Embolic stroke of undetermined source (ESUS) – Classification of a new stroke entity

Kitsiou A, Zuhorn F, Wachter R, Israel CW, Schäbitz W-R, Rogalewski A. Embolischer Schlaganfall mit ungeklärter Emboliequelle (ESUS) – Klassifikation einer neuen Schlaganfallentität. DMW - Deutsche Medizinische Wochenschrift. 2021;146(06):403-409.Als embolischer Schlaganfall mit ungeklärter Emboliequelle (ESUS) wird eine Subgruppe kryptogener Schlaganfälle bezeichnet, welche durch ein embolisches Infarktmuster definiert werden, wenn gleichzeitig trotz einer sorgfältig durchgeführten Diagnostik keine eindeutige und spezifische Emboliequelle identifiziert werden kann. In diesem Übersichtsartikel werden die Grundlagen des ESUS-Konzepts analysiert und ein Überblick über die Evidenz jüngster Kohortenstudien gegeben. Es werden die Definition, Ätiologie und die Diagnostik eines ESUS neu bewertet. Durch eine gezielte Diagnostik bei ESUS-Patienten kann die Anzahl kryptogener Schlaganfälle durch Stellen einer spezifischen Diagnose reduziert werden

Atrial Fibrillation in Patients with Embolic Stroke of Undetermined Source during 3 Years of Prolonged Monitoring with an Implantable Loop Recorder

Kitsiou A, Rogalewski A, Kalyani M, et al. Atrial Fibrillation in Patients with Embolic Stroke of Undetermined Source during 3 Years of Prolonged Monitoring with an Implantable Loop Recorder. Thrombosis and Haemostasis. 2021;121(06):826-833.Background: Undocumented atrial fibrillation (AF) is suspected as a main stroke cause in patients with embolic stroke of undetermined source (ESUS), but its prevalence is largely unknown. This prospective study therefore aimed at delineating the prevalence of AF in patients with ESUS using continuous cardiac monitoring by implantable loop recorder (ILR) with daily remote interrogation over a period of 3 years and its clinical consequences, including recurrent stroke. Methods: In consecutive patients with an ESUS diagnosis after complete work-up, an ILR was implanted and followed by daily remote monitoring until AF was detected or a follow-up of at least 3 years was completed. Additionally, the ILR was interrogated in-hospital in 6-month intervals. Results: A total of 123 patients (74 male, mean age 65 ± 9 years) were enrolled and completed the 3 years study period. AF was detected in 51 patients (41.4%). In 43 of the 51 AF positive patients (84%) oral anticoagulation was established. Recurrent strokes occurred in 18 patients (14.6%) of this ESUS population, 9 of these patients being AF positive (17.6% of the AF-positive patients) and 9 being AF negative (12.5% of AF-negative patients). Patients with AF were slightly older than patients without AF (63.1 ± 8.8 vs. 67.5 ± 9.6 years, p = 0.12). Other parameters such as CHA2DS2-VASc score, infarct localization, micro- and macroangiopathy, carotid or aortic plaques, or stroke recurrence were not significantly different between groups. Conclusion In ESUS patients, early implantation of an ILR with cardiac monitoring and remote transmission over a 3-year period detected AF in 41.4% and resulted in oral anticoagulation in 84% of these patients

Detection of atrial fibrillation in patients with embolic stroke of undetermined source by prolonged monitoring with implantable loop recorders

Israel C, Kitsiou A, Kalyani M, et al. Detection of atrial fibrillation in patients with embolic stroke of undetermined source by prolonged monitoring with implantable loop recorders. Thrombosis and Haemostasis. 2017;117(10):1962-1969.Recently, the clinical entity embolic stroke of undetermined source (ESUS) has been defined for patients with ischemic strokes, where neither a cardioembolic nor a non-cardiac source can be detected. These patients may suffer from asymptomatic atrial fibrillation (AF), terminating spontaneously and thus eluding detection. Implantable loop recorders (ILR) with automatic AF detection algorithms can detect short-lasting, subclinical AF. The aim of this study was to prospectively assess and predict AF detection in patients with ESUS using ILR with daily remote interrogation. Patients with acute ESUS received an ILR, were seen every 6 months and additionally interrogated their ILR daily using remote monitoring. The incidence of AF detection was assessed and parameters which might predict AF detection (clinical and from magnetic resonance tomography) were analysed. ILR implantation was performed in 123 patients on average 20 days after stroke. During a mean follow-up of 12.7±5.5 months, AF was documented and manually confirmed in 29 of 123 patients (23.6%). First AF detection occurred on average after 3.6±3.4 months of monitoring. Patients with AF were on average older, had a higher CHA2DS2-VASc score and more often cerebral microangiopathy. In conclusion, AF can be documented in approximately 25% of patients with the diagnosis of ESUS after careful work-up within a year of monitoring by an ILR and daily remote interrogation. This had important therapeutic consequences (initiation of anticoagulation for secondary stroke prevention) in these patients

