Real-world setting comparison of bridging therapy versus direct mechanical thrombectomy for acute ischemic stroke: A meta-analysis.

BACKGROUND AND PURPOSE: Intravenous Thrombolysis (IVT) prior to Mechanical Thrombectomy (MT) for Acute Ischaemic Stroke (AIS) due to Large-Vessel Occlusion (LVO) remains controversial. Therefore, the authors performed a meta-analysis of the available real-world evidence focusing on the efficacy and safety of Bridging Therapy (BT) compared with direct MT in patients with AIS due to LVO. METHODS: Four databases were searched until 01 February 2023. Retrospective and prospective studies from nationwide or health organization registry databases that compared the clinical outcomes of BT and direct MT were included. Odds Ratios (ORs) and 95 % Confidence Intervals (CIs) for efficacy and safety outcomes were pooled using a random-effects model. RESULTS: Of the 12 studies, 86,695 patients were included. In patients with AIS due to LVO, BT group was associated with higher odds of achieving excellent functional outcome (modified Rankin Scale score 0-1) at 90 days (OR = 1.48, 95 % CI 1.25-1.75), favorable discharge disposition (to the home with or without services) (OR = 1.33, 95 % CI 1.29-1.38), and decreased mortality at 90 days (OR = 0.62, 95 % CI 0.56-0.70), as compared with the direct MT group. In addition, the risk of symptomatic intracranial hemorrhage did not increase significantly in the BT group. CONCLUSION: The present meta-analysis indicates that BT was associated with favorable outcomes in patients with AIS due to LVO. These findings support the current practice in a real-world setting and strengthen their validity. For patients eligible for both IVT and MT, BT remains the standard treatment until more data are available.

Is time really brain in stroke therapy?: A meta-analysis of mechanical thrombectomy up to 155 h post ictus.

BACKGROUND AND OBJECTIVES: Mechanical thrombectomy (MT) has been established as the gold standard of treatment for patients with Acute Ischemic Stroke (AIS) who present up to 6 h after the onset of the stroke. Recently, the DEFUSE-3 and DAWN trials established the safety of starting the MT procedure up to 16 and 24 h after the patient was last seen well, respectively. The purpose of this study is to assess the safety and functional effects of thrombectomy in individuals with AIS detected at a late stage (> 24 h). MATERIALS AND METHODS: PubMed, Web of Science, Embase, and Cochrane databases were thoroughly searched for research on MT in patients in the extremely late time window after AIS. The primary outcomes were symptomatic cerebral hemorrhage, 90-day mortality, Thrombolysis in Cerebral Infarction (TICI) 2b-3, and Modified Rankin Scale (mRS) 0-2. RESULTS: Our study included fifteen studies involving a total of 1,221 patients who presented with AIS and an extended time window. The primary outcome of interest was the favorable functional outcome, mRS 0-2 at 90 days. The pooled proportion for this outcome was 45% (95% confidence interval 34-58%). Other outcomes included the TICI 2b or 3 (successful recanalization), which was reported in 12 studies and had a 79% incidence in the study population (95% CI 68-87%). Complications included: symptomatic intracranial hemorrhage (sICH), which revealed an incidence of 7% in the study population (95% CI 5-10%); and 90-day mortality, which reported a 27% incidence (95% CI 24-31%). In addition, we conducted a comparative analysis between endovascular treatment and standard medical therapy. CONCLUSION: Our meta-analysis provides evidence that supports the need of further randomized and prospective clinical trials to better assess the effectiveness and safety of MT in these patients.

Mechanical Thrombectomy for Aseptic, Atraumatic, Medically Refractory Cerebral Venous Sinus Thrombosis: a Systematic Review.

BACKGROUND: Cerebral venous sinus thrombosis (CVST) follows a severe clinical course in 13.5% of cases. Practice guidelines recommend endovascular therapy (EVT); no randomised control trials (RCTs) exist comparing EVTs. PURPOSE: To determine whether specific EVTs are superior to alternatives. DATA SOURCES: CENTRAL, Medline, Embase, five other databases and four clinical trials registers. Grey literature searches, reference checking, citation searching, and author contact. STUDY SELECTION: All CVST cases treated with mechanical thrombectomy (MT) were includible. Paediatric, and trauma-related or infection-related thromboses were excluded. DATA ANALYSIS: Standard Cochrane review procedures. Primary outcome measures; clinical efficacy (modified Rankin Score, mRS), technical efficacy (recanalisation), and clinical safety (procedure-related complications and death). Subgroup analyses were performed, comparing outcome measures between demographic groups, clinico-radiological severity, interventional strategies, and degrees of recanalisation. DATA SYNTHESIS: In this study 124 papers were included (n = 486). All patients underwent MT, with 69.5% of patients receiving concomitant chemolysis. New/expanding intracerebral haemorrhage (ICH) occurred in 5.1%; non-haemorrhagic complications in 1.4%; 10.7% died. Predictors of poor efficacy included age ≥ 55 years, altered mental status (AMS), Glasgow Coma Scale (GCS) < 8. Predictive of poor safety outcomes included pre-existing ICH, deep system thrombosis, and AMS. Complete recanalisation was associated with improved clinical efficacy and safety outcomes. LIMITATIONS: The review is based on case reports/series, increasing bias-risk. Myriad of potentially includible studies were necessarily excluded due to lack of requisite details. CONCLUSION: Predictors of poor outcomes with medical therapy predict poor outcomes with MT; these measures should not dictate candidacy. Complete recanalisation predicts favorable clinical and safety outcomes. Local chemolysis is safe, improves recanalisation, and should be recommended, provided there is no contraindication. Clot maceration strategies and stent-retriever thrombectomy are associated with superior clinical efficacy and safety endpoints, as compared with balloon angioplasty and rheolysis.

