Holter-ECG monitoring is a critical component of post-stroke diagnostics, guiding cardiac work-up and secondary stroke prevention. Abnormal ECG findings beyond atrial fibrillation (AF) in stroke patients remain understudied. The prospective multicenter MonDAFIS trial randomized patients with acute ischemic stroke or transient ischemic attack (TIA) without known AF to Holter-ECG recording up to 7 days or usual care. Holter-ECG findings from the first 72 h of the intervention arm were analyzed to provide a reference guide in clinical practice. Furthermore, 24-hour and 72-hour Holter-ECG monitoring were compared to analyze the value of prolonged monitoring. 24-hour Holter-ECGs from 1,665 patients (median age 67; 40.4% women) identified supraventricular tachycardia (SVT) in 4.1% and newly-diagnosed AF in 2.2% of patients. Premature ventricular complexes were common (85.8%), ventricular couplets (28.0%) or bigeminy (14.0%) less common. Non-sustained ventricular tachycardia (nsVT) was detected in 1.7% of patients. Extended 72-hour-monitoring in 1,283 patients led to higher detection rates across all abnormalities, doubling nsVT (4.4%) and SVT (8.8%) detection rates. Generally, we observed higher detection rates with older age. Detection rates of supraventricular arrhythmias were higher in women, whereas men exhibited higher rates of ventricular abnormalities. Post-stroke ECG monitoring detects various arrhythmias beyond AF in a substantial proportion of individuals. Longer monitoring and older age are associated with increased detection rates, with notable sex-specific differences.

Background: Cerebrovascular events are a potentially serious complication of giant cell arteritis (GCA) with intracranial involvement. However, diagnosing GCA in this context remains challenging, as classical clinical features may be absent.Objectives: To identify characteristic cerebellar infarct patterns associated with intracranial GCA and to differentiate them from other common causes of posterior circulation stroke.Design: Multicenter retrospective study.Methods: A total of 125 patients with cerebellar infarctions of various etiologies were included. Among these, 19 patients had confirmed intracranial GCA. Infarct patterns were compared to those seen in strokes of cardioembolic origin (n = 42), arterio-arterial embolism from proximal vertebral artery atherosclerosis (n = 13), local atherosclerotic stenosis of the V4 segment (n = 21), and vertebral artery dissection (n = 30). Infarct topography was assessed using acute-phase diffusion-weighted magnetic resonance imaging. Sensitivity and specificity were calculated for individual imaging features.Results: Distinct imaging signatures were observed in patients with GCA. A "corona-like" infarct pattern, defined by sparing of the medial branch of the proximal posterior inferior cerebellar artery (PICA), demonstrated a sensitivity of 79% and a specificity of 64%. A patchy infarct pattern, characterized by scattered non-confluent lesions, was present in 53% of GCA cases and showed high specificity (93%). When both features were present, specificity increased to 98% and sensitivity was reduced to 47%.Conclusion: Our findings reveal a distinct cerebellar infarct pattern associated with intracranial GCA, characterized by a corona-like configuration and patchy lesions predominantly involving the lateral PICA territory. Recognition of this imaging phenotype may enhance diagnostic accuracy in challenging cases and facilitate the timely initiation of immunosuppressive therapy.

