Clinical relevance of intracranial hemorrhage after thrombectomy versus medical management for large core infarct: a secondary analysis of the SELECT2 randomized trial.

BACKGROUND: The incidence of intracerebral hemorrhage (ICH) and its effect on the outcomes after endovascular thrombectomy (EVT) for patients with large core infarcts have not been well-characterized. METHODS: SELECT2 trial follow-up imaging was evaluated using the Heidelberg Bleeding Classification (HBC) to define hemorrhage grade. The association of ICH with clinical outcomes and treatment effect was examined. RESULTS: Of 351 included patients, 194 (55%) and 189 (54%) demonstrated intracranial and intracerebral hemorrhage, respectively, with a higher incidence in EVT (134 (75%) and 130 (73%)) versus medical management (MM) (60 (35%) and 59 (34%), both P<0.001). Hemorrhagic infarction type 1 (HBC=1a) and type 2 (HBC=1b) accounted for 93% of all hemorrhages. Parenchymal hematoma (PH) type 1 (HBC=1c) and type 2 (HBC=2) were observed in 1 (0.6%) EVT-treated and 4 (2.2%) MM patients. Symptomatic ICH (sICH) (SITS-MOST definition) was seen in 0.6% EVT patients and 1.2% MM patients. No trend for ICH with core volumes (P=0.10) or Alberta Stroke Program Early CT Score (ASPECTS) (P=0.74) was observed. Among EVT patients, the presence of any ICH did not worsen clinical outcome (modified Rankin Scale (mRS) at 90 days: 4 (3-6) vs 4 (3-6); adjusted generalized OR 1.00, 95% CI 0.68 to 1.47, P>0.99) or modify EVT treatment effect (Pinteraction=0.77). CONCLUSIONS: ICH was present in 75% of the EVT population, but PH or sICH were infrequent. The presence of any ICH did not worsen functional outcomes or modify EVT treatment effect at 90-day follow-up. The high rate of hemorrhages overall still represents an opportunity for adjunctive therapies in EVT patients with a large ischemic core.

Endovascular Thrombectomy Treatment Effect in Direct vs Transferred Patients With Large Ischemic Strokes: A Prespecified Analysis of the SELECT2 Trial.

Importance: Patients with large ischemic core stroke have poor clinical outcomes and are frequently not considered for interfacility transfer for endovascular thrombectomy (EVT). Objective: To assess EVT treatment effects in transferred vs directly presenting patients and to evaluate the association between transfer times and neuroimaging changes with EVT clinical outcomes. Design, Setting, and Participants: This prespecified secondary analysis of the SELECT2 trial, which evaluated EVT vs medical management (MM) in patients with large ischemic stroke, evaluated adults aged 18 to 85 years with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) as well as an Alberta Stroke Program Early CT Score (ASPECTS) of 3 to 5, core of 50 mL or greater on imaging, or both. Patients were enrolled between October 2019 and September 2022 from 31 EVT-capable centers in the US, Canada, Europe, Australia, and New Zealand. Data were analyzed from August 2023 to January 2024. Interventions: EVT vs MM. Main Outcomes and Measures: Functional outcome, defined as modified Rankin Scale (mRS) score at 90 days with blinded adjudication. Results: A total of 958 patients were screened and 606 patients were excluded. Of 352 enrolled patients, 145 (41.2%) were female, and the median (IQR) age was 66.5 (58-75) years. A total of 211 patients (59.9%) were transfers, while 141 (40.1%) presented directly. The median (IQR) transfer time was 178 (136-230) minutes. The median (IQR) ASPECTS decreased from the referring hospital (5 [4-7]) to an EVT-capable center (4 [3-5]). Thrombectomy treatment effect was observed in both directly presenting patients (adjusted generalized odds ratio [OR], 2.01; 95% CI, 1.42-2.86) and transferred patients (adjusted generalized OR, 1.50; 95% CI, 1.11-2.03) without heterogeneity (P for interaction = .14). Treatment effect point estimates favored EVT among 82 transferred patients with a referral hospital ASPECTS of 5 or less (44 received EVT; adjusted generalized OR, 1.52; 95% CI, 0.89-2.58). ASPECTS loss was associated with numerically worse EVT outcomes (adjusted generalized OR per 1-ASPECTS point loss, 0.89; 95% CI, 0.77-1.02). EVT treatment effect estimates were lower in patients with transfer times of 3 hours or more (adjusted generalized OR, 1.15; 95% CI, 0.73-1.80). Conclusions and Relevance: Both directly presenting and transferred patients with large ischemic stroke in the SELECT2 trial benefited from EVT, including those with low ASPECTS at referring hospitals. However, the association of EVT with better functional outcomes was numerically better in patients presenting directly to EVT-capable centers. Prolonged transfer times and evolution of ischemic change were associated with worse EVT outcomes. These findings emphasize the need for rapid identification of patients suitable for transfer and expedited transport. Trial Registration: ClinicalTrials.gov Identifier: NCT03876457.

Endovascular Thrombectomy for Large Ischemic Stroke Across Ischemic Injury and Penumbra Profiles.