MicroCT and Histological Analysis of Clot Composition in Acute Ischemic Stroke : A Comparative Study of MT-Retrieved Clots and Clot Analogs.

PURPOSE: Assessing clot composition on prethrombectomy computed tomography (CT) imaging may help in stroke treatment planning. In this study we seek to use microCT imaging of fabricated blood clots to understand the relationship between CT radiographic signals and the biological makeup. METHODS: Clots (n = 10) retrieved by mechanical thrombectomy (MT) were collected, and 6 clot analogs of varying RBC composition were made. We performed paired microCT and histological image analysis of all 16 clots using a ScanCo microCT 100 (4.9 µm resolution) and standard H&E staining (imaged at 40×). From these data types, first order statistic (FOS) radiomics were computed from microCT, and percent composition of RBCs (%RBC) was computed from histology. Polynomial and linear regression (LR) were used to build statistical models based on retrieved thrombus microCT and %RBC that were evaluated for their ability to predict the %RBC of clot analogs from mean HU. Correlation analyses of microCT FOS with composition were completed for both retrieved clots and analogs. RESULTS: The LR model fits relating MT-retrieved clot %RBC with mean (R2 = 0.625, p = 0.006) and standard deviation (R2 = 0.564, p < 0.05) in HUs on microCT were significant. Similarly, LR models relating analog histological %RBC to analog protocol %RBC (R2 = 0.915, p = 0.003) and mean HUs on microCT (R2 = 0.872, p = 0.007) were also significant. When the LR model built using MT-retrieved clots was used to predict analog %RBC from mean HUs, significant correlation was observed between predictions and actual histological %RBC (R2 = 0.852, p = 0.009). For retrieved clots, significant correlations were observed for energy and total energy with %RBC and %FP (|R| > 0.7, q < 0.01). Analogs further demonstrated significant correlation between FOS energy, total energy, variance and %WBC (|R| > 0.9, q < 0.01). CONCLUSION: MicroCT can be used to build models that predict AIS clot composition from routine CT parameters and help us to better understand radiomic signatures associated with clot composition and first pass outcomes. In future work, such observations can be used to better infer clot composition and inform thrombectomy prognostics from pretreatment CTs.

The role of intravenous thrombolysis before mechanical Thrombectomy: A subgroup analysis of the RESILIENT trial.

BACKGROUND: Randomized trials have recently evaluated the non-inferiority of direct thrombectomy versus intravenous thrombolysis (IVT) followed by endovascular therapy in anterior circulation large vessel occlusion (LVO) stroke in patients eligible for IVT within 4.5 h from stroke onset with controversial results. We aimed to assess the effect of IVT on the clinical outcome of mechanical thrombectomy (MT) in the RESILIENT trial. METHODS: RESILIENT was a randomized, prospective, multicenter, controlled trial assessing the safety and efficacy of thrombectomy versus medical treatment alone. A total of 221 patients were enrolled. The trial showed a substantial benefit of MT when added to medical management. All eligible patients received intravenous tPA within the 4.5-h-window. Ordinal logistic and binary regression analyses using intravenous tPA as an interaction term were performed with adjustments for potential confounders, including age, baseline NIHSS score, occlusion site, and ASPECTS. A p-value <0.05 was considered statistically significant. RESULTS: Among 221 randomized patients (median NIHSS, 18 IQR [14-21]), 155 (70%) were treated with IVT. There was no difference in the mRS ordinal shift and frequency of functional independence between patients who received or not IV tPA; the odds ratio for the ordinal mRS shift was 2.63 [1.48-4.69] for the IVT group and 1.54 [0.63-3.74] for the no IVT group, with a p-value of 0.42. IVT also did not affect the frequency of good recanalization (TICI 2b or higher) and hemorrhagic transformation. CONCLUSIONS: The large effect size of MT on LVO outcomes was not significantly affected by IVT. TRIAL REGISTRATION: RESILIENT ClinicalTrials.gov number, NCT02216643.

