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Background: Transcarotid artery revascularization (TCAR) is an increasingly popular technique for the management of extracranial carotid stenosis. Its off-label use in the treatment of intracranial neurovascular disease is poorly described. Our objective is to describe the use of a dedicated open transcarotid access system for the treatment of neurovascular pathologies other than extracranial carotid stenosis., Methods: We conducted a retrospective review of a prospectively maintained database of consecutive patients who underwent treatment of neurovascular disease at a single academic center using the ENROUTE Transcarotid Arterial Sheath. Demographics, procedural characteristics, and patient outcomes were reported., Results: Twenty patients were included in the study between September 2017 and March 2023. The following pathologies were treated: intracranial atherosclerotic disease (ICAD, nine patients), complex cervico-petrous carotid disease (five patients), intracranial aneurysms (three patients), and large vessel occlusion-acute ischemic stroke (three patients). Eighteen of the 20 cases were performed with active carotid flow reversal. All cases were successfully completed. There were no access-related complications. One periprocedural complication was incurred: a microguidewire perforation during an exchange maneuver for the treatment of ICAD., Conclusion: An open transcarotid approach using a dedicated transcarotid system may offer a safe alternative access strategy for the endovascular treatment of complex neurovascular pathologies when a traditional transfemoral or transradial approach is contraindicated or failed., Competing Interests: Competing interests: BJC received consulting fees from QApel, Penumbra, and Silk Road. CCM serves as site-PI for TCAR-DWI (Silk Road Medical), national-PI for NITE1 (Silk Road Medical), and is a paid consultant for Silk Road Medical., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Competing interests: SOG: research support from the NIH-NINDS (R01NS127114-01, RO3NS126804-01), Stryker (N/A), Medtronic(N/A), Microvention(N/A), Methinks(N/A), IschemiaView(N/A), Viz.ai(N/A), and Siemens(N/A); and consulting fees from Medtronic and Stryker Neurovascular. TN: advisory board for Idorsia, Brainomix. NP: research support from the NIH/NINDS (K23NS110980) and Liminal Sciences (N/A). TGJ: advisor and investor for Anaconda, Route92, Viz.AI, FreeOx, Blockade Medical, and Methinks; grant support from Medtronic (N/A) and from Stryker Neurovascular (N/A) in his capacity as principal investigator for DAWN and AURORA; he received personal fees in his role on the Data Safety Monitoring Board. The other co-authors do not report conflicts of interests., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Preeclampsia is associated with autonomic dysregulation during pregnancy; however, less is known about autonomic function in the first week postpartum after preeclampsia., Methods: We retrospectively analyzed data from a prospective cohort of women with and without preeclampsia. Continuous blood pressure and heart rate were measured with finger plethysmography within 7 days postpartum. Frequency-domain blood pressure and heart rate variability (HRV) were calculated using spectral analysis. Time-domain HRV was calculated as the root mean square of successive R-R interval differences. We compared results between those with and without preeclampsia, as well as between those with new-onset preeclampsia, chronic hypertension with superimposed preeclampsia, and normotensive participants., Results: A total of 70 postpartum women were enrolled: 20 normotensive, 29 new-onset preeclampsia, and 21 superimposed preeclampsia. Both low- and high-frequency blood pressure variabilities were higher in those with preeclampsia compared with controls ( P =0.04 and P =0.02, respectively). This difference was driven by those with new-onset preeclampsia. The preeclampsia group had lower high-frequency HRV ( P <0.005), a higher low-/high-frequency ratio of HRV ( P <0.005), and lower time-domain HRV ( P =0.01); this difference was seen in those with and without chronic hypertension., Conclusions: Postpartum patients with preeclampsia with and without chronic hypertension had lower HRV compared with normotensive postpartum controls. Higher blood pressure variability was observed only in those with nonsuperimposed preeclampsia, suggesting that the autonomic profile of preeclampsia may differ in patients with chronic hypertension., Competing Interests: None.

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., Competing Interests: Competing interests: NP reports research support from the NIH/NINDS (K23NS110980) and Liminal Sciences. SOG reports research support from the NIH-NINDS (R01NS127114-01), Stryker, Medtronic, Microvention, Methinks, IschemiaView, Viz.ai, and Siemens; and consulting fees from Medtronic and Stryker Neurovascular. The other authors do not report conflict of interests., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Recent trials confirmed the efficacy and safety of endovascular thrombectomy in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS); however, evidence in tandem lesions is limited. This study evaluates endovascular thrombectomy safety and efficacy in patients with acute large-vessel occlusion with tandem lesions, stratified by baseline ASPECTS., Methods and Results: We conducted a retrospective analysis of data from 16 centers. Inclusion criteria included the following: age ≥18 years, anterior circulation tandem lesions, endovascular thrombectomy <24 hours of symptom onset, and ≥70% internal carotid artery stenosis/occlusion. Patients were categorized into low (0-5) and high (6-10) ASPECTS. Inverse probability of treatment weighting matching was used to balance the groups. Primary outcomes included the following: 90-day modified Rankin Scale (mRS) score 0 to 2 and symptomatic intracranial hemorrhage. Secondary outcomes included the following: ordinal mRS, mRS 0 to 3, modified Thrombolysis in Cerebral Infarction ≥2b and 2c-3, petechial hemorrhage, parenchymal hematoma (1/2), early neurologic improvement, and mortality. Of 691 patients, 44 had ASPECTS 0 to 5 and 505 had ASPECTS 6 to 10. Patients with low ASPECTS had lower odds of 90-day mRS 0 to 2 (adjusted odds ratio [OR], 0.48; P =0.036) and higher odds of symptomatic intracranial hemorrhage (adjusted OR, 3.78; P =0.014). Additional significant differences were found in mRS shift, mRS 0 to 3, parenchymal hematoma 2, and mortality. In interaction analysis, the association between low ASPECTS and functional outcome persisted only in the internal carotid artery occlusion subgroup, with no significant interaction indicating no reason to suppose a difference between the effect of both subgroups., Conclusions: Endovascular thrombectomy in patients with tandem lesions with low ASPECTS is associated with reduced odds of functional recovery and increased symptomatic intracranial hemorrhage risk, when compared with patients with high ASPECTS. However, 30% of patients with low ASPECTS achieved 90-day functional independence, suggesting potential benefit for a nonnegligible proportion of patients.

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.

Background: The Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II randomized controlled trial used a tier-based management protocol based on brain tissue oxygen (PbtO 2 ) and intracranial pressure (ICP) monitoring to reduce brain tissue hypoxia after severe traumatic brain injury. We performed a secondary analysis to explore the relationship between brain tissue hypoxia, blood pressure (BP), and interventions to improve cerebral perfusion pressure (CPP). We hypothesized that BP management below the lower limit of autoregulation would lead to cerebral hypoperfusion and brain tissue hypoxia that could be improved with hemodynamic augmentation., Methods: Of the 119 patients enrolled in the Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II trial, 55 patients had simultaneous recordings of arterial BP, ICP, and PbtO 2 . Autoregulatory function was measured by interrogating changes in ICP and PbtO 2 in response to fluctuations in CPP using time-correlation analysis. The resulting autoregulatory indices (pressure reactivity index and oxygen reactivity index) were used to identify the "optimal" CPP and limits of autoregulation for each patient. Autoregulatory function and percent time with CPP outside personalized limits of autoregulation were calculated before, during, and after all interventions directed to optimize CPP., Results: Individualized limits of autoregulation were computed in 55 patients (mean age 38 years, mean monitoring time 92 h). We identified 35 episodes of brain tissue hypoxia (PbtO 2  < 20 mm Hg) treated with CPP augmentation. Following each intervention, mean CPP increased from 73 ± 14 mm Hg to 79 ± 17 mm Hg (p = 0.15), and mean PbtO 2 improved from 18.4 ± 5.6 mm Hg to 21.9 ± 5.6 mm Hg (p = 0.01), whereas autoregulatory function trended toward improvement (oxygen reactivity index 0.42 vs. 0.37, p = 0.14; pressure reactivity index 0.25 vs. 0.21, p = 0.2). Although optimal CPP and limits remained relatively unchanged, there was a significant decrease in the percent time with CPP below the lower limit of autoregulation in the 60 min after compared with before an intervention (11% vs. 23%, p = 0.05)., Conclusions: Our analysis suggests that brain tissue hypoxia is associated with cerebral hypoperfusion characterized by increased time with CPP below the lower limit of autoregulation. Interventions to increase CPP appear to improve autoregulation. Further studies are needed to validate the importance of autoregulation as a modifiable variable with the potential to improve outcomes., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

