Cerebral small vessel disease burden and cognitive and functional outcomes after stroke: A multicenter prospective cohort study.

INTRODUCTION: It remains unknown whether the global small vessel disease (SVD) burden predicts post-stroke outcomes. METHODS: In a prospective multicenter study of 666 ischemic and hemorrhagic stroke patients, we quantified magnetic resonance imaging (MRI)-based SVD markers (lacunes, white matter hyperintensities, microbleeds, perivascular spaces) and explored associations with 6- and 12-month cognitive (battery of 15 neuropsychological tests) and functional (modified Rankin scale) outcomes. RESULTS: A global SVD score (range 0-4) was associated with cognitive impairment; worse performance in executive function, attention, language, and visuospatial ability; and worse functional outcome across a 12-month follow-up. Although the global SVD score did not improve prediction, individual SVD markers, assessed across their severity range, improved the calibration, discrimination, and reclassification of predictive models including demographic, clinical, and other imaging factors. DISCUSSION: SVD presence and severity are associated with worse cognitive and functional outcomes 12 months after stroke. Assessing SVD severity may aid prognostication for stroke patients. HIGHLIGHTS: In a multi-center cohort, we explored associations of small vessel disease (SVD) burden with stroke outcomes. SVD burden associates with post-stroke cognitive and functional outcomes. A currently used score of SVD burden does not improve the prediction of poor outcomes. Assessing the severity of SVD lesions adds predictive value beyond known predictors. To add predictive value in assessing SVD in stroke patients, SVD burden scores should integrate lesion severity.

Revacept, an Inhibitor of Platelet Adhesion in Symptomatic Carotid Stenosis: A Multicenter Randomized Phase II Trial.

BACKGROUND: Patients with symptomatic internal carotid artery (ICA) stenosis are at high risk of recurrent ischemic stroke and require early interventional treatment and antiplatelet therapy. Increased bleeding rates might counterbalance the periprocedural efficacy of intensified platelet inhibition. We aim to investigate, whether Revacept, a competitive antagonist of glycoprotein VI, adjunct to standard antiplatelet therapy reduces the occurrence of ischemic lesions in patients with symptomatic ICA stenosis. METHODS: International, multicenter (16 sites), 3-arm, randomized (1:1:1), double-blind, and placebo-controlled study with parallel groups, including patients with symptomatic ICA stenosis. A single infusion over 20 minutes of either placebo, 40 mg or 120 mg Revacept in addition to guideline-conform antiplatelet therapy was evaluated with regard to the exploratory efficacy end point: Number of new ischemic lesions on diffusion-weighted magnetic resonance imaging after treatment initiation. Main clinical outcome was the combined safety and efficacy end point including any stroke or death, transient ischemic attack, myocardial infarction, coronary intervention, and bleeding complications during follow-up. RESULTS: Out of 160 randomized patients, 158 patients (68±10.1 years, 24% female) received study medication (51 patients placebo, 54 patients 40 mg Revacept and 53 patients 120 mg Revacept) and were followed for 11.2±2.3 months. A total of 1.16 (95% CI, 0.88-1.53)/1.05 (95% CI, 0.78-1.42; P=0.629)/0.63 (95% CI, 0.43-0.93) new diffusion-weighted magnetic resonance imaging lesions per patient were detected in the placebo/40 mg/120 mg Revacept groups, without statistical evidence of a difference. A reduction of the combined safety and efficacy end point during the study period was observed in patients who received 120 mg (HR, 0.46 [95% CI, 0.21-0.99]; P=0.047), but not 40 mg Revacept compared with placebo (HR, 0.72 [95% CI, 0.37-1.42]; P=0.343). CONCLUSIONS: Revacept 120 mg reduced the combined safety and efficacy end point in patients with symptomatic ICA stenosis. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique Identifier: NCT01645306.

Patient-Centered Outcomes in a Randomized Trial Investigating a Multimodal Prevention Program After Transient Ischemic Attack or Minor Stroke: The INSPiRE-TMS Trial.

