The prognostic value of combined uric acid and neutrophil-to-lymphocyte ratio in acute ischemic stroke patients treated with intravenous thrombolysis.

BACKGROUND: Serum uric acid (UA) and the neutrophil-to-lymphocyte ratio (NLR) have been reported to be associated with outcomes in acute ischemic stroke (AIS). However, whether UA is related to the prognosis of AIS patients undergoing intravenous thrombolysis (IVT) remains inconclusive. We sought to explore the combined effect of UA and NLR on the prognosis of AIS treated with IVT. METHODS: A total of 555 AIS patients receiving IVT treatment were enrolled. Patients were categorized into four groups according to the levels of UA and NLR: LNNU (low NLR and normal UA), LNHU (low NLR and high UA), HNNU (high NLR and normal UA), and HNHU (high NLR and high UA). Multivariable logistic regression analysis was used to evaluate the value of serum UA level and NLR in predicting prognosis. The primary outcomes were major disability (modified Rankin scale (mRS) score 3-5) and death within 3 months. RESULTS: After multivariate adjustment, a high NLR (≥ 3.94) increased the risk of 3-month death or major disability (OR, 2.23; 95% CI, 1.42 to 3.55, p < 0.001). However, there was no statistically significant association between a high UA level (≥ 313.00 µmol/L) and clinical outcome. HNHU was associated with a 5.09-fold increase in the risk of death (OR, 5.09; 95% CI, 1.31-19.83; P value = 0.019) and a 1.98-fold increase in the risk of major disability (OR, 1.98; 95% CI 1.07-3.68; P value = 0.030) in comparison to LNNU. CONCLUSIONS: High serum UA levels combined with high NLR were independently associated with 3-month death and major disability in AIS patients after IVT.

Observation of efficacy of rt-PA thrombolysis combined with Solitaire AB stent mechanical thrombectomy in patients with acute ischemic stroke: a retrospective analysis.

OBJECTIVE: To observe and analyze the efficacy of recombinant tissue-plasminogen activator (rt-PA) thrombolysis combined with Solitaire AB stent mechanical thrombectomy in patients with acute ischemic stroke. METHODS: Clinical efficacy, neurological function, oxidative stress response, adverse reactions, and quality of life were compared between the two groups. RESULTS: Lower NIHSS scores were observed among patients who received treatment within 2 h after stroke onset when compared with those in a timeframe of 2-6 h, suggesting better neurological function recovery of the patients with early intervention and thus emphasizing the importance of early treatment for patients with stroke onset. Clinical efficacy in the combination group was significantly higher than in the control group (p < 0.05). After treatment, Paraoxonase-1 (PON-1) levels were higher, while lipoprotein-associated phospholipase A2 (Lp-PLA2) and Serum Amyloid A (SAA) levels were lower in the combination group compared to the control group (p < 0.05). The incidence of adverse reactions was significantly lower in the combination group (p < 0.05). At discharge, we observed significantly more patients with good recovery in the combination group when compared to the control group (p < 0.05), suggesting better quality of life of the patients, while this statistical significance was no longer observable at 90 days after discharge (p > 0.05). CONCLUSION: For acute ischemic stroke patients, rt-PA thrombolysis combined with Solitaire AB stent mechanical thrombectomy treatment is effective. It promotes neurological function recovery, improves vascular stenosis, reduces inflammation and adverse reactions, and enhances quality of life, showing promising clinical applications.

Remote ischemic conditioning attenuates blood-brain barrier disruption after recombinant tissue plasminogen activator treatment via reducing PDGF-CC.