Mechanical thrombectomy with intra-arterial thrombolysis versus mechanical thrombectomy alone in patients with acute ischemic stroke: A systematic review and meta-analysis.

BACKGROUND: There is conflicting evidence as to whether intra-arterial thrombolysis (IAT) adds benefit in patients with acute stroke who undergo mechanical thrombectomy (MT). METHODS: We conducted a systematic review to identify studies that evaluate IAT in patients with acute stroke who undergo MT. Data were extracted from relevant studies found through a search of PubMed, Scopus, and Web of Science until February 2023. Statistical pooling with random effects meta-analysis was undertaken to evaluate odds of functional independence, mortality, and near-complete or complete angiographic recanalization with IAT compared to no IAT. RESULTS: A total of 18 studies were included (3 matched, 14 unmatched, and 1 randomized). The odds ratio (OR) for functional independence (modified Rankin Scale: 0-2) at 90 days was 1.14 (95% confidence interval (CI): 0.95-1.37, p = 0.17, 16 studies involving 7572 patients) with IAT with moderate between-study heterogeneity (I2 = 38.1%). The OR for functional independence with IAT was 1.28 (95% CI: 0.92-1.78, p = 0.15) in studies that were either matched or randomized and 1.24 (95% CI: 0.97-1.58, p = 0.08) in studies with the highest quality score. IAT was associated with higher odds of near-complete or complete angiographic recanalization (OR: 1.65, 95% CI: 1.03-2.65, p = 0.04) in studies that were either matched or of randomized comparisons. CONCLUSION: Although the odds of functional independence appeared to be higher with IAT and MT compared with MT alone, none of the results were statistically significant. A prominent effect of the design and quality of the studies was observed on the association between IAT and functional independence at 90 days.

Effects of intravenous thrombolysis on stent retriever and aspiration thrombectomy outcomes: a systematic review and meta-analysis of the randomized controlled trials.

BACKGROUND: Risks and benefits of intravenous thrombolysis (IVT) in patients undergoing mechanical thrombectomy (MT) have been a topic of interest. However, IVT's specific effects on stent retriever (SR) and aspiration thrombectomy (ASP) outcomes remain largely unexplored. In this meta-analysis, we aimed to investigate the effects of IVT on SR and ASP thrombectomy outcomes. METHODS: In accordance with PRISMA guidelines, a systematic literature review was conducted using Medline, Embase, Scopus, Web of Science, and Cochrane Center of Clinical Trials databases. Outcomes of interest included successful recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b), modified first pass efficacy (mFPE), functional independence (modified Rankin Scale (mRS) ≤2), symptomatic intracranial hemorrhage (sICH), and embolization to new territories (ENT). RESULTS: Four randomized controlled trials with 1176 patients were included. SR and ASP resulted in similar mTICI ≥2b, mFPE, and mRS 0-2 rates in patients with and without IVT administration. SR without IVT was associated with a significantly lower rate of mFPE compared with the SR+IVT (RR 0.85, 95% CI 0.74 to 0.97). Furthermore, ASP without IVT resulted in a lower rate of mRS 0-2 than the ASP+IVT with a strong trend towards significance (RR 0.78, 95% CI 0.60 to 1.01). Finally, bridging therapy did not increase sICH and ENT rates after ASP or SR thrombectomy. CONCLUSIONS: Our findings suggest that SR and ASP thrombectomy have comparable safety and efficacy profiles, regardless of prior IVT administration. Additionally, our results indicate that the addition of IVT may improve certain efficacy outcomes based on the employed first-line MT technique.

The utility of NIRS in follow-up of patients with acute ischaemic stroke treated with IV thrombolysis and mechanical thrombectomy in the emergency department.

Revascularization treatments (IV thrombolysis, mechanical thrombectomy) related to ischemic stroke have developed in recent years. With devices such as NIRS, non-invasive monitoring of treatment efficacy is provided. In this study, we aimed to use near-infrared spectroscopy (NIRS) as an objective monitoring method to see the effect of intravenous (IV) thrombolysis or mechanical thrombectomy treatments applied for cerebral oxygenation in patients with acute ischemic stroke. This study was carried out as a prospective study involving patients admitted to the emergency department in the years 2021-2022. NIRS measured regional oxygen saturation (rSO2) of both hemispheres of the brain before IV thrombolysis treatment, during the treatment at 0. min, 15. min, 30. min, 45. min, 60. min, after the treatment, and before and after the mechanical thrombectomy procedure. The significance level of the change in rSO2 values measured by NIRS was examined. 80 patients were included in the study. IV thrombolysis was applied to 58 patients, mechanical thrombectomy was applied to 5 of them, and both treatments were applied to 17 of them. In patients receiving IV thrombolysis, a significant difference was found in the affected hemisphere between the NIRS values measured at 0.min-15.min, 0.min-30.min, 0.min-45.min, 0.min-60.min, 0.min-post-treatment, 15.min-60.min (p < 0.001). In the patients included in the study, there was a strong and significant negative correlation between the deltaNIHSS value and the deltaNIRS values in the affected hemisphere (r=- 0.307, p = 0.013). There was a significant increase in the NIRS measurement values during and after the IV thrombolysis treatment in the affected hemisphere in the group with clinical improvement (p < 0.001). It is thought that IV thrombolysis or mechanical thrombectomy treatment applied to patients admitted to the emergency department with acute ischemic stroke can be followed objectively by NIRS.

