Randomised comparison of a balloon-expandable and self-expandable valve with quantitative assessment of aortic regurgitation using magnetic resonance imaging.

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is a safe and effective treatment for inoperable, intermediate- or high-risk patients with severe symptomatic aortic stenosis and has been associated with excellent clinical outcomes. A clinically relevant remaining problem is aortic regurgitation (AR) post-TAVI, which is associated with increased mortality. Therefore, we conducted a prospective randomised trial to assess the safety and efficacy of a first-generation self-expandable valve (SEV; CoreValve) and a third-generation balloon-expandable valve (BEV; Sapien 3) with respect to clinical outcomes and AR as determined quantitatively by magnetic resonance imaging (MRI). METHODS: The ELECT study was an investigator-initiated, single-centre trial involving patients with severe symptomatic aortic stenosis and with a clinical indication for transfemoral TAVI. Fifty-six patients were randomly assigned to the BEV or SEV group. RESULTS: AR determined quantitatively by MRI was lower in the BEV than in the SEV group [regurgitant fraction: 1.1% (0-8.0) vs 8.7% (3.0-14.8) for SEV; p = 0.01]. Secondary endpoints according to the criteria of the Second Valve Academic Research Consortium (VARC-2) showed BEV to have better early safety [0 (0%) vs 8 (30%); p = 0.002] at 30 days and a lower risk of stroke [0 (0%) vs 5 (21%); p = 0.01], major adverse cardiac and cerebrovascular events [0 (0%) vs 10 (38%); p < 0.001] or death [0 (0%) vs 5 (19%); p = 0.02] in the 1st year compared with SEV. CONCLUSIONS: The use of the latest generation of BEV was associated with less AR as quantitatively assessed by MRI. Although the use of MRI to quantify AR is not feasible in daily clinical practice, it should be considered as a surrogate endpoint for clinical outcomes in comparative studies of valves for TAVI. ClinicalTrials.gov number NCT01982032.

MRI Vessel Wall Imaging after Intra-Arterial Treatment for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Vessel wall imaging is increasingly performed in the diagnostic work-up of patients with ischemic stroke. The aim of this study was to compare vessel wall enhancement after intra-arterial thrombosuction with that in patients not treated with thrombosuction. MATERIALS AND METHODS: From 2009 to 2017, forty-nine patients with an ischemic stroke underwent 7T MR imaging within 3 months after symptom onset as part of a prospective intracranial vessel wall imaging study. Fourteen of these patients underwent intra-arterial treatment using thrombosuction (intra-arterial treatment group). In the intra-arterial treatment group, vessel walls were evaluated for major vessel wall changes. All patients underwent pre- and postcontrast vessel wall imaging to assess enhancing foci of the vessel wall using coregistered subtraction images. A Wilcoxon signed rank test was performed to test for differences. RESULTS: In the intra-arterial treatment group, 11 of 14 patients (79%) showed vessel wall enhancement compared with 17 of 35 patients without intra-arterial treatment (49%). In the intra-arterial treatment group, more enhancing foci were detected on the ipsilateral side (n = 18.5) compared with the contralateral side (n = 3, P = .005). Enhancement was more often concentric on the ipsilateral side (n = 8) compared with contralateral side (n = 0, P = .01). No differences were found in the group without intra-arterial treatment between the number and configuration of ipsilateral and contralateral enhancing foci. CONCLUSIONS: Patients with intra-arterial treatment by means of thrombosuction showed more (concentric) enhancing foci of the vessel wall ipsilateral compared with contralateral to the treated artery than the patients without intra-arterial treatment, suggesting reactive changes of the vessel wall. This finding should be taken into account when assessing vessel wall MR images in patients with stroke.

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.

Fourth European stroke science workshop.

Lake Eibsee, Garmisch-Partenkirchen, 16 to 18 November, 2017: The European Stroke Organisation convened >120 stroke experts from 21 countries to discuss latest results and hot topics in clinical, translational and basic stroke research. Since its inception in 2011, the European Stroke Science Workshop has become a cornerstone of European Stroke Organisation's academic activities and a major highlight for researchers in the field. Participants include stroke researchers at all career stages and with different backgrounds, who convene for plenary lectures and discussions. The workshop was organised in seven scientific sessions focusing on the following topics: (1) acute stroke treatment and endovascular therapy; (2) small vessel disease; (3) opportunities for stroke research in the omics era; (4) vascular cognitive impairment; (5) intracerebral and subarachnoid haemorrhage; (6) alternative treatment concepts and (7) neural circuits, recovery and rehabilitation. All sessions started with a keynote lecture providing an overview on current developments, followed by focused talks on a timely topic with the most recent findings, including unpublished data. In the following, we summarise the key contents of the meeting. The program is provided in the online only Data Supplement. The workshop started with a key note lecture on how to improve the efficiency of clinical trial endpoints in stroke, which was delivered by Craig Anderson (Sydney, Australia) and set the scene for the following discussions.

