We conducted an investigator-initiated, retrospective, open-label trial involving patients with acute ischemic stroke who either were directly sent to our CSC or were secondarily transferred from a PSC to undergo MTE at the CSC between January 1, 2013, and December 31, 2016. The study protocol was approved by our Ethics Committee (Faculty of Medicine, University of Freiburg, 077/09). Members of the trial steering committee and the local investigators designed the study, collected and analyzed the data, wrote the manuscript, and made the decision to submit the manuscript for publication.

At the time of patient inclusion, our Interdisciplinary NeuroVascular Network South-West (INVAS) stroke network comprised 12 PSCs and one CSC at the University Hospital Freiburg. The catchment area of the INVAS stroke network covers a surface area of 9,357 km² and a population of 2.3 million. It includes the rather densely populated Rhine valley as well as remote rural and mountainous regions of the southern black forest.¹ Depending on the location of the patient presenting with symptoms of an acute ischemic stroke, transfer occurred either to one of the PSC or directly to the CSC. The decision of transportation destination was performed by an emergency medical team. Patients from the PSC were discussed via a telestroke platform with the attending stroke neurologist at the CSC. Patients from the PSC deemed eligible for MTE were secondarily transferred to the CSC. For definitions of PSC and CSC, please refer to the recent publication of Ernst et al. (4).

Patients from both PSC and CSC were eligible for MTE if they were >18 years of age, had a score of 6 or higher on the National Institutes of Health Stroke Scale (NIHSS) or a relevant functional deficit, a suspected (dense vessel sign) or proven [computed tomography angiography (CTA)/magnetic resonance angiography (MRA)] LVO of the anterior circulation, or a small core infarct with an Alberta Stroke Program Early CT Score (ASPECTS) >4. Initiation of MTE had to be possible within 6 h after stroke onset. Patients from PSC had repeated magnetic resonance imaging (MRI) or CT imaging if time from initial imaging to arrival at the CSC exceeded 2 h. Patients from both the PSC and CSC who did not present contraindication to systemic lysis received a weight-adapted dose of rtPA within 4.5 h after onset of acute ischemic stroke.

The majority of patients were treated under general anesthesia. The standard procedure included a 9F femoral access and 8F or 9F balloon guide catheters for the carotid artery. Thrombus retrieval stent retrievers were used for the large majority of cases (Table 1). Medical management and acute poststroke care after the procedure were consistent with the European Stroke Organization (ESO)/European Society for Minimally Invasive Neurological Therapy (ESMINT) and AHA guidelines (2, 5). A CT scan was performed within 24 h after the revascularization procedure to detect the presence of intracerebral hemorrhage (ICH).

All patients underwent clinical examination at baseline and discharge. Baseline data collected from the patients' medical chart included gender, age, stroke onset time, baseline NIHSS, time of initial CT/MRI, IVT given, time of IVT, time of CT/MRI at CSC for patients transferred from PSC, time of first angiographic run, time of recanalization, 24-h NIHSS, and NIHSS at discharge.

In addition, an independent rater who did not participate in the endovascular stroke treatment of included patients, with >10 years of experience in neuroimaging (R.H.), qualitatively evaluated pre-therapeutic MR, CT, and digital subtraction angiography (DSA) images as well as final angiograms after MTE and follow-up CT at 24 h. The extent of the initial core infarct was determined on pre-therapeutic CT or diffusion-weighted imaging (DWI) using ASPECTS (6). Revascularization was assessed by applying the modified thrombolysis in cerebral infarction (TICI) classification (7). Intracranial hemorrhage was defined on follow-up CT at 24 h as symptomatic in case of parenchymal hematoma with a clinical worsening of at least four points on the NIHSS scale according to the European Cooperative Acute Stroke Study (ECASS) definition (8). In addition, subarachnoid hemorrhages were reported.

The primary study outcome measure was disability at 90 days, as assessed by applying the mRS. Secondary clinical efficacy outcomes were NIHSS at discharge, mortality at 90 days, and the rate of symptomatic ICH (sICH), asymptomatic lobar hematoma, and subarachnoid hemorrhages. The last recorded NIHSS score was used as discharge NIHSS in patients who had deceased during hospitalization. The technical efficacy outcomes were successful reperfusion defined as angiographic demonstration of TICI scores of 2b (50–99% reperfusion) or 3 (complete reperfusion). In addition, we analyzed different time intervals including onset to first imaging, onset to IVT, onset to first angiographic run, and onset to recanalization/end of MTE for MS and DS patients. In DS patients, we additionally determined the transfer time defined as the time interval between first imaging at PSC and patient arrival at the CSC.