Background Excessive supraventricular ectopic activity (ESVEA) is regarded as a risk marker for later atrial fibrillation (AF) detection. Methods and Results The investigator‐initiated, prospective, open, multicenter MonDAFIS (Impact of Standardized Monitoring for Detection of Atrial Fibrillation in Ischemic Stroke) study randomized 3465 patients with acute ischemic stroke without known AF 1:1 to usual diagnostic procedures for AF detection or additive Holter monitoring in hospital for up to 7 days, analyzed in a core laboratory. Secondary study objectives include the comparison of recurrent stroke, myocardial infarction, major bleeding, and all‐cause death within 24 months in patients with ESVEA (defined as ectopic supraventricular beats ≥480/day or atrial runs of 10–29 seconds or both) versus patients with newly diagnosed AF versus patients without ESVEA or AF (non‐ESVEA/AF), randomized to the intervention group. Overall, 1435 (84.8%) of 1714 patients randomized to the intervention group had analyzable study ECG monitoring of at least 48 hours' duration within the first 72 hours of monitoring. ESVEA was detected in 363 (25.3%) patients, while AF was first detected in 48 (3.3%) patients. Within 24 months, AF was newly detected in 67 (18.5%) patients with ESVEA versus 60 (5.9%) patients without ESVEA/AF‐ ( P <0.001). The composite outcome at 24 months was not different between patients with ESVEA and patients without ESVEA/AF (15.2% versus 12.6%; P =0.242). All‐cause death was numerically higher in patients with ESVEA (6.6% versus 3.2%), but failed statistical significance ( P =0.433) in multivariate analysis (including age, heart failure, stroke severity, and creatinine at baseline). Conclusions ESVEA in the acute phase of ischemic stroke or transient ischemic attack is associated with AF detection during follow‐up and therefore may be used to select patients for prolonged ECG monitoring. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02204267.

Neurovascular networks (NVNs) in Germany are supra-regional care structures for patients with neurovascular diseases. Each NVN consists of a tertiary care center serving as the coordinating center—in some cases, two or three coordinating centers—and at least three partner hospitals. Since 2018, 19 neurovascular networks (NVNs) have been audited and certified. NVNs play a crucial role in stroke care in Germany, as first described and quantified in 2020. The present article provides an update on interdisciplinary NVNs in Germany and outlines recent developments in neurovascular patient care. Audit reports from 19 NVNs, certified between 2021 and 2024, were analyzed, and compared to previously reported data from 2017 to 2019. Additionally, structural and quality-related parameters for coordinating centers and partner hospitals were compared. The number of NVNs increased from 15 to 19, with approximately 120,000 from an estimated 262,000 neurovascular patients in Germany now treated annually in certified NVN hospitals. In particular, annual thrombectomy rates at coordinating centers have increased over-proportionally (> 4400, as compared to previously < 2500), and surgical treatments for intracerebral hemorrhages have also increased. Process times—door-to-needle and door-to-groin times—remained stable or exhibited slight increases. Substantial variability was observed among NVN partner hospitals regarding procedural volumes. The treatment of patients with neurovascular diseases in Germany has expanded considerably within certified NVN hospitals in recent years. The NVNs ensure comprehensive, high-quality stroke care nationwide.

ABSTRACTAimsAtrial fibrillation (AF) accounts for about 20% of all ischemic strokes worldwide. It is known that AF impairs health‐related quality of life (HRQOL) in the general population, but data on HRQOL in stroke patients with newly diagnosed AF are sparse.MethodsPost hoc analysis of the prospective, investigator‐initiated, multicenter MonDAFIS study (NCT02204267) to analyze whether AF‐related oral anticoagulation (OAC), and/or AF‐symptom severity are associated with HRQOL after ischemic stroke or transient ischemic attack (TIA). HRQOL was measured using the EQ‐5D‐3L‐questionnaire (including EQ‐index/EQ‐VAS) at baseline and after 12 months using multivariable linear mixed models. AF symptom severity was assessed using the European Heart Rhythm Association classification and symptom severity score (EHRA score) categorizing patients with no/mild/severe/disabling AF‐related symptoms.ResultsA first episode of AF was detected in 261/2927 (8.9%) patients within 12 months after the index stroke and 227/2920 (7.8%) patients had AF and were anticoagulated at 12 months. HRQOL (measured by EQ‐index, n = 2495 patients) was higher in AF patients on OAC compared to AF patients without OAC at 12 months after stroke (mean difference: MD: –16.8, 95% CI: 5.6 to 28.0), and similar in AF patients under OAC compared with patients without AF (MD: 2.0, 95% CI: –2.2 to 6.3). AF‐related symptoms were negatively associated with HRQOL (measured by EQ‐index) indicating that stroke patients with AF‐related symptoms had a lower HRQOL compared to asymptomatic AF patients (mild vs. asymptomatic: MD: –9.0, 95% CI: –17.7 to –0.3; severe/disabling vs. asymptomatic: MD: –19.1, 95% CI: –34.7 to –3.4).DiscussionStroke patients with newly diagnosed AF are at risk of lower quality of life at 12 months, depending on OAC status and AF symptom severity.

