Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, blinded-outcome, randomised non-inferiority trial.

BACKGROUND: Whether thrombectomy alone is equally as effective as intravenous alteplase plus thrombectomy remains controversial. We aimed to determine whether thrombectomy alone would be non-inferior to intravenous alteplase plus thrombectomy in patients presenting with acute ischaemic stroke. METHODS: In this multicentre, randomised, open-label, blinded-outcome trial in Europe and Canada, we recruited patients with stroke due to large vessel occlusion confirmed with CT or magnetic resonance angiography admitted to endovascular centres. Patients were randomly assigned (1:1) via a centralised web server using a deterministic minimisation method to receive stent-retriever thrombectomy alone or intravenous alteplase plus stent-retriever thrombectomy. In both groups, thrombectomy was initiated as fast as possible with any commercially available Solitaire stent-retriever revascularisation device (Medtronic, Irvine, CA, USA). In the combined treatment group, intravenous alteplase (0·9 mg/kg bodyweight, maximum dose 90 mg per patient) was administered as early as possible after randomisation for 60 min with 10% of the calculated dose given as an initial bolus. Personnel assessing the primary outcome were masked to group allocation; patients and treating physicians were not. The primary binary outcome was a score of 2 or less on the modified Rankin scale at 90 days. We assessed the non-inferiority of thrombectomy alone versus intravenous alteplase plus thrombectomy in all randomly assigned and consenting patients using the one-sided lower 95% confidence limit of the Mantel-Haenszel risk difference, with a prespecified non-inferiority margin of 12%. The main safety endpoint was symptomatic intracranial haemorrhage assessed in all randomly assigned and consenting participants. This trial is registered with ClinicalTrials.gov, NCT03192332, and is closed to new participants. FINDINGS: Between Nov 29, 2017, and May 7, 2021, 5215 patients were screened and 423 were randomly assigned, of whom 408 (201 thrombectomy alone, 207 intravenous alteplase plus thrombectomy) were included in the primary efficacy analysis. A modified Rankin scale score of 0-2 at 90 days was reached by 114 (57%) of 201 patients assigned to thrombectomy alone and 135 (65%) of 207 patients assigned to intravenous alteplase plus thrombectomy (adjusted risk difference -7·3%, 95% CI -16·6 to 2·1, lower limit of one-sided 95% CI -15·1%, crossing the non-inferiority margin of -12%). Symptomatic intracranial haemorrhage occurred in five (2%) of 201 patients undergoing thrombectomy alone and seven (3%) of 202 patients receiving intravenous alteplase plus thrombectomy (risk difference -1·0%, 95% CI -4·8 to 2·7). Successful reperfusion was less common in patients assigned to thrombectomy alone (182 [91%] of 201 vs 199 [96%] of 207, risk difference -5·1%, 95% CI -10·2 to 0·0, p=0·047). INTERPRETATION: Thrombectomy alone was not shown to be non-inferior to intravenous alteplase plus thrombectomy and resulted in decreased reperfusion rates. These results do not support omitting intravenous alteplase before thrombectomy in eligible patients. FUNDING: Medtronic and University Hospital Bern.

[Prehospital stroke treatment in German-speaking countries]. / Praxis der präklinischen Schlaganfallversorgung im deutschsprachigen Raum: Eine Umfrage unter den ärztlichen Leitungen Rettungsdienst in Deutschland, Österreich und der Schweiz.

Background: The prognosis of stroke patients can be improved by adherence to clinical guidelines. Objective: To analyse the current state of organisation of prehospital stroke treatment in Germany, Austria and Switzerland with a focus on guideline adherence. Materials and methods: All medical directors of emergency medical services (MDEMS) in Germany (n = 178), Austria (n = 9) and Switzerland (n = 32) were invited to complete an anonymous online survey (unipark.com, Tivian XI GmbH, Cologne, Germany) which was available for 10 weeks from April-June 2020. Participants were asked for information regarding structural organisation, clinical treatment and strategic/tactical aspects. Results: The survey was completed 69 times and 65 datasets were analysed (4 participants without MDEMS status): 73.8% (n = 48) were MDEMS from Germany, 15.4% (n = 10) from Switzerland and 10.8% from Austria (n = 7). The survey results show relevant differences in the infrastructure of and the approach to prehospital stroke treatment. Standard operating procedures for stroke treatment were in place in 93.3% (n = 61) of the EMS areas. Furthermore, 37% (n = 24) of the EMS areas differentiated between stroke with mild and severe symptoms and 15.4% (n = 10) used specific scores for the prehospital prediction of large vessel occlusion strokes (LVOS). Conclusions: Our data highlight the heterogeneity of prehospital stroke treatment in Germany, Austria and Switzerland. Consistent use of appropriate scores for LVOS prediction and a higher adherence to recent clinical guideline in general are measures that should be taken to optimise the prehospital treatment of stroke patients.

