Observer variability of absolute and relative thrombus density measurements in patients with acute ischemic stroke

Introduction: Thrombus density may be a predictor for acute ischemic stroke treatment success. However, only limited data on observer variability for thrombus density measurements exist. This study assesses the variability and bias of four common thrombus density measurement methods by expert and non-expert observers. Methods: For 132 consecutive patients with acute ischemic stroke, three experts and two trained observers determined thrombus density by placing three standardized regions of interest (ROIs) in the thrombus and corresponding contralateral arterial segment. Subsequently, absolute and relative thrombus densities were determined using either one or three ROIs. Intraclass correlation coefficient (ICC) was determined, and Bland–Altman analysis was performed to evaluate interobserver and intermethod agreement. Accuracy of the trained observer was evaluated with a reference expert observer using the same statistical analysis. Results: The highest interobserver agreement was obtained for absolute thrombus measurements using three ROIs (ICCs ranging from 0.54 to 0.91). In general, interobserver agreement was lower for relative measurements, and for using one instead of three ROIs. Interobserver agreement of trained non-experts and experts was similar. Accuracy of the trained observer measurements was comparable to the expert interobserver agreement and was better for absolute measurements and with three ROIs. The agreement between the one ROI and three ROI methods was good. Conclusion: Absolute thrombus density measurement has superior interobserver agreement compared to relative density measurement. Interobserver variation is smaller when multiple ROIs are used. Trained non-expert observers can accurately and reproducibly assess absolute thrombus densities using three ROIs

Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data

Background: CT perfusion (CTP) and diffusion or perfusion MRI might assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of irreversibly injured ischaemic core and potentially salvageable penumbra volumes were associated with functional outcome and whether they interacted with the treatment effect of endovascular thrombectomy on functional outcome. Methods: In this systematic review and meta-analysis, the HERMES collaboration pooled patient-level data from all randomised controlled trials that compared endovascular thrombectomy (predominantly using stent retrievers) with standard medical therapy in patients with anterior circulation ischaemic stroke, published in PubMed from Jan 1, 2010, to May 31, 2017. The primary endpoint was functional outcome, assessed by the modified Rankin Scale (mRS) at 90 days after stroke. Ischaemic core was estimated, before treatment with either endovascular thrombectomy or standard medical therapy, by CTP as relative cerebral blood flow less than 30% of normal brain blood flow or by MRI as an apparent diffusion coefficient less than 620 μm2/s. Critically hypoperfused tissue was estimated as the volume of tissue with a CTP time to maximum longer than 6 s. Mismatch volume (ie, the estimated penumbral volume) was calculated as critically hypoperfused tissue volume minus ischaemic core volume. The association of ischaemic core and penumbral volumes with 90-day mRS score was analysed with multivariable logistic regression (functional independence, defined as mRS score 0–2) and ordinal logistic regression (functional improvement by at least one mRS category) in all patients and in a subset of those with more than 50% endovascular reperfusion, adjusted for baseline prognostic variables. The meta-analysis was prospectively designed by the HERMES executive committee, but not registered. Findings: We identified seven studies with 1764 patients, all of which were included in the meta-analysis. CTP was available and assessable for 591 (34%) patients and diffusion MRI for 309 (18%) patients. Functional independence was worse in patients who had CTP versus those who had diffusion MRI, after adjustment for ischaemic core volume (odds ratio [OR] 0·47 [95% CI 0·30–0·72], p=0·0007), so the imaging modalities were not pooled. Increasing ischaemic core volume was associated with reduced likelihood of functional independence (CTP OR 0·77 [0·69–0·86] per 10 mL, pinteraction=0·29; diffusion MRI OR 0·87 [0·81–0·94] per 10 mL, pinteraction=0·94). Mismatch volume, examined only in the CTP group because of the small numbers of patients who had perfusion MRI, was not associated with either functional independence or functional improvement. In patients with CTP with more than 50% endovascular reperfusion (n=186), age, ischaemic core volume, and imaging-to-reperfusion time were independently associated with functional improvement. Risk of bias between studies was generally low. Interpretation: Estimated ischaemic core volume was independently associated with functional independence and functional improvement but did not modify the treatment benefit of endovascular thrombectomy over standard medical therapy for improved functional outcome. Combining ischaemic core volume with age and expected imaging-to-reperfusion time will improve assessment of prognosis and might inform endovascular thrombectomy treatment decisions. Funding: Medtronic

