Cervical Dissection in Patients With Tandem Lesions Is Associated With Distal Embolism and Lower Recanalization Success.

BACKGROUND: Tandem lesions consist of cervical internal carotid artery (ICA) stenosis or occlusion, most commonly of atherosclerosis or dissection etiology, plus a large vessel occlusion. In this study, we compare outcomes in patients with atherosclerosis versus dissection of the cervical ICA. METHODS: This multicenter retrospective cohort study includes data from tandem lesion patients who underwent endovascular treatment from 2015 to 2020. Atherosclerosis was defined as ICA stenosis/occlusion associated with a calcified lesion and dissection by the presence of a tapered or flame-shaped lesion and intramural hematoma. Primary outcome: 90-day functional independence (modified Rankin Scale score, 0-2); secondary outcomes: 90-day favorable shift in the modified Rankin Scale score, modified Thrombolysis in Cerebral Infarction score 2b-3, modified Thrombolysis in Cerebral Infarction score 2c-3, symptomatic intracranial hemorrhage, parenchymal hematoma type 2, petechial hemorrhage, distal embolization, early neurological improvement, and mortality. Analysis was performed with matching by inverse probability of treatment weighting. RESULTS: We included 526 patients (68 [59-76] years; 31% females); 11.2% presented dissection and 88.8%, atherosclerosis. Patients with dissection were younger, had lower rates of hypertension, hyperlipidemia, diabetes, and smoking history. They also exhibited higher rates of ICA occlusion, multiple stents (>1), and lower rates of carotid self-expanding stents. After matching and adjusting for covariates, there were no differences in 90-day functional independence. The rate of successful recanalization was significantly lower in the dissection group (adjusted odds ratio, 0.38 [95% CI, 0.16-0.91]; P=0.031), which also had significantly higher rates of distal emboli (adjusted odds ratio, 2.53 [95% CI, 1.15-5.55]; P=0.021). There were no differences in other outcomes. Acute ICA stenting seemed to increase the effect of atherosclerosis in successful recanalization. CONCLUSIONS: This study reveals that among patients with acute stroke with tandem lesions, cervical ICA dissection is associated with higher rates of distal embolism and lower rates of successful recanalization than atherosclerotic lesions. Using techniques to minimize the risk of distal embolism may mitigate this contrast. Further prospective randomized trials are warranted to fully understand these associations.

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.

Low dose intravenous cangrelor versus glycoprotein IIb/IIIa inhibitors in endovascular treatment of tandem lesions.

OBJECTIVES: Intravenous (IV) periprocedural antiplatelet therapy (APT) for patients undergoing acute carotid stenting during mechanical thrombectomy (MT) is not fully investigated. We aimed to compare the safety profile of IV low dose cangrelor versus IV glycoprotein IIb/IIIa (GP-IIb/IIIa) inhibitors in patients with acute tandem lesions (TLs). MATERIALS AND METHODS: We retrospectively identified all cases of periprocedural administration of IV cangrelor or GP-IIb/IIIa inhibitors during acute TLs intervention from a multicenter collaboration. Patients were divided in two groups according to the IV APT regimen at the time of MT procedure: 1) cangrelor and 2) GP-IIb/IIIa inhibitors (tirofiban and eptifibatide). Safety outcomes included rates of symptomatic intracranial hemorrhage (sICH), parenchymal hematoma type 1 and 2 (PH1-PH2), and hemorrhagic infarction type 1 and 2 (HI1-HI2). RESULTS: Sixty-three patients received IV APT during MT, 30 were in the cangrelor group, and 33 were in the GP-IIb/IIIa inhibitors group. There were no significant differences in the rates of sICH (3.3% vs. 12.1%, aOR=0.21, 95%CI 0.02-2.18, p=0.229), HI1-HI2 (21.4% vs 42.4%, aOR=0.21, 95%CI 0.02-2.18, p=0.229), and PH1-PH2 (17.9% vs. 12.1%, aOR=1.63, 95%CI 0.29-9.83, p=0.577) between both treatment groups. However, there was a trend toward reduced hemorrhage rates with cangrelor. Cangrelor was associated with increased odds of complete reperfusion (aOR=5.86; 95%CI 1.57-26.62;p=0.013). CONCLUSIONS: In this retrospective non-randomized cohort study, our findings suggest that low dose cangrelor has similar safety and increased rate of complete reperfusion compared to IV GP-IIb/IIIa inhibitors. Further prospective studies are warranted to confirm this association.

Angiography Suite Cone-Beam Computed Tomography Perfusion Imaging in Large-Vessel Occlusion Patients Using RAPID Software: A Pilot Study.

[Figure: see text].

Clinically Approximated Hypoperfused Tissue in Large Vessel Occlusion Stroke.

