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Objective: The hyperintense acute reperfusion marker (HARM) on fluid-attenuated inversion recovery (FLAIR) images is associated with blood-brain barrier (BBB) permeability changes. The aim of this study was to examine the influence of contrast agent dosage on HARM incidence in acute ischaemic stroke patients., Methods: We prospectively included 529 acute ischaemic stroke patients (204 females, median age 71 years). Patients underwent a first stroke-MRI within 24 hours from symptom onset and had a follow-up on day 2. The contrast agent Gadobutrol was administered to the patients for perfusion imaging or MR angiography. The total dosage was calculated as ml/kg body weight and ranged between 0.04 and 0.31 mmol/kg on the first examination. The incidence of HARM was evaluated on day 2 FLAIR images., Results: HARM was detected in 97 patients (18.3%). HARM incidence increased significantly with increasing dosages of Gadobutrol. Also, HARM positive patients were significantly older. HARM was not an independent predictor of worse clinical outcome, and we did not find an association with increase risk of haemorrhagic transformation., Conclusions: A higher dosage of Gadobutrol in acute stroke patients on initial MRI is associated with increased HARM incidence on follow-up. MRI studies on BBB should therefore standardize contrast agent dosages., Key Points: • Hyperintense acute reperfusion marker on MRI indicates blood-brain barrier disruption. • This observational study on stroke patients characterizes HARM. • Incidence depends on contrast agent dosage on the previous day. • HARM is also associated with older age and poor kidney function. • Interpretation of HARM must take dosage into consideration.

Background: Although post-stroke depression is widely recognized, less is known about depressive symptoms in the acute stage of stroke and especially in young stroke patients. We thus investigated depressive symptoms and their determinants in such a cohort., Methods: The Stroke in Young Fabry Patients study (sifap1) prospectively recruited a large multinational European cohort (n = 5,023) of patients with a cerebrovascular event aged 18-55. For assessing clinically relevant depressive symptoms (CRDS, defined by a BDI-score ≥18) the self-reporting Beck Depression Inventory (BDI) was obtained on inclusion in the study. Associations with baseline parameters, stroke severity (National Institutes of Health Stroke Scale, NIHSS), and brain MRI findings were analyzed., Results: From the 2007 patients with BDI documentation, 202 (10.1%) had CRDS. CRDS were observed more frequently in women (12.6 vs. 8.2% in men, p < 0.001). Patients with CRDS more often had arterial hypertension, diabetes mellitus, and hyperlipidemia than patients without CRDS (hypertension: 58.0 vs. 47.1%, p = 0.017; diabetes mellitus: 17.9 vs. 8.9%, p < 0.001; hyperlipidemia: 40.5 vs. 32.3%, p = 0.012). In the subgroup of patients with ischemic stroke or TIA (n = 1,832) no significant associations between CRDS and cerebral MRI findings such as the presence of acute infarcts (68.1 vs. 65.8%, p = 0.666), old infarctions (63.4 vs. 62.1%, p = 0.725) or white matter hyper-intensities (51.6 vs. 53.7%, p = 0.520) were found., Conclusion: Depressive symptoms were present in 10.1% of young stroke patients in the acute phase, and were related to risk factors but not to imaging findings., (© 2015 S. Karger AG, Basel.)

Background: Vascular hyperintensities of brain-supplying arteries on stroke FLAIR MRI are common and represent slow flow or stasis. FLAIR vascular hyperintensities (FVH) are discussed as an independent marker for cerebral hypoperfusion, but the impact on infarct size and clinical outcome in acute stroke patients is controversial. This study evaluates the association of FVH with infarct morphology, clinical stroke severity and infarct growth in patients with symptomatic internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion., Methods: MR images of 84 patients [median age 73 years (IQR 65-80), 56.0% male, median NIHSS 7 (IQR 3-13)] with acute stroke due to symptomatic ICA or MCA occlusion or stenosis were reviewed. Vessel occlusions were identified by MRA time of flight and graded with the TIMI score. Diffusion and perfusion deficit volumes on admission and FLAIR lesion volumes on discharge were assessed. The presence and number of FVH were evaluated according to MCA-ASPECT areas, and associations with MR volumes, morphology of infarction, recanalization status, presence of white matter disease and hemorrhagical transformation as well as with stroke severity (NIHSS), stroke etiology and thrombolysis rate were analyzed., Results: FVH were detectable in 75 (89.3%) patients. The median number of FVH was 4 (IQR 2-7). Patients with FVH >4 presented with more severe strokes due to NIHSS (p = 0.021), had larger initial DWI lesions (p = 0.008), perfusion deficits (p = 0.001) and mismatch volumes/ratios (p = 0.005). The final infarct volume was larger (p = 0.005), and hemorrhagic transformation was more frequent (p = 0.029) in these patients., Conclusions: The presence of FVH indicates larger ischemic areas in brain parenchyma predominantly caused by proximal anterior circulation vessel occlusion. A high count of FVH might be a further surrogate marker for initial ischemic mismatch and stroke severity., (Copyright © 2012 S. Karger AG, Basel.)