Importance: Whether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain. Objective: To describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect. Design, Setting, and Participants: An exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 and September 2022. Intervention: EVT vs MM. Main Outcomes and Measures: Primary outcome was functional outcome-90-day mRS score (0, no symptoms, to 6, death) assessed by adjusted generalized OR (aGenOR; values >1 represent more favorable outcomes). Benefit of EVT vs MM was assessed across levels of ischemic injury defined by noncontrast CT using ASPECTS score and by the volume of brain with severely reduced blood flow on CT perfusion or restricted diffusion on MRI. Results: Among 352 patients randomized, 336 were analyzed (median age, 67 years; 139 [41.4%] female); of these, 168 (50%) were randomized to EVT, and 2 additional crossover MM patients received EVT. In an ordinal analysis of mRS at 90 days, EVT improved functional outcomes compared with MM within ASPECTS categories of 3 (aGenOR, 1.71 [95% CI, 1.04-2.81]), 4 (aGenOR, 2.01 [95% CI, 1.19-3.40]), and 5 (aGenOR, 1.85 [95% CI, 1.22-2.79]). Across strata for CT perfusion/MRI ischemic core volumes, aGenOR for EVT vs MM was 1.63 (95% CI, 1.23-2.16) for volumes ≥70 mL, 1.41 (95% CI, 0.99-2.02) for ≥100 mL, and 1.47 (95% CI, 0.84-2.56) for ≥150 mL. In the EVT group, outcomes worsened as ASPECTS decreased (aGenOR, 0.91 [95% CI, 0.82-1.00] per 1-point decrease) and as CT perfusion/MRI ischemic core volume increased (aGenOR, 0.92 [95% CI, 0.89-0.95] per 10-mL increase). No heterogeneity of EVT treatment effect was observed with or without mismatch, although few patients without mismatch were enrolled. Conclusion and Relevance: In this exploratory analysis of a randomized clinical trial of patients with extensive ischemic stroke, EVT improved clinical outcomes across a wide spectrum of infarct volumes, although enrollment of patients with minimal penumbra volume was low. In EVT-treated patients, clinical outcomes worsened as presenting ischemic injury estimates increased. Trial Registration: ClinicalTrials.gov Identifier: NCT03876457.

Longitudinal Morphometric Changes in the Corticospinal Tract Shape After Hemorrhagic Stroke.

Deep intracerebral hemorrhage (ICH) exerts a direct force on corticospinal tracts (CST) causing shape deformation. Using serial MRI, Generalized Procrustes Analysis (GPA), and Principal Components Analysis (PCA), we temporally evaluated the change in CST shape. Thirty-five deep ICH patients with ipsilesional-CST deformation were serially imaged on a 3T-MRI with a median imaging time of day-2 and 84 of onset. Anatomical and diffusion tensor images (DTI) were acquired. Using DTI color-coded maps, 15 landmarks were drawn on each CST and the centroids were computed in 3 dimensions. The contralesional-CST landmarks were used as a reference. The GPA outlined the shape coordinates and we superimposed the ipsilesional-CST shape at the two-time points. A multivariate PCA was applied to identify eigenvectors associated with the highest percentile of change. The first three principal components representing CST deformation along the left-right (PC1), anterior-posterior (PC2), and superior-inferior (PC3) respectively were responsible for 57.9% of shape variance. The PC1 (36.1%, p < 0.0001) and PC3 (9.58%, p < 0.01) showed a significant deformation between the two-time points. Compared to the contralesional-CST, the ipsilesional PC scores were significantly (p < 0.0001) different only at the first-timepoint. A significant positive association between the ipsilesional-CST deformation and hematoma volume was observed. We present a novel method to quantify CST deformation caused by ICH. Deformation most often occurs in left-right axis (PC1) and superior-inferior (PC3) directions. As compared to the reference, the significant temporal difference at the first time point suggests CST restoration over time.

Trial of Endovascular Thrombectomy for Large Ischemic Strokes.

BACKGROUND: Trials of the efficacy and safety of endovascular thrombectomy in patients with large ischemic strokes have been carried out in limited populations. METHODS: We performed a prospective, randomized, open-label, adaptive, international trial involving patients with stroke due to occlusion of the internal carotid artery or the first segment of the middle cerebral artery to assess endovascular thrombectomy within 24 hours after onset. Patients had a large ischemic-core volume, defined as an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower scores indicating larger infarction) or a core volume of at least 50 ml on computed tomography perfusion or diffusion-weighted magnetic resonance imaging. Patients were assigned in a 1:1 ratio to endovascular thrombectomy plus medical care or to medical care alone. The primary outcome was the modified Rankin scale score at 90 days (range, 0 to 6, with higher scores indicating greater disability). Functional independence was a secondary outcome. RESULTS: The trial was stopped early for efficacy; 178 patients had been assigned to the thrombectomy group and 174 to the medical-care group. The generalized odds ratio for a shift in the distribution of modified Rankin scale scores toward better outcomes in favor of thrombectomy was 1.51 (95% confidence interval [CI], 1.20 to 1.89; P<0.001). A total of 20% of the patients in the thrombectomy group and 7% in the medical-care group had functional independence (relative risk, 2.97; 95% CI, 1.60 to 5.51). Mortality was similar in the two groups. In the thrombectomy group, arterial access-site complications occurred in 5 patients, dissection in 10, cerebral-vessel perforation in 7, and transient vasospasm in 11. Symptomatic intracranial hemorrhage occurred in 1 patient in the thrombectomy group and in 2 in the medical-care group. CONCLUSIONS: Among patients with large ischemic strokes, endovascular thrombectomy resulted in better functional outcomes than medical care but was associated with vascular complications. Cerebral hemorrhages were infrequent in both groups. (Funded by Stryker Neurovascular; SELECT2 ClinicalTrials.gov number, NCT03876457.).

