The predictive value of the CTA Vasospasm Score on delayed cerebral ischaemia and functional outcome after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Delayed cerebral ischaemia (DCI) is a severe complication of aneurysmal subarachnoid hemorrhage that can significantly impact clinical outcome. Cerebral vasospasm is part of the pathophysiology of DCI and therefore a computed tomography angiography (CTA) Vasospasm Score was developed and an exploration was carried out of whether this score predicts DCI and subsequent poor outcome after aneurysmal subarachnoid hemorrhage. METHODS: The CTA Vasospasm Score sums the degree of angiographic cerebral vasospasm of 17 intradural arterial segments. The score ranges from 0 to 34 with a higher score reflecting more severe vasospasm. Outcome measures were cerebral infarction due to DCI (CI-DCI), radiological and clinical DCI, and unfavorable functional outcome defined as a modified Rankin Scale >2 at 6 months. Receiver operating characteristic analyses were used to assess predictive value and to determine optimal cut-off scores. Inter-rater reliability was evaluated by Cohen's kappa coefficient. RESULTS: This study included 59 patients. CI-DCI occurred in eight patients (14%), DCI in 14 patients (24%) and unfavorable outcome in 12 patients (20%). Median CTA Vasospasm Scores were higher in patients with (CI-)DCI and poor outcome. Receiver operating characteristic analysis revealed the highest area under the curve on day 5: CI-DCI 0.89 (95% confidence interval [CI] 0.79-0.99), DCI 0.68 (95% CI 0.50-0.87) and functional outcome 0.74 (95% CI 0.57-0.91). Cohen's kappa between the two raters was moderate to substantial (0.57-0.63). CONCLUSIONS: This study demonstrates that the CTA Vasospasm Score on day 5 can reliably identify patients with a high risk of developing (CI-)DCI and unfavorable outcome.

Early Thromboembolic Stroke Risk of Postoperative Atrial Fibrillation Following Cardiac Surgery.

OBJECTIVE: The authors aimed to study the association between postoperative atrial fibrillation (POAF) and thromboembolic stroke and to determine risk factors for thromboembolic stroke after cardiac surgery. DESIGN: The authors performed a secondary analysis from a randomized controlled trial (GRIP-COMPASS). The patients with thromboembolic stroke were compared with those without thromboembolic stroke, and the difference in the incidence of POAF between these groups was assessed. Odds ratios (OR) were calculated using logistic regression analyses. Brain imaging was studied for the occurrence of thromboembolic stroke during hospital admission, and POAF was monitored for seven days. To assess which characteristics were associated with occurrence of thromboembolic stroke, stepwise backward regression analysis was performed. PARTICIPANTS: All adult consecutive cardiac surgery patients admitted postoperatively to the intensive care unit. SETTING: Academic tertiary care medical center. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 910 patients included in this study, 26 patients (2.9%) had a thromboembolic stroke during hospital admission. The incidence of POAF during the first seven days after cardiac surgery in those with thromboembolic stroke was 65%, compared with 39% in those without thromboembolic stroke: adjusted OR 3.01 (95% confidence interval, 1.13-8.00). POAF, a history of peripheral vascular disease, a higher EuroSCORE, and a longer duration of surgery were associated with thromboembolic stroke. CONCLUSIONS: POAF within seven days after cardiac surgery was associated with a three-fold increased risk for a thromboembolic stroke during hospital admission. Expeditious treatment of POAF may, therefore, reduce early stroke risk after cardiac surgery.

The Unruptured Intracranial Aneurysm Treatment Score as a predictor of aneurysm growth or rupture.