Functional long-term outcome following endovascular thrombectomy in patients with acute ischemic stroke

Rogalewski A, Klein N, Friedrich A, et al. Functional long-term outcome following endovascular thrombectomy in patients with acute ischemic stroke. Neurological Research and Practice. 2024;6(1): 2.**Abstract** Endovascular thrombectomy (EVT) is the most effective treatment for acute ischemic stroke caused by large vessel occlusion (LVO). Yet, long-term outcome (LTO) and health-related quality of life (HRQoL) in these patients have rarely been addressed, as opposed to modified Rankin scale (mRS) recordings. We analysed demographic data, treatment and neuroimaging parameters in 694 consecutive stroke patients in a maximum care hospital. In 138 of these patients with respect on receipt of written informed consent, LTO and HRQoL were collected over a period of 48 months after EVT using a standardised telephone survey (median 2.1 years after EVT). Age  2 according to the telephone survey more often had complaints regarding mobility, self‐care, and usual activity domains of the HRQoL. Our results underline a sustainable positive effect of effective EVT on the quality of life in LVO stroke. Additionally, predictive parameters of outcome were identified, that may support clinical decision making in LVO stroke

Detection of Atrial Fibrillation on Stroke Units: Comparison of Manual versus Automatic Analysis of Continuous Telemetry

Rogalewski A, Plümer J, Feldmann T, et al. Detection of Atrial Fibrillation on Stroke Units: Comparison of Manual versus Automatic Analysis of Continuous Telemetry. Cerebrovascular Diseases. 2020;49(6):647-655.Background: Detection of atrial fibrillation (AF) is one of the primary diagnostic goals for patients on a stroke unit. Physician-based manual analysis of continuous ECG monitoring is regarded as the gold standard for AF detection but requires considerable resources. Recently, automated computer-based analysis of RR intervals was established to simplify AF detection. The present prospective study analyzes both methods head to head regarding AF detection specificity, sensitivity, and overall effectiveness. Methods: Consecutive stroke patients without history of AF or proof of AF in the admission ECG were enrolled over the period of 7 months. All patients received continuous ECG telemetry during the complete stay on the stroke unit. All ECGs underwent automated analysis by a commercially available program. Blinded to these results, all ECG tracings were also assessed manually. Sensitivity, specificity, time consumption, costs per day, and cost-effectiveness were compared. Results: 216 consecutive patients were enrolled (70.7 ± 14.1 years, 56% male) and 555 analysis days compared. AF was detected by manual ECG analysis on 37 days (6.7%) and automatically on 57 days (10.3%). Specificity of the automated algorithm was 94.6% and sensitivity 78.4% (28 [5.0%] false positive and 8 [1.4%] false negative). Patients with AF were older and had more often arterial hypertension, higher NIHSS at admission, more often left atrial dilatation, and a higher CHA2DS2-VASc score. Automation significantly reduced human resources but was more expensive compared to manual analysis alone. Conclusion: Automatic AF detection is highly specific, but sensitivity is relatively low. Results of this study suggest that automated computer-based AF detection should be rather complementary to manual ECG analysis than replacing it

Long-term functional outcome and quality of life 2.5 years after thrombolysis in acute ischemic stroke

Schäbitz M, Möller L, Friedrich A, et al. Long-term functional outcome and quality of life 2.5 years after thrombolysis in acute ischemic stroke. Neurological Research and Practice. 2023;5(1): 62.**Background** Evaluation of outcome after stroke is largely based on assessment of gross function 3 months after stroke onset using scales such as mRS. Cognitive or social functions, level of symptom burden or emotional health are not usually assessed, nor are data available on long-term functional outcomes years after stroke. **Methods** Analysis of 1141 patients with AIS treated with IVT from two major German university hospitals between 2017 and 2020. Patient characteristics and short-term outcome were analysed from patient records. Long-term outcome of 228 patients with prior written informed consent was assessed via telephone survey using mRS and PROMs (EQ-5D-5L, EQ-VAS) 2.5 years after stroke. **Results** Predictors of excellent to good long-term outcome were younger age, event to door time ≤ 2 h, NIHSS ≤ 6 on admission and NIHSS ≤ 6 after IVT. Stroke recurrence was a negative predictor. Predictors of excellent quality of life at 2.5 years included age < 73 years, lower NIHSS after IVT, absence of hypertension. Quality of life was rated in all dimensions with a medium score of 1 and a medium EQ-VAS of 70, representing the good general health status of this stroke population. **Conclusion** Main predictors of an excellent to good long-term outcome and excellent QoL 2.5 years after stroke are younger age, lower NIHSS, and event to door time ≤ 2 h. Research on long-term outcome after disease and treatment is of utmost importance, as it has the ability to reveal the patient true functional outcome and quality of life and to provide information on the status of independence and self-esteem

Abstract-Nummer 159.

