A Managed Care System with Telemedicine Support for Neurological Emergencies.

OBJECTIVES: Telemedicine is frequently used to provide remote neurological expertise for acute stroke workup and was associated with better functional outcomes when combined with a stroke unit system-of-care. We investigated whether such system-of-care yields additional benefits when implemented on top of neurological competence already available onsite. METHODS: Quality improvement measures were implemented within a "hub-and-spoke" teleneurology network in 11 hospitals already provided with onsite or telestroke expertise. Measures included dedicated units for neurological emergencies, standardization of procedures, multiprofessional training, and quality-of-care monitoring. Intervention effects were investigated in a controlled study enrolling patients insured at 3 participating statutory health insurances diagnosed with acute stroke or other neurological emergencies. Outcomes during the intervention period between November 2017 and February 2020 were compared with those pre-intervention between October 2014 and March 2017. To control for temporal trends, we compared outcomes of patients with respective diagnoses in 11 hospitals of the same region. Primary outcome was the composite of up-to-90-day death, new disability with the need of ambulatory or nursing home care, expressed by adjusted hazard ratio (aHR). RESULTS: We included 1,418 patients post-implementation (55% female, mean age 76.7 ± 12.8 year) and 2,306 patients pre-implementation (56%, 75.8 ± 13.0 year, respectively). The primary outcome occurred in 479/1,418 (33.8%) patients post-implementation and in 829/2,306 (35.9%) pre-implementation. The aHR for the primary outcome was 0.89 (95% confidence interval [CI]: 0.79-0.99, p = 0.04) with no improvement seen in non-participating hospitals between post- versus pre-implementation periods (aHR 1.04; 95% CI: 0.95-1.15). INTERPRETATION: Implementation of a multicomponent system-of-care was associated with a lower risk of poor outcomes. ANN NEUROL 2023;93:511-521.

Association Between Dispatch of Mobile Stroke Units and Functional Outcomes Among Patients With Acute Ischemic Stroke in Berlin.

Importance: Effects of thrombolysis in acute ischemic stroke are time-dependent. Ambulances that can administer thrombolysis (mobile stroke units [MSUs]) before arriving at the hospital have been shown to reduce time to treatment. Objective: To determine whether dispatch of MSUs is associated with better clinical outcomes for patients with acute ischemic stroke. Design, Setting, and Participants: This prospective, nonrandomized, controlled intervention study was conducted in Berlin, Germany, from February 1, 2017, to October 30, 2019. If an emergency call prompted suspicion of stroke, both a conventional ambulance and an MSU, when available, were dispatched. Functional outcomes of patients with final diagnosis of acute cerebral ischemia who were eligible for thrombolysis or thrombectomy were compared based on the initial dispatch (both MSU and conventional ambulance or conventional ambulance only). Exposure: Simultaneous dispatch of an MSU (computed tomographic scanning with or without angiography, point-of-care laboratory testing, and thrombolysis capabilities on board) and a conventional ambulance (n = 749) vs conventional ambulance alone (n = 794). Main Outcomes and Measures: The primary outcome was the distribution of modified Rankin Scale (mRS) scores (a disability score ranging from 0, no neurological deficits, to 6, death) at 3 months. The coprimary outcome was a 3-tier disability scale at 3 months (none to moderate disability; severe disability; death) with tier assignment based on mRS scores if available or place of residence if mRS scores were not available. Common odds ratios (ORs) were used to quantify the association between exposure and outcome; values less than 1.00 indicated a favorable shift in the mRS distribution and lower odds of higher levels of disability. Results: Of the 1543 patients (mean age, 74 years; 723 women [47%]) included in the adjusted primary analysis, 1337 (87%) had available mRS scores (primary outcome) and 1506 patients (98%) had available the 3-tier disability scale assessment (coprimary outcome). Patients with an MSU dispatched had lower median mRS scores at month 3 (1; interquartile range [IQR], 0-3) than did patients without an MSU dispatched (2; IQR, 0-3; common OR for worse mRS, 0.71; 95% CI, 0.58-0.86; P < .001). Similarly, patients with an MSU dispatched had lower 3-month coprimary disability scores: 586 patients (80.3%) had none to moderate disability; 92 (12.6%) had severe disability; and 52 (7.1%) had died vs patients without an MSU dispatched: 605 (78.0%) had none to moderate disability; 103 (13.3%) had severe disability; and 68 (8.8%) had died (common OR for worse functional outcome, 0.73, 95% CI, 0.54-0.99; P = .04). Conclusions and Relevance: In this prospective, nonrandomized, controlled intervention study of patients with acute ischemic stroke in Berlin, Germany, the dispatch of mobile stroke units, compared with conventional ambulances alone, was significantly associated with lower global disability at 3 months. Clinical trials in other regions are warranted.

