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The optimal management of post-stroke cognitive impairment remains controversial. These joint European Stroke Organisation (ESO) and European Academy of Neurology (EAN) guidelines provide evidence-based recommendations to assist clinicians in decision making around prevention, diagnosis, treatment and prognosis. These guidelines were developed according to ESO standard operating procedure and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews and, where possible, meta-analyses of the literature, assessed the quality of the available evidence and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available to provide recommendations based on the GRADE approach. There was limited randomised controlled trial evidence regarding single or multicomponent interventions to prevent post-stroke cognitive decline. Interventions to improve lifestyle and treat vascular risk factors may have many health benefits but a beneficial effect on cognition is not proven. We found no evidence around routine cognitive screening following stroke but recognise the importance of targeted cognitive assessment. We described the accuracy of various cognitive screening tests but found no clearly superior approach to testing. There was insufficient evidence to make a recommendation for use of cholinesterase inhibitors, memantine nootropics or cognitive rehabilitation. There was limited evidence on the use of prediction tools for post-stroke cognitive syndromes (cognitive impairment, dementia and delirium). The association between post-stroke cognitive impairment and most acute structural brain imaging features was unclear, although the presence of substantial white matter hyperintensities of presumed vascular origin on acute MRI brain may help predict cognitive outcomes. These guidelines have highlighted fundamental areas where robust evidence is lacking. Further, definitive randomised controlled trials are needed, and we suggest priority areas for future research. ispartof: European Stroke Journal vol:6 issue:3 pages:1-177 ispartof: location:England status: Published online

The increasing burden of stroke and dementia emphasizes the need for new, well-tolerated and cost-effective primary prevention strategies that can reduce the risks of stroke and dementia worldwide, and specifically in low- and middle-income countries (LMICs). This paper outlines conceptual frameworks of three primary stroke prevention strategies: (a) the “polypill” strategy; (b) a “population-wide” strategy; and (c) a “motivational population-wide” strategy. (a) A polypill containing generic low-dose ingredients of blood pressure and lipid-lowering medications (e.g. candesartan 16 mg, amlodipine 2.5 mg, and rosuvastatin 10 mg) seems a safe and cost-effective approach for primary prevention of stroke and dementia. (b) A population-wide strategy reducing cardiovascular risk factors in the whole population, regardless of the level of risk is the most effective primary prevention strategy. A motivational population-wide strategy for the modification of health behaviors (e.g. smoking, diet, physical activity) should be based on the principles of cognitive behavioral therapy. Mobile technologies, such as smartphones, offer an ideal interface for behavioral interventions (e.g. Stroke Riskometer app) even in LMICs. (c) Community health workers can improve the maintenance of lifestyle changes as well as the adherence to medication, especially in resource poor areas. An adequate training of community health workers is a key point. Conclusion An effective primary stroke prevention strategy on a global scale should integrate pharmacological (polypill) and lifestyle modifications (motivational population-wide strategy) interventions. Side effects of such an integrative approach are expected to be minimal and the benefits among individuals at low-to-moderate risk of stroke could be significant. In the future, pragmatic field trials will provide more evidence.

Background and purpose The aim of this pooled patient-level data analysis was to test if multidomain interventions, addressing several modifiable vascular risk factors simultaneously, are more effective than usual post-stroke care for the prevention of cognitive decline after stroke. Methods This pooled patient-level data analysis included two randomized controlled trials using a multidomain approach to target vascular risk factors in stroke patients and cognition as primary outcome. Changes from baseline to 12 months in the trail making test (TMT)-A, TMT-B and 10-words test were analysed using stepwise backward linear mixed models with study as random factor. Two analyses were based on the intention-to-treat (ITT) principle using different imputation approaches and one was based on complete cases. Results Data from 322 patients (157 assigned to multidomain intervention and 165 to standard care) were analysed. Differences between randomization groups for TMT-A scores were found in one ITT model (P = 0.014) and approached significance in the second ITT model (P = 0.087) and for complete cases (P = 0.091). No significant intervention effects were found for any of the other cognitive variables. Conclusion We found indications that multidomain interventions compared with standard care can improve the scores in TMT-A at 1 year after stroke but not those for TMT-B or the 10-words test. These results have to be interpreted with caution due to the small number of patients.

This review summarizes the potential for polypill therapies for stroke prevention. While a number of studies applying different approaches regarding polypill have been performed, none of them has had a focus on stroke as the main outcome. A combination pill containing drugs such as statins, diuretics, and other antihypertensives is currently available in various formats. Estimates focusing mostly on primary prevention show that using such a combination drug a reduction in the 5-year stroke incidence by 50% can be achieved – especially in low- and middle-income countries with a high prevalence of risk factors even among people at young ages. A combination of a large supporting population-wide program with a registry-based quality control is the most likely perspective and can be achieved within a reasonable time frame and potentially have significant influence in young stroke populations.

