S100b in acute ischemic stroke clots is a biomarker for post-thrombectomy intracranial hemorrhages

Background and purposePost-thrombectomy intracranial hemorrhages (PTIH) are dangerous complications of acute ischemic stroke (AIS) following mechanical thrombectomy. We aimed to investigate if S100b levels in AIS clots removed by mechanical thrombectomy correlated to increased risk of PTIH.MethodsWe analyzed 122 thrombi from 80 AIS patients in the RESTORE Registry of AIS clots, selecting an equal number of patients having been pre-treated or not with rtPA (40 each group). Within each subgroup, 20 patients had developed PTIH and 20 patients showed no signs of hemorrhage. Gross photos of each clot were taken and extracted clot area (ECA) was measured using ImageJ. Immunohistochemistry for S100b was performed and Orbit Image Analysis was used for quantification. Immunofluorescence was performed to investigate co-localization between S100b and T-lymphocytes, neutrophils and macrophages. Chi-square or Kruskal-Wallis test were used for statistical analysis.ResultsPTIH was associated with higher S100b levels in clots (0.33 [0.08–0.85] vs. 0.07 [0.02–0.27] mm2, H1 = 6.021, P = 0.014*), but S100b levels were not significantly affected by acute thrombolytic treatment (P = 0.386). PTIH was also associated with patients having higher NIHSS at admission (20.0 [17.0–23.0] vs. 14.0 [10.5–19.0], H1 = 8.006, P = 0.005) and higher number of passes during thrombectomy (2 [1–4] vs. 1 [1–2.5], H1 = 5.995, P = 0.014*). S100b co-localized with neutrophils, macrophages and with T-lymphocytes in the clots.ConclusionsHigher S100b expression in AIS clots, higher NIHSS at admission and higher number of passes during thrombectomy are all associated with PTIH. Further investigation of S100b expression in AIS clots by neutrophils, macrophages and T-lymphocytes could provide insight into the role of S100b in thromboinflammation

Neuroimaging characteristics and outcomes of acute ischemic stroke patients due to large vessel occlusion following reperfusion treatment

