Follow-up infarct volume as a mediator of endovascular treatment effect on functional outcome in ischaemic stroke.

OBJECTIVE: The putative mechanism for the favourable effect of endovascular treatment (EVT) on functional outcome after acute ischaemic stroke is preventing follow-up infarct volume (FIV) progression. We aimed to assess to what extent difference in FIV explains the effect of EVT on functional outcome in a randomised trial of EVT versus no EVT (MR CLEAN). METHODS: FIV was assessed on non-contrast CT scan 5-7 days after stroke. Functional outcome was the score on the modified Rankin Scale at 3 months. We tested the causal pathway from intervention, via FIV to functional outcome with a mediation model, using linear and ordinal regression, adjusted for relevant baseline covariates, including stroke severity. Explained effect was assessed by taking the ratio of the log odds ratios of treatment with and without adjustment for FIV. RESULTS: Of the 500 patients included in MR CLEAN, 60 died and four patients underwent hemicraniectomy before FIV was assessed, leaving 436 patients for analysis. Patients in the intervention group had better functional outcomes (adjusted common odds ratio (acOR) 2.30 (95% CI 1.62-3.26) than controls and smaller FIV (median 53 vs. 81 ml) (difference 28 ml; 95% CI 13-41). Smaller FIV was associated with better outcome (acOR per 10 ml 0.60, 95% CI 0.52-0.68). After adjustment for FIV the effect of intervention on functional outcome decreased but remained substantial (acOR 2.05, 95% CI 1.44-2.91). This implies that preventing FIV progression explains 14% (95% CI 0-34) of the beneficial effect of EVT on outcome. CONCLUSION: The effect of EVT on FIV explains only part of the treatment effect on functional outcome. KEY POINTS: • Endovascular treatment in acute ischaemic stroke patients prevents progression of follow-up infarct volume on non-contrast CT at 5-7 days. • Follow-up infarct volume was related to functional outcome, but only explained a modest part of the effect of intervention on functional outcome. • A large proportion of treatment effect on functional outcome remains unexplained, suggesting FIV alone cannot be used as an early surrogate imaging marker of functional outcome.

Ruptured middle cerebral artery aneurysms with a concomitant intraparenchymal hematoma: the role of hematoma volume.

PURPOSE: To study whether clinical outcome data from our patient cohort could give support to the new recommendation in the AHA/ASA guidelines for the management of aneurysmal subarachnoid hemorrhage that states "that microsurgical clipping may receive increased consideration in patients with ruptured middle cerebral artery (MCA) aneurysms and large (>50 mL) intraparenchymal hematomas", while clinical outcome data supporting this recommendation are sparse. METHODS: We reviewed the clinical and radiological data of 81 consecutive patients with MCA aneurysms and concomitant hematomas admitted between January 2006 and December 2015. The relation between (semi-automatically quantified) hematoma volume (< or > 50 ml), neurological condition on admission (poor: GCS < 8 or non-reactive pupils), treatment strategies (no treatment, coiling, or clipping with or without decompression and/or clot removal), and outcome (favorable: mRS score 0-3) was evaluated. RESULTS: Clinical outcome data were available for 76 patients. A significant difference in favorable outcome (17 vs 68%) was seen when comparing patients with poor and good neurological condition on admission (p < 0.01). Patients with hematomas > 50 ml had similar outcomes for coiling and clipping, all underwent decompression. Patients with hematomas < 50 ml did not show differences in favorable outcome when comparing coiling and clipping with (33 and 31%) or without decompression (90 and 88%). CONCLUSION: Poor neurological condition on admission, and not large intraparenchymal hematoma volume, was associated with poor clinical outcome. Therefore, even in patients with large hematomas, the neurological condition on admission and the aneurysm configuration seem to be equally important factors to determine the most appropriate treatment strategy.

Added value of multiphase CTA imaging for thrombus perviousness assessment.