Heart failure (HF) is associated with poor outcome after stroke, but data from large prospective trials are sparse. We assessed the impact of HF on clinical endpoints in patients hospitalized with acute ischemic stroke or transient ischemic attack (TIA) enrolled in the prospective, multicenter Systematic Monitoring for Detection of Atrial Fibrillation in Patients with Acute Ischemic Stroke (MonDAFIS) trial. HF was defined as left ventricular ejection fraction (LVEF) < 55

Mechanical thrombectomy (MT) for acute ischemic stroke with medium vessel occlusions is still a matter of debate. We sought to identify factors associated with clinical outcome after MT for M2-occlusions based on data from the German Stroke Registry-Endovascular Treatment (GSR-ET). All patients prospectively enrolled in the GSR-ET from 05/2015 to 12/2021 were analyzed (NCT03356392). Inclusion criteria were primary M2-occlusions and availability of relevant clinical data. Factors associated with excellent/good outcome (modified Rankin scale mRS 0–1/0–2), poor outcome/death (mRS 5–6) and mRS-increase pre-stroke to day 90 were determined in multivariable logistic regression. 1348 patients were included. 1128(84%) had successful recanalization, 595(44%) achieved good outcome, 402 (30%) had poor outcome. Successful recanalization (odds ratio [OR] 4.27 [95% confidence interval 3.12–5.91], p < 0.001), higher Alberta stroke program early CT score (OR 1.25 [1.18–1.32], p < 0.001) and i.v. thrombolysis (OR 1.28 [1.07–1.54], p < 0.01) increased probability of good outcome, while age (OR 0.95 [0.94–0.95], p < 0.001), higher pre-stroke-mRS (OR 0.36 [0.31–0.40], p < 0.001), higher baseline NIHSS (OR 0.89 [0.88–0.91], p < 0.001), diabetes (OR 0.52 [0.42–0.64], p < 0.001), higher number of passes (OR 0.75 [0.70–0.80], p < 0.001) and intracranial hemorrhage (OR 0.26 [0.14–0.46], p < 0.001) decreased the probability of good outcome. Additional predictors of mRS-increase pre-stroke to 90d were dissections, perforations (OR 1.59 [1.11–2.29], p < 0.05) and clot migration, embolization (OR 1.67 [1.21–2.30], p < 0.01). Corresponding to large-vessel-occlusions, younger age, low pre-stroke-mRS, low severity of acute clinical disability, i.v. thrombolysis and successful recanalization were associated with good outcome while diabetes and higher number of passes decreased probability of good outcome after MT in M2 occlusions. Treatment related complications increased probability of mRS increase pre-stroke to 90d.

Abstract Background Embolic stroke of undetermined source (ESUS) accounts for a substantial proportion of ischaemic strokes. A stroke recurrence score has been shown to predict the risk of recurrent stroke in patients with ESUS based on a combination of clinical and imaging features. This study aimed to externally validate the performance of the ESUS recurrence score using data from a randomized controlled trial. Methods The validation dataset consisted of eligible stroke patients with available magnetic resonance imaging (MRI) data enrolled in the PreDAFIS sub-study of the MonDAFIS study. The score was calculated using three variables: age (1 point per decade after 35 years), presence of white matter hyperintensities (2 points), and multiterritorial ischaemic stroke (3 points). Patients were assigned to risk groups as described in the original publication. The model was evaluated using standard discrimination and calibration methods. Results Of the 1054 patients, 241 (22.9%) were classified as ESUS. Owing to insufficient MRI quality, three patients were excluded, leaving 238 patients (median age 65.5 years [IQR 20.75], 39% female) for analysis. Of these, 30 (13%) patients experienced recurrent ischaemic stroke or transient ischemic attack (TIA) during a follow-up period of 383 patient-years, corresponding to an incidence rate of 7.8 per 100 patient-years (95% CI 5.3–11.2). Patients with an ESUS recurrence score value of ≥ 7 had a 2.46 (hazard ratio (HR), 95% CI 1.02–5.93) times higher risk of stroke recurrence than patients with a score of 0–4. The cumulative probability of stroke recurrence in the low-(0–4), intermediate-(5–6), and high-risk group (≥ 7) was 9%, 13%, and 23%, respectively (log-rank test, χ2 = 4.2, p = 0.1). Conclusions This external validation of a published scoring system supports a threshold of ≥ 7 for identifying ESUS patients at high-risk of stroke recurrence. However, further adjustments may be required to improve the model’s performance in independent cohorts. The use of risk scores may be helpful in guiding extended diagnostics and further trials on secondary prevention in patients with ESUS. Trial registration: Clinical Trials, NCT02204267. Registered 30 July 2014, https://clinicaltrials.gov/ct2/show/NCT02204267 .

