Dippel, D.W.J.

Ambivalence among neurologists and neurosurgeons on the treatment of chronic subdural hematoma: A national survey (Article)

2013-03-19T00:00:00Z

No class I evidence exists about the optimal treatment of chronic subdural hematoma (CSDH). The aim of this study was to evaluate current practice of CSDH patients with different neurological grades, and probable ambivalence towards various treatment paradigms, especially primary treatment with high-dose corticosteroids, among vascular neurologists and neurosurgeons. A questionnaire survey containing 4 questions, 1 consisting of cases, was sent to every vascular neurologist (n = 83) and neurosurgical centre (n = 15) in the Netherlands. The various treatment options were related to the treating physician, geographical distribution, both in general and for individual case. Sixty-two percent of surveys were returned. The proportion of patients primarily treated with corticosteroids was 17. 5 % in 2009 and 20. 5 % in 2010. Surgery by either burr holes or craniotomy was favoured by 61. 1 % as primary treatment, and conservative treatment with corticosteroids by 22. 4 %. Case studies revealed that surgery was preferred in case of severe neurological symptoms, whereas wait-and-see policy was preferred in case of mild symptoms without midline shift, of which 28 % would administer corticosteroids. Variety in answers was obtained in less pronounced cases. In the Netherlands, neurologists and neurosurgeons appear to favour surgery in CSDH patients as primary treatment, especially in severe cases. An ambivalent approach towards treatment protocols was shown, especially in patients with mild symptoms, regardless of hematoma size. A regimen of high-dose corticosteroids only, is preferred by about a quarter and predominantly in milder cases, and might depend on geographical distribution. These results suggest the need for a well-designed randomized trial.

Increased benefit of alteplase in patients with ischemic stroke and a high body temperature (Article)

2013-02-01T00:00:00Z

Background: In observational studies, a high body temperature has been associated with unfavorable outcome. In in vitro studies, the fibrinolytic activity of alteplase decreased 5% per degree Celsius reduction in temperature. The modifying effect of body temperature on treatment with alteplase in patients with acute ischemic stroke is unclear. We assessed the influence of baseline body temperature on the effect of alteplase on functional outcome in patients with acute ischemic stroke, included in the Paracetamol (Acetaminophen) in Stroke (PAIS) trial. Methods: PAIS was a randomized, double-blind clinical trial to assess the effect of high-dose paracetamol on functional outcome in patients with acute stroke. For this study, we selected all patients with ischemic stroke and randomization within 6 h of symptom onset. We estimated the effect of treatment with alteplase on the modified Rankin Scale score at 3 months with ordinal logistic regression, stratified by baseline body temperature. We made adjustments for confounding factors and expressed associations as adjusted odds ratios (aOR) with 95% confidence intervals (CI). We also tested for interaction between treatment with alteplase and body temperature. Results: We included 647 of the 1,400 patients in PAIS in our study. Treatment with alteplase was associated with improved functional outcome at 3 months (aOR 1.51, 95% CI 1.09-2.08). In the 286 patients (44%) with a baseline body temperature of 37.0°C or higher, alteplase was associated with a larger effect (aOR 2.13, 95% CI 1.28-3.45) than in patients with a temperature below 37.0°C (aOR 1.11, 95% CI 0.71-1.69). A test for interaction between body temperature and alteplase did not reach statistical significance (p = 0.18). Conclusion: Patients with ischemic stroke and a high body temperature may have a larger benefit of treatment with alteplase than patients with lower body temperatures. These findings are in line with those from in vitro studies, in which lowering temperature decreased the fibrinolytic activity of the enzyme alteplase. This interaction should be explored further in randomized clinical trials of thrombolytic therapy or modification of body temperature. Trials of therapeutic hypothermia should be controlled for treatment with thrombolytics, and trials of thrombolytic treatment should consider body temperature as a potential effect modifier. Copyright

Rotterdam Aphasia Therapy Study (RATS) - 3: " The efficacy of intensive cognitive-linguistic therapy in the acute stage of aphasia"; design of a randomised controlled trial (Article)

2013-01-23T00:00:00Z

Background: Aphasia is a severely disabling condition occurring in 20 to 25% of stroke patients. Most patients with aphasia due to stroke receive speech and language therapy. Methodologically sound randomised controlled trials investigating the effect of specific interventions for patients with aphasia following stroke are scarce. The currently available evidence suggests that intensive speech and language therapy is beneficial for restoration of communication, but the optimal timing of treatment is as yet unclear.In the Rotterdam Aphasia Therapy Study-3 we aim to test the hypothesis that patients with aphasia due to stroke benefit more from early intensive cognitive-linguistic therapy than from deferred regular language therapy.Methods/design: In a single blinded, multicentre, randomised controlled trial, 150 patients with first ever aphasia due to stroke will be randomised within two weeks after stroke to either early intensive cognitive-linguistic therapy (Group A) or deferred regular therapy (Group B). Group A will start as soon as possible, at the latest two weeks after stroke, with a four week period of one hour a day treatment with cognitive-linguistic therapy. In Group B professional speech and language therapy is deferred for four weeks. After this period, patients will follow the conventional procedure of speech and language therapy. Participants will be tested with an extensive linguistic test battery at four weeks, three months and six months after inclusion. Primary outcome measure is the difference in score between the two treatment groups on the Amsterdam-Nijmegen Everyday Language Test, a measure of everyday verbal communication, four weeks after randomisation.Trial registration: This trial is registered in the Dutch Trial Register (http://www.trialregister.nl), NTR3271.

Expert versus proxy rating of verbal communicative ability of people with aphasia after stroke (Article)

2012-11-01T00:00:00Z

Abstract In randomized clinical trials of aphasia treatment, a functional outcome measure like the Amsterdam-Nijmegen Everyday Language Test (ANELT), administered by speech-language therapists, is often used. However, the agreement between this expert rating and the judgment of the proxy about the quality of the daily life communication of the person with aphasia is largely unknown. We examined the association between ANELT scores by speech-language therapists and proxy judgments on the Partner Communication Questionnaire both at 3 and 6 months in 39 people with aphasia after stroke. We also determined which factors affected the level of agreement between expert and proxy judgment of the communicative ability at 6 months in 53 people with aphasia. We found moderate agreement (at 3 months r =.662; p = <.0001 and at 6 months r =.565; p =.0001), with proxies rating slightly higher than experts. Less severe aphasia, measured with the Aphasia Severity Rating Scale, was associated with better agreement. In conclusion, although proxies were slightly more positive than experts, we found moderate agreement between expert and proxy rating of verbal communicative ability of people with aphasia after stroke, especially in milder cases. (JINS, 2012, 18, 1064-1070) Copyright

Long-term prognosis of aphasia after stroke (Article)

2012-10-31T00:00:00Z

Background: The long-term functional outcome of aphasia after stroke is uncertain, even though this information is needed as early as possible for adequate patient care and support. This observational prospective study was aimed at predicting functional outcome at 1 year after stroke. Methods: We examined linguistic components (ScreeLing) and functional verbal communication (Aphasia Severity Rating Scale, ASRS) in 147 aphasic patients. The ScreeLing was administered at 1, 2 and 6 weeks after stroke; the ASRS at 1 week and 1 year. The relationships between linguistic, demographic and stroke characteristics, and good functional outcome at 1 year (ASRS 4 or 5) were examined with logistic regression analyses. Results: The baseline linguistic components (ie, semantics, phonology and syntax) were significant predictors (p<0.001) for 1-year outcome in univariable analyses. In multivariable analysis, these variables explained 46.5% of the variance, with phonology being the only significant predictor (p=0.003). Age, Barthel Index score, educational level and haemorrhagic stroke were identified as other significant predictors of outcome. A prognostic model of these five baseline predictors explained 55.7% of the variance. The internally validated area under the receiver operating characteristic curve (AUC) was 0.89, indicating good predictive performance. Adding the degree of phonological recovery between 1 and 6 weeks after stroke to this model increased the explained variance to 65% and the AUC to 0.91. Conclusions: The outcome of aphasia at 1 year after stroke can be predicted in the first week by the phonology score, the Barthel Index score, age, educational level and stroke subtype, with phonology being the strongest predictor. Copyright Article author (or their employer) 2012.

The effectiveness of thrombolysis with intravenous alteplase for acute ischemic stroke in daily practice (Article)

2012-06-01T00:00:00Z

Background: Thrombolysis with intravenous alteplase has been proven an effective treatment for patients with acute ischemic stroke in randomized clinical trials. In daily practice, the effect of thrombolysis may be less, and complications may occur more often. Aims: The aim of this study was to assess effectiveness and safety of thrombolysis in an unselected observational cohort of patients. Methods: During a two-year period, all patients over 18 years with acute stroke who were admitted within four-hours from onset of symptoms in 12 centers were registered. We compared outcomes in patients who were treated with alteplase with patients who were not treated with alteplase. The primary outcome was good functional outcome at three-months measured with the modified Rankin Scale ≤2). The safety end point was symptomatic intracranial hemorrhage and mortality. We used a multivariable logistic regression model to adjust for baseline imbalances and multilevel analysis to take into account within center correlations. Results: Overall, 1657 patients with ischemic stroke were admitted within four-hours from onset of symptoms and 696 (42%) were treated with alteplase. Treatment with alteplase was associated with a favorable outcome (adjusted odds ratio 1·3; 95% confidence interval 1·0 to 1·7). After further adjustment for potential clustering effects, the adjusted odds ratio for good outcome was 1·4 (95% confidence interval 1·0 to 1·8). Thirty-six (5%) of the 696 patients treated with alteplase had a symptomatic intracranial bleeding complication. Conclusions: Thrombolysis for ischemic stroke with intravenous alteplase is an effective treatment also in an unselected observational cohort of patients. © 2011 The Authors. International Journal of Stroke

Real-life costs and effects of an implementation program to increase thrombolysis in stroke (Article)

2012-01-01T00:00:00Z

Objectives: We have shown that a Breakthrough Series–based implementation program increases the number of patients with acute ischemic stroke treated with alteplase 4.5% in real-life settings. It is unclear whether such an implementation program is cost-effective. Methods: The practice study includes 12 randomized hospitals and 5,515 patients. Its present cost-effectiveness analysis involves 1,657 patients with ischemic stroke admitted within 4 hours from onset. Defined primary outcomes are thrombolysis rate and actual health care costs up to 3 months, including additional implementation efforts. Secondary outcomes are lifetime qualityadjusted years (QALYs) and lifetime costs of individual trial patients, using a validated probabilistic, disability-stratified stroke life table. Differences in outcome include95%confidence intervals (CI), adjusted for intracluster correlation. Results: The thrombolysis rate in the intervention group was 44.3% vs 39.8% in the control group (difference 4.5%; 95% CI 3.1% to 5.9%. Mean costs per patient at 3 months (euros were converted to 2010 USD) were $9,192 USD in the intervention group and $9,647 USD in the control group (difference !$455 USD; 95% CI !$232 to !$679 USD). Lifetime QALYs in the intervention group were 3.89 and in the control group 3.84 (difference 0.05; 95% CI !0.04 to 0.14). The mean lifetime costs in the intervention group were $22,994 USD against $24,315 USD in the control group (difference !$1,321 USD; 95% CI !$1,722 to !$921 USD). Conclusions: A Breakthrough Series implementation program of thrombolysis increases thrombolysis. It saves short- and long-term health care costs due to lower hospital admission and residential costs, increasing stroke care efficiency.

Real-life costs and effects of an implementation program to increase thrombolysis in stroke (Article)

2012-01-01T00:00:00Z

Prediction of intracranial findings on CT-scans by alternative modelling techniques (Article)

2011-10-27T00:00:00Z

Background: Prediction rules for intracranial traumatic findings in patients with minor head injury are designed to reduce the use of computed tomography (CT) without missing patients at risk for complications. This study investigates whether alternative modelling techniques might improve the applicability and simplicity of such prediction rules. Methods. We included 3181 patients with minor head injury who had received CT scans between February 2002 and August 2004. Of these patients 243 (7.6%) had intracranial traumatic findings and 17 (0.5%) underwent neurosurgical intervention. We analyzed sensitivity, specificity and area under the ROC curve (AUC-value) to compare the performance of various modelling techniques by 10 × 10 cross-validation. The techniques included logistic regression, Bayes network, Chi-squared Automatic Interaction Detection (CHAID), neural net, support vector machines, Classification And Regression Trees (CART) and "decision list" models. Results: The cross-validated performance was best for the logistic regression model (AUC 0.78), followed by the Bayes network model and the neural net model (both AUC 0.74). The other models performed poorly (AUC < 0.70). The advantage of the Bayes network model was that it provided a graphical representation of the relationships between the predictors and the outcome. Conclusions: No alternative modelling technique outperformed the logistic regression model. However, the Bayes network model had a presentation format which provided more detailed insights into the structure of the prediction problem. The search for methods with good predictive performance and an attractive presentation format should continue.

Phonology is the strongest language component in predicting aphasia outcome after stroke (Article)

2011-10-20T00:00:00Z

The prognostic value of pulsatility index, flow velocity, and their ratio, measured with TCD ultrasound, in patients with a recent TIA or ischemic stroke (Article)

2011-10-01T00:00:00Z

Background- Increased flow velocities, and combinations of low mean flow velocity (MFV) and a high pulsatility index (PI) are associated with intracranial arterial disease. We investigated the association of MFV and the ratio of PI and MFV (PI-MFV ratio) in the middle cerebral artery (MCA) with recurrence of vascular events in patients with a transient ischemic attack (TIA) or minor ischemic stroke. Methods- Five hundred and ninety-eight consecutive patients underwent TCD investigation. Outcome events were fatal or non-fatal stroke and the composite of stroke, myocardial infarction, or vascular death (major vascular events). Hazard ratios (HR) were estimated with Cox proportional hazards multiple regression method, adjusted for age, gender, and vascular risk factors. Results- TCD registration was successful in 489 patients. Mean follow-up was 2.1years. Cumulative incidence was 9% for all stroke and 12% for major vascular events. MFV over 60.5cm/s increased the risk for both stroke (HR 2.8; 95% CI: 1.3-6.0) and major vascular events (HR 2.6; 95% CI: 1.3-5.0). Each unit increase in PI-MFV ratio was associated with a HR 2.8 (95% CI: 1.7-4.8) for stroke and HR 2.2 (95% CI: 1.3-3.6) for major vascular events. Conclusion- In patients with a TIA or non-disabling ischemic stroke, MFV and the PI-MFV ratio in the MCA are independent prognostic factors for recurrent vascular events.

Fibrinogen γ' levels in patients with intracerebral hemorrhage (Article)

2011-09-13T00:00:00Z

Background: The fibrinogen γ' variant (γ') has both antithrombotic and prothrombotic properties when compared to normal fibrinogen. It may therefore be of relevance in intracerebral hemorrhage and intraventricular extension of the bleeding. Objective: To study the role of γ' in intracerebral hemorrhage, and in intraventricular extension of the hemorrhage. Patients/Methods: We performed a case-control study in 156 controls and 55 patients with intracerebral hemorrhage, with and without intraventricular extension. Levels of fibrinogen γ' and the γ'/total fibrinogen ratio were measured in all participants. Results: Levels of γ' were increased in patients with intracerebral hemorrhage when compared with controls (0.40 vs 0.32 g/l, p < 0.001). The γ'/total fibrinogen ratio was similar in patients and controls (0.092 vs 0.096 p = 0.42). There was evidence for an unfavorable outcome in patients with fibrinogen levels in the highest tertile compared with the lowest tertile (OR 4.0, 95%CI 1.1-15.2), and a nonsignificant trend toward unfavorable outcome with higher levels of γ' (p-value for trend = 0.06). Conclusions: Our study shows that absolute levels of fibrinogen γ' are increased in patients with intracerebral hemorrhage, but relative levels are similar in patients and controls, suggesting that the absolute rise in γ' is an acute phase response.

Do centres with well-developed protocols, training and infrastructure have higher rates of thrombolysis for acute ischaemic stroke? (Article)

2011-09-01T00:00:00Z

Background: The introduction of intravenous thrombolysis with recombinant tissue Plasminogen Activator (rt-PA) has greatly improved the effectiveness of acute ischaemic stroke care. However, in most hospitals only 2-10% of all admitted stroke patients are treated with thrombolysis. Aim: The purpose of this study is to identify if available protocols, training and infrastructure influence the thrombolysis rate. Design: Cohort study of 12 hospitals in the Netherlands. Methods: In a cohort of patients admitted with acute stroke within 24 h from onset of symptoms, data were obtained. Stroke service characteristics of 12 hospitals were acquired through structured interviews with intra- and extramural representatives, in order to asses (i) protocols, (ii) training and (iii) complexity of infrastructure. Data were analysed with multi-level logistic regression to relate the likelihood of treatment with thrombolysis to availability and completeness of protocols, training and infrastructure both outside (extramural) and inside (intramural) each centre. Results: Overall 5515 patients were included in the study. Thrombolysis rates varied from 5.7% to 21.7%. An association was observed between thrombolysis rates and extramural training [odds ratio (OR): 1.11; 95% confidence interval (CI): 0.99-1.25] and availability of intramural protocols (OR: 1.46; 95% CI: 1.12-1.91). After adjustment for hospital size and teaching vs. nonteaching hospital, these associations became stronger; extramural training [adjusted OR (aOR): 1.14; 95% CI: 1.01-1.30] and availability of intramural protocols (aOR: 1.77; 95% CI: 1.30-2.39). Conclusions: Extramural training and intramural protocols are important tools to increase thrombolysis rates for acute ischaemic stroke in hospitals. Intramural protocols and extramural training should be aimed at all relevant professionals.

A 3-year evolution of linguistic disorders in aphasia after stroke (Article)

2011-09-01T00:00:00Z

Aphasia recovery after stroke has been the subject of several studies, but in none the deficits on the various linguistic levels were examined, even though in the diagnosis and treatment of aphasia the emphasis lays more and more on these linguistic level disorders. In this observational prospective follow-up study, we explored whether it is meaningful to investigate the recovery of semantics, phonology, and syntax separately. Fifteen patients with aphasia poststroke were assessed at 3 and 10 days, 7 weeks, 4 and 7 months, and 3 years postonset with the ScreeLing, a linguistic level test, the Aphasia Severity Rating Scale (spontaneous speech) and the Token Test. Group results showed improvement for the overall ScreeLing (P<0.01) and its subparts semantics (P<0.01) and syntax (P<0.01) up to 7 weeks, just as the Token Test (P<0.01). Phonology improved up to 4 months (P<0.05) and spontaneous speech up to 7 months (P<0.05). The recovery pattern of the three linguistic levels did not follow a parallel course, with a great deal of variability in linguistic recovery curves between and within patients. These results suggest that it is meaningful to assess the recovery of the linguistic levels separately, starting from the acute stage poststroke.