BACKGROUND AND PURPOSE: The Unruptured Intracranial Aneurysm Treatment Score (UIATS) was built to harmonize the treatment decision making on unruptured intracranial aneurysms. Therefore, it may also function as a predictor of aneurysm progression. In this study, we aimed to assess the validity of the UIATS model to identify aneurysms at risk of growth or rupture during follow-up. METHODS: We calculated the UIATS for a consecutive series of conservatively treated unruptured intracranial aneurysms, included in our prospectively kept neurovascular database. Computed tomography angiography and/or magnetic resonance angiography imaging at baseline and during follow-up was analyzed to detect aneurysm growth. We defined rupture as a cerebrospinal fluid or computed tomography-proven subarachnoid hemorrhage. We calculated the area under the receiver operator curve, sensitivity, and specificity, to determine the performance of the UIATS model. RESULTS: We included 214 consecutive patients with 277 unruptured intracranial aneurysms. Aneurysms were followed for a median period of 1.3 years (range 0.3-11.7 years). During follow-up, 17 aneurysms enlarged (6.1%), and two aneurysms ruptured (0.7%). The UIATS model showed a sensitivity of 80% and a specificity of 44%. The area under the receiver operator curve was 0.62 (95% confidence interval 0.46-0.79). CONCLUSIONS: Our observational study involving consecutive patients with an unruptured intracranial aneurysm showed poor performance of the UIATS model to predict aneurysm growth or rupture during follow-up.

Impairments in Emotion Recognition and Risk-Taking Behavior After Isolated, Cerebellar Stroke.

An increasing amount of research has shown a cerebellar involvement in higher order cognitive functions, including emotional processing and decision-making. However, it has not been investigated whether impairments in facial emotion recognition, which could be a marker of impaired emotional experiences, are related to risky decision-making in these patients. Therefore, we aimed to investigate facial emotion recognition and risky decision-making in these patients as well as to investigate a relationship between these constructs. Thirteen patients with a discrete, isolated, cerebellar lesion as a consequence of a stroke were included in the study. Emotion recognition was assessed with the Facial Expressions of Emotions-Stimuli and Test (FEEST). Risk-taking behavior was assessed with the Action Selection Test (AST). Furthermore, 106 matched healthy controls performed the FEEST and 20 matched healthy controls performed the AST. Compared with healthy controls, patients were significantly worse in the recognition of emotional expressions and they took significantly more risks. In addition, a worse ability to recognize fearful facial expressions was strongly related to an increase in risky decisions in the AST. Therefore, we suggest that tests of emotion recognition should be incorporated into the neuropsychological assessment after cerebellar stroke to boost detection and treatment of these impairments in these patients.

Mutations in CYB561 Causing a Novel Orthostatic Hypotension Syndrome.

RATIONALE: Orthostatic hypotension is a common clinical problem, but the underlying mechanisms have not been fully delineated. OBJECTIVE: We describe 2 families, with 4 patients in total, experiencing severe life-threatening orthostatic hypotension because of a novel cause. METHODS AND RESULTS: As in dopamine ß-hydroxylase deficiency, concentrations of norepinephrine and epinephrine in the patients were low. Plasma dopamine ß-hydroxylase activity, however, was normal, and the DBH gene had no mutations. Molecular genetic analysis was performed to determine the underlying genetic cause. Homozygosity mapping and exome and Sanger sequencing revealed pathogenic homozygous mutations in the gene encoding cytochrome b561 (CYB561); a missense variant c.262G>A, p.Gly88Arg in exon 3 in the Dutch family and a nonsense mutation (c.131G>A, p.Trp44*) in exon 2 in the American family. Expression of CYB561 was investigated using RNA from different human adult and fetal tissues, transcription of RNA into cDNA, and real-time quantitative polymerase chain reaction. The CYB561 gene was found to be expressed in many human tissues, in particular the brain. The CYB561 protein defect leads to a shortage of ascorbate inside the catecholamine secretory vesicles leading to a functional dopamine ß-hydroxylase deficiency. The concentration of the catecholamines and downstream metabolites was measured in brain and adrenal tissue of 6 CYB561 knockout mice (reporter-tagged deletion allele [post-Cre], genetic background C57BL/6NTac). The concentration of norepinephrine and normetanephrine was decreased in whole-brain homogenates of the CYB561(-/-) mice compared with wild-type mice (P<0.01), and the concentration of normetanephrine and metanephrine was decreased in adrenal glands (P<0.01), recapitulating the clinical phenotype. The patients responded favorably to treatment with l-dihydroxyphenylserine, which can be converted directly to norepinephrine. CONCLUSIONS: This study is the first to implicate cytochrome b561 in disease by showing that pathogenic mutations in CYB561 cause an as yet unknown disease in neurotransmitter metabolism causing orthostatic hypotension.

