Variation in perioperative cerebral and hemodynamic monitoring during carotid endarterectomy.

BACKGROUND: Hemodynamic disturbances cause half of the perioperative strokes following carotid endarterectomy (CEA). Guidelines strongly recommend strict pre- and postoperative blood pressure (BP) monitoring in CEA patients, but do not provide firm practical recommendations. Although in the Netherlands 50 centres perform CEA, no national protocol on perioperative hemodynamic, and cerebral monitoring exists. To assess current monitoring policies of all Dutch CEA-centres, a national survey was conducted. METHODS: Between May and July 2017 all 50 Dutch CEA-centres were invited to complete a 42-question survey addressing perioperative hemodynamic and cerebral monitoring during CEA. Nonresponders received a reminder after 1 and 2 months. By November 2017 the survey was completed by all centres. RESULTS: Preoperative baseline BP was based on a single bilateral BP-measurement at the outpatient-clinic in the majority of centres (n = 28). In 43 centres (86%) pre-operative monitoring (transcranial Doppler (TCD, n = 6), electroencephalography (EEG, n = 11), or TCD + EEG (n = 26)) was performed as a baseline reference. Intraoperatively, large diversity for type of anaesthesia (general: 45 vs. local [LA]:5) and target systolic BP (>100 mm hg - 160 mm hg [n = 12], based on preoperative outpatient-clinic or admission BP [n = 18], other [n = 20]) was reported. Intraoperative cerebral monitoring included EEG + TCD (n = 28), EEG alone (n = 13), clinical neurological examination with LA (n = 5), near-infrared spectroscopy with stump pressure (n = 1), and none due to standard shunting (n = 3). Postoperatively, significant variation was reported in standard duration of admission at a recovery or high-care unit (range 3-48 hr, mean:12 hr), maximum accepted systolic BP (range >100 mm hg - 180 mm Hg [n = 32]), postoperative cerebral monitoring (standard TCD [n = 16], TCD on indication [n = 5] or none [n = 24]) and in timing of postoperative cerebral monitoring (range directly postoperative - 24 hr postoperative; median 3 hr). CONCLUSIONS: In Dutch centres performing CEA the perioperative hemodynamic and cerebral monitoring policies are widely diverse. Diverse policies may theoretically lead to over- or under treatment. The results of this national audit may serve as the baseline dataset for development of a standardized and detailed (inter)national protocol on perioperative hemodynamic and cerebral monitoring during CEA.

Validity of an enhanced EQ-5D-5L measure with an added cognitive dimension in patients with stroke.

OBJECTIVE: The 5-level EuroQoL (EQ-5D-5L) is a patient-reported outcome measure frequently used in stroke research. However, it does not assess the cognitive problems many patients with stroke experience. The aim of this article is to compare the content validity, internal consistency and discriminative ability of the EQ-5D-5L with and without an additional cognitive domain (EQ-5D-5L+C), administered three months post-stroke. DESIGN: Cross-sectional study. SETTING: Six general hospitals in the Netherlands. SUBJECTS: In all, 360 individuals with stroke three months after the event. INTERVENTIONS: Not applicable. MAIN MEASURES: The modified Rankin Scale and EQ-5D-5L+C were administered in telephone interviews three months post-stroke. RESULTS: A total of 360 patients with stroke were included. Mean age was 68.8 years (standard deviation (SD) = 11.7), 143 (40%) were female, 334 (93%) had had an ischemic stroke, 165 (46%) had a National Institutes of Health Stroke Scale (NIHSS) score ⩽ 4 at presentation and the Barthel Index was 17.2 (SD = 4) four days post-stroke. Cognitive problems were reported by 199 (55%) patients three months post-stroke. Internal consistencies of the EQ-5D-5L and EQ-5D-5L+C were 0.75 and 0.77, respectively. Adding a cognitive domain resulted in a decrease of the ceiling effect from 22% to 14%. Both EQ-5D-5L and EQ-5D-5L+C showed good discriminative ability, but differences between patients with different modified Rankin Scale scores and with/without reported decrease in health and daily activities were slightly larger with the EQ-5D-5L+C compared to the EQ-5D-5L. CONCLUSIONS: The EQ-5D-5L+C, which includes a cognitive domain that is highly significant for stroke patients, showed increased content validity and good discriminative ability, without losing internal consistency.

Complex clinical scenarios with the use of direct oral anticoagulants in patients with atrial fibrillation: a multidisciplinary expert advisory board.