Incidence, treatment, and case-fatality of non-traumatic subarachnoid haemorrhage in the Netherlands (Article)

2011-07-01T00:00:00Z

Background: Non-traumatic subarachnoid haemorrhage (SAH) is a devastating disorder and in the majority of cases it is caused by rupture of an intracranial aneurysm. No actual data are available on the incidence of non-traumatic SAH and aneursymal SAH (aSAH) in the Netherlands and little is known about treatment patterns of aSAH. Our purpose was therefore to assess the incidence, treatment patterns, and case-fatality of non-traumatic (a)SAH within the Dutch general population. Methods: Two population based data sources were used for this retrospective cohort study. One was the nationwide hospital discharge registry (National Medical Registration, LMR). Cases were patients hospitalized for SAH (ICD-9-code 430) in 2001-2005. The second source was the Integrated Primary Care Information (IPCI) database, a medical record database allowing for case validation. Cases were patients with validated non-traumatic (a)SAH in 1996-2006. Incidence, treatment, and case-fatality were assessed. Results: The incidence rate (IR) of non-traumatic SAH was 7.12 per 100,000 PY (95%CI: 6.94-7.31) and increased with age. The IR of aSAH was 3.78 (95%CI: 2.98-4.72). Women had a twofold increased risk of non-traumatic SAH; this difference appeared after the fourth decade. Non-traumatic SAH fatality was 30% (95%CI: 29-31%). Of aSAH patients 64% (95%CI: 53-74%) were treated with a clipping procedure, and 26% (95%CI: 17-37%) with coiling. Conclusion: Non-traumatic SAH is a rare disease with substantial case-fatality; rates in the Netherlands are similar to other countries. Case-fatality is also similar as well as age and sex patterns in incidence.

Effects of high-dose paracetamol on blood pressure in acute stroke (Article)

2011-06-10T00:00:00Z

den Hertog HM, van der Worp HB, van Gemert HMA, van Gijn J, Koudstaal PJ, Dippel DWJ. Effects of high-dose paracetamol on blood pressure in acute stroke., Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2011.01529.x., © 2011 John Wiley & Sons A/S. 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 24h of stroke onset who were randomized to treatment with either paracetamol (6g daily) or placebo. Blood pressures were measured at 12, 24, and 48h 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 4.5mm Hg (95% CI 0.6-8.5) at 12h from the start of treatment. This effect was no longer present after 24 and 48h. Conclusion- High-dose paracetamol reduces not only body temperature but also systolic blood pressure in the first 12h after start of treatment. Both effects may improve functional outcome after stroke, but this needs further study.

Prevalence and calcification of intracranial arterial stenotic lesions as assessed with multidetector computed tomography angiography (Article)

2011-05-01T00:00:00Z

BACKGROUND AND PURPOSE-Intracranial arterial stenosis (ICAS) in patients with recent ischemic stroke is associated with a high risk of recurrent stroke. More insight into the pathophysiology of ICAS could help identify patients at high risk requiring more aggressive secondary prevention. We evaluated the prevalence, distribution, calcification, and the risk factors predisposing ICAS in a European stroke population. METHODS-Consecutive patients with a transient ischemic attack or ischemic stroke (n=786) were evaluated for the presence and distribution of ICAS (≥30% luminal narrowing) by CT angiography. ICAS were categorized as symptomatic or asymptomatic, and the presence of calcification was assessed. The association of traditional cerebrovascular risk factors and the erythrocyte sedimentation rate with ICAS was analyzed. RESULTS-In 178 of 786 patients (23%), 288 ICAS were observed. Most stenoses (n=194/288; 67%) were located in the posterior circulation arteries. In 59 of 786 patients (8%), ICAS were considered symptomatic. ICAS in the basilar artery and arteries beyond the circle of Willis were mainly noncalcified. In addition to age, gender, and several traditional cerebrovascular risk factors, erythrocyte sedimentation rate was independently associated with the presence of ICAS (OR, 1.20; 95% CI, 1.06-1.36) and with the presence of noncalcified ICAS in particular (OR, 1.20; 95% CI, 1.05-1.37). CONCLUSIONS-ICAS was observed in a noteworthy number of European stroke patients. Particularly, the majority of ICAS was observed in the posterior circulation, possibly conferring worse prognosis. ICAS in distal arteries were mainly noncalcified. Association of noncalcified ICAS and erythrocyte sedimentation rate may indicate a prominent role for inflammatory factors in intracranial atherosclerotic disease.

Promoting thrombolysis in acute ischemic stroke (Article)

2011-05-01T00:00:00Z

BACKGROUND AND PURPOSE-Thrombolysis with intravenous recombinant tissue plasminogen activator is an effective treatment for acute ischemic stroke, but the number of treatable patients is limited. The PRomoting ACute Thrombolysis in Ischemic StrokE (PRACTISE) trial evaluated the effectiveness of a multidimensional implementation strategy for thrombolysis with intravenous recombinant tissue plasminogen activator in acute ischemic stroke. METHODS-The PRACTISE trial was a national multicenter cluster-randomized controlled trial with randomization after pairwise matching. Twelve hospitals, both urban and community, academic and nonacademic, in the Netherlands participated. All patients admitted with stroke within 24 hours from onset of symptoms were registered. The intervention included 5 implementation meetings based on the Breakthrough Series model. The primary outcome was treatment with thrombolysis. Secondary outcomes were admission within 4 hours after onset of symptoms, death or disability at 3 months, and quality of life. RESULTS-Overall 5515 patients were included in the study' 308 patients (12.2%) in the control centers and 393 patients (13.1%) in the intervention centers were treated with thrombolysis (adjusted OR, 1.25; 95% CI, 0.93 to 1.68). Among the 1657 patients with ischemic stroke admitted within 4 hours from onset, 391 (44.5%) of 880 in the intervention centers were treated with thrombolysis and 305 (39.3%) of 777 in the control centers; the adjusted OR for treatment with thrombolysis was 1.58 (95% CI, 1.11 to 2.27). CONCLUSIONS-An intensive implementation strategy increases the proportion of patients with acute stroke treated with thrombolysis in real-life settings. An apparently pivotal factor in the improvement of the treatment rate is better application of contraindications for thrombolysis.

Platelet aggregation inhibitors, vitamin K antagonists and risk of subarachnoid hemorrhage (Article)

2011-03-01T00:00:00Z

Background: Use of platelet aggregation inhibitors and vitamin K antagonists has been associated with an increased risk of intracranial hemorrhage (ICH). Whether the use of these antithrombotic drugs is associated with an increased risk of subarachnoid hemorrhage (SAH) remains unclear, especially as confounding by indication might play a role. Objective: The aim of the present study was to investigate whether use of platelet aggregation inhibitors or vitamin K antagonists increase the risk of SAH. Methods: We applied population-based case-control, case-crossover and case-time-control designs to estimate the risk of SAH while addressing issues both of confounding by indication and time varying exposure within the PHARMO Record Linkage System database. This system includes drug dispensing records from community pharmacies and hospital discharge records of more than 3million community-dwelling inhabitants in the Netherlands. Patients were considered a case if they were hospitalized for a first SAH (ICD-9-CM code 430) in the period between 1st January 1998 and 31st December 2006. Controls were selected from the source population, matched on age, gender and date of hospitalization. Conditional logistic regression was used to estimate multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of SAH during use of platelet aggregation inhibitors or vitamin K antagonists. In the case-crossover and case-time-control designs we selected 11 control periods preceding the index date in successive steps of 1month in the past. Results: In all, 1004 cases of SAH were identified. In the case-control analysis the adjusted OR for the risk of SAH in current use of platelet aggregation inhibitors was 1.32 (95% CI: 1.02-1.70) and in current use of vitamin K antagonists 1.29 (95% CI: 0.89-1.87) compared with no use. In the case-crossover analysis the ORs for the risk of SAH in current use of platelet aggregation inhibitors and vitamin K antagonists were 1.04 (95% CI: 0.56-1.94) and 2.46 (95% CI: 1.04-5.82), respectively. In the case-time-control analysis the OR for platelet aggregation inhibitors was 0.50 (95% CI: 0.26-0.98) and for vitamin K antagonists 1.98 (95% CI: 0.82-4.76). Conclusion: The use of platelet aggregation inhibitors was not associated with an increased SAH risk; the modest increase observed in the case-control analysis could be as a result of confounding. The use of vitamin K antagonists seemed to be associated with an increased risk of SAH. The increase was most pronounced in the case-crossover analysis and therefore cannot be explained by unmeasured confounding.

An early rise in body temperature is related to unfavorable outcome after stroke: Data from the PAIS study (Article)

2011-02-01T00:00:00Z

Subfebrile temperature or fever is present in about a third of patients on the first day after stroke onset and is associated with poor outcome. However, the temporal profile of this association is not well established. We aimed to assess the relationship between body temperature on admission as well as the change in body temperature from admission to 24 h thereafter and functional outcome and death. We analyzed data of 1,332 patients admitted within 12 h of stroke onset. The relation between body temperature on admission or the change in body temperature from admission to 24 h thereafter (adjusted for body temperature on admission) on the one hand and unfavorable outcome (death, or a modified Rankin Scale score >2) at 3 months on the other were expressed as odds ratio per 1.0°C increase in body temperature. Adjustments for potential confounders were made with a multiple logistic regression model. No relation was found between admission body temperature and poor outcome (aOR 1.06; 95% CI 0.85-1.32) and death (aOR 1.23; 95% CI 0.95-1.60). In contrast, increased body temperature in the first 24 h after stroke onset was associated with poor outcome (aOR 1.30; 95% CI 1.05-1.63) and death (aOR 1.51; 95% CI 1.15-1.98). An early rise in body temperature rather than high body temperature on admission is a risk factor for unfavorable outcome in patients with acute stroke.

Association between carotid artery plaque ulceration and plaque composition evaluated with multidetector CT angiography (Article)

2011-02-01T00:00:00Z

Background and Purpose- Symptomatic carotid artery plaque ulceration is associated with distinct plaque components such as a large lipid-rich necrotic core (LR-NC) in ischemic stroke patients with a 50% carotid stenosis. We evaluated the associations between carotid artery plaque ulceration and plaque characteristics in ischemic stroke patients with 50% stenosis, as well as in those with a low degree of stenosis (0% to 49%). Methods- Consecutive patients (n=346) with symptoms in the anterior circulation were evaluated with multidetector CT angiography (MDCTA) for the presence of atherosclerotic plaque, degree of stenosis, and plaque ulceration in the symptomatic carotid artery. Plaque volume and plaque component proportions of LR-NC, fibrous tissue, and calcification were measured. The associations between plaque ulceration and plaque characteristics were analyzed using logistic regression. Results- Atherosclerotic plaque was present in 185 patients. Plaque ulcerations were present in 38 (21%) patients, of which half had a low degree stenosis (0% to 49%). Plaque volume was significantly larger in ulcerated plaques. After adjustment for age, sex, and degree of stenosis, LR-NC proportion was strongly associated with plaque ulceration (odds ratio, 2.21; 95% CI, 1.49 to 3.27), whereas calcification proportion was inversely associated with plaque ulceration (odds ratio, 0.60; 95% CI, 0.40 to 0.89). These associations remained significant in patients with a low degree stenosis (0% to 49%). CONCLUSION-: Plaque volume, degree of stenosis, and LR-NC proportion evaluated noninvasively with MDCTA are associated with carotid artery plaque ulceration, even in patients with a low degree stenosis (0% to 49%). Plaque volume and composition analysis with MDCTA may identify rupture prone plaques and improve risk stratification in ischemic stroke patients.

Evolution of atherosclerotic carotid plaque morphology: Do ulcerated plaques heal? A serial multidetector ct angiography study (Article)

2011-02-01T00:00:00Z

Background: Atherosclerotic carotid plaque rupture may lead to thromboembolization, causing transient ischemic attack or ischemic stroke. Carotid plaque ulceration on angiography is associated with plaque rupture. Although healing of ruptured plaques has been described in coronary arteries, little is known about the natural development of plaque ulcerations in carotid arteries. We therefore explored the evolution of carotid plaque surface morphology with serial multidetector CT angiography (MDCTA). Methods: From a registry of patients with transient ischemic attack or minor ischemic stroke, we selected 83 patients who had undergone serial MDCTA of the carotid arteries. Arteries subjected to revascularization procedures between the two scans were excluded (n = 11). Plaque surface morphology was classified as smooth, irregular or ulcerated on both baseline and follow-up MDCTA. Progression (i.e. development of irregularities or ulceration) and regression (i.e. disappearance of irregularities or ulceration) in morphology were evaluated. Results: The mean time interval between the MDCTA scans was 21 ± 13 months. At baseline, 28 (18%) arteries were normal, 124 (80%) contained atherosclerotic plaque and 3 (2%) were occluded. Plaque surface morphology was smooth in 86 arteries (55%), irregular in 23 (15%) and ulcerated in 15 (10%). At follow-up, surface morphology was unchanged in 88% of arteries, had progressed in 8% and regressed in 4%. Most importantly, plaque morphology remained unchanged in most ulcerated plaques (10/15; 67%). One ulcerated plaque had progressed, whereas 4 had regressed. New ulcerations had developed in 2 nonulcerated plaques. Conclusion: MDCTA allows evaluation of temporal changes in atherosclerotic carotid plaque morphology. Plaque surface morphology remained unchanged in most arteries. Carotid ulcerations persist for a long time, and may remain a potential source of thromboembolism. Copyright

Variation in the von Willebrand factor gene is associated with von Willebrand factor levels and with the risk for cardiovascular disease (Article)

2011-01-27T00:00:00Z

High levels of von Willebrand factor (VWF) are associated with an increased risk for cardiovascular disease (CVD). Although VWF levels are strongly heritable and genetic susceptibility is an important risk factor for CVD, information on the contribution of common VWF gene variants to VWF levels and CVD risk is limited. In a case-control study of 421 young patients with a first event of acute coronary heart disease (CHD) or ischemic stroke (IS), and 409 healthy control participants (men aged ≤ 45 years, women aged ≤ 55 years), 27 haplotypetagging single-nucleotide polymorphisms (ht-SNPs), covering the total common VWF gene variation, were selected and genotyped. The associations between these SNPs, VWF antigen (VWF:Ag) levels, VWF collagen-binding (VWF:CB) activity, and CVD risk was investigated. Two new associations were identified. For ht-SNP rs4764478 (intron 45), the increase in VWF:Ag levels and VWF:CB activity per minor allele was 0.082 (± 0.026) IU/mL (P = .001) and 0.096 (± 0.030) IU/mL (P = .002), respectively. ht-SNP rs216293 (intron 17) was associated with CVD risk (odds ratio, 1.44; 95% confidence interval [CI], 1.12-1.86 per minor allele). We confirmed the association between rs1063857 and CVD risk. Our data show that common variants in the VWF gene are associated with VWF levels and with the risk for CVD.

Effect of genetic variations in syntaxin-binding protein-5 and syntaxin-2 on von willebrand factor concentration and cardiovascular risk (Article)

2010-12-01T00:00:00Z

Background - Elevated von Willebrand factor (VWF) plasma levels are associated with an increased risk of cardiovascular disease. A meta-analysis of genomewide association studies on VWF identified novel candidate genes, that is, syntaxin-binding protein 5 (STXBP5) and syntaxin 2 (STX2), which are possibly involved in the secretion of VWF. We investigated whether VWF antigen levels (VWF:Ag), VWF collagen-binding activity (VWF:CB) and the risk of arterial thrombosis are affected by common genetic variations in these genes. Methods and Results - In 463 young white subjects (men ≤45 years of age and women ≤55 years of age), who were included 1 to 3 months after a first event of arterial thrombosis, and 406 control subjects, we measured VWF:Ag and VWF:CB. Nine haplotype tagging single-nucleotide polymorphisms of STXBP5 and STX2 were selected and subsequently analyzed using linear regression with additive genetic models adjusted for age, sex, and ABO blood group. The minor alleles of rs9399599 and rs1039084 in STXBP5 were associated with lower VWF plasma levels and activity, whereas the minor allele of rs7978987 in STX2 was associated with higher VWF plasma levels and activity. The minor alleles of the single-nucleotide polymorphisms in STX2 were associated with a reduced risk of arterial thrombosis (rs1236: odds ratio, 0.73 [95% confidence interval, 0.59, 0.89]; rs7978987: odds ratio, 0.81 [95% confidence interval, 0.65, 1.00]; rs11061158: odds ratio, 0.69 [95% confidence interval, 0.55, 0.88]). Conclusions-Genetic variability in STXBP5 and STX2 affects both VWF concentration and activity in young individuals with premature arterial thrombosis. Furthermore, in our study, genetic variability in STX2 is associated with the risk of arterial thrombosis. However, at this point, the underlying mechanism remains unclear.

Lifetime health effects and medical costs of integrated stroke services - a non-randomized controlled cluster-trial based life table approach (Article)

2010-11-17T00:00:00Z

Background: Economic evaluation of stroke services indicates that such services may lead to improved quality of life at affordable cost. The present study assesses lifetime health impact and cost consequences of stroke in an integrated service setting.Methods: The EDISSE study is a prospective non-randomized controlled cluster trial that compared stroke services (n = 151 patients) to usual care (n = 187 patients). Health status and cost trial-data were entered in multi-dimensional stroke life-tables. The tables distinguish four levels of disability which are defined by the modified Rankin scale. Quality-of-life scores (EuroQoL-5D), transition and survival probabilities are based on concurrent Dutch follow-up studies. Outcomes are quality-adjusted life years lived and lifetime medical cost by disability category. An economic analysis compares outcomes from a successful stroke service to usual care, by bootstrapping individual costs and effects data from patients in each arm.Results: Lifetime costs and QALYs after stroke depend on age-of-onset of first-ever stroke. Lifetime QALYs after stroke are 2.42 (90% CI - 0.49 - 2.75) for male patients in usual care and 2.75 (-0.61; 6.26) for females. Lifetime costs for men in the usual care setting are €39,335 (15,951; 79,837) and €42,944 (14,081; 95,944) for women. A comparison with the stroke service results in an ICER of €11,685 saved per QALY gained (€14,211 and €7,745 for men and women respectively). This stroke service is with 90% certainty cost-effective.Conclusions: Our analysis shows the potential of large health benefits and cost savings of stroke services, taking a lifetime perspective, also in other European settings.

