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Abstract Background Several factors are frequently considered for outcome prediction rin stroke patients. We assessed the value of digital subtraction angiography (DSA)-based brain perfusion measurements after mechanical thrombectomy (MT) for outcome prediction in acute ischaemic stroke. Methods From DSA image data (n = 90; 38 females; age 73.3 ± 13.1 years [mean ± standard deviation]), time-contrast agent (CA) concentration curves were acquired, and maximum slope (MS), time to peak (TTP), and maximum CA concentration (CAmax) were calculated using an arterial input function. This data was used to predict neurological deficits at 24 h and upon discharge by using multiple regression analysis; the predictive capability was compared with the predictive power of the “Thrombolysis in cerebral infarction” (TICI) score. Intraclass correlation coefficients (ICC) of the NIHSS values were analysed. Results The comparison of means revealed a linear trend after stratification into TICI classes for CAmax (TICI 0: 0.07 ± 0.02 a.u. to TICI 3: 0.22 ± 0.07 a.u.; p

Abstract Objective Mechanical thrombectomy (MT) has become standard treatment in acute ischemic stroke due to large vessel occlusion (LVO). However, optimal blood pressure (BP) management following successful recanalization remains unclear. We aim to investigate the association of strictly achieving BP targets of ≤160/90 mmHg with the extent of neuronal loss and functional outcome. Methods In patients prospectively enrolled in the Gutenberg‐Stroke‐Study (May 2018–November 2019), BP was measured half‐hourly for 24 h following MT. Based on achieving BP target of ≤160/90 mmHg, patients with successful recanalization of LVO were divided into “low‐BP” group (BP ≤ 160/90 mmHg) or “high‐BP” group (BP > 160/90 mmHg). Neuronal loss was quantified by serum‐based measurement of neurofilament light chain (sNfL) after three days. BP groups and association of BP parameters with sNfL were investigated by correlation analyses and multiple regression modeling. Results Of 253 enrolled patients (mean age 73.1 ± 12.9 years, 53.4% female), 165 met inclusion criteria. 21.2% (n = 35) strictly achieved “low‐BP” target. “low‐BP” was associated with unfavorable functional outcome at 90‐day follow‐up (aOR [95%CI]: 5.88 [1.88–18.32], p = 0.002) and decreased health‐related quality of life (mean EQ‐5D‐index 0.45 ± 0.28 vs 0.63 ± 0.31, p = 0.009). sNfL levels were increased in “low‐BP” patients (median [IQR] 239.7 [168.4–303.4] vs 118.8 [52.5–220.5] pg/mL, p = 0.026). Hypotensive episodes were more frequent in the “low‐BP” group (48.6% vs 29.2%, p = 0.031). sNfL level could identify patients who had experienced hypotensive episodes with high discriminative ability (AUC [95%CI]: 0.68 [0.56–0.78], p = 0.007). Interpretation Strict BP control (≤160/90 mmHg) within 24 h following successful recanalization of LVO by MT is associated with increased neuronal injury, displayed by higher sNfL levels, and poorer functional outcome, potentially indicating hypotension‐induced neuronal loss during post‐MT phase.

Background and Purpose Prolonged electrocardiography (ECG)-monitoring in stroke patients improves the detection of paroxysmal atrial fibrillation (pAF). However, most randomized studies only had short follow-up. We aimed to provide 3-year follow-up data for AF detection and stroke recurrence risk. Methods We randomized 402 patients aged ≥60 years with acute ischemic strokes without AF to either enhanced and prolonged monitoring (EPM; 3×10-day Holter-ECG-monitoring) or standard-of-care (≥24 hours ECG-monitoring). The endpoint of the current analysis was AF within 36 months analyzed by intention to treat. Long-term follow-up was performed for 36 months. Results Two hundred and seventy-four patients (80%) participated in the extended follow-up (median duration of follow-up was 36 months [interquartile range, 12 to 36]). During the first 6 months, more AF was documented in the EPM arm compared to the control arm (13.5% vs. 5.1%; 95% confidence interval, 2.9% to 14.4%; P=0.004). During months 6 to 36, AF was less detected in the EPM intervention arm than in the control arm (2.0% vs. 7.3%; 95% confidence interval, 0.7% to 9.9%; P=0.028). Overall, the detection rate of AF within 36 months was numerically higher within the EPM group (15.0% vs. 11.1%, P=0.30). Numerically less patients in the EPM arm had recurrent ischemic strokes (5.5% vs. 9.1%, P=0.18), transient ischemic attacks (3.0% vs. 4.5%, P=0.44) or died (4.5% vs. 6.6%, P=0.37). Conclusions Enhanced and prolonged ECG monitoring increased AF detection during the first six months, but there was significantly more clinical AF during months 6 to 36 observed in the usual-care arm. This suggests that EPM leads to an earlier detection of clinically relevant AF.