Background and aim Behavioral and lifestyle interventions in stroke patients need to be intense enough to result in sustainable treatment differences among groups of a randomized trial. Therefore, we report the effects of multidomain interventions on lifestyle and laboratory parameters after 12 and 24 months from a trial that examined whether intensive risk factor management can prevent cognitive decline in ischemic stroke patients. Methods This prospective randomized, open-label, blinded endpoint trial recruited patients within three months after acute stroke in five Austrian neurological clinics during June 2010 and November 2012. One hundred and one patients were randomized into multidomain intervention and 101 into standard care. Lifestyle interventions were individualized to match predefined targets of regular physical activity, healthy diet, and adequate physiological risk factor control. Results A total of 167 participants (80 intervention, 87 control) completed the 12-month visit and 155 (76 intervention, 79 control) the 24-month visit. During the first 12 months, adherence to healthy lifestyle and adequately controlled physiological parameters (measured by summary scores) improved significantly in the intervention group compared to controls (p Conclusions These results demonstrate that intensified individualized multidomain lifestyle interventions in stroke patients are effective in promoting healthy lifestyle in stroke care.

Background and Purpose— Acute stroke management requires minimization of prehospital time. This study addresses the value of helicopter transport compared with other means of transportation to a stroke unit and compares their rates of thrombolysis on a nationwide basis. Methods— Prospective data collection and prespecified evaluation of data from 32 stroke units between 2003 and 2009 were used. We distinguished between patients transported either directly to a stroke unit or transferred indirectly via a peripheral hospital. Thus, there were 6 transport groups: helicopter emergency service (HEMS) direct and indirect, ambulance accompanied by an emergency physician direct and indirect, and ambulance without physician direct and indirect. Demographic and clinical factors, time delays, and rates of thrombolysis of patients transported by helicopter were compared with factors of patients transported otherwise. Results— Of 21 712 ischemic stroke patients, 905 patients (4.1%) were transported by helicopter. Of these, 752 patients (3.4%) were transported by direct HEMS, and 153 patients (0.7%) were transported by indirect HEMS. Thrombolysis rates were highest for HEMS (24% direct, 29% indirect) transport, followed by ambulance accompanied by an emergency physician (18% direct, 15% indirect). The probability of receiving thrombolysis was highest for indirect HEMS transport (OR 3.6, 2.2–6.0), followed by indirect ambulance accompanied by an emergency physician transport (OR 1.5, 1.1–1.9). The shortest times, 90 minutes or less from stroke onset to hospital arrival, were achieved with direct AMBP and direct HEMS transport. Conclusions— The shortest hospital arrival times and highest thrombolysis rates were seen in ischemic stroke patients transported by helicopter.

The massive numbers of sperm males transfer during a single mating are physiologically costly and the amount of sperm that can be stored is limited. Therefore, males can perform only a finite number of successive copulations without loss of fertility, and males should allocate sperm prudently. We investigated sperm availability and depletion in male black scavenger flies, Sepsis cynipsea (Diptera: Sepsidae), asking whether males adjust copula duration according to nutrition, their sperm stores, their own and their partner’s body size, as predicted by theory. We created a gradient of sperm limitation by restricting dung (their protein resource as adults) and subjecting males to a varying number of copulations. While male fertility did not depend on access to fresh dung (contrary to females), it did decline after three copulations, and more so when males were small. Larger females tended to lay more unfertilized eggs after copulating with previously mated males. However, copula duration was not influenced by a male’s number of previous copulations, and therefore apparently not by his current sperm stores. Nevertheless, copula duration varied with male size, with small males copulating longer, and with female size, as copulations lasted longer with larger females, suggesting that males are investing more sperm in larger, more fecund females. While male copula adjustments to their own nutrition and body size may be simple (proximate) physiological responses, responses to female size indicate more strategic and sophisticated sperm-allocation strategies than previously thought.