Bypassing the Closest Stroke Center for Thrombectomy Candidates: What Additional Delay to Thrombolysis Is Acceptable?

Background and Purpose- Patients with acute ischemic stroke who have large vessel occlusion benefit from direct transport to a comprehensive stroke center (CSC) capable of endovascular therapy. To avoid harm for patients without large vessel occlusion from delayed access to intravenous thrombolysis (IVT), it has been suggested to only redirect patients with high likelihood of large vessel occlusion for whom the additional delay to intravenous thrombolysis (IVT) caused by transport to the CSC is below a certain threshold. However, which threshold achieves the greatest clinical benefit is unknown. Methods- We used mathematical modeling to calculate additional-delay-to-IVT thresholds associated with the greatest reduction in disability-adjusted life years in abstracted 2-stroke center and multiple-stroke center scenarios. Model parameters were extracted from recent meta-analyses or large prospective cohort studies. Uncertainty was quantified in probabilistic and 2-way univariate sensitivity analyses. Results- Assuming ideal treatment time performance metrics, transport to the nearest CSC was the preferred strategy irrespective of additional delay-to-IVT when the transfer time between primary stroke center and CSC was <40 minutes (95% credible interval: 25-66 minutes); otherwise, the optimal additional delay-to-IVT-threshold ranged from 28 to 139 minutes. In multiple-stroke center scenarios, optimal additional-delay-to-IVT thresholds were 30 to 54 minutes in urban and 49 to 141 minutes in rural settings; use of optimal thresholds as compared with a 15 minute-threshold saved 0 to 0.11 and 0 to 0.37 disability-adjusted life years per triage case, respectively. Assuming slower treatment times at primary stroke centers and CSCs yielded longer permissible additional delays. Conclusions- Our results suggest that patients with acute ischemic stroke with suspected large vessel occlusion should be redirected to a CSC if the additional delay to IVT is <30 minutes in urban and 50 minutes in rural settings.

Benefit of Intravenous Thrombolysis in Acute Ischemic Stroke Patients With High Cerebral Microbleed Burden.

Background and Purpose- Cerebral microbleeds (CMBs) are a risk factor for intracranial hemorrhage. Whether intravenous thrombolysis (IVT) improves functional outcome in acute ischemic stroke patients with CMBs is unknown. We aimed to estimate the treatment effect of IVT in patients with acute ischemic stroke and a high burden (>10) of CMBs. Methods- We devised a multistep algorithm to model 90-day modified Rankin Scale scores in patients with ≤10 versus >10 CMBs who do or do not receive IVT. Parameters were extracted from recently published meta-analyses and included pairwise relationships between CMBs, IVT, 3-month functional outcome, and intracranial hemorrhage. Uncertainty was quantified in probabilistic sensitivity analyses. Results- In patients with >10 CMBs as compared with ≤10 CMBs, point estimates of the odds ratios for favorable outcome (modified Rankin Scale ≤2) associated with IVT were 7% to 10% lower but still >1 (range, 1.03-1.51). On the other hand, IVT in patients with >10 CMBs significantly increased the odds of mortality. The point estimates for the net treatment effect of IVT (change in the utility-weighted modified Rankin Scale score) in patients with >10 CMBs were in favor of withholding IVT in older patients with more severe strokes and longer treatment delays. However, because the general pretest probability of >10 CMBs is low (0.6%-2.7%), pretreatment magnetic resonance imaging to quantify CMB burden would be justified only if it delayed IVT by <10 minutes. Conclusions- High CMB burden modifies the treatment effect of IVT. In patients with >10 CMBs, IVT is associated with higher mortality and, in older patients with severe strokes and longer treatment delays, a net utility loss. Patients with higher-than-average pretest probability of >10 CMB might profit from magnetic resonance imaging screening if it does not increase the treatment time.

Association Between Thrombus Perviousness Assessed on Computed Tomography and Stroke Cause.