Distribution of Cardioembolic Stroke: A Cohort Study.

BACKGROUND: A cardiac origin in ischemic stroke is more frequent than previously assumed, but it is not clear which patients benefit from cardiac work-up if obvious cardiac pathology is absent. We hypothesized that thromboembolic stroke with a cardiac source occurs more frequently in the posterior circulation compared with thromboembolic stroke of another etiology. METHODS: We performed a multicenter observational study in 3,311 consecutive patients with ischemic stroke who were enrolled in an ongoing prospective stroke registry of 8 University hospitals between September 2009 and November 2014 in The Netherlands. In this initiative, the so-called Parelsnoer Institute-Cerebrovascular Accident Study Group, clinical data, imaging, and biomaterials of patients with stroke are prospectively and uniformly collected. We compared the proportions of posterior stroke location in patients with a cardiac stroke source with those with another stroke etiology and calculated risk ratios (RR) with corresponding 95% CI with Poisson regression analyses. To assess which patient or disease characteristics were most strongly associated with a cardiac etiology in patients with ischemic stroke, we performed a stepwise backward regression analysis. RESULTS: For the primary aim, 1,428 patients were eligible for analyses. The proportion of patients with a posterior stroke location among patients with a cardiac origin of their stroke (28%) did not differ statistically significant to those with another origin (25%), age and sex adjusted RR 1.16; 95% CI 0.96-1.41. For the secondary aim, 1,955 patients were eligible for analyses. No recent history of smoking, no hyperlipidemia, coronary artery disease, a higher age, and a higher National Institutes of Health Stroke Scale (NIHSS) score were associated with a cardiac etiology of ischemic stroke. CONCLUSIONS: We could not confirm our hypothesis that thromboembolic stroke localized in the posterior circulation is associated with a cardioembolic source of ischemic stroke, and therefore posterior stroke localization on itself does not necessitate additional cardiac examination. The lack of determinants of atherosclerosis, for example, no recent history of smoking and no hyperlipidemia, coronary artery disease, a higher age, and a higher NIHSS score are stronger risk factors for a cardiac source of ischemic stroke.

Centralising acute stroke care within clinical practice in the Netherlands: lower bounds of the causal impact.

BACKGROUND: Authors in previous studies demonstrated that centralising acute stroke care is associated with an increased chance of timely Intra-Venous Thrombolysis (IVT) and lower costs compared to care at community hospitals. In this study we estimated the lower bound of the causal impact of centralising IVT on health and cost outcomes within clinical practice in the Northern Netherlands. METHODS: We used observational data from 267 and 780 patients in a centralised and decentralised system, respectively. The original dataset was linked to the hospital information systems. Literature on healthcare costs and Quality of Life (QoL) values up to 3 months post-stroke was searched to complete the input. We used Synthetic Control Methods (SCM) to counter selection bias. Differences in SCM outcomes included 95% Confidence Intervals (CI). To deal with unobserved heterogeneity we focused on recently developed methods to obtain the lower bounds of the causal impact. RESULTS: Using SCM to assess centralising acute stroke 3 months post-stroke revealed healthcare savings of $US 1735 (CI, 505 to 2966) while gaining 0.03 (CI, - 0.01 to 0.73) QoL per patient. The corresponding lower bounds of the causal impact are $US 1581 and 0.01. The dominant effect remained stable in the deterministic sensitivity analyses with $US 1360 (CI, 476 to 2244) as the most conservative estimate. CONCLUSIONS: In this study we showed that a centralised system for acute stroke care appeared both cost-saving and yielded better health outcomes. The results are highly relevant for policy makers, as this is the first study to address the issues of selection and unobserved heterogeneity in the evaluation of centralising acute stroke care, hence presenting causal estimates for budget decisions.

