Feasibility and comparability of different platelet function tests in acute stroke with or without prior antiplatelet therapy.

Background: The clinical course of ischemic and hemorrhagic strokes can be influenced by the coagulation status of individual patients. The prior use of antiplatelet therapy (APT) such as acetylsalicylic acid (ASA) or P2Y12-antagonists has been inconsistently described as possibly increasing the risk of hemorrhagic transformation or expansion. Since clinical studies describing prior use of antiplatelet medication are overwhelmingly lacking specific functional tests, we aimed to implement testing in routine stroke care. Methods: We used fluorescence-activated cell sorting (FACS) with antibodies against CD61 for thrombocyte identification and CD62p or platelet activation complex-1 (PAC-1) to determine platelet activation. Aggregometry and automated platelet functioning analyzer (PFA-200) were employed to test thrombocyte reactivity. FACS and aggregometry samples were stimulated in vitro with arachidonic acid (AA) and adenosine diphosphate (ADP) to measure increase in CD62p-/PAC-1-expression or aggregation, respectively. Results: Between February and July 2023, 20 blood samples (n = 11 ischemic strokes; n = 7 hemorrhagic strokes; n = 2 controls) were acquired and analyzed within 24 h of symptom onset. N = 11 patients had taken ASA, n = 8 patients no APT and n = 1 ASA+clopidogrel. ASA intake compared to no APT was associated with lower CD62p expression after stimulation with AA on FACS analysis (median 15.8% [interquartile range {IQR} 12.6-37.2%] vs. 40.1% [IQR 20.3-56.3%]; p = 0.020), lower platelet aggregation (9.0% [IQR 7.0-12.0%] vs. 88.5% [IQR 11.8-92.0%]; p = 0.015) and longer time to plug formation with PFA-200 (248.0 s [IQR 157.0-297] vs. 121.5 s [IQR 99.8-174.3]; p = 0.027). Significant correlations were noted between AA-induced CD62p expression and aggregometry analysis (n = 18; ρ = 0.714; p < 0.001) as well as a negative correlation between CD62p increase and PFA clot formation time (n = 18; ρ = -0.613; p = 0.007). Sensitivity for ASA intake was highest for PFA (81.8% for values ≥155.5 s). The combination of ASA + clopidogrel also affected ADP-induced CD62p and PAC-1 expression. Conclusion: In the clinical setting it is feasible to use differentiated platelet analytics to determine alterations caused by antiplatelet therapy. Among the tests under investigation, PFA-200 showed the highest sensitivity for the intake of ASA in stroke patients. FACS analysis on the other hand might be able to provide a more nuanced approach to altered platelet reactivity.

Elective carotid stenting fulfills quality standards defined in guidelines. / Elektives Carotis-Stenting erfüllt die in Leitlinien festgelegten Qualitätsstandards.

PURPOSE: According to evidence from randomized trials and current guidelines, elective carotid artery stenting (CAS) is still considered second-line therapy compared with carotid endarterectomy (CEA). However, the publication of randomized comparative trials for patients with symptomatic stenoses occurred well over 10 years ago. In view of problems regarding German quality assurance when differentiating elective from emergency interventions and low case numbers for CAS indications, it seemed reasonable to present neurologically controlled CAS results and to investigate whether elective CAS consistently fulfills the strict quality criteria and what differences exist with respect to emergency CAS interventions in acute ischemic stroke. MATERIALS AND METHODS: Between 01/2012 and 07/2022, 141 elective CAS procedures were performed to treat patients with symptomatic (n = 123) and asymptomatic (n = 18) stenoses. Protection by a filter system was achieved in 134 of these elective procedures (95 %). During the same period, 158 patients underwent carotid stenting for acute stroke. Complication rates were determined using neurologically controlled data. CAS-related complications (stent thrombosis, stent-associated vascular damage, thromboembolism, and symptomatic hemorrhage) were extracted from emergency interventions, and clinical outcome (NIHSS progression) was determined during the inpatient stay. RESULTS: The rate of stroke and death determined during the inpatient stay for elective symptomatic patients was 0.8 %. Early treatment within the first 7 days after the index event, age > 70 years, and operator experience were not significant risk factors for the occurrence of complications. No complications were observed after CAS of asymptomatic stenoses. The procedure-related complication rate for emergency procedures was 7.8 %, which was significantly higher than after elective CAS, as expected (p < 0.006). CONCLUSION: Even with limited indications and limited case numbers, compliance with the strict quality criteria of the current S3 Guideline 2022 for elective CAS interventions is possible for both symptomatic and asymptomatic stenoses in an experienced center. Emergency CAS interventions have significantly higher complication rates under other conditions and must be considered separately with regard to quality assurance. KEY POINTS: · Elective carotid stenting fulfills the strict quality criteria of the current S3 guideline 2022.. · Emergency carotid stenting has significantly higher complication rates than elective procedures.. · Elective and emergency carotid stenting cannot be meaningfully compared.. CITATION FORMAT: · Keil F, Stahn S, Reitz SC et al. Elective carotid stenting fulfills quality standards defined in guidelines. Fortschr Röntgenstr 2023; DOI: 10.1055/a-2175-4029.

