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Background Type 2 diabetes is a condition associated with a state of low-grade inflammation caused by adipose tissue dysfunction and insulin resistance. High sensitive-CRP (hs-CRP) is a marker for systemic low-grade inflammation and higher plasma levels have been associated with cardiovascular events in various populations. The aim of the current study is to evaluate the relation between hs-CRP and incident cardiovascular events and all-cause mortality in high-risk type 2 diabetes patients. Methods Prospective cohort study of 1679 type 2 diabetes patients included in the Second Manifestations of ARTerial disease (SMART). Cox proportional hazard models were used to evaluate the risk of hs-CRP on cardiovascular events (composite of myocardial infarction, stroke and vascular mortality) and all-cause mortality. Hs-CRP was log-transformed for continuous analyses. Findings were adjusted for age, sex, BMI, current smoking and alcohol use, non-HDL-cholesterol and micro-albuminuria. Results 307 new cardiovascular events and 343 deaths occurred during a median follow-up of 7.8 years (IQR 4.2–11.1). A one unit increase in log(hs-CRP) was related to an increased vascular- and all-cause mortality risk (HR 1.21, 95% CI 1.01–1.46 and HR 1.26, 95% CI 1.10–1.45 respectively). No relation was found between log(hs-CRP) and myocardial infarction or stroke. The relations were similar in patients with and without previous vascular disease. Conclusion Low grade inflammation, as measured by hs-CRP, is an independent risk factor for vascular- and all-cause mortality but not for cardiovascular events in high-risk type 2 diabetes patients. Chronic low-grade inflammation may be a treatment target to lower residual cardiovascular risk in type 2 diabetes patients.

Aims To determine the (cost)-effectiveness of blood pressure lowering, lipid-lowering, and antithrombotic therapy guided by predicted lifetime benefit compared to risk factor levels in patients with symptomatic atherosclerotic disease. Methods and results For all patients with symptomatic atherosclerotic disease in the UCC-SMART cohort (1996–2018; n = 7697) two treatment strategies were compared. The lifetime benefit-guided strategy was based on individual estimation of gain in cardiovascular disease (CVD)-free life with the SMART-REACH model. In the risk factor-based strategy, all patients were treated the following: low-density lipoprotein cholesterol (LDL-c) Conclusion Residual risk reduction guided by lifetime benefit estimation results in more CVD-free life years and more CVD events avoided compared to the conventional risk factor-based strategy. Lifetime benefit-based treatment is an effective and potentially cost-effective strategy for reducing residual CVD risk in patients with clinical manifest vascular disease.

Background Cardiovascular disease (CVD) and cancer share many common risk factors; patients with CVD also may be at risk of developing cancer. Objectives The aim of this study was to derive and externally validate prediction models for the estimation of lifetime and 10-year risk for total, colorectal, and lung cancer in patients with established CVD. Methods Data from patients with established CVD from the UCC-SMART cohort (N = 7,280) were used for model development, and from the CANTOS trial (N = 9,322) for model validation. Predictors were selected based on previously published cancer risk scores, clinical availability, and presence in the derivation dataset. Fine and Gray competing risk-adjusted lifetime models were developed for the outcomes total, colorectal, and lung cancer. Results Selected predictors were age, sex, smoking, weight, height, alcohol use, antiplatelet use, diabetes, and C-reactive protein. External calibration for the 4-year risk of lung, colorectal, and total cancer was reasonable in our models, as was discrimination with C-statistics of 0.74, 0.64, and 0.63, respectively. Median predicted lifetime and 10-year risks in CANTOS were 26% (range 1% to 52%) and 13% (range 1% to 31%) for total cancer; 4% (range 0% to 13%) and 2% (range 0% to 6%) for colorectal cancer; and 5% (range 0% to 37%) and 2% (range 0% to 24%) for lung cancer. Conclusions Lifetime and 10-year risk of total, colorectal, and lung cancer can be estimated reasonably well in patients with established CVD with readily available clinical predictors. With additional study, these tools could be used in clinical practice to further aid in the emphasis of healthy lifestyle changes and to guide thresholds for targeted diagnostics and screening., Central Illustration

Introduction The Meta VCI Map consortium performs meta-analyses on strategic lesion locations for vascular cognitive impairment using lesion-symptom mapping. Integration of data from different cohorts will increase sample sizes, to improve brain lesion coverage and support comprehensive lesion-symptom mapping studies. Methods Cohorts with available imaging on white matter hyperintensities or infarcts and cognitive testing were invited. We performed a pilot study to test the feasibility of multicenter data processing and analysis and determine the benefits to lesion coverage. Results Forty-seven groups have joined Meta VCI Map (stroke n = 7800 patients; memory clinic n = 4900; population-based n = 14,400). The pilot study (six ischemic stroke cohorts, n = 878) demonstrated feasibility of multicenter data integration (computed tomography/magnetic resonance imaging) and achieved marked improvement of lesion coverage. Discussion Meta VCI Map will provide new insights into the relevance of vascular lesion location for cognitive dysfunction. After the successful pilot study, further projects are being prepared. Other investigators are welcome to join., Highlights • Lesion location is an important determinant of cognitive impact of vascular damage. • Previous lesion-symptom mapping studies had limited brain lesion coverage. • Meta VCI Map provides a platform for multicenter lesion-symptom mapping research. • The pilot study shows that multicenter data integration is feasible and improves coverage. • Multicenter studies enable comprehensive assessment of strategic lesion locations.

Objective: To investigate sex differences in presence and location of atherosclerosis in a large population of acute ischaemic stroke patients. Methods: Participants were included from the Dutch acute stroke study (DUST), a large prospective multicentre cohort study. All patients received CT/CT-angiography within 9 hours of stroke onset. We assessed the presence of any sign of atherosclerosis in the intra- and extracranial circulation. In addition, we determined the burden of intracranial atherosclerosis by quantifying intracranial internal carotid artery (ICA) calcifications, resulting in calcium volumes. Relative risks between women and men were calculated using multivariable Poisson regression, and adjusted (aRR) for potential confounders (age, hypertension, hyperlipidemia, diabetes, smoking and alcohol use). Results: We included 1397 patients with a mean age of 67 years, of whom 600 (43%) were women. Presence of atherosclerosis in intracranial vessel segments was found as frequently in women as in men (71% versus 72%, aRR 0.95; 95%CI 0.89-1.01). In addition, intracranial ICA calcium volume did not differ between women and men (median volume 124 mm 3 , IQR 35.5-304.5 in women versus 112 mm 3 , IQR 33.0-276.5 in men; tertile largest volume 37% in women versus 33% in men, aRR 1.00; 95% CI 0.95-1.05). Extracranial atherosclerosis was less common in women compared with men (74% vs 81%, aRR 0.86; 95%CI 0.81-0.92). (Table) Conclusions: In patients with acute ischemic stroke the prevalence of intracranial atherosclerosis does not differ between women and men, while extracranial atherosclerosis is less often present in women compared with men.