Background and Purpose: Patient selection for thrombectomy of acute ischemic stroke caused by large vessel occlusion in the delayed time window (>6 hours) is dependent on delineation of clinical-core mismatch or radiological target mismatch using perfusion imaging. Selection paradigms not involving advanced imaging and software processing may reduce time to treatment and broaden eligibility. We aim to develop a conversion factor to approximately determine the volume of hypoperfused tissue using the National Institutes of Health Stroke Scale (NIHSS) score (clinically approximated hypoperfused tissue [CAT] volume) and explore its ability to identify patients eligible for thrombectomy in the late-time window. Methods: We performed a retrospective analysis of anterior circulation large vessel occlusion strokes at 3 comprehensive stroke centers. Demographic, clinical, and imaging (computed tomography perfusion processed using RAPID, IschemaView) information was analyzed. A conversion factor, which is a multiple of the NIHSS score (for NIHSS score <10 and ≥10), was derived from an initial cohort to calculate CAT volumes. Accuracy of CAT-based thrombectomy eligibility criteria (using CAT volume instead of Tmax >6 seconds volume) was tested using DEFUSE-3 criteria (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) eligibility as a gold standard in an independent cohort. Results: Of the 309 large vessel occlusion strokes (age, 70±14, 46% male, median NIHSS 16 [12­20]) included in this study, 38% of patients arrived beyond 6 hours of time from last known well. Conversion factors derived (derivation cohort-center A: 187) based on median values of Tmax>6 second volume for NIHSS score <10 subgroup was 15 and for NIHSS score ≥10 subgroup was 6. Subsequently calculated CAT volume­based eligibility criteria yielded a sensitivity of 100% and specificity of 92% in detecting DEFUSE-3 eligible patients (area under the curve, 0.92 [95% CI, 0.82­1]) in the validation cohort (center B and C:122). Conclusions: Clinical severity of stroke (NIHSS score) may be used to calculate the volume of hypoperfused tissue during large vessel occlusion stroke. CAT volumes for NIHSS score <10 (using a factor of 15) and ≥10 (using a factor of 6) subgroups can accurately identify DEFUSE-3-eligible patients.

Repeated Mechanical Endovascular Thrombectomy for Recurrent Large Vessel Occlusion: A Multicenter Experience.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is now the standard of care for large vessel occlusion (LVO) stroke. However, little is known about the frequency and outcomes of repeat MT (rMT) for patients with recurrent LVO. METHODS: This is a retrospective multicenter cohort of patients who underwent rMT at 6 tertiary institutions in the United States between March 2016 and March 2020. Procedural, imaging, and outcome data were evaluated. Outcome at discharge was evaluated using the modified Rankin Scale. RESULTS: Of 3059 patients treated with MT during the study period, 56 (1.8%) underwent at least 1 rMT. Fifty-four (96%) patients were analyzed; median age was 64 years. The median time interval between index MT and rMT was 2 days; 35 of 54 patients (65%) experienced recurrent LVO during the index hospitalization. The mechanism of stroke was cardioembolism in 30 patients (56%), intracranial atherosclerosis in 4 patients (7%), extracranial atherosclerosis in 2 patients (4%), and other causes in 18 patients (33%). A final TICI recanalization score of 2b or 3 was achieved in all 54 patients during index MT (100%) and in 51 of 54 patients (94%) during rMT. Thirty-two of 54 patients (59%) experienced recurrent LVO of a previously treated artery, mostly the pretreated left MCA (23 patients, 73%). Fifty of the 54 patients (93%) had a documented discharge modified Rankin Scale after rMT: 15 (30%) had minimal or no disability (modified Rankin Scale score ≤2), 25 (50%) had moderate to severe disability (modified Rankin Scale score 3-5), and 10 (20%) died. CONCLUSIONS: Almost 2% of patients treated with MT experience recurrent LVO, usually of a previously treated artery during the same hospitalization. Repeat MT seems to be safe and effective for attaining vessel recanalization, and good outcome can be expected in 30% of patients.

Safety and Feasibility of Symptomatic Carotid Artery Stent-Assisted Revascularization within 48 Hours after Symptoms Onset.

OBJECTIVE: We aimed to evaluate the safety and feasibility of carotid artery stenting (CAS) performed in the hyperacute period. METHODS: We analyzed a retrospective database of CAS patients from our center. We included patients with symptomatic isolated ipsilateral extracranial carotid stenosis and acute tandem occlusions who underwent CAS. Hyperacute CAS (HCAS) and acute CAS (ACAS) groups were defined as CAS within 48 hours and >48 hours to 14 days from symptoms onset, respectively. The primary outcome was a composite of any stroke, myocardial infarction, or death at 3 months of follow-up. Secondary outcomes were periprocedural complications and restenosis or occlusion rates. RESULTS: We included 97 patients, 39 with HCAS and 58 with ACAS. There was no significant difference between groups for the primary outcome (HCAS 3.3% vs. ACAS 6.1%; p = 1). There were no differences in the rate of perioperative complications between groups although a trend was observed (HCAS 15.3% vs. ACAS 3.4%; p = .057). The rate of restenosis or occlusion between groups (HCAS 8.1% vs. ACAS 9,1%; log-rank test p = .8) was similar with a median time of follow-up of 13.7 months. CONCLUSION: Based on this study, CAS may be feasible in the hyperacute period. However, there are potential higher rates of perioperative complications in the hyperacute group, primarily occurring in MT patients with acute tandem occlusion. A larger multicenter study may be needed to further corroborate our findings.