Introducing the "Temporal Thumb Sign" in Pediatric Patients With New-Onset Idiopathic Seizures With and Without Elevated Cerebrospinal Fluid Opening Pressure.

BACKGROUND: Temporal lobe changes, such as anterior temporal lobe meningoceles or encephaloceles, have been documented as possible epileptogenic foci in a subset of pediatric patients with seizures. In our study, we aim to analyze a different structural change in the temporal lobe, remodeling of the posterior temporal skull base by the inferior temporal gyrus called the "temporal thumb sign" (TTS), in pediatric patients presenting with new-onset seizures with or without elevated opening pressure (OP), patients presenting with confirmed diagnosis of idiopathic intracranial hypertension (IIH) without seizure presentation, and healthy controls. METHODS: Magnetic resonance imaging scans of 163 pediatric patients were studied retrospectively for the presence of TTS. We analyzed the scans of 43 patients with elevated OP and confirmed IIH, 40 patients with elevated OP and new-onset idiopathic seizures, 40 patients with normal OP and new-onset idiopathic seizures, and 40 age- and sex-matched healthy controls. RESULTS: The TTS was detected most frequently in patients with elevated OP and seizures at 72.5% compared with patients with IIH with no seizures and patients with normal OP and seizures (32.6% and 27.5%, respectively). The TTS had a frequency of 12.5% in the control group. The TTS had the highest combination of specificity and sensitivity (72.5% and 72.5%) in patients with seizures and elevated OP compared with patients with seizures and normal OP (P value < 0.001). CONCLUSIONS: Our results suggest the Kamali "temporal thumb sign" is a novel imaging feature that may be used as a sensitive and specific imaging finding associated with seizures and elevated OP in the pediatric population.

Mediation of Successful Reperfusion Effect through Infarct Growth and Cerebral Edema: A Pooled, Patient-Level Analysis of EXTEND-IA Trials and SELECT Prospective Cohort.

OBJECTIVE: Reperfusion therapy is highly beneficial for ischemic stroke. Reduction in both infarct growth and edema are plausible mediators of clinical benefit with reperfusion. We aimed to quantify these mediators and their interrelationship. METHODS: In a pooled, patient-level analysis of the EXTEND-IA trials and SELECT study, we used a mediation analysis framework to quantify infarct growth and cerebral edema (midline shift) mediation effect on successful reperfusion (modified Treatment in Cerebral Ischemia ≥ 2b) association with functional outcome (modified Rankin Scale distribution). Furthermore, we evaluated an additional pathway to the original hypothesis, where infarct growth mediated successful reperfusion effect on midline shift. RESULTS: A total 542 of 665 (81.5%) eligible patients achieved successful reperfusion. Baseline clinical and imaging characteristics were largely similar between those achieving successful versus unsuccessful reperfusion. Median infarct growth was 12.3ml (interquartile range [IQR] = 1.8-48.4), and median midline shift was 0mm (IQR = 0-2.2). Of 249 (37%) demonstrating a midline shift of ≥1mm, median shift was 2.75mm (IQR = 1.89-4.21). Successful reperfusion was associated with reductions in both predefined mediators, infarct growth (ß = -1.19, 95% confidence interval [CI] = -1.51 to -0.88, p < 0.001) and midline shift (adjusted odds ratio = 0.36, 95% CI = 0.23-0.57, p < 0.001). Successful reperfusion association with improved functional outcome (adjusted common odds ratio [acOR] = 2.68, 95% CI = 1.86-3.88, p < 0.001) became insignificant (acOR = 1.39, 95% CI = 0.95-2.04, p = 0.094) when infarct growth and midline shift were added to the regression model. Infarct growth and midline shift explained 45% and 34% of successful reperfusion effect, respectively. Analysis considering an alternative hypothesis demonstrated consistent results. INTERPRETATION: In this mediation analysis from a pooled, patient-level cohort, a significant proportion (~80%) of successful reperfusion effect on functional outcome was mediated through reduction in infarct growth and cerebral edema. Further studies are required to confirm our findings, detect additional mediators to explain successful reperfusion residual effect, and identify novel therapeutic targets to further enhance reperfusion benefits. ANN NEUROL 2023;93:793-804.