Background and Purpose: Perfusion imaging is widely used in stroke, but there are uncertainties with regard to the choice of arterial input function (AIF). Two important aspects of AIFs are signal-to-noise ratio and bolus-related signal drop, ideally close to 63%. We hypothesized that distal branches of the middle cerebral artery (MCA) provide higher quality of AIF compared with proximal branches., Methods: Over a period of 3 months, consecutive patients with suspected stroke were examined in a 3-T MRI scanner within 24 hours of symptom onset. AIFs were selected manually in M1, M2, and M3 branches of the MCA contralateral to the suspected ischemia. Signal-to-noise ratio and bolus-related signal drop were analyzed. Perfusion maps were created for every patient and mean values at the insular level as well as relative ranges were compared., Results: Mean age of 132 included patients (53 females) was 67.3 years (SD, 14.9) and median National Institutes of Health Stroke Scale was 3 (interquartile range [IQR] 0 to 6). For further analyses, 4 patients were excluded due to discontinuation of scanning or insufficient bolus arrival (signal drop <15%). Median signal-to-noise ratio was highest in M3 branches (36.41; IQR, 29.29 to 43.58). Median signal-to-noise ratio in M2 branches was intermediate (27.54; IQR, 20.78 to 34.00) and median signal-to-noise ratio in M1 was low (12.40; IQR, 9.11 to 17.15). Using AIFs derived from M1 and M2 branches of the MCA median signal drop was 77% (IQR, 72% to 82%) and 78% (IQR, 73% to 83%), respectively. Signal drop was significantly reduced when AIF was selected in M3 branches with a median of 72% (IQR, 63% to 77%; P<0.01). Highest variability of 3456 perfusion maps was found in those derived from M1., Conclusions: The level of AIF selection in the MCA has a major impact on reliability and even quantitative parameters of perfusion maps. For better comparison of perfusion maps, the AIF should be defined by selection of distal branches of the MCA contralateral to the suspected ischemia. In future trials involving perfusion imaging, the MCA segment used for the AIF should be specified.

Background: The mismatch between diffusion weighted imaging (DWI) lesion and perfusion imaging (PI) deficit volumes has been used as a surrogate of ischemic penumbra. This pathophysiology-orientated patient selection criterion for acute stroke treatment may have the potential to replace a fixed time window. Two recent trials - DEFUSE and EPITHET - investigated the mismatch concept in a multicenter prospective approach. Both studies randomized highly selected patients (n = 74/n = 100) and therefore confirmation in a large consecutive cohort is desirable. We here present a single-center approach with a 3T MR tomograph next door to the stroke unit, serving as a bridge from the ER to the stroke unit to screen all TIA and stroke patients. Our primary hypothesis is that the prognostic value of the mismatch concept is depending on the vessel status. Primary endpoint of the study is infarct growth determined by imaging, secondary endpoints are neurological deficit on day 5-7 and functional outcome after 3 months., Methods and Design: 1000Plus is a prospective, single centre observational study with 1200 patients to be recruited. All patients admitted to the ER with the clinical diagnosis of an acute cerebrovascular event within 24 hours after symptom onset are screened. Examinations are performed on day 1, 2 and 5-7 with neurological examination including National Institute of Health Stroke Scale (NIHSS) scoring and stroke MRI including T2*, DWI, TOF-MRA, FLAIR and PI. PI is conducted as dynamic susceptibility-enhanced contrast imaging with a fixed dosage of 5 ml 1 M Gadobutrol. For post-processing of PI, mean transit time (MTT) parametric images are determined by deconvolution of the arterial input function (AIF) which is automatically identified. Lesion volumes and mismatch are measured and calculated by using the perfusion mismatch analyzer (PMA) software from ASIST-Japan. Primary endpoint is the change of infarct size between baseline examination and day 5-7 follow up., Discussions: The aim of this study is to describe the incidence of mismatch and the predictive value of PI for final lesion size and functional outcome depending on delay of imaging and vascular recanalization. It is crucial to standardize PI for future randomized clinical trials as for individual therapeutic decisions and we expect to contribute to this challenging task., Trial Registration: clinicaltrials.gov NCT00715533.