Patterns of Care and Clinical Outcomes in Patients with Cerebral Sinus Venous Thrombosis.

OBJECTIVES: To explore the association between rurality, transfer patterns and level of care with clinical outcomes of CVST patients in a rural Midwestern state. MATERIALS AND METHODS: CVST patients admitted to the hospitals between 2005 and 2014 were identified by inpatient diagnosis codes from statewide administrative claims dataset. Records were linked across interhospital transfers using probabilistic linkage. Rurality was defined by Rural-Urban Commuting Areas using the 2-category approximation. Driving distances were estimated using GoogleMaps Application Programming Interface. Hospital stroke certification was defined by the Joint Commission. Severity of CVST was estimated by cost of care corrected for inflation and cost-to-charge ratios. Outcome was discharge disposition and total length of stay (LOS). Wilcoxon rank-sum, Chi-square, Fisher's exact tests and linear and logistic regressions were used. RESULTS: 168 CVST patients were identified (79.8% female; median age = 32, IQR = 24.0-45.5). Median LOS was four days (IQR = 2-7) and patients traveled a median of 8.1 miles (IQR = 2.5-28.5) to the first hospital; 42% of patients were transferred to a second hospital, 5% to a third. More than half (58.3%) bypassed the nearest hospital. 86% visit a primary or comprehensive stroke center (CSC) during their acute care. Rurality was not significantly associated with LOS or discharge disposition after adjusting for age, sex and cost of care. Patients in CSC demonstrated greater likelihood of being discharged home compared to at a primary stroke center after adjusting for age and disease severity (p = 0.008). CONCLUSIONS: While rurality was not significantly associated with LOS or disposition outcome, care at a CSC increases likelihood of being discharge home.

In-House Anesthesia and Interventional Radiology Technologist Support Optimize Mechanical Thrombectomy Workflow after Hours.

BACKGROUND AND PURPOSE: Prior literature suggests after-hours delay leads to poor functional outcomes in stroke patients undergoing thrombectomy. We aimed to evaluate the impact of time of presentation on mechanical thrombectomy (MT) metrics and its association with long-term functional outcome in an Interventional Radiology (IR) suite equipped operating room (OR) setting. METHODS: Retrospective review of prospectively maintained database on all stroke patients undergoing mechanical thrombectomy between January 2015 and December 2018 at our CSC. Work hours were defined by official OR work hours (Monday-Friday 7 AM and 5 PM) and after-hours as between 5 PM and 7 AM during weekdays and weekends as well as official hospital holidays. Primary outcome was 90-day modified Rankin Scale (mRS). Secondary outcomes included door to groin puncture time and procedural complications. RESULTS: A total of 315 patients were included in the analyses. 209 (66.4%) received mechanical thrombectomy after hours and 106 (33.6%) during work hours. There was no difference in the shift distribution of functional outcome on the mRS at 90 days (OR: 1.14, CI: 0.72-1.78, p=0.58) and the percentage of patients achieving functional independence (mRS 0-2) at 90 days (43.1% vs. 41.3%; p=0.83) between the after hour and work hour groups respectively. Similarly, there was no difference in median door to groin times and procedural complications among both groups, with significant year on year improvement in overall time metrics. CONCLUSIONS: Our study showed that undergoing MT during off-hours had similar functional outcomes when compared to MT during working hours in an OR setting. The after-hours deleterious effect might disappear when MT is performed in a system with 24-hours in-house Anesthesia and IR tech services.

Endovascular treatment of acute ischemic stroke patients with tandem lesions: antegrade versus retrograde approach.