BACKGROUND AND PURPOSE: A recent study proposed that thrombus perviousness (TP)-the degree to which contrast agents penetrate the thrombus in an occluded vessel measured on noncontrast computed tomography (NCCT) and CT angiography-may be associated with cardioembolic stroke cause with high specificity. Our aim was to investigate which clinical and laboratory parameters affect measures of TP and to validate its diagnostic accuracy in an independent cohort of patients with acute ischemic stroke. METHODS: Seventy-five patients from a prospectively maintained database with proximal occlusions of the middle cerebral artery (M1) were retrospectively analyzed. Thrombi were segmented on coregistered noncontrast computed tomography and CT angiography to determine the thrombus attenuation increase and void fraction (attenuation increase relative to contralateral side). RESULTS: TP measures were significantly higher in patients with cardioembolic stroke compared to patients with stroke attributed to large artery atherosclerosis (median thrombus attenuation increase [interquartile range], 2.79 [-3.54 to 8.85] versus -5.11 [-11.23 to -1.47]; P=0.001). In linear regression analysis for TP including age, time to scan, prior medication with antiplatelets or anticoagulants, and selected laboratory parameters, only stroke cause was significantly associated with TP. In multivariable binary logistic regression analysis for dichotomized stroke cause (ie, cardioembolic versus noncardioembolic stroke), only thrombus attenuation increase was independently associated with cardioembolic stroke (odds ratio of 1.12 [95% CI, 1.04-1.22]; P=0.004). Receiver operating characteristic analysis indicated that TP can identify cardioembolic stroke with an area under the curve of 0.75 (95% CI, 0.63-0.87) for thrombus attenuation increase. With a cutoff value of 6.23 Hounsfield units, cardioembolic strokes were identified with 100% specificity. Results for void fraction were similar. CONCLUSIONS: The assessment of TP on baseline noncontrast computed tomography/CT angiography in patients with M1 occlusion may aid in determining cardioembolic stroke cause and guide secondary prevention. Selected clinical and laboratory parameters other than stroke cause did not affect TP measures.

Hypothalamic-Pituitary-Adrenocortical Axis Activity in Alcohol-Dependent Patients During Treatment with High-Dose Baclofen.

AIMS: Activity of the hypothalamic-pituitary-adrenocortical (HPA) axis has been reported to be affected in alcohol use disorder (AUD). It has been suggested that pharmacological relapse prevention in AUD might exert its effects partly by modulation of HPA axis activity. Here, we assessed the effects of high-dose treatment with baclofen on HPA axis activity in alcohol-dependent patients within a 24-week randomized, placebo-controlled trial (BACLAD study). METHODS: Plasma levels of copeptin, adrenocorticotropic hormone (ACTH), and cortisol were measured at 3 timepoints in alcohol-dependent patients during the study. Corresponding plasma levels in healthy controls were assessed once. RESULTS: ACTH blood levels were significantly higher in the group of alcohol-dependent patients compared to controls. In patients receiving individually titrated high-dose baclofen, plasma cortisol levels decreased significantly, whereas no significant alterations were found in the placebo group. CONCLUSIONS: Our study underlines again the role of HPA axis alterations in AUD. Furthermore, a decrease in hormonal stress levels during treatment with high-dose baclofen might contribute to the relapse preventive effects of this compound.

Impact of Prehospital Triage Scales to Detect Large Vessel Occlusion on Resource Utilization and Time to Treatment.

BACKGROUND AND PURPOSE: Prehospital stroke severity scales may help to triage acute ischemic stroke patients with large vessel occlusion (LVO) for direct transportation to a comprehensive stroke center. The impact on resource use and time to reperfusion treatment for patients with and without LVO is unknown. METHODS: Based on empirical distributions of stroke symptom severity, prehospital delay times, and stroke symptom severity-dependent likelihood of LVO, we simulate prehospital incidents of stroke-like symptoms in abstract geographical environments to estimate the impact of prehospital triage strategies based on different cutoffs of the rapid arterial occlusion evaluation scale. RESULTS: Compared with transporting each patient to the nearest stroke center, implementation of a prehospital triage strategy based on a rapid arterial occlusion evaluation scale cutoff score ≥5 is associated with more patients with suspected acute stroke at comprehensive stroke centers and less patients at primary stroke centers (+11.7% [95% confidence interval: +8.1% to +15.3%] and -18.4% [-19.1% to -17.7%], respectively). Mean time to groin puncture is reduced by 29.6 minutes (-35.2 to -24.7 minutes) while mean time to thrombolysis does not change significantly (±0.0 minutes [-0.3 to +0.3 minutes]). The total number of secondary transfers is reduced by 60.9% (-62.8% to -59.0%); mean time of ambulance use per patient is unchanged. Results are robust with regards to variation in model parameters. CONCLUSIONS: Implementation of prehospital triage based on stroke severity scales would have strong impact on patient flow and distribution. The benefit of earlier thrombectomy for patients with LVO may outweigh the harm associated with delayed access to thrombolysis for some patients without LVO. Randomized trials using clinical stroke severity scales as a triage tool are needed to confirm our findings.