Blood Pressure Trajectory Groups and Outcome After Endovascular Thrombectomy: A Multicenter Study.

BACKGROUND: Elevated blood pressure after endovascular thrombectomy (EVT) has been associated with an increased risk of hemorrhagic transformation and poor functional outcomes. However, the optimal hemodynamic management after EVT remains unknown, and the blood pressure course in the acute phase of ischemic stroke has not been well characterized. This study aimed to identify patient subgroups with distinct blood pressure trajectories after EVT and study their association with radiographic and functional outcomes. METHODS: This multicenter retrospective cohort study included consecutive patients with anterior circulation large-vessel occlusion ischemic stroke who underwent EVT. Repeated time-stamped blood pressure data were recorded for the first 72 hours after thrombectomy. Latent variable mixture modeling was used to separate subjects into five groups with distinct postprocedural systolic blood pressure (SBP) trajectories. The primary outcome was functional status, measured on the modified Rankin Scale 90 days after stroke. Secondary outcomes included hemorrhagic transformation, symptomatic intracranial hemorrhage, and death. RESULTS: Two thousand two hundred sixty-eight patients (mean age [±SD] 69±15, mean National Institutes of Health Stroke Scale 15±7) were included in the analysis. Five distinct SBP trajectories were observed: low (18%), moderate (37%), moderate-to-high (20%), high-to-moderate (18%), and high (6%). SBP trajectory group was independently associated with functional outcome at 90 days (P<0.0001) after adjusting for potential confounders. Patients with high and high-to-moderate SBP trajectories had significantly greater odds of an unfavorable outcome (adjusted odds ratio, 3.5 [95% CI, 1.8-6.7], P=0.0003 and adjusted odds ratio, 2.2 [95% CI, 1.5-3.2], P<0.0001, respectively). Subjects in the high-to-moderate group had an increased risk of symptomatic intracranial hemorrhage (adjusted odds ratio, 1.82 [95% CI, 1-3.2]; P=0.04). No significant association was found between trajectory group and hemorrhagic transformation. CONCLUSIONS: Patients with acute ischemic stroke demonstrate distinct SBP trajectories during the first 72 hours after EVT that have differing associations with functional outcome. These findings may help identify potential candidates for future blood pressure modulation trials.

What is the added value of CT-angiography in patients with transient ischemic attack?

BACKGROUND: Transient ischemic attack (TIA) is an important predictor for a pending stroke. Guidelines recommend a workup for TIA-patients similar to that of stroke patients, including an assessment of the extra- and intracranial arteries for vascular pathologies with direct therapeutic implications via computed tomography angiography (CTA). Aim of our study was a systematic analysis of TIA-patients receiving early CTA-imaging and to evaluate the predictive value of TIA-scores and clinical characteristics for ipsilateral vascular pathologies and the need of an invasive treatment. METHODS: We analysed clinical and imaging data from TIA patients being admitted to a tertiary university hospital between September 2015 and March 2018. Following subgroups were identified: 1) no- or low-grade vascular pathology 2) ipsilateral high-risk vascular pathology and 3) high-risk findings that needed invasive, surgical or interventional treatment. We investigated established TIA-scores (ABCD2-, the ABCD3- and the SPI-II score) and various clinical characteristics as predictive factors for ipsilateral vascular pathologies and the need for invasive treatment. RESULTS: Of 812 patients, 531 (65.4%) underwent initial CTA in the emergency department. In 121 (22.8%) patients, ipsilateral vascular pathologies were identified, of which 36 (6.7%) needed invasive treatment. The ABCD2-, ABCD3- and SPI-II-scores were not predictive for ipsilateral vascular pathologies or the need for invasive treatment. We identified male sex (OR 1.579, 95%CI 1.049-2.377, p = 0.029), a short duration of symptoms (OR 0.692, 95% CI 0.542-0.884, p = 0.003), arterial hypertension (OR 1.718, 95%CI 0.951-3.104, p = 0.073) and coronary heart disease (OR 1.916, 95%CI 1.184-3.101, p = 0.008) as predictors for ipsilateral vascular pathologies. As predictors for the need of invasive treatment, a short duration of symptoms (OR 0.565, 95%CI 0.378-0.846, p = 0.006), arterial hypertension (OR 2.612, 95%OR 0.895-7.621, p = 0.079) and hyperlipidaemia (OR 5.681, 95%CI 0.766-42.117, p = 0.089) as well as the absence of atrial fibrillation (OR 0.274, OR 0.082-0.917, p = 0.036) were identified. CONCLUSION: More than every fifth TIA-patient had relevant vascular findings revealed by acute CTA. TIA-scores were not predictive for these findings. Patients with a short duration of symptoms and a vascular risk profile including coronary heart disease, arterial hypertension and hyperlipidaemia most likely might benefit from early CTA to streamline further diagnostics and therapy.