BACKGROUND: The INSPiRE-TMS trial (Intensified Secondary Prevention Intending a Reduction of Recurrent Events in Transient Ischemic Attack and Minor Stroke Patients) investigated effects of a multicomponent support program in patients with nondisabling stroke or transient ischemic attack. Although secondary prevention targets were achieved more frequently in the intensified care group, no significant differences were seen in rates of recurrent major vascular events. Here, we present the effects on prespecified patient-centered outcomes. METHODS: In a multicenter trial, we randomized patients with modifiable risk factors either to the intensified or conventional care alone program. Intensified care was provided by stroke specialists and used feedback and motivational interviewing strategies (≥8 outpatient visits over 2 years) aiming to improve adherence to secondary prevention targets. We measured physical fitness, disability, cognitive function and health-related quality of life by stair-climbing test, modified Rankin Scale, Montreal Cognitive Assessment, and European Quality of Life 5 Dimension 3 Level during the first 3 years of follow-up. RESULTS: Of 2072 patients (mean age: 67.4years, 34% female) assessed for the primary outcome, patient-centered outcomes were collected in 1,771 patients (877 intensified versus 894 conventional care group). Physical fitness improved more in the intensified care group (mean between-group difference in power (Watt): 24.5 after 1 year (95% CI, 5.5-43.5); 36.1 after 2 years (95% CI, 13.1-59.7) and 29.6 (95% CI, 2.0-57.3 after 3 years). At 1 year, there was a significant shift in ordinal regression analysis of modified Rankin Scale in favor of the intensified care group (common odds ratio, 1.23 [95% CI, 1.03-1.47]) but not after 2 (odds ratio, 1.17 [95% CI, 0.96-1.41]) or 3 years (odds ratio, 1.16 [95% CI, 0.95-1.43]) of follow-up. However, Montreal Cognitive Assessment and European Quality of Life 5 Dimension scores showed no improvement in the intensified intervention arm after 1, 2, or 3 years of follow-up. CONCLUSIONS: Patients of the intensified care program group had slightly better results for physical fitness and modified Rankin Scale after 1 year, but none of the other patient-centered outcomes was significantly improved. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01586702.

Histology of Cerebral Clots in Cryptogenic Stroke Varies According to the Presence of a Patent Foramen Ovale.

Although a pathophysiological impact remains difficult to prove in individual patient care, a patent foramen ovale (PFO) is currently considered of high relevance for secondary prophylaxis in selected patients with cryptogenic ischemic stroke. By quantification of histological clot composition, we aimed to enhance pathophysiological understanding of PFO attributable ischemic strokes. Retrospectively, we evaluated all cerebral clots retrieved by mechanical thrombectomy for acute ischemic stroke treatment between 2011 and 2021 at our comprehensive stroke care center. Inclusion criteria applied were cryptogenic stroke, age (≤60 years), and PFO status according to transesophageal echocardiography, resulting in a study population of 58 patients. Relative clot composition was calculated using orbit image analysis to define the ratio of main histologic components (fibrin/platelets (F/P), red blood cell count (RBC), leukocytes). Cryptogenic stroke patients with PFO (PFO+, n = 20) displayed a significantly higher percentage of RBC (0.57 ± 0.17; p = 0.002) and lower percentage of F/P (0.38 ± 0.15; p = 0.003) compared to patients without PFO (PFO-, n = 38) (RBC: 0.41 ± 0.21; F/P: 0.52 ± 0.20). In conclusion, histologic clot composition in cryptogenic stroke varies depending on the presence of a PFO. Our findings histologically support the concept that a PFO may be of pathophysiological relevance in cryptogenic ischemic stroke.

Misconceptions regarding the adequacy of best medical intervention alone for asymptomatic carotid stenosis.