Damage to axons is a core feature of ischemic stroke and cerebrovascular disease. The burden of axonal injury is correlated with the acute clinical deficits, the underlying burden of ischemic brain injury, the prognosis of recovery, and may be a meaningful therapeutic target for brain repair. Neurofilament light chain (NfL) has been identified as a blood-based biomarker that reflects neuroaxonal damage resulting from stroke. However, the utility of NfL as a blood-based biomarker in stroke is confounded by studies examining different temporal windows and patient populations. We conducted a systematic review and meta-analysis to verify the utility of blood NfL as a diagnostic, prognostic, and monitoring stroke biomarker. Nineteen studies reporting serum/plasma NfL values for a total of 4,237 distinct patients with stroke were identified. Using available summary data from the 10 studies that employed a common immunoassay platform, we utilized random effects linear mixed modeling and weighted averages to create a phasic model of serum/plasma NfL values in distinct time periods of acute stroke. Weighted averages show that blood NfL levels vary significantly across three distinct temporal epochs of acute (0–7 days), subacute (9–90 days), and chronic (>90 days) stroke with a steep peak in the early subacute period between 14 and 21 days after stroke. Blood NfL values can function as a diagnostic biomarker in distinguishing acute ischemic stroke from transient ischemic attack as well as amongst other cerebrovascular subtypes. Release of NfL into the bloodstream after stroke follows a distinct temporal dynamic that lags several weeks behind stroke onset and reliably associates with a stroke diagnosis despite some variability based on stroke subtype and severity. Identification of these temporal dynamics and the contribution of co- existent cerebrovascular disease states can improve the value of NfL as a stroke biomarker.

Abstract Objective Identification of ischemic stroke patients at high risk for paroxysmal atrial fibrillation (pAF) during 72 hours Holter ECG might be useful to individualize the allocation of prolonged ECG monitoring times, currently not routinely applied in clinical practice. Methods In a prospective multicenter study, the first analysable hour of raw ECG data from prolonged 72 hours Holter ECG monitoring in 1031 patients with acute ischemic stroke/TIA presenting in sinus rhythm was classified by an automated software (AA) into “no risk of AF” or “risk of AF” and compared to clinical variables to predict AF during 72 hours Holter‐ECG. Results pAF was diagnosed in 54 patients (5.2%; mean age: 78 years; female 56%) and was more frequently detected after 72 hours in patients classified by AA as “risk of AF” (n = 21, 17.8%) compared to “no risk of AF” (n = 33, 3.6%). AA‐based risk stratification as “risk of AF” remained in the prediction model for pAF detection during 72 hours Holter ECG (OR3.814, 95% CI 2.024‐7.816, P

BackgroundMechanical thrombectomy (MT) rates for the treatment of acute ischaemic stroke due to large vessel occlusion are steadily increasing, but are delivered in heterogenic settings. We aim to investigate effects of procedural load in centers with established MT-structures by comparing high- vs. low-volume centers with regard to procedural characteristics and functional outcomes.MethodsData from 5,379 patients enrolled in the German Stroke Registry Endovascular Treatment (GSR-ET) between June 2015 and December 2019 were compared between three groups: high volume: ≥180 MTs/year, 2,342 patients; medium volume: 135–179 MTs/year, 2,202 patients; low volume:

Patients with stroke or transient ischemic attacks (TIAs) and internal carotid artery stenosis harbor an increased risk of recurrent stroke especially within 2 weeks after the first event. In addition, the revascularization procedure itself (carotid endarterectomy [CEA] or carotid artery stenting [CAS]) is associated with both clinically apparent and silent brain infarctions, mainly caused by the embolic nature of the ruptured carotid plaque. The glycoprotein VI (GPVI) fusion protein Revacept is a highly specific antithrombotic drug without direct inhibition of systemic platelet function that might reduce periprocedural distal embolization from the vulnerable ruptured plaque located at the internal carotid artery. By shielding collagen at the site of vascular injury, Revacept inhibits plaque-mediated platelet adhesion and aggregation, while not directly affecting systemic hemostasis. In this phase II study, 158 patients with symptomatic carotid artery stenosis with recent TIA or stroke were randomized to receive a single dose of either Revacept (40 or 120 mg) or placebo. All patients were on standard secondary preventive therapy (statins and platelet inhibition) and underwent CEA, CAS, or best medical therapy according to current guidelines. The efficacy of Revacept was evaluated by exploratory assessment of new diffusion-weighted imaging lesions on magnetic resonance imaging after the revascularization procedure; a combination of cardiovascular events (ischemic and hemorrhagic stroke, TIA, myocardial infarction, or coronary intervention) and bleeding complications served to assess clinically critical patients' outcome and safety. This exploratory phase II randomized, double-blind clinical trial provides valuable insights on the safety, tolerability, and efficacy of Revacept in patients with symptomatic carotid artery stenosis.

Background: The COVID-19 pandemic might affect health care resources and alter patient admission to hospital in case of stroke or transient ischemic attack (TIA). We aim to determine whether the COVID-19 pandemic is affecting utilization of recanalization procedures and numbers of patients with stroke and TIA admitted to a primary care stroke center.Methods: In this retrospective observational study, we compared patients admitted from January 2019 until February 2020 with patients admitted during the COVID-19 pandemic (March/April 2020) in Germany. We included patients with stroke (hemorrhagic or ischemic) or TIA as classified by International Statistical Classification of Diseases and Related Health Problems version 10 (ICD-10).Results: The number of patients per month with ischemic stroke or TIA was found to have significantly decreased from January 2019 until February 2020 compared to the COVID-19 pandemic (March/April 2020) (ischemic stroke 69.1 ± 4.5 vs. 55 ± 5.7, p < 0.001, TIA 22.1 ± 4.1 vs. 14.5 ± 6.4, p < 0.034). Contrarily, percentages and numbers of recanalization procedures per month were not influenced by the COVID-19 pandemic (intravenous thrombolysis [iv-tPA] 9.4 ± 3.7 vs. 10.5 ± 0.5, p = 0.697, mechanical thrombectomy [MT] 13.1 ± 3.1 vs. 14.5 ± 3.5, p = 0.580, iv-TPA or MT 19.4 ± 4.1 vs. 19.0 ± 0.0, p = 0.889).Conclusions: During the COVID-19 pandemic, resources of the healthcare system in a primary care university hospital in Germany still allowed for unchanged numbers of recanalization procedures due to ischemic stroke. However, the numbers of patients admitted to the hospital specifically due to ischemic stroke or TIA decreased, suggesting that the awareness for non-disabling stroke symptoms has to be increased.

BackgroundThe cardiac diagnostic workup of stroke patients, especially the value of echocardiography and enhanced and prolonged Holter-ECG monitoring, is still a matter of debate. We aimed to analyse the impact of pathologies detected by echocardiography and ECG monitoring on therapeutic decisions and prognosis.MethodsFind-AFRANDOMISED was a prospective multicenter study which randomised 398 acute ischemic stroke patients ≥ 60 years to enhanced and prolonged Holter-ECG monitoring or usual stroke unit care. This substudy compared therapeutic consequences of echocardiography and routine Holter-ECG or enhanced and prolonged Holter-ECG monitoring, respectively, and prognosis of patients with or without pathologic findings in echocardiography or Holter-ECG monitoring.Results50.3% received enhanced and prolonged Holter-ECG monitoring and 49.7% routine ECG monitoring. 82.9% underwent transthoracic echocardiography (TTE), 38.9% transesophageal echocardiography (TEE) and 25.6% both procedures. 14/89 TEE pathologies and 1/90 TTE pathology led to a change in therapy, resulting in a number needed to change decision (NNCD) of 12 and 330 (p < 0.001), respectively. In comparison, enhanced and prolonged Holter-ECG monitoring found atrial fibrillation (AF) in 27 of 200 patients, and routine ECG monitoring in twelve of 198 patients, leading to therapeutic changes in all patients (NNCD 8 and 17, respectively, p < 0.001).ConclusionsMost changes in therapeutic decisions were triggered by enhanced and prolonged Holter-ECG monitoring, which should therefore play a more prominent role in future guidelines. Echocardiography identifies a patient group at high cardiovascular risk, but rarely result in therapeutic changes. Whether this patient group requires further cardiovascular workup remains unknown. This should be further investigated by interdisciplinary neurocardiologic teams and in appropriate future trials.Trial registrationClinicalTrials.gov NCT01855035.