Prevention with low-dose aspirin plus dipyridamole in patients with disabling stroke (Article)

2010-11-01T00:00:00Z

Background and Purpose: The combination of low-dose aspirin and dipyridamole is more effective than aspirin alone in reducing the risk of recurrent stroke and other major cardiovascular events in patients with a recent transient ischemic attack or minor stroke. It is unknown whether this also applies to patients with a disabling stroke. Methods: We reanalyzed the data of 5700 patients from ESPRIT and ESPS-2 to study the effect of aspirin and dipyridamole according to modified Rankin scale (mRS) score at baseline. Primary outcome was vascular events (stroke, myocardial infarction, or vascular death). We used proportional hazards regression to estimate the treatment effect across mRS strata at baseline, and we tested for interactions with treatment. Results: In total, 426 patients (7.5%) had mRS score of 4 or 5 at baseline. The risk of an outcome event increased with mRS score. The relative risk associated with the combination of aspirin and dipyridamole compared to aspirin alone in patients with mRS score 0 to 5 was 0.79 (95% confidence interval, 0.69-0.91). The relative risk according to mRS subcategory score 0 to 4 at baseline varied between 0.73 and 0.96 for vascular events and between 0.62 and 0.96 for stroke. The number of patients with mRS score 5 was too small for reliable estimates, but the data suggest a beneficial effect. There was no evidence of interaction between treatment effect and mRS score at baseline. CONCLUSION-: The beneficial effect of the combination of low-dose aspirin and dipyridamole was present in all subcategories of the mRS score.

Microstructural brain injury in post-concussion syndrome after minor head injury (Article)

2010-10-06T00:00:00Z

Introduction: After minor head injury (MHI), post-concussive symptoms commonly occur. The purpose of this study was to correlate the severity of post-concussive symptoms in MHI patients with MRI measures of microstructural brain injury, namely mean diffusivity (MD) and fractional anisotropy (FA), as well as the presence of microhaemorrhages. Methods: Twenty MHI patients and 12 healthy controls were scanned at 3 T using diffusion tensor imaging (DTI) and high-resolution gradient recalled echo (HRGRE) T2*-weighted sequences. One patient was excluded from the analysis because of bilateral subdural haematomas. DTI data were preprocessed using Tract Based Spatial Statistics. The resulting MD and FA images were correlated with the severity of post-concussive symptoms evaluated with the Rivermead Postconcussion Symptoms Questionnaire. The number and location of microhaemorrhages were assessed on the HRGRE T2*-weighted images. Results: Comparing patients with controls, there were no differences in MD. FA was decreased in the right temporal subcortical white matter. MD was increased in association with the severity of post-concussive symptoms in the inferior fronto-occipital fasciculus (IFO), the inferior longitudinal fasciculus and the superior longitudinal fasciculus. FA was reduced in association with the severity of post-concussive symptoms in the uncinate fasciculus, the IFO, the internal capsule and the corpus callosum, as well as in the parietal and frontal subcortical white matter. Microhaemorrhages were observed in one patient only. Conclusions: The severity of post-concussive symptoms after MHI was significantly correlated with a reduction of white matter integrity, providing evidence of microstructural brain injury as a neuropathological substrate of the post-concussion syndrome.

Efficacy of early cognitive-linguistic treatment and communicative treatment in aphasia after stroke: A randomised controlled trial (RATS-2) (Article)

2010-10-01T00:00:00Z

Background: The two main approaches in aphasia treatment are cognitive-linguistic treatment (CLT), aimed at restoring the linguistic levels affected, semantics, phonology or syntax, and communicative treatment, aimed at optimising information transfer by training compensatory strategies and use of residual language skills. The hypothesis that CLT is more effective than communicative treatment in the early stages after stroke was tested in this study. Methods: In this multicentre, randomised, parallel group trial with blinded outcome assessment, 80 patients with aphasia after stroke were included within 3 weeks post-stroke. Patients received 6 months of CLT, comprising semantic and/or phonological training, or communicative treatment for at least 2 h per week. They were assessed before treatment and at 3 and 6 months with the Amsterdam-Nijmegen Everyday Language Test (ANELT-A, primary outcome) and semantic and phonological tests (secondary outcomes). The intervention effect was evaluated by means of analysis of covariance, with adjustment for baseline scores. Results: There was no difference between the mean ANELT-A score of the CLT group (n=38) and the communicative treatment group (n=42), at 3 months (adjusted difference 1.5, 95% CI -2.6 to 5.6) or at 6 months (adjusted difference 1.6, 95% CI -2.3 to 5.6) post-stroke. On two of six specific semantic and phonological tests, the mean scores differed significantly, both in favour of CLT. Conclusion: This study does not confirm the hypothesis that patients with aphasia after stroke benefit more from CLT, aimed at activation of the underlying semantic and phonologic processes, than from general, non-specific communicative treatment (ISRCTN67723958 Current Controlled Trials).

Prediction of major vascular events in patients with transient ischemic attack or ischemic stroke: A comparison of 7 models (Article)

2010-10-01T00:00:00Z

Background And Purpose-: In patients with a recent TIA or minor stroke, prediction of long-term risk of major vascular events is important, but difficult. We aimed to study the external validity of currently available prediction models. Methods-: We validated predictions from 3 population-based models (Framingham, SCORE, and INDIANA project) and 4 stroke cohort-based models (Stroke Prognosis Instrument II, Oxford TIA, Dutch TIA study, and the ABCD study) in an independent cohort of patients with a recent TIA or minor stroke. The validation cohort consisted of 592 patients with TIA or minor stroke, with a mean follow-up of 2 years. The primary outcome was the 2-year risk of the composite outcome event of nonfatal stroke, myocardial infarction, or vascular death. We used calibration graphs and c-statistics to evaluate the 7 models. Results-: The 2-year risk of the primary outcome event was 12%. Calibration was adequate for stroke population-based studies. After adjustment for baseline risk and for prevalence of risk factors, calibration was adequate for the Dutch TIA, the ABCD, and Stroke Prognosis Instrument II models. Discrimination ranged from 0.61 to 0.68. Conclusions-: Discrimination was poor for all currently available risk prediction models for patients with a recent TIA or minor stroke, indicating the need for stronger predictors. Clinical usefulness may be best for the ABCD model, which had a limited number of easily obtainable variables, a reasonable c-statistic (0.64), and good calibration.

A review of hereditary and acquired coagulation disorders in the aetiology of ischaemic stroke (Article)

2010-10-01T00:00:00Z

The diagnostic workup in patients with ischaemic stroke often includes testing for prothrombotic conditions. However, the clinical relevance of coagulation abnormalities in ischaemic stroke is uncertain. Therefore, we reviewed what is presently known about the association between inherited and acquired coagulation disorders and ischaemic stroke, with a special emphasis on the methodological aspects. Good-quality data in this field are scarce, and most studies fall short on epidemiological criteria for causal inference. While inherited coagulation disorders are recognised risk factors for venous thrombosis, there is no substantial evidence for an association with arterial ischaemic stroke. Possible exceptions are the prothrombin G20210A mutation in adults and protein C deficiency in children. There is proof of an association between the antiphospholipid syndrome and ischaemic stroke, but the clinical significance of isolated mildly elevated antiphospholipid antibody titres is unclear. Evidence also suggests significant associations of increased homocysteine and fibrinogen concentrations with ischaemic stroke, but whether these associations are causal is still debated. Data on other acquired coagulation abnormalities are insufficient to allow conclusions regarding causality. For most coagulation disorders, a causal relation with ischaemic stroke has not been definitely established. Hence, at present, there is no valid indication for testing all patients with ischaemic stroke for these conditions. Large prospective population-based studies allowing the evaluation of interactive and subgroup effects are required to appreciate the role of coagulation disorders in the pathophysiology of arterial ischaemic stroke and to guide the management of individual patients. © 2010 The Authors. Journal compilation

Suspected carotid artery stenosis: Cost-effectiveness of CT angiography in work-up of patients with recent TIA or minor ischemic stroke (Article)

2010-08-01T00:00:00Z

Purpose: To assess the effectiveness and cost-effectiveness of state-of-the-art noninvasive diagnostic imaging strategies in patients with a transient ischemic attack (TIA) or minor stroke who are suspected of having carotid artery stenosis (CAS). Materials and Methods: All prospectively evaluated patients provided informed consent, and the local ethics committee approved this study. Diagnostic performance, treatment, long-term events, quality of life, and costs resulting from strategies employing duplex ultrasonography (US), computed tomographic (CT) angiography, contrast material-enhanced magnetic resonance (MR) angiography, and combinations of these modalities were modeled in a decision tree and Markov model. Data sources included a prospective diagnostic cohort study, a meta-analysis, and a review of the literature. Outcomes were costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios, and net health benefits (QALY-equivalents), with a willingness-to-pay threshold of €50 000 per QALY and a societal perspective. The strategy with the highest net health benefit was considered the most cost effective. Extensive one-way, two-way, and probabilistic sensitivity analyses to explore the effect of varying parameter values were performed. The reference case analysis assumed that patients underwent surgery 2-4 weeks after the first symptoms, and the effect of earlier intervention was explored. Results: The reference case analysis showed that duplex US combined with CT angiography and surgery for 70%-99% stenoses was the most cost-effective strategy, with a net health benefit of 13.587 and 15.542 QALY-equivalents in men and women, respectively. In men, the CT angiography strategy with a 70%-99% cutoff yielded slightly more QALYs, at an incremental cost of €71 419 per QALY, compared with duplex US combined with CT angiography. In patients with a high-risk profile, in patients with a high prior probability of disease, and when patients could be treated within 2 weeks after the first symptoms, the CT angiography strategy with surgery for 50%-99% stenoses was the most cost-effective strategy. Conclusion: In diagnosing CAS, duplex US should be the initial test, and, if its results are positive, CT angiography should be performed; patients with 70%-99% stenoses should then undergo carotid endarterectomy. In patients with a high-risk profile, a high probability of CAS, or who can undergo surgery without delay, immediate CT angiography and surgery for 50%-99% stenoses is indicated.

Screening for coagulation disorders in patients with ischemic stroke (Article)

2010-08-01T00:00:00Z

The role of coagulation disorders in the pathogenesis of (recurrent) ischemic stroke is uncertain. Therefore, the clinical utility of screening patients with ischemic stroke for these conditions and the therapeutic implications of a detected coagulation disorder in a patient who experienced ischemic stroke are uncertain. We reviewed the currently available data on the relationship between various inherited and acquired coagulation abnormalities (factor V Leiden and prothrombin G20210A mutations, deficiencies of protein C, protein S and anti-thrombin, hyperhomocysteinemia, the antiphospholipid syndrome and increased levels of fibrinogen) and ischemic stroke. Based on the existing evidence we discuss the usefulness of screening stroke patients for prothrombotic conditions and current recommendations regarding the optimal management of ischemic stroke patients in whom a coagulation disorder is found.

Predictive value of the NIHSS for ADL outcome after ischemic hemispheric stroke: Does timing of early assessment matter? (Article)

2010-07-15T00:00:00Z

Background and purpose: Early prediction of future functional abilities is important for stroke management. The objective of the present study was to investigate the predictive value of the 13-item National Institutes of Health Stroke Scale (NIHSS), measured within 72 h after stroke, for the outcome in terms of activities of daily living (ADL) 6 months post stroke. The second aim was to examine if the timing of NIHSS assessment during the first days post stroke affects the accuracy of predicting ADL outcome 6 months post stroke. Methods: Baseline characteristics including neurological deficits were measured in 188 stroke patients, using the 13-item NIHSS, within 72 h and at 5 and 9 days after a first-ever ischemic hemispheric stroke. Outcome in terms of ADL dependency was measured with the Barthel Index (BI) at 6 months post stroke. The area under the curve (AUC) from the receiver operating characteristic (ROC) was used to determine the discriminative properties of the NIHSS at days 2, 5 and 9 for outcome of the BI. In addition, at optimal cut-off odds ratio (OR), sensitivity, specificity, positive (PPV) and negative predicted values (NPV) for the different moments of NIHSS assessment post stroke were calculated. Results: One hundred and fifty-nine of the 188 patients were assessed at a mean of 2.2 (1.3), 5.4 (1.4) and 9.0 (1.8) days after stroke. Significant Spearman rank correlation coefficients were found between BI at 6 months and NIHSS scores on days 2 (rs= 0.549, p < 0.001), 5 (rs= 0.592, p < 0.001) and 9 (rs= 0.567, p < 0.001). The AUC ranged from 0.789 (95%CI, 0.715-0.864) for measurements on day 2 to 0.804 (95%CI, 0.733-0.874) and 0.808 (95%CI, 0.739-0.877) for days 5 and 9, respectively. Odds ratio's ranged from 0.143 (95%CI, 0.069-0.295) for assessment on day 2 to a maximum of 0.148 (95%CI, 0.073-0.301) for day 5. The NPV gradually increased from 0.610 (95%CI, 0.536-0.672) for assessment on day 2 to 0.679 (95%CI, 0.578-0.765) for day 9, whereas PPV declined from 0.810 (95%CI, 0.747-0.875) for assessment on day 2 to 0.767 (95%CI, 0.712-0.814) for day 9. The overall accuracy of predictions increased from 71.7% for assessment on day 2 to 73.6% for day 9. Conclusions: When measured within 9 days, the 13-item NIHSS is highly associated with final outcome in terms of BI at 6 months post stroke. The moment of assessment beyond 2 days post stroke does not significantly affect the accuracy of prediction of ADL dependency at 6 months. The NIHSS can therefore be used at acute hospital stroke units for early rehabilitation management during the first 9 days post stroke, as the accuracy of prediction remained about 72%, irrespective of the moment of assessment.

Statin treatment after a recent TIA or stroke: Is effectiveness shown in randomized clinical trials also observed in everyday clinical practice? (Article)

2010-07-01T00:00:00Z

Aim and background - The benefit of statin treatment in patients with a previous ischemic stroke or transient ischemic attack (TIA) has been demonstrated in randomized clinical trials (RCT). However, the effectiveness in everyday clinical practice may be decreased because of a different patient population and less controlled setting. We aim to describe statin use in an unselected cohort of patients, identify factors related to statin use and test whether the effect of statins on recurrent vascular events and mortality observed in RCTs is also observed in everyday clinical practice. Methods - In 10 centers in the Netherlands, patients admitted to the hospital or visiting the outpatient clinic with a recent TIA or ischemic stroke were prospectively and consecutively enrolled between October 2002 and May 2003. Statin use was determined at discharge and during follow-up. We used logistic regression models to estimate the effect of statins on the occurrence of vascular events (stroke or myocardial infarction) and mortality within 3 years. We adjusted for confounders with a propensity score that relates patient characteristics to the probability of using statins. Results - Of the 751 patients in the study, 252 (34%) experienced a vascular event within 3 years. Age, elevated cholesterol levels and other cardiovascular risk factors were associated with statin use at discharge. After 3 years, 109 of 280 (39%) of the users at discharge had stopped using statins. Propensity score adjusted analyses showed a beneficial effect of statins on the occurrence of the primary outcome (odds ratio 0.8, 95% CI: 0.6-1.2). Conclusion - In our study, we found poor treatment adherence to statins. Nevertheless, after adjustment for the differences between statin users and non-statin users, the observed beneficial effect of statins on the occurrence of vascular events within 3 years, although not statistically significant, is compatible with the effect observed in clinical trials. Copyright

Atherosclerotic plaque ulceration in the symptomatic internal carotid artery is associated with nonlacunar ischemic stroke (Article)

2010-06-01T00:00:00Z

Background and Purpose: Atherosclerotic carotid plaque ulceration is considered a marker of previous plaque rupture and subsequent thromboembolism. It can be accurately detected with multidetector CTA. We hypothesized that atherosclerotic plaque ulceration is associated with nonlacunar ischemic stroke rather than lacunar stroke. Methods: Prospectively, 750 consecutive patients with transient ischemic attack or ischemic stroke symptoms in the anterior cerebral circulation were evaluated for the presence of atherosclerotic plaque ulceration in the symptomatic carotid artery with multidetector CTA. Patients with stroke attributable to cardiac embolism or other specific etiologies and patients with amaurosis fugax were excluded. Ischemic strokes in the remaining 534 patients were classified as nonlacunar (n≤236) or lacunar (n≤298) based on clinical symptoms and multidetector CT of the brain. Ulceration was defined as extension of contrast material beyond the vascular lumen into the surrounding plaque. RESULTS: Plaque ulceration in the symptomatic carotid artery was more common in nonlacunar strokes (n≤47; 20%) as compared to lacunar strokes (n≤20; 7%; P<0.001). After adjustment for age, gender, cardiovascular risk factors, and degree of stenosis, ulcerations were independently associated with nonlacunar stroke compared to lacunar stroke (odds ratio, 2.70; 95% confidence interval, 1.43-5.09). Conclusions: Atherosclerotic carotid plaque ulceration is associated with nonlacunar ischemic stroke, independent of the degree of carotid stenosis. These results suggest that nonlacunar stroke and lacunar stroke are caused by different pathophysiological mechanisms.