Thrombectomy Outcomes With General vs Nongeneral Anesthesia: A Pooled Patient-Level Analysis From the EXTEND-IA Trials and SELECT Study.

BACKGROUND AND OBJECTIVES: The effect of anesthesia choice on endovascular thrombectomy (EVT) outcomes is unclear. Collateral status on perfusion imaging may help identify the optimal anesthesia choice. METHODS: In a pooled patient-level analysis of EXTEND-IA, EXTEND-IA TNK, EXTEND-IA TNK part II, and SELECT, EVT functional outcomes (modified Rankin Scale score distribution) were compared between general anesthesia (GA) vs non-GA in a propensity-matched sample. Furthermore, we evaluated the association of collateral flow on perfusion imaging, assessed by hypoperfusion intensity ratio (HIR) - Tmax > 10 seconds/Tmax > 6 seconds (good collaterals - HIR < 0.4, poor collaterals - HIR ≥ 0.4) on the association between anesthesia type and EVT outcomes. RESULTS: Of 725 treated with EVT, 299 (41%) received GA and 426 (59%) non-GA. The baseline characteristics differed in presentation National Institutes of Health Stroke Scale score (median [interquartile range] GA: 18 [13-22], non-GA: 16 [11-20], p < 0.001) and ischemic core volume (GA: 15.0 mL [3.2-38.0] vs non-GA: 9.0 mL [0.0-31.0], p < 0.001). In addition, GA was associated with longer last known well to arterial access (203 minutes [157-267] vs 186 minutes [138-252], p = 0.002), but similar procedural time (35.5 minutes [23-59] vs 34 minutes [22-54], p = 0.51). Of 182 matched pairs using propensity scores, baseline characteristics were similar. In the propensity score-matched pairs, GA was independently associated with worse functional outcomes (adjusted common odds ratio [adj. cOR]: 0.64, 95% CI: 0.44-0.93, p = 0.021) and higher neurologic worsening (GA: 14.9% vs non-GA: 8.9%, aOR: 2.10, 95% CI: 1.02-4.33, p = 0.045). Patients with poor collaterals had worse functional outcomes with GA (adj. cOR: 0.47, 95% CI: 0.29-0.76, p = 0.002), whereas no difference was observed in those with good collaterals (adj. cOR: 0.93, 95% CI: 0.50-1.74, p = 0.82), p interaction: 0.07. No difference was observed in infarct growth overall and in patients with good collaterals, whereas patients with poor collaterals demonstrated larger infarct growth with GA with a significant interaction between collaterals and anesthesia type on infarct growth rate (p interaction: 0.020). DISCUSSION: GA was associated with worse functional outcomes after EVT, particularly in patients with poor collaterals in a propensity score-matched analysis from a pooled patient-level cohort from 3 randomized trials and 1 prospective cohort study. The confounding by indication may persist despite the doubly robust nature of the analysis. These findings have implications for randomized trials of GA vs non-GA and may be of utility for clinicians when making anesthesia type choice. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that use of GA is associated with worse functional outcome in patients undergoing EVT. TRIAL REGISTRATION INFORMATION: EXTEND-IA: ClinicalTrials.gov (NCT01492725); EXTEND-IA TNK: ClinicalTrials.gov (NCT02388061); EXTEND-IA TNK part II: ClinicalTrials.gov (NCT03340493); and SELECT: ClinicalTrials.gov (NCT02446587).

Accuracy of CT Perfusion-Based Core Estimation of Follow-up Infarction: Effects of Time Since Last Known Well.

BACKGROUND AND OBJECTIVES: To assess the accuracy of baseline CT perfusion (CTP) ischemic core estimates. METHODS: From SELECT (Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke), a prospective multicenter cohort study of imaging selection, patients undergoing endovascular thrombectomy who achieved complete reperfusion (modified Thrombolysis In Cerebral Ischemia score 3) and had follow-up diffusion-weighted imaging (DWI) available were evaluated. Follow-up DWI lesions were coregistered to baseline CTP. The difference between baseline CTP core (relative cerebral blood flow [rCBF] <30%) volume and follow-up infarct volume was classified as overestimation (core ≥10 mL larger than infarct), adequate, or underestimation (core ≥25 mL smaller than infarct) and spatial overlap was evaluated. RESULTS: Of 101 included patients, median time from last known well (LKW) to imaging acquisition was 138 (82-244) minutes. The median baseline ischemic core estimate was 9 (0-31.9) mL and median follow-up infarct volume was 18.4 (5.3-68.7) mL. All 6/101 (6%) patients with overestimation of the subsequent infarct volume were imaged within 90 minutes of LKW and achieved rapid reperfusion (within 120 minutes of CTP). Using rCBF <20% threshold to estimate ischemic core in patients presenting within 90 minutes eliminated overestimation. Volumetric correlation between the ischemic core estimate and follow-up imaging improved as LKW time to imaging acquisition increased: Spearman ρ <90 minutes 0.33 (p = 0.049), 90-270 minutes 0.63 (p < 0.0001), >270 minutes 0.86 (p < 0.0001). Assessment of the spatial overlap between baseline CTP ischemic core lesion and follow-up infarct demonstrated that a median of 3.2 (0.0-9.0) mL of estimated core fell outside the subsequent infarct. These regions were predominantly in white matter. DISCUSSION: Significant overestimation of irreversibly injured ischemic core volume was rare, was only observed in patients who presented within 90 minutes of LKW and achieved reperfusion within 120 minutes of CTP acquisition, and occurred primarily in white matter. Use of a more conservative (rCBF <20%) threshold for estimating ischemic core in patients presenting within 90 minutes eliminated all significant overestimation cases. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov: NCT03876457.

