Reperfusion Therapy For Stroke Research Articles

Clinical case of bridged reperfusion therapy in massive ischemic stroke in the territory of left internal carotid artery on the background of dissection

Stroke remains the most common cause of death and permanent disability in the developed countries of the world. One of the main predictors of a good outcome is both mostly fast and safety recanalization of the occluded vessel of the brain. Over the past decade, endovascular therapy became a promising therapeutic approach for patients with acute ischemic stroke in combination with early usage of high-resolution methods of neuroimaging. This article discusses a clinical case of severe ischemic stroke due to occlusion of a major artery, confirmed by CT angiography. The efficacy of reperfusion therapy with intravenous administration of alteplase in combination with thrombectomy was demonstrated, the most common intra-arterial recanalization complications were pointed out. The early recognition of sudden complications with rapid decision-making for therapy modification during bridged reperfusion therapy is important for improving results of trearment.

Reperfusion therapy for ischemic stroke without prior neuroimaging

Clinical guidelines and the order of providing care in acute cerebrovascular accidents (CVA) have been developed for standard clinical situations, primarily for patients admitted to medical institutions in an emergency state. However, there are clinical situations when a generally accepted order of therapeutic and diagnostic measures concerning patients with stroke is unjustified and, on the contrary, its implementation threatens life and health of a patient. These situations include ischemic strokes developing intraoperatively during such endovascular interventions as diagnostic cerebral and coronary angiography and transcutaneous neuro- and cardiovascular surgery. Ischemic cerebral events after diagnostic endovascular procedures are relatively rare complications, but their development can lead to unfavorable consequences. Thus, the rates of transient cerebral circulatory disorders after cerebral angiography, a stroke with a reversible neurological deficit, and an ischemic stroke with a persistent neurological deficit are 2.45 %, 0.3 %, and 1.0 % respectively, while total mortality due to acute cerebrovascular pathology is 0.14 %. The rate of cerebral stroke after coronary angiography and percutaneous coronary interventions is up to 0.4 %. Prevention of neurologic complications in diagnostic and surgical transcutaneous interventions is strongly dependant on their correct technique, rational perioperative antithrombotic therapy, and lesser duration of endovascular operations.

Sex differences in stroke reperfusion therapy in Aotearoa (New Zealand).

Stroke is a leading cause of death in Aotearoa (New Zealand), and stroke reperfusion therapy is a key intervention. Sex differences in stroke care have previously been asserted internationally. This study assessed potential differences in stroke reperfusion rates and quality metrics by sex in Aotearoa (New Zealand). This study used data from three overlapping sources. The National Stroke Reperfusion Register provided 4-year reperfusion data from 2018 to 2021 on all patients treated with reperfusion therapy (intravenous thrombolysis and thrombectomy), including time delays, treatment rates, mortality and complications. Linkage to Ministry of Health administrative and REGIONS Care study data provided an opportunity to control for confounders and explore potential mechanisms. T-test and Wilcoxon rank-sum analyses were used for continuous variables, while the chi-squared test and logistic regression were used for comparing dichotomous variables. Fewer women presented with ischaemic stroke (12 186 vs 13 120) and were 4.2 years older than men (median (interquartile range (IQR)) 79 (68-86) vs 73 (63-82) years). Women were overall less likely to receive reperfusion therapy (13.9% (1704) vs 15.8% (2084), P < 0.001) with an adjusted odds ratio of 0.83 (0.77-0.90), P < 0.001. The adjusted odds ratio for thrombolysis was lower for women (0.82 (0.76-0.89), P < 0.001), but lower rates of thrombectomy fell just short of statistical significance ((0.89 (0.79-1.00), P = 0.05). There were no significant differences in complications, delays or documented reasons for non-thrombolysis. Women were less likely to receive thrombolysis, even after adjusting for age and stroke severity. We found no definitive explanation for this disparity.

No-reflow after stroke reperfusion therapy: An emerging phenomenon to be explored.