BACKGROUND: Medical intervention (risk factor identification, lifestyle coaching, and medication) for stroke prevention has improved significantly. It is likely that no more than 5.5% of persons with advanced asymptomatic carotid stenosis (ACS) will now benefit from a carotid procedure during their lifetime. However, some question the adequacy of medical intervention alone for such persons and propose using markers of high stroke risk to intervene with carotid endarterectomy (CEA) and/or carotid angioplasty/stenting (CAS). Our aim was to examine the scientific validity and implications of this proposal. METHODS: We reviewed the evidence for using medical intervention alone or with additional CEA or CAS in persons with ACS. We also reviewed the evidence regarding the validity of using commonly cited makers of high stroke risk to select such persons for CEA or CAS, including markers proposed by the European Society for Vascular Surgery in 2017. RESULTS: Randomized trials of medical intervention alone versus additional CEA showed a definite statistically significant CEA stroke prevention benefit for ACS only for selected average surgical risk men aged less than 75 to 80 years with 60% or greater stenosis using the North American Symptomatic Carotid Endarterectomy Trial criteria. However, the most recent measurements of stroke rate with ACS using medical intervention alone are overall lower than for those who had CEA or CAS in randomized trials. Randomized trials of CEA versus CAS in persons with ACS were underpowered. However, the trend was for higher stroke and death rates with CAS. There are no randomized trial results related to comparing current optimal medical intervention with CEA or CAS. Commonly cited markers of high stroke risk in relation to ACS lack specificity, have not been assessed in conjunction with current optimal medical intervention, and have not been shown in randomized trials to identify those who benefit from a carotid procedure in addition to current optimal medical intervention. CONCLUSIONS: Medical intervention has an established role in the current routine management of persons with ACS. Stroke risk stratification studies using current optimal medical intervention alone are the highest research priority for identifying persons likely to benefit from adding a carotid procedure.

Clinical associations of T2-weighted lesion load and lesion location in small vessel disease: Insights from a large prospective cohort study.

BACKGROUND: Subcortical T2-weighted (T2w) lesions are very common in older adults and have been associated with dementia. However, little is known about the strategic lesion distribution and how lesion patterns relate to vascular risk factors and cognitive impairment. AIM: The aim of this study was to analyze the association between T2w lesion load and location, vascular risk factors, and cognitive impairment in a large cohort of older adults. METHODS: 1017 patients participating in a large prospective cohort study (INtervention project on cerebroVAscular disease and Dementia in the district of Ebersberg, INVADE II) were analyzed. Cerebral T2w white matter and deep grey matter lesions, the so-called white matter hyperintensities (WMHs), were outlined semi-automatically on fluid attenuated inversion recovery images and normalized to standard stereotaxic space (MNI152) by non-linear registration. Patients were assigned to either a low-risk or a high-risk group. The risk assessment considered ankle brachial index, intima media thickness, carotid artery stenosis, atrial fibrillation, previous cerebro-/cardiovascular events and peripheral artery disease as well as a score based on cholesterol levels, blood pressure and smoking. Separate lesion distributions were obtained for the two risk groups and compared using voxel-based lesion-symptom mapping. Moreover, we assessed the relation between lesion location and cognitive impairment (demographically adjusted z-scores of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery Plus, CERAD-NAB Plus) using voxel-based statistics (α = 0.05). RESULTS: A total of 878 out of 1017 subjects (86%) had evaluable MRI data and were included in the analyses (mean age: 68.2 ±â€¯7.6 years, female: 515). Patients in the high-risk group were characterized by a significantly higher age, a higher proportion of men, a higher lesion load (p < 0.001), and a worse performance in some of the cognitive subdomain scores (p < 0.05). Voxels with significant associations to the subjects' cerebrovascular risk profiles were mainly found at locations of the corpus callosum, superior corona radiata, superior longitudinal fasciculus, internal and external capsule, and putamen. While several cognitive domains have shown significant associations with the participants' total lesion burden (p < 0.05), no focal WMH locations were found to be associated with cognitive impairment. CONCLUSION: Age, gender, several cognitive scores, and WMH lesion load were shown to be significantly associated with vascular risk factors in a population of older, but cognitively preserved adults. Vascular risk factors seem to promote lesion formation most severely at well-defined locations. While lesion load showed weak associations to some cognitive scores, no focal locations causing specific cognitive disturbances were identified in this large cohort of older adults.