Endovascular Thrombectomy Versus Medical Management in Isolated M2 Occlusions: Pooled Patient-Level Analysis from the EXTEND-IA Trials, INSPIRE, and SELECT Studies.

OBJECTIVE: The objective of this study was to evaluate functional and safety outcomes of endovascular thrombectomy (EVT) versus medical management (MM) in patients with M2 occlusion and examine their association with perfusion imaging mismatch and stroke severity. METHODS: In a pooled, patient-level analysis of 3 randomized controlled trials (EXTEND-IA, EXTEND-and IA-TNK parts 1 and 2) and 2 prospective nonrandomized studies (INSPIRE and SELECT), we evaluated EVT association with 90-day functional independence (modified Rankin Scale [mRS] = 0-2) in isolated M2 occlusions as compared to medical management overall and in subgroups by mismatch profile status and stroke severity. RESULTS: We included 517 patients (EVT = 195 and MM = 322), baseline median (interquartile range [IQR]) National Institutes of Health Stroke Scale (NIHSS) was 13 (8-19) in EVT versus 10 (6-15) in MM, p < 0.001. Pretreatment ischemic core did not differ (EVT = 10 [0-24] ml vs MM = 9 [3-21] ml, p = 0.59). Compared to MM, EVT was more frequently associated with functional independence (68.3 vs 61.6%, adjusted odds ratio [aOR] = 2.42, 95% confidence interval [CI] = 1.25-4.67, p = 0.008, inverse probability of treatment weights [IPTW]-OR = 1.75, 95% CI = 1.00-3.75, p = 0.05) with a shift toward better mRS outcomes (adjusted cOR = 2.02, 95% CI:1.23-3.29, p = 0.005), and lower mortality (5 vs 10%, aOR = 0.32, 95% CI = 0.12-0.87, p = 0.025). EVT was associated with higher functional independence in patients with a perfusion mismatch profile (EVT = 70.7% vs MM = 61.3%, aOR = 2.29, 95% CI = 1.09-4.79, p = 0.029, IPTW-OR = 2.02, 1.08-3.78, p = 0.029), whereas no difference was found in those without mismatch (EVT = 43.8% vs MM = 62.7%, p = 0.17, IPTW-OR: 0.71, 95% CI = 0.18-2.78, p = 0.62). Functional independence was more frequent with EVT in patients with moderate or severe strokes, as defined by baseline NIHSS above any thresholds from 6 to 10, whereas there was no difference between groups with milder strokes below these thresholds. INTERPRETATION: In patients with M2 occlusion, EVT was associated with improved clinical outcomes when compared to MM. This association was primarily observed in patients with a mismatch profile and those with higher stroke severity. ANN NEUROL 2022;91:629-639.

Endovascular thrombectomy in patients with large core ischemic stroke: a cost-effectiveness analysis from the SELECT study.

BACKGROUND: It is unknown whether endovascular thrombectomy (EVT) is cost effective in large ischemic core infarcts. METHODS: In the prospective, multicenter, cohort study of imaging selection study (SELECT), large core was defined as computed tomography (CT) ASPECTS<6 or computed tomography perfusion (CTP) ischemic core volume (rCBF<30%) ≥50 cc. A Markov model estimated costs, quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) of EVT compared with medical management (MM) over lifetime. The willingness to pay (WTP) per QALY was set at $50 000 and $100 000 and the net monetary benefits (NMB) were calculated. Probabilistic sensitivity analysis (PSA) and cost-effectiveness acceptability curves (CEAC) for EVT were assessed in SELECT and other pivotal trials. RESULTS: From 361 patients enrolled in SELECT, 105 had large core on CT or CTP (EVT 62, MM 43). 19 (31%) EVT vs 6 (14%) MM patients achieved modified Rankin Scale (mRS) score 0-2 (OR 3.27, 95% CI 1.11 to 9.62, P=0.03) with a shift towards better mRS (cOR 2.12, 95% CI 1.05 to 4.31, P=0.04). Over the projected lifetime of patients presenting with large core, EVT led to incremental costs of $33 094 and a gain of 1.34 QALYs per patient, resulting in ICER of $24 665 per QALY. EVT has a higher NMB compared with MM at lower (EVT -$42 747, MM -$76 740) and upper (EVT $155 041, MM $57 134) WTP thresholds. PSA confirmed the results and CEAC showed 77% and 92% acceptability of EVT at the WTP of $50 000 and $100 000, respectively. EVT was associated with an increment of $29 225 in societal costs. The pivotal EVT trials (HERMES, DAWN, DEFUSE 3) were dominant in a sensitivity analysis at the same inputs, with societal cost-savings of $37 901, $86 164 and $22 501 and a gain of 1.62, 2.36 and 2.21 QALYs, respectively. CONCLUSIONS: In a non-randomized prospective cohort study, EVT resulted in better outcomes in large core patients with higher QALYs, NMB and high cost-effectiveness acceptability rates at current WTP thresholds. Randomized trials are needed to confirm these results. CLINICAL TRIAL REGISTRATION: NCT02446587.