Clinical relevance of short-term follow-up of unruptured intracranial aneurysms.

OBJECTIVE: Unruptured intracranial aneurysms are common incidental findings on brain imaging. Short-term follow-up for conservatively treated aneurysms is routinely performed in most cerebrovascular centers, although its clinical relevance remains unclear. In this study, the authors assessed the extent of growth as well as the rupture risk during short-term follow-up of conservatively treated unruptured intracranial aneurysms. In addition, the influence of patient-specific and aneurysm-specific factors on growth and rupture risk was investigated. METHODS: The authors queried their prospective institutional neurovascular registry to identify patients with unruptured intracranial aneurysms and short-term follow-up imaging, defined as follow-up MRA and/or CTA within 3 months to 2 years after initial diagnosis. Medical records and questionnaires were used to acquire baseline information. The authors measured aneurysm size at baseline and at follow-up to detect growth. Rupture was defined as a CT scan-proven and/or CSF-proven subarachnoid hemorrhage (SAH). RESULTS: A total of 206 consecutive patients with 267 conservatively managed unruptured aneurysms underwent short-term follow-up at the authors' center. Seven aneurysms (2.6%) enlarged during a median follow-up duration of 1 year (range 0.3-2.0 years). One aneurysm (0.4%) ruptured 10 months after initial discovery. Statistically significant risk factors for growth or rupture were autosomal-dominant polycystic kidney disease (RR 8.3, 95% CI 2.0-34.7), aspect ratio > 1.6 or size ratio > 3 (RR 10.8, 95% CI 2.2-52.2), and initial size ≥ 7 mm (RR 10.7, 95% CI 2.7-42.8). CONCLUSIONS: Significant growth of unruptured intracranial aneurysms may occur in a small proportion of patients during short-term follow-up. As aneurysm growth is associated with an increased risk of rupture, the authors advocate that short-term follow-up is clinically relevant and has an important role in reducing the risk of a potential SAH.

COOLIST (Cooling for Ischemic Stroke Trial): A Multicenter, Open, Randomized, Phase II, Clinical Trial.

BACKGROUND AND PURPOSE: Animal studies suggest that cooling improves outcome after ischemic stroke. We assessed the feasibility and safety of surface cooling to different target temperatures in awake patients with acute ischemic stroke. METHODS: A multicenter, randomized, open, phase II, clinical trial, comparing standard treatment with surface cooling to 34.0°C, 34.5°C, or 35.0°C in awake patients with acute ischemic stroke and an National Institutes of Health Stroke Scale score of ≥6, initiated within 4.5 hours after symptom onset and maintained for 24 hours. The primary outcome was feasibility, defined as the proportion of patients who had successfully completed the assigned treatment. Safety was a secondary outcome. RESULTS: Inclusion was terminated after 22 patients because of slow recruitment. Five patients were randomized to 34.0°C, 6 to 34.5°C, 5 to 35.0°C (cooling was initiated in 4), and 6 to standard care. No (0%), 1 (17%), and 3 (75%) patients, respectively, completed the assigned treatment (P=0.03). No (0%), 2 (33%), and 4 (100%) patients reached the target temperature (P=0.01). Pneumonia occurred in 8 cooled patients but not in controls (absolute risk increase, 53%; 95% confidence interval, 28-79%; P=0.002). CONCLUSIONS: In awake patients with acute ischemic stroke, surface cooling is feasible to 35.0°C, but not to 34.5°C and 34.0°C. Cooling is associated with an increased risk of pneumonia. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR2616.

Centralising and optimising decentralised stroke care systems: a simulation study on short-term costs and effects.