Topographic Mapping of Isolated Thalamic Infarcts Using Vascular and Novel Probabilistic Functional Thalamic Landmarks.

PURPOSE: We aimed to re-evaluate the relationship between thalamic infarct (TI) localization and clinical symptoms using a vascular (VTM) and a novel functional territorial thalamic map (FTM). METHODS: Magnetic resonance imaging (MRI) and clinical data of 65 patients with isolated TI were evaluated (female n = 23, male n = 42, right n = 23, left n = 42). A VTM depicted the known seven thalamic vascular territories (VT: inferolateral, anterolateral, inferomedial, posterior, central, anteromedian, posterolateral). An FTM was generated from a probabilistic thalamic nuclei atlas to determine six functionally defined territories (FT: anterior: memory/emotions; ventral: motor/somatosensory/language; medial: behavior/emotions/nociception, oculomotor; intralaminar: arousal/pain; lateral: visuospatial/somatosensory/conceptual and analytic thinking; posterior: audiovisual/somatosensory). Four neuroradiologists independently assigned diffusion-weighted imaging (DWI) lesions to the territories mapped by the VTM and FTM. Findings were correlated with clinical features. RESULTS: The most frequent symptom was a hemisensory syndrome (58%), which was not specific for any territory. A co-occurrence of hemisensory syndrome and hemiparesis had positive predictive values (PPV) of 76% and 82% for the involvement of the inferolateral VT and ventral FT, respectively. Thalamic aphasia had a PPV of 63% each for involvement of the anterolateral VT and ventral FT. Neglect was associated with involvement of the inferolateral VT/ventral FT. Interrater reliability for the assignment of DWI lesions to the VTM was fair (κ = 0.36), but good (κ = 0.73) for the FTM. CONCLUSION: The FTM revealed a greater reproducibility for the topographical assignment of TI than the VTM. Sensorimotor hemiparesis and neglect are predictive for a TI in the inferolateral VT/ventral FT. The hemisensory syndrome alone does not allow any topographical assignment.

Divergence and Convergence of Sex-Specific Time Trends in Ischemic Stroke: 10-Year Analysis of a State-Wide Registry in Germany.

Background The incidence of ischemic stroke was previously expected to rise among countries with an aging population. Lately, several studies from developed countries have reported a decline in certain cohorts. Whether this applies to all sexes, however, is uncertain, with limited data on the temporal development in incidence, treatment, and recovery. Methods and Results We analyzed a prospective stroke inpatient quality-assurance registry of the federal state of Hesse, Germany. Recruitment of all patients with a final diagnosis of ischemic stroke at hospital discharge (International Classification of Diseases, Tenth Revision [ICD-10]: I63) is mandatory by law. Incidence rates were calculated based on census data of all inhabitants and stratified according to age. Between 2010 and 2019, there were 141 277 patients included, 73 770 (52.2%) male patients and 67 507 (47.8%) female patients. Overall, the incidence of ischemic stroke was 228 per 100 000 in 2010 and 226 per 100 000 in 2019 (-0.8%; odds ratio [OR], 0.99 [95% CI, 0.96-1.02]; P=0.50). For male patients, the incidence increased continuously from 236 per 100 000 to 245 per 100 000 (+3.8%); in female patients it decreased from 220 per 100 000 to 208 per 100 000 (-5.6%). After adjusting for age, the OR for ischemic stroke between male and female patients was 1.40 in 2010 (95% CI, 1.35-1.44; P<0.001) and 1.48 in 2019 (95% CI, 1.43-1.53; P<0.001). This development was most pronounced in male patients aged 45 to 59 years with an increase from 151 per 100 000 to 176 per 100 000. In this age group, male patients showed increasing rates of prior strokes and atrial fibrillation, surpassing the prevalence in female patients over time. After multivariable regression analysis, male patients had a lower modified Rankin Scale at discharge compared with female patients, but this difference has decreased since 2015 (common OR in 2010, 0.83 [95% CI, 0.78-0.88]; common OR in 2019, 0.90 [95% CI, 0.84-0.95]), which coincided with rising rates of endovascular treatment. Conclusions Over the past decade in the federal state of Hesse, the overall incidence of ischemic stroke has declined predominantly in the female population. In contrast, for male patients, the incidence has risen by about 4%, with a steeper increase of 16% in male patients aged 45 to 59 years, which might be related to increasing rates of recurrent strokes and atrial fibrillation in this cohort. This finding provides a cautionary tale for effective secondary prevention. Female patients were generally less likely to achieve a favorable outcome, but since the introduction of endovascular treatment, the outcome gap is decreasing.