Treatment of acute ischemic stroke with the recombinant tissue plasminogen activator (rtPA) is associated with increased blood-brain barrier (BBB) disruption and hemorrhagic transformation. Remote ischemic conditioning (RIC) has demonstrated neuroprotective effects against acute ischemic stroke. However, whether and how RIC regulates rtPA-associated BBB disruption remains unclear. Here, a rodent model of thromboembolic stroke followed by rtPA thrombolysis at different time points was performed with or without RIC. Brain infarction, neurological outcomes, BBB permeability, and intracerebral hemorrhage were assessed. The platelet-derived growth factor CC (PDGF-CC)/PDGFRα pathway in the brain tissue, PDGF-CC levels in the skeletal muscle and peripheral blood were also measured. Furthermore, impact of RIC on serum PDGF-CC levels were measured in healthy subjects and AIS patients. Our results showed that RIC substantially reduced BBB injury, intracerebral hemorrhage, cerebral infarction, and neurological deficits after stroke, even when rtPA was administrated in a delayed therapeutic time window. Mechanistically, RIC significantly decreased PDGFRα activation in ischemic brain tissue and reduced blood PDGF-CC levels, which partially resulted from PDGF-CC reduction in the skeletal muscle of RIC-applied hindlimbs and platelets. Intravenous or intraventricular recombinant PDGF-CC supplementation abolished RIC protective effects on BBB integrity. Moreover, similar changes of PDGF-CC in serum by RIC were also observed in healthy humans and acute ischemic stroke patients. Together, our study demonstrates that RIC can attenuate rtPA-aggravated BBB disruption after ischemic stroke via reducing the PDGF-CC/PDGFRα pathway and thus supports RIC as a potential approach for BBB disruption prevention or treatment following thrombolysis.

The potential role of micro-RNA 125b-5p level in predicting outcome from thrombolytic therapy in patients with acute ischemic stroke.

Several studies highlighted a significant role of specific miRNA as diagnostic and prognostic biomarkers for acute ischemic stroke. The aim of this work was to study micro-RNA 125b-5p level in patients with acute ischemic stroke in relation to stroke etiology, risk factors, severity and outcome. This case-control study was conducted on 40 patients with acute ischemic stroke eligible for receiving rt-PA and 40 age and sex matched healthy controls, Patients were submitted to neurological and radiological assessment. Functional outcome after 3 months was assessed using the modified Rankin Scale (mRS). Plasma micro-RNA 125b-5p levels were measured for both patients and control groups by quantitative real time PCR. MiRNA-125b-5p was extracted from the plasma samples then Real-time quantitative reversed transcription PCR (RT-qPCR) analysis was done. To analyze miRNA-125b-5p expression in plasma, the ∆Cq value of miRNA-125b-5p was calculated by subtracting Cq of miRNA-125b-5p from the average Cq of MiRNA RNU6B. Stroke patients had significantly higher circulating micro-RNA 125b-5p levels in comparison to healthy controls (P value = 0.01). The circulating levels of micro-RNA 125b-5p were positively correlated with stroke severity assessed by National Institutes of Health Stroke Scale (NIHSS) and infarction size. Stroke patients with poor outcome had significantly higher circulating levels of micro-RNA 125b-5p in comparison to those with good outcome (P value ≤ 0.001). The circulating levels of micro-RNA 125b-5p were significantly higher in patients who developed complications after receiving rt-PA (P value ≤ 0.001). Logistic regression model revealed that each unit increase in micro-RNA125b-5p decreased the odds of good outcome by 0.095 (95% CI 0.016-0.58, P value = 0.011). Plasma micro-RNA 125b-5p is significantly elevated is ischemic stroke patients. It is positively correlated with stroke severity and strongly associated with poor outcome and complications after thrombolytic therapy.

Technical note: Novel use of recombinant tissue plasminogen activator for the evacuation of an acute extensive spinal epidural haematoma in a patient with coagulopathy.

Spontaneous extensive spinal epidural haematoma poses a unique challenge for the neurosurgeon. Performing extensive laminectomies to remove all of the compressive haematoma can destabilise the patient's spinal column, which may require fixation. This is further complicated in patients with significant coagulopathy. We present a novel use of recombinant tissue plasminogen activator (rt-PA) in a patient with therapeutic coagulopathy, presenting with myelopathy secondary to an acute extensive spinal epidural haematoma. To the best of our knowledge, this is the first case of acute multilevel spinal epidural haematoma that has been successfully evacuated via single level laminectomy and topically applied rt-PA.

Deciphering the contextual barriers to mainstreaming the implementation of stroke thrombolysis in a Ghanaian hospital: Findings from the activate mixed-methods study.