Variation in the C-reactive protein gene is associated with serum levels of CRP in patients with acute ischemic stroke (Article)

2010-03-01T00:00:00Z

Background and Purpose: Elevated levels of C-reactive protein (CRP) are found in up to three quarters of patients with acute ischemic stroke and are associated with poor outcome. We investigated whether haplotypes representing common variations in the CRP gene are associated with levels of CRP in patients with acute ischemic stroke. Methods: We included 185 patients with ischemic stroke in whom CRP was measured within 24 h of symptom onset. Common haplotypes within the CRP gene were determined by 3 genotype-tagging single-nucleotide polymorphisms (SNPs). Results: Four haplotypes with frequencies >5% covered 99.2% of the genetic variation. Haplotype 4 (CCG, frequency 8.3%) was associated with a 20.6 mg/l (95% CI, 9.8-30.4) stronger increase in CRP level as compared with haplotype 1 (CTC, frequency 33.7%). Conclusion: Variation in the CRP gene is associated with levels of CRP in acute ischemic stroke. Copyright

Minor head injury: CT-based strategies for management--a cost-effectiveness analysis (Article)

2010-02-01T00:00:00Z

Purpose: To compare the cost-effectiveness of using selective computed tomographic (CT) strategies with that of performing CT in all patients with minor head injury (MHI). Materials and methods: The internal review board approved the study; written informed consent was obtained from all interviewed patients. Five strategies were evaluated, with CT performed in all patients with MHI; selectively according to the New Orleans criteria (NOC), Canadian CT head rule (CCHR), or CT in head injury patients (CHIP) rule; or in no patients. A decision tree was used to analyze short-term costs and effectiveness, and a Markov model was used to analyze long-term costs and effectiveness. n-Way and probabilistic sensitivity analyses and value-of-information (VOI) analysis were performed. Data from the multicenter CHIP Study involving 3181 patients with MHI were used. Outcome measures were first-year and lifetime costs, quality-adjusted life-years, and incremental cost-effectiveness ratios. Results: Study results showed that performing CT selectively according to the CCHR or the CHIP rule could lead to substantial U.S. cost savings ($120 million and $71 million, respectively), and the CCHR was the most cost-effective at reference-case analysis. When the prediction rule had lower than 97% sensitivity for the identification of patients who required neurosurgery, performing CT in all patients was cost-effective. The CHIP rule was most likely to be cost-effective. At VOI analysis, the expected value of perfect information was $7 billion, mainly because of uncertainty about long-term functional outcomes. Conclusion: Selecting patients with MHI for CT renders cost savings and may be cost-effective, provided the sensitivity for the identification of patients who require neurosurgery is extremely high. Uncertainty regarding long-term functional outcomes after MHI justifies the routine use of CT in all patients with these injuries.

Active von Willebrand factor and the risk of stroke (Article)

2010-02-01T00:00:00Z

Functional Magnetic Resonance Imaging to Determine Hemispheric Language Dominance Prior to Carotid Endarterectomy (Article)

2010-01-01T00:00:00Z

BACKGROUND AND PURPOSE We describe a left-handed patient with transient aphasia and bilateral carotid stenosis. Computed tomography (CT) arteriography showed a 90% stenosis of the right and 30% stenosis of the left internal carotid artery. Head CT and magnetic resonance imaging (MRI) of the brain showed no recent ischemic changes. As only the symptomatic side would require surgical intervention, and because hemispheric dominance for language in left-handed patients may be either left or right sided, a preoperative assessment of hemispheric dominance was required. METHODS We used functional MRI to determine hemispheric dominance for language and hence to establish the indication for carotid endarterectomy surgery. RESULTS Functional MRI demonstrated right hemispheric dominance for language and right-sided carotid endarterectomy was performed. CONCLUSIONS We propose that the clinical use of functional MRI as a noninvasive imaging technique for the assessment of hemispheric language dominance may be extended to the assessment of hemispheric language dominance prior to carotid endarterectomy.

Comparing and ranking hospitals based on outcome: Results from The Netherlands Stroke Survey (Article)

2009-12-11T00:00:00Z

Background: Measuring quality of care and ranking hospitals with outcome measures poses two major methodological challenges: case-mix adjustment and variation that exists by chance. Aim: To compare methods for comparing and ranking hospitals that considers these. Methods: The Netherlands Stroke Survey was conducted in 10 hospitals in the Netherlands, between October 2002 and May 2003, with prospective and consecutive enrolment of patients with acute brain ischaemia. Poor outcome was defined as death or disability after 1 year (modified Rankin scale of >3). We calculated fixed and random hospital effects on poor outcome, unadjusted and adjusted for patient characteristics. We compared the hospitals using the expected rank, a novel statistical measure incorporating the magnitude and the uncertainty of differences in outcome. Results: At 1 year after stroke, 268 of the total 505 patients (53%) had a poor outcome. There were substantial differences in outcome between hospitals in unadjusted analysis (X2= 48, 9 df, P<0.0001). Adjustment for 12 confounders led to halving of the X2(X2= 24). The same pattern was observed in random effects analysis. Estimated performance of individual hospitals changed considerably between unadjusted and adjusted analysis. Further changes were seen with random effect estimation, especially for smaller hospitals. Ordering by expected rank led to shrinkage of the original ranks of 1-10 towards the median rank of 5.5 and to a different order of the hospitals, compared to ranking based on fixed effects. Conclusion: In comparing and ranking hospitals, case-mix-adjusted random effect estimates and the expected ranks are more robust alternatives to traditional fixed effect estimates and simple rankings.

Lower levels of ADAMTS13 are associated with cardiovascular disease in young patients (Article)

2009-11-01T00:00:00Z

ADAMTS13 may play a role in arterial thrombosis by cleaving the highly active and thrombogenic ultralarge Von Willebrand Factor (VWF) multimers into less active VWF multimers. The aim was to investigate the relationship between plasma levels of ADAMTS13, VWF and genetic variation in the ADAMTS13 gene with cardiovascular disease. We performed a case-control study in 374 patients with a first-ever arterial thrombosis before the age of 45 years in males and 55 years in women. We included 218 patients with coronary heart disease (CHD), 109 patients with ischemic stroke (IS) and 47 patients with peripheral arterial disease (PAD) and 332 healthy population-based controls. ADAMTS13 and VWF levels were measured 1-3 months after the event. ADAMTS13 levels were associated with cardiovascular disease (OR antigen 5.1 (95% CI 3.1-8.5, p < 0.001) and OR activity 4.4 (95% CI 2.5-7.5, p < 0.001), in the lowest quartiles). VWF levels were associated with cardiovascular disease (OR antigen 2.1 (95% CI 1.3-3.3, p = 0.001) and OR activity 2.0 (95% CI 1.3-3.1, p = 0.003), in the highest quartile). Patients with combined low ADAMTS13 levels and high VWF levels had an odds ratio of 7.7 (95% CI 3.3-17.7) (p for trend <0.0001). No association was found between genetic variation in the ADAMTS13 gene with levels of ADAMTS13 or with risk of cardiovascular disease. In conclusion, levels of ADAMTS13 and VWF are strongly associated with the risk of cardiovascular disease.

Hospital rates of thrombolysis for acute ischemic stroke: The influence of organizational culture (Article)

2009-10-01T00:00:00Z

Background and Purpose-: The purpose of this study was to determine if organizational culture explains differences in rates of intravenous thrombolysis for acute ischemic stroke between different hospitals. Methods-: A cohort study was done in 12 centers admitting 5515 consecutive patients with acute stroke in The Netherlands. A multilevel logistic regression model was used to relate the likelihood of treatment with thrombolysis to characteristics of the organizational culture of the centers. Organizational culture was defined by 10 characteristics and scored by a panel. A sum score was created by adding all scores and dividing by 10. Results-: Thrombolysis rates varied from 5.7% to 21.7%. We observed an association between thrombolysis and the availability of informal and formal feedback (OR, 1.18; 95% CI, 1.09 to 1.28); a learning culture (OR, 1.12; 95% CI, 1.02 to 1.23); uncompromising, individual clinical leadership (OR, 1.12; 95% CI, 1.03 to 1.23); explicit goals (OR, 1.08; 95% CI, 1.01 to 1.17); and with the sum score (OR, 1.12; 95% CI, 1.02 to 1.23). Conclusions-: Several cultural characteristics of the hospital organization are related to thrombolysis rate. Organizational culture may be an important target for interventions aimed at increasing rates of thrombolysis for acute ischemic stroke in hospitals.

Cooling therapy for acute stroke (Article)

2009-09-18T00:00:00Z

Background: Increased body temperatures are common in patients with acute stroke and are associated with poor outcome. In animal models of focal cerebral ischaemia, temperature-lowering therapy reduces infarct volume. In patients with acute stroke, lowering temperature may therefore improve outcome. This is an update of a Cochrane review first published in 1999. Objectives: To assess the effects of pharmacological and physical strategies to reduce body or brain temperature in patients with acute stroke. Search strategy: We searched the Cochrane Stroke Group trials register (last searched December 2007). In addition, we searched MEDLINE and EMBASE (January 1998 to December 2007). We scanned references and contacted authors of included trials. For the previous version of this review, the authors contacted pharmaceutical companies and manufactures of cooling equipment in this field. Selection criteria: We considered all completed randomised or non-randomised controlled clinical trials, published or unpublished,where pharmacological or physical strategies or both to reduce temperature were applied in patients with acute ischaemic stroke or intracerebral haemorrhage. Outcome measures were death or dependency (modified Rankin Scale score 3) at the end of follow up, and adverse effects. Data collection and analysis: Two review authors independently applied the inclusion criteria, assessed trial quality, and extracted and cross-checked the data. Main results: We included five pharmacological temperature reduction trials and three physical cooling trials involving a total of 423 participants. We found no statistically significant effect of pharmacological or physical temperature-lowering therapy in reducing the risk of death or dependency (odds ratio (OR) 0.9, 95% confidence interval (CI) 0.6 to 1.4) or death (OR 0.9, 95% CI 0.5 to 1.5). Both interventions were associated with a non-significant increase in the occurrence of infections. Authors' conclusions: There is currently no evidence from randomised trials to support routine use of physical or pharmacological strategies to reduce temperature in patients with acute stroke. Large randomised clinical trials are needed to study the effect of such strategies.

Postconcussion syndrome after minor head injury: Brain activation of working memory and attention (Article)

2009-09-15T00:00:00Z

After minor head injury (MHI) postconcussive symptoms (PCS) such as memory and attention deficits frequently occur. It has been hypothesised that PCS are caused by microstructural damage to the brain due to shearing injury, which is not detectable with conventional imaging, and may be responsible for a functional deficit. The purpose of this study was to correlate functional magnetic resonance imaging brain activation of working memory and selective attention with PCS. 21 MHI patients and 12 healthy controls were scanned at 3T. Stimulation paradigms were the n-back and Counting Stroop tasks to engage working memory and selective attention, respectively. Functional data analysis consisted of random effects group analyses, correlating brain activation patterns with the severity of PCS as evaluated with the Rivermead postconcussion symptoms questionnaire. At minimal working memory load, activation was seen in patients with greater severity of PCS in the working memory network. With an increase of working memory load, increase of activation was more pronounced in patients with greater severity of PCS. At high and increased working memory load, activation associated with the severity of PCS was seen in the posterior parietal area, parahippocampal gyrus, and posterior cingulate gyrus. Activation related to selective attention processing was increased with greater severity of PCS. The increased activity in relation to working memory and attention, and the recruitment of brain areas outside the working memory network at high working memory load, may be considered a reflection of the brain's compensatory response to microstructural injury in patients with PCS.

Preventive antibiotics for infections in acute stroke: A systematic review and meta-analysis (Article)

2009-09-01T00:00:00Z

Objective: To provide a systematic overview and meta-analysis of randomized clinical trials evaluating preventive antibiotics in patients with acute stroke. Data Sources: The MEDLINE (1966-February 2009) and Cochrane databases and reference lists of retrieved articles. Study Selection: Randomized controlled trials on preventive antibiotic treatment in stroke. For inclusion, at least case fatality or infection rate had to be recorded. Data Extraction: Each study was scored for methodological key issues and appraised by the Jadad scale. We extracted the data using a predetermined protocol and included all patients who were randomized or who started therapy in an intent-to-treat analysis. Data Synthesis: We identified 4 randomized clinical trials including 426 patients; 94% had ischemic stroke. Study interventions were fluoroquinolones in 2 and tetracycline or a combination of β-lactam antibiotic with β-lactamase inhibitor in 1. Therapy was started within 24 hours of stroke onset. Duration of therapy varied between 3 and 5 days. The methodological quality ranged from 2 to 5 on the Jadad scale, and studies were subject to potential bias. The proportion of patients with infection was significantly smaller in the antibiotic group than in the placebo/control group (32 of 136 [23.5%] vs 53 of 139 [38.1%] patients). The pooled odds ratio for infection was 0.44 (95% confidence interval, 0.23-0.86). Ten of 210 patients (4.8%) in the antibiotic group died, compared with 13 of 216 (6.0%) in the placebo/control group. The pooled odds ratio for mortality was 0.63 (95% confidence interval, 0.22-1.78). No major harm or toxicity was reported. Conclusions: In adults with acute stroke, preventive antibiotics reduced the risk of infection, but did not reduce mortality. The observed effect warrants evaluation of preventive antibiotics in large stroke trials.

Patients Enrolled in Large Randomized Clinical Trials of Antiplatelet Treatment for Prevention After Transient Ischemic Attack or Ischemic Stroke Are Not Representative of Patients in Clinical Practice: the Netherlands Stroke Survey (Article)

2009-08-01T00:00:00Z

Background and Purpose—Many randomized clinical trials have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of new vascular events in patients with a recent transient ischemic attack or ischemic stroke. Evidence from these trials forms the basis for national and international guidelines for the management of nearly all such patients in clinical practice. However, abundant and strict enrollment criteria may limit the validity and the applicability of results of randomized clinical trials to clinical practice. We estimated the eligibility for participation in landmark trials of antiplatelet drugs of an unselected group of patients with stroke or transient ischemic attack from a national stroke survey. Methods—Nine hundred seventy-two patients with transient ischemic attack or ischemic stroke were prospectively and consecutively enrolled in the Netherlands Stroke Survey. We applied 7 large antiplatelet trials’ enrollment criteria. Results—In total, 886 patients were discharged alive and available for secondary prevention. Mean follow-up was 2.5 years. The annual rate of transient ischemic attack, stroke, or nonfatal myocardial infarction was 6.7%. The proportions of patients fulfilling the trial enrollment criteria ranged from 25% to 67%. Mortality was significantly higher in ineligible patients (27% to 41%) than in patients fulfilling enrollment criteria (16% to 20%). Rates of vascular events were not higher in trial-eligible patients than in ineligible patients. Conclusions—Our data confirm that patients with ischemic attack and stroke enrolled in randomized clinical trials are only partially representative of patients in clinical practice. Use of less strict enrollment criteria could enhance “generalizability” and result in more efficient selection of patients for randomized clinical trials. (Stroke. 2009;40:2662-2668.)

Withdrawal of statins and risk of subarachnoid hemorrhage (Article)

2009-08-01T00:00:00Z

BACKGROUND AND PURPOSE-: Vascular endothelium, which can be affected by statins, is believed to play a substantial role in subarachnoid hemorrhage (SAH). Our objective was to estimate the association between use and withdrawal of statins and the risk of SAH. METHODS-: We conducted a population-based case-control study within the PHARMO database. A case was defined as a person hospitalized for SAH (ICD-9-CM code 430) in the period January 1, 1998 to December 31, 2006. Ten randomly chosen controls were matched to each case on age, gender, and calendar date. RESULTS-: During the study period 1004 incident cases of SAH were identified. Current use of statins did not significantly decrease the risk of SAH (OR=0.77, 95% CI 0.55 to 1.07). The odds ratio for recent withdrawal compared to nonusers was 1.62 (95% CI 0.96 to 2.73). Compared to current use, recent withdrawal was associated with an increased risk of SAH (OR=2.34, 95% CI 1.35 to 4.05). Interaction analysis showed that the effect of statin withdrawal was highest in patients who had also recently stopped antihypertensive drugs (OR=6.77, 95% CI 2.10 to 21.8). CONCLUSIONS-: Current use of statins seems to lower the risk of SAH, although the reduction was not significant in new users. Statin withdrawal increased the risk of SAH by a factor 2, even more in patients who had also recently stopped their antihypertensive treatment.

High-dose paracetamol in stroke: new trials are necessary and feasible (Article)

2009-08-01T00:00:00Z

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

2009-07-17T00:00:00Z

Acute ischemic stroke may trigger an inflammatory response that leads to increased levels of C-reactive protein (CRP). High levels of CRP may be associated with poor outcome because they reflect either an inflammatory reaction or tissue damage. We evaluated the prognostic value of CRP within 12 h of onset of ischemic stroke. Levels of CRP were routinely obtained within 12 h of symptom onset in 561 patients with ischemic stroke. CRP values were dichotomized as\\7 or C7 mg/L. The full range of CRP values was used to detect a possible level-risk relationship. We studied the relation between CRP values and poor outcome (modified Rankin Scale score[2) or death at 3 months. A multiple logistic regression model was applied to adjust for age, sex, NIHSS score, current cigarette smoking, diabetes mellitus, hypertension, statin use, and stroke subtype. After adjustment for potential confounders, patients with CRP levels C7 mg/L had a significantly increased risk of poor outcome (adjusted OR 1.6, 95% CI 1.1–2.4) or death (adjusted OR 1.7, 95% CI 1.0–2.9) at 3 months. In addition, the risk of poor outcome or death at 3 months increased with higher levels of CRP. CRP within 12 h of ischemic stroke is an independent prognostic factor of poor outcome at 3 months.

Temperature-lowering therapy for acute stroke (Article)

2009-07-01T00:00:00Z

Reply to: Inadequate Acoustical Temporal Bone Window in Patients with Transient Ischemic Attack or Minor Stroke: Role of Skull Thickness and Bone Density (Article)

2009-07-01T00:00:00Z

The role of thrombin activatable fibrinolysis inhibitor in arterial thrombosis at a young age: The ATTAC study (Article)

2009-05-29T00:00:00Z

Background and objectives: Thrombin activatable fibrinolysis inhibitor (TAFI) attenuates fibrinolysis and may therefore contribute to the pathophysiology of arterial thrombosis. The aim of the present study was to elucidate the pathogenetic role of TAFI levels and genotypes in young patients with arterial thrombosis. Patients and methods: In a case-control study, 327 young patients with a recent first-ever event of coronary heart disease (CHD subgroup) or cerebrovascular disease (ischemic stroke subgroup) and 332 healthy young controls were included. TAFI levels [intact TAFI, activation peptide (TAFI-AP) and (in)activated TAFI (TAFIa(i)] and TAFI activity were measured and genetic variations in the TAFI gene (-438G/A, 505G/A and 1040C/T) were determined. Results: In the total group of patients, TAFIa(i) levels were higher (145.1 ± 37.5%) than in controls (137.5 ± 31.3%, P = 0.02). Plasma levels of intact TAFI, TAFI-AP and TAFI activity were similar in patients and controls. In the CHD subgroup (n = 218), intact TAFI levels were higher (109.4 ± 23.0%) than in controls (102.8 ± 20.7%, P = 0.02). In 325Ile/Ile homozygotes, lower TAFI levels and a decreased risk of arterial thrombosis were observed (OR 0.58, 95% CI 0.34-0.99) compared with patients with the common 325Thr/Thr genotype. This association was most evident in CHD patients (OR 0.48, 95% CI 0.26-0.90). Haplotype analyses supported a role for the Thr325Ile polymorphism. Conclusions: TAFIa(i) levels were higher in patients with cardiovascular disease. Furthermore, the TAFI 325Thr/Ile polymorphism was associated with lower TAFI levels and with the risk of cardiovascular disease in young patients, especially in CHD.