Background. Atrial fibrillation (AF) is an important cause of embolic stroke of undetermined source (ESUS). Imaging-patterns like multiple infarcts, simultaneous involvement of different circulations, infarcts of different ages, and isolated cortical infarcts are likely to indicate cardioembolic stroke. The aim of our study was to evaluate the association between embolic stroke patterns, ESUS, and the new diagnosis of AF. Methods. Stroke etiology and imaging characteristics from patients included in the Find-AF study were obtained. Embolic stroke patterns in CT- or MR-imaging were correlated with the diagnosis of ESUS as well as the short- (on baseline ECG and during 7-day Holter) and long-term (12-month follow-up) diagnosis of AF. Results. From 281 patients included in the Find-AF study, 127 (45.2%) patients with ischemic lesions detected in CT or MRI were included. 26 (20.5%) of these patients had ESUS. At least one embolic stroke pattern was detected in 67 (52.7%) patients. Embolic stroke patterns were not associated with ESUS (OR 1.57, 0.65–3.79, p=0.317), the short-term (OR 0.64, 0.26–1.58, p=0.327) or long-term diagnosis of AF (OR 0.72, 0.31–1.68, p=0.448). Conclusions. This secondary data analysis of the Find-AF study could not provide evidence for an association between embolic stroke patterns, ESUS, and the new diagnosis of AF.

Patients with retinal vascular occlusion disease have an increased risk for ischemic stroke and share some risk factors with cerebrovascular disease. The purpose of this study was to analyze the prevalence of atrial fibrillation (AF) in subjects with retinal vascular occlusive disease and anterior ischemic optic neuropathy and to compare these data to an ischemic stroke group.Prospective, observational single-center trial. Subjects with retinal artery occlusion (RAO), retinal vein occlusion (RVO) and anterior ischemic optic neuropathy (AION) were included. Patients with ischemic stroke (IS) from a previous observational trial were used as control. Investigation included 7-day Holter ECG, echocardiography, duplex ultrasonography of the carotid arteries, and 24-hour blood pressure monitoring. Further vascular risk factors were documented.During the 1-year study period, 101 patients were recruited. The control group with ischemic stroke consisted of 272 subjects. At inclusion, the prevalence of AF was 12% (RAO), 10.2% (RVO), 11.1% (NAION) and 15.8% (IS). The final prevalence after Holter ECG rose to 16% (RAO), 18.4% (RVO), 14.8% (NAION) and 26.5% (IS). No significant difference was measured between groups.We detected a similar prevalence of AF in all groups. RVO patients tended to exhibit a higher AF detection rate and lower number needed to screen than RAO and NAION. The detection of AF rose considerably via Holter ECG. As a consequence, we recommend prolonged ECG monitoring in patients with acute ophthalmic vascular diseases.