Optimal cut-off criteria for duplex ultrasound compared with computed tomography angiography for the diagnosis of restenosis in stented carotid arteries in the international carotid stenting study.

INTRODUCTION: Previous studies that reported duplex-ultrasound cut-off criteria, based on blood velocity parameters, for the degree of stenosis in a stented carotid artery were either retrospective, or the reference test was carried out only when a patient was suspected of having restenosis at duplex ultrasound, which is likely to have resulted in verification bias. We performed a prospective study of diagnostic accuracy to find new blood velocity cut-offs in duplex ultrasound for in-stent restenosis. PATIENTS AND METHODS: Stented patients within the international carotid stenting study were eligible. Patients had a carotid computed tomography angiography in addition to routine duplex ultrasound performed at a yearly follow-up. Duplex-ultrasound bloodflow velocity parameters were compared to the degree of stenosis on computed tomography angiography. The results were analysed using receiver-operating-characteristic curves. RESULTS: We included 103 patients in this study. On computed tomography angiography, 30 (29.1%) patients had a 30%-49% in-stent restenosis, 21 (20.4%) patients had 50%-69% in-stent restenosis and 5 (4.9%) patients a ≥70% in-stent restenosis. The cut-off value ≥50% stenosis was a peak systolic velocity of 125 cm/s (sensitivity: 63% (95% CI: 41-79), specificity: 83% (95% CI: 72-90)). DISCUSSION: This study provides a level 2b evidence for new cut-off values for in-stent restenosis. Unfortunately, we could not say anything about severe stenosis because of the low number of severe stenosis after one year. CONCLUSIONS: The 125 cm/s cut-off value on duplex ultrasound is lower than found in previous studies and equal to unstented arteries. Duplex-ultrasound measurements made in stented carotid arteries should not be corrected for the presence of a stent when determining the degree of stenosis.

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.

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.

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.

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.

Flow velocities in the external carotid artery following carotid revascularization.

OBJECTIVE: To study the changes in peak systolic velocities of the ipsilateral external carotid artery (ECA) following carotid revascularization. METHODS: All patients randomized to carotid artery stenting (CAS) or carotid endarterectomy (CEA) in the International Carotid Stenting Study (ICSS; ISRCTN25337470) in our center were included. Peak systolic velocities (PSV) were assessed with duplex ultrasound (DUS) at baseline, at 30 days, and at 12 and 24 months after treatment. Our primary outcome measure was the change in blood flow velocities in the ECA (ΔPSVECA). Secondary outcome measure was the prevalence of post interventional ECA occlusion. RESULTS: Of 270 patients enrolled in ICSS at our center, 224 patients (mean age, 68.8 years; 154 males) were included in the present study (116 CAS, 108 CEA). Baseline PSV in the ipsilateral ECA was similar between the groups. Following CAS, PSV gradually increased during follow-up, whereas PSV remained relatively stable after CEA; mean difference of PSV between CAS and CEA: 23 cm/s (95% CI, -5 to 52), 58 cm/s (95% CI, 27-89), and 69 cm/s (95% CI, 31-107) at 30 days, 12 months, and 24 months. One new ECA occlusion occurred after CAS and two after CEA. CONCLUSION: Blood flow velocities in the ipsilateral ECA increase significantly after CAS but not after CEA. However, this does not lead to a higher rate of ECA occlusion in the first 2 years after revascularization. We conclude that CAS is not inferior to CEA in preserving the ECA as a possible potential collateral pathway for cerebral blood supply within 2 years following revascularization.

Interprocedural comparison of changes in natural flow velocity patterns in the internal carotid artery following CAS or CEA.

