ODT
Screening tools such as the Face Arm Speech Test (FAST) developed for prehospital identification of stroke patients are less sensitive for identification of PCS compared to ACS [
21]. This lack of early identification of symptoms might account for delays in prehospital management leading ultimately to ineligibility for thrombolytic treatment. However, there is limited evidence from the literature whether stroke localization is related to delay in preclinical time intervals so far: two prior studies both from the pre-rt-PA era [
22,
23] did not detect significant differences and only one of them stratified stroke type according to the OCSP classification [
23]. In our study, we detected in all patients, irrespective of rt-PA treatment, substantially longer durations of prehospital patient management in patients with PCS as compared to patients with ACS. On average, patients with PCS lost 27 min. Relevantly, only half of patients with PCS arrived within 3 h in hospital compared to 2/3 in ACS. Based on these data, we estimated that on average 100 patients with PCS per year potentially eligible for rt-PA treatment might have been missed due to prehospital delays. As a consequence, faster prehospital management could result in an almost twofold increase of the thrombolysis rate in patients with PCS.
In addition, prehospital loss of patients potentially eligible for rt-PA treatment might also explain the observed lack of association of infarct localization (i.e., ACS versus PCS) and the ODT in the selected group of patients treated with rt-PA, which is in agreement with previous work [
12].
The delay of patients with PCS reflects that diagnostic tools used in the prehospital setting do not focus on PCS-related symptoms. Therefore, both education and optimized screening tools need to take typical symptoms of PCS into account. For instance, adding elements used by the three-step bedside examination for differential diagnosis of acute vestibular syndrome may increase detection rates of PCS [
24]. Moreover, addition of ataxia testing as well as visual field testing may substantially increase specificity and sensitivity of the FAST-test [
21]. Furthermore, most symptoms preceding PCS—so-called transient neurological attacks (TNAs)—do not satisfy traditional definitions of TIAs [
16]. Therefore, evaluation of TNAs could be useful in screening for PCS. Randomized studies testing prehospital screening tools that include those tests for PCS are warranted.
DNT
In patients with PCS, the DNT was on average 13 min longer compared to patients with ACS. This is a substantial delay, given that even small reductions in time-to-thrombolysis translate into a significant gain of healthy lifetime [
14]. While we did not observe any differences in DNT in patients with mild stroke, we detected a significant delay in DNT for patients with PCS with moderate and severe deficits. In those with the most severe strokes, this observation might be explained by a greater necessity for intensive care measures in patients with PCS. However, the observed delay in DNT in PCS did not only include patients with the most severe strokes but also those with moderate severity. There are some possible explanations for this finding: First, the NIHSS has limitations for assessment of PCS and symptoms not measured by the NIHSS might contribute to time delays [
3,
5,
12]. This is reflected by our observation of overall lower NIHSS scores in patients with PCS, which is in agreement with previous work [
3,
5,
12,
25,
26]. It is, therefore, possible that clinical deficits have been underestimated by the NIHSS [
25,
26]. Second, incorrect patient triage might have contributed to the delay in DNT. Even if in the ASUR, the majority of patients subsequently receiving treatment with rt-PA arrived via ambulance making triage errors in the ER less likely, we cannot exclude that triage errors or errors in hospital pre-notification may have contributed to delays in DNT [
28]. Third, in PCS, MRI has been more often performed which might have contributed to the observed delay; however, the prolonged DNT was irrespective of type of imaging in the multivariate analysis.
Time to treatment has been associated with clinical outcome after ischemic stroke in clinical studies and large clinical registers [
15,
29,
30]. Reductions in prehospital time intervals have been associated with better functional outcome and a shorter DNT has been associated with lower in-hospital mortality as well as lower rates of symptomatic intracranial hemorrhage [
27,
31]. Therefore, we believe that the pre- and intra-hospital delays we observed in patients with PCS are clinically relevant. Our study outnumbers previous studies analyzing time intervals stratified by infarct localization using data of a nationwide cohort of patients (Supplementary Table IV). In addition, previous studies focused exclusively on rt-PA-treated patients and did not analyze ODT in untreated patients; therefore, estimates of patients potentially lost for rt-PA-treatment were not possible.
In contrast to previous work suggesting greater ischemic tolerance in posterior circulation as compared to anterior cerebral circulation [
32], more recent data from the same group could not support this hypothesis [
33]. In a post hoc analysis of the IST-3 trial, no differences were found between ACS and PCS; however, this subgroup analysis was certainly underpowered [
34]. Therefore, at the current stage, there is no evidence that the time-window for intravenous thrombolysis is different in PCS and ACS and delays might have similar negative effects on outcome and should be avoided irrespective of stroke localization.
The observed in pre- and intra-hospital delays of our study may have implications for daily routine and demonstrate the need for improvement in organization of stroke pathways. Pre- and intra-hospital screening tool and triage systems need to implement typical symptoms of PCS to alert stroke code protocols in a timely manner.
Our study has limitations. First, data collected in registries do not compensate for randomized studies, as occurrence of selection bias cannot be excluded. However, entry of patient data into the ASUR is mandatory and the registry is part of a governmental quality assessment program. Hence, we assume that almost all patients undergoing treatment with rt-PA are included into the ASUR. Second, diagnosis of PCS was clinically determined according to the OCSP classification [
19]. Importantly, the OCSP classification has an excellent sensitivity and specificity for patients with strokes in the posterior circulation; correct classification rates of more than 85% have been previously reported [
35]. Nevertheless, we cannot exclude that some patients with lacunar strokes in the brainstem might have been classified as lacunar syndrome according to the OCSP classification [
19,
35]. Third, we were missing data on affected vessel pathology, since CTA or MRA are not mandatory for diagnosis in the ASUR. Therefore, it was not possible to focus on specific conditions, such as basilar artery occlusion. However, basilar artery occlusion was the focus of large, multinational registries [
36‐
39] and treatment options in basilar occlusion are currently evaluated in the ongoing BASICS study [
40]. Fourth, as only patients admitted to stroke units were included into the ASUR, we were not able to analyze patients misdiagnosed prior to admission. However, as in all centers participating in the ASUR recruitment is done exclusively by neurologists specialized in acute stroke care, we assume that false-negative rates were low. Fifth, we cannot exclude that some stroke patients have not been admitted to stroke units but directly to general neurological wards. This might have affected predominantly patients with minor symptoms or those with very long ODTs.