BACKGROUND: Each year, stroke-related death and disability claim over 143 million years of healthy life globally. Despite accounting for much of the global stroke burden, acute stroke care in Low-and-Middle-Income Countries remains suboptimal. Thrombolysis, an effective treatment option for stroke, is only received by a minority of stroke patients in these settings. AIM: To determine the context-specific barriers and facilitators for the implementation of mainstream stroke thrombolysis in a Ghanaian hospital. METHODS: We employed a mixed-methods approach involving key stakeholders (recipients, providers, and leaders) in the acute stroke care continuum. Surveys were administered to acute stroke patients, and in-depth key informant interviews were conducted with experts in stroke care, including a neurologist, medical director, neurology residents, a stroke nurse, emergency physicians, a radiologist, and a pharmacist. The data collected from these interviews were transcribed and analysed using content analysis with the CFIR (Consolidated Framework for Implementation Research) model as a guiding template. Two independent coders were involved in the analysis process to ensure reliability and accuracy. RESULTS: The stroke thrombolysis rate over a 6-month period was 0.83% (2 out of 242), with an average door-to-needle time among thrombolyzed patients being 2 hours, 37 minutes. Only 12.8% of patients (31 out of 242) presented within 4.5 hours of stroke symptom onset. The most significant obstacle to the implementation of acute stroke thrombolysis was related to the characteristics of the individuals involved, notably delays in presenting to the hospital among stroke patients due to a lack of knowledge about stroke symptoms and cultural beliefs. Additionally, a significant bottleneck that contributed to the discrepancy between the number of patients who presented within the 4.5-6 hour window and the number of patients who actually received thrombolysis was the inability to pay for the cost of thrombolytic agents. This was followed by challenges in the implementation processes. CONCLUSIONS: Addressing challenges related to stroke awareness, and financial constraints via multi-level stakeholder engagement, and enactment of stroke protocols are crucial steps in ensuring a successful implementation of a stroke thrombolysis program in a resource-limited setting.

[A Case of the Internal Carotid Artery Occlusion Immediately After Intravenous Recombinant Tissue Plasminogen Activator Treatment for Contralateral Middle Cerebral Artery Occlusion].

Early recurrent ischemic stroke (ERIS), as well as symptomatic intracranial hemorrhage (SICH) and progressive stroke (PS), causes early neurological deterioration. Here we report a case of a patient with right internal carotid artery (ICA) occlusion immediately after intravenous recombinant tissue plasminogen activator (rt-PA) treatment for left middle cerebral artery (MCA) occlusion. A 79-year-old woman with drowsiness, aphasia and right hemiparesis was brought to our hospital. MRI showed acute infarction in the left internal capsule and occlusion of the left middle cerebral artery. rt-PA was administered intravenously to the patient 2 hours after the onset of the event. Her consciousness disturbance and aphasia improved, but the right hemiparesis did not. We performed emergent endovascular thrombectomy, but the right ICA (cervical portion) was occluded during the surgery. Finally, the endovascular thrombectomy achieved the recanalization of the left MCA and right ICA. When performing intravenous thrombolysis, we should beware the possibility of re-occlusion and prepare for interventional treatment.

Spatiotemporal lipidomics reveals key features of brain lipid dynamic changes after cerebral ischemia and reperfusion therapy.

Reperfusion therapy with recombinant tissue plasminogen activator (rtPA) or mechanical thrombectomy is the most effective treatment for ischemic stroke. However, a large proportion of stroke patients remain severely disabled even after receiving timely reperfusion therapy. It remains unclear how reperfusion therapy results in secondary injury to the brain tissue and whether different reperfusion therapies induce differential effects. Here, we comprehensively determined the spatiotemporal dynamic changes in brain lipids during the acute phase after reperfusion in a mouse model of transient middle cerebral artery occlusion, with or without rtPA administration, using desorption electrospray ionization (DESI)-mass spectrometry imaging (MSI). Several phospholipids, sphingolipids, and neutral lipids were significantly altered both spatially and temporally at multiple timepoints after reperfusion, many of which were closely associated with expansion of the brain infarction territory and neurological function impairment. Furthermore, rtPA treatment significantly increased brain infarction, cerebral edema, and neurological deficits. Consistently, rtPA treatment caused extensive brain lipid alterations by facilitating brain-wide changes in lipid metabolism and inducing ischemic region-specific lipid changes. Overall, these results provide novel insights into how reperfusion therapy affects brain tissue and the outcome of stroke patients, and thus may facilitate the optimization of the treatment of ischemic stroke.

Safety and efficacy of low-dose rt-PA with tirofiban to treat acute non-cardiogenic stroke: a single-center randomized controlled study.