Stroke is a leading cause of serious long-term disability in adults and is the second leading cause of death worldwide. Early reperfusion and neuroprotection techniques have been the focus of much effort with the aim of very acute treatment of the stroke. Targeting different mechanisms, pharmacological therapies have the potential to reduce disability in a large fraction of patients who survive the acute stroke. The brain's capacity to reorganize after stroke through plasticity mechanisms can be modulated by pharmacological agents. A number of therapeutic interventions are under study, including small molecules, growth factors, and monoclonal antibodies. Recently it has been shown that the SSRI fluoxetine improved motor deficit in patients with ischaemic stroke and hemiplegia which appeared to be independent of the presence of depression. In this context, it is of major importance to support innovative research in order to promote the emergence of new pharmacological treatments targeting neurological recovery after stroke, as opposed to acute de-occlusion and neuroprotection. This paper is the work of a group of 14 scientists with aim of (1) addressing key areas of the basic and clinical aspects of human brain plasticity after stroke and potential pharmacological targets for recovery, (2) asking questions about the most appropriate characteristics of clinical trials testing drugs in post stroke recovery and (3) proposing recommendations for future clinical trials. © 2013 Springer-Verlag Berlin Heidelberg.

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 β 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.

Summary The plasma concentration of adiponectin, an adipokine that has anti-inflammatory, anti-atherogenic and insulin sensitizing properties, is lower in obese subjects and could therefore be a target for therapy. In order to review and meta-analyse prospective cohort studies investigating adiponectin concentration and the risk for incident coronary heart disease (CHD) or stroke, a systematic search of MEDLINE, EMBASE and Cochrane databases was performed. Two independent reviewers selected prospective cohort studies investigating the relationship between adiponectin level and incident CHD or stroke using ‘adiponectin’ and ‘cardiovascular disease’ or ‘stroke’ and their synonyms, excluding patients with clinically manifest vascular disease. Random-effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (95% CI). Generalized least squares regression was used to assess dose–response relationships for adiponectin concentrations from studies that provided RRs solely based upon categorical data regression. In total, 16 prospective cohort studies, comprising 23,919 patients and 6,870 CHD or stroke outcome events, were included in the meta-analyses. An increase of 1 standard deviation in log-transformed adiponectin did not lower the risk for CHD (RR 0.97; 95% CI 0.86–1.09). A 10 μg mL–1 increase in adiponectin conferred a RR of 0.91 (95% CI 0.80–1.03) for CHD and a RR 1.01 (95% CI 0.97–1.06) for stroke. In conclusion, plasma adiponectin is not related to the risk for incident CHD or stroke.

Background: Cerebral hyperperfusion syndrome (CHS) after carotid endarterectomy (CEA) is a potential life-threatening complication. Therefore, early identification and treatment of patients at risk is essential. CHS can be predicted by a doubling of postoperative transcranial Doppler (TCD)-derived mean middle cerebral artery blood velocity (Vmean) compared to preoperative values. However, in approximately 15% of CEA patients, an adequate TCD signal cannot be obtained due to an insufficient temporal bone window. Moreover, the use of TCD requires specifically skilled personnel. An alternative and promising technique of noninvasive cerebral monitoring is relative frontal lobe oxygenation (rSO2) measured by near-infrared spectroscopy (NIRS), which offers on-line information about cerebral oxygenation without the need for specialized personnel. In this study, we assess whether NIRS and perioperative TCD are related to the onset CHS following CEA. Methods: Patients who underwent CEA under general anesthesia and had a sufficient TCD window were prospectively included. The Vmean and rSO2 measured before induction of anesthesia were compared to measurements performed in the first postoperative hour (ΔVmean, ΔrSO2, respectively). Logistic regression analysis was performed to determine the relationship between ΔV and ΔrSO2 and the occurrence of CHS. Subsequently, receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff values. Diagnostic values were shown as positive and negative predictive values (PPV and NPV). Results: In total, 151 patients were included, of which 7 patients developed CHS. The ΔVmean and ΔrSO2 differed between CHS and non-CHS patients (median, interquartile range), i.e. 74% (67–103) versus 16% (–2 to 41), p = 0.001, and 7% (4–15) versus 1% (–6 to 7), p = 0.009, respectively. The mean arterial blood pressure did not change. Postoperative ΔVmean and ΔrSO2 were significantly related to the occurrence of CHS [odds ratio (OR) 1.40 (95% CI 1.02–1.93) per 30% increase in Vmean and OR 1.82 (95% CI 1.11–2.99) per 5% increase in rSO2]. ROC curve analysis showed an area under the curve of 0.88 (p = 0.001) for ΔVmean and an optimal cutoff value of 67% increase (PPV 38% and NPV 99%), and an area under the curve of 0.79 (p = 0.009) for ΔrSO2 and an optimal cutoff value of 3% rSO2 increase (PPV 11% and NPV 100%). The combination of both monitoring techniques provided a PPV of 58% and an NPV of 99%. Conclusions: Both TCD and NIRS measurements can be used to safely identify patients not at risk of developing CHS. It appears that NIRS is a good alternative when a TCD signal cannot be obtained.

Background: Assessment of outcome after childhood stroke is important both for clinical practice and for research purposes. The objective of this study was to compare two frequently used outcome measures. Methods: In 40 children with arterial ischemic stroke (AIS), dichotomized outcome obtained from the Pediatric Stroke Outcome Measure (PSOM) was compared with a dichotomized modified Rankin Scale (mRS) combined with information on type of school attendance. In addition, we compared dichotomized outcome, obtained from the PSOM and the mRS combined with school attendance, with the results of pediatric quality of life (PedsQL) questionnaires and the impressions of the child’s general functioning on a visual analogue scale (VAS) that was filled out by parents and investigators. Results: In 35 children (88%), outcome classification was concordant between the two outcome measures. Five children had a poor outcome according to the PSOM and good outcome with the mRS including school performance. In these patients, mRS outcome classification agreed better with the impression of the investigators, as reflected by VAS scores ≧7.5. For both the PSOM and mRS in combination with school performance, patients with a good outcome had significantly higher PedsQL and VAS scores than those with a poor outcome (p values Conclusions: In children with AIS, both PSOM and mRS combined with school type correlated significantly with quality of life and VAS scores of general functioning. The mRS combined with school type is easier to obtain than the PSOM, reflects function rather than deficits, includes an important measure of cognitive outcome, and corresponds better with the doctor’s impression of outcome.