Ischemic Infarction in Young Adults: A Review for Radiologists.

Ischemic strokes in young adults are devastatingly debilitating and increasingly frequent. Stroke remains the leading cause of serious disability in the United States. The consequences of this familiar disease in this atypical age group are especially detrimental and long lasting. Ischemic stroke in young adults is now emerging as a public health issue, one in which radiologists can play a key role. The incidence of ischemic infarction in young adults has risen over the past couple of decades. Increased public awareness, increased use of MRI and angiography, and more accurate diagnosis may in part explain the increased detection of stroke in young adults. The increased prevalence of stroke risk factors in young adults (especially sedentary lifestyle and hypertension) may also contribute. However, compared with older adults, young adults have fewer ischemic infarcts related to the standard cardiovascular risk factors and large- or small-vessel disease. Instead, their infarcts most commonly result from cardioembolic disease and other demonstrated causes (ie, dissection). Thus, radiologists must expand their differential diagnoses to appropriately diagnose ischemic strokes and identify their causes in the young adult population. From the more frequent cardioembolism and dissection to the less common vasculitis, drug-related, CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), moyamoya, and hypercoagulable state-related infarcts, this article covers a wide breadth of causes and imaging findings of ischemic stroke in young adults. ©RSNA, 2019.

Serial Cerebral Metabolic Changes in Patients With Ischemic Stroke Treated With Autologous Bone Marrow Derived Mononuclear Cells.

Purpose: Cell-based therapy offers new opportunities for the development of novel treatments to promote tissue repair, functional restoration, and cerebral metabolic balance. N-acetylasperate (NAA), Choline (Cho), and Creatine (Cr) are three major metabolites seen on proton magnetic resonance spectroscopy (MRS) that play a vital role in balancing the biochemical processes and are suggested as markers of recovery. In this preliminary study, we serially monitored changes in these metabolites in ischemic stroke patients who were treated with autologous bone marrow-derived mononuclear cells (MNCs) using non-invasive MRS. Materials and Methods: A sub-group of nine patients (3 male, 6 female) participated in a serial MRS study, as part of a clinical trial on autologous bone marrow cell therapy in acute ischemic stroke. Seven to ten million mononuclear cells were isolated from the patient's bone marrow and administered intravenously within 72 h of onset of injury. MRS data were obtained at 1, 3, and 6 months using a whole-body 3.0T MRI. Single voxel point-resolved spectroscopy (PRESS) was obtained within the lesion and contralesional gray matter. Spectral analysis was done using TARQUIN software and absolute concentration of NAA, Cho, and Cr was determined. National Institute of Health Stroke Scale (NIHSS) was serially recoreded. Two-way analysis of variance was performed and p < 0.05 considered statistically significant. Results: All metabolites showed statistically significant or clear trends toward lower ipsilesional concentrations compared to the contralesional side at all time points. Statistically significant reductions were found in ipsilesional NAA at 1M and 3M, Cho at 6M, and Cr at 1M and 6M (p < 0.03), compared to the contralesional side. Temporally, ipsilesional NAA increased between 3M and 6M (p < 0.01). On the other hand, ipsilesional Cho showed continued decline till 6M (p < 0.01). Ipsilesional Cr was stable over time. Contralesional metabolites were relatively stable over time, with only Cr showing a reduction 3M (p < 0.02). There was a significant (p < 0.03) correlation between ipsilesional NAA and NIHSS at 3M follow-up. Conclusion: Serial changes in metabolites suggest that MRS can be applied to monitor therapeutic changes. Post-treatment increasing trends of NAA concentration and significant correlation with NIHSS support a potential therapeutic effect.

Ongoing Secondary Degeneration of the Limbic System in Patients With Ischemic Stroke: A Longitudinal MRI Study.