The Paracetamol (Acetaminophen) In Stroke (PAIS) trial: a multicentre, randomised, placebo-controlled, phase III trial (Article)

2009-05-01T00:00:00Z

Background: High body temperature in the first 12-24 h after stroke onset is associated with poor functional outcome. The Paracetamol (Acetaminophen) In Stroke (PAIS) trial aimed to assess whether early treatment with paracetamol improves functional outcome in patients with acute stroke by reducing body temperature and preventing fever. Methods: In a multicentre, randomised, double-blind, placebo-controlled trial, patients with ischaemic stroke or intracerebral haemorrhage and body temperature between 36°C and 39°C were randomly assigned treatment with paracetamol (6 g daily) or placebo within 12 h from symptom onset. Treatment allocation was based on a computer-generated list of random numbers with varying block size. The primary outcome was improvement beyond expectation on the modified Rankin scale at 3 months, according to the sliding dichotomy approach. This trial is registered, number ISRCTN74418480. Findings: Between March, 2003, and May, 2008, 1400 patients were randomly allocated treatment. 260 (37%) of 697 patients receiving paracetamol and 232 (33%) of 703 receiving placebo improved beyond expectation (adjusted odds ratio [OR] 1·20, 95% CI 0·96-1·50). In a post-hoc analysis of patients with baseline body temperature 37-39°C, treatment with paracetamol was associated with improved outcome (1·43, 1·02-1·97). There were 55 serious adverse events in the paracetamol group (8%) and 70 in the placebo group (10%). Interpretation: These results do not support routine use of high-dose paracetamol in patients with acute stroke. Paracetamol might have a beneficial effect on functional outcome in patients admitted with a body temperature 37-39°C, but this post-hoc finding needs further study. Funding: Netherlands Heart Foundation.

Atherosclerotic plaque volume and composition in symptomatic carotid arteries assessed with multidetector CT angiography; relationship with severity of stenosis and cardiovascular risk factors (Article)

2009-04-22T00:00:00Z

The purpose of this study was to examine the volume and the composition of atherosclerotic plaque in symptomatic carotid arteries and to investigate the relationship between these plaque features and the severity of stenosis and the presence of cardiovascular risk factors. One hundred patients with cerebrovascular symptoms underwent CT angiography. We measured plaque volume (PV) and the relative contribution of plaque components (calcifications, fibrous tissue, and lipid) in the symptomatic artery. The contribution of different components was measured as the number of voxels within defined ranges of HU values (calcification >130 HU, fibrous tissue 60-130 HU, lipid core <60 HU). Fifty-seven patients had atherosclerotic plaque in the symptomatic carotid artery. The severity of stenosis and PV were moderately correlated. Age and smoking were independently related to PV. Patients with hypercholesterolemia had significantly less lipid and more calcium in their plaques than patients without hypercholesterolemia. Other cardiovascular risk factors were not significantly related to PV or plaque composition. Luminal stenosis of the carotid artery partly reflects the amount of atherosclerotic carotid disease. Plaque volume and plaque composition are associated with cardiovascular risk factors.

Atherosclerotic plaque surface morphology in the carotid bifurcation assessed with multidetector computed tomography angiography (Article)

2009-04-01T00:00:00Z

Background and Purpose - Complicated (irregular or ulcerated) carotid plaques have proven to be independent predictors of stroke. We analyzed the frequency and location of plaque irregularities in a large cohort of patients with ischemic cerebrovascular disease and the relation with severity of stenosis, cardiovascular risk factors, and symptomatology. Methods - Multidetector CT angiography images from 406 patients were evaluated. Plaque surface morphology was classified as smooth, irregular, or ulcerated. The location of the ulceration was defined as proximal or distal to the point of maximum stenosis. Results - Atherosclerotic plaques with an open lumen were present in 448 carotid arteries; these plaques were classified as: smooth, 276 (62%); irregular, 99 (22%); and ulcerated, 73 (16%). Sixty-two (69%) of the ulcerations were located proximal to the point of maximum luminal stenosis. Complicated plaques were significantly (P<0.001) more common in carotid arteries with stenosis >30% than in those with stenosis <30%. There is an association between complicated plaques and hypercholesterolemia (OR, 3.0) and a trend toward an association with smoking (OR, 1.9). Complicated plaques are more often present in the symptomatic carotid artery than in the contralateral asymptomatic carotid artery; however, this is fully attributed to a significantly higher degree of stenosis in the symptomatic arteries. Conclusions - Multidetector CT angiography allows the classification of atherosclerotic carotid plaque surface. Complicated plaques are frequent in atherosclerotic carotid disease, especially with higher stenosis degree. Ulcerations are mostly located in the proximal part of the atherosclerotic plaque. Hypercholesterolemia and smoking are related with the presence of complicated plaques.

Stroke-associated infection is an independent risk factor for poor outcome after acute ischemic stroke: Data from the netherlands stroke survey (Article)

2009-04-01T00:00:00Z

Background: Infections are a common and serious threat to patients with acute ischemic stroke. The aim of this study was to assess the effect of infection on mortality and functional outcome at discharge and at 1 year. Methods: From a consecutive cohort study in 11 centers, the Netherlands Stroke Survey, we selected 521 patients with ischemic stroke admitted to hospital within 48 h of onset. Stroke-associated infection was defined as infection occurring within 7 days after admission. Poor outcome (modified Rankin score >2) was recorded at discharge and at 1 year. Results: Stroke-associated infection occurred in 78 patients (15%); 39 of these (7.5%) had pneumonia and 23 (4.4%) had urinary tract infection. Overall, 276 patients (53%) had a poor outcome at 1 year. Poor outcome was recorded in 69 patients with stroke-associated infection (88%), and 37 of the 78 patients with stroke-associated infection (47%) had died at 1 year. After adjustment for confounders, stroke-associated infection was associated with poor outcome at discharge [odds ratio (OR) 2.6, 95% confidence interval (CI) 1.0-6.7] and at 1 year (OR 3.8, 95% CI 1.8-8.9). Pneumonia had a stronger association with poor outcome at 1 year (OR 10, 95% CI 2.2-46). Conclusions: This study suggests that stroke-associated infection, in particular pneumonia, is independently associated with poor functional outcome after ischemic stroke.

Hypofibrinolysis is a risk factor for arterial thrombosis at young age (Article)

2009-04-01T00:00:00Z

The relationship between defective fibrinolysis and arterial thrombosis is uncertain. The evaluation of the plasma fibrinolytic potential might provide stronger evidence linking fibrinolysis to arterial thrombosis than the evaluation of the individual fibrinolytic factors. We determined the plasma fibrinolytic potential of 335 young survivors of a first arterial thrombosis, including coronary artery disease (n = 198), ischaemic stroke (n = 103) and peripheral artery disease (n = 34), enrolled in a population-based case-control study and of 330 healthy individuals. Patients had significantly higher clot lysis times (CLTs) than the controls. Odds ratios (ORs) were calculated as a measure of relative risk. The OR for arterial thrombosis was determined in these subjects who had a CLT above the 60th, 70th, 80th, 90th and 95th percentiles of the values found in the control subjects. We found a progressive increase in risk of arterial thrombosis in subjects with hypofibrinolysis (OR: 1·7, 2·0, 2·3, 2·3 and 2·9, respectively). Relative risk estimates obtained in the whole group were comparable those obtained in the event-subgroups. In conclusion, a low plasma fibrinolytic potential, found in 10% of the population, increases the relative risk of arterial thrombosis twofold. This points to an important contribution of hypofibrinolysis to the burden of arterial thrombosis.

A prospective study on coping strategies and quality of life in patients after stroke, assessing prognostic relationships and estimates of cost-effectiveness (Article)

2009-03-01T00:00:00Z

Objective: To examine the prognostic value of coping strategies of patients after stroke at time of discharge on quality of life approximately one year later. In addition, we estimated the maximum cost of improving quality of life by enhancing coping strategies using strict assumptions. Methods: Eighty patients with a stroke completed several questionnaires, at discharge to home and 9-12 months later (follow-up). Questionnaires measured quality of life, coping strategies Tenacious Goal Pursuit and Flexible Goal Adjustment. First, a regression analysis was carried out predicting quality of life at follow-up from coping strategies at discharge. Secondly, a maximum in terms of acceptable cost was calculated for several possible effect sizes. Results: Both coping strategies at discharge were positively associated with quality of life at follow-up. With regards to cost-effectiveness, a medium effect size would result in an increase in quality of life of approximately 10%. The maximum acceptable cost of an intervention for a single patient is therefore set at €2500, assuming a benefit of one year and a cost per quality adjusted life year of €25,000. Conclusion: Coping strategies at discharge are predictive of quality of life one year later. The costs of improving quality of life are thought to be within the limits that determine a cost-effective intervention.

Impact of early surgery after aneurysmal subarachnoid haemorrhage (Article)

2009-02-01T00:00:00Z

Objectives - To investigate the effect of early aneurysm surgery (<72 h) on outcome in patients with subarachnoid haemorrhage (SAH). Materials and methods - We studied two consecutive series of patients with aneurysmal SAH [postponed surgery (PS) cohort, n = 118, 1989-1992: surgery was planned on day 12 and early surgery (ES) cohort, n = 85, 1996-1998: ES was performed only in patients with Glasgow Coma Scale (GCS) >13]. We used multivariable logistic regression analysis to assess outcome at 3 months. Results - Favourable outcome (Glasgow Outcome Scale 4 or 5) was similar in both cohorts. Cerebral ischemia occurred significantly more often in the ES cohort. The occurrence of rebleeds was similar in both cohorts. External cerebrospinal fluid (CSF) drainage was performed more often in the ES cohort (51% vs 19%). Patients with cisternal sum score (CSS) of subarachnoid blood <15 on admission [adjusted odds ratio (OR) for favourable outcome: 6.4, 95% confidence interval (CI) 1.0-39.8] and patients with both CSS <15 and GCS > 12 on admission benefited from the strategy including ES (OR 10.5, 95% CI 1.1-99.4). Conclusions - Our results support the widely adopted practice of ES in good-grade SAH patients.

Improving adherence to guidelines for acute stroke management (Article)

2009-01-13T00:00:00Z

Intracranial internal carotid artery calcifications: Association with vascular risk factors and ischemic cerebrovascular disease (Article)

2009-01-01T00:00:00Z

BACKGROUND AND PURPOSE: Atherosclerotic calcifications are present not only in the extracranial carotid bifurcation but also in the intracranial part of the internal carotid artery. We assessed the association between intracranial internal carotid artery calcifications and cardiovascular risk factors in patients with ischemic cerebrovascular disease and the association between calcifications and the presence of this disease. MATERIALS AND METHODS: Patients undergoing multidetector CT (MDCT) angiography of the carotid arteries for assessment of stenosis degree were included in the study. A semiautomatic custom-made system to quantify calcifications was developed. The associations between the volume of calcifications and cardiovascular risk factors and the type of ischemic cerebrovascular symptoms were assessed with logistic regression. RESULTS: MDCT angiography was performed in 406 patients (age, 62 ± 14 years; 242 men). Men had a significantly higher calcification volume (66 mm3) than women (33 mm3). Calcification volume was positively associated with age in both men and women. Smoking, hypercholesterolemia, and a history of cardiac disease were independently related to the presence of calcifications. A history of cardiac disease and ischemic cerebrovascular disease were independently related to the volume of calcifications. No association was found between calcifications and the presence or type of ischemic cerebrovascular disease in the vascular territory of the intracranial internal carotid artery. CONCLUSIONS: Calcifications were associated with higher age and male gender. The presence and volume of calcifications were independently associated with cardiovascular risk factors. Calcifications were not related to the presence or type of ischemic cerebrovascular disease.

Cooling therapy for acute stroke. (Article)

2009-01-01T00:00:00Z

BACKGROUND: Increased body temperatures are common in patients with acute stroke and are associated with poor outcome. In animal models of focal cerebral ischaemia, temperature-lowering therapy reduces infarct volume. In patients with acute stroke, lowering temperature may therefore improve outcome. This is an update of a Cochrane review first published in 1999. OBJECTIVES: To assess the effects of pharmacological and physical strategies to reduce body or brain temperature in patients with acute stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (last searched December 2007). In addition, we searched MEDLINE and EMBASE (January 1998 to December 2007). We scanned references and contacted authors of included trials. For the previous version of this review, the authors contacted pharmaceutical companies and manufactures of cooling equipment in this field. SELECTION CRITERIA: We considered all completed randomised or non-randomised controlled clinical trials, published or unpublished, where pharmacological or physical strategies or both to reduce temperature were applied in patients with acute ischaemic stroke or intracerebral haemorrhage. Outcome measures were death or dependency (modified Rankin Scale score >/= 3) at the end of follow up, and adverse effects. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the inclusion criteria, assessed trial quality, and extracted and cross-checked the data. MAIN RESULTS: We included five pharmacological temperature reduction trials and three physical cooling trials involving a total of 423 participants. We found no statistically significant effect of pharmacological or physical temperature-lowering therapy in reducing the risk of death or dependency (odds ratio (OR) 0.9, 95% confidence interval (CI) 0.6 to 1.4) or death (OR 0.9, 95% CI 0.5 to 1.5). Both interventions were associated with a non-significant increase in the occurrence of infections. AUTHORS' CONCLUSIONS: There is currently no evidence from randomised trials to support routine use of physical or pharmacological strategies to reduce temperature in patients with acute stroke. Large randomised clinical trials are needed to study the effect of such strategies.

Low protein Z levels but not the protein Z gene G79A polymorphism are a risk factor for ischemic stroke (Article)

2008-12-01T00:00:00Z

Background: Protein Z (PZ) is a vitamin K-dependent plasma protein that plays a role in both pro-and anticoagulant pathways, but its exact physiological function remains unclear. The aim of this study was to determine the association between the G79A PZ gene polymorphism in intron F, PZ levels and the occurrence of ischemic stroke. Methods: We performed a case-control study in 118 Caucasian patients with first ever ischemic stroke or TIA confirmed by CT, and 113 age-and sex-matched population controls. Venous blood samples for PZ levels were collected 7 to 14 days and 3 months after stroke onset. Estimates of relative risk (odds ratios) were adjusted for vascular risk factors. Results: The adjusted relative risk of ischemic stroke associated with PZ levels in the lowest quartile versus the highest quartile was 3.0 (95% CI: 1.1-8.7) at 7-14 days, and 5.1 (95% CI: 1.2-21.9) at 3 months after the stroke. PZ levels in the convalescent sample were significantly lower than in the acute sample. In the convalescent sample, odds ratios increased with lower quartiles of protein Z level (test for trend p = 0.02). Thirty-nine patients (33%) and 32 (28%) controls were heterozygous for the G79A PZ gene polymorphism and 4 (3%) patients and 4 (4%) controls had the AA-genotype. The PZ levels were significantly lower in subjects with the AA-genotype and intermediate in heterozygote subjects. The odds ratio of ischemic stroke associated with A-allele carriers versus GG-homozygotes was 1.2 (95% CI: 0.7-2.1). Conclusion: No association between the G79A PZ gene polymorphism and the occurrence of stroke was observed. However, low PZ levels are independently associated with an increased risk of ischemic stroke.

Strongly increased levels of fibrinogen elastase degradation products in patients with ischemic stroke (Article)

2008-12-01T00:00:00Z

Ischemic stroke is associated with leucocyte activation. Activated leucocytes release elastase, an enzyme that can degrade fibrinogen. Fibrinogen elastase degradation products (FgEDP) may serve as a specific marker of elastase proteolytic activity. In a case-control study of 111 ischemic stroke patients and 119 controls, significantly higher FgEDP levels were observed in cases than in controls, both in the acute phase and in the convalescent phase. Results were only slightly affected by adjustment for cardiovascular risk factors, C-reactive protein and fibrinogen. Our findings suggest that FgEDP might be involved in the pathogenesis of stroke.

Correction: PAIS: paracetamol (acetaminophen) in stroke; protocol for a randomized, double blind clinical trial. [ISCRTN74418480]. (Article)

2008-11-04T00:00:00Z

BACKGROUND: The Paracetamol (Acetaminophen) In Stroke (PAIS) study is a phase III multicenter, double blind, randomized, placebo-controlled clinical trial of high-dose acetaminophen in patients with acute stroke. The trial compares treatment with a daily dose of 6 g acetaminophen, started within 12 hours after the onset of symptoms, with matched placebo. The purpose of this study is to assess whether treatment with acetaminophen for 3 days will result in improved functional outcome through a modest reduction in body temperature and prevention of fever.The previously planned statistical analysis based on a dichotomization of the scores on the modified Rankin Scale (mRS) may not make the most efficient use of the available baseline information. Therefore, the planned primary analysis of the PAIS study has been changed from fixed dichotomization of the mRS to a sliding dichotomy analysis. METHODS: Instead of taking a single definition of good outcome for all patients, the definition is tailored to each individual patient's baseline prognosis on entry into the trial. CONCLUSION: The protocol change was initiated because of both advances in statistical approaches and to increase the efficiency of the trial by improving statistical power. TRIAL REGISTRATION: Current Controlled Trials [ISCRTN74418480].