PURPOSE: Thrombus perviousness has been associated with favorable functional outcome in acute ischemic stroke (AIS) patients. Measuring thrombus perviousness on CTA may be suboptimal due to potential delay in contrast agent arrival in occluded arteries at the moment of imaging. Dynamic sequences acquired over time can potentially overcome this issue. We investigate if dynamic CTA has added value in assessing thrombus perviousness. METHODS: Prospectively collected image data of AIS patients with proven occlusion of the anterior or posterior circulation with thin-slice multi-phase CTA (MCTA) and non-contrast CT were co-registered (n = 221). Thrombus attenuation increase (TAI; a perviousness measure) was measured for the arterial, venous, and delayed phase of the MCTA and time-invariant CTAs (TiCTA). Associations with favorable clinical outcome (90-day mRS ≤ 2) were assessed using univariate and multivariable regressions and calculating areas under receiver operating curves (AUC). RESULTS: TAI determined from the arterial phase CTA was superior in the association with favorable outcome with OR = 1.21 per 10 HU increase (95%CI 1.04-1.41, AUC 0.62, p = 0.014) compared to any other phase (venous 1.14(95%CI 1.01-1.30, AUC 0.58, p = 0.033), delayed 1.046(95%CI 0.919-1.19, AUC 0.53, p = 0.50)), and TiCTA (1.15(95%CI 1.02-1.30, AUC 0.60, p = 0.022). In the multivariable model, only TAI on arterial phase was significantly associated with favorable outcome (aOR 1.59, 95%CI 1.04-2.43, p = 0.032). CONCLUSION: Association between TAI with functional outcome was optimal on arterial-phase CTA such that dynamic CTA imaging has no additional benefits in current thrombus perviousness assessment, thereby suggesting that the delay of contrast arrival at the clot is a key variable for patient functional outcome.

Quantitative agreement between [(15)O]H2O PET and model free QUASAR MRI-derived cerebral blood flow and arterial blood volume.

The purpose of this study was to assess whether there was an agreement between quantitative cerebral blood flow (CBF) and arterial cerebral blood volume (CBVA) measurements by [(15)O]H2O positron emission tomography (PET) and model-free QUASAR MRI. Twelve healthy subjects were scanned within a week in separate MRI and PET imaging sessions, after which quantitative and qualitative agreement between both modalities was assessed for gray matter, white matter and whole brain region of interests (ROI). The correlation between CBF measurements obtained with both modalities was moderate to high (r(2): 0.28-0.60, P < 0.05), although QUASAR significantly underestimated CBF by 30% (P < 0.001). CBVA was moderately correlated (r(2): 0.28-0.43, P < 0.05), with QUASAR yielding values that were only 27% of the [(15)O]H2O-derived values (P < 0.001). Group-wise voxel statistics identified minor areas with significant contrast differences between [(15)O]H2O PET and QUASAR MRI, indicating similar qualitative CBVA and CBF information by both modalities. In conclusion, the results of this study demonstrate that QUASAR MRI and [(15)O]H2O PET provide similar CBF and CBVA information, but with systematic quantitative discrepancies.

Prose memory impairment in amyotrophic lateral sclerosis patients is related to hippocampus volume.

BACKGROUND AND PURPOSE: Thirty per cent of amyotrophic lateral sclerosis (ALS) patients have non-motor symptoms, including executive and memory deficits. The in vivo anatomical basis of memory deficits in ALS has not been elucidated. In this observational study, brain atrophy in relation to memory function was investigated in ALS patients and controls. METHODS: Twenty-six ALS patients without dementia and 21 healthy volunteers matched for gender, age and education level underwent comprehensive neuropsychological evaluation and T1- and T2-weighted 3 T magnetic resonance imaging scanning of the brain. Grey and white matter brain volumes were analysed using voxel-based morphometry and age related white matter changes were assessed. The most frequently abnormal memory test (<2 SD below normative data corrected for age, gender and education) was correlated with regional brain volume variations by multiple regression analyses with age, gender and total grey matter volumes as covariates. RESULTS: Immediate and delayed story recall scores were abnormal in 23% of ALS patients and correlated to bilateral hippocampus grey matter volume (r = 0.52 for both memory tests; P < 0.05; corrected for age, gender and total grey matter volume). This correlation was not found in healthy controls with similar age, education, anxiety and depression levels and white matter changes. CONCLUSIONS: Prose memory impairment is a frequent finding in this cohort and is associated with hippocampus volume in ALS patients without dementia. These findings complement previous hippocampus changes in imaging studies in ALS and suggest involvement of the hippocampus in cognitive dysfunction of ALS.

CT angiography versus 3D rotational angiography in patients with subarachnoid hemorrhage.