Thrombus Permeability in Admission Computed Tomographic Imaging Indicates Stroke Pathogenesis Based on Thrombus Histology.

Background and Purpose- Intracranial thrombi can be characterized according to their permeability as measured by contrast agent penetration. Thrombus composition and its associated pathogenesis are important factors affecting treatment and secondary prevention. We aimed to explore the histopathologic factors explaining the heterogeneity of thrombus permeability measures and evaluated potential correlations with stroke pathogenesis. Methods- Thrombus densities were measured in thin-slice noncontrast computed tomography and automatically aligned computed tomographic angiography images of 133 patients with large-vessel occlusions of the middle cerebral artery. Change in thrombus attenuation (Δt) and corrected void fraction (ε; attenuation increase corrected for contralateral artery densities) were calculated. First, these thrombus perviousness measures were correlated with histological thrombus components (especially fractions of fibrin-platelet accumulation and red blood cells) and stroke pathogenesis (n=32). For validation, an association between perviousness and pathogenesis was assessed in a second, independent cohort (n=101). Results- Thrombus perviousness estimates were correlated with both fibrin/platelets fractions (Δt: r=0.43, P=0.016/ε: r=0.45, P=0.01) and inversely with red blood cells counts (Δt: r=-0.46, P=0.01/ε: r=-0.49, P=0.006). In the first cohort, Δt was substantially higher in samples from patients with cardioembolic stroke pathogenesis as compared with noncardioembolic-derived thrombi ( P=0.026). In the validation cohort, thrombus perviousness measures differed significantly between cardioembolic (Δt: median [ interquartile range]=12.53 [8.70-17.90]; ε: median [interquartile range]=0.054 [0.036-0.082]) and noncardioembolic thrombi (Δt: median [interquartile range]=3.2 [2.17-6.44], P<0.001; ε: median [interquartile range]=0.020 [0.011-0.027], P<0.001) and were associated with pathogenesis (Δt: ß=0.45, P=0.016/ε: ß=83.6, P=0.013) in a binary logistic regression model. Conclusions- Permeable thrombi showed a strong correlation with lower fractions of red blood cells counts and more fibrin/platelets conglomerations, concurrent with an association with cardioembolic origin. This novel information about thrombus perviousness may be valuable as a new and simple to acquire imaging marker for identifying stroke pathogenesis using early and readily available imaging.

Association of clinical headache features with stroke location: An MRI voxel-based symptom lesion mapping study.

Background We have recently shown that the presence of headache in ischemic stroke is associated with lesions of the insular cortex. The aim of this post-hoc subgroup analysis was to investigate the association of specific headache features with stroke location in patients with acute ischemic stroke. Methods In this observational study, patients (mean age: 61.5, 58% males) with ischemic stroke and acute headache (n = 49) were investigated. Infarcts were manually outlined on 3D diffusion weighted magnetic resonance imaging (MRI) scans and transformed into standard stereotaxic space; lesions of the left hemisphere were mirrored in the x-axis to allow a voxel-wise group analysis of all patients. We analyzed the association of lesion location and the following phenotypical characteristics by voxel-based symptom lesion mapping: Headache intensity, different qualities of headache (pulsating, tension-type like and stabbing), and the presence of nausea, of cranial autonomic symptoms and of light or noise sensitivity. Results Headache intensity was associated with lesions of the posterior insula, the operculum and the cerebellum. "Pulsating" headache occurred with widespread cortical and subcortical strokes. The presence of "tension-like" and "stabbing" headache was not related to specific lesion patterns. Nausea was associated with lesions in the posterior circulation territory. Cranial-autonomic symptoms were related to lesions of the parietal lobe, the somatosensory cortex (SI) and the middle temporal cortex. The presence of noise sensitivity was associated with cerebellar lesions, whereas light sensitivity was not related to specific lesions in our sample. Conclusion Headache phenotype in ischemic stroke appears to be related to specific ischemic lesion patterns.

A short time interval between the neurologic index event and carotid endarterectomy is not a risk factor for carotid surgery.