Safety Outcomes of Mechanical Thrombectomy Versus Combined Thrombectomy and Intravenous Thrombolysis in Tandem Lesions.

BACKGROUND: We aimed to describe the safety and efficacy of mechanical thrombectomy (MT) with or without intravenous thrombolysis (IVT) for patients with tandem lesions and whether using intraprocedural antiplatelet therapy influences MT's safety with IVT treatment. METHODS: This is a subanalysis of a pooled, multicenter cohort of patients with acute anterior circulation tandem lesions treated with MT from 16 stroke centers between January 2015 and December 2020. Primary outcomes included symptomatic intracranial hemorrhage (sICH) and parenchymal hematoma type 2. Additional outcomes included hemorrhagic transformation, successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b-3), complete reperfusion (modified Thrombolysis in Cerebral Infarction score 3), favorable functional outcome (90-day modified Rankin Scale score 0-2), excellent functional outcome (90-day modified Rankin Scale score 0-1), in-hospital mortality, and 90-day mortality. RESULTS: Of 691 patients, 512 were included (218 underwent IVT+MT and 294 MT alone). There was no difference in the risk of sICH (adjusted odds ratio [aOR], 1.22 [95% CI, 0.60-2.51]; P=0.583), parenchymal hematoma type 2 (aOR, 0.99 [95% CI, 0.47-2.08]; P=0.985), and hemorrhagic transformation (aOR, 0.95 [95% CI, 0.62-1.46]; P=0.817) between the IVT+MT and MT alone groups after adjusting for confounders. Administration of IVT was associated with an increased risk of sICH in patients who received intravenous antiplatelet therapy (aOR, 3.04 [95% CI, 0.99-9.37]; P=0.05). The IVT+MT group had higher odds of a 90-day modified Rankin Scale score 0 to 2 (aOR, 1.72 [95% CI, 1.01-2.91]; P=0.04). The odds of successful reperfusion, complete reperfusion, 90-day modified Rankin Scale score 0 to 1, in-hospital mortality, or 90-day mortality did not differ between the IVT+MT versus MT alone groups. CONCLUSIONS: Our study showed that the combination of IVT with MT for tandem lesions did not increase the overall risk of sICH, parenchymal hematoma type 2, or overall hemorrhagic transformation independently of the cervical revascularization technique used. However, intraprocedural intravenous antiplatelet therapy during acute stent implantation might be associated with an increased risk of sICH in patients who received IVT before MT. Importantly, IVT+MT treatment was associated with a higher rate of favorable functional outcomes at 90 days.

Thrombolysis and thrombectomy for stroke in octogenarians and nonagenarians: A regional observational study.

INTRODUCTION: Elderly patients are a growing population in stroke units, characterized by higher frailty, but underrepresented in clinical trials about acute care. We investigated efficacy of intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) in elderlies in current practice. METHODS: We assessed consecutive patients with acute ischemic stroke (AIS) hospitalized in the four stroke units of the French Northern Alps Emergency Network between 2015 and 2020. We compared baseline characteristics, early neurological evolution and outcome of patients aged 80-89 and≥90years old (yo). RESULTS: Among 8367 patients, 2744 (32.8%) were 80-89 yo and 541 (6.5%) were≥90 yo. IVT and/or MT were performed in 787 patients≥80 yo (632 patients aged 80-89, 155 patients aged>90). Early neurological improvement was more frequent in patients≥80 yo treated by IVT and/or MT compared to untreated patients (45.6% versus 38.4%, P=0.002). After adjustment, reperfusion treatments improved likelihood of good outcome at discharge (OR=2.0 [1.6-2.7]) and reduced in-hospital mortality (OR=0.5 [0.4-0.7]). Age and initial NIHSS score were independent factors of poor functional outcome at discharge and in-hospital mortality. The rate of successful recanalization was comparable between octogenarians and nonagenarians (87% versus 85.2%, P=0.8). Octogenarians had better functional outcome at discharge compared to nonagenarians [modified Rankin scale (mRS) 0-2: 36% versus 25.7%, P=0.02], whatever IVT or MT strategy. In-hospital mortality was lower for octogenarians compared to nonagenarians (19.5% versus 27.1%, P=0.04). DISCUSSION: IVT and MT improve early neurological recovery and functional outcome at discharge of both octogenarians and nonagenarians in current practice. Despite a poorer outcome for nonagenarians than octogenarians, these reperfusion treatments should not be withheld on the basis of age only.