BACKGROUND AND PURPOSE: The recanalization rate after intravenous thrombolysis (IVT) is not enough and there is still the possibility of re-occlusion. We aim to investigate the effectiveness and safety of infusing tirofiban after IVT. METHODS: We performed a prospective controlled study of 60 patients with acute non-cardiogenic ischemic stroke who were hospitalized in Yantai Yuhuangding Hospital from January 2018 to December 2019. The patients were divided into 2 groups: those who received tirofiban for 24 h after IVT (rt-PA + T group) and those who did not receive postprocedural intravenous tirofiban (rt-PA group). The rt-PA + T group received low-dose rt-PA (0.6 mg/kg). The rt-PA group received standard dose rt-PA (0.9 mg/kg). The main outcome measure were safety, included the symptomatic intracranial hemorrhage (sICH), any ICH, severe systemic bleeding, and mortality. The secondary outcome measure is curative efficacy which were evaluated by the 7d-NIHSS score and functional outcomes at 90 days. During hospitalization, the deterioration of neurological function was recorded. RESULTS: All patients completed the follow-up with complete data, there were 30 patients in each of groups. The general characteristics between the two group patients had no statistically significant differences. Compared with the rt-PA + T group and the rt-PA group, in terms of safety, the rates of the sICH, severe systemic bleeding, and mortality in both groups were 0, and there was no statistically significant difference in the rates of any ICH between the two groups (10.0% vs. 3.3%, P = 0.306). In terms of efficacy, the rate of the early neurological deterioration events (END) was no statistical significance (0 vs. 6.6%, P = 0.246). There was no significant difference in the NIHSS score between the two groups before the IVT, and also at 24 h, however, the 7d-NIHSS score was lower in the rt-PA + T group compared with the rt-PA group (2.33 ± 1.85 vs. 4.80 ± 4.02, P = 0.004). At 90 days, 83.3% of patients in the rt-PA + T group had favorable functional outcomes compared with 60.0% of patients in the rt-PA group (P = 0.045). CONCLUSIONS: Low-dose rt-PA combined with tirofiban in acute non-cardiogenic ischemic stroke did not increase the risk of ICH, and mortality, and it was associated with neurological improvement. TRIAL REGISTRATION: The trial has been registered at the ChiCTR and identified as ChiCTR1800014666 (28/01/2018).

Initial medical protocol efforts using both CT and MRI/MRA for acute cerebral infarction.

BACKGROUND: Earlier administration of intravenous recombinant tissue-type plasminogen activator (rtPA) and mechanical thrombectomy (MT) improves the neurological prognosis of patients with acute ischemic stroke (AIS). We introduced a new protocol that includes head and chest computed tomography (CT) and magnetic resonance imaging (MRI)/ magnetic resonance angiography (MRA) for all patients, which is quite different from previously evaluated protocols. This study aimed to examine whether this protocol could contribute to the prompt therapeutic intervention of AIS. METHODS: This is a retrospective observational study analyzing patients with AIS who were transported to our hospital by ambulance between January 2015 and November 2021. An AIS initial treatment protocol was introduced in April 2020, under which, CT and MRI/MRA imaging were performed in all patients, and the indication for rtPA and MT were determined. The participants were divided into those who were treated before and after the protocol introduction (conventional treatment and protocol groups, respectively). The time from hospital arrival to the start of rtPA administration (door-to-needle time: DNT) and the time from hospital arrival to the start of endovascular treatment (door-to-puncture time: DPT) were compared between the groups. RESULT: A total of 121 patients were analyzed, wherein 63 patients received rtPA (18 in the conventional treatment group and 45 in the protocol group) and 98 patients received MT (32 in the conventional treatment group and 66 in the protocol group). The median DNT was 97.0 (IQR 49.0-138.0) min vs. 56.5 (IQR 41.0-72.0) min (p < 0.001) for the conventional treatment and the protocol groups, respectively. The median DPT was 129.0 (IQR 62.0-196.0) min vs. 55.0 (IQR 40.5-69.5) min (p < 0.001), respectively. Moreover, DNT was achieved within 60 min in 5.6% vs. 69.9% (p < 0.001) and DPT within 90 min in 25.0% vs. 85.7% (p < 0.001), respectively. CONCLUSION: The introduction of a protocol, including CT/MRI imaging, significantly shortened DNT and DPT.

Histological composition of retrieved emboli in acute ischemic stroke is independent of pre-thrombectomy alteplase use.