OBJECTIVE: Current guidelines recommend that carotid endarterectomy (CEA) be performed as early as possible after the neurologic index event in patients with 50% to 99% carotid artery stenosis. However, recent registry data showed that patients treated ≤48 hours had a significantly increased perioperative risk. Therefore, the aim of this single-center study was to determine the effect of the time interval between the neurologic index event and CEA on the periprocedural complication rate at our institution. METHODS: Prospectively collected data for 401 CEAs performed between 2004 and 2014 for symptomatic carotid stenosis were analyzed. Patients were divided into four groups according to the interval between the last neurologic event and surgery: group I, 0 to 2 days; group II, 3 to 7 days; group III, 8 to 14 days; and group IV, 15 to 180 days. The primary end point was the combined rate of in-hospital stroke or mortality. Data were analyzed by way of χ2 tests and multivariable regression analysis. RESULTS: The patients (68% men) had a median age of 70 years (interquartile range, 63-76 years). The index events included transient ischemic attack in 43.4%, amaurosis fugax in 25.4%, and an ipsilateral stroke in 31.2%. CEA was performed using the eversion technique in 61.1% of patients, and 50.1% were treated under locoregional anesthesia. The perioperative combined stroke and mortality rate was 2.5% (10 of 401), representing a perioperative mortality rate of 1.0% and stroke rate of 1.5%. Overall, myocardial infarction, cranial nerve injuries, and postoperative bleeding occurred in 0.7%, 2.2%, and 1.7%, respectively. We detected no significant differences for the combined stroke and mortality rate by time interval: 3% in group I, 3% in group II, 2% in group III, and 2% in group IV. Multivariable regression analysis showed no significant effect of the time interval on the primary end point. CONCLUSIONS: The combined mortality and stroke rate was 2.5% and did not differ significantly between the four different time interval groups. CEA was safe in our cohort, even when performed as soon as possible after the index event.

The CD31 molecule: a possible neuroprotective agent in acute ischemic stroke?

BACKGROUND: The transmembrane receptor molecule CD31 is known to have immunomodulatory functions, suggesting a possible neuroprotective effect in the context of acute ischemic stroke by restricting an over-activation of secondary immunological processes. This study examines the density of CD31+ cells in mechanically extracted thrombi of stroke patients with the aim to test whether the occurrence of CD31+ cells was associated with a beneficial clinical outcome in those patients. METHODS: Thrombi of 122 consecutive patients with large anterior circulation stroke were collected during intracranial mechanical recanalization. Out of these, 86 immunostained specimens of adequate quality could be analysed. The density of CD31+ cells was quantified and compared with clinical outcome data of the affected patients. RESULTS: The density of CD31+ cells was positively related to early patient improvement (ΔNIHSS, r = 0.283, p = 0,012) with an even clearer relationship after exclusion of patients who died in the early hospital phase (r = 0.371, p = 0.001). This finding stayed stable also in the multivariate analysis after corrrection for other outcome-influencing factors (p = 0.049). CONCLUSION: This study shows a stable relation between CD31+ cells and early clinical improvement of patients with acute ischemic stroke. This finding is in line with recent reports showing immunomodulatory and potential neuroprotective effects of CD31, suggesting that CD31 may be a promising neuroprotective agent in stroke patients.

Headache in acute ischaemic stroke: a lesion mapping study.

Headache is a common symptom in acute ischaemic stroke, but the underlying mechanisms are incompletely understood. The aim of this lesion mapping study was to identify brain regions, which are related to the development of headache in acute ischaemic stroke. Patients with acute ischaemic stroke (n = 100) were assessed by brain MRI at 3 T including diffusion weighted imaging. We included 50 patients with stroke and headache as well as 50 patients with stroke but no headache symptoms. Infarcts were manually outlined and images were transformed into standard stereotaxic space using non-linear warping. Voxel-wise overlap and subtraction analyses of lesions as well as non-parametric statistics were conducted. The same analyses were carried out by flipping of left-sided lesions, so that all strokes were transformed to the same hemisphere. Between the headache group as well as the non-headache there was no difference in infarct volumes, in the distribution of affected vascular beds or in the clinical severity of strokes. The headache phenotype was tension-type like in most cases. Subtraction analysis revealed that in headache sufferers infarctions were more often distributed in two well-known areas of the central pain matrix: the insula and the somatosensory cortex. This result was confirmed in the flipped analysis and by non-parametric statistical testing (whole brain corrected P-value < 0.01). To the best of our knowledge, this is the first lesion mapping study investigating potential lesional patterns associated with headache in acute ischaemic stroke. Insular strokes turned out to be strongly associated with headache. As the insular cortex is a well-established region in pain processing, our results suggest that, at least in a subgroup of patients, acute stroke-related headache might be centrally driven.