In the field of stroke thrombectomy, ineffective clinical and angiographic reperfusion after successful recanalization has drawn attention. Partial or complete microcirculatory reperfusion failure after the achievement of full patency of a former obstructed large vessel, known as the "no-reflow phenomenon" or "microvascular obstruction," was first reported in the 1960s and was later detected in both experimental models and patients with stroke. The no-reflow phenomenon (NRP) was reported to result from intraluminal occlusions formed by blood components and extraluminal constriction exerted by the surrounding structures of the vessel wall. More recently, an emerging number of clinical studies have estimated the prevalence of the NRP in stroke patients following reperfusion therapy, ranging from 3.3% to 63% depending on its evaluation methods or study population. Studies also demonstrated its detrimental effects on infarction progress and neurological outcomes. In this review, we discuss the research advances, underlying pathogenesis, diagnostic techniques, and management approaches concerning the no-reflow phenomenon in the stroke population to provide a comprehensive understanding of this phenomenon and offer references for future investigations.

Challenges in adapting a stroke unit in a middle-income country: warning about costs and underfunding to achieve the Brazilian Ministry of Health's benchmark.

Since the implementation of the stroke care line in Brazil, the relationship (adequacy) of costs spent during hospitalization with the Brazilian Ministry of Health indicators for a stroke unit have not yet been analyzed. This study aimed to assess the adequacy of a comprehensive stroke center for key performance indicators and analyze the costs involved in hospitalization. We verified the association between stroke severity at admission and care costs during hospitalization. A retrospective medical chart review of 451 patients was performed using semiautomatic electronic data from a single comprehensive stroke center in Brazil between July 2018 and January 2020. Clinical and resource utilization data were collected, and the mean acute treatment cost per person was calculated. The Kruskal-Wallis test with Dunn's post-test was used to compare the total costs between stroke types and reperfusion therapies. A robust linear regression test was used to verify the association between stroke severity at hospital admission and the total hospitalization costs. Good adequacy rates were observed for several indicators. Data from 451 patients were analyzed. The stroke unit had good adaptation to key performance indicators, but some critical points needed revision and improvement to adapt to the requirements of the Ministry of Health. The average total cost of the patient's stay was the USD 2,637.3, with the daily hospitalization, procedure, operating room, and materials/medication costs equating to USD 2,011.1, USD 220.7, USD 234.1, and USD 98.8, respectively. There was a positive association between the total cost and length of hospital stay (p < 0.001). The stroke unit complied with most of the main performance indicators proposed by the Brazilian Ministry of Health. Underfunding of the costs involved in the hospitalization of patients was verified, and high costs were associated with the length of stay, stroke severity, and mechanical thrombectomy.

Global stroke statistics 2023: Availability of reperfusion services around the world.

Disparities in the availability of reperfusion services for acute ischemic stroke are considerable globally and require urgent attention. Contemporary data on the availability of reperfusion services in different countries are used to provide the necessary evidence to prioritize where access to acute stroke treatment is needed. To provide a snapshot of published literature on the provision of reperfusion services globally, including when facilitated by telemedicine or mobile stroke unit services. We searched PubMed to identify original articles, published up to January 2023 for the most recent, representative, and relevant patient-level data for each country. Keywords included thrombolysis, endovascular thrombectomy and telemedicine. We also screened reference lists of review articles, citation history of articles, and the gray literature. The information is provided as a narrative summary. Of 11,222 potentially eligible articles retrieved, 148 were included for review following de-duplications and full-text review. Data were also obtained from national stroke clinical registry reports, Registry of Stroke Care Quality (RES-Q) and PRE-hospital Stroke Treatment Organization (PRESTO) repositories, and other national sources. Overall, we found evidence of the provision of intravenous thrombolysis services in 70 countries (63% high-income countries (HICs)) and endovascular thrombectomy services in 33 countries (68% HICs), corresponding to far less than half of the countries in the world. Recent data (from 2019 or later) were lacking for 35 of 67 countries with known year of data (52%). We found published data on 74 different stroke telemedicine programs (93% in HICs) and 14 active mobile stroke unit pre-hospital ambulance services (80% in HICs) around the world. Despite remarkable advancements in reperfusion therapies for stroke, it is evident from available patient-level data that their availability remains unevenly distributed globally. Contemporary published data on availability of reperfusion services remain scarce, even in HICs, thereby making it difficult to reliably ascertain current gaps in the provision of this vital acute stroke treatment around the world.