Background: In patients with acute stroke, systemic thrombolysis needs to be administered within 3 hours of symptom onset. The aim of the present study was to reduce prehospital delays in a population-based intervention., Methods: We performed a cluster-randomized trial with 48 zip code areas as cluster units in the catchment area of 3 inner-city hospitals in Berlin, Germany. The primary end point was time between symptom onset and hospital admission. The intervention consisted of an educational letter indicating stroke symptoms and emphasizing the importance of calling the emergency medical services. We additionally included a bookmark and sticker with the emergency medical services' telephone number. We fitted a series of log-normal survival regression models (time to admission) with frailty terms shared by inhabitants of the same zip code area., Results: A total of 75 720 inhabitants received the intervention. Between 2004 and 2005, 741 patients with cerebrovascular events were admitted from the control areas (n = 24) and 647 from the intervention areas (n = 24). A prehospital time of 2 hours or less and 3 hours or less was achieved by 22% and 28% of patients, respectively, in the control group compared with 26% and 34%, respectively, in the intervention group. In the log-normal model, time to hospital was reduced by 27% in the intervention group in women (acceleration factor, 0.73; 95% confidence interval, 0.58-0.94), while no significant effect was found in men., Conclusions: The population-based intervention was effective in reducing prehospital delays in women but not in men. Future research should focus on the potential transferability of the intervention, its sustainability, and sex-specific impact.

Background: Stroke is associated with a considerable burden of disease worldwide. Data about prevalence needs regular updating to facilitate health care planning and resource allocation. The purpose of the present study was to determine stroke prevalence in a large urban population in an easy and reliable way., Methods: In a population survey a total of 75,720 households with at least 1 person >or=50 years received information about stroke symptoms by mail. In addition, the Stroke Symptom Questionnaire assessing the prevalence of stroke and of stroke symptoms was sent. Stroke prevalence was determined by a single physician-diagnosed stroke-screening question or by the combination of the latter with reported visual impairment and/or articulation problems in the past., Results: A total of 28,090 persons responded (37.5%). Mean (+/-SD) age was 64.4 +/- 9.7 years, 62.9 +/- 8.9 for men (43.3%), and 65.5 +/- 10.2 for women. Of all participants 2.7% reported impaired vision, 2.8% facial weakness, 2.8% articulation problems, 3.9% limb weakness, and 5% sensory disturbances. A total of 4.5% reported a physician-diagnosed stroke (women 4.3%; men 4.9%). Combining reported stroke history with reported impaired vision and/or articulation problems, the prevalence of stroke increased to 7.6% (men 8.4%; women 7.2%). Factors associated with higher prevalence were higher age, male gender, non-German nationality, lower education, positive family history of stroke, and living alone., Conclusions: The combination of questions concerning a prior stroke and stroke symptoms is a useful and easy approach to assess prevalence. It results in prevalence numbers which might compensate for an underestimation of stroke numbers., ((c) 2008 S. Karger AG, Basel.)

Objectives: Atrial fibrillation (AF) is an important risk factor for stroke. The primary purpose of this study was to determine the resource use for patients admitted to hospital with acute stroke and to calculate stroke-related direct costs, stratifying the results according to the presence of AF as a risk factor., Methods: Data from 558 consecutive patients hospitalized with confirmed acute stroke between August 2000 and July 2001 were analyzed as part of the Berlin Acute Stroke Study. Sociodemographic variables were assessed by direct interview, while hospital data were derived from patient medical records. Patients or their carers completed a follow-up questionnaire about resource utilization and absenteeism from work during the 12-month period after hospital admission., Results: Out of the 367 patients with follow-up data and ECG findings, 71 (19%) had AF. Patients with AF were generally older, more likely to be female, and had more severe strokes compared with those without AF. Mean direct costs per patient were significantly higher in those with AF-related strokes (EURO 11,799 vs EURO 8817 for non-AF-related strokes; P < 0.001). After adjustment for confounding factors, direct costs were comparable in the two groups, except for acute hospitalization costs, which remained significantly higher in the group with AF (P < 0.05)., Conclusion: Medical care for stroke patients with AF is associated with higher costs compared with those without AF; this is explained mainly by confounding factors and driven essentially by a significant difference in acute hospitalization costs.