The studies involving human participants were reviewed and approved by the Ethics Committee of the Faculty of Medicine, University of Freiburg, Freiburg, Germany.

The data are expressed with standard descriptive statistics, including median, interquartile range (IQR) or range for ordinal and numerical variables, and absolute and relative frequencies for nominal variables as appropriate. Relative frequencies were rounded to whole numbers according to the common rules.

Comparisons among groups on baselines variables, peri-procedural time intervals, and outcome variables were made using Pearson's chi-square test for nominal variables (age, gender, IVT, target vessels, stent retrievers and catheters, mRS 0–2, TICI 2b/3, mortality, and hemorrhage data) and Mann–Whitney U-test for ordinal and numerical variables (age, NIHSS, ASPECTS, number of passes, and time intervals). Statistical significance was set at p < 0.05 for all contrasts of hypothesis. For small sample sizes with n < 30 (sICH and asymptomatic lobar hemorrhage), Fisher's exact test was used. Primary endpoint analysis was amended by logistic regression analysis.

The analyses were performed with IBM SPSS Statistics version 24. Outcome analyses of cerebral hemorrhages were conducted with R Studio software version 1.3.959. The figure was drawn with the use of Microsoft Excel 2013. No missing values were imputed. Statistical consulting was provided by the Institute of Medical Biometry and Statistics of the University of Freiburg.

From January 1, 2013, to December 31, 2016, 385 patients were included in the analysis population. Two-hundred and twenty-two patients were directly admitted to the CSC with acute ischemic stroke and were treated with MTE (MS). One-hundred and sixty-three patients were admitted at PSC and transferred after telestroke consultation for MTE to the CSC (DS). Of 163 patients from the DS group (DS-total), 110 patients actually were treated by MTE (DS-received MTE) at the CSC. Patient demographics, NIHSS at presentation, initial ASPECTS score, and target vessel for MTE are summarized in Table 1. Supplementary Table 1 outlines the different reasons for not performing MTE in 53 patients from the DS-total group.

Mean age was 74 years (IQR 64–82) in the MS group compared to 75 years (IQR 62–80) in the DS-total group. In the MS group, 51% (114/222) of patients treated were female, whereas 46% (75/163) of the DS-total group were women. The median NIHSS did not differ significantly between groups and was 15 (IQR 12.5–18.5) for the MS group and 16 (IQR 11–19) for the DS-total group. With median ASPECTS scores of 8 (IQR 7–10), these were slightly lower in the MS group when compared to the DS-total group with 9 (IQR 7–9). Distribution of target vessels was slightly different between groups with 60% (134/222) middle cerebral artery (MCA) occlusions in the MS arm of the trial compared to 46% (51/110) MCA occlusion in the DS-received MTE group. The rate of patients with tandem occlusions (combined occlusion of the cervical ICA and MCA) was higher in the DS-received MTE group [36% (40/110)] than in the MS group [19% (41/222)].

There was a significantly better primary outcome of functional independence (mRS 0–2) at 90 days in patients from the MS group compared to patients from the DS group [MS: 37% vs. DS-total: 26% (p = 0.024)/DS-received MTE: 24% (p = 0.017)]. Regression analysis showed a 1.7-fold increase in the good clinical outcome in MS-group patients (unadjusted OR 1,698; 95% KI 1,069–2,697; p = 0.025).

Data for this monocentric trial were collected in a non-randomized fashion. The retrospective analysis of the prospectively maintained database included self-adjudicated primary imaging and clinical outcomes. We were confronted with the methodological problem on how to deal with patients diagnosed with LVO at the PSC secondarily sent to the CSC for MTE and who finally did not receive an MTE for different reasons (e.g., improvement under IV Alteplase and extended core infarct on secondary imaging at the CSC). Patients with LVO who improved prior to transfer from PSC to CSC were not included, leading to a potential time-reset effect (24). The findings of our trial reflect the specifics of our stroke network covering vast rural areas, and the generalizability of these results may thereby be limited.

Our data suggest that patients who had an acute ischemic stroke admitted directly to a CSC may have better 90-day outcomes than those transferred secondarily for thrombectomy from a PSC. Also, in accordance with others, time to recanalization has an especially significant influence on good clinical outcome with the necessity of eliminating influenceable time-consuming steps in acute stroke organization. As a consequence, on the one hand, we have come up with a study of an acute LVO detected by LVO scoring in the field with helicopter-based direct transfer to the CSC² as well as a reorganization of acute stroke care in DS patients bypassing secondary imaging at CSC with direct transfer to the angio-suite.