Emergence of surfactant-​free micelles from ternary solutions

Curious effects ranging from enzyme activity to anomalies in evapn. rates that have been known for over fifty years suggest the existence and thermodn. stability of surfactant-free micelles. Only recently, joint X-ray, light and neutron scattering expts. have demonstrated that aggregates and bulk pseudo-phases coexist in presumably normal solns., in which a water insol. component is solubilized in a certain domain of concn. of a hydrotrope component like ethanol. Nevertheless, nothing is known about the mol.-level shape and structure of such aggregates. In this work we characterize mixts. of octanol, ethanol, and water by mol. dynamics simulations. For compns. in the "pre-ouzo" region (close to the single phase stability limit) we observe micelle-like aggregates that are clearly distinct from simple crit. d. fluctuations. We define an ethanol partition in the pseudo-phase from an integral of the van der Waals dispersion energy term. From this partition, octanol-rich aggregates swollen with ethanol appear with an emerging interface. Ethanol is present in the water pseudo-phase with an exponential decay similar to the one predicted by Marcelja and Radic forty years ago

Acute Endovascular Treatment of Patients With lschemic Stroke From Intracranial Large Vessel Occlusion and Extracranial Carotid Dissection

Introduction: Carotid artery dissection (CAD) and atherosclerotic carotid artery occlusion (ACAO) are major causes of a tandem occlusion in patients with intracranial large vessel occlusion (LVO). Presence of tandem occlusions may hamper intracranial access and potentially increases the risk of procedural complications of endovascular treatment (EVT). Our aim was to assess neurological, functional and technical outcome and complications of EVT for intracranial LVO in patients with CAD in comparison to patients with ACAO and to patients without CAD or ACAO. Methods: We analyzed data of the MR CLEAN trial intervention arm and MR CLEAN Registry, acquired in 16 Dutch EVT-centers. Primary outcome was the change in stroke severity by comparing the National Institute of Health Stroke Scale (NIHSS) score at 24-48 h after treatment vs. baseline. Secondary outcomes included reperfusion rate and symptomatic intracranial hemorrhage (sICH). We compared outcomes and complications between patients with CAD vs. patients with ACAO and patients without CAD or ACAO. Results: In total, we identified 74 (4.7%) patients with CAD, 92 (5.9%) patients with ACAO and 1398 (89.4%) patients without CAD or ACAO. Neurological improvement at short-term after EVT in patients with CAD was significantly better compared to ACAO (raw mean -5 vs. mean -1 NIHSS point; p = 0.03) and did not differ compared to patients without CAD or ACAO (-4 NIHSS points; p = 0.62). Rates of successful reperfusion in patients with CAD (47%) was comparable to patients with ACAO (47%; p = 1.00), but was less often achieved compared to patients without CAD or ACAO (58%; p = 0.08). Occurrence of sICH did not differ significantly between CAD patients (5%) and ACAO (11%; p = 0.33) or without CAD/ACAO (6%; p = 1.00). Conclusion: EVT in patients with intracranial LVO due to CAD results in neurological improvement comparable to patients without tandem occlusions. Therefore, carotid artery dissection by itself should not be a contraindication for endovascular treatment in stroke patients with intracranial large vessel occlusion. Although more challenging endovascular procedures are to be suspected in both patients with CAD or ACAO, accurate distinction between CAD and ACAO might influence clinical decision making as better clinical outcome can be expected in patients with CAD

Treatment of dissecting aneurysms of the PICA: anatomical considerations and clinical outcome