Background and Purpose: Many patients develop a depression after having suffered a stroke. Such a Post-Stroke Depression (PSD) impairs rehabilitation and quality of life. PSD is underdiagnosed in spite of available treatment. Several questionnaires have been created to diagnose a PSD. But questionnaires have been considered cumbersome and time-consuming. The aim of this study was to find out whether two simple, standardised questions will identify those stroke patients, who have developed a PSD., Methods: The two case-finding questions and the Beck Depression Inventory (BDI) were sent to patients of the Berlin Acute Stroke Study (BASS) four years after their stroke. Incomplete questionnaires were complemented via mail or telephone. Severity of depression was assessed by means of BDI., Results: Out of 211 patients, 199 responded to the questionnaire (94 %). 193 questionnaires were complete (97 %). Forty-two patients affirmed both case-finding questions (22 %). Compared to patients, who did not affirm both questions, these patients had a higher BDI score (19 +/- 8 vs. 7 +/- 5; p < 0.001). The sensitivity and specificity of the two questions were 89 % and 90 %, respectively. The positive and negative predictive value were 60 % and 98 % respectively. The number of confirmed questions (0, 1, 2) correlated well with the BDI score (r (2) = 0.67, p < 0.001)., Conclusions: Two standardized questions can identify patients with PSD for further diagnostic evaluation and therapy. Diagnosis of PSD might be facilitated by using them as screening instrument.

Background and Purpose: Increased knowledge of stroke risk factors in the general population may lead to improved prevention of stroke. The objective of the present study was to assess knowledge of stroke risk factors and to determine factors associated with knowledge., Methods: In a population-based survey, we sent a questionnaire to randomly selected residents in Berlin who were > or =50 years of age enquiring about knowledge of stroke risk factors. Knowledge was assessed in an open-ended question. In addition, we enquired about the source of participants' information. Sociodemographic factors, including age, sex, educational level, and nationality, were also assessed., Results: A total of 28,090 of 75,720 residents (response rate, 37%) responded to the questionnaire. Of all respondents, 68% were able to name > or =1 correct stroke risk factor, and 13% named 4 correct risk factors. The majority of respondents named mass media as source of information (82%), followed by family/friends (45%) and by general physicians (20%). In multivariable analysis, increased knowledge of stroke risk factors was significantly associated with younger age, a higher educational level, not living alone, a German nationality, and having received any information about stroke during the last year. However, characteristics of respondents using the respective sources of information varied significantly., Conclusions: Mass media was most frequently named as a source of information about stroke risk factors. Source of information used varied according to population characteristics. Health education programs should take this into account and be adapted accordingly.

Study Objective: Differences between men and women in management and outcome following cerebrovascular events have been described. However, most of the differences observed have only been partially adjusted for baseline differences, or not at all. The objective of the present study was to compare acute and follow-up management between men and women after stroke and transitory ischemic attacks, adjusting for potential confounders., Design: Patients with symptoms of stroke were included at admission to one of four participating hospitals in the inner city of Berlin, Germany. Risk factors, clinical characteristics, and acute management were assessed from medical records. Patients were asked about socioeconomic factors and follow-up management in a baseline interview and by postal questionnaire, respectively. The follow-up was 12 months. Multiple logistic regression analyses were used to assess odds ratios for management variables., Results: A total of 558 patients were included (55% men, mean age 65+/-13 years; 45% women, 69+/-14 years). Indications for admission were stroke (74%) and transitory ischemic attacks (26%). In multivariable analyses, there were no differences in diagnostic procedures performed at baseline and in follow-up management between men and women. However, women were significantly more likely to receive hypoglycemic drugs (odds ratio 2.49; 95% confidence interval 1.33-4.63) in the acute management period. Regarding the need for nursing support/a nursing home after 12 months, there were no significant differences between men and women., Conclusions: After adjustment for differences in baseline characteristics, we only found few differences in acute and long-term management between men and women following hospital admission after suffering a cerebrovascular event., (Copyright (c) 2006 S. Karger AG, Basel.)

Background: It is unclear whether clinical signs and symptoms differ in the presentation of transient ischemic attack (TIA) and stroke, apart from temporal dynamics., Methods: Signs and symptoms of patients diagnosed with TIA or stroke were prospectively collected and compared by means of an age-adjusted logistic regression analysis. Risk factors, prehospital medication, and diagnostic workup were obtained from the charts., Results: Four hundred five patients diagnosed with stroke (68+/-12 years old, 45% female) and 143 diagnosed with TIA (64+/-14 years old, 48% female) were included. Signs and symptoms of patients with TIA were less often "classic" such as paresis (48% vs 71%, P<0.001) or sensory loss (38% vs 48%, P=0.03). The etiology of TIA was more often classified as "undetermined" (57% vs 46%, P<0.05)., Conclusions: Transient ischemic attack needs special attention and intensive diagnostic workup, because it bears a considerable risk of death and disability but presents less often with classic signs and symptoms and its etiology often remains undetermined.