Background In patients with acute ischemic stroke, little is known regarding the frequency of abnormal ECG findings other than atrial fibrillation and their association with cardiovascular outcomes. We aim to analyze the frequency and type of abnormal ECG findings, subsequent changes in medical treatment, and their association with cardiovascular outcomes in patients with acute ischemic stroke. Methods and Results In the investigator‐initiated multicenter MonDAFIS (impact of standardized monitoring for detection of atrial fibrillation in ischemic stroke) study, 3465 patients with acute ischemic stroke or transient ischemic attack and without known atrial fibrillation were randomized 1:1 to receive Holter‐ECG for up to 7 days in‐hospital with systematic evaluation in a core cardiology laboratory (intervention group) or standard diagnostic care (control group). Outcomes included predefined abnormal ECG findings (eg, pauses, atrial fibrillation, brady‐/tachycardias), medical management in the intervention group, and combined vascular end point (recurrent stroke, myocardial infarction, major bleeds, or all‐cause death) and mortality at 24 months in both randomization groups. Predefined abnormal ECG findings were detected in 326 of 1693 (19.3%) patients in the intervention group. Twenty of these 326 patients (6.1%) received a pacemaker, and 62 of 326 (19.0%) patients had newly initiated or discontinued β‐blocker medication. Discontinuation of β‐blockers was associated with a higher death rate in the control group than in the intervention group during 24 months after enrollment (adjusted hazard ratio, 11.0 [95% CI, 2.4–50.4]; P=0.025 for interaction). Conclusions Systematic in‐hospital Holter ECG reveals abnormal findings in 1 of 5 patients with acute stroke, and mortality was lower at 24 months in patients with systematic ECG recording in the hospital. Further studies are needed to determine the potential impact of medical management of abnormal ECG findings. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02204267.

Purpose Endovascular treatment (ET) in patients with large vessel occlusion stroke (LVOS) with unknown onset or an extended time window can be safe and effective if patients are selected by defined clinical and imaging criteria; however, it is unclear if these criteria should also be applied to patients with unknown onset and unknown time last known well. In this study, we aimed to assess whether absent information on the time patients were last known to be well impacts outcome in patients with unknown onset LVOS. Methods We analyzed patients who were enrolled in the German Stroke Registry-Endovascular Treatment between 2015 and 2019. Patients with unknown onset and unknown time last known well (LKWu) were compared to patients with known onset (KO) and to patients with unknown onset but known time last known well (LKWk) regarding clinical and imaging baseline characteristics and outcome. Results Out of 5909 patients, 561 presented with LKWu (9.5%), 1849 with LKWk (31.3%) and 3499 with KO (59.2%). At 90 days, functional independency was less frequent in LKWu (27.0%) compared to KO (42.6%) and LKWk patients (31.8%). These differences were not significant after adjusting for confounders. A main confounder was the initial Alberta stroke program early CT score. Conclusion The LKWu patients had a similar outcome after ET as KO and LKWk patients after adjusting for confounders. Thus, ET should not be withheld if the time last known well is unknown. Instead, LKWu patients may be selected for ET using the same criteria as in LKWk patients.