OBJECTIVE: The optimal technique for treating tandem lesions (TLs) with endovascular therapy is debatable. The authors evaluated the functional, safety, and procedural outcomes of different approaches in a multicenter study. METHODS: Anterior circulation TL patients treated from January 2015 to December 2020 were divided on the basis of antegrade versus retrograde approach and included. The evaluated outcomes were favorable modified Rankin Scale (mRS) score (mRS score 0-2) at 3 months, ordinal shift in mRS score, successful recanalization, excellent recanalization, first-pass effect (FPE), time from groin puncture to successful recanalization, symptomatic intracranial hemorrhage (sICH), and 90-day mortality. RESULTS: Among 691 patients treated at 16 centers, 286 patients (174 antegrade and 112 retrograde approach patients) with acute stenting were included in the final analysis. There were no significant differences in mRS score 0-2 at 90 days (52.2% vs 50.0%, adjusted odds ratio [aOR] 0.83, 95% CI 0.42-1.56, p = 0.54), favorable shift in 90-day mRS score (aOR 1.03, 95% CI 0.66-1.29, p = 0.11), sICH (4.0% vs 4.5%, aOR 0.64, 95% CI 0.24-1.51, p = 0.45), successful recanalization (89.4% vs 93%, aOR 0.49, 95% CI 0.19-1.28, p = 0.19), excellent recanalization (51.4% vs 58.9%, aOR 0.59, 95% CI 0.40-1.07, p = 0.09), FPE (58.3% vs 69.7%, aOR 0.62, 95% CI 0.44-1.15, p = 0.21), and mortality at 90 days (16.6% vs 14.0%, aOR 0.94, 95% CI 0.35-2.44, p = 0.81) between the groups. The median (interquartile range) groin puncture to recanalization time was significantly longer in the antegrade group (59 [43-90] minutes vs 49 [35-73] minutes, p = 0.036). CONCLUSIONS: The retrograde approach was associated with faster recanalization times with a similar functional and safety profile when compared with the antegrade approach in patients with acute ischemic stroke with TL.

Mediation Analysis of Acute Carotid Stenting in Tandem Lesions: Effect on Functional Outcome in a Multicenter Registry.

BACKGROUND AND OBJECTIVES: Current evidence suggests that acute carotid artery stenting (CAS) for cervical lesions is associated with better functional outcomes in patients with acute stroke with tandem lesions (TLs) treated with endovascular therapy (EVT). However, the underlying causal pathophysiologic mechanism of this relationship compared with a non-CAS strategy remains unclear. We aimed to determine whether, and to what degree, reperfusion mediates the relationship between acute CAS and functional outcome in patients with TLs. METHODS: This subanalysis stems from a multicenter retrospective cohort study across 16 stroke centers from January 2015 to December 2020. Patients with anterior circulation TLs who underwent EVT were included. Successful reperfusion was defined as a modified Thrombolysis in Cerebral Infarction scale ≥2B by the local team at each participating center. Mediation analysis was conducted to examine the potential causal pathway in which the relationship between acute CAS and functional outcome (90-day modified Rankin Scale) is mediated by successful reperfusion. RESULTS: A total of 570 patients were included, with a median age (interquartile range) of 68 (59-76), among whom 180 (31.6%) were female. Among these patients, 354 (62.1%) underwent acute CAS and 244 (47.4%) had a favorable functional outcome. The remaining 216 (37.9%) patients were in the non-CAS group. The CAS group had significantly higher rates of successful reperfusion (91.2% vs 85.1%; p = 0.025) and favorable functional outcomes (52% vs 29%; p = 0.003) compared with the non-CAS group. Successful reperfusion was a strong predictor of functional outcome (adjusted common odds ratio [acOR] 4.88; 95% CI 2.91-8.17; p < 0.001). Successful reperfusion partially mediated the relationship between acute CAS and functional outcome, as acute CAS remained significantly associated with functional outcome after adjustment for successful reperfusion (acOR 1.89; 95% CI 1.27-2.83; p = 0.002). Successful reperfusion explained 25% (95% CI 3%-67%) of the relationship between acute CAS and functional outcome. DISCUSSION: In patients with TL undergoing EVT, successful reperfusion predicted favorable functional outcomes when CAS was performed compared with non-CAS. A considerable proportion (25%) of the treatment effect of acute CAS on functional outcome was found to be mediated by improvement of successful reperfusion rates.

Anesthetic management for large vessel occlusion acute ischemic stroke with tandem lesions.