The 36-item short-form health survey (SF-36) is one of the most commonly used health status instruments in patients with cerebrovascular disease. However, responsiveness to change in health-related quality of life (HRQoL) has not yet been assessed for the SF-36 and its shortened version, the SF-12. The main objective of the present study was to determine responsiveness to change of the SF-12 in patients with cerebrovascular disease. Patients with stroke/transient ischaemic attack (TIA) were included at admission to one of four participating hospitals. HRQoL was assessed with the Physical (PCS-12) and Mental (MCS-12) Component Summary scales at baseline (referring to the status prior to the event) and after 12 months. Responsiveness to change was determined with the standardized response mean (SRM) and classified as small (SRM 0.20-0.49), moderate (0.50-0.79) or large (> or =0.80). A total of 558 patients were included [55% men, mean age 65 (SD, 13) years; 45% women, mean age 69 (SD, 14) years]. Indications for admission were stroke (74%) and TIA (26%). In patients with stroke, SRMs were small for the PCS-12 [SRM 0.49; absolute change -5.9 (SD, 12)] and moderate for the MCS-12 [SRM 0.52; absolute change -6.6 (SD, 13)]. In patients with TIA, SRMs were below 0.2 for the PCS-12 [absolute change -0.7 (SD, 11)] and small for the MCS-12 [SRM 0.34; absolute change -3.7 (SD, 11)]. SRMs increased with stroke severity as indicated by the NIHSS score. The SF-12 summary scales showed a small to moderate responsiveness to change in patients after stroke. Responsiveness to change was higher in patients with increased symptom severity.

Study Objective: We determine the interval between stroke symptom onset and time to emergency department (ED) arrival and factors associated with delays in presentation., Methods: All patients with acute stroke presenting at 4 hospitals in a metropolitan area and consenting to an interview were prospectively included over a 12-month period, excluding patients with presentation greater than 7 days after onset of symptoms and discharge or death within 24 hours after ED arrival. Initially, National Institutes of Health Stroke Scale and times of symptom onset and of ED arrival were registered by a neurologist. Sociodemographic factors and data about the course of events were obtained by standardized interview conducted with patients or proxies. In a multivariable analysis, an extended Cox proportional hazards model was used, and hazard ratios were determined., Results: Primary analyses were performed for 558 interviewed patients (mean age 66.8+/-13.5 years, 45% female patients) with confirmed stroke; 452 (81%) patients had a known onset of symptoms. Median interval between symptom onset and ED arrival was 151 minutes (range 5 to 9,590 minutes). Transport by emergency medical services (adjusted hazard ratio 0.28 [95% confidence interval (CI) 0.19 to 0.41]), increasing age (hazard ratio 0.99 [95% CI 0.98 to 0.99]), greater stroke severity (National Institutes of Health Stroke Scale score; hazard ratio 0.93 [95% CI 0.90 to 0.96]), having transient ischemic attack rather than persistent symptoms (hazard ratio 0.32 [95% CI 0.22 to 0.46]) and symptoms considered urgent (hazard ratio 0.68 [95% CI 0.55 to 0.84]) were the factors most strongly associated with a shorter out-of-hospital interval., Conclusion: There are considerable delays between stroke symptom onset and ED arrival. Programs to improve awareness of patients with stroke to seek medical help immediately may reduce unnecessary delays to ED arrival.

Background and Purpose: We investigated whether transient ischemic attacks (TIAs) before stroke can induce tolerance by raising the threshold of tissue vulnerability in the human brain., Methods: Sixty-five patients with first-ever ischemic territorial stroke received diffusion- and perfusion-weighted MRI within 12 hours of symptom onset. Epidemiological and clinical data, lesion volumes in T2, apparent diffusion coefficient (ADC) maps and perfusion maps, and cerebral blood flow and cerebral blood volume values were compared between patients with and without a prodromal TIA., Results: Despite similar size and severity of the perfusion deficit, initial diffusion lesions tended to be smaller and final infarct volumes were significantly reduced (final T2: 9.1 [interquartile range, 19.7] versus 36.5 [91.2] mL; P=0.014) in patients with a history of TIA (n=16). This was associated with milder clinical deficits., Conclusions: The beneficial effect of TIAs on lesion size in ADC and T2 suggests the existence of endogenous neuroprotection in the human brain.