Blood Pressure Goals and Clinical Outcomes after Successful Endovascular Therapy: A Multicenter Study.

OBJECTIVE: Elevated systolic blood pressure (SBP) after successful revascularization (SR) via endovascular therapy (EVT) is a known predictor of poor outcome. However, the optimal SBP goal following EVT is still unknown. Our objective was to compare functional and safety outcomes between different SBP goals after EVT with SR. METHODS: This international multicenter study included 8 comprehensive stroke centers and patients with anterior circulation large vessel occlusion who were treated with EVT and achieved SR. SR was defined as modified thrombolysis in cerebral ischemia 2b to 3. Patients were divided into 3 groups based on SBP goal in the first 24 hours after EVT. Inverse probability of treatment weighting (IPTW) propensity analysis was used to assess the effect of different SBP goals on clinical outcomes. RESULTS: A total of 1,019 patients were included. On IPTW analysis, the SBP goal of <140mmHg was associated with a higher likelihood of good functional outcome and lower odds of hemicraniectomy compared to SBP goal of <180mmHg. Similarly, SBP goal of <160mmHg was associated with lower odds of mortality compared to SBP goal of <180mmHg. In subgroup analysis including only patients with pre-EVT SBP of ≥140mmHg, an SBP of <140mmHg was associated with a higher likelihood of good functional outcome, lower odds of symptomatic intracranial hemorrhage, and lower odds of requirement for hemicraniectomy compared to SBP goal of <180mmHg. INTERPRETATION: SBP goals of <140 and < 160mmHg following SR with EVT appear to be associated with better clinical outcomes than SBP of <180mmHg. ANN NEUROL 2020;87:830-839.

Clinical Ethics Consultation in Neurology - a case series.

BACKGROUND: The concept of clinical ethics consultation (CECs) was implemented to provide support in ethical controversies in clinical settings and are offered in at least every second hospital in Germany. Neurological disorders often require complex decision-making. The aims of this study were to determine which situations lead to CEC in neurology and to investigate the influence of the individual patient's wishes on the recommendation. METHODS: Standardised CEC protocols in the years 2011 to 2017 at the University Hospitals of Goettingen and Jena were retrospectively surveyed. The contents were categorised along existing protocol templates of CEC scenarios and subsequently paraphrased and reduced to significant meanings. RESULTS: 27 CEC scenarios which were facilitated by various professional disciplines were reviewed. Stroke was the most frequent underlying condition. Nearly all patients were not able to consent. Mostly, the relatives acted as representatives or health advocates. In 67 % of cases, a sense of conflict triggered a CEC; in 33 % a sense of uncertainty was the reason for the CEC request. In 21 CEC scenarios, a recommendation was reached in consensus with all parties involved. In 59 % of cases, a decision was made to continue medical therapy. In seven cases, the patient's wishes led to a limitation of therapy, while in just two cases this decision was made primarily relying on the patient's best interest. In only 13 % of cases, a valid advance directive led to respective therapeutic consequences. CONCLUSIONS: CEC is feasible for consensus-finding not only in conflicts, but also in situations of therapeutic uncertainty in neurology. There is a special importance of the patient's wishes in decision-making in neurology. However, only in a few cases were advance directives precise and specific enough to have sufficient and decisive weight in therapeutic decision-making.

Comparing the diagnostic value of Echocardiography In Stroke (CEIS) - results of a prospective observatory cohort study.