Background: Advanced neuroimaging (AN) incorporates the knowledge gained from basic research on the pathophysiology of acute ischemic stroke (AIS) over the past decades. The technological evolution and the optimization of the parameters of perfusion imaging offer one of the most important tools that we have to our disposal in the effort to overcome the time limitations and expand the use of reperfusion therapies in the acute phase of IS. In this PhD thesis, we assessed whether and how the prior use of AN and more specifically the use of CTP/MRP with post-processing of the raw data with the RAPID software, regardless of the time passed since the onset of symptoms, increased the application of reperfusion therapies and influenced the outcomes of patients with AIS who received these treatments. At the same time, we evaluated the potential impact of new thrombolytic agents on patients’ outcomes.Methodology1. Potential eligibility for IVT in the extended time window was evaluated by using inclusion criteria from the EXTEND trial. All patients underwent baseline emergent neurovascular imaging using either computed tomography angiography/ computed tomography perfusion (CTA/CTP) or magnetic resonance angiography/magnetic resonance perfusion (MRA/MRP). Images were post processed by the automated software RAPID. 2. We retrospectively evaluated consecutive AIS patients during a six-year period. The study population was divided into two groups according to the neuroimaging protocol used prior to intravenous thrombolysis (IVT) administration (AN+ Vs AN-). Safety outcomes included any intracranial hemorrhage and 3-month mortality. Effectiveness outcomes included door-to-needle time, neurological status on discharge, and functional status at three months assessed by the modified Rankin Scale (mRS). 3. In the second part of this PhD thesis, we prospectively evaluated patients with AIS due to large vessel occlusion (LVO), treated with IVT with or without mechanical thrombectomy in two tertiary stroke centers. Patients were divided into two groups according to the thrombolytic agent used: the first group was treated with standard-dose alteplase (0.9 mg/kg) and the second with 0.25 mg/kg of tenecteplase. Safety outcomes included prevalence of symptomatic intracranial hemorrhage (sICH) and mortality. Efficacy outcomes included averted thrombectomy, major neurological improvement at 24 h (defined as decrease in baseline NIHSS score of 8 points or greater) and functional status on discharge and on 3 months assessed by modified Rankin Scale (mRS). 4. Finally, we assessed all potential eligible studies identified by searching MEDLINE and Scopus databases in order to evaluate the available evidence on the safety and efficacy of intravenous tenecteplase compared with intravenous alteplase provided by nonrandomized studies. Estimates using random-effects models were pooled. Results: In the context of the descriptive analysis, we discovered that 9.8% of patients with IS acutely present within the time window of 4.5–9 hours, and of these, roughly one in three patients (3.2% overall) may undergo reperfusion treatments either with IVT in the so-called extended window based on the criteria of the EXTEND study or with mechanical thrombectomy (MT) based on the criteria of the DEFUSE-3 study. We then extended our observation to a time period of six years before and after the incorporation of AN in our AIS imaging protocol, finding that the use of AN resulted in an increase in the number of patients undergoing reperfusion treatments by approximately 50%. Although the onset-to-treatment time was longer in the AN+ cohort, the two groups did not differ in door-to-needle time, discharge NIHSS-score, symptomatic ICH, any ICH, 3-month favorable functional outcome (mRS-scores of 0–1), 3-month functional independence (mRS-scores of 0–2), distribution of 3-month mRS-scores, or 3-month mortality. In the study comparing tenecteplase to alteplase, nineteen AIS patients with LVO received tenecteplase and 39 received alteplase. We observed a non-significant higher rate of averted thrombectomies (32% versus 18%, p = 0.243) and a non-significant higher rate of sICH (16% versus 5%, p = 0.201) in the tenecteplase group. The rate of 24 h major neurological improvement was higher in the tenecteplase group (64% versus 33%, p = 0.046) but this was