Clinical benefit of improved Prehospital stroke scales to detect stroke patients with large vessel occlusions: results from a conditional probabilistic model.

BACKGROUND: Clinical scales to detect large vessel occlusion (LVO) may help to determine the optimal transport destination for patients with suspected acute ischemic stroke (AIS). The clinical benefit associated with improved diagnostic accuracy of these scales has not been quantified. METHODS: We used a previously reported conditional model to estimate the probability of good outcome (modified Rankin scale sore ≤2) for patients with AIS and unknown vessel status occurring in regions with greater proximity to a primary than to a comprehensive stroke center. Optimal rapid arterial occlusion evaluation (RACE) scale cutoff scores were calculated based on time-dependent effect-size estimates from recent randomized controlled trials. Probabilities of good outcome were compared between a triage strategy based on these cutoffs and a strategy based on a hypothetical perfect LVO detection tool with 100% diagnostic accuracy. RESULTS: In our model, the additional benefit of a perfect LVO detection tool as compared to optimal transport-time dependent RACE cutoff scores ranges from 0 to 5%. It is largest for patients with medium stroke symptom severity (RACE score 5) and in geographic environments with longer transfer time between the primary and comprehensive stroke center. CONCLUSION: Based on a probabilistic conditional model, the results of our simulation indicate that more accurate prehospital clinical LVO detections scales may be associated with only modest improvements in the expected probability of good outcome for patients with suspected acute ischemic stroke and unknown vessel status.

A case report of delayed cortical infarction adjacent to sulcal clots after traumatic subarachnoid hemorrhage in the absence of proximal vasospasm.

BACKGROUND: Cortical ischemic lesions represent the predominant pathomorphological pattern of focal lesions after aneurysmal subarachnoid hemorrhage (aSAH). Autopsy studies suggest that they occur adjacent to subarachnoid blood and are related to spasm of small cortical rather than proximal arteries. Recent clinical monitoring studies showed that cortical spreading depolarizations, which induce cortical arterial spasms, are involved in lesion development. If subarachnoid blood induces adjacent cortical lesions, it would be expected that (i) they also develop after traumatic subarachnoid hemorrhage (tSAH), and (ii) lesions after tSAH can occur in absence of angiographic vasospasm, as was found for aSAH. CASE PRESENTATION: An 86-year-old woman was admitted to our hospital with fluctuating consciousness after hitting her head during a fall. The initial computed tomography (CT) was significant for tSAH in cortical sulci. On day 8, the patient experienced a secondary neurological deterioration with reduced consciousness and global aphasia. Whereas the CT scan on day 9 was still unremarkable, magnetic resonance imaging (MRI) on day 10 revealed new cortical laminar infarcts adjacent to sulcal blood clots. Proximal vasospasm was ruled out using MR and CT angiography and Doppler sonography. CT on day 14 confirmed the delayed infarcts. CONCLUSIONS: We describe a case of delayed cortical infarcts around sulcal blood clots after tSAH in the absence of proximal vasospasm, similar to results found previously for aSAH. As for aSAH, this case suggests that assessment of angiographic vasospasm is not sufficient to screen for risk of delayed infarcts after tSAH. Electrocorticography is suggested as a complementary method to monitor the hypothesized mechanism of spreading depolarizations.

Optimal Transport Destination for Ischemic Stroke Patients With Unknown Vessel Status: Use of Prehospital Triage Scores.