Posterior inferior cerebellar artery (PICA) dissecting aneurysms require rapid and aggressive treatment by sacrificing the parent vessel of the aneurysm-bearing dissected vessel. We assessed the clinical consequences of PICA occlusion in view of the local vascular anatomy. We performed a retrospective search of our neurovascular database in the period 2007-2012. Patient characteristics, including clinical presentation, WFNS (World Federation of Neurosurgical Societies) grading and Glasgow Outcome Scale (GOS), were recorded. CT and CT angiographic findings as well as the detailed vascular anatomy including collateral circulation were assessed. We identified 10 patients (5 male; mean age 50 years). Eight patients presented with WFNS grade I and II, one with grade IV and one with grade V. All patients were treated with parent vessel occlusion (PVO). An extradural PICA origin was seen in three patients. Collateral circulation was visible before PVO in two and after PVO in seven additional patients. Despite the presence of collaterals, mild cerebellar ischemia occurred in three patients, without development of a Wallenberg syndrome. Outcome was favorable in 9 patients (8 patients GOS 5, one patient GOS 4). One patient died due to the mass effect of the initial cerebellar hematoma. PVO to treat PICA dissecting aneurysms was well tolerated with a 90% favorable outcome. Regional collateral circulation and vascular variations permitted relative safe vessel occlusion with only minor cerebellar symptoms in this small group of patient

Cranial Computed Tomography, Lumbar Puncture, and Clinical Deterioration in Bacterial Meningitis: A Nationwide Cohort Study

Background. It is unclear how often lumbar puncture (LP) is complicated by cerebral herniation in patients with bacterial meningitis and whether cranial computed tomography (CT) can be used to identify patients at risk for herniation. Methods. We performed a nationwide prospective cohort study of patients with community-acquired bacterial meningitis from 2006 to 2014 and identified patients with clinical deterioration possibly caused by LP. For systematic evaluation of contraindications for LP on cranial CT, these patients were matched to patients in the cohort without deterioration. Four experts, blinded for outcome, scored cranial CT results for contraindications for LP. A Fleiss' generalized ? for this assessment was determined. Results. Of 1533 episodes, 47 (3.1%) had deterioration possibly caused by LP. Two patients deteriorated within 1 hour after LP (0.1%). In 43 of 47 patients with deterioration, cranial CT was performed prior to LP, so CT results were matched with 43 patients without deterioration. The interrater reliability of assessment of contraindications for LP on cranial CT was moderate (Fleiss' generalized ? = 0.47). A contraindication for LP was reported by all 4 raters in 6 patients ith deterioration (14%) and in 5 without deterioration (11%). Conclusions. LP can be performed safely in the large majority of patients with bacterial meningitis, as it is only very rarely complicated by cerebral herniation. Cranial CT can be considered a screening method for contraindications for LP, but the interrater reliability of this assessment is moderate

Decompressive craniectomy in aneurysmal subarachnoid haemorrhage for hematoma or oedema versus secondary infarction

PURPOSE: Decompressive craniectomy (DC) has been proposed as lifesaving treatment in aneurysmal subarachnoid haemorrhage (aSAH) patients with elevated intracranial pressure (ICP). However, data is sparse and controversy exists whether the underlying cause of elevated ICP influences neurological outcome. The purpose of this study is to clarify the role of the underlying cause of elevated ICP on outcome after DC. MATERIALS AND METHODS: We retrospectively studied the one-year neurological outcome in a single-centre cohort to identify predictors of favourable (Glasgow Outcome Scale (GOS) 4-5) and unfavourable (GOS 1-3) outcome. Additionally, available individual patient data in the literature was reviewed with a special emphasis on the underlying reason for DC. RESULTS: From 2006-2015, 53 consecutive aSAH patients underwent DC. Nine (17%) achieved favourable, 44 (83%) unfavourable outcome (31 patients died). One fourth of the patients undergoing DC for hematoma or (hematoma-related) oedema survived favourably (increasing to 46% for patients aged <51 years), versus none of the patients undergoing DC for secondary infarction. Analysis of individual data of 105 literature patients showed a similar trend, although overall outcome was much better: half of the patients undergoing DC for hematoma/oedema regained independence, versus less than one-fourth of patients undergoing DC for secondary infarction. CONCLUSIONS: DC in aSAH patients is associated with high rates of unfavourable outcome and mortality, but hematoma or oedema as underlying reason for DC is associated with better outcome profiles compared to secondary infarction. Future observational cohort studies are needed to further explore the different outcome profiles among subpopulations of aSAH patients requiring DC