Near occlusion (NO) of the internal carotid artery (ICA) with full collapse (NOFC) is a rare condition, with a prevalence of around 1%. Guidelines on carotid stenosis recommend a conservative treatment in patients with a single-event ipsilateral to a NOFC, but the optimal treatment for patients with recurrent symptoms associated with NOFC remains uncertain. We describe a consecutive series of patients with recurrent symptoms associated with NOFC (RSNOFC) who underwent carotid endarterectomy (CEA).From 2008 to 2017, 17 consecutive patients with RSNOFC were treated according to our standardized multidisciplinary work-up and protocol and included for this single-center cohort study. NO was defined according to the angiographic North American Symptomatic Carotid Endarterectomy Trial criteria. Only patients with NOFC were included in this study.Standard longitudinal CEA was performed in 15 patients, whereas in 2 patients the ICA was ligated with concomitant endarterectomy of the ECA. Within 30 postoperative days, one patient died from a hemorrhagic infarction. During follow-up (median 23 months) one patient died of unknown cause 90 days after CEA. No TIA, stroke, myocardial infarction or re-stenosis occurred in the remaining patients.In patients with RSNOFC, CEA may be considered a potential treatment option. Although procedural risks in this small subgroup may be higher as compared to patients with low-to-moderate risk anatomy, this risk may outbalance the natural course.

Background: In patients with acute ischaemic stroke and hyperglycaemia, prolonged strict glycaemic control may improve clinical outcome. The question is how to achieve this prolonged strict glycaemic control. In this study, the efficacy and safety of two regimens with different basal to meal related insulin ratio are described. Methods: 33 patients with ischaemic stroke and hyperglycaemia at admission were randomised in an open design to receive: (1) conventional glucose lowering therapy, (2) strict glucose control with predominantly basal insulin using intravenous insulin or (3) strict glucose control with predominantly meal related insulin using subcutaneous insulin in the first 5 days after stroke. The target range of glucose control for the last two groups was 4.4-6.1 mmol/l. 16 consecutive patients without hyperglycaemia at admission were included to serve as normoglycaemic controls. Results: The median area under the curve (AUC) in the meal related insulin group was 386 mmol/l x 58 h (range 286-662) for days 2-5, and did not differ from the hyperglycaemic control group (median AUC 444 mmol/l x 58 h; range 388-620). There was also no difference in median AUC of the basal insulin group (453 mmol/l x 58 h, range 347-629) and the hyperglycaemic control group on days 2-5. In the first 12 hours, glucose profiles were lower in the groups treated with strict glucose control; median AUC was 90 mmol/l x 12 h (range 77-189) for the hyperglycaemic control group versus 81 mmol/l x 12 h (range 60-118) for the meal related insulin group (p = 0.03) and 74 mmol/l x 12 h (range 52-97) for the basal insulin group (p = 0.008). Conclusion: In intermittently fed ischaemic stroke patients, strict glycaemic control between day 2 and day 5 with two different basal bolus regimens did not result in lower glucose profiles due to postprandial hyperglycaemia. Continuous enteral feeding may therefore be needed to achieve prolonged strict glycaemic control in acute stroke patients

Although hundreds of genetic association studies of ischaemic stroke have been published, the failure to replicate associations has led to scepticism about their findings. Possible explanations for this failure are: (1) a false-positive association in the initial study; (2) a false-negative association in a replication study; (3) methodological differences (e.g. study populations or study designs). We review underlying causes for replication failure, such as small sample size, multiple testing and publication bias, and methods to deal with these problems. We also make suggestions about the design of genetic association studies in ischaemic stroke with regard to stroke subtype classification, candidate pathways, subgroups, intermediate phenotypes and potential clinical impact.

Background and aim: Published data suggest that patients with cerebral ischaemia and atrial fibrillation (CIAF) have higher inhospital mortality than patients with cerebral ischaemia of arterial origin (CIAO). Data on long term risks are scarce. We compared the long term risks of death and vascular events (VE) between these groups. Methods: We extended the follow-up of 2473 patients from the Dutch TIA Trial (recruitment March 1986 to March 1989, all treated with aspirin; CIAO) and 186 Dutch participants of the European Atrial Fibrillation Trial (recruitment June 1988 to May 1992, 26% on anticoagulants during the trial; CIAF). Hazard ratios (HRs) for death and VE of CIAF versus CIAO were analysed by means of Cox regression analysis and adjusted for age, sex and several cardiovascular risk factors. Results: After a mean follow-up of 10.1 years, 1484 patients with CIAO had died and 1336 had suffered at least one VE (377 cardiac, 455 stroke). Mean follow-up of the CIAF patients was 6.8 years; 150 patients had died and 136 had suffered at least one VE (41 cardiac, 63 stroke). Adjusted HRs (CIAF vs CIAO) were 1.46 (95% CI 1.22 to 1.74) for death, 1.49 (1.24 to 1.79) for first VE, 1.94 (1.47 to 2.55) for first stroke and 1.41 (1.01 to 1.96) for first cardiac event. These HRs were essentially the same as those for the duration of the trials. Conclusion: Our study shows that the long term risk of death or vascular events is 1.5 times higher in patients with CIAF than in those with CIAO, after adjustment for differences between the groups.

Background and Aim: The prediction of prognosis after cerebral infarction might be improved by genetic information. The aim of the Prognostic Modelling in Ischaemic Stroke study is to develop 2 different prognostic models on the basis of traditional vascular risk factors and genetic information in patients who have suffered from cerebral ischaemia of arterial origin, 1 concerning new ischaemic and the other new haemorrhagic events. Methods: Polymorphisms and haplotypes describing the haemostatic system and those that influence antithrombotic drug activity will be identified in a cohort of 1,200 patients with cerebral ischaemia of arterial origin who will be followed up for a mean of 6.5 years. In total, 312 ischaemic and 78 haemorrhagic events are anticipated. With a prevalence of a genetic characteristic of 10% a relative risk of 1.4 (95% confidence interval = 1.1–1.8) for ischaemic events and of 1.8 (95% confidence interval = 1.0–3.2) for haemorrhagic events can be estimated with sufficient precision. To determine the additional prognostic value of genetic characteristics the area under the ROC curves of 2 separate models will be compared: 1 based on non-genetic risk factors only, the other also including genetic data.