Measurement of Platelet Function in an Experimental Stroke Model With Aspirin and Clopidogrel Treatment.

Dual antiplatelet treatment (DAPT) increases the risk of tPA-associated hemorrhagic transformation (HT) in ischemic stroke. To investigate the effects of DAPT in rodents, reliable indicators of platelet function utilizing a minimally invasive procedure are required. We here established a fluorescence-based assay to monitor DAPT efficiency in a mouse model of ischemic stroke with HT. Male C57/BL6 mice were fed with aspirin and clopidogrel (ASA+CPG). Venous blood was collected, stimulated with thrombin, labeled with anti-CD41-FITC and anti-CD62P-PE, and analyzed by flow cytometry. Subsequently, animals were subjected to experimental stroke and tail bleeding tests. HT was quantified using NIH ImageJ software. In ASA+CPG mice, the platelet activation marker CD62P was reduced by 40.6 ± 4.2% (p < 0.0001) compared to controls. In vitro platelet function correlated inversely with tail bleeding tests (r = -0.8, p = 0.0033, n = 12). Twenty-four hours after drug withdrawal, platelet activation rates in ASA+CPG mice were still reduced by 20.2 ± 4.1% (p = 0.0026) compared to controls, while tail bleeding volumes were increased by 4.0 ± 1.4 µl (p = 0.004). Conventional tests using light transmission aggregometry require large amounts of blood and thus cannot be used in experimental stroke studies. In contrast, flow cytometry is a highly sensitive method that utilizes small volumes and can easily be incorporated into the experimental stroke workflow. Our test can be used to monitor the inhibitory effects of DAPT in mice. Reduced platelet activation is indicative of an increased risk for tPA-associated cerebral hemorrhage following experimental stroke. The test can be applied to individual animals and implemented flexibly prior and subsequent to experimental stroke.

Dual Antiplatelet Therapy Increases Hemorrhagic Transformation Following Thrombolytic Treatment in Experimental Stroke.

Background and Purpose- Dual antiplatelet treatment poses a risk for increased hemorrhagic transformation (HT) following intravenous thrombolysis and mechanical thrombectomy. The aim of this study was to implement a model of experimental stroke with tissue-type plasminogen activator (tPA)-associated HT in mice on dual antiplatelet treatment to enable mechanistic studies and also to allow for an initial assessment of therapeutic approaches to limit HT. Methods- Male C57BL6 mice were fed with Aspirin and Clopidogrel via drinking water for 3 days. Subsequently, mice were subjected to 2-hour transient middle cerebral artery occlusion, and tPA was infused when indicated. HT was quantified by measuring hemorrhaged areas in brain sections with ImageJ. TTC staining was used to determine infarct size. Platelet function was tested in vitro using flow cytometry and in vivo with standard tail bleeding tests. Results- Both flow cytometry and tail bleeding volumes indicated significantly reduced platelet function following Aspirin and Clopidogrel treatment. While tPA administered 2 hours after onset of middle cerebral artery occlusion did not cause bleeding in control mice (0.51±0.13 mm2), HT significantly increased by 18.9±5.4 mm2 (P=0.0045) in Aspirin and Clopidogrel mice treated with tPA. HT in aspirin and clopidogrel mice not treated with tPA was nonsignificantly elevated by 8.0±4.6 mm2 (P=0.3784) compared with controls. Infarct sizes did not differ between groups. The HT persisted when the tPA dosage was reduced. Conclusions- We successfully established a translational stroke model of tPA treatment under dual antiplatelet treatment. The impaired platelet function led to an increased risk for HT in tPA-treated mice. Reducing the dosage of tPA did not prevent this hemorrhagic complication.