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., Competing Interests: Disclosures A.E. Hassan reports compensation from Penumbra, Inc, for consultant services; employment by Valley Baptist Medical Center; compensation from Cerenovus for consultant services; compensation from Medtronic for consultant services; compensation from viz AI for consultant services; compensation from MicroVention, Inc, for consultant services; compensation from Stryker Corporation for consultant services; and compensation from GE Healthcare for consultant services. Dr Divani reports employment by the University of New Mexico. Dr Abraham reports compensation from Penumbra, Inc, for consultant services; compensation from Stryker Corporation for consultant services; and compensation from Q’Apel for consultant services. Dr Fifi reports compensation from Cerenovus for consultant services; compensation from Mivi for data and safety monitoring services; employment by Mount Sinai Health System; compensation from MicroVention, Inc, for consultant services; compensation from Stryker Corporation for consultant services; grants from viz AI; stock holdings in Imperitive Care; compensation from Penumbra, Inc, for consultant services; and compensation from Medtronic for consultant services. Dr Siegler reports grants from Philips and viz AI. Dr Nguyen reports compensation from Brainomix for consultant services; compensation from Aruna for consultant services; and compensation from the American Stroke Association for other services. Dr Sheth reports compensation from viz AI for consultant services; compensation from Imperative Care, Inc, for consultant services; employment by UTHealth McGovern Medical School; compensation from Motif Neurosciences for other services; compensation from Penumbra, Inc, for consultant services; and grants from the National Institutes of Health. Dr Yoo reports compensation from Vesalio for consultant services; grants from Genentech USA, Inc, to other services; compensation from the National Institutes of Health for data and safety monitoring services; compensation from Rapid Medical, Ltd, for consultant services; stock holdings in Galaxy Therapeutics; compensation from Johnson & Johnson Medical Devices & Diagnostics Group-Latin America, L.L.C. for consultant services; compensation from ZOLL Circulation, Inc, for consultant services; grants from Medtronic to other services; employment by HCA Healthcare; grants from Johnson & Johnson Medical Devices & Diagnostics Group-Latin America, L.L.C. to other services; grants from Penumbra, Inc, to other services; stock holdings in Insera; compensation from Nicolab for consultant services; compensation from Penumbra, Inc, for consultant services; grants from Stryker to other services; stock options in Nicolab; compensation from Philips for consultant services; compensation from the American Heart Association for other services. Dr De Leacy reports compensation from Stryker Corporation for consultant services; stock holdings in endostream; stock holdings in Spartan Micro; stock holdings in Synchron; stock holdings in Q’Apel; compensation from Imperative Care, Inc, for consultant services; stock holdings in Vastrax; and compensation from Johnson & Johnson for consultant services. Dr Mokin reports stock holdings in QAS.AI; compensation from MicroVention, Inc, for consultant services; compensation from Balt USA, LLC for consultant services; stock holdings in Serenity Medical; stock holdings in Bendit Technology; compensation from Medtronic for consultant services; compensation from Johnson & Johnson Medical Devices & Diagnostics Group-Latin America, L.L.C. for consultant services; stock holdings in Borvo Medical; stock holdings in BrainQ; stock holdings in Quantanosis.AI; compensation from Rapid Pulse for consultant services; stock holdings in Sim&Cure; stock holdings in Synchrone; stock holdings in Radical Catheter Technologies; and stock holdings in Endostream. Dr Yavagal reports stock options in Rapid Medical; compensation from Stryker Corporation for consultant services; compensation from Johnson & Johnson Health Care Systems, Inc, for consultant services; stock holdings in Athersys; compensation from Poseydon for consultant services; compensation from Gravity Medical Technology for consultant services; compensation from Medtronic USA, Inc, for consultant services; compensation from Athersys for consultant services; compensation from Vascular Dynamics for consultant services; and stock options in Poseydon. Dr Ribo reports stock holdings in Methinks; stock holdings in Anaconda Biomed; compensation from Philips for consultant services; compensation from Stryker Corporation for consultant services; stock holdings in Nora; compensation from Cerenovus for consultant services; compensation from AptaTargets for consultant services; and compensation from Medtronic MiniMed, Inc, for consultant services. Dr Jovin reports employment by Cooper University Healthcare; stock options in Gravity; compensation from Johnson & Johnson Cerenovus for data and safety monitoring services; stock options in Anaconda; stock options in Route92; stock options in Galaxy; stock options in Methinks; stock options in viz AI; stock options in StataDx; stock options in Basking; compensation from Contego Medical, Inc, for consultant services; stock options in Freeox Biotech; stock options in Kandu; grants from Stryker Corporation; and grants from Medtronic USA, Inc. Dr Ortega-Gutierrez reports grants from MicroVention, Inc; grants from Siemens; grants from the National Institutes of Health; compensation from Medtronic for consultant services; compensation from Stryker for consultant services; compensation from MicroVention, Inc, for consultant services; grants from Methinks; grants from the National Institutes of Health; grants from Stryker; and employment by Carver College of Medicine–University of Iowa. The other authors report no conflicts.

Background: Personalized blood pressure (BP) management for patients with acute ischemic stroke after successful endovascular thrombectomy lacks evidence. We aimed to investigate whether the deviation of BP from cerebral autoregulation limits is associated with worse outcomes., Methods and Results: We determined autoregulation by measuring mean velocity index and calculated the percentage of time and the burden (defined as the time-BP area) with BP outside the autoregulatory limits of each subject within 48 hours after endovascular thrombectomy. In total, 91 patients with large vessel occlusion stroke who had achieved successful recanalization were prospectively enrolled between May 2020 and February 2022. The burden with BP outside the autoregulatory limits was associated with poor outcome (modified Rankin Scale score 3-6) at 90 days (adjusted odds ratio, 1.28 [95% CI, 1.03-1.59]). The percentage of time with BP out of the autoregulatory limits was correlated with early neurological deterioration (National Institute of Health Stroke Scale scores increased ≥2 at 7 days) (adjusted odds ratio, 1.38 [95% CI, 1.04-1.83]). The burden of BP that decreased below the autoregulatory lower limit was associated with significant infarct growth (volume of infarct growth >11.6 mL) at 7 days (adjusted odds ratio, 1.21 [95% CI, 1.01-1.44]). The percentage of time that BP exceeded the autoregulatory upper limit was associated with symptomatic intracranial hemorrhage within 48 hours (adjusted odds ratio, 1.55 [95% CI, 1.02-2.34])., Conclusions: Both the percentage of time and the burden of BP that deviates from the autoregulation-preserved range are associated with unfavorable clinical outcomes. This study highlights the potential benefits of autoregulation-guided BP management strategy after successful recanalization.

Background: Intracerebral hemorrhage (ICH) is a major cause of maternal morbidity, but its pathophysiology is poorly characterized. We investigated characteristics of pregnancy-associated ICH (P-ICH), compared with ICH in similar aged nonpregnant adults of both sexes., Methods and Results: We performed a retrospective analysis of 134 adults aged 18 to 44 years admitted to our center with nontraumatic ICH from January 1, 2012, to December 31, 2021. We compared ICH characteristics among 3 groups: those with P-ICH (pregnant or within 12 months of end of pregnancy); nonpregnant women; and men. We categorized ICH pathogenesis according to a modified scheme, SMASH-UP (structural, medications, amyloid angiopathy, systemic, hypertension, undetermined, posterior reversible encephalopathy syndrome/reversible cerebral vasoconstriction syndrome), and calculated odds ratios and 95% CIs for primary (spontaneous small-vessel) ICH versus secondary ICH (structural lesions or coagulopathy related), using nonpregnant women as the reference. We also compared specific ICH pathogenesis by SMASH-UP criteria and functional outcomes between groups. Of 134 young adults with nontraumatic ICH, 25 (19%) had P-ICH, of which 60% occurred postpartum. Those with P-ICH had higher odds of primary ICH compared with nonpregnant women (adjusted odds ratio, 4.5 [95% CI, 1.4-14.7]). The odds of primary ICH did not differ between men and nonpregnant women. SMASH-UP pathogenesis for ICH differed significantly between groups ( P <0.001). While the in-hospital mortality rate was lowest in the P-ICH group (4%) compared with nonpregnant women (13%) and men (24%), 1 in 4 patients with P-ICH were bedbound and dependent at the time of discharge., Conclusions: In our cohort of young adults with ICH, 1 in 5 was pregnancy related. P-ICH differed in pathogenesis compared with non-pregnancy-related ICH in young adults, suggesting unique pathophysiology.

Background: Data on systolic blood pressure (SBP) trajectories in the first 24 hours after endovascular thrombectomy (EVT) in acute ischemic stroke are limited. We sought to identify these trajectories and their relationship to outcomes., Methods: We combined individual-level data from 5 studies of patients with acute ischemic stroke who underwent EVT and had individual blood pressure values after the end of the procedure. We used group-based trajectory analysis to identify the number and shape of SBP trajectories post-EVT. We used mixed effects regression models to identify associations between trajectory groups and outcomes adjusting for potential confounders and reported the respective adjusted odds ratios (aORs) and common odds ratios., Results: There were 2640 total patients with acute ischemic stroke included in the analysis. The most parsimonious model identified 4 distinct SBP trajectories, that is, general directional patterns after repeated SBP measurements: high, moderate-high, moderate, and low. Patients in the higher blood pressure trajectory groups were older, had a higher prevalence of vascular risk factors, presented with more severe stroke syndromes, and were less likely to achieve successful recanalization after the EVT. In the adjusted analyses, only patients in the high-SBP trajectory were found to have significantly higher odds of early neurological deterioration (aOR, 1.84 [95% CI, 1.20-2.82]), intracranial hemorrhage (aOR, 1.84 [95% CI, 1.31-2.59]), mortality (aOR, 1.75 [95% CI, 1.21-2.53), death or disability (aOR, 1.63 [95% CI, 1.15-2.31]), and worse functional outcomes (adjusted common odds ratio,1.92 [95% CI, 1.47-2.50])., Conclusions: Patients follow distinct SBP trajectories in the first 24 hours after an EVT. Persistently elevated SBP after the procedure is associated with unfavorable short-term and long-term outcomes., Competing Interests: Disclosures A.H. Katsanos serves as the PI for the Blood Pressure Management in Stroke Following Endovascular Treatment trial. The other authors report no conflicts.