Reperfusion therapies for ischemic stroke in dementia and cognitive impairment: A systematic review and meta-analysis.

Endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT) have an unclear benefit in those with pre-stroke dementia or cognitive impairment, as these patients were often excluded from landmark stroke trials. We performed a systematic review and meta-analysis to assess the outcomes of IVT and EVT in these populations. Our systematic review, conforming to the Meta-Analysis of Observational Studies in Epidemiology guidelines, investigated studies on acute ischemic stroke patients with pre-stroke dementia or cognitive impairment treated with IVT or EVT. Primary outcome was favorable 90-day outcome (mRS 0-2). Secondary outcomes included 90-day mortality, symptomatic intracranial hemorrhage (SICH), and radiographic intracranial hemorrhage (ICH). Nine articles were identified, with five observational studies of IVT use in patients with (n = 1078) and without dementia (n = 2805) being selected for the meta-analysis. There were no significant differences in favorable outcome (adjusted OR: 0.61, 95% CI 0.24-1.59), mortality (unadjusted OR: 1.19, 95% CI 0.86-1.64), ICH (unadjusted OR: 1.32, 95% CI 0.79-2.19), and symptomatic ICH (unadjusted OR: 0.94, 95% CI 0.70-1.25) for patients undergoing IVT with pre-stroke dementia versus those without. One EVT study (n = 615 with dementia vs n = 9600 without) found no significant differences in outcomes apart from an increased odds of ICH for those with pre-existing dementia (adjusted OR: 1.57, 95% CI 1.03-2.40). A pooled analysis of three IVT studies showed no significant association of cognitive impairment (n = 93 vs n = 211 without) with all assessed outcomes, whereas a study of EVT found that pre-stroke cognitive impairment was associated with poor 90-day outcomes (mRS 3-6). These results suggest no substantial safety issues in the use of IVT or EVT for patients with pre-existing dementia or cognitive impairment compared to those without. However, the efficacy of these therapies in this demographic remains uncertain. Further rigorous studies that include a more nuanced outcome measurement approach are warranted. URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021240499.

Retracted: Predictive Value of CT Perfusion Imaging on the Basis of Automatic Segmentation Algorithm to Evaluate the Collateral Blood Flow Status on the Outcome of Reperfusion Therapy for Ischemic Stroke

Retracted: Predictive Value of CT Perfusion Imaging on the Basis of Automatic Segmentation Algorithm to Evaluate the Collateral Blood Flow Status on the Outcome of Reperfusion Therapy for Ischemic Stroke

Endovascular Reperfusion Therapy in Minor Stroke with Neurologic Deterioration beyond 24 Hours from Onset.

Patients with minor stroke (National Institutes of Health Stroke Scale score ≤5) and large vessel occlusion (LVO) often experience neurological deterioration >24 hours after onset. However, the efficacy of endovascular reperfusion therapy in these patients remains unclear. The aim of this study was to determine the efficacy and safety of reperfusion therapy in patients with minor stroke and neurological deterioration >24 hours after onset. Data were retrospectively reviewed from patients between January 2019 and April 2022 who met the following criteria: (1) minor stroke and small definitive ischemic lesions at initial visit, (2) onset to neurological deterioration >24 hours, (3) cortical signs, Alberta Stroke Program Early computed tomography (CT) Score >6 points, and large artery occlusion confirmed by CT angiography at neurological deterioration. Efficacy and safety outcomes were based on final thrombolysis in cerebral infarction (TICI), incidence of symptomatic intracranial hemorrhage (ICH), and mortality. Outcomes were assessed using the modified Rankin Scale (mRS) at 3 months. Good outcome was defined as a mRS of 0, 1, or 2. Data from 26 patients (38.4% female, mean age 75.8 years) were analyzed; 18 (69.2%) had a good outcome. A final TICI of 2b or 3 was observed in 24 (92.3%) patients. No other adverse events, including dissection, vasospasm or distal embolization, were observed during the procedures. Hemorrhagic events occurred in 8 patients after the procedure; however, there were no symptomatic ICHs. Good prognostic factors were younger age (P=0.062) and carotid stenting (P=0.025). Endovascular reperfusion therapy performed in selected patients with minor stroke, LVO, and neurological deterioration >24 hours after stroke onset demonstrated favorable outcomes and safety.