BACKGROUND AND PURPOSE: Patients with acute ischemic stroke (AIS) and large vessel occlusion may benefit from direct transportation to an endovascular capable comprehensive stroke center (mothership approach) as opposed to direct transportation to the nearest stroke unit without endovascular therapy (drip and ship approach). The optimal transport strategy for patients with AIS and unknown vessel status is uncertain. The rapid arterial occlusion evaluation scale (RACE, scores ranging from 0 to 9, with higher scores indicating higher stroke severity) correlates with the National Institutes of Health Stroke Scale and was developed to identify patients with large vessel occlusion in a prehospital setting. We evaluate how the RACE scale can help to inform prehospital triage decisions for AIS patients. METHODS: In a model-based approach, we estimate probabilities of good outcome (modified Rankin Scale score of ≤2 at 3 months) as a function of severity of stroke symptoms and transport times for the mothership approach and the drip and ship approach. We use these probabilities to obtain optimal RACE cutoff scores for different transfer time settings and combinations of treatment options (time-based eligibility for secondary transfer under the drip and ship approach, time-based eligibility for thrombolysis at the comprehensive stroke center under the mothership approach). RESULTS: In our model, patients with AIS are more likely to benefit from direct transportation to the comprehensive stroke center if they have more severe strokes. Values of the optimal RACE cutoff scores range from 0 (mothership for all patients) to >9 (drip and ship for all patients). Shorter transfer times and longer door-to-needle and needle-to-transfer (door out) times are associated with lower optimal RACE cutoff scores. CONCLUSIONS: Use of RACE cutoff scores that take into account transport times to triage AIS patients to the nearest appropriate hospital may lead to improved outcomes. Further studies should examine the feasibility of translation into clinical practice.

Gadopentetate but not gadobutrol accumulates in the dentate nucleus of multiple sclerosis patients.

BACKGROUND: Previous studies have postulated an association between dentate nucleus T1 hyperintensity and multiple sclerosis (MS)-related progressive neurodegeneration. Therefore, MS patients have been excluded from most studies investigating brain deposition of gadolinium-based contrast agents (GBCAs). OBJECTIVE: To study the hypothesis that dentate nucleus T1 hyperintensity in MS patients is associated with GBCA administration. METHODS: In a cohort of 97 MS patients, the dentate-to-pons signal intensity ratio (DPSIR) was calculated for 265 consecutive T1-weighted magnetic resonance (MR) scans (including sessions with and without the administration of GBCA). Patients exclusively received either gadopentetate dimeglumine (Gd-DTPA, linear) or gadobutrol (Gd-BT-DO3A, macrocyclic). RESULTS: In patients receiving Gd-DTPA, DPSIR increased significantly between the first and the last scan (+0.009, p < 0.001), and following magnetic resonance imaging (MRI) with Gd-DTPA administration as compared to following an MRI without Gd-DTPA administration (+0.005 vs -0.001; p = 0.022). Additionally, there was a positive linear relationship between the number of Gd-DTPA administrations and the increase in DPSIR ( p = 0.017). No DPSIR increase was observed after Gd-BT-DO3A administration. CONCLUSION: Dentate nucleus T1 hyperintensity in MS patients is associated with Gd-DTPA (but not Gd-BT-DO3A) administration, suggesting an alternative explanation for the association of T1 hyperintensity with disease duration and severity.

Datawarehouse-enabled quality control of atrial fibrillation detection in the stroke unit setting.

Objective: (1) To assess the accuracy of a standard operating procedure (SOP) regarding the utilization of atrial fibrillation (AF) alarms in everyday clinical practice, and (2) to evaluate the performance of automated continuous surveillance for atrial fibrillation (AF) in hospitalized acute stroke patients. Design: Retrospective cohort study. Setting: Two stroke units from two tertiary care hospitals in Berlin, Germany. Participants: We identified 635 patients with ischemic stroke diagnosis for the time period between 01. January and 30. September 2021 of which 176 patients had recorded AF alarms during monitoring. Of those, 115 patients were randomly selected for evaluation. After excluding 6 patients with hemorrhagic stroke in their records, 109 patients (mean age: 79.1 years, median NIHSS at admission: 6, 57% female) remained for analysis. Intervention: Using a clinical data warehouse for comprehensive data storage we retrospectively downloaded and visualized ECG data segments of 65 s duration around the automated AF alarms. We restricted the maximum number of ECG segments to ten per patient. Each ECG segment plot was uploaded into a REDCap database and categorized as either AF, non-AF or artifact by manual review. Atrial flutter was subsumed as AF. These classifications were then matched with 1) medical history and known diseases before stroke, 2) discharge diagnosis, and 3) recommended treatment plan in the medical history using electronic health records. Main outcome measures: The primary outcome was the proportion of previously unknown AF diagnoses correctly identified by the monitoring system but missed by the clinical team during hospitalization. Secondary outcomes included the proportion of patients in whom a diagnosis of AF would likely have led to anticoagulant therapy. We also evaluated the accuracy of the automated detection system in terms of its positive predictive value (PPV). Results: We evaluated a total of 717 ECG alarm segments from 109 patients. In 4 patients (3.7, 95% confidence interval [CI] 1.18-9.68%) physicians had missed AF despite at least one true positive alarm. All four patients did not receive long-term secondary prevention in form of anticoagulant therapy. 427 out of 717 alarms were rated true positives, resulting in a positive predictive value of 0.6 (CI 0.56-0.63) in this cohort. Conclusion: By connecting a data warehouse, electronic health records and a REDCap survey tool, we introduce a path to assess the monitoring quality of AF in acute stroke patients. We find that implemented standards of procedure to detect AF during stroke unit care are effective but leave room for improvement. Such data warehouse-based concepts may help to adjust internal processes or identify targets of further investigations.