Background and Purpose: A reliable scoring method for ischemic cerebral white matter hyperintensities (WMH) will help to clarify the causes and consequences of these brain lesions. We compared an automated and two visual WMH scoring methods in their relations with age and cognitive function. Methods: MRI of the brain was performed on 154 participants of the Utrecht Diabetic Encephalopathy Study. WMH volumes were obtained with an automated segmentation method. Visual rating of deep and periventricular WMH (DWMH and PWMH) was performed with the Scheltens scale and the Rotterdam Scan Study (RSS) scale, respectively. Cognition was assessed with a battery of 11 tests. Results: Within the whole study group, the association with age was most evident for the automated measured WMH volume (β = 0.43, 95% CI = 0.29–0.57). With regard to cognition, automated measured WMH volume and Scheltens DWMH were significantly associated with information processing speed (β = –0.22, 95% CI = –0.40 to –0.06; β = –0.26, 95% CI = –0.42 to –0.10), whereas RSS PWMH were associated with attention and executive function (β = –0.19, 95% CI = –0.36 to –0.02). Conclusion: Measurements of WMH with an automated quantitative segmentation method are comparable with visual rating scales and highly suitable for use in future studies to assess the relationship between WMH and subtle impairments in cognitive function.

Background: Brain arteriovenous malformations (BAVMs) are thought to be sporadic developmental vascular lesions, but familial occurrence has been described. We compared 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-58 years), which was younger than in the reference population (difference between means 8 years, 95% confidence interval (CI) 3-13 years). Patients with familial BAVMs did not differ from the reference populations with respect to sex and 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 13-30 years), which suggests clinical anticipation. Conclusions: Few patients with familial BAVMs have been described. These patients were diagnosed at 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.

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

Item does not contain fulltext BACKGROUND: The presence of prodromal transient ischemic attacks (TIAs) has been associated with a favorable outcome in anterior circulation stroke. We aimed to determine the association between prodromal TIAs or minor stroke and outcomes at 1 month, in the Basilar Artery International Cooperation Study, a registry of patients presenting with an acute symptomatic and radiologically confirmed basilar artery occlusion. METHODS: A total of 619 patients were enrolled in the registry. Information on prodromal TIAs was available for 517 patients and on prodromal stroke for 487 patients. We calculated risk ratios and corresponding 95% confidence intervals (CIs) for poor clinical outcome (modified Rankin Scale score >/=4) according to the variables of interest. RESULTS: Prodromal minor stroke was associated with poor outcome (crude risk ratio [cRR], 1.26; 95% CI, 1.12-1.42), but TIAs were not (cRR, .93; 95% CI, .79-1.09). These associations remained essentially the same after adjustment for confounding variables. CONCLUSIONS: Prodromal minor stroke was associated with an unfavorable outcome in patients with basilar artery occlusion, whereas prodromal TIA was not.

Background: Stroke may have a major effect on survivors and on the healthcare system. Aims: To study the functional status and use of healthcare facilities in long-term survivors of a transient ischaemic attack (TIA) or minor ischaemic stroke (MIS) and evaluate associations with baseline and follow-up characteristics. Methods: Follow-up of patients who had participated in the Dutch TIA Trial or the European Atrial Fibrillation Trial was extended to a mean period of 15.6 years. Patients were interviewed through a postal questionnaire (n = 468) and a sample of this group was also interviewed at home (n = 198). Demographic data, information on comorbidity, functional status (Barthel Index, Frenchay Activities Index and modified Rankin Scale) and use of healthcare facilities were recorded. Results: About one third of the survivors interviewed at home experienced any residual disability and 26% were moderately to severely handicapped. Factors associated with poor functional status were advanced age and the presence of any infarct on a baseline computed tomography scan, the recurrence of a new major stroke or the presence of comorbidity of locomotion. One third of survivors used any kind of professional care, which was predominantly related to the functional status at follow-up. Conclusions: Recurrent stroke and the presence of comorbidity of locomotion are important determinants of long-term disability of survivors of a TIA or an MIS, which, in turn, is strongly associated with the long-term use of professional care. The need for measuring comorbidity with regard to functional status is recommended in research on stroke outcome.

Objective: Transient ischemic attacks are common and important harbingers of subsequent stroke. Management varies widely, and most published guidelines have not been updated in several years. We sought to create comprehensive, unbiased, evidence-based guidelines for the management of patients with transient ischemic attacks. Methods: Fifteen expert panelists were selected based on objective criteria, using publication metrics that predicted nomination by practitioners in the field. Prior published guidelines were identified through systematic review, and recommendations derived from them were rated independently for quality by the experts. Highest quality recommendations were selected and subsequently edited by the panelists using a modified Delphi approach with multiple iterations of questionnaires to reach consensus on new changes. Experts were provided systematic reviews of recent clinical studies and were asked to justify wording changes based on new evidence and to rate the final recommendations based on level of evidence and quality. No expert was allowed to contribute to recommendations on a topic for which there could be any perception of a conflict of interest. Results: Of 257 guidelines documents identified by systematic review, 13 documents containing 137 recommendations met all entry criteria. Six iterations of questionnaires were required to reach consensus on wording of 53 final recommendations. Final recommendations covered initial management, evaluation, medical treatment, surgical treatment, and risk factor management. Interpretation: The final recommendations on the care of patients with transient ischemic attacks emphasize the importance of urgent evaluation and treatment. The novel approach used to develop these guidelines is feasible, allows for rapid updating, and may reduce bias.

To examine whether intravenous recombinant tissue plasminogen activator (rt-PA) treatment given in the acute phase of ischaemic stroke has a favourable effect on cognitive and functional outcome at six months post-stroke.The present study included 92 patients with a first-ever symptomatic infarct, of whom 25 (27%) were subjected to rt-PA treatment in the first three hours post-stroke. Multivariate logistic regression analyses adjusted for stroke severity, education, age, and sex were performed to examine whether rt-PA treatment influenced cognitive outcome (assessed with a neuropsychological examination covering 7 cognitive domains), basic ADL independence (modified Barthel Indexor = 19), and instrumental ADL independence (Frenchay Activities Indexor = 15) after six months.The adjusted odds ratio for intact cognition was 1.0 (95% CI 0.2 to 4.3), that for basic ADL outcome 13.5 (95 % CI 1.4 to 129.4) and for instrumental ADL 7.1 (95 % CI 1.2 to 42.2).Our findings suggest that rt-PA treatment is associated with a favourable basic and instrumental ADL outcome, but not with a beneficial cognitive outcome after 6 months.

Objective: To study the association between the epsilon 4 allele of apolipoprotein E (APOE epsilon 4) 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 APOE epsilon 4 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 APOE epsilon 4 allele compared to patients without an APOE epsilon 4 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 APOE epsilon 4 allele and the occurrence of delirium in the acute phase after stroke.

