on the variation in door-to-reperfusion time was marginal (2%-7%). Of the between-hospital variation, CTA-to-groin time explained 83%, whereas groin-to-reperfusion time explained 15%. Within-hospital variation was mostly explained by CTA-to-groin time (33%) and groin-to-reperfusion time (42%). Similar results were found for transferred patients. Conclusions Door-to-reperfusion time varies between, but even more within, hospitals providing endovascular treatment for ischemic stroke. Quality of stroke care improvements should not only be guided by between-hospital comparisons, but also aim to reduce variation between patients within a hospital, and should specifically focus on CTA-to-groin time and groin-to-reperfusion time

High Early Fluid Input After Aneurysmal Subarachnoid Hemorrhage: Combined Report of Association With Delayed Cerebral Ischemia and Feasibility of Cardiac Output–Guided Fluid Restriction

Background: Guidelines on the management of aneurysmal subarachnoid hemorrhage (aSAH) recommend euvolemia, whereas hypervolemia may cause harm. We investigated whether high early fluid input is associated with delayed cerebral ischemia (DCI), and if fluid input can be safely decreased using transpulmonary thermodilution (TPT). Methods: We retrospectively included aSAH patients treated at an academic intensive care unit (2007-2011; cohort 1) or managed with TPT (2011-2013; cohort 2). Local guidelines recommended fluid input of 3 L daily. More fluids were administered when daily fluid balance fell below +500 mL. In cohort 2, fluid input in high-risk patients was guided by cardiac output measured by TPT per a strict protocol. Associations of fluid input and balance with DCI were analyzed with multivariable logistic regression (cohort 1), and changes in hemodynamic indices after institution of TPT assessed with linear mixed models (cohort 2). Results: Cumulative fluid input 0 to 72 hours after admission was associated with DCI in cohort 1 (n=223; odds ratio [OR] 1.19/L; 95% confidence interval 1.07-1.32), whereas cumulative fluid balance was not. In cohort 2 (23 patients), using TPT fluid input could be decreased from 6.0 ± 1.0 L before to 3.4 ± 0.3 L; P =.012), while preload parameters and consciousness remained stable. Conclusion: High early fluid input was associated with DCI. Invasive hemodynamic monitoring was feasible to reduce fluid input while maintaining preload. These results indicate that fluid loading beyond a normal preload occurs, may increase DCI risk, and can be minimized with TPT