Transient focal cerebral ischaemia and bilateral pulmonary embolism after desmopressin treatment for von Willebrand's disease (Article)

2008-09-12T00:00:00Z

Inadequate Acoustical Temporal Bone Window in Patients with a Transient Ischemic Attack or Minor Stroke: Role of Skull Thickness and Bone Density (Article)

2008-06-01T00:00:00Z

Transcranial Doppler (TCD) ultrasonography may provide important diagnostic and prognostic information in patients with ischemic stroke or transient ischemic attack. TCD also enhances the effect of thrombolytic treatment in patients with acute stroke. In some patients, especially elderly women, TCD cannot be performed because of temporal bone window failure (WF). We investigated whether skull thickness or bone density on computed tomography scans predicts WF. In 182 patients with a transient ischemic attack or minor ischemic stroke, skull thickness and bone density measurements were made at the level of the temporal bone window. Multiple logistic regression analysis was used to relate independent variables to WF and to adjust the estimates for possible confounding factors. TCD signals were absent on the symptomatic side in 22 female and 11 male patients (18%). Both skull thickness and radiodensity at the level of the temporal bone window were strongly related to WF as well as age and female gender. After adjustment according to age and gender, skull thickness at the temporal bone window was an independent prognostic factor of WF (odds ratio [OR]: 2.3 per mm increase in skull thickness, 95% confidence interval [CI]: 1.4 to 3.8). Radiodensity of the temporal bone decreased with age in women (-52 HU per 10 y over 50 y of age, 95% CI: -73 to -30) but in men (-10 HU per 10 y over 50 y of age, 95% CI: -33 to 13), no statistically significant association was observed. We computed probabilities of WF for each patient individually. With a probability cut point of 50%, 33% of the patients with WF and 97% of the patient without WF were correctly identified. The area under the receiver operating characteristic (ROC) curve of this simple prediction model including age, gender and skull thickness was 0.88; the area under the ROC curve of a gender-stratified model including age, skull thickness and radiodensity was 0.90. This difference was not statistically or clinically significant p = 0.13). WF is more common in women because density of the temporal bone in elderly women is low. Absence of WF can be predicted by a combination of three simple parameters: skull thickness, age and gender. This may help to select patients with ischemic stroke for diagnostic TCD screening and to facilitate targeted delivery of ultrasound-enhanced thrombolysis. (E-mail: a.wijnhoud@erasmusmc.nl).

Epidural blood patch in post dural puncture headache: A randomised, observer-blind, controlled clinical trial (Article)

2008-05-01T00:00:00Z

Objectives: To determine the efficacy of epidural blood patch (EDBP) for the treatment of post dural puncture headache (PDPH). Methods: We randomised 42 patients who presented with PDPH, lasting 24 h to 1 week, to receive EDBP (n = 19) or conservative treatment (n = 23). The primary end point was any headache at 24 h after the start of treatment. Secondary end points were presence and severity of headache after 1 week. Stratified Mantel-Haenzel analysis was used to adjust for confounders. Results: Two patients refused to participate directly after randomisation and allocation to conservative treatment. They were excluded from the study. At 24 h after the start of treatment, headache was present in 11 (58%) patients allocated to EDBP and in 19 (90%) patients allocated to conservative treatment (RR 0.64, 95% CI 0.43 to 0.96). At day 7, headache was present in three (16%) patients allocated to EDBP and in 18 (86%) allocated to conservative treatment (RR 0.18, 95% CI 0.06 to 0.53). Headache was mild in all three EDBP patients, but in 10 of 18 conservatively treated patients who had not recovered by day 7 it was classified as moderate or severe. Adjustments for confounders did not affect these results. Conclusions: EDBP is an effective treatment for PDPH. It offers complete resolution of symptoms in a large proportion of patients. In the remaining patients, it reduces headache severity and allows them to return to their everyday activities.

Assessment of atherosclerotic carotid plaque volume with multidetector computed tomography angiography (Article)

2008-03-31T00:00:00Z

Purpose: The amount of atherosclerotic plaque and its components (calcifications, fibrous tissue, and lipid core) could be better predictors of acute events than the now currently used degree of stenosis. Therefore, we evaluated a dedicated software tool for volume measurements of atherosclerotic carotid plaque and its components in multidetector computed tomography angiography (MDCTA) images. Materials and Methods: Data acquisition was approved by the Institutional Review Board and all patients gave written informed consent. MDCTA images of 56 carotid arteries were analyzed by three observers. Plaque volumes were assessed by manual drawing of the outer vessel contour. The luminal boundary was determined based on a Hounsfield-Unit (HU) threshold. The contribution of different components was measured by the number of voxels within defined ranges of HU-values (calcification >130 HU, fibrous tissue 60-130 HU, lipid core <60 HU). Interobserver variability (IOV) was assessed. Results: Plaque volume was 1,259 ± 621 mm3. The calcified, fibrous and lipid volumes were 238 ± 252 mm3, 647± 277 mm3 and 376± 283 mm3, respectively. IOV was moderate with interclass correlation coefficients (ICC) ranging from 0.76 to 0.99 and coefficients of variation (COV) ranging from 3% to 47%. Conclusion: Atherosclerotic carotid plaque volume and plaque component volumes can be assessed with MDCTA with a reasonable observer variability.

Outcome after Complicated Minor Head Injury (Article)

2008-03-01T00:00:00Z

BACKGROUND AND PURPOSE: Functional outcome in patients with minor head injury with neurocranial traumatic findings on CT is largely unknown. We hypothesized that certain CT findings may be predictive of poor functional outcome. Materials and METHODS: All patients from the CT in Head Injury Patients (CHIP) study with neurocranial traumatic CT findings were included. The CHIP study is a prospective, multicenter study of consecutive patients, > or =16 years of age, presenting within 24 hours of blunt head injury, with a Glasgow Coma Scale (GCS) score of 13-14 or a GCS score of 15 and a risk factor. Primary outcome was functional outcome according to the Glasgow Outcome Scale (GOS). Other outcome measures were the modified Rankin Scale (mRS), the Barthel Index (BI), and number and severity of postconcussive symptoms. The association between CT findings and outcome was assessed by using univariable and multivariable regression analysis. RESULTS: GOS was assessed in 237/312 patients (76%) at an average of 15 months after injury. There was full recovery in 150 patients (63%), moderate disability in 70 (30%), severe disability in 7 (3.0%), and death in 10 (4.2%). Outcome according to the mRS and BI was also favorable in most patients, but 82% of patients had postconcussive symptoms. Evidence of parenchymal damage was the only independent predictor of poor functional outcome (odds ratio = 1.89, P = .022). CONCLUSION: Patients with neurocranial complications after minor head injury generally make a good functional recovery, but postconcussive symptoms may persist. Evidence of parenchymal damage on CT was predictive of poor functional outcome.

Fibrinogen γ′ in ischemic stroke: A case-control study (Article)

2008-03-01T00:00:00Z

BACKGROUND AND PURPOSE - To determine the contribution of fibrinogen γ′ levels and FGG haplotypes to ischemic stroke. METHODS - Associations between fibrinogen γ′ levels, fibrinogen γ′/total fibrinogen ratio, and FGG haplotypes with the risk of ischemic stroke were determined in 124 cases and 125 controls. RESULTS - Fibrinogen γ′/total fibrinogen ratio was higher in patients than in controls during the acute phase of the stroke and lower in the convalescent phase 3 months after the stroke. FGG haplotype 3 (H3) was associated with a reduced risk of ischemic stroke (odds ratio 0.60; 95% CI, 0.38 to 0.94), but not with the fibrinogen γ′/total fibrinogen ratio. In contrast, FGG-H2 was associated with a decreased fibrinogen γ′/total fibrinogen ratio, but not with risk of stroke. CONCLUSIONS - Fibrinogen γ′/total fibrinogen ratio is associated with ischemic stroke, especially in the acute phase of the disease. In addition, FGG-H3 haplotype appears to be protective against ischemic stroke.

Frequency of the von Willebrand factor Tyr1584Cys polymorphism in arterial thrombosis [1] (Article)

2008-03-01T00:00:00Z

Is a fetal origin of the posterior cerebral artery a risk factor for TIA or ischemic stroke? A study with 16-multidetector-row CT angiography (Article)

2008-02-01T00:00:00Z

Background and purpose: Fetal origin of the posterior cerebral artery (PCA) is not uncommon. Whether patients with this anomaly have a higher risk of ischemic stroke in the territory of the PCA is not known. The clinical benefit of screening for a fetal origin in patients with TIA or stroke in the territory of the PCA and an ipsilateral atherosclerotic carotid stenosis is not clear. This study assessed the frequency of a fetal origin of the PCA in patients with a TIA or infarct in the territory of the PCA with 16-multidetector-row CT angiography (CTA). Methods: 82 patients (52 male; mean age = 64; range 19 to 90 years) with isolated homonymous hemianopia and/or a PCA infarct underwent CTA of the carotid artery and circle of Willis. Results: A fetal origin of the PCA at the symptomatic side was present in 14 patients (17 %) and at the asymptomatic side in 18 patients (22%) (OR: 0.7; 95 % CI: 0.3 to 1.7). Severity of stenosis (NASCET criteria) of the ICA at the symptomatic side was < 30%, 30-49% and ≥ 50% in 72, 2 and 8 patients, respectively. Number and frequency of a fetal origin in these groups were 12 (17 %), 0 (0%) and 2 (25 %), respectively. There was no association between a severe carotid stenosis and a fetal origin of the PCA at the symptomatic side. Conclusion: This study does not provide arguments for an increased risk of ischemic stroke in the territory of the PCA in patients with a fetal origin of the PCA. A few patients with a TIA or infarct in the territory of the PCA have a fetal origin of the PCA in combination with a high-grade stenosis of the ipsilateral ICA, but not more often than one would expect from chance. Nevertheless, these patients may benefit from carotid endarterectomy.

Variation between hospitals in patient outcome after stroke is only partly explained by differences in quality of care. Data from the Netherlands Stroke Survey (Article)

2008-01-21T00:00:00Z

Background and purpose:Patient outcome is often used as an indicator of quality of hospital care. The aim of this study is to investigate whether there is a straightforward relationship between quality of care and outcome and whether outcome measures could be used to assess quality of care after stroke. Methods:In 10 centers in the Netherlands, 579 patients with acute ischemic stroke were prospectively and consecutively enrolled. Poor outcome was defined as a score on the modified Rankin scale ≥ 3 at 1 year. Quality of the care was assessed by relating diagnostic, therapeutic and preventive procedures to indication. Multiple logistic regression models were used to compare observed proportions of patients with poor outcome with expected proportions, after adjustment for patient characteristics and quality of care parameters. Results:271 (53%) patients were dead or disabled at 1 year. Poor outcome varied across the centers from 29% to 78%. Large differences between centers were also observed in clinical characteristics, prognostic factors and quality of care. For example, between hospital quartiles based on outcome, age ≥ 70 varied from 50% to 65%, presence of vascular risk factors from 88% to 96%, intravenous fluids when indicated from 35% to 81%, and antihypertensive therapy when indicated from 60% to 85%. The largest part of variation in patient outcome between centers was explained by differences in patient characteristics(Akaike’s Information Criterion (AIC) = 134.0). Quality of care parameters explained a small part of the variation in patient outcome (AIC = 5.5). Conclusions:Patient outcome after stroke varies largely between centers and is for a substantial part explained by differences in patient characteristics at time of hospital admission. Only a small part of the hospital variation in patient outcome is related to differences in quality of care. Unadjusted proportions of poor outcome after stroke are not valid as indicators of quality of care. Keywords: Outcome, Quality of care, Stroke

Methodological quality and publication bias in observational studies on risk of rupture of unruptured intracranial aneurysms (Letter To Editor)

2008-01-01T00:00:00Z

To the Editor: We would like to comment on some aspects of the very interesting updated meta-analysis on risk of rupture of unruptured intracranial aneurysms by Wermer and colleagues.1 First, with regard to the assessment of methodological quality of the included studies, the authors have rated studies as “good” when they fulfilled 3 criteria with regard to design, completeness of follow-up and certainty of diagnosis of subarachnoid hemorrhage. ...

Minor head injury: Guidelines for the Use of CT - A Multicenter Validation Study (Article)

2007-12-01T00:00:00Z

Abstract PURPOSE: To prospectively and externally validate published national and international guidelines for the indications of computed tomography (CT) in patients with a minor head injury. MATERIALS AND METHODS: The study protocol was institutional review board approved. All patients implicitly consented to use of their deidentified data for research purposes. Between February 2002 and August 2004, data were collected in consecutive adult patients with blunt minor head injury (Glasgow Coma Scale score of 13-14 or 15) and a risk factor for neurocranial traumatic complications at presentation at four Dutch university hospitals. Primary outcome was any neurocranial traumatic CT finding. Secondary outcomes were clinically relevant traumatic CT findings and neurosurgical intervention. Sensitivity and specificity of each guideline for all outcomes and the number of patients needed to scan to detect one outcome (ie, the number of patients needed to undergo CT to find one patient with a neurocranial traumatic CT finding, a clinically relevant traumatic CT finding, or a CT finding that required neurosurgical intervention) were estimated. RESULTS: Data were available for 3181 patients. Only the European Federation of Neurological Societies guidelines reached a sensitivity of 100% for all outcomes. Specificity was 0.0%-0.5%. The Dutch guidelines had the lowest sensitivity (76.5%) for neurosurgical interventions. The best specificities for traumatic CT findings and neurosurgical interventions were reached with the criteria proposed by the United Kingdom National Institute for Clinical Excellence (NICE) (46.1% and 43.6%, respectively), albeit at relatively low sensitivities (82.1% and 94.1%, respectively). The number of patients needed to scan ranged from six to 13 for traumatic CT findings and from 79 to 193 for neurosurgical interventions. CONCLUSION: All validated guidelines demonstrated a trade-off between sensitivity and specificity. The lowest number of patients needed to scan for either of the outcomes was reached with the NICE criteria. Supplemental material: radiology.rsnajnls.org/cgi/content/full/2452061509/DC1

Intravenous thrombolysis in acute ischaemic stroke: from trial exclusion criteria to clinical contraindications. An international Delphi study (Article)

2007-07-01T00:00:00Z

OBJECTIVE: Several studies indicate that only a small proportion of patients with acute ischaemic stroke are treated with intravenous thrombolysis. Indications and contraindications for this treatment are usually based on the inclusion and exclusion criteria of randomised clinical trials. The trial context of these criteria hampers implementation in real life settings. We therefore aimed to obtain specialist opinion in a Delphi consensus on these contraindications. METHODS: We used the Delphi approach on an international group of specialists in the field of thrombolysis. Inclusion and exclusion criteria were reworded into 18 quantitatively phrased propositions. Feedback consisted of the median score, interquartile range and the panellist's own score in the previous round. For each item, we defined consensus as the achievement of an interdecile range within two prespecified clinically relevant units. RESULTS: Thirty-one specialists participated in the first round and 30 completed all three rounds. Consensus was reached on 12 of the 18 propositions: previous ischaemic stroke, head trauma and gastrointestinal tract bleeding should not have taken place earlier than 1.5 months, 2 months and 14 days, respectively; the severity of the neurological deficit is defined as a National Institutes of Health Stroke Scale (NIHSS) score of 2-3 or more, and blood pressure level should not be >185/110 mmHg; platelet count should be >90x10(12)/l, glucose levels 2.7-22 mmol/l, international normalised ratio <1.5 and activated partial thromboplastin time <50 s. No consensus was reached on propositions concerning the stroke onset to treatment time, patient's age, recent medical procedures, spontaneous improvement rate and blood pressure treatment. CONCLUSIONS: We present specialists' opinion on contraindications for intravenous thrombolysis in ischaemic stroke. The results of this study may be relevant for routine clinical practice as they may help to increase the number of treated patients.

Cost effectiveness of using computed tomography (CT) for minor head injury compared with several other management strategies (Letter To Editor)

2007-05-01T00:00:00Z

Letters to the editor [1] (Article)

2007-05-01T00:00:00Z

Coping strategies as determinants of quality of life in stroke patients: A longitudinal study (Article)

2007-05-01T00:00:00Z

Background: Quality of life (QoL) is reduced for stroke patients and coping strategies have been suggested as determinants of QoL. Thus far the relationship between coping and QoL has only been examined in small-scale cross-sectional designs. Therefore, the current study set out to examine this relationship in a longitudinal setting. Methods: Stroke patients who were discharged home were interviewed at 4 different time points; just before discharge (T1), and 2 months (T2), 5 months (T3) and 9-12 months after discharge (T4). QoL was measured by the EQ-5D index score and the SF-36 utility score and coping expressed in terms of tenacious goal pursuit and flexible goal adjustment. Modified Rankin scale was assessed as a measure of general functioning. Results: Eighty stroke patients were included. Coping was not predictive of QoL at T1 and T2 but rather at T3 and T4. At T4 both coping strategies determined the levels of QoL as measured with the EQ-5D index score; higher levels of tenacious goal pursuit as well as flexible goal adjustment were associated with higher levels of QoL. This regression model explained 44% of the variance. Conclusions: Coping is a powerful determinant of QoL, but only more than 5 months after discharge; before this time QoL is mainly determined by general functioning. Both coping strategies were important determinants of QoL. Copyright

Knowledge and understanding of disease process, risk factors and treatment modalities in patients with a recent TIA or minor ischemic stroke (Article)

2007-05-01T00:00:00Z

Background: Patients with acute stroke often have a striking lack of knowledge of causes, warning signs, and risk factors. Lack of knowledge may lead to inappropriate secondary prevention behavior. We investigated the knowledge of patients with a TIA or minor stroke about specific aspects of their disease 3 months after the event. Methods: Patients with a TIA or minor stroke who participated in a randomized controlled trial of the effect of health education by an individualized multimedia computer program (IMCP) were included. All patients received information about their disease from their treating neurologist and half of the patients received extra information through the IMCP. The patients' knowledge was tested after 3 months by means of a questionnaire that contained items on pathogenesis, warning signs, vascular diseases, risk factors, lifestyle and treatment. The highest possible score was 71 points. Results: The 57 patients had a mean total score of 41.2 points (SD 10.4) of the maximum 71. Only 15 (26%) correctly identified the brain as the affected organ in stroke and TIA, and only 21 (37%) could give a correct description of a TIA or stroke. In contrast, 80-90% of the patients identified hypertension and/or obesity as vascular risk factors. Knowledge of various treatment modalities of hypertension, hypercholesterolemia and obesity was moderate to high (40-91% adequate responses). Conclusion: The vast majority of patients with TIA or stroke lack specific knowledge about their disease, but they do have a reasonable knowledge of general vascular risk factors and treatment. This suggests that counseling by neurologists of patients with a TIA or stroke can be improved. Copyright

A history of loss of consciousness or post-traumatic amnesia in minor head injury: "conditio sine qua non" or one of the risk factors? (Article)

2007-04-01T00:00:00Z

OBJECTIVE: A history of loss of consciousness (LOC) or post-traumatic amnesia (PTA) is commonly considered a prerequisite for minor head injury (MHI), although neurocranial complications also occur when LOC/PTA are absent, particularly in the presence of other risk factors. The purpose of this study was to evaluate whether known risk factors for complications after MHI in the absence of LOC/PTA have the same predictive value as when LOC/PTA are present. METHODS: A prospective multicentre study was performed in four university hospitals between February 2002 and August 2004 of consecutive blunt head injury patients (> or = 16 years) presenting with a normal level of consciousness and a risk factor. Outcome measures were any neurocranial traumatic CT finding and neurosurgical intervention. Common odds ratios (OR) were estimated for each of the risk factors and tested for homogeneity. RESULTS: 2462 patients were included: 1708 with and 754 without LOC/PTA. Neurocranial traumatic findings on CT were present in 7.5% and were more common when LOC/PTA was present (8.7%). Neurosurgical intervention was required in 0.4%, irrespective of the presence of LOC/PTA. ORs were comparable across the two subgroups (p>0.05), except for clinical evidence of a skull fracture, with high ORs both when LOC/PTA was present (OR = 37, 95% CI 17 to 80) or absent (OR = 6.9, 95% CI 1.8 to 27). LOC and PTA had significant ORs of 1.9 (95% CI 1.0 to 2.7) and 1.7 (95% CI 1.3 to 2.3), respectively. CONCLUSION: Known risk factors have comparable ORs in MHI patients with or without LOC or PTA. MHI patients without LOC or PTA need to be explicitly considered in clinical guidelines.