Purpose: Ongoing post-stroke structural degeneration and neuronal loss preceding neuropsychological symptoms such as cognitive decline and depression are poorly understood. Various substructures of the limbic system have been linked to cognitive impairment. In this longitudinal study, we investigated the post-stroke macro- and micro-structural integrity of the limbic system using structural and diffusion tensor magnetic resonance imaging. Materials and Methods: Nineteen ischemic stroke patients (11 men, 8 women, average age 53.4 ± 12.3, range 18-75 years), with lesions remote from the limbic system, were serially imaged three times over 1 year. Structural and diffusion-tensor images (DTI) were obtained on a 3.0 T MRI system. The cortical thickness, subcortical volume, mean diffusivity (MD), and fractional anisotropy (FA) were measured in eight different regions of the limbic system. The National Institutes of Health Stroke Scale (NIHSS) was used for clinical assessment. A mixed model for multiple factors was used for statistical analysis, and p-values <0.05 was considered significant. Results: All patients demonstrated improved NIHSS values over time. The ipsilesional subcortical volumes of the thalamus, hippocampus, and amygdala significantly decreased (p < 0.05) and MD significantly increased (p < 0.05). The ipsilesional cortical thickness of the entorhinal and perirhinal cortices was significantly smaller than the contralesional hemisphere at 12 months (p < 0.05). The cortical thickness of the cingulate gyrus at 12 months was significantly decreased at the caudal and isthmus regions as compared to the 1 month assessment (p < 0.05). The cingulum fibers had elevated MD at the ipsilesional caudal-anterior and posterior regions compared to the corresponding contralesional regions. Conclusion: Despite the decreasing NIHSS scores, we found ongoing unilateral neuronal loss/secondary degeneration in the limbic system, irrespective of the lesion location. These results suggest a possible anatomical basis for post stroke psychiatric complications.

Endovascular Thrombectomy for Mild Strokes: How Low Should We Go?

Background and Purpose- Endovascular thrombectomy (EVT) is effective for acute ischemic stroke with large vessel occlusion and National Institutes of Health Stroke Scale (NIHSS) ≥6. However, EVT benefit for mild deficits large vessel occlusions (NIHSS, <6) is uncertain. We evaluated EVT efficacy and safety in mild strokes with large vessel occlusion. Methods- A retrospective cohort of patients with anterior circulation large vessel occlusion and NIHSS <6 presenting within 24 hours from last seen normal were pooled. Patients were divided into 2 groups: EVT or medical management. Ninety-day mRS of 0 to 1 was the primary outcome, mRS of 0 to 2 was the secondary. Symptomatic intracerebral hemorrhage was the safety outcome. Clinical outcomes were compared through a multivariable logistic regression after adjusting for age, presentation NIHSS, time last seen normal to presentation, center, IV alteplase, Alberta Stroke Program early computed tomographic score, and thrombus location. We then performed propensity score matching as a sensitivity analysis. Results were also stratified by thrombus location. Results- Two hundred fourteen patients (EVT, 124; medical management, 90) were included from 8 US and Spain centers between January 2012 and March 2017. The groups were similar in age, Alberta Stroke Program early computed tomographic score, IV alteplase rate and time last seen normal to presentation. There was no difference in mRS of 0 to 1 between EVT and medical management (55.7% versus 54.4%, respectively; adjusted odds ratio, 1.3; 95% CI, 0.64-2.64; P=0.47). Similar results were seen for mRS of 0 to 2 (63.3% EVT versus 67.8% medical management; adjusted odds ratio, 0.9; 95% CI, 0.43-1.88; P=0.77). In a propensity matching analysis, there was no treatment effect in 62 matched pairs (53.5% EVT, 48.4% medical management; odds ratio, 1.17; 95% CI, 0.54-2.52; P=0.69). There was no statistically significant difference when stratified by any thrombus location; M1 approached significance ( P=0.07). Symptomatic intracerebral hemorrhage rates were higher with thrombectomy (5.8% EVT versus 0% medical management; P=0.02). Conclusions- Our retrospective multicenter cohort study showed no improvement in excellent and independent functional outcomes in mild strokes (NIHSS, <6) receiving thrombectomy irrespective of thrombus location, with increased symptomatic intracerebral hemorrhage rates, consistent with the guidelines recommending the treatment for NIHSS ≥6. There was a signal toward benefit with EVT only in M1 occlusions; however, this needs to be further evaluated in future randomized control trials.

Phase-contrast cerebrospinal fluid flow magnetic resonance imaging in qualitative evaluation of patency of CSF flow pathways prior to infusion of chemotherapeutic and other agents into the fourth ventricle.

PURPOSE: Nuclear medicine studies have previously been utilized to assess for blockage of cerebrospinal fluid (CSF) flow prior to intraventricular chemotherapy infusions. To assess CSF flow without nuclear medicine studies, we obtained cine phase-contrast MRI sequences that assess CSF flow from the fourth ventricle down to the sacrum. METHODS: In three clinical trials, 18 patients with recurrent malignant posterior fossa tumors underwent implantation of a ventricular access device (VAD) into the fourth ventricle, either with or without simultaneous tumor resection. Prior to infusing therapeutic agents into the VAD, cine MRI phase-contrast CSF flow sequences of the brain and total spine were performed. Velocity encoding (VENC) of 5 and 10 cm/s was used to confirm CSF flow from the fourth ventricular outlets to the cervical, thoracic, and lumbar spine. Qualitative CSF flow was characterized by neuroradiologists as present or absent. RESULTS: All 18 patients demonstrated CSF flow from the outlets of the fourth ventricle down to the sacrum with no evidence of obstruction. One of these patients, after disease progression, subsequently showed obstruction of CSF flow. No patient required a nuclear medicine study to assess CSF flow prior to initiation of infusions. Fourteen patients have received infusions to date, and none has had neurological toxicity. CONCLUSIONS: CSF flow including the fourth ventricle and the total spine can be assessed noninvasively with phase-contrast MRI sequences. Advantages over nuclear medicine studies include avoiding both an invasive procedure and radiation exposure.

