http://repub.eur.nl/res/aut/1715/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/26045/ 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. http://repub.eur.nl/res/pub/32946/ 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. http://repub.eur.nl/res/pub/31568/ 2010-12-01T00:00:00Z Accurately quantifying aneurysm shape parameters is of clinical importance, as it is an important factor in choosing the right treatment modality (i.e. coiling or clipping), in predicting rupture risk and operative risk and for pre-surgical planning. The first step in aneurysm quantification is to segment it from other structures that are present in the image. As manual segmentation is a tedious procedure and prone to inter- and intra-observer variability, there is a need for an automated method which is accurate and reproducible. In this paper a novel semi-automated method for segmenting aneurysms in Computed Tomography Angiography (CTA) data based on Geodesic Active Contours is presented and quantitatively evaluated. Three different image features are used to steer the level set to the boundary of the aneurysm, namely intensity, gradient magnitude and variance in intensity. The method requires minimum user interaction, i.e. clicking a single seed point inside the aneurysm which is used to estimate the vessel intensity distribution and to initialize the level set. The results show that the developed method is reproducible, and performs in the range of interobserver variability in terms of accuracy. http://repub.eur.nl/res/pub/28037/ 2010-03-25T00:00:00Z Intracranial aneurysm volume and shape are important factors for predicting rupture risk, for pre-surgical planning and for follow-up studies. To obtain these parameters, manual segmentation can be employed; however, this is a tedious procedure, which is prone to inter- and intra-observer variability. Therefore there is a need for an automated method, which is accurate, reproducible and reliable. This study aims to develop and validate an automated method for segmenting intracranial aneurysms in Computed Tomography Angiography (CTA) data. Also, it is investigated whether prior smoothing improves segmentation robustness and accuracy. The proposed segmentation method is implemented in the level set framework, more specifically Geodesic Active Surfaces, in which a surface is evolved to capture the aneurysmal wall via an energy minimization approach. The energy term is composed of three different image features, namely; intensity, gradient magnitude and intensity variance. The method requires minimal user interaction, i.e. a single seed point inside the aneurysm needs to be placed, based on which image intensity statistics of the aneurysm are derived and used in defining the energy term. The method has been evaluated on 15 aneurysms in 11 CTA data sets by comparing the results to manual segmentations performed by two expert radiologists. Evaluation measures were Similarity Index, Average Surface Distance and Volume Difference. The results show that the automated aneurysm segmentation method is reproducible, and performs in the range of inter-observer variability in terms of accuracy. Smoothing by nonlinear diffusion with appropriate parameter settings prior to segmentation, slightly improves segmentation accuracy. http://repub.eur.nl/res/pub/25293/ 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. http://repub.eur.nl/res/pub/25380/ 2009-04-07T00:00:00Z http://repub.eur.nl/res/pub/28800/ 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. http://repub.eur.nl/res/pub/36339/ 2007-01-01T00:00:00Z Objective: Testing the hypothesis that depressive symptoms in dementia reflect dysfunction in fronto-subcortical pathways. Background: Both depression and dementia can be the result of vascular damage of the brain. The nature of the depressive symptomatology seems to be related to concommittant cognitive disturbances in that subjects show more so-called motivational symptoms of depression. These symptoms can be the result of frontal-subcortical dysfunction. It could be very helpful for clinical practice if these subjects could be identified by simple diagnostic procedures. Methods: Associations were computed between measures of depressive symptoms and a set of neuropsychological tests in a sample of 54 subjects with a post-stroke dementia. Results: Allthough we used an extensive set of neuropsychological tests, most subjects were able to participate only in a small part of them, because of disease severity. Our hypothesis was supported by a negative correlation between scores on the verbal semantic fluency task and the total numbers of motivational depressive symptoms. None of the neuropsychological tests was significantly related to the number of mood symptoms neither did they correlate with the total number of depressive symptoms. Conclusion: This study gives further evidence for the assumption that motivational-based depressive symptoms partially originate from fronto-subcortical dysfunction. Copyright http://repub.eur.nl/res/pub/13865/ 