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.

Mode of Onset Modifies the Effect of Time to Endovascular Reperfusion on Clinical Outcomes after Acute Ischemic Stroke: An Analysis of the DAWN Trial.

OBJECTIVE: We aimed to assess the impact of time to endovascular thrombectomy (EVT) on clinical outcomes in the DAWN trial, while also exploring the potential effect modification of mode of stroke onset on this relationship. METHODS: The association between every 1-h treatment delay with 90-day functional independence (modified Rankin Scale [mRS] score 0-2), symptomatic intracranial hemorrhage, and 90-day mortality was explored in the overall population and in three modes of onset subgroups (wake-up vs. witnessed vs. unwitnessed). RESULTS: Out of the 205 patients, 98 (47.8%) and 107 (52.2%) presented in the 6 to 12 hours and 12 to 24 hours time window, respectively. Considering all three modes of onset together, there was no statistically significant association between time last seen well to randomization with either functional independence or mortality at 90 days in either the endovascular thrombectomy (mRS 0-2 1-hour delay OR 1.07; 95% CI 0.93-1.24; mRS 6 OR 0.84; 95% CI 0.65-1.03) or medical management (mRS 0-2 1-hour delay OR 0.98; 95% CI 0.80-1.14; mRS 6 1-hour delay OR 0.94; 95% CI 0.79-1.09) groups. Moreover, there was no significant interaction between treatment effect and time (p = 0.439 and p = 0.421 for mRS 0-2 and 6, respectively). However, within the thrombectomy group, the models that tested the association between time last seen well to successful reperfusion (modified Treatment in Cerebral Infarction ≥2b) and 90-day functional independence showed a significant interaction with mode of presentation (p = 0.013). This appeared to be driven by a nominally positive slope for both witnessed and unwitnessed strokes versus a significantly (p = 0.018) negative slope in wake-up patients. There was no association between treatment times and symptomatic intracranial hemorrhage. INTERPRETATION: Mode of onset modifies the effect of time to reperfusion on thrombectomy outcomes, and should be considered when exploring different treatment paradigms in the extended window. ANN NEUROL 2024.

Projections of Endovascular Therapy-Eligible Patients With Stroke for the US Population.

BACKGROUND: As stroke endovascular thrombectomy (EVT) treatment indications expand, understanding population-based EVT eligibility becomes critical for resource planning. We aimed to project current and future population-based EVT eligibility in the United States. METHODS: We conducted a post hoc analysis of the physician-adjudicated GCNKSS (Greater Cincinnati Northern Kentucky Stroke Study; 2015 epoch), a population-based, cross sectional, observational study of stroke incidence, treatment, and outcomes across a 5-county region. All hospitalized patients ≥18 years of age with acute ischemic stroke were ascertained using the International Classification of Diseases, Ninth Revision codes 430-436 and Tenth Revision codes I60-I67 and G45-G46 and extrapolated to the US adult census 2020. We determined the rate of EVT eligibility within the GCNKSS population using time from last known well to presentation (0-5 versus 5-23 hours), presenting National Institutes of Health Stroke Scale, and prestroke modified Rankin Scale. Both conservative and liberal estimates of prevalence of large vessel occlusion and large core were then applied based on literature review (unavailable within the 2015 GCNKSS). This eligibility was then extrapolated to the 2020 US population. RESULTS: Of the 1 057 183 adults within GCNKSS in 2015, 2741 had an ischemic stroke and 2176 had data available for analysis. We calculated that 8659 to 17 219 patients (conservative to liberal) meet the current guideline-recommended EVT criteria (nonlarge core, no prestroke disability, and National Institutes of Health Stroke Scale score ≥6) in the United States. Estimates (conservative to liberal) for expanded EVT eligibility subpopulations include (1) 5316 to 10 635 by large core; (2) 10 635 to 21 270 by mild presenting deficits with low National Institutes of Health Stroke Scale score; (3) 13 572 to 27 089 by higher prestroke disability; and (4) 7039 to 14 180 by >1 criteria. These expanded eligibility subpopulations amount to 36 562 to 73 174 patients. CONCLUSIONS: An estimated 8659 to 17 219 adult patients in the United States met strict EVT eligibility criteria in 2020. A 4-fold increase in population-based EVT eligibility can be anticipated with incremental adoption of recent or future positive trials. US stroke systems need to be rapidly optimized to handle all EVT-eligible patients with stroke.