Background and Purpose— There is no conclusive experimental support that decompressive surgery in late stages of space-occupying cerebral infarction will improve outcome. We studied the effects of delayed decompressive surgery on the development of tissue damage, edema formation, and cerebral perfusion with different MRI techniques in a rat model of space-occupying cerebral infarction. Methods— Permanent middle cerebral artery (MCA) occlusion was performed in 6 Fisher 344 rats. Decompressive surgery was performed 17 hours after the occlusion. Each animal was assessed before surgery and 2 and 4 hours after surgery by means, of diffusion-weighted T2-weighted, and flow-sensitive alternating inversion recovery perfusion-weighted MRI. Ischemic damage was also evaluated in hematoxylin-eosin-stained brain sections. Results— Lesion volume as derived from apparent diffusion coefficient (ADC) maps decreased from 522±98 mm 3 before to 405±100 mm 3 ( P =0.016) 4 hours after decompressive surgery, whereas lesion volume from T2 maps increased from 420±66 mm 3 before to 510±92 mm 3 ( P =0.048) 4 hours after decompressive surgery. Midline shift decreased from 1.4±0.1 mm to 0.5±0.2 mm ( P =0.001). Blood flow in the noninfarcted area of the ipsilateral hemisphere improved from 25±9 mL/min/100 g of tissue to 38±9 mL/min/100 g of tissue ( P =0.035). Despite the pseudonormalization of ADC, irreversible damage was found in the entire MCA territory on histological evaluation. Conclusions— In rats with space-occupying cerebral infarction, delayed decompressive surgery leads to a decrease in lesion volume derived from ADC maps, which is probably because of an increase of extracellular water formation. There are no signs that this reflects rescue of ischemic tissue.

Vascular disease probably plays an important role in the pathogenesis of cerebral complications that are associated with diabetes mellitus. Previous studies showed that treatment with the angiotensin converting enzyme-inhibitor enalapril (24 mg/kg) prevented neurophysiological and cognitive deficits in streptozotocin diabetic rats, and improved cerebral blood flow, despite a reduction in systemic mean arterial blood pressure. The present study examined if these effects could be sustained with long-term treatment, and if treatment with a lower dose (12 mg/kg) could prevent peripheral and central neurophysiological deficits without causing hypotension. Sciatic nerve conduction velocities were measured every three weeks after diabetes induction, until 24 weeks. Brain stem auditory (BAEP) and visual evoked potentials (VEP) were measured every three weeks from 10 weeks after diabetes induction, until 25 weeks. Nerve conduction velocity was decreased, and BAEP and VEP latencies increased in untreated diabetic rats. At the end of follow-up 12 mg/kg enalapril partially prevented evoked potential abnormalities, but not nerve conduction deficits, whereas 24 mg/kg enalapril largely prevented deficits in nerve conduction velocity (p

Background and Purpose —Body temperature is a strong predictor of outcome in acute stroke. However, it is unknown whether antipyretic treatment leads to early and clinically worthwhile reduction of body temperature in patients with acute stroke, especially when they have no fever. The main purpose of this trial was to study whether early treatment of acute ischemic stroke patients with acetaminophen (paracetamol) reduces body temperature. Methods —Seventy-five patients with acute ischemic stroke confined to the anterior circulation were randomized to treatment with either 500 mg (low dose) or 1000 mg (high dose) acetaminophen or with placebo, administered as suppositories 6 times daily during 5 days. Body temperatures were measured with a rectal electronic thermometer at the start of treatment and after 24 hours and with an infrared tympanic thermometer at 2-hour intervals during the first 24 hours and at 6-hour intervals thereafter. The primary outcome measure was rectal temperature at 24 hours after the start of treatment. Results —Treatment with high-dose acetaminophen resulted in 0.4°C lower body temperatures than placebo treatment at 24 hours (95% CI 0.1°C to 0.7°C). The mean reduction from baseline temperature with high-dose acetaminophen was 0.3°C (95% CI 0°C to 0.6°C) higher than that in placebo-treated patients. Treatment with low-dose acetaminophen did not result in lower body temperatures. After 5 days of treatment, no differences in temperature were found between the placebo and the high- or low-dose acetaminophen groups. Conclusions —Treatment with a daily dose of 6000 mg acetaminophen may result in a small, but potentially beneficial, decrease in body temperature shortly after ischemic stroke, even in normothermic and subfebrile patients. Further studies should determine whether this effect is reproducible and whether early reduction of body temperature leads to improved outcome.

OBJECTIVES—The aetiology of clinical symptoms in patients with severe internal carotid artery (ICA) lesions may be thromboembolic or haemodynamic. The purpose was to assess whether changes in cerebropetal blood flow caused by an ICA occlusion have an effect on clinical symptoms and cerebral metabolism. METHODS—Forty three patients with an ICA occlusion who had hemispheric ischaemia (transient ischaemic attack or stroke), retinal ischaemia, or without symptoms, and 34 patients without significant ICA lesions with either hemispheric ischaemia or no symptoms were studied. Magnetic resonance angiography (MRA) was used to investigate total cerebropetal flow (flow in the ICAs plus basilar artery) and the flow in the middle cerebral arteries. Cerebral metabolic changes in the flow territory of the middle cerebral artery were determined with proton MR spectroscopy. RESULTS—Low total cerebropetal flow (r=−0.15, p

Cardiovascular disease and cancer share important risk factors and pathophysiology, including smoking, obesity, physical inactivity, insulin resistance, and inflammation. As the survival of acute ischemic events has increased notably, the number of patients in the chronic phase of vascular disease

Objective: To assess whether patients with carotid artery occlusion (CAO) who have clinical features suggesting a haemodynamic origin have a poor haemodynamic or metabolic state of the brain. Methods: In 117 patients with ischaemic symptoms of the eye or brain that were transient or at most moderately disabling and associated with a CAO, we compared CO2 reactivity, quantitative flow measurement by magnetic resonance (MR) angiography, metabolic ratios measured by 1H-MR spectroscopy, collateral blood flow patterns and the presence of infarcts of the borderzone type between patients grouped by the following clinical features: (1) presence or absence of at least one of the ‘classical’ haemodynamic symptoms: limb shaking, retinal claudication, precipitation of symptoms by exercise, by rising from a sitting or lying position, by transition from a cold to a warm environment, or by documented hypotension, and (2) symptoms having occurred after demonstration of the CAO or only before the occlusion was documented. Results: Patients with (n = 16) and without (n = 101) one of the ‘classical’ haemodynamic symptoms did not differ in any of the measured indices. Patients with recurrent symptoms after documentation of the CAO (n = 56) had lower CO2 reactivity (difference 8.3%, 95% confidence interval 0.1–16.5) than those with symptoms only before documentation of the occlusion (n = 61), whereas no significant differences were found in any of the other measured indices. The difference in CO2 reactivity was no longer significant after adjustment for the interval between the patients’ last symptoms and the CO2 reactivity measurement. Conclusion: In patients with CAO we could not find an association between symptoms that have been associated with hypoperfusion and a poor haemodynamic or metabolic state of the brain.