Background About 25% of all ischaemic strokes are related to cardio-embolism, most often due to atrial fibrillation (AF). Little is known about the extent and standardization of routine cardiac diagnostic work-up at certified stroke-units in Germany. Methods The MonDAFIS study included non-AF patients with acute ischaemic stroke or transient ischaemic attack (TIA) at 38 certified stroke-units in Germany. Here, we analysed routine diagnostic work-up and disregarded study-related Holter-ECG monitoring. We compared duration of stroke-unit stay, number of 24-h Holter-ECGs, and echocardiography performed between university-based comprehensive stroke centres (UCSC, 12 hospitals, 1606 patients), non university-based comprehensive stroke centres (nUCSC, 14 hospitals, 892 patients), and primary stroke centres at non-university hospitals (PCS, 12 hospitals, 933 patients) using multivariable mixed regression analyses. Detection of a first AF episode in-hospital was also compared between hospitals of different stroke-unit levels. Results In 3431 study patients (mean age 66.2 years, 39.5% female, median NIHSS = 2 on admission), median duration of the stroke-unit stay was 72 h (IQR 42–86). Stroke-unit stay was longer (categorised ≤ 24/ > 24- ≤ 72/ > 72 h) for patients with severe stroke (NIHSS score ≥ 5/ < 5: OR = 1.6, 95%CI 1.3–2.0) and for patients with ischaemic stroke vs. TIA (OR = 1.7, 95%CI 1.4–2.1). Overall, 2149/3396 (63.3%) patients underwent at least one additional 24-h Holter-ECG (median 1 [IQR 0–1], range 0–7). Holter-ECG rate was 47% in UCSC, 71% in nUCSC, and 84% in PCS. Compared to PCS, AF was less often detected in-hospital in UCSC (OR = 0.65, 95%CI 0.45–0.93) and nUCSC (OR = 0.69, 95%CI 0.46–1.04). Transoesophageal echocardiography (TEE) only was performed in 513/3391 (15.1%) study patients, transthoracic echocardiography (TTE) only in 1228/3391 (36.2%), and TEE combined with TTE in 1020/3391 (30.1%) patients. Patients younger than 60 years (vs. ≥ 60 years) underwent TEE more often than those older than 60 years (OR = 3.44, 95%CI 2.67–4.42). TEE (IQR 34–65%) and TTE rate (IQR 40–85%) varied substantially among study centres. Echocardiography rate (TTE and/or TEE) was 74.0% in UCSC, 85.4% in nUCSC, and 90.3% in PSC, respectively. Conclusions In the MonDAFIS study, the routine use of echocardiography and Holter-ECG monitoring varied in participating stroke centres and at stroke-unit level, if grouped according to stroke-unit certification grade and hospitals´ university status. Trial registration Clinical Trials, NCT02204267. Registered 30 July 2014, https://clinicaltrials.gov/ct2/show/NCT02204267 .

Background and Purpose: Rapid access to acute stroke treatment improves clinical outcomes in patients with ischemic stroke. We aimed to shorten the time to admission and to acute stroke treatment for patients with acute stroke in the Hamburg metropolitan area by collaborative multilevel measures involving all hospitals with stroke units, the Emergency Medical Services (EMS), and health-care authorities. Methods: In 2007, an area-wide stroke care quality project was initiated. The project included mandatory admission of all stroke patients in Hamburg exclusively to hospitals with stroke units, harmonized acute treatment algorithms among all hospitals, repeated training of the EMS staff, a multimedia educational campaign, and a mandatory stroke care quality monitoring system based on structured data assessment and quality indicators for procedural measures. We analyzed data of all patients with acute stroke who received inhospital treatment in the city of Hamburg during the evaluation period from the quality assurance database data and evaluated trends of key quality indicators over time. Results: From 2007 to 2016, a total of 83,395 patients with acute stroke were registered. During this period, the proportion of patients admitted within ≤3 h from symptom onset increased over time from 27.8% in 2007 to 35.2% in 2016 (p < 0.001). The proportion of patients who received rapid thrombolysis (within ≤30 min after admission) increased from 7.7 to 54.1% (p < 0.001). Conclusions: Collaborative stroke care quality projects are suitable and effective to improve acute stroke care.