Integrated transcriptomic and proteomic profiling reveals the key molecular signatures of brain endothelial reperfusion injury.

Reperfusion therapy after ischemic stroke often causes brain microvascular injury. However, the underlying mechanisms are unclear. Transcriptomic and proteomic analyses were performed on human cerebral microvascular endothelial cells following oxygen-glucose deprivation (OGD) or OGD plus recovery (OGD/R) to identify molecules and signaling pathways dysregulated by reperfusion. Major findings were further validated in a mouse model of cerebral ischemia and reperfusion. Transcriptomic analysis identified 390 differentially expressed genes (DEGs) between the OGD/R and OGD group. Pathway analysis indicated that these genes were mostly associated with inflammation, including the TNF signaling pathway, TGF-β signaling pathway, cytokine-cytokine receptor interaction, NOD-like receptor signaling pathway, and NF-κB signaling pathway. Proteomic analysis identified 201 differentially expressed proteins (DEPs), which were primarily associated with extracellular matrix destruction and remodeling, impairment of endothelial transport function, and inflammatory responses. Six genes (DUSP1, JUNB, NFKBIA, NR4A1, SERPINE1, and THBS1) were upregulated by OGD/R at both the mRNA and protein levels. In mice with cerebral ischemia and reperfusion, brain TNF signaling pathway was activated by reperfusion, and inhibiting TNF-α with adalimumab significantly attenuated reperfusion-induced brain endothelial inflammation. In addition, the protein level of THBS1 was substantially upregulated upon reperfusion in brain endothelial cells and the peri-endothelial area in mice receiving cerebral ischemia. Our study reveals the key molecular signatures of brain endothelial reperfusion injury and provides potential therapeutic targets for the treatment of brain microvascular injury after reperfusion therapy in ischemic stroke.

Was COVID-19 Associated With Worsening Inequities in Stroke Treatment and Outcomes?

Background COVID-19 stressed hospitals and may have disproportionately affected the stroke outcomes and treatment of Black and Hispanic individuals. Methods and Results This retrospective study used 100% Medicare Provider Analysis and Review file data from between 2016 and 2020. We used interrupted time series analyses to examine whether the COVID-19 pandemic exacerbated disparities in stroke outcomes and reperfusion therapy. Among 1 142 560 hospitalizations for acute ischemic strokes, 90 912 (8.0%) were Hispanic individuals; 162 752 (14.2%) were non-Hispanic Black individuals; and 888 896 (77.8%) were non-Hispanic White individuals. The adjusted odds of mortality increased by 51% (adjusted odds ratio [aOR], 1.51 [95% CI, 1.34-1.69]; P<0.001), whereas the rates of nonhome discharges decreased by 11% (aOR, 0.89 [95% CI, 0.82-0.96]; P=0.003) for patients hospitalized during weeks when the hospital's proportion of patients with COVID-19 was >30%. The overall rates of motor deficits (P=0.25) did not increase, and the rates of reperfusion therapy did not decrease as the weekly COVID-19 burden increased. Black patients had lower 30-day mortality (aOR, 0.70 [95% CI, 0.69-0.72]; P<0.001) but higher rates of motor deficits (aOR, 1.14 [95% CI, 1.12-1.16]; P<0.001) than White individuals. Hispanic patients had lower 30-day mortality and similar rates of motor deficits compared with White individuals. There was no differential increase in adverse outcomes or reduction in reperfusion therapy among Black and Hispanic individuals compared with White individuals as the weekly COVID-19 burden increased. Conclusions This national study of Medicare patients found no evidence that the hospital COVID-19 burden exacerbated disparities in treatment and outcomes for Black and Hispanic individuals admitted with an acute ischemic stroke.

Reperfusion Therapies in Acute Ischemic Stroke Beyond the Conventional Time Window: A Narrative Review.