marginally attenuated in multivariable analyses (adjusted OR 10.22, 95% CI: 0.73–142.98; p = 0.084). Discharge mRS, 3-months mRS, and 3-month functional independence (mRS scores of 0–2) did not differ (p > 0.2) between the two groups. The rates of 3-month mortality (11% versus 18%, p = 0.703) were similar in the two groups. No independent association between thrombolytic agent and safety or efficacy outcomes emerged in the multivariable logistic regression analyses. Combining the results of this study with five other studies, we performed a meta-analysis including a total of 1820 patients (618 [34%] treated with tenecteplase). We observed that patients receiving tenecteplase had higher odds of 3-month good functional outcome (crude odds ratio [OR], 1.22; 95% CI, 0.90-1.66; adjusted OR, 1.60, 95% CI, 1.08-2.37), successful recanalization (crude OR, 2.82; 95% CI, 1.12-7.10; adjusted OR, 2.38; 95% CI, 1.18-4.81), and early neurological improvement (crude OR, 4.88; 95% CI, 2.03-11.71; adjusted OR, 7.60; 95% CI, 1.97-29.41). No significant differences were detected in 3-month excellent functional outcome proportions (mRS score 0-1; crude OR, 1.53; 95% CI, 0.81-2.91; adjusted OR, 2.51; 95% CI, 0.66- 9.49), symptomatic intracranial hemorrhage (crude OR, 0.97; 95% CI, 0.44-2.16; adjusted OR, 1.16; 95% CI, 0.13-10.50), or parenchymal hematoma (crude OR, 1.20; 95% CI, 0.24-5.95). Conclusions In conclusion, the use of AN in unselected patients with AIS who are potential candidates for reperfusion therapies, increases the delivery yield of these treatments without delaying door-to-needle times or raising questions about their safety or efficacy. Regarding the choice of the optimal thrombolytic agent, our findings provide indications that intravenous tenecteplase may be an alternative treatment option for patients with AIS as it is associated with more favorable clinical outcomes and equal safety compared to intravenous alteplase. However, this hypothesis will be further evaluated in the ongoing large randomized studies.Εισαγωγή: Η ΠΝ ενσωματώνει όλη τη γνώση που αποκτήθηκε από την βασική έρευνα σχετικά με την παθοφυσιολογία του οξέος ΙΑΕΕ κατά τις τελευταίες δεκαετίες. Η τεχνολογική εξέλιξη και η αξιολόγηση των βέλτιστων παραμέτρων της ΠΝ, προσφέρει σήμερα ένα από τα πιο σημαντικά εργαλεία που διαθέτουμε στην προσπάθεια να ξεπεράσουμε τους χρονικούς περιορισμούς και να επεκτείνουμε τη χρήση των θεραπειών επαναιμάτωσης στην οξεία φάση του ΙΑΕΕ. Στην παρούσα διατριβή αξιολογήσαμε εάν και πώς η προηγούμενη χρήση της ΠΝ και πιο συγκεκριμένα η χρήση της ΑΤΑ/ΜΤΑ με μετεπεξεργασία των πρωταρχικών δεδομένων από το λογισμικό RAPID, ανεξάρτητα από το χρόνο από την έναρξη των συμπτωμάτων, αύξησε την εφαρμογή των θεραπειών επαναιμάτωσης και επηρέασε τα αποτελέσματα των ασθενών με ΟΙΑΕΕ που έλαβαν αυτές τις θεραπείες. Παράλληλα αξιολογήσαμε το πώς επιδρούν νέες θρομβολυτικές θεραπείες την έκβαση των ασθενών. Μεθοδολογία:1. Η πιθανή καταλληλότητα για θεραπείες επαναιμάτωσης στο εκτεταμένο χρονικό παράθυρο αξιολογήθηκε χρησιμοποιώντας κριτήρια συμπερίληψης που βασίζονται στην ΠΝ. Όλοι οι ασθενείς υποβλήθηκαν αρχικά σε επείγουσα ΠΝ χρησιμοποιώντας είτε ΑΤ/ΑΤΑ είτε ΜΤ/ΜΤΑ. Οι εικόνες υποβλήθηκαν σε επεξεργασία από το αυτοματοποιημένο λογισμικό RAPID.2. Αξιολογήσαμε αναδρομικά διαδοχικούς ασθενείς κατά τη διάρκεια μιας περιόδου έξι ετών. Ο πληθυσμός της μελέτης χωρίστηκε σε δύο ομάδες σύμφωνα με το πρωτόκολλο νευροαπεικόνισης που χρησιμοποιήθηκε. Τα καταληκτικά σημεία ασφαλείας περιελάμβαναν οποιαδήποτε ενδοκρανιακή αιμορραγία και θνησιμότητα 3 μηνών. Τα καταληκτικά σημεία αποτελεσματικότητας περιελάμβαναν χρόνο door-to-needle, νευρολογική κατάσταση (NIHSS-score) κατά την έξοδο και λειτουργική κατάσταση σε τρεις μήνες που αξιολογήθηκαν με την κλίμακα mRS.3. Στο δεύτερο σκέλος της μελέτης αξιολογήσαμε προοπτικά ασθενείς με ΟΙΑΕΕ λόγω απόφραξης ΜΕΑΚ, οι οποίοι υποβλήθηκαν σε θεραπεία με ΕΘ με ή χωρίς ΜΘ σε δύο κέντρα αναφοράς ΑΕΕ. Οι ασθενείς υποβλήθηκαν σε θεραπεία με τυπική δόση αλτεπλάσης (0,9 mg/kg) ή 0,25 mg/kg τενεκτεπλάσης. Τα καταληκτικά σημεία ως προς την ασφάλεια περιλάμβαναν ποσοστά sICH και θνητότητας. Τα καταληκτικά σημεία ως προς την αποτελεσματικότητα περιλάμβαναν αποτροπή θρομβεκτομής λόγω επιτυχούς επανακαναλοποίησης, αξιοσημείωτη νευρολογική βελτίωση στις 24 ώρες (που ορίζεται ως μείωση της κλίμακας NIHSS 8 