BackgroundTime is essential for the treatment of acute stroke. Much time is lost outside the hospital, either due to failure in identifying stroke symptoms or due to a delay in notification or transport. We review studies reporting factors associated with better stroke knowledge and shorter time delays. We summarise the evidences for the effect of stroke knowledge and education on people's reaction in the acute situation of stroke.MethodsWe searched MEDLINE for studies reporting factors associated with prehospital time of stroke patients, or knowledge of stroke symptoms. Further, we searched for studies reporting educational interventions aimed at increasing stroke symptom knowledge in the population.FindingsWe included a total of 182 studies. Surprisingly, those factors associated with better stroke knowledge such as education and sociodemographic variables were not related to shorter time delays. Few studies report shorter time delays or better stroke knowledge in persons having suffered a previous stroke. Factors associated with shorter time delays were more severe stroke and symptoms regarded as serious, but not better knowledge about the most frequent symptoms such as hemiparesis or disorders of speech. Only 25–56% of patients recognised their own symptoms as stroke. While stroke education increases the knowledge of warning signs, a few population studies measured the impact of education on time delays; in such studies, time delays decreased after education. This may partly be mediated by better organisation of EMS and hospitals.InterpretationThere is a discrepancy between theoretical stroke knowledge and the reaction in an acute situation. Help-seeking behaviour is more dependent on the perceived severity of symptoms than on symptom knowledge. Bystanders play an important role in the decision to call for help and should be included in stroke education. Education is effective and should be culturally adapted and presented in a social context. It is unclear which educational concept is best suited to enhance symptom recognition in the acute situation of stroke, especially in view of discrepancies between knowledge and action.

Background and Purpose— Acute-onset dysphagia after stroke is frequently associated with an increased risk of aspiration pneumonia. Because most screening tools are complex and biased toward fluid swallowing, we developed a simple, stepwise bedside screen that allows a graded rating with separate evaluations for nonfluid and fluid nutrition starting with nonfluid textures. The Gugging Swallowing Screen (GUSS) aims at reducing the risk of aspiration during the test to a minimum; it assesses the severity of aspiration risk and recommends a special diet accordingly. Methods— Fifty acute-stroke patients were assessed prospectively. The validity of the GUSS was established by fiberoptic endoscopic evaluation of swallowing. For interrater reliability, 2 independent therapists evaluated 20 patients within a 2-hour period. For external validity, another group of 30 patients was tested by stroke nurses. For content validity, the liquid score of the fiberoptic endoscopic evaluation of swallowing was compared with the semisolid score. Results— Interrater reliability yielded excellent agreement between both raters (κ=0.835, P P =0.001), therefore confirming the subtest sequence of GUSS. Conclusions— The GUSS offers a quick and reliable method to identify stroke patients with dysphagia and aspiration risk. Such a graded assessment considers the pathophysiology of voluntary swallowing in a more differentiated fashion and provides less discomfort for those patients who can continue with their oral feeding routine for semisolid food while refraining from drinking fluids.

Previous univariate studies of the fly Sepsis cynipsea (Diptera: Sepsidae) have demonstrated spatiotemporally variable and consequently overall weak sexual selection favouring large male size, which is nevertheless stronger on average than fecundity selection favouring larger females. To identify specific target(s) of selection on body size and additional traits possibly affecting mating success, two multivariate field studies of sexual selection were conducted. In one study using seasonal replicates from three populations, we assessed 15 morphological traits. No clear targets of sexual selection on male size could be detected, perhaps because spatiotemporal variation in selection was again strong. In particular, there was no (current) selection on male abdomen length or fore coxa length, the only traits for which S. cynipsea males are not smaller than females. Interestingly, copulating males had a consistently shorter fore femur base, a secondary sexual trait, and a wider clasper (hypopygium) gap, an external genital trait. In a second study using daily and seasonal replicates from one population, we included physiological measures of energy reserves (lipids, glucose, glycogen), in addition to hind tibia length and fluctuating asymmetry (FA) of all pairs of legs. This study again confirmed the mating advantage of large males, and additionally suggests independent positive influences of lipids (the long-term energy stores), with effects of glucose and glycogen (the short-term energy stores) tending to be negative. FA of paired traits was not associated with male mating success. Our study suggests that inclusion of physiological measures and genital traits in phenomenological studies of selection, which is rare, would be fruitful in other species.

In brood parasites, knowledge of spacing behaviour, habitat use and territoriality may reveal cues about how parasites find and use their hosts. To study the use of space and habitat of European cuckoos, Cuculus canorus, we radio-tagged 16 females during four consecutive reproductive seasons. We hypothesized that during the laying period cuckoo females should (1) use habitats selectively, and (2) attempt to monopolize potential egg laying areas to reduce competition for host nests. Our data are consistent with the first hypothesis: the use of pond edges compared to forest and transitional habitats was significantly greater than expected from the habitat availability in the total area and within individual female home ranges. All 26 directly observed egg layings and 27 nest visits without laying occurred at pond edges in nests of Acrocephalus spp. Females spent significantly more time at pond edges on egglaying days than on non-laying days. The second hypothesis was not supported: female home ranges overlapped similarly in all three major habitat categories of the potential egg laying areas, and only little aggression was observed between females. We discuss whether female cuckoos may lack territorial behaviour because they are not able to defend egg laying areas economically or because defence is not necessary due to sufficient availability of suitable host nests.