The risk of developing atrial fibrillation (AF) and the risk of stroke both increase with advancing age. As such, many individuals have, or will develop, an indication for oral anticoagulation to reduce the risk of stroke. Currently, a large number of anticoagulants are available, including vitamin K antagonists, direct thrombin or factor Xa inhibitors (the last two also referred to as direct oral anticoagulants or DOACs), and different dosages are available. Of the DOACs, rivaroxaban can be obtained in the most different doses: 2.5 mg, 5 mg, 15 mg and 20 mg. Many patients develop co-morbidities and/or undergo procedures that may require the temporary combination of anticoagulation with antiplatelet therapy. In daily practice, clinicians encounter complex scenarios that are not always described in the treatment guidelines, and clear recommendations are lacking. Here, we report the outcomes of a multidisciplinary advisory board meeting, held in Utrecht (The Netherlands) on 3 June 2019, on decision making in complex clinical situations regarding the use of DOACs. The advisory board consisted of Dutch cardiovascular specialists: (interventional) cardiologist, internist, neurologist, vascular surgeon and general practitioners invited according to personal title and specific field of expertise.

Experience of a single center in the conservative approach of 20 consecutive cases of asymptomatic extracranial carotid artery aneurysms.

BACKGROUND AND PURPOSE: The clinical course and optimal treatment strategy for asymptomatic extracranial carotid artery aneurysms (ECAAs) are unknown. We report our single-center experience with conservative management of patients with an asymptomatic ECAA. METHODS: A search in our hospital records from 1998 to 2013 revealed 20 patients [mean age 52 (SD 12.5) years] with 23 ECAAs, defined as a 150% or more fusiform dilation or any saccular dilatation compared with the healthy internal carotid artery. None of the aneurysms were treated and we had no pre-defined follow-up schedule for these patients. The primary study end-point was the yearly rate for ipsilateral ischemic stroke. Secondary end-points were ipsilateral transient ischemic attack, any stroke-related death, other symptoms related to the aneurysm or growth defined as any diameter increase. RESULTS: The ECAA was either fusiform (n = 6; mean diameter 10.2 mm) or saccular (n = 17; mean diameter 10.9 mm). Eleven (55%) patients with 13 ECAAs received antithrombotic medication. During follow-up [median 46.5 (range 1-121) months], one patient died due to ipsilateral stroke and the ipsilateral cerebral stroke rate was 1.1 per 100 patient-years (95% confidence interval, 0.01-6.3). Three patients had ECAA growth, two of whom were asymptomatic and one was the patient who suffered a stroke. CONCLUSIONS: In this retrospective case series of patients with an asymptomatic ECAA, the risk of cerebral infarction is small but not negligible. Conservative management seems justified, in particular in patients without growth. Large prospective registry data are necessary to assess follow-up imaging strategies and the role of antiplatelet therapy.

Relation between adiposity and vascular events, malignancy and mortality in patients with stable cerebrovascular disease.

BACKGROUND: Abdominal adiposity is associated with various risk factors including hypertension, and is therefore particularly relevant in patients with stable cerebrovascular disease (CeVD). A U-shaped relation between body mass index (BMI, kg m-2) and cardiovascular events is often described. Whether this U-shape persists for abdominal adiposity, and consequently which reference values should guide clinical practice, is unclear. We described the relation between multiple adiposity measurements and risk of vascular events, vascular mortality, malignancy and all-cause mortality in patients with clinically stable CeVD. METHODS: During a median follow-up time of 6.8 years, 1767 patients were prospectively followed. Relations were assessed using multivariable adjusted Cox proportional hazards models. Adiposity was assessed with BMI, waist circumference (stratified by gender) and the contribution of visceral fat to total abdominal fat (VAT%) measured using ultrasound. Relations were nonlinear if the χ2-statistic of the nonlinear term was significant (P-value<0.05). Nadirs were reported for nonlinear and hazard ratios (HRs) for linear relations. RESULTS: The relations between BMI and outcomes were nonlinear with nadirs ranging between 27.1 (95% confidence interval (CI) 21.9-29.3) kg m2 for vascular mortality and 28.1 (95% CI, 19.0-38.2)) kg m-2 for malignancy. The relation between waist circumference and all-cause mortality was nonlinear with a nadir of 84.0 (95% CI, 18.7-134.8) cm for females and 94.8 (95% CI, 80.3-100.1) cm for males. No nonlinearity was detected for VAT%. A 1-s.d. (9.8%) increase in VAT% was related to both vascular (HR, 1.23, 95% CI 1.00-1.51) and all-cause mortality (HR, 1.22, 95% CI 1.05-1.42). CONCLUSIONS: In patients with CeVD, a BMI around 27-28 kg m-2 relates to the lowest risk of vascular events, vascular mortality, malignancy and all-cause mortality. However, increasing abdominal adiposity confers a higher risk of all-cause mortality. Thus, whereas traditional BMI cutoffs may be re-evaluated in this population, striving for low abdominal obesity should remain a goal.