Schäbitz M, Klein N, Wulff L, et al. Geschlechter-spezifische Unterschiede bei Patienten und Patientinnen mit Thrombolysetherapie. In: Deutsche Gesellschaft für Neurologie, ed. Neurowoche 2022 - Abstracts. Berlin; 2022.Hintergrund: In den letzten Jahren wurde die Bedeutung des ischämischen Schlaganfalls bei Frauen sowohl im klinischen als auch im öffentlichen Gesundheitswesen zunehmend erkannt. Frauen haben aufgrund höherer Lebenserwartung eine höhere Schlaganfallinzidenz, postmenopausal einen Anstieg der Schlaganfallinzidenz, häufigere SchlaganfallRezidive und eine höhere Mortalität. Frauen erhalten eine schlechtere Versorgungsqualität gemessen an Qualitätsparametern der Schlaganfallversorgung und werden seltener nach medikamentösen Leitlinien behandelt. Unerwartet ist auch, dass Frauen seltener eine Thrombolyse erhalten als Männer. Ziele: Ziel war es, Geschlechter-spezifische Analysen der Prozess- und Behandlungsparameter sowie des Langzeit-Outcome in einem Maximalversorgerkrankenhaus bei Patient*Innen mit systemischer Thrombolysetherapie bei ischämischem Schlaganfall durchzuführen. Methoden: Wir analysierten retrospektiv demographische Daten, klinische Behandlungsparameter, neuroradiologische Parameter einschließlich Infarktvolumen, -lokalisation und -morphologie sowie das Ausmaß der zerebralen Mikroangiopathie. Es wurden Qualitätsparameter aller thrombolysierten Patient*Innen (N=815; 47,6 % Frauen) in einem großen deutschen Maximalversorger-Klinikum zwischen 01/2017 und 06/2020 ausgewertet. Das Langzeitergebnis wurde mittels standardisierter Telefonbefragung evaluiert. Ergebnisse: Frauen waren in unserer Kohorte signifikant älter als Männer (78,3±12,5 versus 72,4±13,1 Jahre; p<0,001). Sie waren seltener innerhalb der ersten zwei Stunden nach Symptombeginn in der Klinik (62,7 % vs. 70,7 %, p=0,030). Die door-to-needle time (DNT) war bei Frauen höher als bei Männern (Unterschied im Median 5 Minuten; Z=3,228; p=0,001). Frauen hatten höhere NIHSS Scores bei Aufnahme (Median 6 vs. 5; Z=4,636; p<0,001), hatten seltener einen Diabetes mellitus (18,3 % vs. 28,3 %; p=0,001) und eine höhere Komplikationsrate (40,7 % vs. 31,6 %; p=0,001). Es wurde bei Frauen seltener ein MRT durchgeführt (29,6 % vs. 40,8 %; p=0,001), jedoch häufiger bei durchgeführtem MRT ein Infarkt nachgewiesen (37,4 % vs. 25,9 %; p=0,037). Die Verlaufsparameter - gemessen mittels modified Rankin Scale sowie einem standardisierten, präferenzbasierten Verfahren zur Erhebung des Gesundheitszustands in fünf Dimension (EQ-5D-5LIndex) - ergab ein signifikant schlechteres Langzeit-Outcome bei Frauen. Aufgrund des signifikanten Altersunterschiedes erfolgten Alters-korrigierte Analysen. In der Gruppe der Patienten und Patientinnen bis einschließlich 78 Jahre (Median der Gesamtpopulation) hatten Frauen seltener einen Diabetes mellitus (16,8 % vs. 26,7 %; p=0,018) und häufiger einen Infarktnachweis im MRT (ohne Unterschied in der Häufigkeit der Durchführung) (38,3 % vs. 25,8 %; p=0,039). Bei Patienten und Patientinnen im Alter von 79-86 Jahren ohne Altersunterschied zwischen den Geschlechtergruppen zeigten Frauen einen signifikant höheren Anteil an kryptogenen Schlaganfällen (35,7 % vs. 14,0 %; p=0,002). Darüber hinaus hatten Frauen eine längere DNT (Median 46 vs. 37 Minuten; Z=2,815; p=0,005), hatten seltener einen Diabetes mellitus (17,4 % vs. 31,4 %; p=0,012), wiesen unterschiedliche Grade der zerebralen Mikroangiopathie auf (Abbildung 1) und zeigten ein schlechteres Langzeit-Outcome, gemessen am EQ-5D-5L-Index (Median 0,550 vs. 0,865; p=0,021). Schlussfolgerungen: Diese Studie zeigt, dass im klinischen Alltag signifikante Geschlechter-spezifische Unterschiede in der präklinischen und intrahospitalen Schlaganfallversorgung existieren. Diese sind zu einem gewissen Teil durch ein höheres Alter bei Frauen erklärbar. Alterskorrigiert weisen insbesondere ältere Frauen nach einer intravenösen Thrombolyse ein schlechteres Langzeitergebnis auf. Die Unterschiede beinhalten die DNT, die ätiologische Klassifikation und setzen sich im Langzeitergebnis fort. Diese Daten sind von großer Relevanz, um Frauen eine gleichwertige Qualität der Behandlung zu ermöglichen. Diese Daten legen nahe, die Prozesse auf Ursachen der Geschlechter-spezifischen Unterschiede zu überprüfen und diese – sofern möglich - zu korrigieren