BACKGROUND AND PURPOSE: Given recent evidence suggesting the clot composition may be associated with revascularization outcomes and stroke etiology, clot composition research has been a topic of growing interest. It is currently unclear what effect, if any, pre-thrombectomy thrombolysis has on clot composition. Understanding this association is important as it is a potential confounding variable in clot composition research. We retrospectively evaluated the composition of retrieved clots from ischemic stroke patients who did and did not receive pre-treatment tPA to study the effect of tPA on clot composition. MATERIALS AND METHODS: Consecutive patients enrolled in the Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) were included in this study. All patients underwent mechanical thrombectomy and retrieved clots were sent to a central core lab for processing. Histological analysis was performed using Martius Scarlett Blue (MSB) staining and area of the clot was also measured on the gross photos. Student's t test was used for continuous variables and chi-squared test for categorical variables. RESULTS: A total of 1430 patients were included in this study. Mean age was 68.4±13.5 years. Overall rate of TICI 2c/3 was 67%. A total of 517 patients received tPA (36%) and 913 patients did not (64%). Mean RBC density for the tPA group was 42.97±22.62% compared to 42.80±23.18% for the non-tPA group (P=0.89). Mean WBC density for the tPA group was 3.74±2.60% compared to 3.42±2.21% for the non-tPA group (P=0.012). Mean fibrin density for the tPA group was 26.52±15.81% compared to 26.53±15.34% for the non-tPA group (P=0.98). Mean platelet density for the tPA group was 26.22±18.60% compared to 26.55±19.47% for the non-tPA group (P=0.75). tPA group also had significantly smaller clot area compared to non-tPA group. CONCLUSIONS: Our study 1430 retrieved emboli and ischemic stroke patients shows no interaction between tPA administration and clot composition. These findings suggest that tPA does not result in any histological changes in clot composition.

Extending the window for thrombolysis for treatment of acute ischaemic stroke during pregnancy: a review.

Historically, safety of intravenous recombinant tissue plasminogen activator (IV rt-PA) for the treatment of acute ischaemic stroke (AIS) is limited to use within 4.5 hours from symptom onset. Recent studies suggest the treatment window may be extended when patients have salvageable brain tissue on advanced neuroimaging. This paper describes a novel use of IV rt-PA for treatment of AIS in a pregnant patient within an extended-time window (>4.5 hours, and <9 hours) based on advanced neuroimaging with a favourable outcome. TWEETABLE ABSTRACT: Novel use of IV rt-PA for treatment of AIS in pregnancy within an extended-time window based on advanced imaging with a favourable outcome.

The use of recombinant tissue plasminogen activator in in acute ischemic stroke is associated with increased level of BDNF.

Much concern was directed towards the crucial role of recombinant tissue plasminogen activator (rt-PA) in improving neuroplasticity in patients with acute ischemic stroke. The aim of the work to investigate the effect of treating patients with acute ischemic stroke with rt-PA, on the level of brain derived neurotrophic factor (BDNF) as a marker of neuroplasticity. This study was conducted on 47 patients presenting with acute ischemic stroke (during the first 4.5 h from stroke onset); 26 patients of them eligible for receiving rt-PA (patient group) and 21 patients having contraindications for treatment with rt-PA (control group). Neurological, radiological and laboratory assessment (including BDNF serum level) were done for both groups at stroke onset (before receiving rt-PA) and at day 7. There was a statistically significant increase in BDNF serum level from day 1 to day 7 in rt-PA treated patients in comparison to control group (P-value˂ 0.001). Serum level of BDNF is significantly higher at the onset of stroke in female patients and non-smokers than males or smokers (P-value = 0.011, 0.01 respectively). There was no effect of either age, body mass index, hypertension, diabetes, drug abuse, past or family history of stroke, valvular heart diseases, atrial fibrillation, cardiomyopathy, ejection fraction, carotid atherosclerotic changes, lipid profile or uric acid, on BDNF serum level measured at the onset of stroke. Treatment of patients with acute ischemic stroke with rt-PA causes significant improvement in neuroplasticity through increasing BDNF serum level.

Safety and efficacy of rt-PA treatment for acute stroke in pseudoxanthoma elasticum: the first report.

Pseudoxanthoma elasticum is a rare cause for ischaemic stroke. Little is known about acute and secondary prevention strategies in these subjects given the increased risk of gastrointestinal and urinary bleedings. Here we present the case of a 62 years old man affected by pseudoxanthoma elasticum who presented with acute ischaemic stroke and was successfully treated with intravenous thrombolysis. Neurological signs improved after intravenous thrombolysis without bleeding complication. To our knowledge, this is the first case of pseudoxanthoma elasticum-related stroke undergoing intravenous thrombolysis.