BackgroundDetecting paroxysmal atrial fibrillation (PAF) in patients with cerebral ischemia is challenging. Frequent premature atrial complexes (PAC/h) and the longest supraventricular run on 24-h-Holter (SV-run(24 h)), summarised as excessive supraventricular ectopic activity (ESVEA), may help selecting patients for extended ECG-monitoring, especially in combination with echocardiographic marker LAVI/a' (left atrial volume index/late diastolic tissue Doppler velocity).MethodsRetrospective analysis from the prospective monocentric observational trial Find-AF (ISRCTN-46104198). Patients with acute stroke or TIA were enrolled at the University Hospital Göttingen, Germany. Those with sinus rhythm at presentation received 7-day Holter-monitoring. ESVEA was quantified in one 24-hour interval free from PAF. Echocardiographic parameters were assessed prospectively.ResultsPAF was detected in 23/208 patients (11.1%). The median was 4 [IQR 1; 22] for PAC/h and 5 [IQR 0; 9] for SV-run(24 h). PAF was more prevalent in patients with ESVEA: 19.6% vs. 2.8% for PAC/h >4 vs. ≤ 4 (p5) vs. ≤ 5 beats (p = 0.003). Patients with PAF showed more supraventricular ectopic activity: 29 PAC/h [IQR 9; 143] vs. 4 PAC/h [1]; [14] and longest SV-run(24 h = 10) [5]; [21] vs. 0 [0; 8] beats (both p4 and abnormal LAVI/a' showed high PAF-rates.ConclusionsESVEA discriminated PAF from non-PAF beyond clinical factors including LAVI/a' in patients with cerebral ischemia. Normal LAVI/a'+PAC/h ≤ 4 ruled out PAF, while prevalence was high in those with abnormal LAVI/a'+PAC/h >4.

Background and purposeDiagnosis of paroxysmal atrial fibrillation (AF) can be challenging, but it is highly relevant in patients presenting with sinus rhythm and acute cerebral ischemia. We aimed to evaluate prospectively whether natriuretic peptide levels and kinetics identify patients with paroxysmal AF.MethodsPatients with acute cerebral ischemia were included into the prospective observational Find-AF study. N-terminal pro brain-type natriuretic peptide (NT-proBNP), brain-type natriuretic peptide (BNP) and N-terminal pro atrial-type natriuretic peptide (NT-proANP) plasma levels were measured on admission, after 6 and 24 hours. Patients free from AF at presentation received 7 day Holter monitoring. We prospectively hypothesized that patients presenting in sinus rhythm with NT-proBNP>median were more likely to have paroxysmal AF than patients with NT-proBNPResults281 patients were included, of whom 237 (84.3%) presented in sinus rhythm. 220 patients naïve to AF with an evaluable prolonged Holter ECG were analysed. In patients with NT-proBNP>median (239 pg/ml), 17.9% had paroxysmal AF in contrast to 7.4% with NT-proBNPConclusionsBNP is independently predictive of paroxysmal AF detected by prolonged ECG monitoring in patients with cerebral ischemia and may be used to effectively select patients for prolonged Holter monitoring.

BACKGROUND: Carotid angioplasty and stenting (CAS) may currently be recommended especially in younger patients with a high-grade carotid artery stenosis. However, evidence is accumulating that in-stent restenosis (ISR) could be an important factor endangering the long-term efficacy of CAS. The aim of this study was to investigate the influence of inflammatory serum markers and procedure-related factors on ISR as diagnosed with duplex sonography. METHODS: We analyzed 210 CAS procedures in 194 patients which were done at a single university hospital between May 2003 and June 2010. Periprocedural C-reactive protein (CRP) and leukocyte count as well as stent design and geometry, and other periprocedural factors were analyzed with respect to the occurrence of an ISR as diagnosed with serial carotid duplex ultrasound investigations during clinical long-term follow-up. RESULTS: Over a median of 33.4 months follow-up (IQR: 14.9-53.7) of 210 procedures (mean age of 67.9±9.7 years, 71.9% male, 71.0% symptomatic) an ISR of ≥70% was detected in 5.7% after a median of 8.6 months (IQR: 3.4-17.3). After multiple regression analysis, leukocyte count after CAS-intervention (odds ratio (OR): 1.31, 95% confidence interval (CI): 1.02-1.69; p = 0.036), as well as stent length and width were associated with the development of an ISR during follow-up (OR: 1.25, 95% CI: 1.05-1.65, p = 0.022 and OR: 0.28, 95% CI: 0.09-0.84, p = 0.010). CONCLUSIONS: The majority of ISR during long-term follow-up after CAS occur within the first year. ISR is associated with periinterventional inflammation markers and influenced by certain stent characteristics such as stent length and width. Our findings support the assumption that stent geometry leading to vessel injury as well as periprocedural inflammation during CAS plays a pivotal role in the development of carotid artery ISR.