Decline of thrombolysis rates before endovascular therapy in patients with acute anterior circulation large vessel occlusion ischemic stroke: A multicenter analysis from the German Stroke Registry.

INTRODUCTION: In recent years, the role of intravenous thrombolysis (IVT) before endovascular stroke treatment (EVT) has been discussed intensively. Whether the discussion was accompanied by changing rates of bridging IVT is unknown. METHODS: Data were extracted from the prospectively maintained German Stroke Registry, including patients treated with EVT at one of 28 stroke centers in Germany between 2016 and 2021. Primary outcome parameters were the rate of bridging IVT (a) in the entire registry cohort and (b) in patients without formal contraindications to IVT (i.e. recent oral anticoagulants, time window ⩾4.5 h, extensive early ischemic changes) adjusted for demographic and clinical confounders. RESULTS: 10,162 patients (52.8% women, median age 77 years, median National Institutes of Health Stroke Scale score 14) were analyzed. In the entire cohort, the rate of bridging IVT decreased from 63.8% in 2016 to 43.6% in 2021 (average absolute annual decrease 3.1%, 95% CI 2.4%-3.8%), while the proportion of patients with at least one formal contraindication increased by only 1.2% annually (95% CI 0.6%-1.9%). Among 5460 patients without record of formal contraindications, the rate of bridging IVT decreased from 75.5% in 2016 to 63.2% in 2021 and was significantly associated with admission date in a multivariable model (average absolute annual decrease 1.4%, 95% CI 0.6%-2.2%). Clinical factors associated with lower odds of bridging IVT included diabetes mellitus, carotid-T-occlusion, dual antiplatelet therapy, and direct admission to a thrombectomy center. CONCLUSION: We observed a substantial decline in bridging IVT rates independent of demographic confounders and not explained by an increase in contraindications. This observation deserves further exploration in independent populations.