Assessment of blood flow velocity and pulsatility in cerebral perforating arteries with 7-T quantitative flow MRI.

Thus far, blood flow velocity measurements with MRI have only been feasible in large cerebral blood vessels. High-field-strength MRI may now permit velocity measurements in much smaller arteries. The aim of this proof of principle study was to measure the blood flow velocity and pulsatility of cerebral perforating arteries with 7-T MRI. A two-dimensional (2D), single-slice quantitative flow (Qflow) sequence was used to measure blood flow velocities during the cardiac cycle in perforating arteries in the basal ganglia (BG) and semioval centre (CSO), from which a mean normalised pulsatility index (PI) per region was calculated (n = 6 human subjects, aged 23-29 years). The precision of the measurements was determined by repeated imaging and performance of a Bland-Altman analysis, and confounding effects of partial volume and noise on the measurements were simulated. The median number of arteries included was 14 in CSO and 19 in BG. In CSO, the average velocity per volunteer was in the range 0.5-1.0 cm/s and PI was 0.24-0.39. In BG, the average velocity was in the range 3.9-5.1 cm/s and PI was 0.51-0.62. Between repeated scans, the precision of the average, maximum and minimum velocity per vessel decreased with the size of the arteries, and was relatively low in CSO and BG compared with the M1 segment of the middle cerebral artery. The precision of PI per region was comparable with that of M1. The simulations proved that velocities can be measured in vessels with a diameter of more than 80 µm, but are underestimated as a result of partial volume effects, whilst pulsatility is overestimated. Blood flow velocity and pulsatility in cerebral perforating arteries have been measured directly in vivo for the first time, with moderate to good precision. This may be an interesting metric for the study of haemodynamic changes in aging and cerebral small vessel disease. © 2015 The Authors NMR in Biomedicine Published by John Wiley & Sons Ltd.

Case-finding for cognitive impairment among people with Type 2 diabetes in primary care using the Test Your Memory and Self-Administered Gerocognitive Examination questionnaires: the Cog-ID study.

AIM: To evaluate two cognitive tests for case-finding for cognitive impairment in older patients with Type 2 diabetes. METHODS: Of 1243 invited patients with Type 2 diabetes, aged ≥70 years, 228 participated in a prospective cohort study. Exclusion criteria were: diagnosis of dementia; previous investigation at a memory clinic; and inability to write or read. Patients first filled out two self-administered cognitive tests (Test Your Memory and Self-Administered Gerocognitive Examination). Secondly, a general practitioner, blinded to Test Your Memory and Self-Administered Gerocognitive Examination scores, performed a structured evaluation using the Mini-Mental State Examination. Subsequently, patients suspected of cognitive impairment (on either the cognitive tests or general practitioner evaluation) and a random sample of 30% of patients not suspected of cognitive impairment were evaluated at a memory clinic. Diagnostic accuracy and area under the curve were determined for the Test Your Memory, Self-Administered Gerocognitive Examination and general practitioner evaluation compared with a memory clinic evaluation to detect cognitive impairment (mild cognitive impairment or dementia). RESULTS: A total of 44 participants were diagnosed with cognitive impairment. The Test Your Memory and Self-Administered Gerocognitive Examination questionnaires had negative predictive values of 81 and 85%, respectively. Positive predictive values were 39 and 40%, respectively. The general practitioner evaluation had a negative predictive value of 83% and positive predictive value of 64%. The area under the curve was ~0.70 for all tests. CONCLUSIONS: Both the tests evaluated in the present study can easily be used in case-finding strategies for cognitive impairment in patients with Type 2 diabetes in primary care. The Self-Administered Gerocognitive Examination had the best diagnostic accuracy and therefore we would have a slight preference for this test. Applying the Self-Administered Gerocognitive Examination would considerably reduce the number of patients in whom the general practitioner needs to evaluate cognitive functioning to tailor diabetes treatment.

Cerebellar cortical infarct cavities and vertebral artery disease.