βαθμών ή μεγαλύτερη) και λειτουργική κατάσταση κατά την έξοδο και σε 3 μήνες που αξιολογήθηκε με την κλίμακα mRS.4. Αναζητήσαμε στις βάσεις δεδομένων MEDLINE και Scopus όλες τις μη τυχαιοποιημένες (προοπτικές ή αναδρομικές) μελέτες που συνέκριναν την χρήση της τενεκτεπλάσης σε σχέση με την αλτεπλάση. Διενεργήθηκαν μετά-αναλύσεις κατά ζεύγη με την χρήση του random effects μοντέλου. Αποτελέσματα:Αρχικά διαπιστώσαμε στα πλαίσια των περιγραφικών αναλύσεων ότι ένα ποσοστό 9.8% των ασθενών στην οξεία φάση του ΙΑΕΕ προσέρχονται στο χρονικό παράθυρο των 4.5-9 ωρών και από αυτούς το 30% (δηλαδή 3.2%) είναι δυνατόν να υποβληθεί σε θεραπείες επαναιμάτωσης είτε με ΕΘ στο λεγόμενο εκτεταμένο παράθυρο με βάση τα κριτήρια της μελέτες EXTEND είτε σε ΜΘ με βάση τα κριτήρια της μελέτης DEFUSE-3. Ακολούθως επεκτείναμε την παρατήρησή μας σε ένα χρονικό διάστημα έξι ετών προ και μετά την αλλαγή του πρωτοκόλλου απεικόνισης στην οξεία φάση με την ενσωμάτωση σε αυτό της ΠΝ, διαπιστώνοντας ότι με την χρήση της ΠΝ επετεύχθη αύξηση του αριθμού των ασθενών που υποβάλλονται σε ΕΘ κατά περίπου 50%. Παρόλο που ο χρόνος από την πιθανή έναρξη των συμπτωμάτων έως την ΕΘ ήταν μεγαλύτερος στην υποομάδα των ασθενών που υπεβλήθησαν σε ΠΝ συγκριτικά με τους ασθενείς που δεν είχαν υποβληθεί, οι δύο ομάδες δεν διέφεραν σε στατιστικά σημαντικό βαθμό ως προς τον χρόνο door-to-needle, ως προς την βαρύτητα της νευρολογικής εικόνας με βάση την κλίμακα NIHSS κατά το εξιτήριο, την εμφάνισης sICH ή οποιασδήποτε ενδοκράνιας αιμορραγίας, την καλή λειτουργική έκβαση 3 μηνών (mRS-scores 0-1), την λειτουργική ανεξαρτησία 3 μηνών (mRS-scores 0-2), κατανομή του mRS-score στους 3 μήνες ή την θνητότητα στους 3 μήνες. Στην μελέτη της σύγκρισης της τενεκτεπλάσης με την αλτεπλάση συμπεριλήφθηκαν συνολικά 58 ασθενείς. Παρατηρήσαμε ένα μη στατιστικά σημαντικό υψηλότερο ποσοστό αποτρεπόμενων θρομβεκτομών (32% έναντι 18%, p = 0,243) και ένα μη στατιστικά σημαντικό υψηλότερο ποσοστό sICH (16% έναντι 5%, p = 0,201) στην ομάδα της τενεκτεπλάσης. Το ποσοστό αξιοσημείωτης νευρολογικής βελτίωσης στις 24 ώρες ήταν υψηλότερο στην ομάδα τενεκτεπλάση (64% έναντι 33%, p = 0,046), αλλά το αποτέλεσμα αυτό μειώθηκε οριακά στις πολυπαραγοντικές αναλύσεις (adjusted OR 10,22, 95% CI: 0,73–142,98, p = 0,084) . H mRS κατά το εξιτήριο, η mRS στους 3 μήνες και η λειτουργική ανεξαρτησία στους 3 μήνες (mRS 0-2) δεν διέφεραν (p > 0,2) μεταξύ των δύο ομάδων. Τα ποσοστά θνησιμότητας στους 3 μήνες (11% έναντι 18%, p = 0,703) ήταν παρόμοια στις δύο ομάδες. Δεν προέκυψε ανεξάρτητη συσχέτιση μεταξύ του θρομβολυτικού παράγοντα και των αποτελεσμάτων ασφάλειας ή αποτελεσματικότητας στις πολυπαραγοντικές αναλύσεις λογιστικής παλινδρόμησης. Συνδυάζοντας τα αποτελέσματα της μελέτης αυτής με άλλες πέντε μελέτες, πραγματοποιήσαμε μια μεταναλύση που συμπεριέλαβε συνολικά 1820 ασθενείς (618 [34%] έλαβαν θεραπεία με τενεκτεπλάση). Οι ασθενείς που έλαβαν τενεκτεπλάση είχαν υψηλότερες πιθανότητες καλής λειτουργικής έκβασης στους 3 μήνες (crude odds ratio [OR], 1.22; 95% CI, 0.90-1.66; adjusted OR, 1.60, 95% CI, 1.08-2.37), επιτυχούς επανακαναλοποίησης , (crude OR, 2.82; 95% CI, 1.12-7.10; adjusted OR, 2.38; 95% CI, 1.18-4.81) και πρώιμης αξιοσημείωτης νευρολογικής βελτίωσης (crude OR, 4.88; 95% CI, 2.03-11.71; adjusted OR, 7.60; 95% CI, 1.97-29.41). Δεν καταγράφηκαν σημαντικές διαφορές ως προς τα ποσοστά άριστης λειτουργικής έκβασης 3 μηνών (βαθμολογία mRS 0-1, crude OR, 1.53; 95% CI, 0.81-2.91; adjusted OR, 2.51; 95% CI, 0.66- 9.49), sICH (crude OR, 0.97; 95% CI, 0.44-2.16; adjusted OR, 1.16; 95% CI, 0.13-10.50) ή οποιασδήποτε ενδοκράνιας αιμορραγίας (crude OR, 1.20; 95% CI, 0.24-5.95). Συμπεράσματα: Συμπερασματικά, η εφαρμογή της ΠΝ σε μη επιλεγμένους ασθενείς με ΟΙΑΕΕ που λαμβάνουν θεραπεία επαναιμάτωσης με ΕΘ οδηγεί σε αύξηση των ποσοστών χορήγησης ΕΘ χωρίς καθυστέρηση του χρόνου door-to-needle και χωρίς να εγείρονται ανησυχίες για την ασφάλεια ή την αποτελεσματικότητα των θεραπειών. Σε ό,τι αφορά τις μελέτες σε σχέση με την επιλογή του βέλτιστου θρομβολυτικού παράγοντα φαίνεται ότι η ενδοφλέβια τενεκτεπλάση μπορεί να είναι μια θεραπευτική επιλογή για ασθενείς με ΟΙΑΕΕ καθώς σχετίζεται με πιο ευνοϊκά κλινικά αποτελέσματα και παρόμοια ασφάλεια σε σύγκριση με την ενδοφλέβια αλτεπλάση. Ωστόσο, αυτή η υπόθεση εργασίας θα πρέπει να αξιολογηθεί περαιτέρω σε συνεχιζόμενες τυχαιοποιημένες μεγάλες μελέτες