MDCT detection of fibromuscular dysplasia of the internal carotid artery. (Article)

2007-04-01T00:00:00Z

OBJECTIVE: The purpose of this article is to describe two cases in which fibromuscular dysplasia of the internal carotid artery was diagnosed with CT angiography. CONCLUSIONS: CT angiography can depict the characteristic findings of fibromuscular dysplasia. If patients with cerebrovascular symptoms undergo screening with CT angiography of the supraaortic vessels, more cases of fibromuscular dysplasia will be recognized as a cause of neurologic symptoms.

Predicting Intracranial Traumatic Findings on Computed Tomography in Patients with Minor Head Injury: The CHIP Prediction Rule (Article)

2007-03-01T00:00:00Z

Abstract BACKGROUND: Prediction rules for patients with minor head injury suggest that the use of computed tomography (CT) may be limited to certain patients at risk for intracranial complications. These rules apply only to patients with a history of loss of consciousness, which is frequently absent. OBJECTIVE: To develop a prediction rule for the use of CT in patients with minor head injury, regardless of the presence or absence of a history of loss of consciousness. DESIGN: Prospective, observational study. SETTING: 4 university hospitals in the Netherlands that participated in the CT in Head Injury Patients (CHIP) study. PATIENTS: Consecutive adult patients with minor head injury (> or =16 years of age) with a Glasgow Coma Scale (GCS) score of 13 to 14 or with a GCS score of 15 and at least 1 risk factor. MEASUREMENTS: Outcomes were any intracranial traumatic CT finding and neurosurgical intervention. The authors performed logistic regression analysis by using variables from existing prediction rules and guidelines, with internal validation by using bootstrapping. RESULTS: 3181 patients were included (February 2002 to August 2004): 243 (7.6%) had intracranial traumatic CT findings and 17 (0.5%) underwent neurosurgical intervention. A detailed prediction rule was developed from which a simple rule was derived. Sensitivity of both rules was 100% for neurosurgical interventions, with an associated specificity of 23% to 30%. For intracranial traumatic CT findings, sensitivity and specificity were 94% to 96% and 25% to 32%, respectively. Potential CT reduction by implementing the prediction rule was 23% to 30%. Internal validation showed slight optimism for the model's performance. LIMITATION: External validation of the prediction model will be required. CONCLUSION: The authors propose the highly sensitive CHIP prediction rule for the selective use of CT in patients with minor head injury with or without loss of consciousness.

Therapeutic hypothermia in acute ischemic stroke (Article)

2007-02-01T00:00:00Z

Increased body temperatures are common in the acute phase of stroke. Experimental and clinical studies have suggested that increased body temperatures are related to poor outcome. In animal studies of focal cerebral ischemia, early hypothermia consistently reduced infarct volume. Based on these findings, several Phase II clinical trials have been performed to study physical methods to reduce body temperature in patients with acute stroke. The feasibility and safety of these methods have not yet been established with sufficient certainty. Pharmacological lowering of body temperature may be an attractive alternative approach. In guidelines for the treatment of acute stroke, antipyretics are generally recommended to reduce fever, although their effect on functional outcome is unknown. There is currently no evidence from randomized trials to support routine use of physical or pharmacological cooling in acute stroke. Large randomized clinical trials are needed to study the effect of both physical and medical cooling on functional outcome after stroke.

Effects of an individualized multimedia computer program for health education in patients with a recent minor stroke or transient ischemic attack - A randomized controlled trial (Article)

2007-01-01T00:00:00Z

Background - Transient ischemic attack (TIA) and stroke patients often show a striking lack of knowledge about their disease. We developed a computer program that provided health education fitting the educational level, risk profile and symptoms of patients and evaluated it in a randomized controlled trial. Methods - Transient ischemic attack or minor stroke patients were allocated to health education by a physician (n = 32) or to a combination of education by a physician and the computer program (n = 33). Knowledge was tested by means of a questionnaire at 1 and 12 weeks after inclusion. The maximum possible score was 71 points. Results - Overall knowledge was low - the mean score was 43.6 at 1 week and 42.0 points at 12 weeks for both the groups. The intervention group had slightly better scores at 1 week after using the computer program, 45.4 vs 41.5 (P = 0.09), with the difference increasing to 4.3 points after (post-hoc) adjustment for age and level of education (P = 0.06). After 12 weeks, the score in the intervention group dropped significantly to 42.0 points (P = 0.05), and was no longer different from the standard group Conclusion - This study did not show a lasting effect of health education by an individualized computer program on the knowledge of TIA and minor stroke patients.

Impaired glucose tolerance increases stroke risk in nondiabetic patients with transient ischemic attack or minor ischemic stroke (Article)

2006-06-01T00:00:00Z

BACKGROUND AND PURPOSE: Impaired glucose tolerance, an intermediate metabolic state between normal glucose and diabetes characterized by nonfasting glucose levels between 7.8 to 11.0 mmol/L, is associated with an increased stroke risk in patients with coronary heart disease. Whether impaired glucose tolerance increases the risk of stroke in patients with transient ischemic attack (TIA) or minor ischemic stroke is unknown. METHODS: In total, 3127 patients with a TIA or minor ischemic stroke participated in the Dutch TIA Trial, testing 2 different doses of aspirin and atenolol versus placebo. We estimated the risk of stroke and the risk of myocardial infarction or cardiac death in relation to baseline nonfasting glucose levels (mean 6.0, SD 2.2 mmol/L) with Cox proportional hazards regression analysis, adjusted for cardiovascular risk factors. RESULTS: During 2.6 years follow-up, 272 patients (9%) experienced a stroke and 200 (6%) a myocardial infarction or cardiac death. We found a J-shaped relationship between baseline nonfasting glucose levels and stroke risk. Stroke risk was nearly doubled in patients with impaired glucose tolerance (glucose 7.8 to 11.0 mmol/L) compared with those with normal glucose levels (hazard ratio [HR] 1.8, 95% CI, 1.1 to 3.0) and nearly tripled in diabetic patients (glucose > or =11.1 mmol/L; HR 2.8, 95% CI, 1.9 to 4.1). Patients with low glucose levels (<4.6 mmol/L) had a 50% increased stroke risk (HR 1.5, 95% CI, 1.0 to 2.2) compared with those with normal glucose levels. There was no association between glucose levels and risk of myocardial infarction or cardiac death. CONCLUSIONS: Impaired glucose tolerance is an independent risk factor for future stroke in nondiabetic patients with TIA or minor ischemic stroke.

CT scanning for minor head injury (Letter To Editor)

2006-02-01T00:00:00Z

External validation of the Canadian CT Head Rule and the New Orleans Criteria for CT scanning in patients with minor head injury. (Article)

2005-09-28T00:00:00Z

CONTEXT: Two decision rules for indications of computed tomography (CT) in patients with minor head injury, the Canadian CT Head Rule (CCHR) and the New Orleans Criteria (NOC), suggest that CT scanning may be restricted to patients with certain risk factors, which would lead to important reductions in the use of CT scans. OBJECTIVE: To validate and compare these 2 published decision rules in Dutch patients with head injuries. DESIGN, SETTING, AND PATIENTS: A prospective multicenter study conducted between February 11, 2002, and August 31, 2004, in 4 university hospitals in the Netherlands of 3181 consecutive adult patients with minor head injury who presented with a Glasgow Coma Scale (GCS) score of 13 to 14 or with a GCS score of 15 and at least 1 risk factor. MAIN OUTCOME MEASURES: Primary outcome was any neurocranial traumatic finding on CT scan. Secondary outcomes were neurosurgical intervention and clinically important CT findings. Sensitivity and specificity were estimated for each outcome for the CCHR and the NOC, using both rules as originally derived and also as adapted to apply to an expanded patient population. RESULTS: Of 3181 patients with a GCS score of 13 to 15, neurosurgical intervention was performed in 17 patients (0.5%); neurocranial traumatic CT findings were present in 312 patients (9.8%). Sensitivity for neurosurgical intervention was 100% for both the CCHR and the NOC. The NOC had a higher sensitivity for neurocranial traumatic findings and for clinically important findings (97.7%-99.4%) than did the CCHR (83.4%-87.2%). Specificities were very low for the NOC (3.0%-5.6%) and higher for the CCHR (37.2%-39.7%). The estimated potential reduction in CT scans for patients with minor head injury would be 3.0% for the adapted NOC and 37.3% for the adapted CCHR. CONCLUSIONS: For patients with minor head injury and a GCS score of 13 to 15, the CCHR has a lower sensitivity than the NOC for neurocranial traumatic or clinically important CT findings, but would identify all cases requiring neurosurgical intervention, and has greater potential for reducing the use of CT scans.

PAIS: paracetamol (acetaminophen) in stroke; protocol for a randomized, double blind clinical trial [ISCRTN 74418480]. (Article)

2005-08-19T00:00:00Z

BACKGROUND: In patients with acute stroke, increased body temperature is associated with large lesion volumes, high case fatality, and poor functional outcome. A 1 degrees C increase in body temperature may double the odds of poor outcome. Two randomized double-blind clinical trials in patients with acute ischemic stroke have shown that treatment with a daily dose of 6 g acetaminophen (paracetamol) results in a small but rapid and potentially worthwhile reduction of 0.3 degrees C (95% CI: 0.1-0.5) in body temperature. We set out to test the hypothesis that early antipyretic therapy reduces the risk of death or dependency in patients with acute stroke, even if they are normothermic. METHODS/DESIGN: Paracetamol (Acetaminophen) In Stroke (PAIS) is a randomized, double-blind clinical trial, comparing high-dose acetaminophen with placebo in 2500 patients. Inclusion criteria are a clinical diagnosis of hemorrhagic or ischemic stroke and the possibility to start treatment within 12 hours from onset of symptoms. The study will have a power of 86% to detect an absolute difference of 6% in the risk of death or dependency at three months, and a power of 72% to detect an absolute difference of 5%, at a 5% significance level. DISCUSSION: This is a simple trial, with a drug that only has a small effect on body temperature in normothermic patients. However, when lowering body temperature with acetaminophen does have the expected effectiveness, 20 patients will have to be treated to prevent dependency or death in one.

Efficacy of the epidural blood patch for the treatment of post lumbar puncture headache BLOPP: a randomised, observer-blind, controlled clinical trial [ISRCTN 71598245]. (Article)

2005-07-05T00:00:00Z

BACKGROUND: Post dural punction headache (PDPH) occurs in 10% to 40% of the patients who had a lumbar puncture. Its symptoms can be severe and incapacitating. The epidural blood patch is widely accepted as the treatment of choice for postdural puncture headache. Uncontrolled studies report rapid recovery after patching in 90% to 100% of treated patients. However, sufficient evidence from randomised, controlled clinical trials is lacking. METHODS: BLOPP (blood patch for post dural puncture headache) is a randomised, single centre, observer-blind clinical trial. Patients with PDPH for at least 24 hours and at most 7 days after lumbar puncture will be randomised to treatment with an epidural blood patch (EDBP) or to conventional treatment, i.e. 24 hours bed rest and ample fluid intake. PDPH 24 hours after treatment, classified on a 4-point scale (no, mild, moderate, severe) is the primary outcome. The secondary outcome is the presence of PDPH 7 days after treatment. We estimated that a sample size of 2 x 20 patients would provide us with a power of 80% to detect a relative reduction in number of patients with persisting PDPH after 24 hours of 50% at the usual significance level alpha = 5%, taking into account that in approximately 10% of the patients the PDPH will have resolved spontaneously after one day. DISCUSSION: The EDBP is accepted as the treatment of choice for PDPH although randomised, controlled data is scarce. Our randomised, observer-blind clinical trial enables us to compare the efficacy of two clinically practiced methods of PDPH treatment; EDBP versus conventional treatment, as they are applied in clinical practise.

The -148 C/T fibrinogen gene polymorphism and fibrinogen levels in ischaemic stroke: a case-control study (Article)

2005-01-01T00:00:00Z

BACKGROUND: To determine whether -148 C/T fibrinogen gene promoter polymorphism increases stroke risk by modifying the fibrinogen level. DESIGN: A case-control study of patients with first ever ischaemic stroke, confirmed by computed tomography. METHODS: Venous blood samples were collected for fibrinogen and routine coagulation tests one week after the stroke, and after three months in about half the patients. Population controls were age and sex matched. -148 C/T fibrinogen polymorphism was determined by polymerase chain reaction followed by digestion with restriction enzymes HindIII/AluI. RESULTS: There were 124 patients and 125 controls, mean age 56 years (range 18 to 75); 34 patients (27%) and 41 controls (33%) were heterozygous for -148 C/T fibrinogen polymorphism; six patients (5%) and five controls (4%) had the T/T genotype. The odds ratio of ischaemic stroke associated with CC homozygotes v T carriers was 0.8 (95% confidence interval, 0.5 to 1.4). Relative risk for ischaemic stroke associated with fibrinogen levels in the highest quartile was 3.9 (1.9 to 8.4) at one week, decreasing to 1.4 (0.6 to 3.3) at three months. CONCLUSIONS: -148 C/T fibrinogen gene polymorphism was not a strong risk factor for ischaemic stroke. High fibrinogen levels early after acute stroke probably represent an acute phase response.

Diagnostic value of the Rotterdam-CAMCOG in post-stroke dementia (Article)

2005-01-01T00:00:00Z

BACKGROUND AND OBJECTIVE: Specific screening tests to detect post-stroke dementia are lacking. We recently reported that an adaptation of the Cambridge Cognitive Examination (CAMCOG), the Rotterdam-CAMCOG, had excellent sensitivity and specificity for detecting post-stroke dementia. In this study, we externally validated the diagnostic accuracy of the R-CAMCOG in a new, representative cohort of stroke patients. METHODS: The R-CAMCOG and an extensive neuropsychological examination were administered, independently of each other, in 121 patients aged 55 and over with a stroke in the preceding three to nine months. The gold standard diagnosis of dementia was based on the results of the extensive neuropsychological examination, clinical presentation, and information from a close relative, as well as DSM-IV criteria. RESULTS: Of the 121 patients, 35 had dementia (29%). The diagnostic accuracy at the pre-specified cut-off point of 33/34 was established through receiver operating characteristic (ROC) analyses (sensitivity 66%, specificity 94%). At a cut-off point of 36/37 sensitivity would be 83% and specificity 78%. CONCLUSION: The R-CAMCOG is a useful screening tool for post-stroke dementia in a clinical setting.

Effects of semantic treatment on verbal communication and linguistic processing in aphasia after stroke: a randomized controlled trial. (Article)

2004-01-01T00:00:00Z

BACKGROUND AND PURPOSE: Semantic deficits, deficits in word meaning, have a large impact on aphasic patients' verbal communication. We investigated the effects of semantic treatment on verbal communication in a randomized controlled trial. METHODS: Fifty-eight patients with a combined semantic and phonological deficit were randomized to receive either semantic treatment or the control treatment focused on word sound (phonology). Fifty-five patients completed pretreatment and posttreatment assessment of verbal communication (Amsterdam Nijmegen Everyday Language Test [ANELT]). In an on-treatment analysis (n=46), treatment-specific effects on semantic and phonological measures were explored. RESULTS: Both groups improved on the ANELT, with no difference between groups in overall score (difference, -1.1; 95% confidence interval [CI], -5.3 to 3.1). After semantic treatment, patients improved on a semantic measure (mean improvement, 2.9; 95% CI, 1.2 to 4.6), whereas after phonological treatment, patients improved on phonological measures (mean improvement, 3.0; 95% CI, 1.4 to 4.7, and 3.0; 95% CI, 1.2 to 4.7). CONCLUSIONS: No differences in primary outcome were noted between the 2 treatments. Our findings challenge the current notion that semantic treatment is more effective than phonological treatment for patients with a combined semantic and phonological deficit. The selective gains on the semantic and phonological measures suggest that improved verbal communication was achieved in a different way for each treatment group.

Effect of paracetamol (acetaminophen) and ibuprofen on body temperature in acute ischemic stroke PISA, a phase II double-blind, randomized, placebo-controlled trial [ISRCTN98608690]. (Article)

2003-02-06T00:00:00Z

BACKGROUND: Body temperature is a strong predictor of outcome in acute stroke. In a previous randomized trial we observed that treatment with high-dose acetaminophen (paracetamol) led to a reduction of body temperature in patients with acute ischemic stroke, even when they had no fever. The purpose of the present trial was to study whether this effect of acetaminophen could be reproduced, and whether ibuprofen would have a similar, or even stronger effect. METHODS: Seventy-five patients with acute ischemic stroke confined to the anterior circulation were randomized to treatment with either 1000 mg acetaminophen, 400 mg ibuprofen, or placebo, given 6 times daily during 5 days. Treatment was started within 24 hours from the onset of symptoms. Body temperatures were measured at 2-hour intervals during the first 24 hours, and at 6-hour intervals thereafter. RESULTS: No difference in body temperature at 24 hours was observed between the three treatment groups. However, treatment with high-dose acetaminophen resulted in a 0.3 degrees C larger reduction in body temperature from baseline than placebo treatment (95% CI: 0.0 to 0.6 degrees C). Acetaminophen had no significant effect on body temperature during the subsequent four days compared to placebo, and ibuprofen had no statistically significant effect on body temperature during the entire study period. CONCLUSIONS: Treatment with a daily dose of 6000 mg acetaminophen results in a small, but potentially worthwhile decrease in body temperature after acute ischemic stroke, even in normothermic and subfebrile patients. Further large randomized clinical trials are needed to study whether early reduction of body temperature leads to improved outcome.