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.

Effect of Endovascular Thrombectomy for Acute Ischemic Stroke on Cognitive Outcomes: A Secondary Analysis of the ESCAPE Trial.

BACKGROUND AND OBJECTIVES: The effect of endovascular therapy (EVT) for large vessel occlusion stroke on cognitive outcomes is not well understood. We evaluated the effect of EVT on cognitive function in the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial. METHODS: Patient data from the ESCAPE randomized trial were analyzed. Cognitive assessments completed at 90 days after stroke were the Montreal Cognitive Assessment (MoCA), the Sunnybrook Neglect Assessment Procedure (SNAP), the Boston Naming Test (BNT), Trail-making test A (Trails A), and Trail-making test B (Trails B). We used logistic regression to evaluate the association between EVT and favorable cognitive outcome on the 5 separate tests, adjusting for demographic and clinical factors. We used generalized estimating equations and ordinal regression to determine the odds of favorable outcome with EVT on global cognition incorporating the 5 tests. We added final infarct volume (FIV) to the models to assess the relationship of FIV with cognitive outcome. RESULTS: The ESCAPE trial included 315 patients, 165 randomized to EVT and 150 randomized to control. There was higher odds of favorable outcome with EVT for MoCA (adjusted odds ratio [aOR] 2.32, 95% CI 1.30-4.16), SNAP (aOR 3.85, 95% CI 2.00-7.45), BNT (aOR 2.33, 95% CI 1.30-4.17), trails A (aOR 3.50, 95% CI 1.93-6.36), and trails B (aOR 2.56, 95% CI 1.46-4.48). There was higher odds of favorable outcome with EVT on global binary (aOR 2.57, 95% CI 1.67-3.94) and ordinal analyses (aOR 2.83, 95% CI 1.68-4.76) of cognitive function. After adding FIV to the models, both FIV and EVT were significantly associated with cognitive outcome. There was a significant correlation between global cognitive performance and mRS at day 90 (r = -0.78, p < 0.001), with the largest reductions in favorable cognitive outcome from mRS score 4 to 5 and from mRS 2 to 3. DISCUSSION: In this secondary analysis of the ESCAPE trial, EVT was associated with favorable outcome on 5 separate cognitive tests and in global analyses of cognitive benefit. These results provide novel evidence for the effect of EVT on cognition and support the global benefit of treatment with EVT. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with acute ischemic stroke due to intracranial internal carotid artery (ICA) or M1 segment MCA occlusion, including tandem extracranial ICA occlusions, EVT compared with best medical therapy increased odds of favorable cognitive outcome.

Trial of Thrombectomy for Stroke with a Large Infarct of Unrestricted Size.

BACKGROUND: The use of thrombectomy in patients with acute stroke and a large infarct of unrestricted size has not been well studied. METHODS: We assigned, in a 1:1 ratio, patients with proximal cerebral vessel occlusion in the anterior circulation and a large infarct (as defined by an Alberta Stroke Program Early Computed Tomographic Score of ≤5; values range from 0 to 10) detected on magnetic resonance imaging or computed tomography within 6.5 hours after symptom onset to undergo endovascular thrombectomy and receive medical care (thrombectomy group) or to receive medical care alone (control group). The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). The primary safety outcome was death from any cause at 90 days, and an ancillary safety outcome was symptomatic intracerebral hemorrhage. RESULTS: A total of 333 patients were assigned to either the thrombectomy group (166 patients) or the control group (167 patients); 9 were excluded from the analysis because of consent withdrawal or legal reasons. The trial was stopped early because results of similar trials favored thrombectomy. Approximately 35% of the patients received thrombolysis therapy. The median modified Rankin scale score at 90 days was 4 in the thrombectomy group and 6 in the control group (generalized odds ratio, 1.63; 95% confidence interval [CI], 1.29 to 2.06; P<0.001). Death from any cause at 90 days occurred in 36.1% of the patients in the thrombectomy group and in 55.5% of those in the control group (adjusted relative risk, 0.65; 95% CI, 0.50 to 0.84), and the percentage of patients with symptomatic intracerebral hemorrhage was 9.6% and 5.7%, respectively (adjusted relative risk, 1.73; 95% CI, 0.78 to 4.68). Eleven procedure-related complications occurred in the thrombectomy group. CONCLUSIONS: In patients with acute stroke and a large infarct of unrestricted size, thrombectomy plus medical care resulted in better functional outcomes and lower mortality than medical care alone but led to a higher incidence of symptomatic intracerebral hemorrhage. (Funded by Montpellier University Hospital; LASTE ClinicalTrials.gov number, NCT03811769.).