BACKGROUND: Centralisation of thrombolysis may offer substantial benefits. The aim of this study was to assess short term costs and effects of centralisation of thrombolysis and optimised care in a decentralised system. METHODS: Using simulation modelling, three scenarios to improve decentralised settings in the North of Netherlands were compared from the perspective of the policy maker and compared to current decentralised care: (1) improving stroke care at nine separate hospitals, (2) centralising and improving thrombolysis treatment to four, and (3) two hospitals. Outcomes were annual mean and incremental costs per patient up to the treatment with thrombolysis, incremental cost-effectiveness ratio (iCER) per 1% increase in thrombolysis rate, and the proportion treated with thrombolysis. RESULTS: Compared to current decentralised care, improving stroke care at individual community hospitals led to mean annual costs per patient of $US 1,834 (95% CI, 1,823-1,843) whereas centralising to four and two hospitals led to $US 1,462 (95% CI, 1,451-1,473) and $US 1,317 (95% CI, 1,306-1,328), respectively (P < 0.001). The iCER of improving community hospitals was $US 113 (95% CI, 91-150) and $US 71 (95% CI, 59-94), $US 56 (95% CI, 44-74) when centralising to four and two hospitals, respectively. Thrombolysis rates decreased from 22.4 to 21.8% and 21.2% (P = 0.120 and P = 0.001) in case of increasing centralisation. CONCLUSIONS: Centralising thrombolysis substantially lowers mean annual costs per patient compared to raising stroke care at community hospitals simultaneously. Small, but negative effects on thrombolysis rates may be expected.

Admission hyperglycemia and outcome after intravenous thrombolysis: is there a difference among the stroke-subtypes?

BACKGROUND: The prognostic influence of hyperglycemia in acute stroke has been well established. While in cortical stroke there is a strong association between hyperglycemia and poor outcome, this relation is less clear in lacunar stroke. It has been suggested that this discrepancy is present among patients treated with intravenous tissue plasminogen activator (tPA), but confirmation is needed. METHODS: In two prospectively collected cohorts of patient treated with intravenous tPA for acute ischemic stroke, we investigated the effect of hyperglycemia (serum glucose level >8 mmol/L) on functional outcome in lacunar and non-lacunar stroke. Poor functional outcome was defined as modified Rankin Scale score ≥ 3 at 3 months. RESULTS: A total of 1012 patients was included of which 162 patients (16%) had lacunar stroke. The prevalence of hyperglycemia did not differ between stroke subtypes (22% vs 21%, p = 0.85). In multivariate analysis hyperglycemia was associated with poor functional outcome in non-lacunar stroke (OR 2.1, 95% CI 1.39-3.28, p = 0.001). In patients with lacunar stroke, we did not find an association (OR 1.8, 95% CI 0.62-4.08, p = 0.43). CONCLUSION: This study confirms a difference in prognostic influence of hyperglycemia between non-lacunar and lacunar ischemic stroke.

The Effect of Age and Sex on Clinical Outcome after Intravenous Recombinant Tissue Plasminogen Activator Treatment in Patients with Acute Ischemic Stroke.

BACKGROUND: There are conflicting results regarding the effect of intravenous (IV) recombinant tissue plasminogen activator (rtPA) stroke treatment between men and women. Studies evaluating the impact of sex differences on functional outcome in relation to different age groups are nonexistent. AIM: The objective of the study is to examine the influence of sex differences in relation to age on the prognosis after IV rtPA treatment in acute stroke patients. METHODS: In this cohort study, 887 patients with acute ischemic stroke were treated with rtPA. Functional outcome after 3 months was determined with the modified Rankin Scale (mRS). Good outcome was defined as an mRS score of 2 or lower. Age was stratified in decades (41-50, 51-60, 61-70, 71-80, and >80 years). Multivariable analyses were performed with adjustment for age, sex, stroke severity (National Institutes of Health Stroke Scale [NIHSS]), and stroke subtype (Trial of Org 10172 in Acute Stroke Treatment). RESULTS: Fifty-five percent of the patients were men. The mean age was 67.4 (men) and 72.0 (women) years. Fifty-six percent of the men and 45% of the women had a favorable outcome (P = .001). After adjustment for NIHSS score and stroke subtype, the women had a better outcome in the age group 51-60 years compared with men (odds ratio [OR] .38, 95% confidence interval [CI] .15-.96). In the age group >80 years, men had a better outcome than women (OR 2.69, 95% CI 1.21-5.96). There were no significant differences in the other age groups. CONCLUSION: Men and women have different prognoses after IV rtPA treatment for acute ischemic stroke, which also depends on age. Women in middle age appear to have a better outcome than men, whereas at a more advanced age men appear to have a better outcome than women.