Recombinant Expression of Thrombolytic Agent Reteplase in Marine Microalga Tetraselmis subcordiformis (Chlorodendrales, Chlorophyta).

Tetraselmis subcordiformis, a unicellular marine green alga, is used widely in aquaculture as an initial feeding for fish, bivalve mollusks, penaeid shrimp larvae, and rotifers because of its rich content of amino acids and fatty acids. A stable nuclear transformation system using the herbicide phosphinothricin (PPT) as a selective reagent was established previously. In this research, the recombinant expression in T. subcordiformis was investigated by particle bombardment with the rt-PA gene that encodes the recombinant human tissue-type plasminogen activator (Reteplase), which is a thrombolytic agent for acute myocardial infarction treatment. Transgenic algal strains were selected by their resistance to PPT, and expression of rt-PA was validated by PCR, Southern blotting, and Western blotting, and bioactivity of rt-PA was confirmed by the fibrin agarose plate assay for bioactivity. The results showed that rt-PA was integrated into the genome of T. subcordiformis, and the expression product was bioactive, indicating proper post-transcriptional modification of rt-PA in T. subcordiformis. This report contributes to efforts that take advantage of marine microalgae as cell factories to prepare recombinant drugs and in establishing a characteristic pathway of oral administration in aquaculture.

Mean Platelet Volume is a Prognostic Marker in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis.

BACKGROUND AND OBJECTIVES: There is conflicting data regarding the association between platelet parameters and prognosis of stroke patients treated with intravenous thrombolysis. We aimed to analyze this association in a cohort of patients treated with rtPA. MATERIAL AND METHODS: Retrospective, observational study in adult ischemic stroke patients treated with rtPA between January 2015 and February 2017. Demographic and clinical characteristics, stroke severity (NIHSS), etiology (TOAST), mean platelet volume (MPV), platelet count (PC), platelet distribution width (PDW) and functional outcome (mRS) at discharge and 90 days were recorded. The association between platelet parameters and unfavorable prognosis (mRS 3-6) was tested using non-parametric tests and logistic regression analysis. RESULTS: 267 patients were included, 134 (50.2%) females, with a median (IQR) age of 74 years (64-82). The median admission NIHSS was 14 (8-19) and the most frequent etiology was cardioembolism (n = 115, 43.1%). At discharge, 170 (63.7%) patients had mRS 3-6. MPV values were higher in patients with mRS 3-6 (median 8.2fL versus 7.8fL, p = 0.013). This association remained significant (OR = 1.36, 95% CI 1.003-1.832, p = 0.048) after adjustment for variables associated with prognosis. There were no significant associations between other platelet parameters and prognosis. There was a trend to unfavorable prognosis at 90 days in patients with higher MPV. Regarding the association between platelet parameters and hemorrhagic transformation, higher PDW was associated with more severe hemorrhagic transformation (PH1/PH2). CONCLUSIONS: Higher MPV values were associated with unfavorable prognosis at discharge in patients treated with intravenous thrombolysis. Future studies should address its added value in stroke prediction models.

Urokinase Plasminogen Activator: A Potential Thrombolytic Agent for Ischaemic Stroke.

Stroke continues to be one of the leading causes of mortality and morbidity worldwide. Restoration of cerebral blood flow by recombinant plasminogen activator (rtPA) with or without mechanical thrombectomy is considered the most effective therapy for rescuing brain tissue from ischaemic damage, but this requires advanced facilities and highly skilled professionals, entailing high costs, thus in resource-limited contexts urokinase plasminogen activator (uPA) is commonly used as an alternative. This literature review summarises the existing studies relating to the potential clinical application of uPA in ischaemic stroke patients. In translational studies of ischaemic stroke, uPA has been shown to promote nerve regeneration and reduce infarct volume and neurological deficits. Clinical trials employing uPA as a thrombolytic agent have replicated these favourable outcomes and reported consistent increases in recanalisation, functional improvement and cerebral haemorrhage rates, similar to those observed with rtPA. Single-chain zymogen pro-urokinase (pro-uPA) and rtPA appear to be complementary and synergistic in their action, suggesting that their co-administration may improve the efficacy of thrombolysis without affecting the overall risk of haemorrhage. Large clinical trials examining the efficacy of uPA or the combination of pro-uPA and rtPA are desperately required to unravel whether either therapeutic approach may be a safe first-line treatment option for patients with ischaemic stroke. In light of the existing limited data, thrombolysis with uPA appears to be a potential alternative to rtPA-mediated reperfusive treatment due to its beneficial effects on the promotion of revascularisation and nerve regeneration.