Thrombus Histology Suggests Cardioembolic Cause in Cryptogenic Stroke.

BACKGROUND AND PURPOSE: Ischemic stroke of undetermined cause is a major health issue because of its high frequency and clinical relevance. Histopathologic analysis of human thrombi, retrieved from stroke patients with large-vessel occlusion during mechanical thrombectomy, may provide information about underlying pathologies. This study examines the relationship between stroke causes and histological clot composition to identify specific patterns that might help to distinguish causes of cryptogenic stroke. METHODS: Thrombi of 145 consecutive stroke patients with large-vessel occlusion were collected during intracranial mechanical recanalization. The hematoxylin and eosin-stained specimens were quantitatively analyzed in terms of the relative fractions of the main constituents (red and white blood cells and fibrin/platelets). These data, along with additional clinical and interventional parameters, were compared for different stroke subtypes, as defined by the international Trial of Org 10172 in Acute Stroke Treatment criteria. RESULTS: The composition of thrombi from cardioembolic and noncardioembolic stroke patients differed significantly for all main thrombus components. Cardioembolic thrombi had higher proportions of fibrin/platelets (P=0.009), less erythrocytes (P=0.003), and more leucocytes (P=0.035) than noncardioembolic thrombi. Cryptogenic strokes showed strong overlap with cardioembolic strokes but not with noncardioembolic strokes, in terms of both thrombus histology and interventional and clinical outcome parameters. CONCLUSIONS: Quantitative evaluation of thrombus composition may help to distinguish between different stroke causes. Our findings support the notion that the majority of cryptogenic strokes are cardioembolic.

High-risk plaque features can be detected in non-stenotic carotid plaques of patients with ischaemic stroke classified as cryptogenic using combined (18)F-FDG PET/MR imaging.

PURPOSE: The aim of this study was to investigate in 18 patients with ischaemic stroke classified as cryptogenic and presenting non-stenotic carotid atherosclerotic plaques the morphological and biological aspects of these plaques with magnetic resonance imaging (MRI) and (18)F-fluoro-deoxyglucose positron emission tomography ((18)F-FDG PET) imaging. METHODS: Carotid arteries were imaged 150 min after injection of (18)F-FDG with a combined PET/MRI system. American Heart Association (AHA) lesion type and plaque composition were determined on consecutive MRI axial sections (n = 460) in both carotid arteries. (18)F-FDG uptake in carotid arteries was quantified using tissue to background ratio (TBR) on corresponding PET sections. RESULTS: The prevalence of complicated atherosclerotic plaques (AHA lesion type VI) detected with high-resolution MRI was significantly higher in the carotid artery ipsilateral to the ischaemic stroke as compared to the contralateral side (39 vs 0 %; p = 0.001). For all other AHA lesion types, no significant differences were found between ipsilateral and contralateral sides. In addition, atherosclerotic plaques classified as high-risk lesions with MRI (AHA lesion type VI) were associated with higher (18)F-FDG uptake in comparison with other AHA lesions (TBR = 3.43 ± 1.13 vs 2.41 ± 0.84, respectively; p < 0.001). Furthermore, patients presenting at least one complicated lesion (AHA lesion type VI) with MRI showed significantly higher (18)F-FDG uptake in both carotid arteries (ipsilateral and contralateral to the stroke) in comparison with carotid arteries of patients showing no complicated lesion with MRI (mean TBR = 3.18 ± 1.26 and 2.80 ± 0.94 vs 2.19 ± 0.57, respectively; p < 0.05) in favour of a diffuse inflammatory process along both carotid arteries associated with complicated plaques. CONCLUSION: Morphological and biological features of high-risk plaques can be detected with (18)F-FDG PET/MRI in non-stenotic atherosclerotic plaques ipsilateral to the stroke, suggesting a causal role for these plaques in stroke. Combined (18)F-FDG PET/MRI systems might help in the evaluation of patients with ischaemic stroke classified as cryptogenic.