Hematoma expansion (HE) is a modifiable risk factor and a potential treatment target in patients with intracerebral hemorrhage (ICH). We aimed to train and validate deep-learning models for high-confidence prediction of supratentorial ICH expansion, based on admission non-contrast head Computed Tomography (CT). Applying Monte Carlo dropout and entropy of deep-learning model predictions, we estimated the model uncertainty and identified patients at high risk of HE with high confidence. Using the receiver operating characteristics area under the curve (AUC), we compared the deep-learning model prediction performance with multivariable models based on visual markers of HE determined by expert reviewers. We randomly split a multicentric dataset of patients (4-to-1) into training/cross-validation (n = 634) versus test (n = 159) cohorts. We trained and tested separate models for prediction of ≥6 mL and ≥3 mL ICH expansion. The deep-learning models achieved an AUC = 0.81 for high-confidence prediction of HE ≥6 mL and AUC = 0.80 for prediction of HE ≥3 mL , which were higher than visual maker models AUC = 0.69 for HE ≥6 mL (p = 0.036) and AUC = 0.68 for HE ≥3 mL (p = 0.043). Our results show that fully automated deep-learning models can identify patients at risk of supratentorial ICH expansion based on admission non-contrast head CT, with high confidence, and more accurately than benchmark visual markers., (© 2024. The Author(s).)

Background: Neuroimaging is essential for detecting spontaneous, nontraumatic intracerebral hemorrhage (ICH). Recent data suggest ICH can be characterized using low-field magnetic resonance imaging (MRI). Our primary objective was to investigate the sensitivity and specificity of ICH on a 0.064T portable MRI (pMRI) scanner using a methodology that provided clinical information to inform rater interpretations. As a secondary aim, we investigated whether the incorporation of a deep learning (DL) reconstruction algorithm affected ICH detection., Methods: The pMRI device was deployed at Yale New Haven Hospital to examine patients presenting with stroke symptoms from October 26, 2020 to February 21, 2022. Three raters independently evaluated pMRI examinations. Raters were provided the images alongside the patient's clinical information to simulate real-world context of use. Ground truth was the closest conventional computed tomography or 1.5/3T MRI. Sensitivity and specificity results were grouped by DL and non-DL software to investigate the effects of software advances., Results: A total of 189 exams (38 ICH, 89 acute ischemic stroke, 8 subarachnoid hemorrhage, 3 primary intraventricular hemorrhage, 51 no intracranial abnormality) were evaluated. Exams were correctly classified as positive or negative for ICH in 185 of 189 cases (97.9% overall accuracy). ICH was correctly detected in 35 of 38 cases (92.1% sensitivity). Ischemic stroke and no intracranial abnormality cases were correctly identified as blood-negative in 139 of 140 cases (99.3% specificity). Non-DL scans had a sensitivity and specificity for ICH of 77.8% and 97.1%, respectively. DL scans had a sensitivity and specificity for ICH of 96.6% and 99.3%, respectively., Conclusions: These results demonstrate improvements in ICH detection accuracy on pMRI that may be attributed to the integration of clinical information in rater review and the incorporation of a DL-based algorithm. The use of pMRI holds promise in providing diagnostic neuroimaging for patients with ICH., Competing Interests: Disclosures Dr Sheth is the principal investigator. Dr Sheth reports compensation from CSL Behring for consultant services; grants from BARD; compensation from Astrocyte for consultant services; compensation from Rhaeos for consultant services; compensation from Certus for consultant services; grants from Novartis; a patent pending for Stroke wearables licensed to Alva Health; compensation from Cerevasc for consultant services; compensation from ZOLL Medical Corporation for data and safety monitoring services; grants from Hyperfine; employment by Yale School of Medicine; compensation from Sense for data and safety monitoring services; grants from Hyperfine to other; and grants from Biogen. Dr Kimberly reports grants from NControl Therapeutics; compensation from Astrocyte Pharmaceuticals for consultant services; compensation from Acasti Pharmaceuticals for consultant services; grants from Hyperfine Research Inc; a patent pending for No. 16/486 687, Methods and Compositions for Treating a Brain Injury. licensed to NControl Therapeutics; grants from Biogen; stock holdings in Woolsey Pharmaceuticals; and compensation from NControl Therapeutics for consultant services. Dr de Havenon reports compensation from Novo Nordisk for consultant services; compensation from Integra for consultant services; grants from National Institutes of Health (NIH); stock options in Certus; and stock options in TitinKM. Dr Rosen reports grants from American Heart Association (AHA), Advanced Research Projects Agency–Energy (ARPA-E), Department of Energy (DOE), and the NIH. Dr Rosen is on the scientific advisory board of ABQMR, Synex Medical, Inc, Nanalysis, Inc, O2M Technologies, Inc, Quantum Catalyzer, Inc, and Lincoln Agritech LTD. Dr Rosen is a Founder and equity holder of Hyperfine, Vizma Life Sciences, Intact Data Services, and Q4ML. He acknowledges the support of the Kiyomi and Ed Baird Research Scholar award. Dr Matouk reports compensation from Silk Road Medical, Inc, for consultant services; compensation from MicroVention, Inc, for consultant services; and compensation from Penumbra, Inc, for consultant services. Dr Falcone reports grants from AHA and grants from National Institutes of Health. Dr Sorby-Adams reports grants from Australian-American Fulbright Commission and grants from AHA. The other authors report no conflicts.

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., Competing Interests: Disclosures A.E. Hassan is a consultant/speaker at Medtronic, Microvention, Stryker, Penumbra, Cerenovus, Genentech, GE Healthcare, Scientia, Balt, vizai, Insera therapeutics, Proximie, NeuroVasc, NovaSignal, Vesalio, Rapid Medical, Imperative Care and Galaxy Therapeutics; principal investigator for COMPLETE study—Penumbra, LVO SYNCHRONISE—vizai, Millipede Stroke Trial—Perfuze, RESCUE—ICAD, Medtronic; steering committee/publication committee member for SELECT, DAWN, SELECT 2, EXPEDITE II, EMBOLISE, CLEAR, ENVI, DELPHI, DISTALS. Dr Divani performed fundings at the University of New Mexico Center for Brain Recovery and Repair Center of Biomedical Research Excellence through Grant Number (NIH P20GM109089, Pilot PI), W81XWH-17-2-0053 (PI), 1R21NS130423-01 (PI). Dr Ribo is consultant at aptaTargets, Anaconda Biomed, Philips, Medtronic, Cerenovus, Vesalio, and Rapid Pulse outside the submitted work. Dr Abraham is a consultant at Penumbra Inc, Qapel, Stryker Corporation. Dr Fifi is a consultant at Cerenovus, Stryker Corporation, Microvention Inc; received stock from Cerebrotech, Imperative Care, Sime&Cure; and received grants from viz AI. Data and Safety Monitoring: MIVI. Dr Yoo is a consultant for Johnson & Johnson Medical Devices & Diagnostics Group—Latin America, LLC, Nicolab, Penumbra Inc, Philips, Vesalio, ZOLL Circulation Inc; received grants from Genetech, USA Inc, Johnson & Johnson Medical Devices & Diagnostics Group—Latin America, LLC, Medtronic, Penumbra Inc, Stryker; Employment at HCA Healthcare; received stock from Insera, Nicolab; performed data and safety monitoring at National Institutes of Health. Dr Mokin is a consultant at Johnson & Johnson Medical Devices & Diagnostics Group—Latin America, LLC, Medtronic, MicroVention Inc, received stock from Bendit Technology, BrainQ, Serenity medical, Synchrone. Dr Yavagal is a consultant at Athersys, Gravity Medical Technology, Johnson & Johnson Health Care Systems Inc, Medtronic USA Inc, Poseydon, Stryker Corporation, Vascular Dynamics; received stock from Athersys, Poseydon, Rapid Medical. Dr Jovin is a consultant at Contego Medical Inc received stock from Anaconda, Freeox Biotech, Galaxy, Kandu, Methinks, Route92, vizai. Grant: Medtronicm, USA, Inc, Stryker Corporation; performed data and safety monitoring at Johnson & Johnson, Cerenovus. Dr Sheth is a consultant at vizAI, Penumbra, Imperative Care; received grants from NIH, vizAI; and took ownership for Motif Neuroscience (not related to this article). Dr Ortega-Gutierrez received grants from NIH-NINDS (R01NS127114-01, R03NS126804), Stryker, Medtronics, Microvention, Penumbra, IschemiaView, vizai, and Siemens; he is a consultant at Medtronic and Stryker Neurovascular. The other authors report no conflicts.