INTRODUCTION: CT angiography (CTA) is increasingly used as primary diagnostic tool to replace digital subtraction angiography (DSA) in patients with subarachnoid hemorrhage (SAH). However, 3D rotational angiography (3DRA) has substituted DSA as a reference standard. In this prospective observational study, we compare CTA with 3DRA of all cerebral vessels in a large cohort of patients with SAH. METHODS: Of 179 consecutive patients with SAH admitted between March 2013 and July 2014, 139 underwent 64- to 256-detector row CTA followed by complete cerebral 3DRA within 24 h. In 86 patients (62 %), 3DRA was performed under general anesthesia. Two observers from outside hospitals reviewed CTA data. RESULTS: In 118 of 139 patients (85 %), 3DRA diagnosed the cause of hemorrhage: 113 ruptured aneurysms, three arterial dissections, one micro-arteriovenous malformation (AVM), and one reversible vasoconstriction syndrome. On CTA, both observers missed all five non-aneurysmal causes of SAH. Sensitivity of CTA in depicting ruptured aneurysms was 0.88-0.91, and accuracy was 0.88-0.92. Of 113 ruptured aneurysms, 28 were ≤3 mm (25 %) and of 95 additional aneurysms, 71 were ≤3 mm (75 %). Sensitivity of depicting aneurysms ≤3 mm was 0.28-0.43. Of 95 additional aneurysms, the two raters missed 65 (68 %) and 58 (61 %). Sensitivity in detection was lower in aneurysms of the internal carotid artery than in other locations. CONCLUSION: CTA had some limitations as primary diagnostic tool in patients with SAH. All non-aneurysmal causes for SAH and one in ten ruptured aneurysms were missed. Performance of CTA was poor in aneurysms ≤3 mm. The majority of additional aneurysms were not depicted on CTA.

Accuracy and precision of pseudo-continuous arterial spin labeling perfusion during baseline and hypercapnia: a head-to-head comparison with ¹5O H2O positron emission tomography.

Measurements of the cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) provide useful information about cerebrovascular condition and regional metabolism. Pseudo-continuous arterial spin labeling (pCASL) is a promising non-invasive MRI technique to quantitatively measure the CBF, whereas additional hypercapnic pCASL measurements are currently showing great promise to quantitatively assess the CVR. However, the introduction of pCASL at a larger scale awaits further evaluation of the exact accuracy and precision compared to the gold standard. (15)O H2O positron emission tomography (PET) is currently regarded as the most accurate and precise method to quantitatively measure both CBF and CVR, though it is one of the more invasive methods as well. In this study we therefore assessed the accuracy and precision of quantitative pCASL-based CBF and CVR measurements by performing a head-to-head comparison with (15)O H2O PET, based on quantitative CBF measurements during baseline and hypercapnia. We demonstrate that pCASL CBF imaging is accurate during both baseline and hypercapnia with respect to (15)O H2O PET with a comparable precision. These results pave the way for quantitative usage of pCASL MRI in both clinical and research settings.

Age determination of subdural hematomas: survey among radiologists.

Abusive head trauma is a severe form of child abuse. One important diagnostic finding is the presence of a subdural hematoma. Age determination of subdural hematomas is important to relate radiological findings to the clinical history presented by the caregivers. In court this topic is relevant as dating subdural hematomas can lead to identification of a suspect. The aim of our study is to describe the current practice among radiologists in the Netherlands regarding the age determination of subdural hematomas in children. This is a cross-sectional study, describing the results of an online questionnaire regarding dating subdural hematomas among pediatric and neuro-radiologists in the Netherlands. The questionnaire consisted of sociodemographic questions, theoretical questions and eight pediatric cases in which the participants were asked to date subdural hematomas based on imaging findings. Fifty-one out of 172 radiologists (30 %) filled out the questionnaire. The percentage of participants that reported it was possible to date the subdural hematoma varied between 58 and 90 % for the eight different cases. In four of eight cases (50 %), the age of the subdural hematoma as known from clinical history fell within the range reported by the participants. None of the participants was "very certain" of their age determination. The results demonstrate that there is a considerable practice variation among Dutch radiologists regarding the age determination of subdural hematomas. This implicates that dating of subdural hematomas is not suitable to use in court, as no uniformity among experts exists.