INTRODUCTION: Cerebellar cortical infarct cavities are a newly recognised entity associated with atherothromboembolic cerebrovascular disease and worse physical functioning. We aimed to investigate the relationship of cerebellar cortical infarct cavities with symptomatic vertebrobasilar ischaemia and with vascular risk factors. METHODS: We evaluated the MR images of 46 patients with a recent vertebrobasilar TIA or stroke and a symptomatic vertebral artery stenosis ≥50 % from the Vertebral Artery Stenting Trial (VAST) for the presence of cerebellar cortical infarct cavities ≤1.5 cm. At inclusion in VAST, data were obtained on age, sex, history of vertebrobasilar TIA or stroke, and vascular risk factors. Adjusted risk ratios were calculated with Poisson regression analyses for the relation between cerebellar cortical infarct cavities and vascular risk factors. RESULTS: Sixteen out of 46 (35 %) patients showed cerebellar cortical infarct cavities on the initial MRI, and only one of these 16 patients was known with a previous vertebrobasilar TIA or stroke. In patients with symptomatic vertebrobasilar ischaemia, risk factor profiles of patients with cerebellar cortical infarct cavities were not different from patients without these cavities. CONCLUSION: Cerebellar cortical infarct cavities are seen on MRI in as much as one third of patients with recently symptomatic vertebral artery stenosis. Since patients usually have no prior history of vertebrobasilar TIA or stroke, cerebellar cortical infarct cavities should be added to the spectrum of common incidental brain infarcts visible on routine MRI.

Age-related changes in brain hemodynamics; A calibrated MRI study.

INTRODUCTION: Blood oxygenation-level dependent (BOLD) magnetic resonance imaging signal changes in response to stimuli have been used to evaluate age-related changes in neuronal activity. Contradictory results from these types of experiments have been attributed to differences in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2 ). To clarify the effects of these physiological parameters, we investigated the effect of age on baseline CBF and CMRO2 . MATERIALS AND METHODS: Twenty young (mean ± sd age, 28 ± 3 years), and 45 older subjects (66 ± 4 years) were investigated. A dual-echo pseudocontinuous arterial spin labeling (ASL) sequence was performed during normocapnic, hypercapnic, and hyperoxic breathing challenges. Whole brain and regional gray matter values of CBF, ASL cerebrovascular reactivity (CVR), BOLD CVR, oxygen extraction fraction (OEF), and CMRO2 were calculated. RESULTS: Whole brain CBF was 49 ± 14 and 40 ± 9 ml/100 g/min in young and older subjects respectively (P < 0.05). Age-related differences in CBF decreased to the point of nonsignificance (B=-4.1, SE=3.8) when EtCO2 was added as a confounder. BOLD CVR was lower in the whole brain, in the frontal, in the temporal, and in the occipital of the older subjects (P<0.05). Whole brain OEF was 43 ± 8% in the young and 39 ± 6% in the older subjects (P = 0.066). Whole brain CMRO2 was 181 ± 60 and 133 ± 43 µmol/100 g/min in young and older subjects, respectively (P<0.01). DISCUSSION: Age-related differences in CBF could potentially be explained by differences in EtCO2 . Regional CMRO2 was lower in older subjects. BOLD studies should take this into account when investigating age-related changes in neuronal activity.

Management of extracranial carotid artery aneurysm.

INTRODUCTION: Aneurysms of the extracranial carotid artery (ECAA) are rare. Several treatments have been developed over the last 20 years, yet the preferred method to treat ECAA remains unknown. This paper is a review of all available literature on the risk of complications and long-term outcome after conservative or invasive treatment of patients with ECAA. METHODS: Reports on ECAA treatment until July 2014 were searched in PubMed and Embase using the key words aneurysm, carotid, extracranial, and therapy. RESULTS: A total of 281 articles were identified. Selected articles were case reports (n = 179) or case series (n = 102). Papers with fewer than 10 patients were excluded, resulting in the final selection of 39 articles covering a total of 1,239 patients. Treatment consisted of either conservative treatment in 11% of the cases or invasive treatment in 89% of the cases. Invasive treatment comprised surgery in 94%, endovascular approach in 5%, and a hybrid approach in 1% of the patients. The most common complication described after invasive therapy was cranial nerve damage, which occurred in 11.8% of patients after surgery. The 30 day mortality rate and stroke rate in conservatively treated patients was 4.67% and 6.67%, after surgery 1.91% and 5.16%. Information on confounders in the present study was incomplete. Therefore, adjustments to correct for confounding by indication could not be done. CONCLUSIONS: This review summarizes the largest available series in the literature on ECAA management. The number of ECAAs reported in current literature is scarce. The early and long-term outcome of invasive treatment in ECAA is favorable; however, cranial nerve damage after surgery occurs frequently. Unfortunately, due to limitations in reporting of results and confounding by indication in the available literature, it was not possible to determine the optimal treatment strategy. There is a need for a multicenter international registry to reveal the optimal treatment for ECAA.