BACKGROUND AND PURPOSE: Different flow velocities have been reported after carotid angioplasty with stenting (CAS) than after carotid endarterectomy (CEA). We compared blood flow velocities following CAS and CEA in the International Carotid Stenting Study (ICSS; ISRCTN25337470). MATERIALS AND METHODS: In total, 254 patients (70% male; 129 CAS and 125 CEA) were included. Mean peak systolic velocities (PSVICA) were assessed at baseline, 30 days, 1 and 2 years. Following both treatments, restenosis ≥ 50% was defined as PSVmean >125 cm s(-1). RESULTS: CAS and CEA resulted in a similar reduction in PSVICA 1 month after treatment. Post-intervention analysis for each treatment separately revealed that PSVICA following CAS increased significantly during follow-up (30 days to 2 years; 22.4 cm s(-1); 95% confidence interval (CI), 14.3 to 30.5). On the contrary, PSVICA following CEA remained relatively stable during follow-up (4.7 cm s(-1); 95% CI, -6.5 to 15.9). When we analysed the increase in PSVICA between both treatments after 2 years of follow-up, no significant interprocedural difference was observed. The internal carotid artery/common carotid artery (ICA/CCA) PSV ratio increased after CAS but not after CEA: 1.2 vs. 1.1 (0.04, 95% CI; -0.16 to 0.25) at 30 days; 1.5 vs. 1.1 (0.39, 95% CI; 0.13 to 0.65) at 1 year; and 1.5 vs. 1.1 (0.36; 95% CI, 0.08 to 0.63) at 2 years. The rate of apparent ipsilateral ICA restenosis >50% was higher following CAS (hazard ratio 2.35; 95% CI, 1.35 to 4.09). CONCLUSION: Two years after carotid revascularisation, no significant interprocedural difference was observed in the increase of PSVICA between CAS and CEA. However, the ICA/CCA ratio increased more following CAS resulting in an apparent higher rate of restenosis following CAS.

Effects of high-dose paracetamol on blood pressure in acute stroke.

BACKGROUND: Early administration of paracetamol may improve outcome of patients with acute stroke and a baseline body temperature of 37°C or above by lowering body temperature and preventing fever. Besides its antipyretic effects, paracetamol may affect blood pressure through cyclooxygenase-2 inhibition. We therefore aimed to assess the effect of high-dose paracetamol on blood pressure in patients with acute stroke. METHODS: We analyzed data of 540 patients admitted within 24 h of stroke onset who were randomized to treatment with either paracetamol (6 g daily) or placebo. Blood pressures were measured at 12, 24, and 48 h from the start of treatment. Changes in blood pressure from baseline in the two treatment groups and corresponding 95% confidence intervals (CI) were calculated with linear regression analysis. Adjustments for potential confounders were made with a multiple linear regression model. RESULTS: Treatment with high-dose paracetamol was associated with a significant reduction in systolic blood pressure of 4.5 mm Hg (95% CI 0.6-8.5) at 12 h from the start of treatment. This effect was no longer present after 24 and 48 h. CONCLUSION: High-dose paracetamol reduces not only body temperature but also systolic blood pressure in the first 12 h after start of treatment. Both effects may improve functional outcome after stroke, but this needs further study.

Cognition after carotid endarterectomy or stenting: a randomized comparison.

OBJECTIVE: To compare the effect on cognition of carotid artery stenting (CAS) and carotid endarterectomy (CEA) for symptomatic carotid artery stenosis. METHODS: Patients randomized to CAS or CEA in the International Carotid Stenting Study (ICSS; ISRCTN25337470) at 2 participating centers underwent detailed neuropsychological examinations (NPE) before and 6 months after revascularization. Ischemic brain lesions were assessed with diffusion-weighted imaging before and within 3 days after revascularization. Cognitive test results were standardized into z scores, from which a cognitive sumscore was calculated. The primary outcome was the change in cognitive sumscore between baseline and follow-up. RESULTS: Of the 1,713 patients included in ICSS, 177 were enrolled in the 2 centers during the substudy period, of whom 140 had an NPE at baseline and 120 at follow-up. One patient with an unreliable baseline NPE was excluded. CAS was associated with a larger decrease in cognition than CEA, but the between-group difference was not statistically significant: -0.17 (95% CI -0.38 to 0.03; p = 0.092). Eighty-nine patients had a pretreatment MRI and 64 within 3 days after revascularization. New ischemic lesions were found twice as often after CAS than after CEA (relative risk 2.1; 95% CI 1.0 to 4.4; p = 0.041). CONCLUSIONS: Differences between CAS and CEA in effect on cognition were not statistically significant, despite a substantially higher rate of new ischemic lesions after CAS than after CEA. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that any difference between the effects of CAS and CEA on cognition at 6 months after revascularization is small.

Blunt traumatic carotid artery dissection still a pitfall? The rationale for aggressive screening.