Ultrasound Assessment of Extracranial Carotids and Vertebral Arteries in Acute Cerebral Ischemia

Assessing ischemic etiology and mechanism during the acute phase of an ischemic stroke is crucial in order to tailor and monitor appropriate treatment and determine prognosis. Cervical Duplex Ultrasound (CDU) has evolved since many years as an excellent screening tool for the evaluation of extracranial vasculature. CDU has the advantages of a low cost, easily applicable, bed side examination with high temporal and spatial resolution and without exposing the patients to any significant complications. It represents an easily repeatable test that can be performed in the emergency room as a first-line examination of cervical artery pathology. CDU provides well validated estimates of the type of the atherosclerotic plaque, the degree of stenosis, as well as structural and hemodynamic information directly about extracranial vessels (e.g., subclavian steal syndrome) and indirectly about intracranial circulation. CDU may also aid the diagnosis of non-atherosclerotic lesions of vessel walls including dissections, arteritis, carotid-jugular fistulas and fibromuscular dysplasias. The present narrative review outlines all potential applications of CDU in acute stroke management and also highlights its potential therapeutic implications

HSV-Encephalitis Resembling Acute Cerebral Infarction in a Patient With Atrial Fibrillation Beware of Stroke Mimics

Introduction: Herpes simplex virus-1 (HSV-1) encephalitis, the most common and potentially life-threatening type of encephalitis, may rarely present as a stroke mimic. Prompt diagnosis is of paramount importance for the timely initiation of antiviral treatment and to avert intravenous thrombolysis. Case Report: A 60-year-old man with a history of lone paroxysmal atrial fibrillation without prior antithrombotic treatment was admitted due to mild gait unsteadiness and intermittent dysarthria of acute onset. On admission, the patient was afebrile, whereas neurological examination revealed only a mild pronator drift on the left. Brain magnetic resonance imaging (MRI) showed an extensive right temporo-occipital and thalamic lesion with restricted diffusion and 3 small-sized hemorrhagic foci. Brain MR-angiography did not show large vessel stenosis or occlusion. On the basis of careful observation and the depiction of several imaging discrepancies, such as early vasogenic edema and hemorrhagic transformation, as well as uncus involvement, but also the lack of significant neurological deficits despite the size of the brain lesion we suspected viral encephalitis which was confirmed by the detection of HSV-1 DNA in the cerebrospinal fluid. Conclusion: HSV-encephalitis might occasionally result in the development of unilateral brain MRI lesions with extensive cytotoxic edema, resembling an acute ischemic stroke. Therefore, HSV-encephalitis must be considered in the differential diagnosis of acute ischemic stroke with atypical presentation. The presence of a significant dissociation between the brain MRI lesion volume and the neurological deficits, as well as certain brain MRI imaging discrepancies might serve as “red flags” to extend the diagnostic workup