IV thrombolysis plus thrombectomy versus IV thrombolysis alone for minor stroke with anterior circulation large vessel occlusion from the IRETAS and Italian SITS-ISTR cohorts.

INTRODUCTION: The aim of this study was to compare the outcomes of patients treated with intravenous thrombolysis (IVT) <4.5 h after symptom onset plus mechanical thrombectomy (MT) <6 h with those treated with IVT alone <4.5 h for minor stroke (NIHSS ≤5) with large vessel occlusion (LVO) in the anterior circulation. PATIENTS AND METHODS: Patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) and in the Italian centers included in the SITS-ISTR were analyzed. RESULTS: Among the patients with complete data on 24-h ICH type, 236 received IVT plus MT and 382 received IVT alone. IVT plus MT was significantly associated with unfavorable shift on 24-h ICH types (from no ICH to PH-2) (OR, 2.130; 95% CI, 1.173-3.868; p=0.013) and higher rate of PH (OR, 4.363; 95% CI, 1.579-12.055; p=0.005), sICH per ECASS II definition (OR, 5.527; 95% CI, 1.378-22.167; p=0.016), and sICH per NINDS definition (OR, 3.805; 95% CI, 1.310-11.046; p=0.014). Among the patients with complete data on 3-month mRS score, 226 received IVT plus MT and 262 received IVT alone. No significant difference was reported between IVT plus MT and IVT alone on mRS score 0-1 (72.1% versus 69.1%), mRS score 0-2 (79.6% versus 79%), and death (6.2% versus 6.1%). CONCLUSIONS: Compared with IVT alone, IVT plus MT was associated with unfavorable shift on 24-h ICH types and higher rate of 24-h PH and sICH in patients with minor stroke and LVO in the anterior circulation. However, no difference was reported between the groups on 3-month functional outcome measures.

Stroke with large vessel occlusion in the posterior circulation: IV thrombolysis plus thrombectomy versus IV thrombolysis alone.

Efficacy and safety of mechanical thrombectomy (MT) for stroke with posterior circulation large vessel occlusion (LVO) is still under debate. We aimed to compare the outcomes of stroke patients with posterior circulation LVO treated with intravenous thrombolysis (IVT) (< 4.5 h after symptom onset) plus MT < 6 h after symptom onset with those treated with IVT alone (< 4.5 h after symptom onset). Patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) and in the Italian centers included in the SITS-ISTR were analysed. We identified 409 IRETAS patients treated with IVT plus MT and 384 SITS-ISTR patients treated with IVT alone. IVT plus MT was significantly associated with higher rate of sICH (ECASS II) compared with IVT alone (3.1 vs 1.9%; OR 3.984, 95% CI 1.014-15.815), while the two treatments did not differ significantly in 3-month mRS score ≤ 3 (64.3 vs 74.1%; OR 0.829, 95% CI 0.524-1.311). In 389 patients with isolated basilar artery (BA) occlusion, IVT plus MT was significantly associated with higher rate of any ICH compared with IVT alone (9.4 vs 7.4%; OR 4.131, 95% CI 1.215-14.040), while two treatments did not differ significantly in 3-month mRS score ≤ 3 and sICH per ECASS II definition. IVT plus MT was significantly associated with higher rate mRS score ≤ 2 (69.1 vs 52.1%; OR 2.692, 95% CI 1.064-6.811) and lower rate of death (13.8 vs 27.1%; OR 0.299, 95% CI 0.095-0.942) in patients with distal-segment BA occlusion, while two treatments did not differ significantly in 3-month mRS score ≤ 3 and sICH per ECASS II definition. IVT plus MT was significantly associated with lower rate of mRS score ≤ 3 (37.1 vs 53.3%; OR 0.137, 0.009-0.987), mRS score ≤ 1 (22.9 vs 53.3%; OR 0.066, 95% CI 0.006-0.764), mRS score ≤ 2 (34.3 vs 53.3%; OR 0.102, 95% CI 0.011-0.935), and higher rate of death (51.4 vs 40%; OR 16.244, 1.395-89.209) in patients with proximal-segment BA occlusion. Compared with IVT alone, IVT plus MT was significantly associated with higher rate of sICH per ECASS II definition in patients with stroke and posterior circulation LVO, while two treatment groups did not differ significantly in 3-month mRS score ≤ 3. IVT plus MT was associated with lower rate of mRS score ≤ 3 compared with IVT alone in patients with proximal-segment BA occlusion, whereas no significant difference was found between the two treatments in primary endpoints in patients isolated BA occlusion and in the other subgroups based on site occlusion.

Mechanical Thrombectomy with Intravenous Thrombolysis versus Thrombolysis Alone for the Treatment of Stroke: A Systematic Review of Economic Evaluations.