Detection of atrial fibrillation on stroke units

$\it Background:$ Detection of atrial fibrillation (AF) is one of the primary diagnostic goals for patients on a stroke unit. Physician-based manual analysis of continuous ECG monitoring is regarded as the gold standard for AF detection but requires considerable resources. Recently, automated computer-based analysis of RR intervals was established to simplify AF detection. The present prospective study analyzes both methods head to head regarding AF detection specificity, sensitivity, and overall effectiveness. $\it Methods:$ Consecutive stroke patients without history of AF or proof of AF in the admission ECG were enrolled over the period of 7 months. All patients received continuous ECG telemetry during the complete stay on the stroke unit. All ECGs underwent automated analysis by a commercially available program. Blinded to these results, all ECG tracings were also assessed manually. Sensitivity, specificity, time consumption, costs per day, and cost-effectiveness were compared. $\it Results:$ 216 consecutive patients were enrolled (70.7 ± 14.1 years, 56% male) and 555 analysis days compared. AF was detected by manual ECG analysis on 37 days (6.7%) and automatically on 57 days (10.3%). Specificity of the automated algorithm was 94.6% and sensitivity 78.4% (28 [5.0%] false positive and 8 [1.4%] false negative). Patients with AF were older and had more often arterial hypertension, higher NIHSS at admission, more often left atrial dilatation, and a higher CHA2DS2-VASc score. Automation significantly reduced human resources but was more expensive compared to manual analysis alone. $\it Conclusion:$ Automatic AF detection is highly specific, but sensitivity is relatively low. Results of this study suggest that automated computer-based AF detection should be rather complementary to manual ECG analysis than replacing it

Atrial Fibrillation Risk Assessment after Embolic Stroke of Undetermined Source

von Falkenhausen AS, Feil K, Sinner MF, et al. Atrial Fibrillation Risk Assessment after Embolic Stroke of Undetermined Source. Annals of Neurology. 2022.Objective: Approximately 20% of strokes are embolic strokes of undetermined source (ESUS). Undetected atrial fibrillation (AF) remains an important cause. Yet, oral anticoagulation in unselected ESUS patients failed in secondary stroke prevention. Guidance on effective AF detection is lacking. Here, we introduce a novel, non-invasive AF risk assessment after ESUS. Methods: Catch-Up ESUS is an investigator-initiated, observational cohort study conducted between 2018 and 2019 at the Munich University Hospital. Besides clinical characteristics, patients received & GE;72 h digital electrocardiogram recordings to generate the rhythm irregularity burden. Uni- and multivariable regression models predicted the primary endpoint of incident AF, ascertained by standardized follow-up including implantable cardiac monitors. Predictors included the novel rhythm irregularity burden constructed from digital electrocardiogram recordings. We independently validated our model in ESUS patients from the University Hospital Tubingen, Germany. Results: A total of 297 ESUS patients were followed for 15.6 +/- 7.6 months. Incident AF (46 patients, 15.4%) occurred after a median of 105 days (25th to 75th percentile 31-33 days). Secondary outcomes were recurrent stroke in 7.7% and death in 6.1%. Multivariable-adjusted analyses identified the rhythm irregularity burden as the strongest AF-predictor (hazard ratio 3.12, 95% confidence interval 1.62-5.80, p < 0001) while accounting for the known risk factors age, CHA(2)DS(2)-VASc-Score, and NT-proBNP. Independent validation confirmed the rhythm irregularity burden as the most significant AF-predictor (hazard ratio 2.20, 95% confidence interval 1.45-3.33, p < 0001). Interpretation: The novel, non-invasive, electrocardiogram-based rhythm irregularity burden may help adjudicating AF risk after ESUS, and subsequently guide AF-detection after ESUS. Clinical trials need to clarify if high-AF risk patients benefit from tailored secondary stroke prevention