The aim of this study was to evaluate the differences in cerebral perfusion seen on mean transit time (MTT) and cerebral blood volume (CBV) maps and to assess the subsequent prognostic value of the MTT–DWI (diffusion-weighted MRI) and CBV–DWI mismatch in the first three days of stroke on lesion enlargement and clinical outcome. In 38 patients, imaged 1–46 h after onset of symptoms, lesion volumes on proton-density (PD)-weighted MRI, DWI and PWI (both MTT and CBV maps) were compared with lesion volumes on follow-up PD-weighted scans, and to clinical outcome (National Institutes of Health Stroke Scale, Barthel index, and Rankin scale). The MTT-CBV, MTT–DWI and CBV–DWI mismatches were compared with change in lesion volume between initial and follow-up PD-weighted scans. Lesion volume on both DWI and PWI correlated significantly with clinical outcome parameters (p < 0.001) with strongest correlation for lesion volume on CBV. Perfusion–diffusion mismatches were found for both CBV and MTT and correlated significantly with lesion enlargement on PD-weighted imaging with strongest correlation for the CBV–DWI mismatch. The CBV–DWI mismatch has the highest accuracy in predicting lesion size on follow-up imaging and in predicting clinical outcome. Lesion volume measurements on CBV maps have a higher specificity than on PD-weighted, MTT or DWI images in predicting clinical follow-up imaging and in predicting clinical outcome.

A considerable proportion of patients discontinue dipyridamole therapy because of headache. Risk indicators for the development of dipyridamole induced headache were identified by means of an exploratory analysis of data from the European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) and the Second European Stroke Prevention Study (ESPS 2). In ESPRIT, dipyridamole induced headache was significantly associated with female sex, absence of hypertension and non-smoking (area under the receiver operator characteristic (ROC) curve 0.63 (95% CI 0.58 to 0.68)) and in ESPS 2 with female sex and absence of ischaemic lesions on imaging (area under the ROC curve 0.64 (95% CI 0.59 to 0.69)).

High-flow revascularization of the brain is hampered by the fact that temporary occlusion of a major brain artery, necessary to make the distal end-to-side anastomosis, may result in brain ischemia. The Excimer laser-assisted nonocclusive anastomosis technique circumvents this problem. After connecting donor and recipient vessels, an Excimer laser catheter, introduced by way of an artificial side branch, creates a hole at the anastomosis site. When the catheter is withdrawn, a round full-thickness portion of the recipient artery is removed. When the artificial side branch is occluded with a hemoclip the anastomosis is completed. The recipient vessel stays open during the procedure. In 90 patients a high-flow bypass was made. In 90% several types of extra-intracranial bypasses were created, and in 10% several types of intra-intracranial bypasses were created. Flow recordings by way of an ultrasound device intraoperatively and with a magnetic resonance (MR) flow program postoperatively show the bypasses to have a real “high flow” character. Complications related to this high-flow bypass procedure and ways to prevent them are presented.

Background and Purpose —Diffusion-weighted MRI (DWI) is highly sensitive in detecting early cerebral ischemic changes in acute stroke patients. In this study we compared the sensitivity of DWI with that of conventional MRI techniques. Furthermore, we investigated the prognostic value of the volume of ischemic lesions on DWI scans and of the apparent diffusion coefficient (ADC). Methods —We performed DWI, fluid-attenuated inversion recovery, spin-echo T2-weighted MRI, and spin-echo proton density–weighted MRI in 42 patients with acute stroke and 15 control subjects. The volume of ischemic lesions was measured on early ( Results —With DWI, 98% of the ischemic lesions were detected, and with fluid-attenuated inversion recovery, 91% were detected, whereas with early T2-weighted or proton density–weighted scans, only 71% ( P =0.002, χ 2 ) and 80% ( P =0.02, χ 2 ) of lesions, respectively, were found. Lesion volume on early DWI scans correlated significantly with clinical outcome ratings ( P P P Conclusions —DWI is a better imaging method than conventional MRI in detecting early ischemic lesions in stroke patients. Lesion size as measured on DWI scans and, to a lesser extent, ADC values are potential parameters for predicting clinical outcome in acute stroke patients.

The objective of this study was to evaluate the role of collateral blood flow via the anterior and posterior communicating arteries (ACoA and PCoA) and via the ophthalmic artery (OphA) on cerebral hemodynamics, metabolism, and border zone infarcts in 57 patients with unilateral symptomatic occlusions of the internal carotid artery. Collateral flow via the ACoA and PCoA was determined with magnetic resonance angiography (MRA) and collateral flow via the OphA with transcranial Doppler (TCD). Volume flow was studied with MRA, metabolism with 1H MR spectroscopy, CO2 reactivity with TCD, and the incidence of border zone infarcts with MRI. Compared with controls, patients had deteriorated volume flow, metabolism, and CO2 reactivity. No differences were found between patients with and patients without collateral flow through the ACoA and/or PCoA, or between patients with or without collateral flow via the OphA. Patients without collateral flow via any of these collaterals had decreased volume flow in the middle cerebral artery, decreased N-acetylaspartate/choline, and increased lactate/N-acetylaspartate, compared with the other patients. Patients with symptomatic internal carotid artery occlusion have deteriorated cerebral hemodynamics and metabolism. Different collateral flow patterns via the ACoA, PCoA, or OphA have no effect on the hemodynamic and metabolic parameters, as long as one of these pathways is present.

The accuracy of duplex sonography in predicting the degree of an internal carotid artery (ICA) stenosis is decreased when a contralateral high-grade stenosis or occlusion is present. The purpose of this study was to determine whether this overestimation of the stenosis by duplex sonography is associated with an increase in volume flow through the ipsilateral ICA.Forty-seven patients (89 vessels) with a symptomatic ICA stenosis or occlusion who underwent duplex sonography, intraarterial digital subtraction angiography, and magnetic resonance angiography flow quantification of the ICAs were evaluated.With the use of peak systolic velocity criteria, duplex overestimated stenoses more frequently (chi2: p = 0.03) in vessels with high volume flow (= mean volume flow in control group + 2 SD (274 ml/min), 46% overestimation) than in vessels with normal or low volume flow (274 ml/min, 20% overestimation). A correlation coefficient of 0.75 (p0.001) was found between volume flow and peak systolic velocity in the distal ICA, indicating that increased volume flow causes the peak systolic velocity to increase. Compared with volume flow in the control group (mean +/- SD = 198 +/- 38 ml/min), volume flow was increased in vessels with a 0% to 49% stenosis (mean +/- SD = 272 +/- 100 ml/min, p0.05) and in vessels with a 50% to 69% stenosis (mean +/- SD = 291 +/- 79 ml/min, p0.01) when the contralateral ICA had a 70% to 99% stenosis or occlusion.Increase in volume flow through the ICA frequently causes overestimation of stenoses in the ICA. Increased volume flow is frequently found in ICAs with a70% stenosis that are contralateral to ICAs with a70% stenosis or an occlusion.