Mapping the hemodynamic response in human subjects to a dopaminergic challenge with dextroamphetamine using ASL-based pharmacological MRI.

Pharmacological magnetic resonance imaging (phMRI) maps the neurovascular response to a pharmacological challenge and is increasingly used to assess neurotransmitter systems. Here we investigated the hemodynamic response to a dopaminergic (DAergic) challenge with dextroamphetamine (dAMPH) in humans using arterial spin labeling (ASL) based phMRI. Twelve healthy male subjects aged 21.0years (±1.5) were included. We used a pseudo-continuous ASL sequence (40min) to quantify cerebral blood flow (CBF) and started dAMPH infusion (0.3mg/kg) after 10min. On another day, we measured baseline dopamine D2/3 receptor availability with [(123)I]IBZM single photon emission computed tomography (SPECT). Baseline measures on mood and impulsivity and subjective behavioral responses to dAMPH were obtained. CBF response was corrected for cardiovascular effects using an occipital cortex mask for internal reference. Corrected CBF (sCBF) was analyzed using ROI-based and voxel-based analysis, in addition to independent component analysis (ICA). CBF data was correlated to D2/3 receptor availability and behavioral measures. Subjects reported experiencing euphoria following dAMPH administration. In the striatum sCBF significantly increased, as demonstrated by all three analysis methods. Voxel-based analysis and ICA also showed increased sCBF in the thalamus, anterior cingulate and cerebellum. Decreased sCBF was observed in several cortical areas, the posterior cingulated and paracingulate cortex. Apart from one ICA component, no correlations were found with sCBF changes and D2/3 receptor availability and behavioral measures. Our observations are in line with literature and provide further evidence that ASL-based phMRI with dAMPH is a promising technique to assess DAergic function in human subjects.

Quantification and visualization of flow in the Circle of Willis: time-resolved three-dimensional phase contrast MRI at 7 T compared with 3 T.

The assessment of both geometry and hemodynamics of the intracranial arteries has important diagnostic value in internal carotid occlusion, sickle cell disease, and aneurysm development. Provided that signal to noise ratio (SNR) and resolution are high, these factors can be measured with time-resolved three-dimensional phase contrast MRI. However, within a given scan time duration, an increase in resolution causes a decrease in SNR and vice versa, hampering flow quantification and visualization. To study the benefits of higher SNR at 7 T, three-dimensional phase contrast MRI in the Circle of Willis was performed at 3 T and 7 T in five volunteers. Results showed that the SNR at 7 T was roughly 2.6 times higher than at 3 T. Therefore, segmentation of small vessels such as the anterior and posterior communicating arteries succeeded more frequently at 7 T. Direction of flow and smoothness of streamlines in the anterior and posterior communicating arteries were more pronounced at 7 T. Mean velocity magnitude values in the vessels of the Circle of Willis were higher at 3 T due to noise compared to 7 T. Likewise, areas of the vessels were lower at 3 T. In conclusion, the gain in SNR at 7 T compared to 3 T allows for improved flow visualization and quantification in intracranial arteries.

Detection of patent foramen ovale in patients with ischemic stroke on prospective ECG-gated cardiac CT compared to transthoracic echocardiography.

BACKGROUND: Cardiac CT acquired during the acute stroke imaging protocol is an emerging alternative to transthoracic echocardiography (TTE) to screen for sources of cardioembolism. Currently, its diagnostic accuracy to detect patent foramen ovale (PFO) is unclear. METHODS: This was a substudy of Mind the Heart, a prospective cohort in which consecutive adult patients with acute ischemic stroke underwent prospective ECG-gated cardiac CT during the initial stroke imaging protocol. Patients also underwent TTE. We included patients < 60 years who underwent TTE with agitated saline contrast (cTTE) and assessed sensitivity, specificity, negative and positive predictive value of cardiac CT for the detection of PFO using cTTE as the reference standard. RESULTS: Of 452 patients in Mind the Heart, 92 were younger than 60 years. Of these, 59 (64%) patients underwent both cardiac CT and cTTE and were included. Median age was 54 (IQR 49-57) years and 41/59 (70%) were male. Cardiac CT detected a PFO in 5/59 (8%) patients, 3 of which were confirmed on cTTE. cTTE detected a PFO in 12/59 (20%) patients. Sensitivity and specificity of cardiac CT were 25% (95% CI 5-57%) and 96% (95% CI 85-99%), respectively. Positive and negative predictive values were 59% (95% CI 14-95) and 84% (95% CI 71-92). CONCLUSION: Prospective ECG-gated cardiac CT acquired during the acute stroke imaging protocol does not appear to be a suitable screening method for PFO due to its low sensitivity. Our data suggest that if cardiac CT is used as a first-line screening method for cardioembolism, additional echocardiography remains indicated in young patients with cryptogenic stroke, in whom PFO detection would have therapeutic consequences. These results need to be confirmed in larger cohorts.