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. http://repub.eur.nl/res/pub/8435/ 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. http://repub.eur.nl/res/pub/31910/ 2002-05-15T00:00:00Z With 25 to 30 thousand new patients per year and an incidence of 170/100.000, stroke is a major health problem in the Netherlands, as it is in other western countries. It accounts for almost I 0% of the annual death in the Netherlands. Approximately 80% of stroke is of ischemic origin, and 20% cerebral hemorrhage. For the individual patient, the consequences of stroke are often devastating. Approximately 20% of the patients do not survive the first weeks and case fatality at I year is approximately 35%1 However, mortality strongly depends on type of stroke, and is higher in hemorrhagic than in ischemic cases. Of the survivors, only 65% is discharged home directly. Approximately 15% is discharged to a nursery home, and 20% to a stroke recovery or a rehabilitation center2 Even patients who are discharged to their own home are often not able to live fully independently, partly due to their physical handicap, but often also due to cognitive impairment. In approximately 25% of the cases, cognitive dysfunction is severe enough to the extent that patients fulfill all criteria of dementia. Although the highest incidence of ischemic stroke is between the 6'h and 7'h decade oflife, it is a disease of all ages. In subjects between 15 and 4 5 years of age, the incidence of ischemic stroke is between 6 and 15/1OO.OOO/year. The mortality in this group of relatively young adults, is about 20% in the first 6 years after stroke and only less than half of the survivors is eventually able to perform a job. Although the consequences of stroke are often dramatic for the individual patient, these figures also indicate the large burden of stroke on the community and the health care system. As a result of the high incidence of stroke, a relatively small reduction of a few percent of stroke or stroke recurrence would mean a large reduction in number of patients appealing to the health care system in absolute terms. Obviously, this makes every effort reducing the incidence or recurrence of stroke, even with only a few percent, more than worthwhile http://repub.eur.nl/res/pub/9396/ 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. http://repub.eur.nl/res/pub/9054/ 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. http://repub.eur.nl/res/pub/9146/ 1999-01-01T00:00:00Z BACKGROUND AND PURPOSE: It has been suggested that daily intake of aspirin is associated with a reduction of cognitive decline, both in normal and in demented subjects, but the mechanism is unclear. We have therefore studied the relationship between thromboxane (TX) A(2) biosynthesis, as reflected by the urinary excretion of 11-dehydro-TXB(2), and the presence of dementia in patients after acute stroke. METHODS: Patients from the Rotterdam Stroke Databank were screened for dementia between 3 and 9 months after stroke. Patients had a full neurological examination, neuropsychological screening, and, if indicated, extensive neuropsychological examination. Criteria used for the diagnosis of dementia were from the Diagnostic and Statistical Manual of Mental Disorders, Third Edition (Revised). Urine samples were taken at the time of screening. Urinary 11-dehydro-TXB(2) was measured by means of a previously validated radioimmunoassay. RESULTS: Dementia was diagnosed in 71 patients, and urine samples were available for 62. Median value (range) of 11-dehydro-TXB(2) was 399 (89 to 2105) pmol/mmol creatinine for demented patients versus 273 (80 to 1957) for 69 controls with stroke but without dementia (P=0.013). No difference was found between 44 patients with vascular dementia, 404 (89 to 2105) pmol/mmol creatinine, and 18 patients with Alzheimer's disease plus cerebrovascular disease, 399 (96 to 1467) pmol/mmol creatinine (P=0.68). In a stepwise logistic regression analysis, in which possible confounders such as use of antiplatelet medication, cardiovascular risk factors, and type of stroke were taken into account, increased urinary excretion of 11-dehydro-TXB(2) remained independently related to the presence of dementia (OR 1.12, 95% CI 1.03 to 1.22 per 100 pmol/mmol creatinine). The difference in metabolite excretion rates between demented and nondemented patients was most prominent within the subgroup of ischemic stroke patients who received aspirin (P<0.01). CONCLUSIONS: Increased thromboxane biosynthesis in the chronic phase after stroke is associated with the presence of but not the type of poststroke dementia. It is particularly apparent in patients on aspirin, thereby suggesting the involvement of extraplatelet sources of TXA(2) production in this setting. http://repub.eur.nl/res/pub/8905/ 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. http://repub.eur.nl/res/pub/22516/ 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. http://repub.eur.nl/res/pub/22518/ 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.