INTRODUCTION: The optimal diagnostic strategy for carotid dissection following blunt trauma is yet unclear. The rationale for aggressive screening will be discussed based on a consecutive case series of blunt traumatic carotid artery dissection (CAD). MATERIALS AND METHODS: Five patients admitted to our level I trauma center developed severe complications as a consequence of blunt traumatic CAD. The diagnosis of CAD was delayed in all five patients until serious cerebral ischemia occurred. Despite the current awareness that CAD can result from blunt trauma, this type of injury is often overlooked. Clinical and radiological advances have considerably increased the knowledge of incidence and underlying mechanisms of traumatic CAD. This could have implications for case identification and the evaluation of treatment strategies in clinical trials in the future. CONCLUSION: Screening may increase the rate of early CAD diagnosis, but it is unclear if screening will also result in early detection of a treatable lesion. Trials have to provide the answer to whether initiating therapy will lead to improvements in the outcome in traumatic CAD. We therefore believe that screening is a basic condition for initiation of future clinical trials.

Vasodilatory capacity of the cerebral vasculature in patients with carotid artery stenosis.

BACKGROUND AND PURPOSE: Impairment of the cerebral autoregulation is an important predictor of TIA and stroke in patients with an ICA stenosis. The autoregulative status can be assessed directly by measuring the vasodilatory capacity of the cerebral arteries. The aim of our study was to investigate the vasodilatory capacity of the proximal and distal cerebral vasculature in patients with an ICA stenosis and healthy control subjects by combining MRA with an acetazolamide provocation challenge. MATERIALS AND METHODS: Fourteen functionally independent patients (mean age, 67.2 ± 8.7 years) with a symptomatic ICA stenosis and 19 healthy controls (mean age, 63.1 ± 7.2 years) were included. MRA was performed before and 20 minutes after intravenous administration of acetazolamide. The vasodilatory capacity of 11 proximal and distal cerebral vessels was assessed by measuring the increase in vessel diameter after acetazolamide. RESULTS: In the hemisphere ipsilateral to the ICA stenosis, there was no increase in diameter after acetazolamide, whereas a significant increase was measured in the contralateral hemisphere for the A1 and A2 segments of the ACA, the pericallosal artery, and the BA. A significant diameter increase was measured in all except 1 vessel of the controls. The vasodilatory capacity was significantly lower ipsilateral to the ICA stenosis compared with the A1 segment of the ACA and the P2 segment of the PCA in the controls. CONCLUSIONS: MRA combined with an acetazolamide provocation challenge can measure normal and impaired vasodilatory capacity of the cerebral vasculature.

Interrelation between the degree of carotid stenosis, collateral circulation and cerebral perfusion.

BACKGROUND: In patients with carotid artery stenosis, ipsilateral hemodynamic compromise is associated with an increased risk of stroke. It is unclear which factors determine cerebral perfusion. We studied the effect of both the degree of the stenosis and the collateral circulation via the circle of Willis (CoW) on cerebral perfusion in patients with symptomatic carotid artery stenosis. METHODS: In 88 patients with unilateral symptomatic carotid artery stenosis of > or =50%, CT perfusion was used to measure the relative cerebral blood volume (rCBV), the difference in mean transit time (DeltaMTT) and the relative cerebral blood flow (rCBF). CT angiography was used to measure the degree of carotid stenosis and to assess the configuration of the CoW. Differences in mean rCBF, rCBV and DeltaMTT between patients with a carotid stenosis of < or =69, 70-79, 80-89 and 90-99%, and between patients with a complete and those with an incomplete CoW were determined by analysis of covariance. RESULTS: The ipsilateral rCBF showed a gradual decrease with increasing severity of carotid stenosis (1.09 +/- 0.06, 0.93 +/- 0.06, 0.90 +/- 0.04 and 0.83 +/- 0.04 ml/100 g/min, respectively; p = 0.005), and the DeltaMTT showed a gradual increase (-0.02 +/- 0.33, 0.16 +/- 0.34, 1.08 +/- 0.22 and 1.47 +/- 0.20 s, respectively; p < 0.001). The rCBV was not related to the severity of stenosis. No relation was found between the configuration of the CoW and the cerebral perfusion parameters. CONCLUSIONS: Cerebral perfusion is inversely related to the degree of stenosis in patients with symptomatic carotid artery stenosis. A relation between the configuration of the CoW and cerebral perfusion was not detected, suggesting that other collateral pathways play an important role.

Magnesium and headache after aneurysmal subarachnoid haemorrhage.