Early Experience With Artificial Intelligence Software to Detect Intracranial Occlusive Stroke in Trauma Patients.

Objective Identifying ischemic stroke is a diagnostic challenge in the trauma subpopulation. We describe our early experience with artificial intelligence-assisted image analysis software for automatically identifying acute ischemic stroke in trauma patients.  Methods Patients were retrospectively screened for (i) admission to the trauma service at a level one trauma center between 2020 and 2022, (ii) radiologist-confirmed intracranial occlusion, (iii) occlusion identified on computed tomography angiography performed within 24 hours of admission, (iv) no intracranial hemorrhage, and (v) contemporaneous analysis with the large vessel occlusion (LVO) detection program. Baseline characteristics, stroke detection, response-activation, and outcome data were summarized.  Results Of 9893 trauma patients admitted, 88 (0.89%) patients had a cerebral stroke diagnosis, of which 10 patients (10/88; 11.4%) met inclusion criteria. Most patients were admitted following a fall (8/10; 80%). Six (6/10; 60.0%) patients had LVOs. The program correctly detected 83.3% (5/6) of patients, and these patients were triaged in less than one hour from arrival on average. The program did not falsely identify non-LVOs as LVOs for any patients. Conclusions Identifying adjunct tools to aid timely identification and treatment of ischemic stroke in trauma patients is necessary to increase the chances for meaningful neurological recovery. Our early experience exhibited potential for using automated software to aid occlusion identification and subsequent stroke team mobilization. Future studies in larger cohorts will expand upon these preliminary findings to establish the accuracy and clinical benefit of automated stroke detection tool integration for the trauma population.

Development of a 3D Brain Model to Study Sex-Specific Neuroinflammation After Hemorrhagic Stroke.

Subarachnoid hemorrhage (SAH) accounts for 5% of stroke, with women having a decreased inflammatory response compared to men; however, this mechanism has yet to be identified. One hurdle in SAH research is the lack of human brain models. Studies in murine models are helpful, but human models should be used in conjunction for improved translatability. These observations lead us to develop a 3D system to study the sex-specific microglial and neuroglial function in a novel in vitro human SAH model and compare it to our validated in vivo SAH model. Our lab has developed a 3D, membrane-based in vitro cell culture system with human astrocytes, microglia, and neurons from both sexes. The 3D cultures were incubated with male and female cerebrospinal fluid from SAH patients in the Neuro-ICU. Furthermore, microglial morphology, erythrophagocytosis, microglial inflammatory cytokine production, and neuronal apoptosis were studied and compared with our murine SAH models. The human 3D system demonstrated intercellular interactions and proportions of the three cell types similar to the adult human brain. In vitro and in vivo models of SAH showed concordance in male microglia being more inflammatory than females via morphology and flow cytometry. On the contrary, both in vitro and in vivo models revealed that female microglia were more phagocytic and less prone to damaging neurons than males. One possible explanation for the increased phagocytic ability of female microglia was the increased expression of CD206 and MerTK. Our in vitro, human, 3D cell culture SAH model showed similar results to our in vivo murine SAH model with respect to microglial morphology, inflammation, and phagocytosis when comparing the sexes. A human 3D brain model of SAH may be a useful adjunct to murine models to improve translation to SAH patients.

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.

What Is a Meaningful Difference When Using Infarct Volume as the Primary Outcome?: Results From the HERMES Database.