Mechanical thrombectomy has revolutionized the management of stroke by improving the recanalization rates and reducing deleterious consequences. It is now the standard of care despite the high financial cost. A considerable number of studies have evaluated its cost effectiveness. Therefore, this study aimed to identify economic evaluations of mechanical thrombectomy with thrombolysis compared with thrombolysis alone to provide an update of existing evidence, focusing on the period after proof of effectiveness of mechanical thrombectomy. Twenty-one studies were included in the review: 18 were model-based economic evaluations to simulate long-term outcomes and costs, and 19 were conducted in high-income countries. Incremental cost-effectiveness ratios ranged from -$5,670 to $74,216 per quality-adjusted life year. Mechanical thrombectomy is cost-effective in high-income countries and in the populations selected for clinical trials. However, most of the studies used the same data. There is a lack of real-world and long-term data to analyze the cost effectiveness of mechanical thrombectomy in treating the global burden of stroke.

The safety and efficacy of hypothermia combining mechanical thrombectomy or thrombolysis in the treatment of ischemic stroke: A systematic meta-analysis.

BACKGROUND: Stroke is a major global public health problem, affecting 13.7 million people worldwide. Previous studies have found a neuroprotective effect of hypothermia therapy and the efficacy and safety of combined hypothermia and mechanical thrombectomy or thrombolysis in the treatment of ischemic stroke have also attracted attention. OBJECTIVE: In the present research, the authors conducted a meta-analysis to comprehensively assess the safety and efficacy of hypothermia combining mechanical thrombectomy or thrombolysis in the treatment of ischemic stroke. METHODS: Articles published from January 2001 to May 2022 were searched from Google Scholar, Baidu Scholar and PubMed to evaluate the clinical significance of hypothermia treatment in ischemic stroke. Complications, short-term mortality, and the modified Rankin Scale (mRS) in the full text was extracted. RESULTS: 89 publications were selected and 9 among them were included in this study with sample size of 643. All selected studies are in accordance with the inclusion criteria. Forest plot of clinical characteristics was as follows: complications (RR = 1.132, 95% CI 0.942‒1.361, p = 0.186, I2 = 37.2%), mortality within 3 months (RR = 1.076, 95% CI 0.694‒1.669, p = 0.744, I2 = 0.00%), mRS ≤ 1 at 3 months (RR = 1.138, 95% CI 0.829‒1.563, p = 0.423, I2 = 26.0%), mRS ≤ 2 at 3 months (RR = 1.672, 95% CI 1.236‒2.263, p = 0.001, I2=49.6%) and mRS ≤ 3 at 3 months (RR = 1.518, 95% CI 1.128‒2.043, p = 0.006, I2 = 0.00%). The funnel plot suggested that there was no significant publication bias in the meta-analysis on complications, mortality within 3 months, mRS ≤ 1 at 3 months and mRS ≤ 2 at 3 months. CONCLUSION: In summary, the results showed that hypothermia treatment was correlated with mRS ≤ 2 at 3 months, but not linked with complications and mortality within 3 months.

Association Between Intravenous Thrombolysis and Clinical Outcomes Among Patients With Ischemic Stroke and Unsuccessful Mechanical Reperfusion.

Importance: Clinical evidence of the potential treatment benefit of intravenous thrombolysis preceding unsuccessful mechanical thrombectomy (MT) is scarce. Objective: To determine whether intravenous thrombolysis (IVT) prior to unsuccessful MT improves functional outcomes in patients with acute ischemic stroke. Design, Setting, and Participants: Patients were enrolled in this retrospective cohort study from the prospective, observational, multicenter German Stroke Registry-Endovascular Treatment between May 1, 2015, and December 31, 2021. This study compared IVT plus MT vs MT alone in patients with acute ischemic stroke due to anterior circulation large-vessel occlusion in whom mechanical reperfusion was unsuccessful. Unsuccessful mechanical reperfusion was defined as failed (final modified Thrombolysis in Cerebral Infarction grade of 0 or 1) or partial (grade 2a). Patients meeting the inclusion criteria were matched by treatment group using 1:1 propensity score matching. Interventions: Mechanical thrombectomy with or without IVT. Main Outcomes and Measures: Primary outcome was functional independence at 90 days, defined as a modified Rankin Scale score of 0 to 2. Safety outcomes were the occurrence of symptomatic intracranial hemorrhage and death. Results: After matching, 746 patients were compared by treatment arms (median age, 78 [IQR, 68-84] years; 438 women [58.7%]). The proportion of patients who were functionally independent at 90 days was 68 of 373 (18.2%) in the IVT plus MT and 42 of 373 (11.3%) in the MT alone group (adjusted odds ratio [AOR], 2.63 [95% CI, 1.41-5.11]; P = .003). There was a shift toward better functional outcomes on the modified Rankin Scale favoring IVT plus MT (adjusted common OR, 1.98 [95% CI, 1.35-2.92]; P < .001). The treatment benefit of IVT was greater in patients with partial reperfusion compared with failed reperfusion. There was no difference in symptomatic intracranial hemorrhages between treatment groups (AOR, 0.71 [95% CI, 0.29-1.81]; P = .45), while the death rate was lower after IVT plus MT (AOR, 0.54 [95% CI, 0.34-0.86]; P = .01). Conclusions and Relevance: These findings suggest that prior IVT was safe and improved functional outcomes at 90 days. Partial reperfusion was associated with a greater treatment benefit of IVT, indicating a positive interaction between IVT and MT. These results support current guidelines that all eligible patients with stroke should receive IVT before MT and add a new perspective to the debate on noninferiority of combined stroke treatment.