Correlation between EEG spectral power and cerebral perfusion in patients with acute ischemic stroke.

Dry electrode electroencephalography (EEG) has the potential to diagnose ischemic stroke in the acute phase. In the current study we determined the correlation between EEG spectral power and ischemic stroke size and location as determined by computed tomography perfusion (CTP). Dry electrode EEG recordings were performed in patients with acute ischemic stroke in the emergency room. CTP preceded the EEG recordings as part of standard imaging protocol. Infarct core volume, total hypoperfused volume and local cerebral blood flow (CBF) were estimated with CTP. Additionally, global and local EEG spectral power were determined. We used Spearman's correlation coefficients to evaluate the correlation between variables. We included 27 patients (median age 72 [IQR:69-80] years, 15/27 [56%] men). Median CTP-to-EEG time was 32 (range:8-138) minutes. Hypoperfused volumes were estimated for 12/27 (44%) patients. Infarct core volume correlated best with global delta power (ρ = 0.76, p < 0.01), total hypoperfused volume with global alpha power (ρ = -0.58, p = 0.05), and local CBF with local alpha power (ρ = 0.43, p < 0.01). We conclude that dry electrode EEG signals slow down with increasing hypoperfused volume, which could potentially be used to discriminate between small and large ischemic strokes.

Cardiac thrombus dissolution in acute ischemic stroke: A substudy of Mind the Heart.

Background: Cardiac thrombi are an important cause of ischemic stroke but are infrequently detected on cardiac imaging. We hypothesized that this might be explained by early dissolution of these cardiac thrombi after stroke occurrence. Methods: We performed a single-center observational pilot study between November 2019 and November 2020, embedded in the larger "Mind-the-Heart" study. We included patients with AIS and a cardiac thrombus in the left atrium or ventricle (filling defect <100 Hounsfield Units) diagnosed on cardiac CT that was acquired during the initial stroke imaging protocol. We repeated cardiac CT within one week to determine if the thrombus had dissolved. Results: Five patients (four men, median age 52 years, three with atrial fibrillation and one with anticoagulation therapy at baseline) were included. Median time from symptom onset to first cardiac CT was 383 (range 42-852) minutes and median time from first to second cardiac CT was three days (range 1-7). Two patients received intravenous thrombolysis (IVT). In total, six thrombi were seen on initial CT imaging (one in the left ventricle, four in the left atrial appendage, one in the left atrium). The left atrium thrombus and one left atrial appendage thrombus had dissolved on follow-up cardiac CT, one of which was in a patient with IVT treatment. Conclusion: This pilot study illustrates that cardiac thrombi can dissolve within days of stroke occurrence both with and without IVT treatment.

Infarct Evolution in Patients with Anterior Circulation Large-Vessel Occlusion Randomized to IV Alteplase and Endovascular Treatment versus Endovascular Treatment Alone.