BACKGROUND: Ischemic stroke lesion volume at follow-up is an important surrogate outcome for acute stroke trials. We aimed to assess which differences in 48-hour lesion volume translate into meaningful clinical differences. METHODS: We used pooled data from 7 trials investigating the efficacy of endovascular treatment for anterior circulation large vessel occlusion in acute ischemic stroke. We assessed 48-hour lesion volume follow-up computed tomography or magnetic resonance imaging. The primary outcome was a good functional outcome, defined as modified Rankin Scale (mRS) scores of 0 to 2. We performed multivariable logistic regression to predict the probability of achieving mRS scores of 0 to 2 and determined the differences in 48-hour lesion volume that correspond to a change of 1%, 5%, and 10% in the adjusted probability of achieving mRS scores of 0 to 2. RESULTS: In total, 1665/1766 (94.2%) patients (median age, 68 [interquartile range, 57-76] years, 781 [46.9%] female) had information on follow-up ischemic lesion volume. Computed tomography was used for follow-up imaging in 83% of patients. The median 48-hour lesion volume was 41 (interquartile range, 14-120) mL. We observed a linear relationship between 48-hour lesion volume and mRS scores of 0 to 2 for adjusted probabilities between 65% and 20%/volumes <80 mL, although the curve sloped off for lower mRS scores of 0-2 probabilities/higher volumes. The median differences in 48-hour lesion volume associated with a 1%, 5%, and 10% increase in the probability of mRS scores of 0 to 2 for volumes <80 mL were 2 (interquartile range, 2-3), 10 (9-11), and 20 (18-23) mL, respectively. We found comparable associations when assessing computed tomography and magnetic resonance imaging separately. CONCLUSIONS: A difference of 2, 10, and 20 mL in 48-hour lesion volume, respectively, is associated with a 1%, 5%, and 10% absolute increase in the probability of achieving good functional outcome. These results can inform the design of future stroke trials that use 48-hour lesion volume as the primary outcome.

General Versus Nongeneral Anesthesia for Middle Meningeal Artery Embolization for Chronic Subdural Hematomas: Multicenter Propensity Score Matched Study.

BACKGROUND AND OBJECTIVES: The choice of anesthesia type (general anesthesia [GA] vs nongeneral anesthesia [non-GA]) in middle meningeal artery embolization (MMAE) procedures for chronic subdural hematomas (cSDH) differs between institutions and left to care team discretion given lack of standard guidelines. We compare the outcomes of GA vs non-GA in MMAE. METHODS: Consecutive patients receiving MMAE for cSDH at 14 North American centers (2018-2023) were included. Clinical, cSDH characteristics, and technical/clinical outcomes were compared between the GA/non-GA groups. Using propensity score matching (PSM), patients were matched controlling for age, baseline modified Rankin Scale, concurrent/prior surgery, hematoma thickness/midline shift, and baseline antiplatelet/anticoagulation. The primary end points included surgical rescue and radiographic success rates (≥50% reduction in maximum hematoma thickness with minimum 2 weeks of imaging). Secondary end points included technical feasibility, procedural complications, and functional outcomes. RESULTS: Seven hundred seventy-eight patients (median age 73 years, 73.2% male patients) underwent 956 MMAE procedures, 667 (70.4%) were non-GA and 280 were GA (29.6%). After running 1:3 PSM algorithm, this resulted in 153 and 296 in the GA and non-GA groups, respectively. There were no baseline/procedural differences between the groups except radial access more significantly used in the non-GA group (P = .001). There was no difference between the groups in procedural technical feasibility, complications rate, length of stay, surgical rescue rates, or favorable functional outcome at the last follow-up. Subsequent 1:1 sensitivity PSM retained the same results. Bilateral MMAE procedures were more performed under non-GA group (75.8% vs 67.2%; P = .01); no differences were noted in clinical/radiographic outcomes between bilateral vs unilateral MMAE, except for longer procedure duration in the bilateral group (median 73 minutes [IQR 48.3-100] vs 54 minutes [39-75]; P < .0001). Another PSM analysis comparing GA vs non-GA in patients undergoing stand-alone MMAE retained similar associations. CONCLUSION: We found no significant differences in radiological improvement/clinical outcomes between GA and non-GA for MMAE.