BACKGROUND: In patients with aneurysmal subarachnoid haemorrhage (SAH), headache typically is severe and often requires treatment with opioids. Magnesium has analgesic effects in several conditions, but whether it reduces headache after SAH is unknown. METHODS: In a cohort of 108 SAH patients included in the randomised controlled trial Magnesium in Aneurysmal Subarachnoid Haemorrhage-II (MASH-II), severity of headache was regularly assessed on an 11-point scale until day 10 after SAH. Headache was treated according to a standardised protocol with acetaminophen, codeine, tramadol or piritramide. Serum magnesium levels were assessed every other day. Differences in mean headache scores between patients with mean high (>1.0 mmol/l) and normal (< or =1.0 mmol/l) magnesium levels were analysed with a Student t test. Crude and adjusted ORs for the use of codeine, tramadol and piritramide for patients with high versus normal magnesium levels were calculated with logistic regression. RESULTS: The 61 patients with high magnesium levels had lower mean headache scores (4.1) than the 47 patients with normal magnesium levels (4.9; mean difference, 0.8; 95% CI 0.1 to 1.6) and required less tramadol (adjusted OR, 0.3; 95% CI 0.1 to 0.7) or piritramide (adjusted OR 0.2; 95% CI 0.1 to 0.5). There were no differences in the use of acetaminophen or codeine. CONCLUSION: In SAH patients, elevated serum magnesium levels are associated with slightly less severe headache and less frequent use of opioids. These data imply that intravenous magnesium therapy, besides a supposed beneficial effect on outcome, also provides pain relief for SAH patients, for whom it might also improve functional outcome.

Noninvasive MR imaging of cerebral perfusion in patients with a carotid artery stenosis.

BACKGROUND: Arterial spin labeling (ASL) perfusion MRI with image acquisition at multiple delay times can be used to measure delays in the arrival of arterial blood to the brain. We assessed the effect of a symptomatic internal carotid artery (ICA) stenosis on ASL timing parameters, and evaluated the effect of collateral flow through the circle of Willis. METHODS: Forty-four functionally independent patients (30 men, 69 +/- 9 years) with a recently symptomatic ICA stenosis > or =50% and 34 sex-matched and age-matched healthy volunteers were investigated. Magnetic resonance angiography and 2-dimensional phase-contrast imaging were used to assess collateral flow in the circle of Willis. RESULTS: In the hemisphere ipsilateral to the ICA stenosis, cerebral blood flow (CBF) was lower (p < 0.01) in the anterior frontal, posterior frontal, parieto-occipital, and occipital regions than in control subjects. The transit times were prolonged (p < 0.01) in the ipsilateral anterior frontal, posterior frontal, and frontoparietal regions when compared with the control subjects. The trailing edge time was prolonged (p < 0.01) in the ipsilateral frontoparietal region when compared to the control subjects. In the 27 patients without a contralateral stenosis, the trailing edge was longer (p < 0.01) in the ipsilateral posterior frontal, frontoparietal, and parieto-occipital regions than in the contralateral regions. Collateral flow via the circle of Willis did not affect CBF and transit or trailing edge times. CONCLUSION: Arterial spin labeling MRI is a noninvasive tool for imaging cerebral blood flow and delays in the arrival of arterial blood to the brain, and can potentially provide valuable information on the quality of perfusion to the brain in patients with cerebrovascular disease.

C-reactive protein in the very early phase of acute ischemic stroke: association with poor outcome and death.

Acute ischemic stroke may trigger an inflammatory response that leads to increased levels of C-reactive protein (CRP). High levels of CRP may be associated with poor outcome because they reflect either an inflammatory reaction or tissue damage. We evaluated the prognostic value of CRP within 12 h of onset of ischemic stroke. Levels of CRP were routinely obtained within 12 h of symptom onset in 561 patients with ischemic stroke. CRP values were dichotomized as <7 or ≥7 mg/L. The full range of CRP values was used to detect a possible level-risk relationship. We studied the relation between CRP values and poor outcome (modified Rankin Scale score >2) or death at 3 months. A multiple logistic regression model was applied to adjust for age, sex, NIHSS score, current cigarette smoking, diabetes mellitus, hypertension, statin use, and stroke subtype. After adjustment for potential confounders, patients with CRP levels ≥7 mg/L had a significantly increased risk of poor outcome (adjusted OR 1.6, 95% CI 1.1­2.4) or death (adjusted OR 1.7, 95% CI 1.0­2.9) at 3 months. In addition, the risk of poor outcome or death at 3 months increased with higher levels of CRP. CRP within 12 h of ischemic stroke is an independent prognostic factor of poor outcome at 3 months.