BACKGROUND AND PURPOSE: Infarct evolution after endovascular treatment varies widely among patients with stroke and may be affected by baseline characteristics and procedural outcomes. Moreover, IV alteplase and endovascular treatment may influence the relationship of these factors to infarct evolution. We aimed to assess whether the infarct evolution between baseline and follow-up imaging was different for patients who received IVT and EVT versus EVT alone. MATERIALS AND METHODS: We included patients from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN)-NO IV trial with baseline CTP and follow-up imaging. Follow-up infarct volume was segmented on 24-hour or 1-week follow-up DWI or NCCT. Infarct evolution was defined as the follow-up lesion volume: CTP core volume. Substantial infarct growth was defined as an increase in follow-up infarct volume of >10 mL. We assessed whether infarct evolution was different for patients with IV alteplase and endovascular treatment versus endovascular treatment alone and evaluated the association of baseline characteristics and procedural outcomes with infarct evolution using multivariable regression. RESULTS: From 228 patients with CTP results available, 145 patients had follow-up imaging and were included in our analysis. For patients with IV alteplase and endovascular treatment versus endovascular treatment alone, the baseline median CTP core volume was 17 (interquartile range = 4-35) mL versus 11 (interquartile range = 6-24) mL. The median follow-up infarct volume was 13 (interquartile range, 4-48) mL versus 17 (interquartile range = 4-50) mL. Collateral status and occlusion location were negatively associated with substantial infarct growth in patients with and without IV alteplase before endovascular treatment. CONCLUSIONS: No statistically significant difference in infarct evolution was found in directly admitted patients who received IV alteplase and endovascular treatment within 4.5 hours of symptom onset versus patients who underwent endovascular treatment alone. Collateral status and occlusion location may be useful predictors of infarct evolution prognosis in patients eligible for IV alteplase who underwent endovascular treatment.

Complex flow patterns in a real-size intracranial aneurysm phantom: phase contrast MRI compared with particle image velocimetry and computational fluid dynamics.

The aim of this study was to validate the flow patterns measured by high-resolution, time-resolved, three-dimensional phase contrast MRI in a real-size intracranial aneurysm phantom. Retrospectively gated three-dimensional phase contrast MRI was performed in an intracranial aneurysm phantom at a resolution of 0.2 × 0.2 × 0.3 mm(3) in a solenoid rat coil. Both steady and pulsatile flows were applied. The phase contrast MRI measurements were compared with particle image velocimetry measurements and computational fluid dynamics simulations. A quantitative comparison was performed by calculating the differences between the magnitude of the velocity vectors and angles between the velocity vectors in corresponding voxels. Qualitative analysis of the results was executed by visual inspection and comparison of the flow patterns. The root-mean-square errors of the velocity magnitude in the comparison between phase contrast MRI and computational fluid dynamics were 5% and 4% of the maximum phase contrast MRI velocity, and the medians of the angle distribution between corresponding velocity vectors were 16° and 14° for the steady and pulsatile measurements, respectively. In the phase contrast MRI and particle image velocimetry comparison, the root-mean-square errors were 12% and 10% of the maximum phase contrast MRI velocity, and the medians of the angle distribution between corresponding velocity vectors were 19° and 15° for the steady and pulsatile measurements, respectively. Good agreement was found in the qualitative comparison of flow patterns between the phase contrast MRI measurements and both particle image velocimetry measurements and computational fluid dynamics simulations. High-resolution, time-resolved, three-dimensional phase contrast MRI can accurately measure complex flow patterns in an intracranial aneurysm phantom.

Tranexamic acid to prevent operation in chronic subdural haematoma (TORCH): study protocol for a randomised placebo-controlled clinical trial.

BACKGROUND: Chronic subdural haematoma (cSDH) occurs mainly in the elderly. Surgical evacuation is effective, but in these old, often frail, patients with multi-comorbidity, surgery carries significant risks for future cognitive functioning and loss of independency. Therefore, a growing interest is noted for a non-surgical treatment with medication such as tranexamic acid (TXA). In five small retrospective series, this antifibrinolytic drug showed a beneficial effect on the spontaneous resolution of the haematoma, and with that, the necessity for surgery. METHODS: For this randomised, placebo-controlled clinical multicentre trial, all cSDH patients, over 50 years old with mild symptoms (Glasgow Coma Score (GCS) ≥ 14, modified National Institutes of Health Stroke Scale (mNIHSS) ≤ 4), a midline shift of ≤ 10 mm and in whom a primary conservative treatment is chosen, are eligible for study participation. After informed consent, 140 patients will be randomised to receive either TXA 500 mg or placebo two times daily for 28 days. The primary outcome is the necessity for surgery within 12 weeks; secondary outcomes are cSDH volume, neurological impairment (mNIHSS), falling incidents, cognitive functioning (Montreal Cognitive Assessment (MOCA)), performance in activities of daily living (Barthel and Lawton score), functional outcome (modified Rankin Scale (mRS)), quality of life (Short Form Health Survey (SF-36) and EuroQol 5-Dimension Health Survey (EQ-5D)), mortality and the use of care and health-related costs (Medical Consumption Questionnaire (iMCQ) and Productivity Cost Questionnaire (iPCQ)) at 12 weeks and 6 months. DISCUSSION: This phase III trial investigating the efficacy of TXA to prevent surgery for cSDH is the first in including patients using anticoagulants and mentally incompetent patients, since these comprise a significant part of the target population. Also, this study is one of the first to prospectively measure functional outcome and quality of life in cSDH patients. Final results of this study are expected in 2024. TRIAL REGISTRATION: Dutch Trial Registry (Nederlands Trial Register) NL6584 . Registered on 11 November 2017 ClinicalTrials.gov NCT03582293 . Registered on 11 July 2018 EU Clinical Trials Register 2017-004311-40 . Registered on 29 March 2018.