Blood Leukocytes as Prognostic Parameter in Stroke Thrombectomy.

PURPOSE: Despite the recent success of mechanical thrombectomy (MT) in the treatment of acute ischemic stroke, prognostic parameters and criteria for patient selection are yet uncertain. Elevated levels of white blood cells (WBCs) constitute an independent risk factor for unfavorable outcome. Here we studied the link between outcome and WBC counts obtained before and after successful MT. METHODS: One hundred fifteen acute stroke patients successfully treated with MT (thrombolysis in cerebral infarction-scores 2b or 3) were included. WBC counts and C-reactive protein (CRP) levels were obtained prior to (WBC-pre, CRP-pre) and 1 day after MT (WBC-post, CRP-post). Clinical outcome measures consisted of National Institute of Health Stroke Scale (NIHSS) scores, and modified Rankin Scale (mRS) on day 90 (mRS-d90), dichotomized between scores ≤5 and >5 (NIHSS) and ≤2 and >2 (mRS). The association between WBC-/CRP-levels and outcome was assessed by correlation- and receiver-operating characteristic analyses. RESULTS: WBC counts on day 1 after MT correlated significantly with NIHSS scores at discharge and mRS-d90. Among patients >50 years, no patient with WBC-post counts exceeding 14.2 G/l had favorable NIHSS scores (≤5), and no one with WBC-post counts ≥12.6 G/l had favorable mRS-d90 outcome-scores (≤2). Further, even WBC-pre counts ≥10.6 G/l predicted unfavorable mRS-d90-scores in this subgroup. CONCLUSION: Elevated WBC counts obtained in routine blood tests may constitute a simple and economic parameter to estimate outcome after successful MT. Moreover, present data suggest that in patients older than 50 years, WBC counts may help to predict outcome even when obtained prior to MT.

Predicting dementia in primary care patients with a cardiovascular health metric: a prospective population-based study.

BACKGROUND: Improving cardiovascular health possibly decreases the risk of dementia. Primary care practices offer a suitable setting for monitoring and controlling cardiovascular risk factors in the older population. The purpose of the study is to examine the association of a cardiovascular health metric including six behaviors and blood parameters with the risk of dementia in primary care patients. METHODS: Participants (N = 3547) were insurants aged ≥55 of the largest German statutory health insurance company, who were enrolled in a six-year prospective population-based study. Smoking, physical activity, body mass index, blood pressure, total cholesterol, and fasting glucose were assessed by general practitioners at routine examinations. Using recommended cut-offs for each factor, the patients' cardiovascular health was classified as ideal, moderate, or poor. Behaviors and blood parameters sub-scores, as well as a total score, were calculated. Dementia diagnoses were retrieved from health insurance claims data. Results are presented as hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: Over the course of the study 296 new cases of dementia occurred. Adjusted for age, sex, and education, current smoking (HR = 1.77, 95% CI 1.09-2.85), moderate (1.38, 1.05-1.81) or poor (1.81, 1.32-2.47) levels of physical activity, and poor fasting glucose levels (1.43, 1.02-2.02) were associated with an increased risk of dementia. Body mass index, blood pressure, and cholesterol were not associated with dementia. Separate summary scores for behaviors and blood values, as well as a total score showed no association with dementia. Sensitivity analyses with differently defined endpoints led to similar results. CONCLUSIONS: Due to complex relationships of body-mass index and blood pressure with dementia individual components cancelled each other out and rendered the sum-scores meaningless for the prediction of dementia.

Systemic thrombolysis in anterior spinal artery syndrome: what has to be considered?