Neurological, cardiac, and systemic complications during the first days to weeks after ischaemic stroke can cause substantial morbidity and mortality. The reported 30-day case fatality rate for cerebral infarction varies between 10 and 17%. The incidence and effects of the various complications vary with time after stroke: transtentorial herniation and other cerebral complications prevail during the 1st week, whereas medical complications are more prominent in the weeks thereafter. Many complications are treatable, and some are preventable. The goal of this report is to provide information on their incidence, consequences, and management.

Background Over the last several years evidence has accumulated that in addition to embolism, a compromised cerebral blood flow may play an important role in causing transient ischemic attacks and ischemic stroke in patients with occlusion of the internal carotid artery. This evidence is found in both clinical features and ancillary investigations, particularly measurements of cerebral blood flow. Summary of Review On the basis of 20 follow-up studies in patients with transient ischemic attacks or minor ischemic stroke associated with an occluded carotid artery, the annual risk of stroke was 5.5% (95% confidence interval [CI], 5.0% to 6.0%), and that of ipsilateral stroke (distinguished in 11 of the 20 studies) was 2.1% (95% CI, 1.6% to 2.8%). Patients with a compromised cerebral blood flow as measured by positron emission tomography, single-photon emission CT, transcranial Doppler, or stable xenon CT (six studies) have an even higher annual risk of stroke (all strokes: 12.5%; 95% CI, 8.9% to 17.6%; ipsilateral stroke: 9.5%; 95% CI, 6.4% to 14.0%). Conclusions Because a compromised cerebral blood flow may be an important causal factor in patients with symptomatic carotid artery occlusion, medical and surgical options for treatment are reviewed in this light.

Background and Purpose Flow measurements in the collateral arteries of patients with internal carotid artery (ICA) occlusions may be important to estimate the risk of future stroke. Quantitative flow measurements in cerebropetal vessels can be reliably assessed by means of magnetic resonance angiography (MRA). Methods Fifty-four patients with transient or minor ischemic neurological deficits and an angiographically proven ICA occlusion and 16 control subjects underwent two-dimensional phase-contrast MRA quantitative flow measurements through the common carotid arteries, basilar artery, ICAs, and middle cerebral arteries (MCA). Results Patients with a unilateral ICA occlusion and a 0% to 69% stenosis of the contralateral ICA had increased flow in the contralateral ICA ( P P P P P P P P Conclusions The contralateral ICA is the main supplying artery in patients with an ICA occlusion. Total cerebropetal flow decreases only when both ICAs are occluded. In patients with symptomatic ICA occlusions, an open contralateral ICA is probably important to retain the cerebral blood flow within normal limits.

We present a review of the literature on multifocal motor neuropathy (MMN), a rare neurological disorder which has features in common with both chronic inflammatory demyelinating neuropathy and lower motor neuron disease. Clinically, MMN is characterised by slowly progressive asymmetrical limb weakness, usually most prominent in the forearms. Weakness may be associated with muscle wasting, fasciculations and decreased tendon reflexes. Serum anti-GM1 ganglioside antibody titres may be increased. The diagnostic hallmark of MMN is the electrophysiological demonstration of persistent localised motor conduction blocks, with otherwise normal or near-normal motor and sensory conduction velocities. The pathogenesis of MMN has not been elucidated completely. There is, however, substantial evidence for an autoimmune mechanism. Based on the possible involvement of the immune system in the pathogenesis of MMN the therapeutic efficacy of several immunomodulatory drugs has been tested. Treatment of MMN patients with human immunoglobulin or cyclophosphamide is usually followed by a marked improvement of strength. The finding that MMN is a potentially treatable disorder underscores the importance of distinguishing MMN from lower motor neuron disease, for which no effective therapy is currently available.

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 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.

Background: Little is known about cerebral blood flow (CBF) in young patients with ischemic stroke caused by an intracranial arteriopathy. Arterial spin labeling (ASL) perfusion is a noninvasive technique for measuring CBF. We aimed to investigate whether, in young patients with unilateral intracranial arteriopathy and previous ischemic stroke, CBF is compromised in noninfarcted brain areas of the symptomatic hemisphere and whether this is related to the severity of the arteriopathy. Methods: Patients aged 5-50 years, with previous middle cerebral artery (MCA) territory infarction and a unilateral intracranial arteriopathy, underwent magnetic resonance imaging (MRI), MR angiography and pseudocontinuous ASL perfusion MRI. We assessed the severity of stenosis of arteries that fed the symptomatic MCA territory, quantified CBF in the noninfarcted cortex of both MCA territories and generated CBF maps for visual CBF interpretation. Results: A total of 17 patients were included (median age 29 years, range 5-49, 29% male). We found a similar median quantified CBF in the symptomatic and asymptomatic MCA territories (86 ml·100 g-1·min-1). CBF maps showed hypoperfusion in the symptomatic MCA territory in 59% of patients compared to 18% based on quantified CBF. Patients with a severe arteriopathy more often showed hypoperfusion on CBF maps than patients with a mild arteriopathy. In 53% of patients, small foci of increased signal intensity were visible on CBF maps around an area of hypoperfusion, indicating vascular artifacts. In these patients, we found large intraindividual variation in the quantified CBF in the symptomatic hemisphere. In 47% of patients, the visual interpretation of perfusion did not correspond with the quantified CBF. Conclusions: This study shows that more than half of young patients with previous ischemic stroke in the MCA territory and a unilateral intracranial arteriopathy have hypoperfusion in the noninfarcted cortex of the symptomatic hemisphere when CBF is visually assessed using a CBF map, in particular in patients with a severe arteriopathy. In the same patients, quantification of CBF shows hypoperfusion in the symptomatic hemisphere in only 18%. This discrepancy is caused by labeled blood within the arteries that has not yet reached the tissue at the time of imaging. Visual assessment can show hypoperfusion, while the quantified CBF in a similar region appears higher when the intravascular labeled blood is included in the region of interest. Further research should focus on elucidating whether cerebral perfusion deficits in young stroke patients with intracranial arteriopathy might help to identify patients who are at risk of poor outcome or stroke recurrence.