Intravenous thrombolysis and mechanical recanalization for acute ischemic stroke in deep brain stimulation patients: a case series.

BACKGROUND: Intravenous thrombolysis (IVT) and endovascular mechanical thrombectomy therapy (MT) are well established in the treatment of acute ischemic stroke. It is currently unclear whether these treatments can be applied in patients with previous deep brain stimulation (DBS) surgery and how long the interval to the DBS operation should be. METHODS: Four patients with ischemic stroke and IVT or MT were included in this retrospective case series. Data on demographics, genesis, severity and course of the stroke and the DBS indication were extracted and evaluated. Furthermore, a literature review was conducted. Outcomes and hemorrhagic complications after IVT, MT or intra-arterial thrombolysis in patients with prior deep brain stimulation surgery and intracranial surgery were analyzed. RESULTS: Four patients with acute ischaemic stroke and previous DBS surgery were treated with IVT (2 patients), MT (1) or a combined therapy of IVT and MT (1). The time interval to the previous DBS surgery was between 6 and 135 months. In these four patients, no bleeding complications occurred. The literature review revealed four publications with a total of 18 patients, who were treated with IVT, MT or intra-arterial thrombolysis. Of these 18 patients, only 1 had undergone deep brain stimulation surgery, the other 17 patients had received brain surgery for other reasons. Bleeding complications occurred in four of the 18 reported patients, but not in the DBS case. All four patients with bleeding complications were reported to have died as a result. In three of the four patients with fatal outcome, surgery was less than 90 days before the onset of stroke. CONCLUSION: IVT and MT were tolerated by four patients with ischemic stroke more than 6 months after DBS surgery without bleeding complications.

Safety and Efficacy of Baseline Antiplatelet Treatment in Patients Undergoing Mechanical Thrombectomy for Ischemic Stroke: Antiplatelets Before Mechanical Thrombectomy.

PURPOSE: To investigate the safety and efficacy of baseline antiplatelet treatment in patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy (MT). MATERIALS AND METHODS: Baseline use of antiplatelet medication before MT for (AIS) may provide benefit on reperfusion and clinical outcome but could also carry an increased risk of intracranial hemorrhage (ICH). All consecutive patients with AIS and treated with MT with and without intravenous thrombolysis (IVT) between January 2012 and December 2019 in all centers performing MT nationwide were reviewed. Data were prospectively collected in national registries (eg, SITS-TBY and RES-Q). Primary outcome was functional independence (modified Rankin Scale 0-2) at 3 months; secondary outcome was ICH. RESULTS: Of the 4,351 patients who underwent MT, 1,750 (40%) and 666 (15%) were excluded owing to missing data from the functional independence and ICH outcome cohorts, respectively. In the functional independence cohort (n = 2,601), 771 (30%) patients received antiplatelets before MT. Favorable outcome did not differ in any antiplatelet, aspirin, and clopidogrel groups when compared with that in the no-antiplatelet group: odds ratio (OR), 1.00 (95% CI, 0.84-1.20); OR, 1.05 (95% CI, 0.86-1.27); and OR, 0.88 (95% CI, 0.55-1.41), respectively. In the ICH cohort (n = 3,685), 1095 (30%) patients received antiplatelets before MT. The rates of ICH did not increase in any treatment options (any antiplatelet, aspirin, clopidogrel, and dual antiplatelet groups) when compared with those in the no-antiplatelet group: OR, 1.03 (95% CI, 0.87-1.21); OR, 0.99 (95% CI, 0.83-1.18); OR, 1.10 (95% CI, 0.82-1.47); and OR, 1.43 (95% CI, 0.87-2.33), respectively. CONCLUSIONS: Antiplatelet monotherapy before MT did not improve functional independence or increase the risk of ICH.

Intra-arterial thrombolysis as adjunct to mechanical thrombectomy in acute ischemic stroke patients in the United States: A case control analysis.