Stroke is the second most common cause of death worldwide, with 50% of survivors experiencing long-term disability. For more than two decades, treatment with intravenous thrombolysis (IVT) and mechanical endovascular thrombectomy (MET), the only approved stroke reperfusion therapies, was restricted to patients within the 4.5-6 hour time window, respectively. Therefore, patients who presented with acute ischemic stroke (AIS) beyond the conventionaltime window were excluded from reperfusion treatment. This narrative review aims to review the scientific literature on the possibilities of reperfusion therapies for patients who present with an unknown time of stroke onset, and those with stroke onset beyond the conventional 4.5-6 hour time window. Beyond the conventional time window, the eligibility of patients for IVT or MET, the two main therapeutic procedures, is decided based on the concept of penumbral imaging. Penumbral imaging identifies patients with hypoperfused but viable brain tissue, who could benefit from reperfusion. On the other hand, clock-based DWI-fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) can detect stroke that has occurred within 4.5 hours in patients with an unknown time of onset, including patients who awaken with stroke. The introduction of penumbral imaging and MRI-based tissue clocking as imaging biomarkers for stroke has revolutionized stroke therapy, potentially allowing for personalized treatment of eligible stroke patients.

Time to Reperfusion Is Not Associated With Functional Outcomes in First‐Pass Reperfusion: Analysis of the STRATIS Registry

Background Time is considered a fundamental driver of treatment success in ischemic stroke reperfusion therapy. First‐pass reperfusion (FPR) is associated with improved outcomes. We explored the association between time to reperfusion, FPR, and functional outcomes in an analysis of the STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) registry data. Methods Registry patients with anterior circulation stroke, treated with endovascular thrombectomy and achieving complete or near‐complete expanded Thrombolysis in Cerebral Infarction scale (eTICI) 2c/3 reperfusion per core laboratory assessment were included. FPR was considered eTICI 2c/3 reperfusion in a single device pass. Patients undergoing multipass reperfusion required ≥2 device passes to achieve the same, total, or near‐total reperfusion (eTICI 2c/3). Logistic regression was used to model functional independence, defined as a modified Rankin scale score of 0 to 2 at 3 months, as a function of time to reperfusion, comparing FPR and multipass reperfusion patient populations. Results Of the 984 patients in the STRATIS registry, 563 patients achieved eTICI 2c/3 reperfusion of anterior circulation large‐vessel occlusions and were eligible for inclusion in the analysis. In patients undergoing multipass reperfusion (n=186), increased time to treatment was associated with a decreased likelihood of a good clinical outcome. Odds ratio for every 60‐minute delay to treatment: 0.71 (95% CI, 0.55–0.90; P =0.005). However, in patients undergoing FPR (n=377), no association between increased time to treatment and good clinical outcomes was observed (odds ratio for every 60‐minute delay to treatment, 0.93 [95% CI, 0.79–1.09]; P =0.347). Conclusion First‐pass reperfusion may compensate for the effects of delays to reperfusion on functional outcomes in ischemic stroke.

Comparison of diffusion weighted imaging b0 with T2*-weighted gradient echo or susceptibility weighted imaging for intracranial hemorrhage detection after reperfusion therapy for ischemic stroke

PurposeDiffusion-weighted imaging (DWI) b0 may be able to substitute T2*-weighted gradient echo (GRE) or susceptibility-weighted imaging (SWI) in case of comparable detection of intracranial hemorrhage (ICH), thereby reducing MRI examination time. We evaluated the diagnostic accuracy of DWI b0 compared to T2*GRE or SWI for detection of ICH after reperfusion therapy for ischemic stroke.MethodsWe pooled 300 follow-up MRI scans acquired within 1 week after reperfusion therapy. Six neuroradiologists each rated DWI images (b0 and b1000; b0 as index test) of 100 patients and, after a minimum of 4 weeks, T2*GRE or SWI images (reference standard) paired with DWI images of the same patients. Readers assessed the presence of ICH (yes/no) and type of ICH according to the Heidelberg Bleeding Classification. We determined the sensitivity and specificity of DWI b0 for detection of any ICH, and the sensitivity for detection of hemorrhagic infarction (HI1 & HI2) and parenchymal hematoma (PH1 & PH2).ResultsWe analyzed 277 scans of ischemic stroke patients with complete image series and sufficient image quality (median age 65 years [interquartile range, 54–75], 158 [57%] men). For detection of any ICH on DWI b0, the sensitivity was 62% (95% CI: 50–76) and specificity 96% (95% CI: 93–99). The sensitivity of DWI b0 was 52% (95% CI: 28–68) for detection of hemorrhagic infarction and 84% (95% CI: 70–92) for parenchymal hematoma.ConclusionDWI b0 is inferior for detection of ICH compared to T2*GRE/SWI, especially for smaller and more subtle hemorrhages. Follow-up MRI protocols should include T2*GRE/SWI for detection of ICH after reperfusion therapy.