Association of hyperglycemia and computed tomographic perfusion deficits in patients who underwent endovascular treatment for acute ischemic stroke caused by a proximal intracranial occlusion: A subgroup analysis of a randomized phase 3 trial (MR CLEAN).

INTRODUCTION: Hyperglycemia is highly prevalent in patients with acute ischemic stroke and is associated with increased risk of symptomatic intracranial hemorrhage, larger infarct size and unfavorable outcome. Furthermore, glucose may modify the effect of endovascular treatment (EVT) in patients with ischemic stroke. Hyperglycemia might lead to accelerated conversion of penumbra into infarct core. However, it remains uncertain whether hyperglycemia on admission is associated with the size of penumbra or infarct core in acute ischemic stroke. In this study, we aimed to assess the association between hyperglycemia and Computed Tomographic Perfusion (CTP) derived parameters in patients who underwent EVT for acute ischemic stroke. METHODS: We used data from the MR CLEAN study (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). Hyperglycemia was defined as admission serum glucose of >7.8 mmol/L. Dichotomized and quantiles of glucose levels were related to size of core, penumbra and core penumbra ratio. Hypoperfused area is mean transient time 45% higher than that of the contralateral hemisphere. Core is the area with cerebral blood volume of <2 mL/100 g and penumbra is the area with cerebral blood volume > 2 mL/100 g. Core-penumbra ratio is the ischemic core divided by the total volume of hypoperfused tissue (core plus penumbra) multiplied by 100. Adjustments were made for age, sex, NIHSS on admission, onset-imaging time and diabetes mellitus. RESULTS: Hundred seventy-three patients were included. Median glucose level on admission was 6.5 mmol/L (IQR 5.8-7.5 mmol/L) and thirty-five patients (20%) were hyperglycemic. Median core volume was 33.3 mL (IQR 13.6-62.4 mL), median penumbra volume was 80.2 mL (IQR 36.3-123.5 mL) and median core-penumbra ratio was 28.5% (IQR 18.6-45.8%). Patients with hyperglycemia on admission had larger core volumes and core penumbra ratio than normoglycemic patients with a regression coefficient of 15.1 (95% confidence interval (CI), 1.8 to 28.3) and 11.5 (95% confidence interval (CI), 3.4 to 19.7) respectively. CONCLUSION: Hyperglycemia on admission was associated with larger ischemic core volume and larger core-penumbra ratio in patients with acute ischemic stroke who underwent endovascular treatment.

Unsupervised Deep Learning for Stroke Lesion Segmentation on Follow-up CT Based on Generative Adversarial Networks.