Younger age at stroke onset but not thrombolytic treatment predicts poststroke epilepsy: An updated meta-analysis.

AIMS: Stroke is the most commonly identified cause of late-onset epilepsy. Risk factors for poststroke epilepsy (PSE) are partially elucidated, and many studies have been performed in recent years. We aimed to update our previous systematic review and meta-analysis on risk factors for PSE. METHODS: PubMed, Google Scholar, and Scopus databases were searched. Articles published in English (1987-2019) were included. Odds ratios (OR) and mean values were calculated for examined variables. RESULTS: Thirty studies with different designs were included, enrolling 26,045 patients who experienced stroke, of whom 1800 had PSE, corresponding to a prevalence of 7%. Cortical lesions (OR: 3.58, 95% confidence interval (CI): 2.35-5.46, p < 0.001), hemorrhagic component (OR: 2.47, 95% CI: 1.68-3.64, p < 0.001), early seizures (ES) (OR: 4.88, 95% CI: 3.08-7.72, p < 0.001), and younger age at stroke onset (difference in means: 2.97 years, 95% CI: 0.78 to 5.16, p = 0.008) favor PSE. Sex and acute treatment with recombinant tissue plasminogen activator (rtPA) do not predict the occurrence of PSE. CONCLUSION: Despite limitations due to the uneven quality and design of the studies, the present meta-analysis confirms that cortical involvement, hemorrhagic component, and ES are associated with a higher risk of PSE. In this update, younger age at stroke onset but not thrombolytic treatment seems to increase the risk for PSE. This article is part of the Special Issue "Seizures & Stroke".

Reperfusion therapies and poststroke seizures.

Seizures are not only a frequent complication of stroke but have been associated with an unfavorable functional and vital outcome of patients who have had stroke. Facing a new paradigm of acute standard stroke care, acute symptomatic seizures in this clinical setting deserve to be rethought. Reperfusion therapies, the gold standard treatment for acute ischemic stroke, improve long-term survival and outcome of patients who have had stroke and have been associated both with clinical seizures and the occurrence of epileptiform activity in the electroencephalogram (EEG). This narrative review describes the different physiopathological mechanisms underlying the possible association between reperfusion therapies and seizures, both acute symptomatic seizures and unprovoked seizures, and the current evidence regarding the risk of poststroke seizures in treated patients. It also identifies the gaps in our knowledge to foster future studies in this field. By different mechanisms, reperfusions therapies may have opposing effects on the risk of poststroke seizures. There is a need for a better definition of the specific physiopathology of seizures in clinical practice, as many factors can be recognized. Additionally, most of the current clinical evidence refers to acute symptomatic seizures and not to unprovoked seizures or poststroke epilepsy, and our analysis does not support the existence of a strong association between thrombolysis and poststroke seizures. So far, the impact of reperfusion therapies on the frequency of poststroke seizures is unclear. To study this effect, many clinical challenges must be overcome, including a better and clear operational definition of seizures and stroke characteristics, the standard of stroke and epilepsy care and EEG monitoring, and the degree of reperfusion success. Prospective, high quality, larger, and longer follow-up multicentric studies are urgently needed. Additionally, stroke registries can also prove useful in better elucidate whether there is an association between reperfusion therapies and seizures. This article is part of the Special Issue "Seizures & Stroke".

A single-centre experience of intravenous thrombolysis for stroke in COVID-19 patients.

The sudden worldwide outbreak of Coronavirus Disease 2019 (COVID-19) has certainly provided new challenges in the management of acute ischaemic stroke, and the risk-benefit ratio of intravenous thrombolysis in COVID-19 positive patients is not well known. We describe four COVID-19 patients treated with intravenous thrombolysis for acute ischaemic stroke. Although rt-PA administration is the main therapeutic strategy, our patients experienced unpredictable complications and showed atypical features: the overall mortality was very high. In conclusion, in this article, we provide information about these cases and discuss the possible explanation behind this trend.