Background and Objectives: It is unclear whether blood pressure variability's (BPV) association with worse outcomes is unique to patients with stroke or a risk factor among all critically ill patients. We (1) determined whether BPV differed between patients with stroke and nonstroke patients, (2) examined BPV's associations with in-hospital death and favorable discharge destination in patients with stroke and nonstroke patients, and (3) assessed how minimum mean arterial pressure (MAP)-a correlate of illness severity and cerebral perfusion-affects these associations., Methods: This is a retrospective analysis of adult intensive care unit patients hospitalized between 2001 and 2012 from the Medical Information Mart for Intensive Care III database. Confounder-adjusted logistic regressions determined associations between BPV, measured as SD and average real variability (ARV), and (1) in-hospital death and (2) favorable discharge, with testing of minimum MAP for effect modification., Results: BPV was higher in patients with stroke (N = 2,248) compared with nonstroke patients (N = 9,085) (SD mean difference 2.3, 95% CI 2.1-2.6, p < 0.01). After adjusting for minimum tertile of MAP and other confounders, higher SD remained significantly associated ( p < 0.05) with higher odds of in-hospital death for patients with acute ischemic strokes (AISs, odds ratio [OR] 2.7, 95% CI 1.5-4.8), intracerebral hemorrhage (ICH, OR 2.6, 95% CI 1.6-4.3), subarachnoid hemorrhage (SAH, OR 3.4, 95% CI 1.2-9.3), and pneumonia (OR 1.9, 95% CI 1.1-3.3) and lower odds of favorable discharge destination in patients with ischemic stroke (OR 0.3, 95% CI 0.2-0.6) and ICH (OR 0.4, 95% CI 0.3-0.6). No interaction was found between minimum MAP tertile with SD ( p > 0.05). Higher ARV was not significantly associated with increased risk of death in any condition when adjusting for illness severity but portended worse discharge destination in those with AIS (OR favorable discharge 0.4, 95% CI 0.3-0.7), ICH (OR favorable discharge 0.5, 95% CI 0.3-0.7), sepsis (OR favorable discharge 0.8, 95% CI 0.6-1.0), and pneumonia (OR favorable discharge 0.5, 95% CI 0.4-0.8)., Discussion: BPV is higher and generally associated with worse outcomes among patients with stroke compared with nonstroke patients. BPV in patients with AIS and patients with ICH may be a marker of central autonomic network injury, although clinician-driven blood pressure goals likely contribute to the association between BPV and outcomes., (© 2023 American Academy of Neurology.)

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.

Background: While recent studies suggest a benefit of mechanical thrombectomy (MT) for the treatment of patients with isolated large vessel occlusions presenting after 24 hours from the last known well (LKW), the effect of MT for acute cervical tandem lesions (TLs) beyond 24 hours remains unknown. We aimed to evaluate the safety and effectiveness of MT beyond 24 hours of LKW in patients with TLs., Methods: We conducted a subanalysis study of patients with anterior circulation TL enrolled in a large, multicenter registry between January 2015 and December 2020. Patients were divided into 2 groups: MT beyond 24 hours versus MT 0-24-hour window. Outcomes of interest were functional independence (90-day modified Rankin scale 0-2), complete reperfusion (modified thrombolysis in cerebral infarction 3), delta NIH Stroke Scale (NIHSS), symptomatic intracranial hemorrhage (sICH), parenchymal hematoma 2 (PH2), in-hospital mortality, and 90-day mortality. Inverse probability of treatment weighting (IPTW) was used to balance the groups., Results: Overall, 589 participants were included, with 33 treated beyond 24 hours and 556 treated in the 0-24-hour window. After IPTW, we found no significant difference in the rates of achieving functional independence (odds ratio (OR)   = 0.51; 95% confidence interval (CI) 0.22-1.16; p  = 0.108), complete reperfusion (OR   = 1.35; 95% CI 0.60-3.05; p  = 0.464), sICH (OR   = 1.96; 95% CI 0.37-10.5; p  = 0.429), delta NIHSS (β   =   -3.61; 95% CI -8.11 to 0.87; p  = 0.114), PH2 (OR   = 1.46; 95% CI 0.29-7.27; p  = 0.642), in-hospital mortality (OR   = 1.74; 95% CI 0.52-5.86; p  = 0.370), or 90-day mortality (OR   = 1.37; 95% CI 0.49-3.83; p  = 0.544) across both time windows., Conclusions: Our results suggest that MT appears to benefit patients with TLs beyond 24 hours from LKW. Future prospective studies are warranted.

In the 20th century, the advent of neuroimaging dramatically altered the field of neurologic care. However, despite iterative advances since the invention of CT and MRI, little progress has been made to bring MR neuroimaging to the point of care. Recently, the emergence of a low-field (<1 T) portable MRI (pMRI) is setting the stage to revolutionize the landscape of accessible neuroimaging. Users can transport the pMRI into a variety of locations, using a standard 110-220 V wall outlet. In this article, we discuss current applications for pMRI, including in the acute and critical care settings, the barriers to broad implementation, and future opportunities., (© 2023 American Academy of Neurology.)

Scientific advances have informed many aspects of acute stroke care but have also highlighted the complexity and heterogeneity of cerebrovascular diseases. While practice guidelines are essential in supporting the clinical decision-making process, they may not capture the nuances of individual cases. Personalized stroke care in ICU has traditionally relied on integrating clinical examinations, neuroimaging studies, and physiologic monitoring to develop a treatment plan tailored to the individual patient. However, to realize the potential of precision medicine in stroke, we need advances and evidence in several critical areas, including data capture, clinical phenotyping, serum biomarker development, neuromonitoring, and physiology-based treatment targets. Mathematical tools are being developed to analyze the multitude of data and provide clinicians with real-time information and personalized treatment targets for the critical care management of patients with cerebrovascular diseases. This review summarizes research advances in these areas and outlines principles for translating precision medicine into clinical practice.

Background and Objectives: Blood pressure (BP) is often not at goal in stroke survivors, leaving individuals vulnerable to additional vascular events. Given that BP is a highly heritable trait, we hypothesize that a higher polygenic susceptibility to hypertension (PSH) leads to worse BP control in stroke survivors., Methods: We conducted a study within the UK Biobank evaluating persons of European ancestry who survived an ischemic or hemorrhagic stroke. To model the PSH, we created polygenic risk scores (PRSs) for systolic and diastolic BP using 732 genetic variants. We divided the PRSs into quintiles and used linear/logistic regression to test whether higher PSH led to higher observed BP, uncontrolled BP (systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg), and resistant BP (uncontrolled BP despite being on ≥3 antihypertensive drugs). We conducted an independent replication using data from the Vitamin Intervention for Stroke Prevention (VISP) trial., Results: We analyzed 5,940 stroke survivors. When comparing stroke survivors with very low vs very high PSH, the mean systolic BP was 137 (SD 18) vs 143 (SD 20, p < 0.001), the mean diastolic BP was 81 (SD 10) vs 84 (SD 11, p < 0.001), the prevalence of uncontrolled BP was 42.8% vs 57.2% ( p < 0.001), and the prevalence of resistant hypertension was 3.9% vs 11% ( p < 0.001). Results remained significant using multivariable models ( p < 0.001) and were replicated in the VISP study (all tests with p < 0.05)., Discussion: A higher PSH is associated with worse BP control in stroke survivors. These findings point to genetic predisposition as an important determinant of poorly controlled BP in this population., (© 2023 American Academy of Neurology.)

Introduction: Observational studies have found an increased risk of hemorrhagic transformation and worse functional outcomes in patients with higher systolic blood pressure variability (BPV). However, the time-varying behavior of BPV after endovascular thrombectomy (EVT) and its effects on functional outcome have not been well characterized., Patients and Methods: We analyzed data from an international cohort of patients with large-vessel occlusion stroke who underwent EVT at 11 centers across North America, Europe, and Asia. Repeated time-stamped blood pressure data were recorded for the first 72 h after thrombectomy. Parameters of BPV were calculated in 12-h epochs using five established methodologies. Systolic BPV trajectories were generated using group-based trajectory modeling, which separates heterogeneous longitudinal data into groups with similar patterns., Results: Of the 2041 patients (age 69 ± 14, 51.4% male, NIHSS 15 ± 7, mean number of BP measurements 50 ± 28) included in our analysis, 1293 (63.4%) had a poor 90-day outcome (mRS ⩾ 3) or a poor discharge outcome (mRS ⩾ 3). We identified three distinct SBP trajectories: low (25%), moderate (64%), and high (11%). Compared to patients with low BPV, those in the highest trajectory group had a significantly greater risk of a poor functional outcome after adjusting for relevant confounders (OR 2.2; 95% CI 1.2-3.9; p  = 0.008). In addition, patients with poor outcomes had significantly higher systolic BPV during the epochs that define the first 24 h after EVT ( p  < 0.001)., Discussion and Conclusions: Acute ischemic stroke patients demonstrate three unique systolic BPV trajectories that differ in their association with functional outcome. Further research is needed to rapidly identify individuals with high-risk BPV trajectories and to develop treatment strategies for targeting high BPV., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Spiotta reports grants and personal fees from Penumbra, grants and personal fees from Stryker, grants from Medtronic, non-financial support from RAPID, personal fees from Terumo, and personal fees from Cerenovus outside the submitted work. Dr. Liman reports personal fees from Stryker outside the submitted work. Dr. de Havenon reports grants from AMAG and grants from Regeneron outside the submitted work. Dr. Ortega-Gutierrez reports grants from Stryker, IschemiaView, Viz.ai, and Siemens; personal fees from Medtronic and personal fees from Stryker outside the submitted work. Dr. Sheth reports grants from NIH, grants from AHA, grants from Hyperfine, grants from Biogen, grants from Zoll, and other support from Alva outside the submitted work., (© European Stroke Organisation 2022.)