Anterior spinal artery syndrome (ASAS) often leads to complete motor paralysis with poor clinical outcome. There is a lack of controlled clinical trials on acute treatment strategies in ASAS. However, systemic thrombolysis with recombinant tissue-plasminogen activator (rt-PA) might be a useful therapeutic option in ASAS. We report the management of a patient with ASAS below thoracic level 10, who was treated with intravenous thrombolysis. An 81 year old patient presented with flaccid paraplegia. After exclusion of aortal dissection, spinal tumour or haemorrhage, the patient was treated with intravenous rt-PA 3 h 40 min after symptom onset. The follow up magnetic resonance imaging (MRI) showed spinal infarction below thoracic segment 10. In the clinical course, the patient partially recovered lower limb muscle strength and was able to walk with assistance. To the best of our knowledge, this is the first case in the literature of ASAS with MRI-proven spinal ischemia and the application of rt-PA. Systemic thrombolysis seems to be justifiable in patients with ASAS after the rule-out of aortal dissection and spinal bleeding.

Semiautomated analysis of carotid artery wall thickness in MRI.

PURPOSE: To develop a semiautomatic method based on level set method (LSM) for carotid arterial wall thickness (CAWT) measurement. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) of diseased carotid arteries was acquired from 10 patients. Ground truth (GT) data for arterial wall segmentation was collected from three experienced vascular clinicians. The semiautomatic variational LSM was employed to segment lumen and arterial wall outer boundaries on 102 MR images. Two computer-based measurements, arterial wall thickness (WT) and arterial wall area (AWA), were computed and compared with GT. Linear regression, Bland-Altman, and bias correlation analysis on WT and AWA were applied for evaluating the performance of the semiautomatic method. RESULTS: Arterial wall thickness measured by radial distance measure (RDM) and polyline distance measure (PDM) correlated well between GT and variational LSM (r = 0.83 for RDM and r = 0.64 for PDM, P < 0.05). The absolute arterial wall area bias between LSM and three observers is less than 10%, suggesting LSM can segment arterial wall well compared with manual tracings. The Jaccard Similarity (Js ) analysis showed a good agreement for the segmentation results between proposed method and GT (Js 0.71 ± 0.08), the mean curve distance for lumen boundary is 0.34 ± 0.2 mm between the proposed method and GT, and 0.47 ± 0.2 mm for outer wall boundary. CONCLUSION: The proposed LSM can generate reasonably accurate lumen and outer wall boundaries compared to manual segmentation, and can work similar to a human reader. However, it tends to overestimate CAWT and AWA compared to the manual segmentation for arterial wall with small area.

Suitability of the 6CIT as a screening test for dementia in primary care patients.

OBJECTIVES: To map the suitability of the Six Item Cognitive Impairment Test's (6CIT) as a screening instrument for dementia in primary care and to assess its feasibility, reliability, and validity in a real-world setting. METHOD: The present study was part of a population-based prospective trial aimed at reducing the incidence of stroke and dementia. The 6CIT was administered by general practitioners (GPs) at routine examinations every two years. Incidence of dementia was obtained from health insurance records. Psychometric qualities of the 6CIT were evaluated for two different cut-offs. RESULTS: At baseline, 72 GPs examined 3908 patients. In total, 528 patients were diagnosed with new dementia. Less than 1% of the tests were not completed. Internal consistency (Cronbach's alpha), stability over time (Pearson's r), and the agreement between successive tests (Cohen's kappa) reached values of 0.58, 0.62, and 0.45, respectively. Sensitivity and specificity reached values of 0.49 and 0.92 at the 7/8 cut-off and of 0.32 and 0.98 at the 10/11 cut-off, respectively. Patients with dementia had significantly higher mean error scores than patients without dementia. High scores at baseline posed a more than fourfold risk of being diagnosed with dementia. CONCLUSION: The 6CIT's psychometric properties in a real-world setting suggest that the test is not suited as a routine screening instrument. Factors inherent to screening in primary care likely contributed to its low reliability and validity. This highlights the need for training GPs in the conduct of cognitive screening before such procedures can be implemented on a routine basis.