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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Accuracy and inter-observer variation in the classification of dysarthria from speech recordings.

BACKGROUND: Dysarthria may be classified as flaccid, spastic, ataxic, hypokinetic, choreatic, dystonic, or mixed. We hypothesized that in routine neurological practice the reliability and accuracy of perceptual analysis alone in the classification of dysarthria is low and that this classification is mainly based on the clinical context rather than on the perception of speech. We therefore studied the accuracy and the inter- observer agreement in the classification of dysarthrias on the basis of perceptual analysis alone. METHODS: Seventy two neurologists and neurological trainees classified recorded speech samples of 100 patients as flaccid, spastic, ataxic, extrapyramidal, or mixed dysarthria, or as not dysarthric. All observers were blinded to the patients' final diagnosis, which was based on all clinical features and investigations. In the analysis the observers were arranged in eight groups of nine observers, or four paired groups with similar levels of clinical experience. Together, the observers in a given group rated all 100 recordings. RESULTS: The accuracy of the classification was poor (35 % were classified correctly) and the inter-observer agreement between paired groups low (kappa 0.16 to 0.32). The level of experience in neurology did not have a significant influence. CONCLUSION: Neurological trainees as well as experienced neurologists have great difficulty in identifying specific types of dysarthria on the basis of perceptual analysis alone. In clinical practice this probably means that most neurologists will classify dysarthria in the context of other features from neurological examination or ancillary investigations.

Hyperglycemia and cognitive outcome after ischemic stroke.

BACKGROUND: Post-stroke hyperglycemia (HG) is associated with poor physical recovery, in particular in patients with cortical stroke. We tested whether HG is also associated with cognitive impairment after ischemic stroke. METHODS: We recruited patients from a prospective consecutive cohort with a first-ever supratentorial infarct. Neuropsychological examination included abstract reasoning, verbal memory, visual memory, visual perception and construction, language, and executive functioning. We related HG (glucose >7.0 mmol/L) to cognition and functional outcome (modified Barthel Index) at baseline and after 6-10 months, and to neurological deficit (National Institutes of Health Stroke Scale) and infarct size at baseline. In additional analyses cortical and subcortical infarcts were considered separately. RESULTS: Of 113 patients, 43 had HG (38%) and 55 had cortical infarcts (49%). Follow-up was obtained from 76 patients (68%). In the acute phase, in patients with cortical infarcts HG was associated with impaired executive function (B=-0.65; 95% confidence limits (CL): -1.3-0.00; p<0.05), larger lesion size (p<0.01), and more severe neurological deficits (p<0.01). These associations were not observed in patients with subcortical infarcts and the association between HG and cognitive functioning at follow-up was not significant in either group. CONCLUSIONS: In first-ever ischemic stroke, HG was not associated with impaired cognition after 6-10 months. In the acute phase of stroke HG was associated with impaired executive function, but only in patients with cortical infarcts.

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.

Appreciation of the informed consent procedure in a randomised trial of decompressive surgery for space occupying hemispheric infarction.

BACKGROUND AND AIM: As non-randomised studies have suggested that surgical decompression may reduce mortality in patients with space occupying hemispheric infarction, randomisation may be considered unethical in controlled trials testing this treatment strategy. We studied differences in recall of information and in appreciation of the informed consent procedure between representatives included in the Hemicraniectomy After Middle cerebral artery infarction with Life-threatening Edema Trial (HAMLET) and representatives of patients participating in the randomised trial of Paracetamol (Acetaminophen) In Stroke (PAIS). METHODS: 1 year after study inclusion, we contacted 30 consecutive representatives who had given informed consent for participation of their relative in HAMLET, and 30 for PAIS. Recall of trial details and appreciation of the informed consent procedure were investigated using standardised questionnaires and compared between the two groups. RESULTS: All 30 PAIS representatives and 28 HAMLET representatives were interviewed. Participation of their relative in a clinical trial was remembered by 86% of HAMLET and 40% of PAIS representatives (p<0.001). HAMLET representatives remembered more trial details (effect of the treatment under study (61% vs 3%, p<0.001); randomised treatment allocation (71% vs 0%, p<0.001)). With respect to appreciation of the informed consent procedure, we found no differences between the groups: in each trial, four representatives (14% vs 13%) had considered the question of randomisation unacceptable. CONCLUSIONS: Participation of patients in a randomised controlled trial of surgical decompression for space occupying infarction is generally considered acceptable by their representatives, and recall of trial details is better than in a trial in which less vital issues are at stake.