Background: We investigated the effects of the side of large vessel occlusion (LVO) on post-thrombectomy infarct volume and clinical outcome with regard to admission National Institutes of Health Stroke Scale (NIHSS) score., Methods: We retrospectively identified patients with anterior LVO who received endovascular thrombectomy and follow-up MRI. Applying voxel-wise general linear models and multivariate analysis, we assessed the effects of occlusion side, admission NIHSS, and post-thrombectomy reperfusion (modified Thrombolysis in Cerebral Infarction, mTICI) on final infarct distribution and volume as well as discharge modified Rankin Scale (mRS) score., Results: We included 469 patients, 254 with left-sided and 215 with right-sided LVO. Admission NIHSS was higher in those with left-sided LVO (median (IQR) 16 (10-22)) than in those with right-sided LVO (14 (8-16), p>0.001). In voxel-wise analysis, worse post-thrombectomy reperfusion, lower admission NIHSS score, and poor discharge outcome were associated with right-hemispheric infarct lesions. In multivariate analysis, right-sided LVO was an independent predictor of larger final infarct volume (p=0.003). There was a significant three-way interaction between admission stroke severity (based on NIHSS), LVO side, and mTICI with regard to final infarct volume (p=0.041). Specifically, in patients with moderate stroke (NIHSS 6-15), incomplete reperfusion (mTICI 0-2b) was associated with larger final infarct volume (p<0.001) and worse discharge outcome (p=0.02) in right-sided compared with left-sided LVO., Conclusions: When adjusted for admission NIHSS, worse post-thrombectomy reperfusion is associated with larger infarct volume and worse discharge outcome in right-sided versus left-sided LVO. This may represent larger tissue-at-risk in patients with right-sided LVO when applying admission NIHSS as a clinical biomarker for penumbra., Competing Interests: Competing interests: DF reports holding an equity interest in ai4medicine with no connection to the presented work. He also reports a pending patent for A clinical decision support system for stroke treatment (EP21159801.6). VIM reports receiving personal fees from ai4medicine outside the presented work. There is no connection, commercial exploitation, transfer or association between the projects of ai4medicine and the presented work. He also reports a pending patent for A clinical decision support system for stroke treatment (EP21159801.6). PS received research funding from Siemens Healthineers and the Neiman Health Policy Institute. KNS reports equity interests in Alva Health and serves on the advisory board for NControl., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: The evidence linking chronic kidney disease (CKD) to spontaneous intracerebral hemorrhage (ICH) is inconclusive owing to possible confounding by comorbidities that frequently coexist in patients with these 2 diseases., Objective: To determine whether there is an association between CKD and ICH risk., Design, Setting, and Participants: A 3-stage study that combined observational and genetic analyses was conducted. First, the association between CKD and ICH risk was tested in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, a multicenter case-control study in the US. All participants with available data on CKD from ERICH were included. Second, this analysis was replicated in the UK Biobank (UKB), an ongoing population study in the UK. All participants in the UKB were included in this study. Third, mendelian randomization analyses were implemented in the UKB using 27 CKD-related genetic variants to test for genetic associations. ERICH was conducted from August 1, 2010, to August 1, 2017, and observed participants for 1 year. The UKB enrolled participants between 2006 and 2010 and will continue to observe them for 30 years. Data analysis was performed from November 11, 2019, to May 10, 2022., Exposures: CKD stages 1 to 5., Main Outcomes and Measures: The outcome of interest was ICH, ascertained in ERICH via expert review of neuroimages and in the UKB via a combination of self-reported data and International Statistical Classification of Diseases, Tenth Revision, codes., Results: In the ERICH study, a total of 2914 participants with ICH and 2954 controls who had available data on CKD were evaluated (mean [SD] age, 61.6 [14.0] years; 2433 female participants [41.5%]; 3435 male participants [58.5%]); CKD was found to be independently associated with higher risk of ICH (odds ratio [OR], 1.95; 95% CI, 1.35-2.89; P < .001). This association was not modified by race and ethnicity. Replication in the UKB with 1341 participants with ICH and 501 195 controls (mean [SD] age, 56.5 [8.1] years; 273 402 female participants [54.4%]; 229 134 male participants [45.6%]) confirmed this association (OR, 1.28; 95% CI, 1.01-1.62; P = .04). Mendelian randomization analyses indicated that genetically determined CKD was associated with ICH risk (OR, 1.56; 95% CI, 1.13-2.16; P = .007)., Conclusions and Relevance: In this 3-stage study that combined observational and genetic analyses among study participants enrolled in 2 large observational studies with different characteristics and study designs, CKD was consistently associated with higher risk of ICH. Mendelian randomization analyses suggest that this association was causal. Further studies are needed to identify the specific biological pathways that mediate this association.

Brain imaging is essential to the clinical management of patients with ischemic stroke. Timely and accessible neuroimaging, however, can be limited in clinical stroke pathways. Here, portable magnetic resonance imaging (pMRI) acquired at very low magnetic field strength (0.064 T) is used to obtain actionable bedside neuroimaging for 50 confirmed patients with ischemic stroke. Low-field pMRI detected infarcts in 45 (90%) patients across cortical, subcortical, and cerebellar structures. Lesions as small as 4 mm were captured. Infarcts appeared as hyperintense regions on T2-weighted, fluid-attenuated inversion recovery and diffusion-weighted imaging sequences. Stroke volume measurements were consistent across pMRI sequences and between low-field pMRI and conventional high-field MRI studies. Low-field pMRI stroke volumes significantly correlated with stroke severity and functional outcome at discharge. These results validate the use of low-field pMRI to obtain clinically useful imaging of stroke, setting the stage for use in resource-limited environments.

Background: Elevated blood pressure after endovascular thrombectomy (EVT) has been associated with an increased risk of hemorrhagic transformation and poor functional outcomes. However, the optimal hemodynamic management after EVT remains unknown, and the blood pressure course in the acute phase of ischemic stroke has not been well characterized. This study aimed to identify patient subgroups with distinct blood pressure trajectories after EVT and study their association with radiographic and functional outcomes., Methods: This multicenter retrospective cohort study included consecutive patients with anterior circulation large-vessel occlusion ischemic stroke who underwent EVT. Repeated time-stamped blood pressure data were recorded for the first 72 hours after thrombectomy. Latent variable mixture modeling was used to separate subjects into five groups with distinct postprocedural systolic blood pressure (SBP) trajectories. The primary outcome was functional status, measured on the modified Rankin Scale 90 days after stroke. Secondary outcomes included hemorrhagic transformation, symptomatic intracranial hemorrhage, and death., Results: Two thousand two hundred sixty-eight patients (mean age [±SD] 69±15, mean National Institutes of Health Stroke Scale 15±7) were included in the analysis. Five distinct SBP trajectories were observed: low (18%), moderate (37%), moderate-to-high (20%), high-to-moderate (18%), and high (6%). SBP trajectory group was independently associated with functional outcome at 90 days ( P <0.0001) after adjusting for potential confounders. Patients with high and high-to-moderate SBP trajectories had significantly greater odds of an unfavorable outcome (adjusted odds ratio, 3.5 [95% CI, 1.8-6.7], P =0.0003 and adjusted odds ratio, 2.2 [95% CI, 1.5-3.2], P <0.0001, respectively). Subjects in the high-to-moderate group had an increased risk of symptomatic intracranial hemorrhage (adjusted odds ratio, 1.82 [95% CI, 1-3.2]; P =0.04). No significant association was found between trajectory group and hemorrhagic transformation., Conclusions: Patients with acute ischemic stroke demonstrate distinct SBP trajectories during the first 72 hours after EVT that have differing associations with functional outcome. These findings may help identify potential candidates for future blood pressure modulation trials.

Summary: In this review, we discuss the utility of quantitative EEG parameters for the detection of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage in the context of the complex pathophysiology of DCI and the limitations of current diagnostic methods. Because of the multifactorial pathophysiology of DCI, methodologies solely assessing blood vessel narrowing (vasospasm) are insufficient to detect all DCI. Quantitative EEG has facilitated the exploration of EEG as a diagnostic modality of DCI. Multiple quantitative EEG parameters such as alpha power, relative alpha variability, and alpha/delta ratio show reliable detection of DCI in multiple studies. Recent studies on epileptiform abnormalities suggest that their potential for the detection of DCI. Quantitative EEG is a promising, continuous, noninvasive, monitoring modality of DCI implementable in daily practice. Future work should validate these parameters in larger populations, facilitated by the development of automated detection algorithms and multimodal data integration., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 by the American Clinical Neurophysiology Society.)

Background and Objectives: Delayed cerebral ischemia (DCI) is the leading complication of subarachnoid hemorrhage (SAH). Because DCI was traditionally thought to be caused by large vessel vasospasm, transcranial Doppler ultrasounds (TCDs) have been the standard of care. Continuous EEG has emerged as a promising complementary monitoring modality and predicts increased DCI risk. Our objective was to determine whether combining EEG and TCD data improves prediction of DCI after SAH. We hypothesize that integrating these diagnostic modalities improves DCI prediction., Methods: We retrospectively assessed patients with moderate to severe SAH (2011-2015; Fisher 3-4 or Hunt-Hess 4-5) who had both prospective TCD and EEG acquisition during hospitalization. Middle cerebral artery (MCA) peak systolic velocities (PSVs) and the presence or absence of epileptiform abnormalities (EAs), defined as seizures, epileptiform discharges, and rhythmic/periodic activity, were recorded daily. Logistic regressions were used to identify significant covariates of EAs and TCD to predict DCI. Group-based trajectory modeling (GBTM) was used to account for changes over time by identifying distinct group trajectories of MCA PSV and EAs associated with DCI risk., Results: We assessed 107 patients; DCI developed in 56 (51.9%). Univariate predictors of DCI are presence of high-MCA velocity (PSV ≥200 cm/s, sensitivity 27%, specificity 89%) and EAs (sensitivity 66%, specificity 62%) on or before day 3. Two univariate GBTM trajectories of EAs predicted DCI (sensitivity 64%, specificity 62.75%). Logistic regression and GBTM models using both TCD and EEG monitoring performed better. The best logistic regression and GBTM models used both TCD and EEG data, Hunt-Hess score at admission, and aneurysm treatment as predictors of DCI (logistic regression: sensitivity 90%, specificity 70%; GBTM: sensitivity 89%, specificity 67%)., Discussion: EEG and TCD biomarkers combined provide the best prediction of DCI. The conjunction of clinical variables with the timing of EAs and high MCA velocities improved model performance. These results suggest that TCD and cEEG are promising complementary monitoring modalities for DCI prediction. Our model has potential to serve as a decision support tool in SAH management., Classification of Evidence: This study provides Class II evidence that combined TCD and EEG monitoring can identify delayed cerebral ischemia after SAH., (© 2021 American Academy of Neurology.)