Background and Purpose: Little is known about different varieties of transient monocular blindness (TMB) in relation to the subsequent occurrence of vascular outcome events. Very fe

Background and Purpose The risk of major vascular events after an initial episode of cerebral ischemia in patients with nonrheumatic atrial fibrillation (NRAF) varies from 2% to 15% in the first year and is approximately 5% yearly thereafter. Few studies have reported on risk factors that can be used to identify high-risk subgroups within this patient population. Methods We studied the predictive value of several easily obtainable clinical characteristics in a group of 375 placebo-treated patients with NRAF and a recent episode of transient or nondisabling cerebral ischemia who were entered in a multicenter clinical trial. The mean follow-up was 1.6 years. Results By means of multivariate modeling, six independent variables were identified: history of previous thromboembolism, ischemic heart disease, enlarged cardiothoracic ratio on chest roentgenogram, systolic blood pressure greater than 160 mm Hg at study entry, NRAF for more than 1 year, and presence of an ischemic lesion on CT scan. These variables could also be used to stratify patients in low-, medium-, and high-risk subgroups for the other two arms of the trial, those treated with anticoagulation and aspirin. Patients older than 75 years with three or more risk factors seemingly benefited less from both aspirin and anticoagulant treatment. Conclusions Easily obtainable patient characteristics are helpful in estimating the potential effect of adequate secondary prevention in patients with NRAF who recently suffered a transient ischemic attack or minor ischemic stroke.

The authors assessed the time of onset of the hypothermic effect of acetaminophen in 102 patients with acute ischemic stroke. These patients were randomized to treatment with either 1000 mg of acetaminophen (n = 52) or placebo (n = 50), given six times daily. Treatment with high-dose acetaminophen resulted in a 0.26 °C (95% CI 0.07 to 0.46 °C) lower mean body temperature than placebo treatment within 4 hours. This effect remained present throughout the next 20 hours. A large phase III trial seems warranted.

We studied the value of clinical and electroencephalographic assessment in patients with acute first-ever supratentorial ischemia in predicting functional outcome after 1 year. In 55 consecutive patients admitted after a median interval of less than 24 hours, the degree of handicap was dichotomized as moderate (Rankin grade 1, 2, or 3) or severe (Rankin grade 4 or 5). Clinical deficits were categorized according to signs of a lacunar or a cortical syndrome. Without knowledge of clinical data, electroencephalograms (EEGs) were classified according to findings predicting good or poor prognosis. The outcome after 1 year was assessed as good (Rankin grade 3 or less) or poor (Rankin grade 4 or 5 or death from stroke) and was correlated to clinical data and to EEG findings in the acute stage. Thirty patients with a moderate handicap on admission all had a good outcome (predictive value [PV] of the initial handicap, 1.00; 95% confidence interval [CI], 0.88 to 1.00). Of the 25 patients with severe handicap on admission a poor outcome occurred in 13 (PV, 0.52; 95% CI, 0.31 to 0.72). If these patients with severe handicap at baseline were subdivided according to clinical features, a lacunar syndrome predicted good outcome in 4 of 5 patients (PV, 0.80; 95% CI, 0.28 to 1.00), but a cortical syndrome predicted poor outcome in only 12 of 20 patients (PV, 0.60; 95% CI, 0.36 to 0.81). Of the 20 patients with severe handicap and a cortical syndrome at baseline, an EEG with features predicting a good prognosis correctly predicted good outcome in 6 of 7 patients (PV, 0.86; 95% CI, 0.42 to 1.00). An EEG with features predicting poor prognosis correctly predicted poor outcome in 11 of 13 patients (PV, 0.85; 95% CI, 0.55 to 0.98). Electroencephalography improves the prediction of functional outcome in patients with a severe neurological deficit in the acute stage of cerebral ischemia. This may have implications for the design of future intervention trials in acute stroke.

Objectives: This prospective cohort study assesses incidence of delirium after stroke. In addition, risk factors during the first week were assessed. Finally, outcome in relation to development of delirium was studied. Methods: A total of 527 consecutive patients with stroke (median age, 72 years; range, 29–96 years) were screened for delirium during the first week after admission. We diagnosed delirium with the Confusion Assessment Method. Cognitive functioning prior to the stroke was assessed with the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Neurologic deficits were assessed with the NIH Stroke Scale. Results: A total of 62 patients with stroke (11.8%) developed delirium during the first week of admission. Independent risk factors were preexisting cognitive decline (odds ratio [OR] for IQCODE above 50: 2.6, 95% confidence interval [CI] 1.2–5.7) and infection (OR 3.4, 95% CI 1.7–6.8). Furthermore, right-sided hemispheric stroke (OR 2.0, 95% CI 1.0–3.0), anterior circulation large-vessel stroke (OR 3.4, 95% CI 1.1–10.2), the highest tertile of the NIH Stroke Scale (OR for highest vs lowest tertile 15.1, 95% CI 3.3–69.0), and brain atrophy (OR for highest versus lowest tertile 2.7, 95% CI 1.1–6.8) increased the risk for delirium. Delirium was associated with a worse outcome in terms of duration of hospitalization, mortality, and functional outcome. Conclusions: Delirium occurs in almost 1 out of every 8 patients with stroke on a stroke unit and is associated with cognitive decline, infection, right-sided hemispheric stroke, anterior circulation large-vessel stroke, stroke severity, and brain atrophy. Delirium after stroke is associated with a worse outcome.

Proposed guidelines for the diagnosis of transient ischaemic attack (TIA) involve interpretation of symptoms, so it can be very difficult to distinguish a TIA from other disorders, such as migraine, epilepsy, syncope, or neurosis. Atypical cerebral and visual events may be classified as TIA. To see whether TIA or stroke patients with atypical cerebral or visual symptoms are at high or low risk of cardiac complications, we prospectively followed 572 patients (entered into the Dutch multicentre TIA trial) with a diagnosis of TIA or minor ischaemic stroke, but whose symptoms did not fully accord with internationally accepted criteria. We compared their outcome with that of 2555 other TIA or stroke patients in the trial, who had unequivocal symptoms; all patients were treated with aspirin. During mean follow-up of 2.6 years the risk of a major vascular event did not differ between the groups (14.5% in patients with atypical symptoms vs 15.1% of patients with typical attacks). Patients with atypical attacks had a lower risk of stroke (5.6% vs 9.4%, hazard ratio 0.6, 95% confidence interval 0.4-0.9) and a higher risk of a major cardiac event (8.4% vs 5.9%, 1.4, 1.0-2.0) than did patients with typical attacks. These differences could not be explained by differences in cardiac risk factors, and were independent of minor discrepancies in baseline characteristics between the groups. A heavy or tired feeling in one or two limbs was the only atypical symptom associated with cerebral rather than cardiac events (ratio cardiac/cerebral events 0.8). For all other atypical symptoms cardiac events were about twice as common as cerebral events (range 1.3-2.5). Our findings suggest that TIA or minor stroke patients with atypical symptoms may have symptomatic heart disease, especially cardiac arrhythmia.