Brain FADE syndrome: the final common pathway of chronic inflammation in neurological disease.

Importance: While the understanding of inflammation in the pathogenesis of many neurological diseases is now accepted, this special commentary addresses the need to study chronic inflammation in the propagation of cognitive Fog, Asthenia, and Depression Related to Inflammation which we name Brain FADE syndrome. Patients with Brain FADE syndrome fall in the void between neurology and psychiatry because the depression, fatigue, and fog seen in these patients are not idiopathic, but instead due to organic, inflammation involved in neurological disease initiation. Observations: A review of randomized clinical trials in stroke, multiple sclerosis, Parkinson's disease, COVID, traumatic brain injury, and Alzheimer's disease reveal a paucity of studies with any component of Brain FADE syndrome as a primary endpoint. Furthermore, despite the relatively well-accepted notion that inflammation is a critical driving factor in these disease pathologies, none have connected chronic inflammation to depression, fatigue, or fog despite over half of the patients suffering from them. Conclusions and relevance: Brain FADE Syndrome is important and prevalent in the neurological diseases we examined. Classical "psychiatric medications" are insufficient to address Brain FADE Syndrome and a novel approach that utilizes sequential targeting of innate and adaptive immune responses should be studied.

Surgical management of stylocarotid Eagle syndrome in a patient with bilateral internal carotid artery dissection: illustrative case.

BACKGROUND: Eagle syndrome is characterized by an elongated styloid process, which can cause acute neurological symptoms when the projection impinges on local structures. One method by which Eagle syndrome can cause acute stroke is via internal carotid artery dissection. OBSERVATIONS: A patient presented with acute aphasia and right-arm weakness. Imaging revealed a left internal carotid artery dissection, which was treated with stenting. Three years later, the patient presented with left-sided weakness, and imaging revealed a new right internal carotid artery dissection. Closer review of the patient's imaging revealed bilateral elongated styloid processes. The patient subsequently underwent staged bilateral styloidectomy and returned to his prior baseline postoperatively. LESSONS: This case report describes a patient with Eagle syndrome who had two internal carotid artery dissections separated by several years. A literature review revealed that styloidectomy is well tolerated in patients with carotid dissection due to Eagle syndrome. Patients with carotid dissection due to Eagle syndrome remain at risk for contralateral dissection, and prophylactic contralateral styloidectomy should be considered.

Evaluation of acute mechanical revascularization in large stroke (ASPECTS ⩽5) and large vessel occlusion within 7 h of last-seen-well: The LASTE multicenter, randomized, clinical trial protocol.