Background and Objectives: To explore the association between blood pressure (BP) levels after endovascular thrombectomy (EVT) and the clinical outcomes of patients with acute ischemic stroke (AIS) patients with large vessel occlusion (LVO)., Methods: A study was eligible if it enrolled patients with AIS >18 years of age with an LVO treated with either successful or unsuccessful EVT and provided either individual or mean 24-hour systolic BP values after the end of the EVT procedure. Individual patient data from all studies were analyzed with a generalized linear mixed-effects model., Results: A total of 5,874 patients (mean age 69 ± 14 years; 50% women; median NIH Stroke Scale score on admission 16) from 7 published studies were included. Increasing mean systolic BP levels per 10 mm Hg during the first 24 hours after the end of the EVT were associated with a lower odds of functional improvement (unadjusted common odds ratio [OR] 0.82, 95% confidence interval [CI] 0.80-0.85; adjusted common OR 0.88, 95% CI 0.84-0.93) and modified Rankin Scale score ≤2 (unadjusted OR 0.82, 95% CI 0.79-0.85; adjusted OR 0.87, 95% CI 0.82-0.93) and a higher odds of all-cause mortality (unadjusted OR 1.18, 95% CI 1.13-1.24; adjusted OR 1.15, 95% CI 1.06-1.23) at 3 months. Higher 24-hour mean systolic BP levels were also associated with an increased likelihood of early neurologic deterioration (unadjusted OR 1.14, 95% CI 1.07-1.21; adjusted OR 1.14, 95% CI 1.03-1.24) and a higher odds of symptomatic intracranial hemorrhage (unadjusted OR 1.20, 95% CI 1.09-1.29; adjusted OR 1.20, 95% CI 1.03-1.38) after EVT., Discussion: Increased mean systolic BP levels in the first 24 hours after EVT are independently associated with a higher odds of symptomatic intracranial hemorrhage, early neurologic deterioration, 3-month mortality, and worse 3-month functional outcomes., (© 2021 American Academy of Neurology.)

Endovascular thrombectomy (EVT) has changed the landscape of acute stroke therapy and has become the standard of care for selected patients presenting with anterior circulation large-vessel occlusion (LVO) stroke. Despite successful reperfusion, many patients with LVO stroke do not regain functional independence. Particularly, patients presenting with extremes of blood pressure (BP) or hemodynamic variability are found to have a worse clinical recovery, suggesting blood pressure optimization as a potential neuroprotective strategy. Current guidelines acknowledge the lack of randomized trials to evaluate the optimal hemodynamic management during the immediate post-stroke period. Following reperfusion, lower blood pressure targets may be warranted to prevent reperfusion injury and promote penumbral recovery, but adequate BP targets adjusted to individual patient factors such as degree of reperfusion, infarct size, and overall hemodynamic status remain undefined. This narrative review outlines the physiological mechanisms of BP control after EVT and summarizes key observational studies and clinical trials evaluating post-EVT BP targets. It also discusses novel treatment strategies and areas of future research that could aid in the determination of the optimal post-EVT blood pressure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Peng, Ortega-Gutiérrez, de Havenon and Petersen.)

Objectives: To test the hypothesis that admission hemoglobin levels are associated with outcome in primary, nontraumatic intracerebral hemorrhage., Design: Individual patient data meta-analysis of three studies of intracerebral hemorrhage., Setting: Two randomized clinical trials and one multiethnic observational study., Patients: Patients with spontaneous, nontraumatic intracerebral hemorrhage., Interventions: None., Measurements and Main Results: Our exposure of interest was admission hemoglobin levels and the primary outcome was 3-month postintracerebral hemorrhage-dichotomized modified Rankin Scale (0-3 vs 4-6). Intermediate outcomes were admission hematoma volume and hematoma expansion defined as 6 mL or 33% increase in hemorrhage size on repeat CT. A total of 4,172 intracerebral hemorrhage patients were included in the study (mean age 63 [sd = 14]; female sex 1,668 [40%]). Each additional g/dL of admission hemoglobin was associated with 14% (odds ratio, 0.86; 95% CI, 0.82-0.91) and 7% (odds ratio, 0.93; 95% CI, 0.88-0.98) reductions in the risk of poor outcome in unadjusted and adjusted analyses, respectively. Dose-response analyses indicated a linear relationship between admission hemoglobin levels and poor outcome across the entire evaluated range (test-for-trend p < 0.001). No consistent associations were found between the admission hemoglobin levels and hematoma volume or hematoma expansion., Conclusions: Higher hemoglobin levels are associated with better outcome in intracerebral hemorrhage. Further research is needed to evaluate admission hemoglobin levels as both a therapeutic target and predictor of outcome., Competing Interests: Ms. Leasure is supported by the National Institutes of Health (NIH) (R03NS112859). Dr. Sansing is supported by the NIH (R01NS095993, R01NS097728, U01NS113445). Dr. Kamel is supported by the NIH (R01NS097443, U01NS095869, R01HL144541, U01NS106513). Dr. Murthy is supported by the NIH (K23NS105948) and the Leon Levy Foundation. Dr. Sheth is supported by the NIH (U24NS107136, U24NS107215, R01NR018335, U01NS106513, R03NS112859) and the American Heart Association (18TPA34170180,17CSA33550004). Dr. Falcone is supported by the National Institute on Aging (K76AG59992), the National Institute of Neurological Disorders and Stroke (R03NS112859), the American Heart Association (18IDDG34280056), a Yale Pepper Scholar Award (P30AG021342), and the Neurocritical Care Society Research Fellowship. Drs. Acosta, Sansing, Langefeld, Woo, Sheth, and Falcone received support for article research from the NIH. Drs. Langefeld’s and Woo’s institutions received funding from the NIH. Dr. Kamel serves as a principal investigator for the NIH-funded AtRial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke (ARCADIA) trial (National Institute of Nuerological Disoders and Stroke U01NS095869), which receives in-kind study drug from the Bristol-Myers-Squibb-Pfizer Alliance for Eliquis and ancillary study support from Roche Diagnostics, serves as Deputy Editor for JAMA Neurology, serves as a steering committee member of Medtronic’s Stroke atrial fibrillation trial (uncompensated), serves on an end point adjudication committee for a trial of empagliflozin for Boehringer-Ingelheim, and has served on an advisory board for Roivant Sciences related to Factor XI inhibition. Dr. Mayer recieved funding from Idorsia, MaxQ AI, Bayer, Brain Cool, Biogen, and Nestle. Dr. Sheth’s institution received funding from Biogen, Novartis, and Bard, and he recieved funding from Hyperfine and Zoll. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: We aimed to compare the outcome of acute ischemic stroke (AIS) patients who received endovascular thrombectomy (EVT) with confirmed COVID-19 to those without., Methods: We performed a retrospective analysis using the Vizient Clinical Data Base and included hospital discharges from April 1 to July 31 2020 with ICD-10 codes for AIS and EVT. The primary outcome was in-hospital death and the secondary outcome was favorable discharge, defined as discharge home or to acute rehabilitation. We compared patients with laboratory-confirmed COVID-19 to those without. As a sensitivity analysis, we compared COVID-19 AIS patients who did not undergo EVT to those who did, to balance potential adverse events inherent to COVID-19 infection., Results: We identified 3165 AIS patients who received EVT during April to July 2020, in which COVID-19 was confirmed in 104 (3.3%). Comorbid COVID-19 infection was associated with younger age, male sex, diabetes, black race, Hispanic ethnicity, intubation, acute coronary syndrome, acute renal failure, and longer hospital and intensive care unit length of stay. The rate of in-hospital death was 12.4% without COVID-19 vs 29.8% with COVID-19 (P<0.001). In mixed-effects logistic regression that accounted for patient clustering by hospital, comorbid COVID-19 increased the odds of in-hospital death over four-fold (OR 4.48, 95% CI 3.02 to 6.165). Comorbid COVID-19 was also associated with lower odds of a favorable discharge (OR 0.43, 95% CI 0.30 to 0.61). In the sensitivity analysis, comparing AIS patients with COVID-19 who did not undergo EVT (n=2139) to the AIS EVT patients with COVID-19, there was no difference in the rate of in-hospital death (30.6% vs 29.8%, P=0.868), and AIS EVT patients had a higher rate of favorable discharge (32.4% vs 47.1%, P=0.002)., Conclusion: In AIS patients treated with EVT, comorbid COVID-19 infection was associated with in-hospital death and a lower odds of favorable discharge compared with patients without COVID-19, but not compared with AIS patients with COVID-19 who did not undergo EVT. AIS EVT patients with COVID-19 were younger, more likely to be male, have systemic complications, and almost twice as likely to be black and over three times as likely to be Hispanic., Competing Interests: Competing interests: Dr. de Havenon has received investigator-initiated funding from AMAG and Regeneron pharmaceuticals. The remaining authors report no potential conflicts of interest., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Elevated systolic blood pressure (SBP) after mechanical thrombectomy (MT) correlates with worse outcome. However, the association between SBP reduction (SBPr) and outcome after successful reperfusion with MT is not well established., Objective: To investigate the association between SBPr in the first 24 hours after successful reperfusion and the functional and safety outcomes of MT., Methods: A multicenter retrospective study, which included 10 comprehensive stroke centers, was carried out. Patients with acute ischemic stroke and anterior circulation large vessel occlusions who achieved successful reperfusion via MT were included. SBPr was calculated using the formula 100×([admission SBP-mean SBP]/admission SBP). Poor outcome was defined as a modified Rankin Scale (mRS) score of 3-6 at 90 days. Safety endpoints included symptomatic intracerebral hemorrhage, mortality, and requirement for hemicraniectomy during admission. A generalized mixed linear model was used to study the association between SBPr and outcomes., Results: A total of 1361 patients were included in the final analysis. SBPr as a continuous variable was inversely associated with poor outcome (OR=0.97; 95% CI 0.95 to 0.98; p<0.001) but not with the safety outcomes. Subanalysis based on reperfusion status showed that SBPr was associated with lower odds of poor outcome only in patients with complete reperfusion (modified Thrombolysis in Cerebral Infarction (mTICI 3)) but not in patients with incomplete reperfusion (mTICI 2b). When SBPr was divided into categories (<1%, 1%-10%, 11%-20%, >20%), the rate of poor outcome was highest in the first group., Conclusion: SBPr in the first 24 hours after successful reperfusion was inversely associated with poor outcome. No association between SBPr and safety outcome was found., Competing Interests: Competing interests: AS has honoris for consulting for Penumbra and Cerenovus. M-NP received honoraria; modest; received speakers’ honoraria from Siemens Healthineers.SQW reports U24NS107235- 01 NIH/NINDS StrokeNET Site Co-I. The other authors report no conflicts., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: We aim to examine effects of collateral status and post-thrombectomy reperfusion on final infarct distribution and early functional outcome in patients with anterior circulation large vessel occlusion ischemic stroke., Methods: Patients with large vessel occlusion who underwent endovascular intervention were included in this study. All patients had baseline computed tomography angiography and follow-up magnetic resonance imaging. Collateral status was graded according to the criteria proposed by Miteff et al and reperfusion was assessed using the modified Thrombolysis in Cerebral Infarction (mTICI) system. We applied a multivariate voxel-wise general linear model to correlate the distribution of final infarction with collateral status and degree of reperfusion. Early favorable outcome was defined as a discharge modified Rankin Scale score ≤2., Results: Of the 283 patients included, 129 (46%) had good, 97 (34%) had moderate, and 57 (20%) had poor collateral status. Successful reperfusion (mTICI 2b/3) was achieved in 206 (73%) patients. Poor collateral status was associated with infarction of middle cerebral artery border zones, whereas worse reperfusion (mTICI scores 0-2a) was associated with infarction of middle cerebral artery territory deep white matter tracts and the posterior limb of the internal capsule. In multivariate regression models, both mTICI ( P <0.001) and collateral status ( P <0.001) were among independent predictors of final infarct volumes. However, mTICI ( P <0.001), but not collateral status ( P =0.058), predicted favorable outcome at discharge., Conclusions: In this cohort of patients with large vessel occlusion stroke, both the collateral status and endovascular reperfusion were strongly associated with middle cerebral artery territory final infarct volumes. Our findings suggesting that baseline collateral status predominantly affected middle cerebral artery border zones infarction, whereas higher mTICI preserved deep white matter and internal capsule from infarction; may explain why reperfusion success-but not collateral status-was among the independent predictors of favorable outcome at discharge. Infarction of the lentiform nuclei was observed regardless of collateral status or reperfusion success.