BACKGROUND: Echocardiography is one of the main diagnostic tools for the diagnostic workup of stroke and is already well integrated into the clinical workup. However, the value of transthoracic vs. transesophageal echocardiography (TTE/TEE) in stroke patients is still a matter of debate. Aim of this study was to characterize relevant findings of TTE and TEE in the management of stroke patients and to correlate them with subsequent clinical decisions and therapies. METHODS: We evaluated n = 107 patients admitted with an ischemic stroke or transient ischemic attack to our stroke unit of our university medical center. They underwent TTE and TEE examination by different blinded investigators. RESULTS: Major cardiac risk factors were found in 8 of 98 (8.2%) patients and minor cardiac risk factors for stroke were found in 108 cases. We found a change in therapeutic regime after TTE or TEE in 22 (22.5%) cases, in 5 (5%) cases TEE leads to the change of therapeutic regime, in 4 (4%) TTE and in 13 cases (13.3%) TTE and TEE lead to the same change in therapeutic regime. The major therapy change was the indication to close a patent foramen ovale (PFO) in 9 (9.2%) patients with TTE and in 10 (10.2%) patients with TEE (p = 1.000). CONCLUSION: Major finding with clinical impact on therapy change is the detection of PFO. But for the detection of PFO, TTE is non inferior to TEE, implicating that TTE serves as a good screening tool for detection of PFO, especially in young age patients. TRIAL REGISTRATION: The trial was registered and approved prior to inclusion by our local ethics committee (1/3/17).

[Interactions between the brain and heart]. / Interaktionen zwischen Gehirn und Herz.

The brain and heart are closely interconnected. Physiologically, the brain influences the way the heart beats. An example for this physiological influence is the control of the heart rate via efferences of the autonomic nervous system. Clinical examples for this direction of interactions include cardiac complications after stroke as well as takotsubo cardiomyopathy; however, the heart and brain are reciprocally connected so that heart activity also influences the brain beyond its function as the generator of bloodflow supplying the brain. Examples for this are the perception of stimuli depending on the time of presentation during the heart cycle. Clinical examples of the direction of this interaction constitute stroke as a thromboembolic complication of atrial fibrillation as well as the correlation of atrial fibrillation and dementia. This review article gives an overview of the bidirectional interactions between the heart and brain, partly including the cardiovascular system, discusses their implications for the clinical routine and gives an outlook on current fields of research.

Brain Natriuretic Peptide and Discovery of Atrial Fibrillation After Stroke: A Subanalysis of the Find-AFRANDOMISED Trial.

Background and Purpose- Diagnosing paroxysmal atrial fibrillation (pAF) can be challenging after acute ischemic stroke. Enhanced and prolonged Holter-ECG monitoring (EPM) improves the detection rate but is not feasible for all patients. We hypothesized that brain natriuretic peptide (BNP) may help to identify patients with stroke at high risk for pAF to select patients for EPM more effectively. Methods- Patients with acute cerebral ischemia ≥60 years presenting in sinus rhythm and without history of AF were included into a prospective, randomized multicenter study to receive either EPM (3× 10-day Holter-ECG) or usual stroke care diagnostic work-up. BNP plasma levels were measured on randomization and 3 months thereafter. Levels were compared between patients with and without pAF detected by means of EPM or usual care. Furthermore, the number needed to screen for EPM depending on BNP cut offs was calculated. Results- A total of 398 patients were analyzed. In 373 patients (93.7%), BNP was measured at baseline and in 275 patients (69.1%) after 3 months. pAF was found in 27 patients by means of EPM and in 9 patients by means of usual care (P=0.002). Median BNP was higher in patients with pAF as compared to patients without AF in both study arms at baseline (57.8 versus 28.3 pg/mL in the EPM arm, P=0.0003; 46.2 versus 27.7 pg/mL, P=0.28 in the control arm) and after 3 months (74.9 versus 31.3 pg/mL, P=0.012 in the EPM arm, 99.3 versus 26.3 pg/mL, P=0.02 in the control arm). Applying a cut off of 100 pg/mL, the number needed to screen was reduced from 18 by usual care to 3 by EPM. Conclusions- BNP measured early after ischemic stroke identifies a subgroup of patients with stroke at increased risk for AF, in whom EPM is particularly efficacious. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01855035.

Blood Pressure and Outcome After Mechanical Thrombectomy With Successful Revascularization.

Background and Purpose- Successful reperfusion can be achieved in more than two-thirds of patients treated with mechanical thrombectomy. Therefore, it is important to understand the effect of blood pressure (BP) on clinical outcomes after successful reperfusion. In this study, we investigated the relationship between BP on admission and during the first 24 hours after successful reperfusion with clinical outcomes. Methods- This was a multicenter study from 10 comprehensive stroke centers. To ensure homogeneity of the studied cohort, we included only patients with anterior circulation who achieved successful recanalization at the end of procedure. Clinical outcomes included 90-day modified Rankin Scale, symptomatic intracerebral hemorrhage (sICH), mortality, and hemicraniectomy. Results- A total of 1245 patients were included in the study. Mean age was 69±14 years, and 51% of patients were female. Forty-nine percent of patients had good functional outcome at 90-days, and 4.7% suffered sICH. Admission systolic BP (SBP), mean SBP, maximum SBP, SBP SD, and SBP range were associated with higher risk of sICH. In addition, patients in the higher mean SBP groups had higher rates of sICH. Similar results were found for hemicraniectomy. With respect to functional outcome, mean SBP, maximum SBP, and SBP range were inversely associated with the good outcome (modified Rankin Scale score, 0-2). However, the difference in SBP parameters between the poor and good outcome groups was modest. Conclusions- Higher BP within the first 24 hours after successful mechanical thrombectomy was associated with a higher likelihood of sICH, mortality, and requiring hemicraniectomy.