RATIONALE: Mechanical thrombectomy (MT), the standard of care for acute ischemic stroke (AIS) secondary to large vessel occlusion (LVO), is generally not offered to patients with large baseline infarct (core). Recent studies demonstrated MT benefit in patients with anterior circulation stroke and large core (i.e. Alberta Stroke Program Early Computed Tomography Score, ASPECTS 3-5). However, its benefit in patients with the largest core (ASPECTS 0-2) remains unproven. AIM: To compare the efficacy and safety of MT plus best medical treatment (BMT) and of BMT alone in patients with ASPECTS 0-5 (baseline computed tomography (CT) or magnetic resonance imaging (MRI)) and anterior circulation LVO within 7 h of last-seen-well. SAMPLE SIZE ESTIMATE: To detect with a two-sided test at 5% significance level (80% power) a common odds ratio of 1.65 for 1-point reduction in the 90-day modified Rankin Scale (mRS) score in the MT + BMT arm versus BMT arm and to anticipate 10% of patients with missing primary endpoint, 450 patients are planned to be included by 36 centers in France, Spain, and the United States. METHODS AND DESIGN: LArge Stroke Therapy Evaluation (LASTE) is an international, multicenter, Prospectively Randomized into two parallel (1:1) arms, Open-label, with Blinded Endpoint (PROBE design) trial. Eligibility criteria are diagnosis of AIS within 6.5 h of last-seen-well (or negative fluid-attenuated inversion recovery (FLAIR) if unknown stroke onset time), ASPECTS 0-5 (ASPECTS 4-5 for ⩾80-year-old patients), and LVO in the anterior circulation (intracranial internal carotid artery (ICA) and M1 or M1-M2 segment of the middle cerebral artery (MCA)). STUDY OUTCOMES: The primary endpoint is the day-90 mRS score distribution (shift analysis) with mRS categories 5 and 6 coalesced into one category. Secondary endpoints include day-180 mRS score, rates of 90-day and 180-day mRS score = 0-2 and 0-3, rate of decompressive craniectomy, the National Institutes of Health Stroke Scale (NIHSS) score change, revascularization and infarct volume growth at 24 h, and quality of life at day 90 and 180. Safety outcomes (90-day all-cause mortality, procedural complications, symptomatic intracerebral hemorrhage, and early NIHSS score worsening) are recorded. A dynamic balanced randomization (1:1) is used to distribute eligible patients into the experimental arm and control arm, by incorporating the center and these pre-specified factors: baseline ASPECTS (0-3 vs 4-5), age (⩽70 vs >70 years), baseline NIHSS (<20 vs ⩾20), intravenous thrombolysis (no vs yes), admission mode (Drip-and-Ship vs Mothership), occlusion site (intracranial ICA vs MCA-M1 or M1-M2), intravenous fibrinolysis (no vs yes), and last-seen-well to randomization time (0-4.5 vs >4.5-6.5 h). DISCUSSION: The LASTE trial will determine MT efficacy and safety in patients with ASPECTS 0-5 and LVO in the anterior circulation. TRIAL REGISTRATION: LASTE Trial NCT03811769.

Tenzing 7 delivery catheter with or without a leading microwire for single pass aspiration thrombectomy: A multicenter experience.

INTRODUCTION: Aspiration mechanical thrombectomy traditionally includes use of an inner microcatheter and leading microwire to navigate an aspiration catheter (AC) to the site of occlusion. Early clinical experience suggests that a leading microwire is often not needed with the Tenzing 7 (T7, Route 92 Medical, San Mateo, CA), a soft tapered tip ledge-reducing delivery catheter. This multicenter experience aims to describe AC delivery success in single-pass thrombectomy using T7 with and without a leading microwire. METHODS: A retrospective review was conducted of consecutive patients who underwent single-pass thrombectomy with T7 at six institutions between 2020 and 2022. We examined the percentage of successful AC delivery, puncture-to-revascularization time, and procedural complication rate. RESULTS: A leading microwire with T7 was used in 19/89 (21%) of patients, and it was not used with T7 in 70/89 (79%) of patients. Successful AC delivery was similar with and without microwires (97% vs. 90%, p = 0.15). Median puncture-to-revascularization times were similar (17 min microwire vs. 16 min no-microwire, p = 0.12). No complications were associated with microwire use; one (1.4%) patient had a T7-related vasospasm resolved with verapamil during thrombectomy without a leading microwire. Differences in complication rates were not statistically significant (p = 0.46). CONCLUSION: In our real-world clinical experience, leading microwire use was infrequently necessary with the T7 delivery catheter. Successful AC delivery and complication rates were similar with and without microwire use in single-pass T7 thrombectomies. Initial pass with T7 may be performed without use of leading microwire, reserving microwire use for refractory cases or known difficult-to-navigate vasculature.

Standalone middle meningeal artery embolization versus middle meningeal artery embolization with concurrent surgical evacuation for chronic subdural hematomas: a multicenter propensity score matched analysis of clinical and radiographic outcomes.