The ThRombolysis in UnconTrolled Hypertension (TRUTH) protocol: an observational study on treatment strategy of elevated blood pressure in stroke patients eligible for IVT.

BACKGROUND: Intravenous thrombolysis (IVT) with (recombinant) tissue plasminogen activator is an effective treatment in acute ischemic stroke. However, IVT is contraindicated when blood pressure is above 185/110 mmHg, because of an increased risk on symptomatic intracranial hemorrhage. In current Dutch clinical practice, two distinct strategies are used in this situation. The active strategy comprises lowering blood pressure with antihypertensive agents below these thresholds to allow start of IVT. In the conservative strategy, IVT is administered only when blood pressure drops spontaneously below protocolled thresholds. A retrospective analysis in two recent stroke trials showed a non-significant signal towards better functional outcome in the active group; robust evidence for either strategy, however, is lacking. We hypothesize that (I) the active strategy leads to a better functional outcome three months after acute ischemic stroke. Secondary hypotheses are that this effect occurs despite (II) increasing the number of symptomatic intracranial hemorrhages, and could be attributable to (III) a higher rate of IVT treatments and (IV) a shorter door-to-needle time. METHODS AND DESIGN: The TRUTH is a prospective, observational, cluster-based, parallel group follow-up study; in which participating centers continue their current local treatment guidelines. Outcomes of patients admitted to centers with an active will be compared to those admitted to centers with a conservative strategy. The primary outcome is functional outcome on the modified Rankin Scale at three months. Secondary outcomes are symptomatic intracranial hemorrhage, IVT treatment and door-to-needle time. We based our sample size estimate on an ordinal analysis of the mRS with the "proportional odds" model. With the aforementioned signal observed in a recent retrospective study in these patients as an estimate of the effect size and with alpha 0 · 05, this analysis would have an 80 % power with a total number of 600 patients. Corrections for expected imbalance in group size and clustering effects resulted in a sample size of 1235 patients. DISCUSSION: The TRUTH is the first large prospective study specifically studying IVT-candidates with elevated blood pressure, and has the potential to change clinical practice and optimize acute stroke care in these patients.

Antithrombotic treatment and intracerebral haemorrhage: between Scylla and Charybdis.

In patients who have intracerebral haemorrhage while on antithrombotic treatment, there is no evidence from randomised clinical trials to support decisions with regard to antithrombotic medication. In the acute phase, we advise stopping all antithrombotic treatment with rapid reversal of antithrombotic effects of oral anticoagulants. After the acute phase, we discourage restarting oral anticoagulants in patients with a lobar haematoma caused by cerebral amyloid angiopathy because of the high risk of recurrent bleeding. In these patients, even treatment with platelet inhibitors needs careful weighing of the risks of bleeding and ischaemic stroke. In patients with non-lobar intracerebral haemorrhage, we suggest considering restarting optimal antithrombotic treatment. This includes treatment with oral anticoagulants for patients with atrial fibrillation and/or mechanical valve prosthesis. After intracerebral haemorrhage during oral anticoagulant therapy in patients with atrial fibrillation, direct anticoagulants may be better than vitamin K antagonists, but we await confirmation of this from ongoing trials.

An early prediction of delirium in the acute phase after stroke.

BACKGROUND: We developed and validated a risk score to predict delirium after stroke which was derived from our prospective cohort study where several risk factors were identified. METHODS: Using the ß coefficients from the logistic regression model, we allocated a score to values of the risk factors. In the first model, stroke severity, stroke subtype, infection, stroke localisation, pre-existent cognitive decline and age were included. The second model included age, stroke severity, stroke subtype and infection. A third model only included age and stroke severity. The risk score was validated in an independent dataset. RESULTS: The area under the curve (AUC) of the first model was 0.85 (sensitivity 86%, specificity 74%). In the second model, the AUC was 0.84 (sensitivity 80%, specificity 75%). The third model had an AUC of 0.80 (sensitivity 79%, specificity 73%). In the validation set, model 1 had an AUC of 0.83 (sensitivity 78%, specificity 77%). The second had an AUC of 0.83 (sensitivity 76%, specificity 81%). The third model gave an AUC of 0.82 (sensitivity of 73%, specificity 75%). We conclude that model 2 is easy to use in clinical practice and slightly better than model 3 and, therefore, was used to create risk tables to use as a tool in clinical practice. CONCLUSIONS: A model including age, stroke severity, stroke subtype and infection can be used to identify patients who have a high risk to develop delirium in the early phase of stroke.