Functional Outcome Following Stroke Thrombectomy in Clinical Practice.

Background and Purpose- Endovascular treatment for large vessel occlusion in ischemic stroke has proven to be effective in large clinical trials. We aimed to provide real-world estimates of endovascular treatment reperfusion rates and functional outcome on a countrywide scale. Methods- Two thousand seven hundred ninety-four patients with large vessel occlusion were included into an investigator-initiated, industry-independent, prospective registry in 25 sites in Germany between June 2015 and April 2018. The primary outcome was the score on the modified Rankin Scale ranging from zero (no symptoms) to 6 (death) at 3 months. Secondary analyses included the prediction of a good outcome (modified Rankin Scale, 0-2). Dichotomized analyses of predictors were performed using logistic regression adjusted for potential confounders. Results- Median age was 75 years (interquartile range, 64-82); median National Institutes of Health Stroke Scale score was 15 (interquartile range, 10-19). Vessel occlusion was in the anterior circulation in 2265 patients (88%) and in the posterior circulation in 303 patients (12%). Intravenous alteplase before endovascular treatment was given in 1457 patients (56%). Successful reperfusion was achieved in 2143 subjects (83%). At 3 months, 854 patients (37%) showed a good outcome; mortality was 29%. There was no difference between anterior and posterior circulation occlusions (P=0.27). Significant predictors for a good outcome were younger age (odds ratio [OR], 1.06; 95% CI, 1.05-1.07), no interhospital transfer (OR, 1.39; 95% CI, 1.03-1.88), lower stroke severity (OR, 1.10; 95% CI, 1.08-1.13), smaller infarct size (OR, 1.26; 95% CI, 1.15-1.39), alteplase use (OR, 1.49; 95% CI, 1.08-2.06), and reperfusion success (OR, 1.69; 95% CI, 1.45-1.96). Conclusions- High rates of favorable outcome can be achieved on a countrywide scale by endovascular treatment. Mortality appears to be greater in the daily routine than otherwise reported by authors of large randomized trials. There were no outcome differences between the anterior and posterior circulation. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT03356392.

Intracranial mechanical thrombectomy of large vessel occlusions in the posterior circulation using SAVE.

BACKGROUND: Mechanical thrombectomy (MT) using stent retriever assisted vacuum-locked extraction (SAVE) is a promising method for anterior circulation strokes. We present our experience with SAVE for large vessel occlusions (LVO) of the posterior circulation. METHODS: We retrospectively analyzed 66 consecutive MT patients suffering from LVO of the posterior circulation. Primary endpoints were first-pass and overall complete/near complete reperfusion, defined as a modified thrombolysis in cerebral infarction (mTICI) score of 2c and 3. Secondary endpoints contained number of passes, time interval from groin puncture to reperfusion and rate of postinterventional symptomatic intracranial hemorrhage (sICH). RESULTS: Median age was 75 years (interquartile range (IQR) 54-81 years). Baseline median National Institutes of Health stroke scale (NIHSS) was 13 (IQR 8-21). Fifty-five (83%) patients had LVO of the basilar artery and 11 (17%) of the posterior cerebral artery. Eighteen (27%) patients were treated with SAVE and 21 (32%) with aspiration only. First pass mTICI2c or 3 and overall mTICI2c or 3 were documented in 11/18 (61%) and 14/18 (78%) with SAVE and in 4/21 (19%) and 13/21 (33%) with aspiration only. Median attempt was 1 (IQR 1-2) with SAVE and 2 (IQR 1-4) with aspiration (p = 0.0249). Median groin to reperfusion time did not differ significantly between groups. The rate of sICH was 5% without any complications in the SAVE cohort. CONCLUSION: Mechanical thrombectomy of posterior large vessel occlusions with SAVE is feasible, safe, and effective with high rates of near-complete and complete reperfusion.

High Systolic Blood Pressure after Successful Endovascular Treatment Affects Early Functional Outcome in Acute Ischemic Stroke.