BACKGROUND AND PURPOSE:Impaired kidney function is associated with an increased risk of vascular events in acute stroke patients, when assessed by single measurements of estimated glomerular filtration rate (eGFR). It is unknown whether repeated measurements provide additional information for risk prediction.METHODS:The MonDAFIS (Systematic Monitoring for Detection of Atrial Fibrillation in Patients with Acute Ischemic Stroke) study randomly assigned 3465 acute ischemic stroke patients to either standard procedures or an additive Holter electrocardiogram. Baseline eGFR (CKD-EPI formula) were dichotomized into values of < versus ≥60 ml/min/1.73 m2 . eGFR dynamics were classified based on two in-hospital values as "stable normal" (≥60 ml/min/1.73 m2 ), "increasing" (by at least 15% from baseline, second value ≥ 60 ml/min/1.73 m2 ), "decreasing" (by at least 15% from baseline of ≥60 ml/min/1.73 m2 ), and "stable decreased" (<60 ml/min/1.73 m2 ). The composite endpoint (stroke, major bleeding, myocardial infarction, all-cause death) was assessed after 24 months. We estimated hazard ratios in confounder-adjusted models.RESULTS:Estimated glomerular filtration rate at baseline was available in 2947 and a second value in 1623 patients. After adjusting for age, stroke severity, cardiovascular risk factors, and randomization, eGFR < 60 ml/min/1.73 m2 at baseline (hazard ratio [HR] = 2.2, 95% confidence interval [CI] = 1.40-3.54) as well as decreasing (HR = 1.79, 95% CI = 1.07-2.99) and stable decreased eGFR (HR = 1.64, 95% CI = 1.20-2.24) were independently associated with the composite endpoint. In addition, eGFR < 60 ml/min/1.732 at baseline (HR = 3.02, 95% CI = 1.51-6.10) and decreasing eGFR were associated with all-cause death (HR = 3.12, 95% CI = 1.63-5.98).CONCLUSIONS:In addition to patients with low eGFR levels at baseline, also those with decreasing eGFR have increased risk for vascular events and death; hence, repeated estimates of eGFR might add relevant information to risk prediction.

Paroxysmal Atrial fibrillation (AF) is often clinically silent and may be missed by the usual diagnostic workup after ischemic stroke. We aimed to determine whether shape characteristics of ischemic stroke lesions can be used to predict AF in stroke patients without known AF at baseline. Lesion shape quantification on brain MRI was performed in selected patients from the intervention arm of the Impact of standardized MONitoring for Detection of Atrial Fibrillation in Ischemic Stroke (MonDAFIS) study, which included patients with ischemic stroke or TIA without prior AF. Multiple morphologic parameters were calculated based on lesion segmentation in acute brain MRI data. Multivariate logistic models were used to test the association of lesion morphology, clinical parameters, and AF. A stepwise elimination regression was conducted to identify the most important variables. A total of 755 patients were included. Patients with AF detected within 2 years after stroke (n = 86) had a larger overall oriented bounding box (OBB) volume (p = 0.003) and a higher number of brain lesion components (p = 0.008) than patients without AF. In the multivariate model, OBB volume (OR 1.72, 95%CI 1.29-2.35, p < 0.001), age (OR 2.13, 95%CI 1.52-3.06, p < 0.001), and female sex (OR 2.45, 95%CI 1.41-4.31, p = 0.002) were independently associated with detected AF. Ischemic lesions in patients with detected AF after stroke presented with a more dispersed infarct pattern and a higher number of lesion components. Together with clinical characteristics, these lesion shape characteristics may help in guiding prolonged cardiac monitoring after stroke.