Familial occurrence of brain arteriovenous malformations: a systematic review.

BACKGROUND: Brain arteriovenous malformations (BAVMs) are thought to be sporadic developmental vascular lesions, but familial occurrence has been described. We compared the characteristics of patients with familial BAVMs with those of patients with sporadic BAVMs. METHODS: We systematically reviewed the literature on patients with familial BAVMs. Three families that were found in our centre were added. Age, sex distribution and clinical presentation of the identified patients were compared with those in population based series of patients with sporadic BAVMs. Furthermore, we calculated the difference in mean age at diagnosis of parents and children to study possible anticipation. RESULTS: We identified 53 patients in 25 families with BAVMs. Mean age at diagnosis of patients with familial BAVMs was 27 years (range 9 months to 58 years), which was younger than in the reference population (difference between means 8 years, 95% CI 3 to 13 years). Patients with familial BAVMs did not differ from the reference populations with respect to sex or mode of presentation. In families with BAVMs in successive generations, the age of the child at diagnosis was younger than the age of the parent (difference between means 22 years, 95% CI 13 to 30 years), which suggests clinical anticipation. CONCLUSIONS: Few patients with familial BAVMs have been described. These patients were diagnosed at a younger age than sporadic BAVMs whereas their mode of presentation was similar. Although there are indications of anticipation, it remains as yet unclear whether the described families represent accidental aggregation or indicate true familial occurrence of BAVMs.

Neuropsychological and neuroanatomical correlates of perseverative responses in subacute stroke.

Patients with left-sided neglect frequently show repetitive behaviour on the ipsilesional side, such as re-markings on cancellation tasks or extensive elaboration on drawings. It is unclear whether these perseverative responses occur as a symptom of hemi-neglect or inattention in general, and/or whether they are related to anatomical brain correlates such as lesion location, lesion side or volume. In a first study, we examined the prevalence and neuropsychological correlates of perseverative responses in 206 subacute stroke patients and 63 healthy controls. Perseverative responses were considered present when there was at least one re-marking on the Star Cancellation, and both the degree and spatial distribution of re-markings were examined. A distinction was made between hemi-neglect and non-lateralized inattention. Spatial and verbal working memory were assessed with the Corsi Block Span and the Digit Span. Verbal and non-verbal executive function was assessed with the Visual Elevator and Letter Fluency. Stroke patients without inattention demonstrated re-markings that were related to executive performance, and the degree of perseveration was equally distributed across the sheet. Hemi-neglect patients but not patients with generalized inattention demonstrated more re-markings than controls, suggesting that a lateralized spatial attention bias triggers the perseverative responses. Patients with left and right hemi-neglect showed the same prevalence of perseveration, but the distribution of re-markings was more lateralized towards the ipsilesional side in patients with right-hemispheric stroke. The degree of perseveration in patients with hemi-neglect was related to the severity of the neglect. The goal of the second study on a subset of patients (n = 127) was to determine the neuroanatomical correlates of perseverative responses in the early phase of stroke. Lesion anatomy was administered by indicating involvement of frontal, parietal, temporal, occipital lobe, caudate nucleus, lenticular nucleus and/or thalamus. Lesion volume was calculated using a manual tracing technique. Lesion analyses indicated that perseverative behaviour is strongly associated with lesions involving the caudate nucleus or the lenticular nucleus, independent of lesion volume. The caudate nucleus was an important correlate of perseveration independent of the presence of hemi-neglect. No association was found between lesion side and perseverative responses, in contrast to previous studies. In conclusion, a stroke involving the basal ganglia and the presence of (left- or right-sided) hemi-neglect are two important associates of perseverative responses in the subacute phase of stroke.

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.