BACKGROUND: Endovascular treatment (EVT) has been shown to significantly improve functional outcome in patients with acute large cerebral vessel occlusions. To date, no evidence-based recommendations on blood pressure management after successful EVT exist. Previous studies showed an association between high pre-EVT systolic blood pressure (SBP) and functional outcome, but do not answer the question on how to manage blood pressure after successful recanalization. The purpose of this study was to determine the role of blood pressure measurements as a predictor for early functional outcome in patients with successful EVT. METHODS: Prospectively derived data from patients with acute large vessel occlusion within the anterior circulation and EVT was analyzed in this monocentric study. Mean systolic- and maximum SBP as well as SBP-peaks have been obtained for the first 24 h after successful EVT. Predictive value of SBP for discharge modified Rankin Scale (mRS) ≤2 has been investigated using logistic regression models. RESULTS: From 168 patients with successful EVT, 74 (44%) had a favorable outcome with an mRS ≤2. Mean- (127 vs. 131 mm Hg, p = 0.035) and maximum SBP (157 vs. 169 mm Hg, p < 0.001) as well as the number of SBP-peaks (0 vs. 1.5, p = 0.004) were lower in patients with favorable outcomes. Multivariable logistic regression showed high mean- and maximum SBP to predict unfavorable outcomes. Cutoff mean SBP was 141 mm Hg and maximum SBP 159 mm Hg. CONCLUSIONS: High SBP in the first 24 h after recanalization of acute anterior cerebral vessel occlusions is associated with unfavorable functional outcome. Interventional studies are needed to determine the role of SBP management as a modifiable parameter in the early phase after successful EVT.

One-Stop Management of Acute Stroke Patients: Minimizing Door-to-Reperfusion Times.

BACKGROUND AND PURPOSE: Intrahospital time delays significantly affect the neurological outcome of stroke patients with large-vessel occlusion. This study was conducted to determine whether a one-stop management can reduce intrahospital times of patients with acute large-vessel occlusion. METHODS: In this observational study, we report the first 30 consecutive stroke patients imaged and treated in the same room. As part of our protocol, we transported patients with a National Institutes of Health Stroke Scale score of ≥10 directly to the angio suite, bypassing multidetector computed tomography (CT). Preinterventional imaging consisted of noncontrast flat detector CT and flat detector CT angiography, acquired with an angiography system. Patients with large-vessel occlusions remained on the angio table and were treated with mechanical thrombectomy; patients with small artery occlusions were treated with intravenous thrombolysis, whereas patients with an intracranial hemorrhage and stroke mimics were treated as per guidelines. Door-to-groin puncture times were recorded and compared with our past results. RESULTS: Thirty patients were transferred directly to our angio suite from June to December 2016. The time from symptom onset to admission was 105 minutes. Ischemic stroke was diagnosed in 22 of 30 (73%) patients, 4 of 30 (13.5%) had an intracranial hemorrhage, and 4 of 30 (13.5) were diagnosed with a Todd's paresis. Time from admission to groin puncture was 20.5 minutes. Compared with 44 patients imaged with multidetector CT in the first 6 months of 2016, door-to-groin times were significantly reduced (54.5 minutes [95% confidence interval, 47-61] versus 20.5 minutes [95% confidence interval, 17-26]). CONCLUSIONS: In this small series, a one-stop management protocol of selected stroke patients using latest generation flat detector CT led to a significant reduction of intrahospital times.

Transcranial doppler sonography is not a valid diagnostic tool for detection of basilar artery stenosis or in-stent restenosis: a retrospective diagnostic study.

BACKGROUND: There are contradictory reports concerning the validity of transcranial sonography (TCD and TCCS) for examinations of the basilar artery. Here we investigated sensitivity and specificity of transcranial sonography for the detection of basilar artery stenosis and in-stent-restenosis compared to cerebral angiography. METHODS: We analyzed data of 104 examinations of the basilar artery. The association between sonographic peak systolic velocity (PSV) and degree of stenosis obtained by cerebral angiography was evaluated applying Spearman's correlation coefficient. Receiver Operating Characteristics (ROC) curves and areas under the curve (AUC) were calculated for the detection of a ≥50% stenosis defined by angiography. Optimal cut-off was derived using the Youden-index. RESULTS: A weak but statistically significant correlation between PSV and the degree of stenosis was found (n=104, rho=0.35, p<0.001). ROC analysis for a detection of ≥50% stenosis showed an AUC of 0.70, a sensitivity of 74.0% and a specificity of 65.0% at the optimal cut off of 124 cm/s. Results were consistent when analyzing examinations done in stented and unstented arteries separately (TCD VS DSA/CTA in unstented artery: AUC=0.66, sensitivity 61.0%, specificity 65.0%, TCD/TCCS VS DSA in stented artery: AUC=0.63, sensitivity 71.0%, specificity 82.0%). Comparing TCCS measurements exclusively to angiography, ROC analysis showed an AUC of 1.00 for the detection of an in-stent-restenosis ≥50% with a sensitivity and specificity of 100% when a PSV of 132 cm/s was used as a cut off value. CONCLUSION: Validity of TCD in the assessment of basilar artery stenosis or in-stent restenosis is poor. First results for TCCS are promising, but due to the small samplesize further studies with larger samples sizes are warranted.