The impact of occlusion location and bridging therapy in patients affected by acute ischemic stroke in determining the total number of passes required to remove the clot and the final revascularization outcome

Purpose Our purpose was to assess the impact of occlusion location in patients suffering from Acute Ischemic Stroke (AIS) on the total number of passes (attempts) necessary to retrieve the clot and on final revascularization outcome. Moreover, we analysed the impact of bridging-therapy, i.e. the concomitant use of IV tPA (intravenous tissue plasminogen activator) and mechanical thrombectomy (MT) on the different categories of occlusion locations. Methods 550 mechanically extracted thrombi were collected from four partner hospitals: Beaumont (Dublin) Sahlgrenska (Gothenburg), National Institute of Clinical Neurosciences (Budapest) and Metropolitan Hospital (Piraeus). In the vast majority of the cases (311 patients, 56.5%) the thrombus was located in the Middle Cerebral Artery (MCA), followed by Carotid Terminus/Internal Carotid Artery (ICA) in 89 cases (16.2%) and by vertebral/basilar artery (45 patients, 8.2%). In 65 cases (11.8%) a tandem occlusion, i.e. the occlusion of both ICA and MCA was found, while a dual occlusion occurred in 26 cases (4.7%). 248 patients (45.1%) underwent bridging-therapy, while 291 patients (52.9%) were treated with MT alone. For 11 patients (2%) we have no information whether tPA was administered or not. Recanalization rate was defined by using the modified Thrombolysis In Cerebral Infarction (mTICI) score. Non-parametric Kruskal-Wallis test using IBM SPSS-25 software was used for statistical analysis. Results Occlusion location had a significant impact on the total number of passes required to retrieve the clot as well as on final revascularization outcome. The cases with tandem and dual occlusion showed higher number of procedural passes and lower percentage of complete revascularizations (mTICI=3, Table 1). Bridging-therapy did not significantly reduce the total number of passes or improve the recanalization rates for patients with singular occlusion. On the other hand, bridging-therapy significantly lowered the total number of passes to remove the clot in patients with dual and tandem occlusion (N=87, mean for MT+tPA= 2.63±1.73, MT alone=3.80±2.14, H1=7.608, p=0.006*), but had no statistically significant effect on the final mTICI score (N=87, H1=0.266, p=0.606). Conclusion This study suggests that occlusion location significantly influences the total number of procedural passes in MT procedures as well as the final revascularization outcome. Furthermore, bridging-therapy lowers the number of procedural passes in cases of tandem and dual occlusion without having significant effect on final mTICI score. Funding: Science Foundation Ireland (Grant Number 13/RC/2073) and Cerenovus.Science Foundation Ireland (Grant Number 13/RC/2073) and Cerenovus.non-peer-reviewe

Advanced Neuroimaging Preceding Intravenous Thrombolysis in Acute Ischemic Stroke Patients Is Safe and Effective

Advanced neuroimaging is one of the most important means that we have in the attempt to overcome time constraints and expand the use of intravenous thrombolysis (IVT). We assessed whether, and how, the prior use of advanced neuroimaging (AN), and more specifically CT/MR perfusion post-processed with RAPID software, regardless of time from symptoms onset, affected the outcomes of acute ischemic stroke (AIS) patients who received IVT. Methods. We retrospectively evaluated consecutive AIS patients who received intravenous thrombolysis monotherapy (without endovascular reperfusion) during a six-year period. The study population was divided into two groups according to the neuroimaging protocol used prior to IVT administration in AIS patients (AN+ vs. AN−). Safety outcomes included any intracranial hemorrhage (ICH) and 3-month mortality. Effectiveness outcomes included door-to-needle time, neurological status (NIHSS-score) on discharge, and functional status at three months assessed by the modified Rankin Scale (mRS). Results. The rate of IVT monotherapy increased from ten patients per year (n = 29) in the AN− to fifteen patients per year (n = 47) in the AN+ group. Although the onset-to-treatment time was longer in the AN+ cohort, the two groups did not differ in door-to-needle time, discharge NIHSS-score, symptomatic ICH, any ICH, 3-month favorable functional outcome (mRS-scores of 0–1), 3-month functional independence (mRS-scores of 0–2), distribution of 3-month mRS-scores, or 3-month mortality. Conclusion. Our pilot observational study showed that the incorporation of advanced neuroimaging in the acute stroke chain pathway in AIS patients increases the yield of IVT administration without affecting the effectiveness and safety of the treatment