BACKGROUND: Endovascular therapy (EVT) stands as an established and effective intervention for acute ischemic stroke in patients harboring tandem lesions (TLs). However, the optimal anesthetic strategy for EVT in TL patients remains unclear. This study aims to evaluate the impact of distinct anesthetic techniques on outcomes in acute ischemic stroke patients presenting with TLs. METHODS: Patient-level data, encompassing cases from 16 diverse centers, were aggregated for individuals with anterior circulation TLs treated between January 2015 and December 2020. A stratification based on anesthetic technique was conducted to distinguish between general anesthesia (GA) and procedural sedation (PS). Multivariable logistic regression models were built to discern the association between anesthetic approach and outcomes, including the favorable functional outcome defined as 90-day modified Rankin Score (mRS) of 0-2, ordinal shift in mRS, symptomatic intracranial hemorrhage (sICH), any hemorrhage, successful recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) score ≥2b), excellent recanalization (mTICI 3), first pass effect (FPE), early neurological improvement (ENI), door-to-groin and recanalization times, intrahospital mortality, and 90-day mortality. RESULTS: Among 691 patients from 16 centers, 595 patients (GA 38.7%, PS 61.3%) were included in the final analysis. There were no significant differences noted in the door-to-groin time (80 (46-117.5) mins vs 54 (21-100), P=0.607) and groin to recanalization time (59 (39.5-85.5) mins vs 54 (38-81), P=0.836) among the groups. The odds of a favorable functional outcome (36.6% vs 52.6%; adjusted OR (aOR) 0.56, 95% CI 0.38 to 0.84, P=0.005) and a favorable shift in the 90-day mRS (aOR 0.71, 95% CI 0.51 to 0.99, P=0.041) were lower in the GA group. No differences were noted for sICH (3.9% vs 4.7%, P=0.38), successful recanalization (89.1% vs 86.5%, P=0.13), excellent recanalization (48.5% vs 50.3%, P=0.462), FPE (53.6% vs 63.4%, P=0.05), ENI (38.9% vs 38.8%, P=0.138), and 90-day mortality (20.3% vs 16.3%, P=0.525). An interaction was noted for favorable functional outcome between the type of anesthesia and the baseline Alberta Stroke Program Early CT Score (ASPECTS) (P=0.033), degree of internal carotid artery (ICA) stenosis (P<0.001), and ICA stenting (P<0.001), and intraparenchymal hematoma between the type of anesthesia and intravenous thrombolysis (P=0.019). In a subgroup analysis, PS showed better functional outcomes in patients with age ≤70 years, National Institutes of Health Stroke Scale (NIHSS) score <15, and acute ICA stenting. CONCLUSIONS: Our findings suggest that the preference for PS not only aligns with comparable procedural safety but is also associated with superior functional outcomes. These results prompt a re-evaluation of current anesthesia practices in EVT, urging clinicians to consider patient-specific characteristics when determining the optimal anesthetic strategy for this patient population.

Hyperacute immune responses associate with immediate neuropathology and motor dysfunction in large vessel occlusions.

OBJECTIVE: Despite successful endovascular therapy, a proportion of stroke patients exhibit long-term functional decline, regardless of the cortical reperfusion. Our objective was to evaluate the early activation of the adaptive immune response and its impact on neurological recovery in patients with large vessel occlusion (LVO). METHODS: Nineteen (13 females, 6 males) patients with acute LVO were enrolled in a single-arm prospective cohort study. During endovascular therapy (EVT), blood samples were collected from pre and post-occlusion, distal femoral artery, and median cubital vein (controls). Cytokines, chemokines, cellular and functional profiles were evaluated with immediate and follow-up clinical and radiographic parameters, including cognitive performance and functional recovery. RESULTS: In the hyperacute phase (within hours), adaptive immune activation was observed in the post-occlusion intra-arterial environment (post). Ischemic vascular tissue had a significant increase in T-cell-related cytokines, including IFN-γ and MMP-9, while GM-CSF, IL-17, TNF-α, IL-6, MIP-1a, and MIP-1b were decreased. Cellularity analysis revealed an increase in inflammatory IL-17+ and GM-CSF+ helper T-cells, while natural killer (NK), monocytes and B-cells were decreased. A correlation was observed between hypoperfused tissue, infarct volume, inflammatory helper, and cytotoxic T-cells. Moreover, helper and cytotoxic T-cells were also significantly increased in patients with improved motor function at 3 months. INTERPRETATION: We provide evidence of the activation of the inflammatory adaptive immune response during the hyperacute phase and the association of pro-inflammatory cytokines with greater ischemic tissue and worsening recovery after successful reperfusion. Further characterization of these immune pathways is warranted to test selective immunomodulators during the early stages of stroke rehabilitation.

Association between intraprocedural drops in blood pressure and infarct growth rate patterns after acute large-vessel occlusions.