Objective: While the benefit of mechanical thrombectomy (MT) for patients with anterior circulation acute ischemic stroke with large-vessel occlusion (AIS-LVO) has been clearly established, difficult vascular access may make the intervention impossible or unduly prolonged. In this study, the authors evaluated safety as well as radiographic and functional outcomes in stroke patients treated with MT via direct carotid puncture (DCP) for prohibitive vascular access., Methods: The authors retrospectively studied patients from their prospective AIS-LVO database who underwent attempted MT between 2015 and 2018. Patients with prohibitive vascular access were divided into two groups: 1) aborted MT (abMT) after failed transfemoral access and 2) attempted MT via DCP. Functional outcome was assessed using the modified Rankin Scale at 3 months. Associations with outcome were analyzed using ordinal logistic regression., Results: Of 352 consecutive patients with anterior circulation AIS-LVO who underwent attempted MT, 37 patients (10.5%) were deemed to have prohibitive vascular access (mean age [± SD] 82 ± 11 years, mean National Institutes of Health Stroke Scale [NIHSS] score 17 ± 5, with females accounting for 75% of the patients). There were 20 patients in the DCP group and 17 in the abMT group. The two groups were well matched for the known predictors of clinical outcome: age, sex, and admission NIHSS score. Direct carotid access was successfully obtained in 19 of 20 patients. Successful reperfusion (thrombolysis in cerebral infarction score 2b or 3) was achieved in 16 (84%) of 19 patients in the DCP group. Carotid access complications included an inability to catheterize the carotid artery in 1 patient, neck hematomas in 4 patients, non-flow-limiting common carotid artery (CCA) dissections in 2 patients, and a delayed, fatal carotid blowout in 1 patient. The neck hematomas and non-flow-limiting CCA dissections did not require any subsequent interventions and remained clinically silent. Compared with the abMT group, patients in the DCP group had smaller infarct volumes (11 vs 48 ml, p = 0.04), a greater reduction in NIHSS score (-4 vs +2.9, p = 0.03), and better functional outcome (shift analysis for 3-month modified Rankin Scale score: adjusted OR 5.2, 95% CI 1.02-24.5; p = 0.048)., Conclusions: DCP for emergency MT in patients with anterior circulation AIS-LVO and prohibitive vascular access is safe and effective and is associated with higher recanalization rates, smaller infarct volumes, and improved functional outcome compared with patients with abMT after failed transfemoral access. DCP should be considered in this patient population.

Hemorrhagic transformation remains a potentially catastrophic complication of reperfusion therapies for the treatment of large-vessel occlusion ischemic stroke. Observational studies have found an increased risk of hemorrhagic transformation in patients with elevated blood pressure as well as a high degree of blood pressure variability, suggesting a link between hemodynamics and hemorrhagic transformation. Current society-endorsed guidelines recommend maintaining blood pressure below a fixed threshold of 180/105 mmHg regardless of thrombolytic or endovascular intervention. However, given the high recanalization rates with mechanical thrombectomy, it is unclear if the same hemodynamic goals from the pre-thrombectomy era apply. Also, individual patient factors such as the degree of reperfusion, infarct size, and collateral status likely need to be considered. In this review, we will discuss current evidence linking hemodynamics to hemorrhagic transformation after mechanical thrombectomy. In addition, we will review the clinical relevance of cerebral autoregulation in stroke, highlighting recent studies that have harnessed autoregulatory physiology to define and trend individualized limits of autoregulation. This review will go on to emphasize the translatability of this approach to stroke management. Finally, we will discuss novel statistical approaches like trajectory analysis to post-thrombectomy hemodynamics., (Copyright © 2020 Silverman, Kodali, Sheth and Petersen.)

Objective: Observational studies point to an inverse correlation between low-density lipoprotein (LDL) cholesterol levels and risk of intracerebral hemorrhage (ICH), but it remains unclear whether this association is causal. We tested the hypothesis that genetically elevated LDL is associated with reduced risk of ICH., Methods: We constructed one polygenic risk score (PRS) per lipid trait (total cholesterol, LDL, high-density lipoprotein [HDL], and triglycerides) using independent genomewide significant single nucleotide polymorphisms (SNPs) for each trait. We used data from 316,428 individuals enrolled in the UK Biobank to estimate the effect of each PRS on its corresponding trait, and data from 1,286 ICH cases and 1,261 matched controls to estimate the effect of each PRS on ICH risk. We used these estimates to conduct Mendelian Randomization (MR) analyses., Results: We identified 410, 339, 393, and 317 lipid-related SNPs for total cholesterol, LDL, HDL, and triglycerides, respectively. All four PRSs were strongly associated with their corresponding trait (all p < 1.00 × 10 -100 ). While one SD increase in the PRSs for total cholesterol (odds ratio [OR] = 0.92; 95% confidence interval [CI] = 0.85-0.99; p = 0.03) and LDL cholesterol (OR = 0.88; 95% CI = 0.81-0.95; p = 0.002) were inversely associated with ICH risk, no significant associations were found for HDL and triglycerides (both p > 0.05). MR analyses indicated that 1mmol/L (38.67mg/dL) increase of genetically instrumented total and LDL cholesterol were associated with 23% (OR = 0.77; 95% CI = 0.65-0.98; p = 0.03) and 41% lower risks of ICH (OR = 0.59; 95% CI = 0.42-0.82; p = 0.002), respectively., Interpretation: Genetically elevated LDL levels were associated with lower risk of ICH, providing support for a potential causal role of LDL cholesterol in ICH. ANN NEUROL 2020 ANN NEUROL 2020;88:56-66., (© 2020 American Neurological Association.)