Off-Label Use of Tenecteplase for the Treatment of Acute Ischemic Stroke A Systematic Review and Meta-analysis

International audienceImportance: Tenecteplase is being evaluated as an alternative thrombolytic agent for the treatment of acute ischemic stroke (AIS) within ongoing randomized clinical trials (RCTs). In addition, nonrandomized clinical experiences with off-label use of tenecteplase vs alteplase for AIS treatment are being published.Objective: To evaluate the available evidence on the safety and efficacy of intravenous tenecteplase compared with intravenous alteplase provided by nonrandomized studies.Data sources: Eligible studies were identified by searching MEDLINE and Scopus databases. No language or other restrictions were imposed. The literature search was conducted on October 12, 2021. This meta-analysis used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) proposal.Study selection: Nonrandomized studies (prospective or retrospective) comparing intravenous tenecteplase (at any dose) with intravenous alteplase in patients with AIS were included in the analysis.Data extraction and synthesis: The crude odds ratios (ORs) and 95% CIs were calculated for the association of tenecteplase vs alteplase with the outcomes of interest and adjusted ORs were extracted if provided. Estimates using random-effects models were pooled.Main outcomes and measures: The primary outcome was the probability of good functional outcome (modified Rankin scale [mRS] score, 0-2) at 90 days.Results: Six studies were identified including a total of 1820 patients (618 [34%] treated with tenecteplase). Patients receiving tenecteplase had higher odds of 3-month good functional outcome (crude odds ratio [OR], 1.22; 95% CI, 0.90-1.66; adjusted OR, 1.60, 95% CI, 1.08-2.37), successful recanalization (crude OR, 2.82; 95% CI, 1.12-7.10; adjusted OR, 2.38; 95% CI, 1.18-4.81), and early neurological improvement (crude OR, 4.88; 95% CI, 2.03-11.71; adjusted OR, 7.60; 95% CI, 1.97-29.41). No significant differences were detected in 3-month excellent functional outcome proportions (mRS score 0-1; crude OR, 1.53; 95% CI, 0.81-2.91; adjusted OR, 2.51; 95% CI, 0.66- 9.49), symptomatic intracranial hemorrhage (crude OR, 0.97; 95% CI, 0.44-2.16; adjusted OR, 1.16; 95% CI, 0.13-10.50), or parenchymal hematoma (crude OR, 1.20; 95% CI, 0.24-5.95).Conclusions and relevance: Evidence from nonrandomized studies suggests tenecteplase is as safe as alteplase and potentially associated with improved functional outcomes compared with alteplase. Based on these findings, enrollment in the ongoing RCTs appears to be appropriate

Advanced Neuroimaging Preceding Intravenous Thrombolysis in Acute Ischemic Stroke Patients Is Safe and Effective

Advanced neuroimaging is one of the most important means that we have in the attempt to overcome time constraints and expand the use of intravenous thrombolysis (IVT). We assessed whether, and how, the prior use of advanced neuroimaging (AN), and more specifically CT/MR perfusion post-processed with RAPID software, regardless of time from symptoms onset, affected the outcomes of acute ischemic stroke (AIS) patients who received IVT. Methods. We retrospectively evaluated consecutive AIS patients who received intravenous thrombolysis monotherapy (without endovascular reperfusion) during a six-year period. The study population was divided into two groups according to the neuroimaging protocol used prior to IVT administration in AIS patients (AN+ vs. AN-). Safety outcomes included any intracranial hemorrhage (ICH) and 3-month mortality. Effectiveness outcomes included door-to-needle time, neurological status (NIHSS-score) on discharge, and functional status at three months assessed by the modified Rankin Scale (mRS). Results. The rate of IVT monotherapy increased from ten patients per year (n = 29) in the AN- to fifteen patients per year (n = 47) in the AN+ group. Although the onset-to-treatment time was longer in the AN+ cohort, the two groups did not differ in door-to-needle time, discharge NIHSS-score, symptomatic ICH, any ICH, 3-month favorable functional outcome (mRS-scores of 0-1), 3-month functional independence (mRS-scores of 0-2), distribution of 3-month mRS-scores, or 3-month mortality. Conclusion. Our pilot observational study showed that the incorporation of advanced neuroimaging in the acute stroke chain pathway in AIS patients increases the yield of IVT administration without affecting the effectiveness and safety of the treatment