Predictive value of thrombus attenuation on thin-slice non-contrast CT for persistent occlusion after intravenous thrombolysis.

BACKGROUND: In stroke erythrocyte-rich thrombi are more sensitive to intravenous thrombolysis with recombinant tissue plasminogen activator (IV-rtPA) and have higher density on non-contrast CT (NCCT). We investigated the relationship between thrombus density and recanalization and whether persistent occlusions can be predicted by Hounsfield unit (HU) measurements. METHODS: In 88 IV-rtPA-treated patients with intracranial ICA or MCA occluding thrombus and follow-up imaging, thrombus and contralateral vessel attenuation measurements were performed on thin-slice NCCT. Mean absolute and relative HU were compared between patients with persistent occlusion (modified Thrombolysis in Cerebral Infarction system, grade 0/1/2a) and recanalization (grade 2b/3). Univariate and multivariate (adjusted for stroke subtype, clot burden score, occlusion site and time to thrombolysis) odds ratios for persistent occlusion were calculated. Additional prognostic value for persistent occlusion was estimated by adding HU measurements to the area under the curve (AUC) of known determinants and calculating optimal cut-off values. RESULTS: Patients with persistent occlusion (n = 19) had significant lower mean HU (absolute 52.2 ± 9.5, relative 1.29 ± 0.20) compared to recanalization (absolute 63.1 ± 10.7, relative 1.54 ± 0.23, both p < 0.0001). Odds ratios for persistent occlusion were 3.1 (95% confidence interval, CI 1.6-6.0) univariate and 3.1 (95% CI 1.7-5.7) multivariate per 10 absolute HU decrease and 3.2 (95% CI 1.6-6.5) univariate and 4.1 (95% CI 1.8-9.1) multivariate per 0.20 relative HU decrease. Attenuation measurements significantly increased the AUC (0.67) of the known determinants to 0.84 (absolute HU) and 0.86 (relative HU). Cut-off values of <56.5 absolute HU and <1.38 relative HU showed optimal predictive values for persistent occlusion. CONCLUSIONS: Thrombus density is related to recanalization rate. Lower absolute and relative HU are independently related to persistent occlusion and HU measurements significantly increase discriminative performances of known recanalization determinants.

Delay to carotid endarterectomy in patients with symptomatic carotid artery stenosis.

OBJECTIVE: In patients with recently symptomatic carotid artery stenosis, guidelines recommend carotid revascularization within 2 weeks of the index event. The "index event" may be defined as either the first or the most recent event. The delay between the index event and carotid endarterectomy (CEA) over a period of 6 years in a single centre was evaluated and the effect of defining the index event as either the first or the most recent event was assessed. DESIGN: Observational study. METHODS: 555 consecutive patients with symptomatic carotid stenosis ≥ 50% treated with CEA between 2007 and 2012 were assessed. In 2010, changes to the in-hospital process of care to reduce delays in referral and CEA were introduced. These changes included, for example, improving access to physicians, imaging, and operating rooms. The delay from symptoms to surgery was expressed in days. RESULTS: The median time between the first event and surgery was reduced from 53 days (interquartile range [IQR] 30-78) in 2007 to 21 days (IQR 12-45) in 2012, and between the most recent event and CEA from 45 days (IQR 28-67) to 17 days (IQR 9-28). Patients referred directly by their general practitioner more often underwent CEA within 2 weeks than patients referred by specialists from other hospitals. Compared to patients with transient ischaemic attack or ocular symptoms, patients with ischaemic stroke more often underwent CEA within 2 weeks. CONCLUSIONS: A small change in the process of care significantly reduced the delay from the index event to CEA, but in 2012 it still exceeded 14 days in the majority of patients. The definition of the "index event" has a large impact on the total duration of delay, and should therefore be uniform across studies.

Delirium in the acute phase after stroke and the role of the apolipoprotein E gene.