Grey-Turner sign disclosing ischemic stroke reperfusion therapy complication.

Grey-Turner sign disclosing ischemic stroke reperfusion therapy complication.

Repurposing the KCa3.1 Blocker Senicapoc for Ischemic Stroke

Senicapoc, a small molecule inhibitor of the calcium-activated potassium channel KCa3.1, was safe and well-tolerated in clinical trials for sickle cell anemia. We previously reported proof-of-concept data suggesting that both pharmacological inhibition and genetic deletion of KCa3.1 reduces infarction and improves neurologic recovery in rodents by attenuating neuroinflammation. Here we evaluated the potential of repurposing senicapoc for ischemic stroke. In cultured microglia, senicapoc inhibited KCa3.1 currents with an IC50 of 7 nM, reduced Ca2+ signaling induced by the purinergic agonist ATP, suppressed expression of pro-inflammatory cytokines and enzymes (iNOS and COX-2), and prevented induction of the inflammasome component NLRP3. When transient middle cerebral artery occlusion (tMCAO, 60 min) was induced in male C57BL/6 J mice, twice daily administration of senicapoc at 10 and 40 mg/kg starting 12 h after reperfusion dose-dependently reduced infarct area determined by T2-weighted magnetic resonance imaging (MRI) and improved neurological deficit on day 8. Ultra-high-performance liquid chromatography/mass spectrometry analysis of total and free brain concentrations demonstrated sufficient KCa3.1 target engagement. Senicapoc treatment significantly reduced microglia/macrophage and T cell infiltration and activation and attenuated neuronal death. A different treatment paradigm with senicapoc started at 3 h and MRI on day 3 and day 8 revealed that senicapoc reduces secondary infarct growth and suppresses expression of inflammation markers, including T cell cytokines in the brain. Lastly, we demonstrated that senicapoc does not impair the proteolytic activity of tissue plasminogen activator (tPA) in vitro. We suggest that senicapoc could be repurposed as an adjunctive immunocytoprotective agent for combination with reperfusion therapy for ischemic stroke.

Experience with non-immunogenic staphylokinase for intravenous thrombolysis in ischemic stroke: analysis of hospital registry data

Introduction. Intravenous thrombolysis (IT) is the primary method of reperfusion therapy for ischemic stroke. Over the past couple of years, there has been a global trend towards the predominant use of the bolus forms of thrombolytic drugs that is caused by necessity to increase the reperfusion therapy rate to achieve its best outcomes.Aim. To evaluate the efficacy and safety of the use of non-immunogenic staphylokinase for IT in ischemic stroke in real-world clinical practice of the regional vascular center.Materials and methods. The clinical outcomes of the cohort of 50 patients who underwent IT with non-immunogenic staphylokinase were analysed.Results. The age of the patients ranged from 46 to 94 years and averaged 71.8 ± 10.0 years; 22% of patients were over 80 years of age. The NIHSS score at admission varied from 3 to 23 scores and averaged 11 (8-14) scores. 36% of patients had large artery occlusions. 14% of patients received a step-wise reperfusion therapy. The median door-to-needle time was 23 (18-26) minutes. 52% of patients didn’t develop any infarction area during control neuroimaging. 62% of patients required no further rehabilitation. Hospital mortality was 12%. 18% of patients developed hemorrhagic conversion mainly in the form of hemorrhagic infarction. 1 patient had a symptomatic hemorrhagic conversion. Major bleeding and angioedema were not observed.Conclusion. The analysis of 50 consecutive cases of IT in ischemic stroke using non-immunogenic staphylokinase indicates the high efficiency and safety of this method of reperfusion therapy.