Predictive Factors for Rebleeding After Aneurysmal Subarachnoid Hemorrhage: Rebleeding Aneurysmal Subarachnoid Hemorrhage Study.

BACKGROUND AND PURPOSE: Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating type of stroke associated with high morbidity and mortality. One of the most feared complications is an early rebleeding before aneurysm repair. Predictors for such an often fatal rebleeding are largely unknown. We therefore aimed to determine predictors for an early rebleeding after aSAH in relation with time after ictus. METHODS: This observational prospective cohort study included all consecutive patients admitted with aSAH between January 1998 and December 2014 (n=1337) at our University Neurovascular Center. Clinical predictors for rebleeding ≤24 hours were identified using multivariable Cox regression analyses. Kaplan-Meier analyses were applied to evaluate the time of rebleeding ≤72 hours after aSAH. RESULTS: A modified Fisher grade of 3 to 4 was a predictor for an in-hospital rebleeding ≤24 hours after ictus (adjusted hazard ratio, 4.4; 95% confidence interval, 2.1-10.6; P<0.001). The numbers needed to treat to prevent 1 rebleeding ≤24 hours was calculated 15 (95% confidence interval, 10-25). Also, the initiation of external cerebrospinal fluid-drainage (adjusted hazard ratio, 1.9; 95% confidence interval, 1.4-2.5; P<0.001) was independently associated with a rebleeding ≤24 hours. Cumulative in-hospital rebleeding rates were 5.8% ≤24 hours, and 1.2% in the time frame 24-72 hours after ictus. CONCLUSIONS: In our opinion, timing of treatment of aSAH patients, especially those with an modified Fisher grade of 3 or 4 in a good clinical condition, should be reconsidered. These aSAH patients might be regarded a medical emergency, requiring aneurysm repair as soon as possible. In this respect, our findings should provoke the debate on timing of aneurysm repair, especially in patients considered to be at high risk for rebleeding.

Co-morbidities in heart failure.

Heart failure is a clinical syndrome characterized by poor quality of life and high morbidity and mortality. Co-morbidities frequently accompany heart failure and further decrease in both quality of life and clinical outcome. We describe that the prevalence of co-morbidities in patients with heart failure is much higher compared to age-matched controls. We will specifically address the most studied organ-related co-morbidities, that is, renal dysfunction, cerebral dysfunction, anaemia, liver dysfunction, chronic obstructive pulmonary disease, diabetes mellitus and sleep apnoea. The pathophysiologic processes underlying the interaction between heart failure and co-morbid conditions are complex and remain largely unresolved. Although common risk factors are likely to contribute, it is reasonable to believe that factors associated with heart failure might cause other co-morbid conditions. Inflammation, neurohumoral pathway activation and hemodynamic changes are potential factors. We try to provide explanations for the observed association between co-morbidities and heart failure, as well as its impact on survival.

Appreciation of CT-negative, lumbar puncture-positive subarachnoid haemorrhage: risk factors for presence of aneurysms and diagnostic yield of imaging.

OBJECTIVE: Patients without a subarachnoid haemorrhage (SAH) on brain CT scan (CT-negative), but a lumbar puncture (LP)-proven SAH, are a challenging patient category. The optimal diagnostic approach is still a matter of debate. Also, there is little knowledge on the probability of finding an underlying vascular lesion. DESIGN: In this observational study, a consecutive cohort of 94 patients with CT-negative, LP-positive SAH was prospectively collected between 1998 and 2013. The yield of diagnostic modalities as well as patient outcome was studied. In addition, risk factors for the presence of a vascular lesion were analysed. RESULTS: In 40 patients (43%), an intracranial vascular abnormality was detected: 37 aneurysms and three arterial dissections. Female gender was significantly associated with detection of a vascular lesion. Time between ictus and diagnosis of SAH was not associated with the presence of vascular pathology. Overall, 99% of patients had a modified Rankin Score of 0-2 after a median follow-up of 72 months. The yield of additional digital subtraction angiography in patients with a negative CT angiography was zero. CONCLUSIONS: In this study, the chance of finding a vascular lesion in a patient with CT-negative, LP-positive SAH was 43%, underlining the need for an adequate diagnostic workup. In general, the patient outcome was favourable. Female gender was found to be predictive for detecting a vascular lesion. In contrast with previous reports, the interval between ictus and LP was not associated with the presence of an aneurysm.