Clinical Relevance of Patent Foramen Ovale and Atrial Septum Aneurysm in Stroke: Findings of a Single-Center Cross-Sectional Study.

BACKGROUND: A significant proportion of ischemic strokes are cryptogenic. In this context, the clinical pertinence of patent foramen ovale (PFO) with and without atrial septum aneurysm (ASA) remains controversial. The aim of this study was to identify how PFO +/-ASA and cryptogenic stroke are associated in a representative sample of stroke patients. METHODS: We enrolled all patients (n = 909) with ischemic stroke or transient ischemic attack admitted to the certified stroke unit or neurological intensive care unit of our university medical center who underwent transesophageal echocardiography (TEE) between 2012 and 2014. The baseline characteristics, cardio-/neurovascular risk factors, clinical parameters and TEE findings were analyzed. RESULTS: PFO was present in 26.2%, and PFO was combined with an ASA in 9.9%. In cryptogenic stroke, the prevalence of PFO was higher compared to other etiologies (30.9 vs. 21.9%; p < 0.002). Patients with PFO had lower National Institute of Health Stroke Score (NIHSS) values at admission than those without (2 [0-5] vs. 3 [1-7]; p = 0.001; 95% CI [0.62-0.88]). No difference was found in NIHSS values of PFO patients with or without ASA (2 [0-5] vs. 2 [0-5]; p = 0.683; 95% CI 0.94 [0.68-1.28]). CONCLUSIONS: Our study indicates that a detected PFO +/-ASA could exhibit a stroke-relevant finding, if classical risk factors for the stroke were lacking.

Added value of CT perfusion compared to CT angiography in predicting clinical outcomes of stroke patients treated with mechanical thrombectomy.

OBJECTIVES: CTP images analyzed with the Alberta stroke program early CT scale (ASPECTS) have been shown to be optimal predictors of clinical outcome. In this study we compared two biomarkers, the cerebral blood volume (CBV)-ASPECTS and the CTA-ASPECTS as predictors of clinical outcome after thrombectomy. METHODS: Stroke patients with thrombosis of the M1 segment of the middle cerebral artery were included in our study. All patients underwent initial multimodal CT with CTP and CTA on a modern CT scanner. Treatment consisted of full dose intravenous tissue plasminogen activator, when applicable, and mechanical thrombectomy. Three neuroradiologists separately scored CTP and CTA images with the ASPECTS score. RESULTS: Sixty-five patients were included. Median baseline CBV-ASPECTS and CTA-ASPECTS for patients with favourable clinical outcome at follow-up were 8 [interquartile range (IQR) 8-9 and 7-9 respectively]. Patients with poor clinical outcome showed a median baseline CBV-ASPECTS of 6 (IQR 5-8, P < 0.0001) and a median baseline CTA-ASPECTS of 7 (IQR 7-8, P = 0.18). Using CBV-ASPECTS and CTA-ASPECTS raters predicted futile reperfusions in 96 % and 56 % of the cases, respectively. CONCLUSIONS: CBV-ASPECTS is a significant predictor of clinical outcome in patients with acute ischemic stroke treated with mechanical thrombectomy. KEY POINTS: • CBV-ASPECTS is a significant predictor of clinical outcome. • Single phase CTA-ASPECTS has low predictive value. • Using CBV-ASPECTS, raters identified futile reperfusions in 96 % of the cases.

CDK5 protects from caspase-induced Ataxin-3 cleavage and neurodegeneration.