BACKGROUND AND PURPOSE: Supervised deep learning is the state-of-the-art method for stroke lesion segmentation on NCCT. Supervised methods require manual lesion annotations for model development, while unsupervised deep learning methods such as generative adversarial networks do not. The aim of this study was to develop and evaluate a generative adversarial network to segment infarct and hemorrhagic stroke lesions on follow-up NCCT scans. MATERIALS AND METHODS: Training data consisted of 820 patients with baseline and follow-up NCCT from 3 Dutch acute ischemic stroke trials. A generative adversarial network was optimized to transform a follow-up scan with a lesion to a generated baseline scan without a lesion by generating a difference map that was subtracted from the follow-up scan. The generated difference map was used to automatically extract lesion segmentations. Segmentation of primary hemorrhagic lesions, hemorrhagic transformation of ischemic stroke, and 24-hour and 1-week follow-up infarct lesions were evaluated relative to expert annotations with the Dice similarity coefficient, Bland-Altman analysis, and intraclass correlation coefficient. RESULTS: The median Dice similarity coefficient was 0.31 (interquartile range, 0.08-0.59) and 0.59 (interquartile range, 0.29-0.74) for the 24-hour and 1-week infarct lesions, respectively. A much lower Dice similarity coefficient was measured for hemorrhagic transformation (median, 0.02; interquartile range, 0-0.14) and primary hemorrhage lesions (median, 0.08; interquartile range, 0.01-0.35). Predicted lesion volume and the intraclass correlation coefficient were good for the 24-hour (bias, 3 mL; limits of agreement, -64-59 mL; intraclass correlation coefficient, 0.83; 95% CI, 0.78-0.88) and excellent for the 1-week (bias, -4 m; limits of agreement,-66-58 mL; intraclass correlation coefficient, 0.90; 95% CI, 0.83-0.93) follow-up infarct lesions. CONCLUSIONS: An unsupervised generative adversarial network can be used to obtain automated infarct lesion segmentations with a moderate Dice similarity coefficient and good volumetric correspondence.

Evolutionary algorithms and decision trees for predicting poor outcome after endovascular treatment for acute ischemic stroke.

Despite the large overall beneficial effects of endovascular treatment in patients with acute ischemic stroke, severe disability or death still occurs in almost one-third of patients. These patients, who might not benefit from treatment, have been previously identified with traditional logistic regression models, which may oversimplify relations between characteristics and outcome, or machine learning techniques, which may be difficult to interpret. We developed and evaluated a novel evolutionary algorithm for fuzzy decision trees to accurately identify patients with poor outcome after endovascular treatment, which was defined as having a modified Rankin Scale score (mRS) higher or equal to 5. The created decision trees have the benefit of being comprehensible, easily interpretable models, making its predictions easy to explain to patients and practitioners. Insights in the reason for the predicted outcome can encourage acceptance and adaptation in practice and help manage expectations after treatment. We compared our proposed method to CART, the benchmark decision tree algorithm, on classification accuracy and interpretability. The fuzzy decision tree significantly outperformed CART: using 5-fold cross-validation with on average 1090 patients in the training set and 273 patients in the test set, the fuzzy decision tree misclassified on average 77 (standard deviation of 7) patients compared to 83 (±7) using CART. The mean number of nodes (decision and leaf nodes) in the fuzzy decision tree was 11 (±2) compared to 26 (±1) for CART decision trees. With an average accuracy of 72% and much fewer nodes than CART, the developed evolutionary algorithm for fuzzy decision trees might be used to gain insights into the predictive value of patient characteristics and can contribute to the development of more accurate medical outcome prediction methods with improved clarity for practitioners and patients.

Impact of the COVID-19 outbreak on acute stroke care.

BACKGROUND AND PURPOSE: There are concerns that the coronavirus disease 2019 (COVID-19) outbreak negatively affects the quality of care for acute cardiovascular conditions. We assessed the impact of the COVID-19 outbreak on trends in hospital admissions and workflow parameters of acute stroke care in Amsterdam, The Netherlands. METHODS: We used data from the three hospitals that provide acute stroke care for the Amsterdam region. We compared two 7-week periods: one during the peak of the COVID-19 outbreak (March 16th-May 3th 2020) and one prior to the outbreak (October 21st-December 8th 2019). We included consecutive patients who presented to the emergency departments with a suspected stroke and assessed the change in number of patients as an incidence-rate ratio (IRR) using a Poisson regression analysis. Other outcomes were the IRR for stroke subtypes, change in use of reperfusion therapy, treatment times, and in-hospital complications. RESULTS: During the COVID-19 period, 309 patients presented with a suspected stroke compared to 407 patients in the pre-COVID-19 period (IRR 0.76 95%CI 0.65-0.88). The proportion of men was higher during the COVID-19 period (59% vs. 47%, p < 0.001). There was no change in the proportion of stroke patients treated with intravenous thrombolysis (28% vs. 30%, p = 0.58) or endovascular thrombectomy (11% vs 12%, p = 0.82) or associated treatment times. Seven patients (all ischemic strokes) were diagnosed with COVID-19. CONCLUSION: We observed a 24% decrease in suspected stroke presentations during the COVID-19 outbreak, but no evidence for a decrease in quality of acute stroke care.