A simulation-based approach for improving utilization of thrombolysis in acute brain infarction.

BACKGROUND: Treatment with tissue plasminogen activator (tPA) is the most effective treatment in acute brain infarction. However, estimated worldwide treatment rates are <10%, with many barriers hampering broad implementation. Organization and resource-intense randomized controlled trials cannot address all potential barriers simultaneously. Simulation, however, may provide an efficient research means for testing interventions aimed at resolving barriers along the care pathway. RESEARCH DESIGN: A simulation-based approach reflecting the setup of a regional Dutch acute stroke pathway was used. First, barriers along the overall pathway were identified. Next, solutions to barriers were configured, and subsequently tested using simulation. RESULTS: Barriers along the stroke pathway and possible solutions were identified from the literature and expert consultation. The simulation model closely reproduced actually observed tPA treatment rate and overall process time (21.8% and 129 min for model outcomes vs. 22.1% and 127 min, P=0.89 and 0.64, respectively). Two barriers were overcome: (1) time spent by ambulance personnel on scene by a scoop-and-run protocol (1.4% increase in tPA rate, 7 min decrease in overall process time), and (2) time to laboratory results by introducing a point-of-care diagnostic device (3.2% increase in tPA rate, 20 min decrease in overall process time). CONCLUSIONS: A simulation-based approach is well suited to efficiently assess solutions to barriers along the overall stroke pathway. Substantial improvements in treatment rates and efficacy of thrombolysis may be achieved by implementing a scoop-and-run protocol and point-of-care device.

The Diagnostic Value of Near-Infrared Spectroscopy to Predict Delayed Cerebral Ischemia and Unfavorable Outcome After Subarachnoid Hemorrhage.

OBJECTIVE: Near-infrared spectroscopy (NIRS) is a noninvasive tool to monitor cerebral regional oxygen saturation. Impairment of microvascular circulation with subsequent cerebral hypoxia during delayed cerebral ischemia (DCI) is associated with poor functional outcome after subarachnoid hemorrhage (SAH). Therefore, NIRS could be useful to predict the risk for DCI and functional outcome. However, only limited data are available on NIRS regional cerebral tissue oxygen saturation (rSO2) distribution in SAH. The aim of this study was to compare the distribution of NIRS rSO2 values in patients with nontraumatic SAH with the occurrence of DCI and functional outcome at 2 months. In addition, the predictive value of NIRS rSO2 was compared with the previously validated SAFIRE grade (derived from Size of the aneurysm, Age, FIsher grade, World Federation of Neurosurgical Societies after REsuscitation). METHODS: In this study, the rSO2 distribution of patients with and without DCI after SAH was compared. The optimal cutoff points to predict DCI and outcome were assessed, and its predictive value was compared with the SAFIRE grade. RESULTS: Of 41 patients, 12 developed DCI, and 9 had unfavorable outcome at 60 days. Prediction of DCI with NIRS had an area under the curve of 0.77 (95% confidence interval 0.62-0.92; P = 0.0028) with an optimal cutoff point of 65% (sensitivity 1.00; specificity 0.45). Prediction of favorable outcome with NIRS had an area under the curve of 0.86 (95% confidence interval 0.74-0.98; P = 0.0003) with an optimal cutoff point of 63% (sensitivity 1.00; specificity 0.63). Regression analysis showed that NIRS rSO2 score is complementary to the SAFIRE grade. CONCLUSIONS: NIRS rSO2 monitoring in patients with SAH may improve prediction of DCI and clinical outcome after SAH.