Background and Objectives To evaluate the long-term safety and efficacy of tocilizumab (TCZ), a humanized anti–interleukin-6 receptor antibody in myelin oligodendrocyte glycoprotein–IgG–associated disease (MOGAD) and neuromyelitis optica spectrum disorders (NMOSD). Methods Annualized relapse rate (ARR), Expanded Disability Status Scale score, MRI, autoantibody titers, pain, and adverse events were retrospectively evaluated in 57 patients with MOGAD (n = 14), aquaporin-4 (AQP4)-IgG seropositive (n = 36), and seronegative NMOSD (n = 7; 12%), switched to TCZ from previous immunotherapies, particularly rituximab. Results Patients received TCZ for 23.8 months (median; interquartile range 13.0–51.1 months), with an IV dose of 8.0 mg/kg (median; range 6–12 mg/kg) every 31.6 days (mean; range 26–44 days). For MOGAD, the median ARR decreased from 1.75 (range 0.5–5) to 0 (range 0–0.9; p = 0.0011) under TCZ. A similar effect was seen for AQP4-IgG+ (ARR reduction from 1.5 [range 0–5] to 0 [range 0–4.2]; p < 0.001) and for seronegative NMOSD (from 3.0 [range 1.0–3.0] to 0.2 [range 0–2.0]; p = 0.031). During TCZ, 60% of all patients were relapse free (79% for MOGAD, 56% for AQP4-IgG+, and 43% for seronegative NMOSD). Disability follow-up indicated stabilization. MRI inflammatory activity decreased in MOGAD (p = 0.04; for the brain) and in AQP4-IgG+ NMOSD (p < 0.001; for the spinal cord). Chronic pain was unchanged. Regarding only patients treated with TCZ for at least 12 months (n = 44), ARR reductions were confirmed, including the subgroups of MOGAD (n = 11) and AQP4-IgG+ patients (n = 28). Similarly, in the group of patients treated with TCZ for at least 12 months, 59% of them were relapse free, with 73% for MOGAD, 57% for AQP4-IgG+, and 40% for patients with seronegative NMOSD. No severe or unexpected safety signals were observed. Add-on therapy showed no advantage compared with TCZ monotherapy. Discussion This study provides Class III evidence that long-term TCZ therapy is safe and reduces relapse probability in MOGAD and AQP4-IgG+ NMOSD.

The most malignant type of intrinsic brain tumor is glioblastoma (WHO grade IV). Primary leptomeningeal spread is rare and leads to a variety of differential considerations, as there is no typical clinical or imaging pattern. Here we present a rare and uncommon case of a primary leptomeningeal glioblastoma in combination with a low-grade glioma in a 21-year-old male, initially presenting with only headache and lower back pain. The presented case illustrates the challenging differential considerations and the severe course of leptomeningeal glioblastomas.

Background and Purpose:In patients with acute mild-moderate ischemic stroke or high-risk transient ischemic attack, the THALES trial (Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and Aspirin for Prevention of Stroke and Death) demonstrated that when added to aspirin, ticagrelor reduced stroke or death but increased risk of severe hemorrhage compared with placebo. The primary efficacy outcome of THALES included hemorrhagic stroke and death, events also counted in the primary safety outcome. We sought to disentangle risk and benefit, assess their relative impact, and attempt to identify subgroups with disproportionate risk or benefit.Methods:In a randomized, placebo-controlled, double-blind trial of patients with mild-to-moderate acute noncardioembolic ischemic stroke or high-risk transient ischemic attack, patients were randomized within 24 hours after symptom onset to a 30-day regimen of either ticagrelor plus aspirin or matching placebo plus aspirin. For the present analyses, we defined the efficacy outcome, major ischemic events, as the composite of ischemic stroke or nonhemorrhagic death, and defined the safety outcome, major hemorrhage, as intracranial hemorrhage or hemorrhagic death. Net clinical impact was defined as the combination of these 2 end points.Results:In 11 016 patients (5523 ticagrelor-aspirin and 5493 aspirin), a major ischemic event occurred in 294 patients (5.3%) in the ticagrelor-aspirin group and in 359 patients (6.5%) in the aspirin group (absolute risk reduction 1.19% [95% CI, 0.31%–2.07%]). Major hemorrhage occurred in 22 patients (0.4%) in the ticagrelor-aspirin group and 6 patients (0.1%) in the aspirin group (absolute risk increase 0.29% [95% CI, 0.10%–0.48%]). Net clinical impact favored ticagrelor-aspirin (absolute risk reduction 0.97% [95% CI, 0.08%–1.87%]). Findings were similar when different thresholds for disability were applied and over a range of predefined subgroups.Conclusions:In patients with mild-moderate ischemic stroke or high-risk transient ischemic attack, ischemic benefits of 30-day treatment with ticagrelor-aspirin outweigh risks of hemorrhage.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03354429.