BACKGROUND: Infarct growth rate (IGR) differs among patients with acute ischemic stroke due to large vessel occlusion (LVO-AIS), and this variability has critical clinical repercussions. We explored IGR patterns and their association with blood pressure during endovascular therapy (EVT). METHODS: This is a two-center cohort observational study that included consecutive anterior circulation LVO-AIS patients who underwent EVT and achieved modified Thrombolysis in Cerebral Infarction (mTICI) 2 c-3. Initial and final infarct volumes (FIV) were defined using admission computed tomography perfusion (CTP) defined as relative cerebral blood flow (rCBF) <30%, and diffusion-weighted imaging-magnetic resonance imaging (DWI-MRI) at 24 hours post-EVT. We categorized IGR patterns as exponential (ExpIGR) and Non-exponential (NonExp) based on their growth curves. We then dichotomized ExpIGR clinical significance based on the association of infarct growth with 90-day Modified Rankin Score (mRS) as ExpIGR-A (>13 mL) and ExpIGR-B (<13 mL). Intraprocedural blood pressure (BP) drops were calculated as the difference between median arterial pressure (MAP) at admission and the lowest intraprocedural MAP reading before recanalization, and the area between admission MAP threshold and all lower measurements of intraprocedural MAP. Logistic and linear regression were used to investigate associations between variables of interest. RESULTS: Of 159 modified Thrombolysis in Cerebral Infarction (mTICI) 2 c-3 patients, we found that 36% demonstrated ExpIGR-A, 31% ExpIGR-B, and 32.7% NonExp patterns. The Exp-A and Exp-B groups differed significantly in National Institutes of Health Stroke Scale (NIHSS) score, Alberta Stroke Program Early CT Score (ASPECTS), glucose, and FIV. The Exp-A and NonExp groups differed in rCBF <30% vol, and time of stroke onset (SO) to admission CTP; and the Exp-B and NonExp groups in NIHSS, rCBF <30%, Tmax <6 s volume, collateral flow measured by hypoperfusion intensity ratio (HIR), and FIV. Hypotensive MAP area (HMA) was independently associated with an ExpIGR-A pattern. Infarct volume increased by 1 mL per 100 units of hypotensive area and 4.2 mL per 0.1 units of HIR, with a significant interaction between both variables. CONCLUSION: After an LVO-AIS, the IGR can be differentiated into two distinct exponential and non-exponential patterns. A subgroup of patients with the exponential pattern experienced clinically meaningful infarct growth rates between CTP acquisition and reperfusion and seem to be highly vulnerable to episodes of sustained intraprocedural BP drops during EVT.

Safety Outcomes of Antiplatelet Therapy During Endovascular Treatment of Tandem Lesions in Acute Ischemic Stroke Patients.

Risk of hemorrhage remains with antiplatelet medications required with carotid stenting during endovascular therapy (EVT) for tandem lesion (TLs). We evaluated the safety of antiplatelet regimens in EVT of TLs. This multicenter study included anterior circulation TL patients from 2015 to 2020, stratified by periprocedural EVT antiplatelet strategy: (1) no antiplatelets, (2) single oral, (3) dual oral, and (4) intravenous IV (in combination with single or dual oral). Primary outcome was symptomatic intracranial hemorrhage (sICH). Secondary outcomes were any hemorrhage, favorable functional status (mRS 0-2) at 90 days, successful reperfusion (mTICI score ≥ 2b), in-stent thrombosis, and mortality at 90 days. Of the total 691 patients, 595 were included in the final analysis. One hundred and nineteen (20%) received no antiplatelets, 134 (22.5%) received single oral, 152 (25.5%) dual oral, and 196 (31.9%) IV combination. No significant association was found for sICH (ref: no antiplatelet: 5.7%; single:4.2%; aOR 0.64, CI 0.20-2.06, p = 0.45, dual:1.9%; aOR 0.35, CI 0.09-1.43, p = 0.15, IV combination: 6.1%; aOR 1.05, CI 0.39-2.85, p = 0.92). No association was found for parenchymal or petechial hemorrhage. Odds of successful reperfusion were significantly higher with dual oral (aOR 5.85, CI 2.12-16.14, p = 0.001) and IV combination (aOR 2.35, CI 1.07-5.18, p = 0.035) compared with no antiplatelets. Odds of excellent reperfusion (mTICI 2c/3) were significantly higher for cangrelor (aOR 4.41; CI 1.2-16.28; p = 0.026). No differences were noted for mRS 0-2 at 90 days, in-stent thrombosis, and mortality rates. Administration of dual oral and IV (in combination with single or dual oral) antiplatelets during EVT was associated with significantly increased odds of successful reperfusion without an increased rate of symptomatic hemorrhage or mortality in patients with anterior circulation TLs.

Clinical and Safety Outcomes of Endovascular Therapy 6 to 24 Hours After Large Vessel Occlusion Ischemic Stroke With Tandem Lesions.

BACKGROUND AND PURPOSE: Effect of endovascular therapy (EVT) in acute large vessel occlusion (LVO) patients with tandem lesions (TLs) within 6-24 hours after last known well (LKW) remains unclear. We evaluated the clinical and safety outcomes among TL-LVO patients treated within 6-24 hours. METHODS: This multicenter cohort was divided into two groups, based on LKW to puncture time: early window (<6 hours), and late window (6-24 hours). Primary clinical and safety outcomes were 90-day functional independence measured by the modified Rankin Scale (mRS: 0-2) and symptomatic intracranial hemorrhage (sICH). Secondary outcomes were successful reperfusion (modified Thrombolysis in Cerebral Infarction score ≥2b), first-pass effect, early neurological improvement, ordinal mRS, and in-hospital and 90-day mortality. RESULTS: Of 579 patients (median age 68, 32.1% females), 268 (46.3%) were treated in the late window and 311 (53.7%) in the early window. Late window group had lower median National Institutes of Health Stroke Scale score at admission, Alberta Stroke Program Early Computed Tomography Score, rates of intravenous thrombolysis, and higher rates for perfusion imaging. After adjusting for confounders, the odds of 90-day mRS 0-2 (47.7% vs. 45.0%, adjusted odds ratio [aOR] 0.71, 95% confidence interval [CI] 0.49-1.02), favorable shift in mRS (aOR 0.88, 95% CI 0.44-1.76), and sICH (3.7% vs. 5.2%, aOR 0.56, 95% CI 0.20-1.56) were similar in both groups. There was no difference in secondary outcomes. Increased time from LKW to puncture did not predicted the probability of 90-day mRS 0-2 (aOR 0.99, 95% CI 0.96-1.01, for each hour delay) among patients presenting <24 hours. CONCLUSION: EVT for acute TL-LVO treated within 6-24 hours after LKW was associated with similar rates of clinical and safety outcomes, compared to patients treated within 6 hours.