Optimizing prediction scores for poor outcome after intra-arterial therapy in anterior circulation acute ischemic stroke.

BACKGROUND AND PURPOSE: Intra-arterial therapy (IAT) promotes recanalization of large artery occlusions in acute ischemic stroke. Despite high recanalization rates, poor clinical outcomes are common. We attempted to optimize a score that combines clinical and imaging variables to more accurately predict poor outcome after IAT in anterior circulation occlusions. METHODS: Patients with acute ischemic stroke undergoing IAT at University of Texas (UT) Houston for large artery occlusions (middle cerebral artery or internal carotid artery) were reviewed. Independent predictors of poor outcome (modified Rankin Scale, 4-6) were studied. External validation was performed on IAT-treated patients at Emory University. RESULTS: A total of 163 patients were identified at UT Houston. Independent predictors of poor outcome (P≤0.2) were identified as score variables using sensitivity analysis and logistic regression. Houston Intra-Arterial Therapy 2 (HIAT2) score ranges 0 to 10: age (≤59=0, 60-79=2, ≥80 years=4), glucose (<150=0, ≥150=1), National Institute Health Stroke Scale (≤10=0, 11-20=1, ≥21=2), the Alberta Stroke Program Early CT Score (8-10=0, ≤7=3). Patients with HIAT2≥5 were more likely to have poor outcomes at discharge (odds ratio, 6.43; 95% confidence interval, 2.75-15.02; P<0.001). After adjusting for reperfusion (Thrombolysis in Cerebral Infarction score≥2b) and time from symptom onset to recanalization, HIAT2≥5 remained an independent predictor of poor outcome (odds ratio, 5.88; 95% confidence interval, 1.96-17.64; P=0.02). Results from the cohort of Emory (198 patients) were consistent; patients with HIAT2 score≥5 had 6× greater odds of poor outcome at discharge and at 90 days. HIAT2 outperformed other previously published predictive scores. CONCLUSIONS: The HIAT2 score, which combines clinical and imaging variables, performed better than all previous scores in predicting poor outcome after IAT for anterior circulation large artery occlusions.

Increased blood-brain barrier permeability on perfusion CT might predict malignant middle cerebral artery infarction.

BACKGROUND AND PURPOSE: Perfusion CT has been used to assess the extent of blood-brain barrier breakdown. The purpose of this study was to determine the predictive value of blood-brain barrier permeability measured using perfusion CT for development of malignant middle cerebral artery infarction requiring hemicraniectomy (HC). METHODS: We retrospectively identified patients from our stroke registry who had middle cerebral artery infarction and were evaluated with admission perfusion CT. Blood-brain barrier permeability and cerebral blood volume maps were generated and infarct volumes calculated. Clinical and radiographic characteristics were compared between those who underwent HC versus those who did not undergo HC. RESULTS: One hundred twenty-two patients (12 HC, 110 no HC) were identified. Twelve patients who underwent HC had developed edema, midline shift, or infarct expansion. Infarct permeability area, infarct cerebral blood volume area, and infarct volumes were significantly different (P < 0.018, P < 0.0211, P < 0.0001, P < 0.0014) between HC and no HC groups. Age (P = 0.03) and admission National Institutes of Health Stroke Scale (P = 0.0029) were found to be independent predictors for HC. Using logistic regression modeling, there was an association between increased infarct permeability area and HC. The OR for HC based on a 5-, 10-, 15-, or 20-cm² increase in infarct permeability area were 1.179, 1.390, 1.638, or 1.932, respectively (95% CI, 1.035 to 1.343, 1.071 to 1.804, 1.108 to 2.423, 1.146 to 3.255, respectively). CONCLUSIONS: Increased infarct permeability area is associated with an increased likelihood for undergoing HC. Because early HC for malignant middle cerebral artery infarction has been associated with better outcomes, the infarct permeability area on admission perfusion CT might be a useful tool to predict malignant middle cerebral artery infarction and need for HC.

Central nervous system complications of blastic hyperleukocytosis in childhood acute lymphoblastic leukemia: diagnostic and prognostic implications.

Intracranial hemorrhage during blastic crisis is a rare but critically important occurrence in children with acute lymphoblastic leukemia. This form of hemorrhage has not been described since the advent of magnetic resonance imaging (MRI), leaving radiologists and clinicians unfamiliar with its unique imaging features. The authors describe 2 boys with severe intracranial pathology secondary to blastic hyperleukocytosis. Both patients were followed with serial MRI. Imaging findings in relation to the pathophysiology of white matter leukostasis are discussed and implications for treatment and prognosis are considered.