OBJECTIVE: To study the association between the epsilon 4 allele of apolipoprotein E (APOEε4) and delirium in a stroke population. METHODS: 527 consecutive stroke patients were screened for delirium during the first week of admission with the confusion assessment method. In three hundred fifty-three patients genomic DNA isolation was available. RESULTS: The incidence of delirium after stroke in the 353 patients was 11.3%. There was no association between APOEε4 and delirium. Even after adjustment for IQCODE, stroke localization, stroke subtype, stroke severity, infection, and brain atrophy no association was found (odds ratio: 0.9; 95% confidence interval: 0.4-2.1). Delirium did not last longer in patients with an APOEε4 allele compared to patients without an APOEε4 allele (median: 5.6 days [range: 1-21] versus median: 4.6 days [range: 1-15], p = 0.5). CONCLUSION: There was no association between the presence of an APOEε4 allele and the occurrence of delirium in the acute phase after stroke.

Risk of vascular events after nondisabling small and large vessel cerebral ischemia.

BACKGROUND: Small- and large-vessel disease (SVD and LVD, respectively) might have a different pathogenesis and prognosis but the long-term risk of death and recurrent stroke appears to be similar in previous studies. In this study, we investigated the long-term vascular prognosis of patients with LVD and SVD in a large cohort of well-documented patients. METHODS: We included 971 patients with transient ischemic attack (TIA) or nondisabling ischemic stroke of atherosclerotic origin referred to a university hospital in the Netherlands between 1994 and 2005 and followed them for the occurrence of vascular events or death. The primary outcome was a composite of stroke, myocardial infarction and vascular death, whichever happened first. Classification of SVD/LVD was primarily based on brain imaging. We used regression analyses to generate hazard ratios (HRs) with 95% confidence intervals (CIs). Sensitivity analyses were performed in subsets of the population, i.e. patients with subtype classification based on imaging, excluding TIA patients, first-ever stroke patients and LVD patients without a symptomatic carotid stenosis. RESULTS: During a mean follow-up of 6.3 years, new vascular events occurred in 56 of 312 SVD patients (3.3%/year) and in 128 of 659 LVD patients (2.9%/year). These were ischemic strokes in 33 of the 56 events in SVD patients (2.0%/year) and 54 of the 128 events in LVD patients (1.2%/year). The corresponding age- and sex-adjusted HR for all new vascular events for LVD versus SVD was 0.76 (95% CI 0.56-1.05) for the total follow-up period. When this risk was split into early risk (<1 year) and late risk (>1 year), it was not significantly different for the 1-year risk of vascular events (HR 1.04, 95% CI 0.57-1.91); however, after 1 year of follow-up, LVD patients had fewer outcome events compared with SVD patients (HR 0.66, 95% CI 0.46-0.96). For ischemic strokes, the overall HR was 0.60 (95% CI 0.39-0.94). As with the primary outcome, here also the 1-year risk was not significantly different from >1-year risk (HR 1.31, 95% CI 0.62-2.81, and HR 0.36, 95% CI 0.21-0.63, respectively). The sensitivity analyses showed virtually the same results. CONCLUSION: In patients with nondisabling cerebrovascular disease, we found, despite no differences at baseline in terms of vascular risk factors, a better long-term prognosis for patients with LVD for all vascular events, especially for recurrent strokes. Our observations support a different pathogenesis in SVD and LVD patients, and optimal prevention is indicated for patients with what was formerly regarded as 'benign' SVD stroke.

Near-infrared spectroscopy to indicate selective shunt use during carotid endarterectomy.

OBJECTIVES: This study assessed the value of cerebral near-infrared spectroscopy (NIRS) and transcranial Doppler (TCD) in relation to electroencephalography (EEG) changes for the detection of cerebral hypoperfusion necessitating shunt placement during carotid endarterectomy (CEA). METHODS: This was a prospective cohort study. Patients with a sufficient TCD window undergoing CEA from February 2009 to June 2011 were included. All patients were continuously monitored with NIRS and EEG. An intraluminal shunt was placed, selectively determined by predefined EEG changes in alpha, beta, theta, or delta activity. Relative changes in regional cerebral oxygen saturation (rSO2) in the frontal lobe and mean blood flow velocity (Vmean) 30 seconds before carotid cross-clamping versus 2 minutes after carotid cross-clamping were related to shunt placement. Receiver operating characteristic curve analysis was performed to determine the optimal thresholds. Diagnostic values were reported as positive and negative predictive value (PPV and NPV). RESULTS: Of a cohort of 151 patients, 17(11%) showed EEG changes requiring shunt placement. The rSO2 and Vmean decreased more in the shunt group than in the non-shunt group (mean ± standard error of the mean) 21 ± 4% versus 7 ± 5% and 76 ± 6% versus 12 ± 3%, respectively (p < .005), Receiver operating characteristic curve analysis revealed a threshold of 16% decrease in rSO2 (PPV 76% and NPV 99%) and 48% decrease in Vmean (PPV 53% and NPV 99%) as the optimal cut-off value to detect cerebral ischemia during CEA under general anesthesia. CONCLUSIONS: Compared with EEG, we found moderate PPV but high NPV for NIRS and TCD to detect cerebral ischemia during CEA under general anesthesia, meaning that both techniques independently may be suitable to exclude patients for unnecessary shunt use and to direct the use of selective shunting. However, the optimal thresholds for NIRS remain to be determined.