Functional and Safety Outcomes of Carotid Artery Stenting and Mechanical Thrombectomy for Large Vessel Occlusion Ischemic Stroke With Tandem Lesions.

Importance: Approximately 10% to 20% of large vessel occlusion (LVO) strokes involve tandem lesions (TLs), defined as concomitant intracranial LVO and stenosis or occlusion of the cervical internal carotid artery. Mechanical thrombectomy (MT) may benefit patients with TLs; however, optimal management and procedural strategy of the cervical lesion remain unclear. Objective: To evaluate the association of carotid artery stenting (CAS) vs no stenting and medical management with functional and safety outcomes among patients with TL-LVOs. Design, Setting, and Participants: This cross-sectional study included consecutive patients with acute anterior circulation TLs admitted across 17 stroke centers in the US and Spain between January 1, 2015, and December 31, 2020. Data analysis was performed from August 2021 to February 2022. Inclusion criteria were age of 18 years or older, endovascular therapy for intracranial occlusion, and presence of extracranial internal carotid artery stenosis (>50%) demonstrated on pre-MT computed tomography angiography, magnetic resonance angiography, or digital subtraction angiography. Exposures: Patients with TLs were divided into CAS vs nonstenting groups. Main Outcomes and Measures: Primary clinical and safety outcomes were 90-day functional independence measured by a modified Rankin Scale (mRS) score of 0 to 2 and symptomatic intracranial hemorrhage (sICH), respectively. Secondary outcomes were successful reperfusion (modified Thrombolysis in Cerebral Infarction score ≥2b), discharge mRS score, ordinal mRS score, and mortality at 90 days. Results: Of 685 patients, 623 (mean [SD] age, 67 [12.2] years; 406 [65.2%] male) were included in the analysis, of whom 363 (58.4%) were in the CAS group and 260 (41.6%) were in the nonstenting group. The CAS group had a lower proportion of patients with atrial fibrillation (38 [10.6%] vs 49 [19.2%], P = .002), a higher proportion of preprocedural degree of cervical stenosis on digital subtraction angiography (90%-99%: 107 [32.2%] vs 42 [20.5%], P < .001) and atherosclerotic disease (296 [82.0%] vs 194 [74.6%], P = .003), a lower median (IQR) National Institutes of Health Stroke Scale score (15 [10-19] vs 17 [13-21], P < .001), and similar rates of intravenous thrombolysis and stroke time metrics when compared with the nonstenting group. After adjustment for confounders, the odds of favorable functional outcome (adjusted odds ratio [aOR], 1.67; 95% CI, 1.20-2.40; P = .007), favorable shift in mRS scores (aOR, 1.46; 95% CI, 1.02-2.10; P = .04), and successful reperfusion (aOR, 1.70; 95% CI, 1.02-3.60; P = .002) were significantly higher for the CAS group compared with the nonstenting group. Both groups had similar odds of sICH (aOR, 0.90; 95% CI, 0.46-2.40; P = .87) and 90-day mortality (aOR, 0.78; 95% CI, 0.50-1.20; P = .27). No heterogeneity was noted for 90-day functional outcome and sICH in prespecified subgroups. Conclusions and Relevance: In this multicenter, international cross-sectional study, CAS of the cervical lesion during MT was associated with improvement in functional outcomes and reperfusion rates without an increased risk of sICH and mortality in patients with TLs.

Endovascular embolization of high-grade cerebral dural arteriovenous fistulas - assessment of long-term recurrences.