This expert opinion paper on cardiac imaging after acute ischemic stroke or transient ischemic attack (TIA) includes a statement of the “Heart and Brain” consortium of the German Cardiac Society and the German Stroke Society. The Stroke Unit-Commission of the German Stroke Society and the German Atrial Fibrillation NETwork (AFNET) endorsed this paper. Cardiac imaging is a key component of etiological work-up after stroke. Enhanced echocardiographic tools, constantly improving cardiac computer tomography (CT) as well as cardiac magnetic resonance imaging (MRI) offer comprehensive non- or less-invasive cardiac evaluation at the expense of increased costs and/or radiation exposure. Certain imaging findings usually lead to a change in medical secondary stroke prevention or may influence medical treatment. However, there is no proof from a randomized controlled trial (RCT) that the choice of the imaging method influences the prognosis of stroke patients. Summarizing present knowledge, the German Heart and Brain consortium proposes an interdisciplinary, staged standard diagnostic scheme for the detection of risk factors of cardio-embolic stroke. This expert opinion paper aims to give practical advice to physicians who are involved in stroke care. In line with the nature of an expert opinion paper, labeling of classes of recommendations is not provided, since many statements are based on expert opinion, reported case series, and clinical experience.

Introduction: In the THALES trial, ticagrelor and aspirin was superior to aspirin alone in reducing the primary endpoint of stroke or death, and subsequent disabling strokes, but increased risk of bleeding, as expected for dual antiplatelet therapy. Aim: Present the bleeding profile of ticagrelor in combination with aspirin in patients with acute cerebrovascular events. Methods: The THALES trial randomized patients with non-cardioembolic, non-severe ischemic stroke (NIHSS≤5) or high-risk TIA to ticagrelor (180mg loading dose on day 1 followed by 90mg twice daily until day 30) or placebo within 24h of symptom onset in 28 countries. All patients received aspirin 300-325mg on day 1 followed by 75-100mg daily until day 30. Primary safety endpoint was time to severe bleeding, defined by GUSTO criteria, within 30 days. Analyses were by intention to treat. (ClinicalTrials.gov number, NCT03354429). Results: Among 11016 patients randomized, 28 (0.5%) in the ticagrelor+aspirin group (T+A) and 7 (0.1%) in the aspirin group (A) had a severe bleeding event; HR 3.99 (1.74-9.14); p=0.001. Among these, 22 (0.4%) (T+A) vs 6 (0.1%) (A) were fatal or intracranial hemorrhages (ICHs) and 6 (0.1%) (T+A) vs 1 (<0.1%) (A) non-fatal events with hemodynamic compromise. ICHs included 10 (0.2%) (T+A) vs 2 (<0.1%) (A) hemorrhagic strokes and 4 (0.1%) (T+A) vs 2 (<0.1%) (A) symptomatic haemorrhagic transformations of ischemic stroke and other ICHs. Most severe bleeding events were spontaneous; 1 (T+A) and 2 (A) were traumatic and 1 in each treatment group were procedural. No predefined subgroup was associated with severe bleeding risk though analyses were limited by a small number of events. Moderate/severe bleeding events occurred in 36 (0.7%) (T+A) vs 11 (0.2%) (A) patients. Bleeding leading to discontinuation occurred in 152 (2.8%) (T+A) vs 32 (0.6%) (A) patients. Conclusion: While the rate of severe bleeding in the patients with acute ischemic stroke or TIA was low, patients randomized to receive ticagrelor more often experienced severe bleeding events. No subgroup with different bleeding risk could be identified. Given the high risk of disability following a subsequent stroke, the benefit of adding ticagrelor to aspirin in reducing subsequent stroke appears to outweigh the risk of bleeding.