Spinocerebellar ataxia type 3 (SCA3) is one of at least nine inherited neurodegenerative diseases caused by an expansion of a polyglutamine tract within corresponding disease-specific proteins. In case of SCA3, mutation of Ataxin-3 results in aggregation of misfolded protein, formation of intranuclear as well as cytosolic inclusion bodies and cell death in distinct neuronal populations. Since cyclin-dependent kinase-5 (CDK5) has been shown to exert beneficial effects on aggregate formation and cell death in various polyglutamine diseases, we tested its therapeutic potential for SCA3. Our data show increased caspase-dependent Ataxin-3 cleavage, aggregation, and neurodegeneration in the absence of sufficient CDK5 activity. This disease-propagating effect could be reversed by mutation of the caspase cleavage site in Ataxin-3. Moreover, reduction of CDK5 expression levels by RNAi in vivo enhances SCA3 toxicity as assayed in a Drosophila model for SCA3. In summary, we present CDK5 as a potent neuroprotectant, regulating cleavage and thereby toxicity of Ataxin-3 and other polyglutamine proteins. We propose that increased caspase-dependent cleavage of mutated Ataxin-3, because of missing CDK5 shielding, leads to aggregation and cell death. Moreover, reduction of CDK5 expression levels by RNAi in vivo enhances SCA3 toxicity as assayed in a Drosophila model for SCA3. We think that CDK5 functions as a shield against cleavage-induced toxification and thereby is an interesting target for therapeutic intervention in polyQ disease in general.

Finding atrial fibrillation in stroke patients: Randomized evaluation of enhanced and prolonged Holter monitoring--Find-AF(RANDOMISED) --rationale and design.

BACKGROUND: Detecting paroxysmal atrial fibrillation (AF) in patients with ischemic strokes presenting in sinus rhythm is challenging because episodes are often short, occur randomly, and are frequently asymptomatic. If AF is detected, recurrent thromboembolism can be prevented efficiently by oral anticoagulation. Numerous uncontrolled studies using various electrocardiogram (ECG) devices have established that prolonged ECG monitoring increases the yield of AF detection, but most established procedures are time-consuming and costly. The few randomized trials are mostly limited to cryptogenic strokes. The optimal method, duration, and patient selection remain unclear. Repeated prolonged continuous Holter ECG monitoring to detect paroxysmal AF within an unspecific stroke population may prove to be a widely applicable, effective secondary prevention strategy. STUDY DESIGN: Find-AFRANDOMISED is a randomized and controlled prospective multicenter trial. Four hundred patients 60 years or older with manifest (symptoms ≥24 hours or acute computed tomography/magnetic resonance imaging lesion) and acute (symptoms ≤7 days) ischemic strokes will be included at 4 certified stroke centers in Germany. Those with previously diagnosed AF/flutter, indications/contraindications for oral anticoagulation, or obvious causative blood vessel pathologies will be excluded. Patients will be randomized 1:1 to either enhanced and prolonged Holter ECG monitoring (10 days at baseline and after 3 and 6 months) or standard of care (≥24-hour continuous ECG monitoring, according to current stroke guidelines). All patients will be followed up for at least 12 months. OUTCOMES: The primary end point is newly detected AF (≥30 seconds) after 6 months, confirmed by an independent adjudication committee. We plan to complete recruitment in autumn 2014. First results can be expected by spring 2016.

Effect of Bridging Thrombolysis on the Efficacy of Stent Retriever Thrombectomy Techniques : Insights from the SWIFT-DIRECT trial.

BACKGROUND: There are little available data regarding the influence of intravenous thrombolysis (IVT) on the efficacy of different first line endovascular treatment (EVT) techniques. METHODS: We used the dataset of the SWIFT-DIRECT trial which randomized 408 patients to IVT + EVT or EVT alone at 48 international sites. The protocol required the use of a stent retriever (SR), but concomitant use of a balloon guide catheter (BGC) and/or distal aspiration (DA) catheter was left to the discretion of the operators. Four first line techniques were applied in the study population: SR, SR + BGC, SR + DA, SR + DA + BGC. To assess whether the effect of allocation to IVT + EVT versus EVT alone was modified by the first line technique, interaction models were fitted for predefined outcomes. The primary outcome was first pass mTICI 2c­3 reperfusion (FPR). RESULTS: This study included 385 patients of whom 172 were treated with SR + DA, 121 with SR + DA + BGC, 57 with SR + BGC and 35 with SR. There was no evidence that the effect of IVT + EVT versus EVT alone would be modified by the choice of first line technique; however, allocation to IVT + EVT increased the odds of FPR by a factor of 1.68 (95% confidence interval, CI 1.11-2.54). CONCLUSION: This post hoc analysis does not suggest treatment effect heterogeneity of IVT + EVT vs EVT alone in different stent retriever techniques but provides evidence for increased FPR if bridging IVT is administered before stent retriever thrombectomy.