Racial and Ethnic Disparities in Stroke Reperfusion Therapy in the USA.

Racial and ethnic inequities in stroke care are ubiquitous. Acute reperfusion therapies, i.e., IV thrombolysis (IVT) and mechanical thrombectomy (MT), are central to acute stroke care and are highly efficacious at preventing death and disability after stroke. Disparities in the use of IVT and MT in the USA are pervasive and contribute to worse outcomes among racial and ethnic minority individuals with ischemic stroke. A meticulous understanding of disparities and underlying root causes is necessary in order to develop targeted mitigation strategies with lasting effects. This review details racial and ethnic disparities in the use of IVT and MT after stroke and highlights inequities in the underlying process measures as well as the contributing root causes. Furthermore, this review spotlights the systemic and structural inequities that contribute to race-based differences in the use of IVT and MT, including geographic and regional differences and differences based on neighborhood, zip code, and hospital type. In addition, recent promising trends suggesting improvements in racial and ethnic IVT and MT disparities and potential approaches for future solutions to achieve equity in stroke care are briefly discussed.

Clinical Biomarkers and Prediction Models for Poststroke Epilepsy: Have We Settled the Scores Yet?

In an era of time-dependent reperfusion and recanalization therapy for stroke leading to improved survival, there is a growing population at risk of poststroke epilepsy (PSE). Accumulating evidence suggests a multidirectional interaction among stroke, PSE, and dementia in stroke survivors. There is no evidence to justify prophylactic antiseizure medication (ASM) to reduce these morbidities. Although several predictive molecular biomarkers and scoring models have been proposed, they remain inadequately validated for stratifying risk and indicating who will benefit from prophylactic ASM. Studies leveraging advances in genetics, metabolomics, electrophysiology, imaging, and artificial intelligence (AI) may help to discover noninvasive molecular biomarkers and easy-to-score models. These discoveries should improve our understanding of epileptogenesis in PSE and identify new pharmacologic targets. Besides, accurately identifying high-risk patients and timely initiating prophylactic ASM therapy has the potential to disrupt the feed-forward multidirectional interaction among stroke, PSE, and dementia.

Kv1.3 as a therapeutic target for immunocytoprotection after reperfusion in ischemic stroke.

The voltage-gated potassium channel Kv1.3, which is expressed on activated, disease-associated microglia and memory T cells, constitutes an attractive target for immunocytoprotection after endovascular thrombectomy (EVT). Using young male mice and rats we previously demonstrated that the Kv1.3 blocker PAP-1 when started 12 hours after reperfusion dose-dependently reduces infarction and improves neurological deficit on day-8 after ischemic stroke. However, these proof-of-concept findings are of limited translational value because the majority of strokes occur in patients over 65 and, when considering overall lifetime risk, in females. We therefore tested whether Kv1.3 deletion or delayed pharmacological therapy would be beneficial in females and aged animals. Transient middle cerebral artery occlusion (tMCAO, 60-min) was induced in 16-week and 80-week-old male and female wild-type C57BL/6J and Kv1.3-/- mice. Stroke outcomes were assessed daily with the 14-score tactile and proprioceptive limp-placing test and on day-8 by T2-weighted MRI. Young and old female mice were treated twice daily with 40 mg/kg of the Kv1.3 blocker PAP-1 starting 12 hours after reperfusion. Kv1.3 deletion provided no significant benefit in young females but improved outcomes in young males, old males and old females compared with wild-type controls of the same sex. PAP-1 treatment improved outcomes in both young and old females. In old females, Kv1.3 deletion and PAP-1 treatment significantly reduced microglia activation and T cell infiltration in the infarcted hemisphere. Our preclinical studies using aged and female mice further validate Kv1.3 inhibitors as potential adjunctive treatments for reperfusion therapy in stroke by providing both genetic and pharmacological verification. Using young male rats, we further explored the treatment window for Kv1.3 inhibitors and found that PAP-1 treatment still provided benefit and reduced inflammatory marker expression in the brain when started 72 hours after reperfusion.