Cerebral Microbleeds and Treatment Effect of Intravenous Thrombolysis in Acute Stroke: An Analysis of the WAKE-UP Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: Cerebral microbleeds (CMBs) are common in patients with acute ischemic stroke and are associated with increased risk of intracerebral hemorrhage (ICH) after intravenous thrombolysis. Whether CMBs modify the treatment effect of thrombolysis is unknown. METHODS: We performed a prespecified analysis of the prospective randomized controlled multicenter Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke (WAKE-UP) trial including patients with acute ischemic stroke with unknown time of symptom onset and diffusion-weighted imaging-fluid-attenuated inversion recovery mismatch on MRI receiving alteplase or placebo. Patients were screened and enrolled between September 2012 and June 2017 (with final follow-up in September 2017). Patients were randomized to treatment with IV thrombolysis with alteplase at 0.9 mg/kg body weight or placebo. CMB status (presence, number, and distribution) was assessed after study completion by 3 raters blinded to clinical information following a standardized protocol. Outcome measures were excellent functional outcome at 90 days, defined by modified Rankin Scale (mRS) score ≤1, and symptomatic ICH according to National Institutes of Neurological Disease and Stroke trial criteria 22 to 36 hours after treatment. RESULTS: Of 503 patients enrolled in the WAKE-UP trial, 459 (91.3%; 288 [63%] men) were available for analysis. Ninety-eight (21.4%) had at least 1 CMB on baseline imaging; 45 (9.8%) had exactly 1 CMB; 37 (8.1%) had 2 to 4 CMBs; and 16 (3.5%) had ≥5 CMBs. Presence of CMBs was associated with a nonsignificant increased risk of symptomatic ICH (11.2% vs 4.2%; adjusted odds ratio [OR] 2.32, 95% confidence interval [CI] 0.99-5.43, p = 0.052) but had no effect on functional outcome at 90 days (mRS score ≤1: 45.8% vs 50.7%; adjusted OR 0.99, 95% CI 0.59-1.64, p = 0.955). Patients receiving alteplase had better functional outcome (mRS score ≤1: 54.6% vs 44.6%, adjusted OR 1.61, 95% CI 1.07-2.43, p = 0.022) without evidence of heterogeneity in relation to CMB presence (p of the interactive term = 0.546). Results were similar for subpopulations with strictly lobar (presumed cerebral amyloid angiopathy related) or not strictly lobar CMB distribution. DISCUSSION: In the randomized-controlled WAKE-UP trial, we saw no evidence of reduced treatment effect of alteplase in patients with acute ischemic stroke with ≥1 CMBs. Additional studies are needed to determine the treatment effect of alteplase and its benefit-harm ratio in patients with a larger number of CMBs. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov identifier NCT01525290; ClinicalTrialsRegister.EU identifier 2011-005906-32. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with acute ischemic stroke with unknown time of onset and diffusion-weighted imaging-fluid-attenuated inversion recovery mismatch who received IV alteplase, CMBs are not significantly associated with functional outcome at 90 days.

Cost Effectiveness of Interhospital Transfer for Mechanical Thrombectomy of Acute Large Vessel Occlusion Stroke: Role of Predicted Recanalization Rates.

BACKGROUND: Emergency interhospital transfer of patients with stroke with large vessel occlusion to a comprehensive stroke center for mechanical thrombectomy is resource-intensive and can be logistically challenging. Imaging markers may identify patients in whom intravenous thrombolysis (IVT) alone is likely to result in thrombus resolution, potentially rendering interhospital transfers unnecessary. Here, we investigate how predicted probabilities to achieve IVT-mediated recanalization affect cost-effectiveness estimates of interhospital transfer. METHODS: We performed a health economic analysis comparing emergency interhospital transfer of patients with acute large vessel occlusion stroke after administration of IVT with a scenario in which patients also receive IVT but remain at the primary hospital. Results were stratified by clinical parameters, treatment delays, and the predicted probability to achieve IVT-mediated recanalization. Estimated 3-month outcomes were combined with a long-term probabilistic model to yield quality-adjusted life years (QALYs) and costs. Uncertainty was quantified in probabilistic sensitivity analyses. RESULTS: Depending on input parameters, marginal costs of interhospital transfer ranged from USD -61 366 (cost saving) to USD +20 443 and additional QALYs gained from 0.1 to 3.0, yielding incremental cost-effectiveness ratios of

No Association Between Thrombus Perviousness and Cardioembolic Stroke Etiology in Basilar Artery Occlusion Stroke.

Background: Thrombus perviousness (TP) quantified by thrombus attenuation increase (TAI) assessed on acute non-contrast computed tomography (NCCT) and CT angiography (CTA) may be associated with stroke etiology in anterior circulation ischemic stroke. We investigated whether TP is associated with stroke etiology and recanalization after mechanical thrombectomy in patients with acute basilar artery occlusion (BAO). Methods: Eighty patients with complete BAO and in-house acute imaging from a prospectively maintained database were included. Two raters independently segmented the complete thrombus on co-registered NCCT and CTA to determine TAI in Hounsfield units (HUCTA-HUNCCT); averaged values of the raters were used for analysis. Recanalization to modified treatment in cerebral ischemia (mTICI) score 2b/3 was considered successful, and 90-day modified Rankin Scale score 0-2 was considered favorable. Results: TAI did not differ between patients with different stroke etiologies; median TAI in patients with cardioembolic stroke (n = 36) was -0.47 (interquartile range -4.08 to 7.72), 1.94 (-8.14 to 10.75) in patients with large artery atherosclerosis (LAA; n = 25), and -0.99 (-6.49 to 5.40) in patients with stroke of undetermined origin (n = 17; p = 0.955). Binary logistic regression analyses did not identify TAI as an independent indicator of cardioembolic stroke (adjusted odds ratio [OR] vs. LAA stroke: 1.0 [95% CI: 0.95-1.0], p = 0.751). There was no association with successful recanalization (adjusted OR 1.4 [0.70-2.7], p = 0.345) or favorable outcome (adjusted OR 1.1 [95% CI: 0.94-1.2], p = 0.304). Conclusion: In contrast to proximal middle cerebral artery occlusions, TP in BAO patients is not associated with cardioembolic stroke etiology. Larger confirmatory studies to establish the potential role of TP for clinical applications should focus on patients with anterior circulation stroke.