We radiotracked 13 common cuckoo females in the southeastern part of the Czech Republic. Seven females laid eggs in the nests of reed warblers, Acrocephalus scirpaceus, sedge warblers, A. schoenobaenus, and marsh warblers, A. palustris. We observed 53 nest visits, of which 26 involved egg laying. Cuckoos spent significantly more time within 50 m of the host nest on the laying day than on the 5 prelaying days. The vantage point used when parasitizing or visiting a nest was on average four times further from the nest than the closest possible vantage point, but there was a positive correlation between these two distances. Cuckoos spent on average 20 min observing host nests from their vantage points before they visited a nest. Comparison of cuckoos’ visits to host nests with and without egg laying revealed no significant differences in the duration of visits or in other measures of behaviour. There was significant variation in behaviour between cuckoos, particularly in the time of day when eggs were laid in host nests. This variation can be attributed to the strong, but not absolute, host and habitat specificity of individuals.

Egg mimicry is an important adaptation of common cuckoos, Cuculus canorus, against rejection of eggs by their respective hosts. A precondition for the maintenance of egg mimicry is that female cuckoos find hosts with a matching egg type. Experimental evidence indicated that habitat imprinting may be important for host selection. We tested whether the spacing and laying patterns of female cuckoos in the field are compatible with the supposed habitat-imprinting mechanism. We observed 16 females, with the help of radiotelemetry; of seven females, we observed directly 26 egg layings and 27 nest visits without laying. As expected if females were imprinted on different vegetation types, (1) the distribution of vegetation types differed between female home ranges, (2) female habitat use differed from average habitat availability within the egg-laying area (habitat preference), (3) females visited nests and deposited their eggs in the habitat they preferred, and (4) females laid their eggs consistently in a particular habitat type, irrespective of the host species. These results indicate that cuckoo females show habitat preference when searching for suitable host nests. Hence our data are compatible with the habitat-imprinting hypothesis, but owing to the habitat specificity of hosts the data cannot disprove a potential role of host specificity in cuckoo females.

Finding, assessing, rejecting, and copulating with a mate is assumed to carry fitness costs, particularly for females, that have to be traded off against fitness benefits of mating such as increased fecundity, fertility, longevity, or better quality offspring. Female dung flies, Sepsis cynipsea (Diptera: Sepsidae), typically attempt to dislodge mounted males harassing them by vigorous shaking. Shaking duration has been shown to reflect both direct and indirect female choice in this species. The latter is an expression of the females' general reluctance to mate due to presumed costs of mating. We investigated the costs of copulation in the laboratory. Females were randomly assigned to one of three treatment groups and allowed to copulate either not at all, once, or twice. The males' armored genitalia injured females internally during copula. Injuries were visible as sclerotized scars in the female ovipositor, and their occurrence increased with mating frequency. Presumably due to these injuries, mated females showed higher mortality. This effect was statistically independent from additional costs of reproduction related to oviposition, as copulation also increased lifetime egg production and tended to augment oviposition rate (eggs per day), while fertility (proportion of offspring emerged) was unaffected. We thus found high mortality costs of copulating, indicating substantial sexual conflict, which helps explain female reluctance to mate in this species. Copyright 2002.

Background In a number of species males damage females during copulation, but the reasons for this remain unclear. It may be that males are trying to manipulate female mating behaviour or their life histories. Alternatively, damage may be a side-effect of male-male competition. In the black scavenger or dung fly Sepsis cynipsea (Diptera: Sepsidae) mating reduces female survival, apparently because males wound females during copulation. However, this damage does not seem to relate to attempted manipulation of female reproduction by males. Here we tested the hypothesis that harming females during mating is an incidental by-product of characters favoured during pre-copulatory male-male competition. We assessed whether males and their sons vary genetically in their ability to obtain matings and harm females, and whether more successful males were also more damaging. We did this by ranking males' mating success in paired competitions across several females whose longevity under starvation was subsequently measured. Results As previously reported, our results show mating is costly for female S. cynipsea. However, variance in female longevity was not explained by male identity, family, body size, number of previous copulations, or copulation duration. Nevertheless, there was a positive correlation between the harm fathers inflicted on their mates (affecting female longevity) and the harm sons inflicted on theirs. Additionally, family identity significantly influenced male copulation success. Conclusion Our results indicate a heritable component of some yet unspecified male trait(s) that influence harm and mating success. However, there was no relationship between copulation success of fathers or sons and the mean longevity of their mates. We therefore found no support for harm being a side effect of traits favoured in pre-copulatory male-male competition.