Management of extracranial carotid artery stenosis during endovascular treatment for acute ischaemic stroke: results from the MR CLEAN Registry.

BACKGROUND: The optimal management of ipsilateral extracranial internal carotid artery (ICA) stenosis during endovascular treatment (EVT) is unclear. We compared the outcomes of two different strategies: EVT with vs without carotid artery stenting (CAS). METHODS: In this observational study, we included patients who had an acute ischaemic stroke undergoing EVT and a concomitant ipsilateral extracranial ICA stenosis of ≥50% or occlusion of presumed atherosclerotic origin, from the Dutch Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry (2014-2017). The primary endpoint was a good functional outcome at 90 days, defined as a modified Rankin Scale score ≤2. Secondary endpoints were successful intracranial reperfusion, new clot in a different vascular territory, symptomatic intracranial haemorrhage, recurrent ischaemic stroke and any serious adverse event. RESULTS: Of the 433 included patients, 169 (39%) underwent EVT with CAS. In 123/168 (73%) patients, CAS was performed before intracranial thrombectomy. In 42/224 (19%) patients who underwent EVT without CAS, a deferred carotid endarterectomy or CAS was performed. EVT with and without CAS were associated with similar proportions of good functional outcome (47% vs 42%, respectively; adjusted OR (aOR), 0.90; 95% CI, 0.50 to 1.62). There were no major differences between the groups in any of the secondary endpoints, except for the increased odds of a new clot in a different vascular territory in the EVT with CAS group (aOR, 2.96; 95% CI, 1.07 to 8.21). CONCLUSIONS: Functional outcomes were comparable after EVT with and without CAS. CAS during EVT might be a feasible option to treat the extracranial ICA stenosis but randomised studies are warranted to prove non-inferiority or superiority.

Intra-arterial thrombolytics during endovascular thrombectomy for acute ischaemic stroke in the MR CLEAN Registry.

INTRODUCTION: The efficacy and safety of local intra-arterial (IA) thrombolytics during endovascular thrombectomy (EVT) for large-vessel occlusions is uncertain. We analysed how often IA thrombolytics were administered in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry, whether it was associated with improved functional outcome and assessed technical and safety outcomes compared with EVT without IA thrombolytics. METHODS: In this observational study, we included patients undergoing EVT for an acute ischaemic stroke in the anterior circulation from the MR CLEAN Registry (March 2014-November 2017). The primary endpoint was favourable functional outcome, defined as an modified Rankin Scale score ≤2 at 90 days. Secondary endpoints were reperfusion status, early neurological recovery and symptomatic intracranial haemorrhage (sICH). Subgroup analyses for IA thrombolytics as primary versus adjuvant revascularisation attempt were performed. RESULTS: Of the 2263 included patients, 95 (4.2%) received IA thrombolytics during EVT. The IA thrombolytics administered were urokinase (median dose, 250 000 IU (IQR, 1 93 750-2 50 000)) or alteplase (median dose, 20 mg (IQR, 12-20)). No association was found between IA thrombolytics and favourable functional outcome (adjusted OR (aOR), 1.16; 95% CI 0.71 to 1.90). Successful reperfusion was less often observed in those patients treated with IA thrombolytics (aOR, 0.57; 95% CI 0.36 to 0.90). The odds of sICH (aOR, 0.82; 95% CI 0.32 to 2.10) and early neurological recovery were comparable between patients treated with and without IA thrombolytics. For primary and adjuvant revascularisation attempts, IA thrombolytics were more often administered for proximal than for distal occlusions. Functional outcomes were comparable for patients receiving IA thrombolytics as a primary versus adjuvant revascularisation attempt. CONCLUSION: Local IA thrombolytics were rarely used in the MR CLEAN Registry. In the relatively small study sample, no statistical difference was observed between groups in the rate of favourable functional outcome or sICH. Patients whom required and underwent IA thrombolytics were patients less likely to achieve successful reperfusion, probably due to selection bias.