INTRODUCTION: Endovascular therapy has shown to be safe and effective for the treatment of cerebral dural arteriovenous fistulas; however, recurrence after complete occlusion is not uncommon, and the timing of recurrence remains unknown. METHODS: A retrospective single-center cohort study was conducted from January 2005 to December 2020. Patients with high-grade (≥Borden II-Cognard IIB) dural arteriovenous fistulas treated with endovascular therapy were included in this study. Clinical and angiographic characteristics were collected for hospitalization and at follow-up. RESULTS: A total of 51 patients with a median age of 61 years were studied; 57% were female. High-flow symptoms related to the high-flow fistula were the most common presentation (67%), and 24% presented with intracranial hemorrhage. Transverse-sigmoid (26%) and cavernous (26%) sinuses were the most common dural arteriovenous fistula locations. A total of 40 patients (70%) had middle meningeal arterial feeders and 4 (7%) had deep cerebral venous drainage. The mean number of embolization procedures per patient was 1.4. Transarterial access was the most frequent approach (61%). Onyx alone was the most common embolic agent (26%). Complete occlusion rate was achieved in 46 patients (80.1%). Last mean radiographic follow-up time was 26.7 months for all 57 dural arteriovenous fistulas. Dural arteriovenous fistula recurrence after radiographic resolution at last treatment was seen in six cases (6/46, 13.1%). Mean time for recurrence was 15.8 months. Mean time of last clinical follow-up was 46.1 months for the 51 patients (100%). A total of 10 (20%) experienced any procedural complications, among which two (4%) became major thromboembolic events. CONCLUSION: Endovascular therapy is safe and effective for the treatment of high-grade dural arteriovenous fistulas. Given the significant recurrence rate of embolized dural arteriovenous fistulas even after 2 years, long-term angiographic follow-up might be needed.

Acute Carotid Artery Stenting Versus Balloon Angioplasty for Tandem Occlusions: A Systematic Review and Meta-Analysis.

Background Despite thrombectomy having become the standard of care for large-vessel occlusion strokes, acute endovascular management in tandem occlusions, especially of the cervical internal carotid artery lesion, remains uncertain. We aimed to compare efficacy and safety of acute carotid artery stenting to balloon angioplasty alone on treating the cervical lesion in tandem occlusions. Similarly, we aimed to explore those outcomes' associations with technique approaches and use of thrombolysis. Methods and Results We performed a systematic review and meta-analysis to compare functional outcomes (modified Rankin Scale), reperfusion, and symptomatic intracranial hemorrhage and 3-month mortality. We explored the association of first approach (anterograde/retrograde) and use of thrombolysis with those outcomes as well. Two independent reviewers performed the screening, data extraction, and quality assessment. A random-effects model was used for analysis. Thirty-four studies were included in our systematic review and 9 in the meta-analysis. Acute carotid artery stenting was associated with higher odds of modified Rankin Scale score ≤2 (odds ratio [OR], 1.95 [95% CI, 1.24-3.05]) and successful reperfusion (OR, 1.89 [95% CI, 1.26-2.83]), with no differences in mortality or symptomatic intracranial hemorrhage rates. Moreover, a retrograde approach was significantly associated with modified Rankin Scale score ≤2 (OR, 1.72 [95% CI, 1.05-2.83]), and no differences were found on thrombolysis status. Conclusions Carotid artery stenting and a retrograde approach had higher odds of successful reperfusion and good functional outcomes at 3 months than balloon angioplasty and an anterograde approach, respectively, in patients with tandem occlusions. A randomized controlled trial comparing these techniques with structured antithrombotic regimens and safety outcomes will offer definitive guidance in the optimal management of this complex disease.

Angiography suite cone-beam CT perfusion for selection of thrombectomy patients: A pilot study.

BACKGROUND AND PURPOSE: The availability of cone-beam CT perfusion (CBCTP) in angiography suites may improve large-vessel occlusion (LVO) triage and reduce reperfusion times for patients presenting during extended time window. We aim to evaluate the perfusion maps correlation and agreement between multidetector CT perfusion (MDCTP) and CBCTP when obtained sequentially in patients undergoing endovascular therapy. METHODS: This is a prospective, pilot, single-arm interventional cohort study of consecutive patients with anterior circulation LVO. All patients underwent MDCTP and CBCTP prior to endovascular therapy, generating cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time-to-maximum/time to peak contrast concentration maps. We compared the two imaging modalities using three different methods: (1) six regions of interest (ROIs) placed in the anterior circulation territory; (2) ROIs placed in all 10 Alberta Stroke Program Early CT Score regions; and (3) ROI drawn around the entire ischemic area. ROI ratios (unaffected/affected area) were compared for all sequences in each method. We used the intraclass correlation coefficient to calculate the correlation between the studies. Bland-Altman plots were also created to measure the degree of agreement. Finally, a sensitivity analysis was done comparing both modalities in patients with low infarct growth rate. RESULTS: Fourteen patients were included (median age 81 years [74-87], 50% males, median National Institutes of Health Stroke Scale 19 [14-22]). Median time between studies was 42 minutes (interquartile range 29-61). Independently of the method used, we found moderate to excellent correlation in CBF, CBV, and MTT between modalities. CBF correlation further improved in patients with low infarct growth. CONCLUSION: These results demonstrate promising accuracy of CBCTP in evaluating ischemic tissue in patients presenting with LVO ischemic stroke.