Background and Purpose- Loss of cerebral autoregulation in the acute phase of ischemic stroke leaves patients vulnerable to blood pressure (BP) changes. Effective BP management after endovascular thrombectomy may protect the brain from hypoperfusion or hyperperfusion. In this observational study, we compared personalized, autoregulation-based BP targets to static systolic BP thresholds. Methods- We prospectively enrolled 90 patients undergoing endovascular thrombectomy for stroke. Autoregulatory function was continuously measured by interrogating changes in near-infrared spectroscopy-derived tissue oxygenation (a cerebral blood flow surrogate) in response to changes in mean arterial pressure. The resulting autoregulatory index was used to trend the BP range at which autoregulation was most preserved. Percent time that mean arterial pressure exceeded the upper limit of autoregulation or decreased below the lower limit of autoregulation was calculated for each patient. Time above fixed systolic BP thresholds was computed in a similar fashion. Functional outcome was measured with the modified Rankin Scale at 90 days. Results- Personalized limits of autoregulation were successfully computed in all 90 patients (age 71.6±16.2, 47% female, mean National Institutes of Health Stroke Scale 13.9±5.7, monitoring time 28.0±18.4 hours). Percent time with mean arterial pressure above the upper limit of autoregulation associated with worse 90-day outcomes (odds ratio per 10% 1.84 [95% CI, 1.3-2.7] P =0.002), and patients with hemorrhagic transformation spent more time above the upper limit of autoregulation (10.9% versus 16.0%, P =0.042). Although there appeared to be a nonsignificant trend towards worse outcome with increasing time above systolic BP thresholds of 140 mm Hg and 160 mm Hg, the effect sizes were smaller compared with the personalized approach. Conclusions- Noninvasive determination of personalized BP thresholds for stroke patients is feasible. Deviation from these limits may increase risk of further brain injury and poor functional outcome. This approach may present a better strategy compared with the classical approach of maintaining systolic BP below a predetermined value, though a randomized trial is needed to determine the optimal approach for hemodynamic management.

Background: We aimed to assess the correlation of lesion location and clinical outcome in patients with large hemispheric infarction (LHI)., Methods: We analyzed admission MRI data from the GAMES-RP trial, which enrolled patients with anterior circulation infarct volumes of 82-300 cm 3 within 10 hours of onset. Infarct lesions were segmented and co-registered onto MNI-152 brain space. Voxel-wise general linear models were applied to assess location-outcome correlations after correction for infarct volume as a co-variate., Results: We included 83 patients with known 3-month modified Rankin scale (mRS). In voxel-wise analysis, there was significant correlation between admission infarct lesions involving the anterior cerebral artery (ACA) territory and its middle cerebral artery (MCA) border zone with both higher 3-month mRS and post-stroke day 3 and 7 National Institutes of Health Stroke Scale (NIHSS) total score and arm/leg subscores. Higher NIHSS total scores from admission through poststroke day 2 correlated with left MCA infarcts. In multivariate analysis, ACA territory infarct volume (P = .001) and admission NIHSS (P = .005) were independent predictors of 3-month mRS. Moreover, in a subgroup of 36 patients with infarct lesions involving right MCA-ACA border zone, intravenous (IV) glibenclamide (BIIB093; glyburide) treatment was the only independent predictor of 3-month mRS in multivariate regression analysis (P = .016)., Conclusions: Anterior extension of LHI with involvement of ACA territory and ACA-MCA border zone is an independent predictor of poor functional outcome, likely due to impairment of arm/leg motor function. If confirmed in larger cohorts, infarct topology may potentially help triage LHI patients who may benefit from IV glibenclamide., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01794182., (Copyright © 2019. Published by Elsevier Inc.)

Background and Purpose- Optimal blood pressure (BP) management during the early stages of aneurysmal subarachnoid hemorrhage remains uncertain. Observational studies have found worse outcomes in patients with increased hemodynamic variability, suggesting BP optimization as a potential neuroprotective strategy. In this study, we calculated personalized BP targets at which cerebral autoregulation was best preserved. We analyzed how deviation from these limits correlates with functional outcome. Methods- We prospectively enrolled 31 patients with aneurysmal subarachnoid hemorrhage. Autoregulatory function was continuously measured by interrogating changes in near-infrared spectroscopy (NIRS)-derived tissue oxygenation-a surrogate for cerebral blood flow-as well as intracranial pressure (ICP) in response to changes in mean arterial pressure using time-correlation analysis. The resulting autoregulatory indices were used to identify the upper and lower limit of autoregulation. Percent time that mean arterial pressure exceeded limits of autoregulation was calculated for each patient. Functional outcome was assessed using the modified Rankin Scale at discharge and 90 days. Associations with outcome were analyzed using ordinal multivariate logistic regression. Results- Personalized limits of autoregulation were computed in all patients (age 57.5±13.4, 23F, mean World Federation of Neurological Surgeons 2±1, monitoring time 67.8±50.8 hours). Optimal BP and limits of autoregulation were calculated on average for 89.5±6.7% of the total monitoring period. ICP- and NIRS-derived optimal pressures strongly correlated with one another ( P <0.0001). Percent time that mean arterial pressure deviated from limits of autoregulation significantly associated with worse functional outcome at discharge (NIRS, P =0.001; ICP, P =0.004) and 90 days (NIRS, P =0.002; ICP, P =0.003), adjusting separately for age, World Federation of Neurological Surgeons, vasospasm, and delayed cerebral ischemia. Conclusions- Both invasive (ICP) and noninvasive (NIRS) determination of personalized BP targets after aneurysmal subarachnoid hemorrhage is feasible, and these 2 approaches revealed significant collinearity. Furthermore, exceeding individualized limits of autoregulation was associated with poor functional outcomes.

Background and Purpose- After large-vessel intracranial occlusion, the fate of the ischemic penumbra, and ultimately final infarct volume, largely depends on tissue perfusion. In this study, we evaluated whether blood pressure reduction and sustained relative hypotension during endovascular thrombectomy are associated with infarct progression and functional outcome. Methods- We identified consecutive patients with large-vessel intracranial occlusion ischemic stroke who underwent mechanical thrombectomy at 2 comprehensive stroke centers. Intraprocedural mean arterial pressure (MAP) was monitored throughout the procedure. ΔMAP was calculated as the difference between admission MAP and lowest MAP during endovascular thrombectomy until recanalization. Sustained hypotension was measured as the area between admission MAP and continuous measurements of intraprocedural MAP (aMAP). Final infarct volume was measured using magnetic resonance imaging at 24 hours, and functional outcome was assessed using the modified Rankin Scale at discharge and 90 days. Associations with outcome were analyzed using linear and ordinal multivariable logistic regression. Results- Three hundred ninety patients (mean age 71±14 years, mean National Institutes of Health Stroke Scale score of 17) were included in the study; of these, 280 (72%) achieved Thrombolysis in Cerebral Infarction 2B/3 reperfusion. Eighty-seven percent of patients experienced MAP reductions during endovascular thrombectomy (mean 31±20 mm Hg). ΔMAP was associated with greater infarct growth ( P=0.036) and final infarct volume ( P=0.035). Mean ΔMAP among patients with favorable outcomes (modified Rankin Scale score, 0-2) was 20±21 mm Hg compared with 30±24 mm Hg among patients with poor outcome ( P=0.002). In the multivariable analysis, ΔMAP was independently associated with higher (worse) modified Rankin Scale scores at discharge (adjusted odds ratio per 10 mm Hg, 1.17; 95% CI, 1.04-1.32; P=0.009) and at 90 days (adjusted odds ratio per 10 mm Hg, 1.22; 95% CI, 1.07-1.38; P=0.003). The association between aMAP and outcome was also significant at discharge ( P=0.002) and 90 days ( P=0.001). Conclusions- Blood pressure reduction before recanalization is associated with larger infarct volumes and worse functional outcomes for patients affected by large-vessel intracranial occlusion stroke. These results underscore the importance of BP management during endovascular thrombectomy and highlight the need for further investigation of blood pressure management after large-vessel intracranial occlusion stroke.

Background and Purpose: We aimed to determine whether subjects aged ≤70 years who were treated with intravenous glyburide (RP-1127; BIIB093; glibenclamide) would have better long-term outcomes than those who received placebo., Methods: GAMES-RP (Glyburide Advantage in Malignant Edema and Stroke-Remedy Pharmaceuticals) was a prospective, double-blind, randomized, placebo-controlled phase 2 clinical trial. Eighty-six participants, aged 18 to 80 years, who presented to 18 centers with large hemispheric infarction (baseline diffusion-weighted imaging volumes, 82-300 cm 3 ) randomized within 10 hours of symptom onset were enrolled. In the current exploratory analysis, we included participants aged ≤70 years treated with intravenous glyburide (n=35) or placebo (n=30) who met per-protocol criteria. Intravenous glyburide or placebo was administered in a 1:1 ratio. We analyzed 90-day and 12-month mortality, functional outcome (modified Rankin Scale, Barthel Index), and quality of life (EuroQol group 5-dimension). Additional outcomes assessed included blood-brain barrier injury (MMP-9 [matrix metalloproteinase 9]) and cerebral edema (brain midline shift)., Results: Participants ≤70 years of age treated with intravenous glyburide had lower mortality at all time points (log-rank for survival hazards ratio, 0.34; P =0.04). After adjustment for age, the difference in functional outcome (modified Rankin Scale) demonstrated a trend toward benefit for intravenous glyburide-treated subjects at 90 days (odds ratio, 2.31; P =0.07). Repeated measures analysis at 90 days, 6 months, and 12 months using generalized estimating equations showed a significant treatment effect of intravenous glyburide on the Barthel Index ( P =0.03) and EuroQol group 5-dimension ( P =0.05). Participants treated with intravenous glyburide had lower plasma levels of MMP-9 (189 versus 376 ng/mL; P <0.001) and decreased midline shift (4.7 versus 9 mm; P <0.001) compared with participants who received placebo., Conclusions: In this exploratory analysis, participants ≤70 years of age with large hemispheric infarction have improved survival after acute therapy with intravenous glyburide., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01794182., (© 2018 American Heart Association, Inc.)