Thromboxane biosynthesis in stroke and post-stroke dementia

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 worthwhil

Interobserver agreement for 10% categories of angiographic carotid stenosis

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

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 .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

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

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

Hypopituitarism after subarachnoid haemorrhage, do we know enough?

BACKGROUND: Fatigue, slowness, apathy and decrease in level of activity are common long-term complaints after a subarachnoid haemorrhage (SAH). They resemble the symptoms frequently found in patients with endocrine dysfunction. Pituitary dysfunction may be the result of SAH or its complications. We therefore hypothesized that it may explain some of the long-term complaints after SAH. We reviewed the literature to clarify the occurrence, pattern and severity of endocrine abnormalities and we attempted to identify risk factors for hypopituitarism after SAH. We also assessed the effect of hypopituitarism on long-term functional recovery after SAH. METHODS: In a MEDLINE search for studies published between 1995 and 2014, we used the term subarachnoid haemorrhage in combination with pituitary, hypopituitarism, growth hormone, gonadotropin, testosterone, cortisol function, thyroid function and diabetes insipidus. We selected all case-series and cohort studies reporting endocrine function at least 3 months after SAH and studied their reported prevalence, pathogenesis, risk factors, clinical course and outcome. RESULTS: We identified 16 studies describing pituitary function in the long term after SAH. The reported prevalence of endocrine dysfunction varied from 0 to 55% and the affected pituitary axes differed between studies. Due to methodological issues no inferences on risk factors, course and outcome could be made. CONCLUSIONS: Neuroendocrine dysfunction may be an important and modifiable determinant of poor functional outcome after SAH. There is an urgent need for well-designed prospective studies to more precisely assess its incidence, clinical course and effect on mood, behaviour and quality of life. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12883-014-0205-0) contains supplementary material, which is available to authorized users

Increased thromboxane biosynthesis is associated with poststroke dementia

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

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

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 age