Incompleteness of the circle of Willis is related to EEG-based shunting during carotid endarterectomy.

OBJECTIVES: The occurrence of cerebral ischemia during carotid endarterectomy (CEA) can be prevented by (selective) placement of an intraluminal shunt during cross-clamping. We set out to develop a rule to predict the likelihood for shunting during CEA based on preoperative assessment of collateral cerebral circulation and patient characteristics. METHODS: Patients who underwent CEA between 2004 and 2010 were included. Patients without preoperative magnetic resonance (MRA) or computed tomography angiography (CTA) were excluded. The primary endpoint was intraluminal shunt placement based on electroencephalography changes. Age, sex, cardiovascular risk factors peripheral artery disease, symptomatic status, degree of ipsilateral and contralateral carotid, status of the vertebral arteries, and morphology of the CoW were studied as potential predictors for shunt use. A prediction model was derived from a multivariable regression model using discrimination, calibration, and bootstrapping approaches and transformed into a clinical prediction model. RESULTS: A total of 431 patients were included, of which 65 patients (15%) received an intraluminal shunt. In the MRA group (n = 285) factors related to shunt use in multivariate analysis were ipsilateral carotid stenosis 90-99% (odds ratio [OR] 0.15, 95% CI 0.04-0.53), contralateral carotid occlusion (OR 4.29, 95% CI 1.68-10.95) and any not-visible anterior (OR 4.96, 95% CI 1.95-12.58) or ipsilateral posterior segment of the CoW (OR 5.08, 95% CI 2.10-12.32). In the CT group none of the factors were independently related to shunt use; therefore, only predictors describing morphology of CoW derived from MRA findings were included in our model. The c-statistic of this model was 0.79 (95% CI 0.72-0.86). Among patients with an estimated chance of needing a shunt of under 10% (49% of the population), the likelihood of shunting was 5%. In those in whom this chance was estimated higher than 30% (13% of the population) the likelihood was 51%. CONCLUSIONS: Among patients scheduled for CEA, assessment of cerebral arteries and of the configuration of the CoW based on MRA-derived images can help to identify patients with low and high likelihood of the need of shunt use during surgery.

Relationship between thrombus attenuation and different stroke subtypes.

INTRODUCTION: More insights in the etiopathogenesis of thrombi could be helpful in the treatment of patients with acute ischemic stroke. The aim of our study was to determine the relationship between presence of a hyperdense vessel sign and thrombus density with different stroke subtypes. METHODS: We included 123 patients with acute ischemic anterior circulation stroke and a visible occlusion on CT-angiography caused by cardioembolism (n = 53), large artery atherosclerosis (n = 55), or dissection (n = 15). Presence or absence of a hyperdense vessel sign was assessed and thrombus density was measured in Hounsfield Units (HU) on non-contrast 1 mm thin slices CT. Subsequently, occurrence of hyperdense vessel sign and thrombus density (absolute HU and rHU (=HU thrombus/HU contralateral)) were related with stroke subtypes. RESULTS: The presence of hyperdense vessel signs differed significantly among subtypes and was found in 45, 64 and 93 % of patients with cardioembolism, large artery atherosclerosis and dissection, respectively (p = 0.003). The mean HU and rHU (+95 % CI) of the thrombi in all vessels were respectively 56.1 (53.2-59.0) and 1.39 (1.33-1.45) in cardioembolism, 64.6 (62.2-66.9) and 1.59 (1.54-1.64) in large artery atherosclerosis and 76.4 (73.0-79.8) and 1.88 (1.79-1.97) in dissection (p < 0.0001). We found the same significant ranking order in the density of thrombi with hyperdense vessel signs (mean HU and rHU (+95 % CI), respectively): cardioembolism 61.3 (57.4-65.3) and 1.49 (57.4-65.3); large artery atherosclerosis 67.3 (64.9-69.7) and 1.65 (1.58-1.71); dissection 76.4 (72.6-80.1) and 1.89 (1.79-1.99, p < 0.0001). CONCLUSION: Presence of a hyperdense vessel sign and thrombus density are related to stroke subtype.