Mechanical thrombectomy in patients with cervical artery dissection and stroke in the anterior or posterior circulation - a multicenter analysis from the German Stroke Registry.

BACKGROUND: Cervical artery dissection (CAD) is a rare cause of acute ischemic stroke (AIS) with large vessel occlusion (LVO) and may constitute a challenge for mechanical thrombectomy (MT). We compared procedural characteristics, reperfusion rates, and clinical outcome in AIS patients undergoing MT with and without CAD. METHODS: We performed a pre-specified analysis of patients registered within the German Stroke Registry, a prospectively maintained multicenter registry of consecutive patients with AIS patients treated by MT. Procedural characteristics included time periods and additional application of medication. RESULTS: Of 2589 patients, 62 (2.4%) were diagnosed with CAD. CAD patients were younger, had lower rates of known vascular risk factors and larger baseline stroke volumes. MT in CAD patients took significantly longer (median [IQR] groin-puncture-to-flow restoration time: 98 [67-136] versus 70 [45-100] minutes; p < 0.001) and more often required use of intra-arterial medication (34.4% versus 15.6%; p < 0.001). Reperfusion success (modified Treatment in Cerebral Infarction score 2b-3: 85.2% versus 83.3%, p = 0.690) and favorable functional outcome after 3 months (modified Rankin Scale score ≤ 2: 70.9% versus 36.4%, adjusted p = 0.086) did not differ significantly between patients with and without CAD. The latter findings held true for both CAD in the anterior and posterior circulation. CONCLUSION: CAD in AIS requiring MT is rare. MT in patients with CAD constitutes a particular procedural challenge, but still achieves favorable radiological and functional outcomes in most patients. Our data provide indirect evidence that MT is of clinical benefit in patients with AIS due to LVO and CAD.

How do treatment times impact on functional outcome in stroke patients undergoing thrombectomy in Germany? Results from the German Stroke Registry.

BACKGROUND: Functional outcome post-stroke depends on time to recanalization. Effect of in-hospital delay may differ in patients directly admitted to a comprehensive stroke center and patients transferred via a primary stroke center. We analyzed the current door-to-groin time in Germany and explored its effect on functional outcome in a real-world setting. METHODS: Data were collected in 25 stroke centers in the German Stroke Registry-Endovascular Treatment a prospective, multicenter, observational registry study including stroke patients with large vessel occlusion. Functional outcome was assessed at three months by modified Rankin Scale. Association of door-to-groin time with outcome was calculated using binary logistic regression models. RESULTS: Out of 4340 patients, 56% were treated primarily in a comprehensive stroke center and 44% in a primary stroke center and then transferred to a comprehensive stroke center ("drip-and-ship" concept). Median onset-to-arrival at comprehensive stroke center time and door-to-groin time were 103 and 79 min in comprehensive stroke center patients and 225 and 44 min in primary stroke center patients. The odds ratio for poor functional outcome per hour of onset-to-arrival-at comprehensive stroke center time was 1.03 (95%CI 1.01-1.05) in comprehensive stroke center patients and 1.06 (95%CI 1.03-1.09) in primary stroke center patients. The odds ratio for poor functional outcome per hour of door-to-groin time was 1.30 (95%CI 1.16-1.46) in comprehensive stroke center patients and 1.04 (95%CI 0.89-1.21) in primary stroke center patients. Longer door-to-groin time in comprehensive stroke center patients was associated with admission on weekends (odds ratio 1.61; 95%CI 1.37-1.97) and during night time (odds ratio 1.52; 95%CI 1.27-1.82) and use of intravenous thrombolysis (odds ratio 1.28; 95%CI 1.08-1.50). CONCLUSION: Door-to-groin time was especially relevant for outcome of comprehensive stroke center patients, whereas door-to-groin time was much shorter in primary stroke center patients.Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03356392. Unique identifier NCT03356392.