BACKGROUND: Although observational studies have reported favorable clinical outcomes associated with intra-arterial thrombolysis as adjunct to mechanical thrombectomy, the cost and length of hospitalization associated with this intervention has not been studied. METHODS: We analyzed the nationally representative data of the United States data from Nationwide Inpatient Sample (NIS) to compare hospitalization cost and duration in addition to other outcomes in patients receiving (n = 1990) with those not receiving intra-arterial thrombolysis (n = 1990) in acute ischemic stroke patients undergoing mechanical thrombectomy using a case control design matched for age, gender, and presence of aphasia, hemiplegia, neglect, coma/stupor, hemianopsia and dysphagia. RESULTS: There was no difference in the median hospitalization cost in patients treated with intra-arterial thrombolysis compared with those not treated with intra-arterial thrombolysis: $36,992 [28,361 to 54,336] versus $35,440 [24,383 to 50,438], (regression coefficient 2,485 [-1,947 to 6,917], p = 0.27). There was no difference in the median length of hospitalization in patients treated with intra-arterial thrombolysis compared with those not treated with intra-arterial thrombolysis: 6 days [3 to 10] versus 6 days [4 to 10], (regression coefficient -0.34 [-1.47 to 0.80], p = 0.56). There was no difference in odds of home-discharge (OR 1.02 95%CI 0.72-1.43, p = 0.93) or post-procedural intracranial hemorrhage (OR 1.16 95%CI 0.83-1.64, p = 0.39) between the two groups. CONCLUSIONS: We did not observe an increase in the cost or length of hospitalization associated with the use of intra-arterial thrombolysis as adjunct to mechanical thrombectomy in acute ischemic stroke patients. If the ongoing randomized clinical trials demonstrate therapeutic efficacy in reducing death or disability, this intervention has a high likelihood of being beneficial overall.

Advances in the Diagnosis and Treatment of Pediatric Arterial Ischemic Stroke.

Though rare, stroke in infants and children is an important cause of mortality and chronic morbidity in the pediatric population. Neuroimaging advances and implementation of pediatric stroke care protocols have led to the ability to rapidly diagnose stroke and in many cases determine the stroke etiology. Though data on efficacy of hyperacute therapies, such as intravenous thrombolysis and mechanical thrombectomy, in pediatric stroke are limited, feasibility and safety data are mounting and support careful consideration of these treatments for childhood stroke. Recent therapeutic advances allow for targeted stroke prevention efforts in high-risk conditions, such as moyamoya, sickle cell disease, cardiac disease, and genetic disorders. Despite these exciting advances, important knowledge gaps persist, including optimal dosing and type of thrombolytic agents, inclusion criteria for mechanical thrombectomy, the role of immunomodulatory therapies for focal cerebral arteriopathy, optimal long-term antithrombotic strategies, the role of patent foramen ovale closure in pediatric stroke, and optimal rehabilitation strategies after stroke of the developing brain.

Interaction between intravenous thrombolysis and clinical outcome between slow and fast progressors undergoing mechanical thrombectomy: a post-hoc analysis of the SWIFT-DIRECT trial.

BACKGROUND: In proximal occlusions, the effect of reperfusion therapies may differ between slow or fast progressors. We investigated the effect of intravenous thrombolysis (IVT) (with alteplase) plus mechanical thrombectomy (MT) versus thrombectomy alone among slow versus fast stroke progressors. METHODS: The SWIFT-DIRECT trial data were analyzed: 408 patients randomized to IVT+MT or MT alone. Infarct growth speed was defined by the number of points of decay in the initial Alberta Stroke Program Early CT Score (ASPECTS) divided by the onset-to-imaging time. The primary endpoint was 3-month functional independence (modified Rankin scale 0-2). In the primary analysis, the study population was dichotomized into slow and fast progressors using median infarct growth velocity. Secondary analysis was also conducted using quartiles of ASPECTS decay. RESULTS: We included 376 patients: 191 IVT+MT, 185 MT alone; median age 73 years (IQR 65-81); median initial National Institutes of Health Stroke Scale (NIHSS) 17 (IQR 13-20). The median infarct growth velocity was 1.2 points/hour. Overall, we did not observe a significant interaction between the infarct growth speed and the allocation to either randomization group on the odds of favourable outcome (P=0.68). In the IVT+MT group, odds of any intracranial hemorrhage (ICH) were significantly lower in slow progressors (22.8% vs 36.4%; OR 0.52, 95% CI 0.27 to 0.98) and higher among fast progressors (49.4% vs 26.8%; OR 2.62, 95% CI 1.42 to 4.82) (P value for interaction <0.001). Similar results were observed in secondary analyses. CONCLUSION: In this SWIFT-DIRECT subanalysis, we did not find evidence for a significant interaction of the velocity of infarct growth on the odds of favourable outcome according to treatment by MT alone or combined IVT+MT. However, prior IVT was associated with significantly reduced occurrence of any ICH among slow progressors whereas this was increased in fast progressors.