Unfavorable Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage WFNS Grade I

Background: Patients with an aneurysmal subarachnoid hemorrhage (aSAH) and World Federation of Neurosurgical Societies (WFNS) grade I on admission are generally considered to have a good clinical outcome. Objective: The objective of this study was to assess the actual clinical outcome of WFNS grade I aSAH patients, and to determine which factors are associated with unfavourable outcome. Methods: For this prospective cohort study, 132 consecutive patients (age 18 years or older) with a WFNS grade I aSAH admitted to our hospital between December 2011 and January 2016 were eligible. Clinical outcome was measured using the modified Rankin Scale (mRS) at 6-month follow-up. Unfavorable outcome was defined as an mRS score of 3–6. Univariable analyses were performed using logistic regression models. Results: Of 116 patients, only 5 patients (4%) had an mRS score of 0 and most (65%) had an mRS score of 2. Twenty-five patients (22%) had an unfavorable outcome. Nine (8%) patients died, of whom 4 died during admission. Factors associated with unfavorable outcome were age (per increasing decade: odds ratio [OR]. 1.78; 95% confidence interval [CI], 1.16–2.72), delayed cerebral ischemia (OR, 4.32; 95% CI, 1.63–11.44), pneumonia (OR, 10.75; 95% CI, 1.94–59.46) and meningitis (OR, 28.47; 95% CI, 1.42–571.15). Conclusions: Despite their neurologically optimal clinical condition on admission, 1 in 5 patients with WFNS grade I aSAH has an unfavorable clinical outcome or is dead at 6-month follow-up. Additional multivariable analysis in larger patient cohorts is necessary to identify the extent to which preventable complications contribute to unfavorable outcomes in these patients

Coiling of Intracranial Aneurysms A Systematic Review on Initial Occlusion and Reopening and Retreatment Rates

Background and Purpose-The proportion of incompletely occluded aneurysms after coiling varies widely between studies. To assess overall outcome of coiling, we systematically reviewed the literature to determine initial occlusion, reopening, and retreatment rates of coiled aneurysms according to predefined criteria and subgroups. Methods-We searched PubMed and EMBASE (January 1999 to September 2008) for studies of >50 coiled aneurysms. Two reviewers independently extracted data. We grouped studies reporting on only ruptured aneurysms, posterior circulation aneurysms, and studies with large proportions of aneurysms >10 mm to assess possible determinants for incomplete occlusion, reopening, and retreatment. Results-Forty-six studies totalling 8161 coiled aneurysms met inclusion criteria. Immediately after coiling, 91.2% (95% CI, 90.6% to 91.9%) of the aneurysms were adequately occluded. Aneurysm reopening occurred in 20.8% (95% CI, 19.8% to 21.9%) and retreatment was performed in 10.3% (95% CI, 9.5% to 11.0%). Reopening rate was lower in studies reporting on ruptured aneurysms only compared with all studies (11.4% versus 20.8%; relative risk, 0.55; 95% CI, 0.47 to 0.64) and higher in studies focusing on posterior circulation aneurysms compared with studies with >85% anterior circulation aneurysms (22.5% versus 15.5%; relative risk, 1.5; 95% CI, 1.2 to 1.7). Regression analysis showed higher retreatment rates with increasing proportion of aneurysms >10 mm (beta = 0.252; 95% CI, 0.073 to 0.432). We could not find a relation between reopening and type of coils used. Conclusion-At follow-up, one fifth of all coiled intracranial aneurysms shows reopening of which half is retreated. Possible risk factors for aneurysm reopening are location in the posterior circulation and size >10 mm. To confirm our findings, a meta-analysis on individual well-reported patient data is desirable. (Stroke. 2009; 40: e523-e529.