Noninvasive detection of a ruptured aneurysm at a basilar artery fenestration with submillimeter multisection CT angiography (Article)

2003-01-01T00:00:00Z

The criterion standard for the detection of intracranial aneurysms is digital subtraction angiography. MR imaging and CT provide good accuracy in the evaluation of brain arteries and aneurysms. We herein report a case of a ruptured aneurysm at a basilar artery fenestration. The diagnosis was assessed with 16-row multisection CT angiography and was confirmed by using digital subtraction angiography. The patient was successfully treated with coil placement.

PISA. The effect of paracetamol (acetaminophen) and ibuprofen on body temperature in acute stroke: protocol for a phase II double-blind randomised placebo-controlled trial [ISRCTN98608690] (Article)

2002-01-01T00:00:00Z

BACKGROUND: During the first days after stroke, one to two fifths of the patients develop fever or subfebrile temperatures. Body temperature is a strong prognostic factor after stroke. Pharmacological reduction of temperature in patients with acute ischaemic stroke may improve their functional outcome. Previously, we studied the effect of high dose (6 g daily) and low dose (3 g daily) paracetamol (acetaminophen) in a randomised placebo-controlled trial of 75 patients with acute ischemic stroke. In the high-dose paracetamol group, mean body temperature at 12 and 24 hours after start of treatment was 0.4 degrees C lower than in the placebo group. The effect of ibuprofen, another potent antipyretic drug, on body-core temperature in normothermic patients has not been studied. AIM: The aim of the present trial is to study the effects of high-dose paracetamol and ibuprofen on body temperature in patients with acute ischaemic stroke, and to study the safety of these treatments. DESIGN: Seventy-five (3 x 25) patients with acute ischaemic stroke confined to the anterior circulation will be randomised to treatment with either: 400 mg ibuprofen, 1000 mg acetaminophen, or with placebo 6 times daily during 5 days. Body-temperatures will be measured with a rectal electronic thermometer at the start of treatment and after 24 hours. An infrared tympanic thermometer will be used to monitor body temperature at 2-hour intervals during the first 24 hours and at 12-hour intervals thereafter. The primary outcome measure will be rectal temperature at 24 hours after the start of treatment. The study results will be analysed on an intent-to-treat basis, but an on-treatment analysis will also be performed. No formal interim analysis will be carried out.

Effect of paracetamol (acetaminophen) on body temperature in acute ischemic stroke: a double-blind, randomized phase II clinical trial (Article)

2001-01-01T00:00:00Z

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 degrees C lower body temperatures than placebo treatment at 24 hours (95% CI 0.1 degrees C to 0.7 degrees C). The mean reduction from baseline temperature with high-dose acetaminophen was 0.3 degrees C (95% CI 0 degrees C to 0.6 degrees 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.

A short screening instrument for poststroke dementia : the R-CAMCOG (Article)

2000-01-01T00:00:00Z

BACKGROUND AND PURPOSE: The CAMCOG is a feasible cognitive screening instrument for dementia in patients with a recent stroke. A major disadvantage of the CAMCOG, however, is its lengthy and relatively complex administration for screening purposes. We therefore developed the Rotterdam CAMCOG (R-CAMCOG), based on the original version. Our aim was to reduce the estimated administration time to 15 minutes or less and to retain or perhaps even improve its diagnostic accuracy. METHODS: We analyzed the item scores on the CAMCOG of 300 consecutive stroke patients, after exclusion of patients with a severe aphasia or lowered consciousness level, who were entered in the Rotterdam Stroke Databank. The diagnosis of dementia was made independent of the R-CAMCOG score, on the basis of clinical examination and neuropsychological test results. The R-CAMCOG was constructed in 3 steps. First, items with floor and ceiling effects were removed. Next, subscales with no additional diagnostic value were excluded. Finally, we removed items that did not contribute to the homogeneity of the subscales. The diagnostic accuracy of the R-CAMCOG and the original CAMCOG was determined by means of the area under the receiver operating characteristic (ROC) curve. RESULTS: In the 3 steps, the number of items was reduced from 59 to 25, divided over the subscales orientation, memory (recent, remote, and learning), perception, and abstraction. The subscale orientation did not reach significance in a logistic regression model but was included in the R-CAMCOG because of its high face validity in dementia screening. Internal validation with ROC analysis suggests that the R-CAMCOG and the CAMCOG are equally accurate in screening for poststroke dementia (area under the curve was 0.95 for both tests). CONCLUSIONS: The R-CAMCOG has overcome the disadvantages of the original CAMCOG. It is a promising, short, and easy-to-administer screening instrument for poststroke dementia. It seems to be sufficiently accurate for this purpose, but the test has yet to be validated in a separate, independent study.

Increased platelet activation in the chronic phase after cerebral ischemia and intracerebral hemorrhage (Article)

1999-01-01T00:00:00Z

BACKGROUND AND PURPOSE: Enhanced thromboxane (TX) biosynthesis has previously been reported in the acute phase after ischemic stroke. We investigated whether enhanced urinary excretion of 11-dehydro-TXB2, a noninvasive index of platelet activation, was present in the chronic phase after a transient ischemic attack (TIA) or stroke, including intracerebral hemorrhage. METHODS: We obtained a single urinary sample from 92 patients between 3 and 9 months after onset of stroke or TIA. The urinary excretion of the major enzymatic metabolite of TXA2, 11-dehydro-TXB2, was measured by a previously validated radioimmunoassay. The excretion rates were compared with those of 20 control patients with nonvascular neurological diseases. RESULTS: Urinary 11-dehydro-TXB2 averaged 294+/-139, 413+/-419, and 557+/-432 pmol/mmol creatinine for patients with TIA, ischemic stroke, and intracerebral hemorrhage, respectively; the values were higher in all subgroups (P<0.01) than that in control patients (119+/-66 pmol/mmol). Increased 11-dehydro-TXB2 excretion was present in 59% of all patients, in 60% (P<0.001) of patients with TIA, in 56% (P<0.001) of patients with ischemic stroke, and in 73% (P<0.001) of patients with intracerebral hemorrhage. Atrial fibrillation, no aspirin use, and severity of symptoms at follow-up contributed independently to the level of 11-dehydro-TXB2 excretion in a multiple linear regression analysis. CONCLUSIONS: Platelet activation is often present in patients in the chronic phase after stroke, including those with intracerebral hemorrhage. Persistent platelet activation, which is associated with atrial fibrillation and poor stroke outcome, can be substantially suppressed by aspirin treatment.

Leptomeningeal metastasis after surgical resection of brain metastases (Article)

1999-01-01T00:00:00Z

OBJECTIVE: To determine the incidence and risk factors for leptomeningeal metastasis after surgery for brain metastasis of solid tumors. METHODS: Review of the records of all patients operated on for brain metastasis between January 1990 and August 1995. RESULTS: In this period 28 patients underwent surgery for brain metastasis, of whom 27 were available for evaluation in this study. Median survival after craniotomy was 11 months. Nine patients (33%) developed leptomeningeal metastasis 2-13 months after surgery, which included six of the nine patients operated on for posterior fossa metastasis (p=0.05). In five patients, leptomeningeal metastasis was the only site of recurrence. Three patients developed the leptomeningeal metastasis as bulky tumour along the spinal cord, which is a rare presentation. No other risk factors for the development of leptomeningeal metastasis other than surgery for posterior fossa metastasis were identified. CONCLUSIONS: There is an increased risk of leptomeningeal metastasis after surgery for posterior fossa metastasis. Future trials should consider the value of an active approach to this complication in these patients.

The CAMCOG: a useful screening instrument for dementia in stroke patients (Article)

1998-01-01T00:00:00Z

BACKGROUND and PURPOSE: Most mental screening tests focus on the detection of cognitive deficits compatible with Alzheimer's disease. Stroke patients who develop a dementia syndrome, however, constitute a more heterogeneous group with both cortical and subcortical disturbances. We assessed the diagnostic accuracy of the CAMCOG (the cognitive and self-contained part of the Cambridge Examination for Mental Disorders of the Elderly) and the Mini-Mental State Examination (MMSE) for dementia in patients with a recent stroke. METHODS: In patients aged 55 and older who were admitted in the Rotterdam Stroke Databank, cognitive functioning was assessed between 3 and 9 months after the most recent stroke. The "gold standard" diagnosis of dementia was compatible with the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised. The CAMCOG and MMSE scores were obtained independent of the diagnostic procedure. RESULTS: Of 300 consecutive patients, 71 (23.7%) were demented. Sixteen severely demented patients could not be tested and were excluded. The CAMCOG and MMSE scores were significantly related to dementia (both P<0.0001) in a logistic regression model. Receiver operating characteristic analysis showed that the CAMCOG was a more accurate screening instrument (area under the curve for CAMCOG, 0.95; for MMSE, 0.90). Two other clinical variables independently improved the diagnostic accuracy of the MMSE and CAMCOG: patients with a left hemispheric lesion had a lower (odds ratio, 0.3; 95% confidence interval, 0.1 to 0.7), and patients with hemorrhagic stroke had a greater chance of being demented (odds ratio, 3; 95% confidence interval, 1 to 10). The effect of left hemispheric lesion as an independent diagnostic factor could not be explained by selection or its association with aphasia alone. CONCLUSIONS: The CAMCOG is a feasible instrument for use in patients with a recent transient ischemic attack or stroke. It is a more accurate screening tool for dementia than the MMSE, especially when type and site of stroke are taken into account.

Interobserver agreement for 10% categories of angiographic carotid stenosis (Article)

1997-12-01T00:00:00Z

BACKGROUND AND PURPOSE: Although the reliability of the assessment of severe 70% to 99% carotid stenosis by carotid angiography has been proven excellent, this may not necessarily be the case for a more detailed classification of carotid stenoses by 10% categories. METHODS: Angiograms of the carotid arteries were assessed pairwise by three independent, experienced observers. The measurements of the degree of stenosis of both the carotid bifurcation and the internal carotid artery were made according to the European Carotid Surgery Trial method. Kappa statistics were used to assess the agreement beyond chance for severe (70% to 99%) carotid stenosis (kappa 1) and for 10% categories of carotid stenosis (kappa 2). The penalty scores were adjusted by weights for the relative difference in risk (RDR) of stroke in the ipsilateral carotid distribution between the 10% categories (kappa 3). An adjustment of the RDR method was made by assuming that only patients with a severe carotid stenosis would undergo surgery, and the penalty would be 0 if no disagreement would exist about the indication for surgery (kappa 4). An even further adjustment (kappa 5) was made by assuming that assessment of the rate of carotid stenosis by one or both observers would lead to different treatment recommendations in 50% of the cases, and accordingly the penalty for disagreement (RDR) was halved. RESULTS: One hundred twenty-one carotid bifurcations in 65 patients with a transient ischemic attack or nondisabling stroke were assessed. The intraclass correlation between the exact estimates of carotid stenosis was .90 (95% confidence interval, .85 to .92). The mean difference in stenosis between the two raters was 0.8% (95% confidence interval, -2.1% to 3.7%). kappa 1 to kappa 5 equaled 0.80, 0.40, 0.79, 0.91, and 0.92, respectively. CONCLUSIONS: Interobserver agreement for distinct 10% categories of angiographic carotid stenosis is moderate, but when realistic risk- and decision-based weights are used, agreement between experienced observers can be almost perfect.

Platelet activation and lipid peroxidation in patients with acute ischemic stroke (Article)

1997-08-01T00:00:00Z

BACKGROUND AND PURPOSE: Both platelet activation and lipid peroxidation are potential sources of vasoactive eicosanoids that can be produced via the cyclooxygenase pathway, ie, thromboxane (TX) A2, or by free radical-catalyzed peroxidation of arachidonic acid, ie, isoprostanes. We investigated the biosynthesis of TXA2 and F2-isoprostanes, as reflected by the urinary excretion of 11-dehydro-TXB2 and 8-epi-prostaglandin (PG) F2 alpha respectively, in 62 consecutive patients (30 men, 32 women; mean age, 67 +/- 14 years) with acute ischemic stroke. METHODS: At least two consecutive 6-hour urine samples were obtained during the first 72 hours after onset of symptoms. Urinary eicosanoids were measured by previously described radioimmunoassays. RESULTS: Repeated periods of enhanced thromboxane biosynthesis were found in 52% of patients. Urinary 11-dehydro-TXB2 averaged 221 +/- 207 (mean +/- SD; n = 197; range, 13 to 967) pmol/mmol creatinine in 30 patients treated with cyclooxygenase inhibitors (mostly aspirin) at the time of study versus 392 +/- 392 (n = 186; range, 26 to 2533) in 32 untreated patients (P < .001). The corresponding values for 8-epi-PGF2 alpha excretion were 74 +/- 42 (range, 14 to 206) and 83 +/- 65 (range, 24 to 570) pmol/mmol creatinine (P > .05). The correlation between the two metabolites was moderate in both untreated patients (r = .41, P < .001) and patients with cyclooxygenase inhibitors (r = .31, P < .001). In a multiple regression analysis, increased thromboxane production was independently associated with severity of stroke on admission, atrial fibrillation, and treatment with cyclooxygenase-inhibiting drugs. CONCLUSIONS: We conclude that during the first few days after an acute ischemic stroke (1) platelet activation occurs repeatedly in a cyclooxygenase-dependent fashion; (2) platelet activation is not associated with concurrent changes in isoprostane biosynthesis; (3) platelet activation is independently associated with stroke severity and atrial fibrillation; and (4) isoprostane biosynthesis is largely independent of platelet cyclooxygenase activity.

We need stronger predictors of major vascular events in patients with a recent transient ischemic attack or nondisabling stroke. Dutch TIA Trial Study Group (Article)

1997-04-01T00:00:00Z

BACKGROUND: It has been proposed that most prognostic factors in patients with transient ischemic attack or nondisabling stroke are weak and consequently that patients at high risk of recurrent major vascular events cannot be reliably identified. METHODS: In the Dutch TIA trial, a multicenter, double-blind study of low-dose versus medium-dose aspirin, 3127 patients were included within 3 months after onset of a transient ischemic attack, amaurosis fugax, or nondisabling stroke. In a previous analysis, we developed a prediction model by means of Cox proportional hazards regression for the composite outcomes of fatal or nonfatal stroke and for myocardial infarction, stroke, or vascular death, based on clinical and demographic information as well as on the results of ancillary investigations. We assessed the discriminatory power and the calibration of the prediction models. RESULTS: The median numbers of prognostic factors for stroke, myocardial infarction, or vascular death outcome and for stroke alone were 3 and 4, respectively. The proportion of patients with a predicted probability exceeding 30% was less than 5% for both models; here the calibration of the models was poor. Only four of the patients with stroke, myocardial infarction, or vascular death were assigned a probability of greater than 50% for that outcome, and only one of the patients with stroke was given such a high probability. The models' discriminatory ability was a little disappointing (areas under the curve of 0.73 and 0.75, respectively). CONCLUSION: This analysis indicates that we need stronger predictors of recurrence risk in patients with a transient ischemic attack or nondisabling stroke.

A behavioral rating scale as a predictor for survival of demented nursing home patients (Article)

1994-05-17T00:00:00Z

As part of a study towards determinants of survival in nursing home patients with dementia, the prognostic value of a behavioral rating scale for nursing home patients is assessed in an 8-year follow-up study. The 2-year survival rate for the entire cohort (n = 569) was 56%. Women (n = 459) had a 2-year survival rate of 62%, and men (n = 110) had a 2-year survival rate of 40%. Items indicating physical impairment, dependency and apathy had most prognostic value. Items measuring aggressive or depressive behavior, and cognitive impairment were less predictive. These results were confirmed in a multivariate proportional hazards analysis. A prognostic model with age, gender and five behavioral items (needs help when walking, occupied in useful activity, restless at night, utters physical complaints, and socializes with other patients) substantially differentiated in survival chances in patients with dementia. The model gives a predicted 2-year survival chance of less than 20% or more than 80% in 80 of the 569 patients. When adjusted for the variables in the model, previous residence had no prognostic value anymore. Possibilities for further work in this area of research are discussed.

Decision analysis in the clinical neurosciences (Doctoral Thesis)

1994-01-26T00:00:00Z

Diagnostic and therapeutic choice in neurology can fortunately be made without formal decision support in the majority of cases. in many patients a diagnosis and treatment choice are relatively easy to establish. This study however, concerns the application of a decision support methodology - clinical decision analysis - to several problems in the clinical neurosdences where diagnosis, prognosis and therapeutic choice are not obvious. Sometimes decision making in clinical medicine can be extremely difficult There may be large interests atstake,and theamount of information that has to beprocessed can be enormous. Data from the patient's history, physical examination, diagnostic procedures, clinical knowledge and the scientific information have to be combined in order to arrive at a prognosis and to develop a diagnostic and therapeutic strategy. Add to this that most diagnostic tests are not completely accurate, that therapy is not always and entirely effective, that diagnostic and therapeutic procedures may be risky, unpleasant, expensive and time-consuming, and that prognosis is most of the times uncertain. The decision process itself is limited by time and by budgetary constraints. The clinician has to recognize situations where the patient's preferences are important, and he has to know when the clinical situation needs a doctor - patient relationship characterized by activity - passivity, guidance - cooperation or mutual participation. Moreover, physicians and their patients (as any human being) find it difficult to handle uncertainty.'" Oinicians often discuss the pro' s and con' sof altemativemanagementstrategies with their senior and junior colleagues, but a language that effectively and explicitly addresses uncertainty and preferences for health outcomes is not part of the physician's standard equipment. Several other factors influence the decision process as welL It has been demonstrated that patient characteristics, (such as social class), physician's personal characteristics (such as age, type of specialty), and the physician's interaction with his profession (for example whether he is in a solo- of group-practice) all may be of influence.