BACKGROUND: Middle meningeal artery embolization (MMAE) has emerged as a promising therapy for chronic subdural hematomas (cSDHs). The efficacy of standalone MMAE compared with MMAE with concurrent surgery is largely unknown. METHODS: cSDH patients who underwent successful MMAE from 14 high volume centers with at least 30 days of follow-up were included. Clinical and radiographic variables were recorded and used to perform propensity score matching (PSM) of patients treated with standalone MMAE or MMAE with concurrent surgery. Multivariable logistic regression models were used for additional covariate adjustments. The primary outcome was recurrence requiring surgical rescue, and the secondary outcome was radiographic failure defined as <50% reduction of cSDH thickness. RESULTS: 722 MMAE procedures in 588 cSDH patients were identified. After PSM, 230 MMAE procedures remained (115 in each group). Median age was 73 years, 22.6% of patients were receiving anticoagulation medication, and 47.9% had no preoperative functional disability. Median midline shift was 4 mm and cSDH thickness was 16 mm, representing modestly sized cSDHs. Standalone MMAE and MMAE with surgery resulted in similar rates of surgical rescue (7.8% vs 13.0%, respectively, P=0.28; adjusted OR (aOR 0.73 (95% CI 0.20 to 2.40), P=0.60) and radiographic failure (15.5% vs 13.7%, respectively, P=0.84; aOR 1.08 (95% CI 0.37 to 2.19), P=0.88) with a median follow-up duration of 105 days. These results were similar across subgroup analyses and follow-up durations. CONCLUSIONS: Standalone MMAE led to similar and durable clinical and radiographic outcomes as MMAE combined with surgery in select patients with moderately sized cSDHs and mild clinical disease.

Large vessel occlusion prediction scale thresholds that are sensitive for DAWN Trial patients.

BACKGROUND: Large vessel occlusion (LVO) prediction scales are used to triage prehospital suspected stroke patients with a high probability of LVO stroke to endovascular therapy centers. The sensitivities of these scales in the 6-to-24-h time window are unknown. Higher scale score thresholds are typically less sensitive and more specific. Knowing the highest scale score thresholds that remain sensitive could inform threshold selection for clinical use. Sensitivities may also vary between left and right-sided LVOs. METHODS: LVO prediction scale scores were retrospectively calculated using the National Institutes of Health Stroke Scale (NIHSS) scores of patients enrolled in the DAWN Trial. All patients had last known well times between 6 and 24 h, NIHSS scores ≥ 10, intracranial internal carotid artery or proximal middle cerebral artery occlusions, and mismatches between their clinical severities and infarct core volumes. Scale thresholds with sensitivities ≥ 85% were identified, along with scores ≥ 5% more sensitive for left or right-sided LVOs. Specificities could not be calculated because all patients had LVOs. RESULTS: A total of 201 out of 206 patients had the required NIHSS subitem scores. CPSS = 3, C-STAT ≥ 2, FAST-ED ≥ 4, G-FAST ≥ 3, RACE ≥ 5, and SAVE ≥ 3 were the highest thresholds that were still 85% sensitive for DAWN Trial LVO stroke patients. RACE ≥ 5 was the only typically used score threshold more sensitive for right-sided LVOs, though similar small differences were seen for other scales at higher thresholds. CONCLUSIONS: Our findings likely represent the maximum sensitivities of the LVO prediction scales tested for ideal thrombectomy candidates in the 6-to-24-h time window because NIHSS scores were documented in hospitals during a clinical trial rather than in the prehospital setting. Patients with NIHSS scores < 10 or more distal LVOs would lower sensitivities further. Selecting even higher scale thresholds for LVO triage would lead to many missed LVO strokes.

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.

Textural Analysis of the Hyperdense Artery Sign in Patients with Acute Ischemic Stroke Predicts the Outcome of Thrombectomy.

Textural analysis is pivotal in augmenting the diagnosis and outcomes of endovascular procedures for stroke patients. Due to the detection of changes imperceptible to the human eye, this type of analysis can potentially aid in deciding the optimal type of endovascular treatment. We included 40 patients who suffered from acute ischemic stroke caused by large vessel occlusion, and calculated 130 different textural features based on the non-enhanced CT scan using an open-source software (3D Slicer). Using chi-squared and Mann-Whitney tests and receiver operating characteristics analysis, we identified a total of 21 different textural parameters capable of predicting the outcome of thrombectomy (quantified as the mTICI score), with variable sensitivity (50-97.9%) and specificity (64.6-99.4%) rates. In conclusion, CT-based radiomics features are potential factors that can predict the outcome of thrombectomy in patients suffering from acute ischemic stroke, aiding in the decision between aspiration, mechanical, or combined thrombectomy procedure.