Effect of CGRP inhibitors on interictal cerebral hemodynamics in individuals with migraine.

Introduction: Calcitonin gene-related peptide (CGRP) plays an important role in cerebral vasodilation, so here we aim to quantify the impact of CGRP monoclonal antibody (mAb) therapy on cerebral hemodynamics. Methods: In 23 patients with chronic and episodic migraine, cerebral hemodynamic monitoring was performed (1) prior to and (2) 3-months into CGRP-mAb therapy. Transcranial Doppler monitored cerebral blood flow velocity (CBFv) in the middle cerebral artery (MCA) and posterior cerebral artery (PCA), from which cerebrovascular reactivity (CVR) and cerebral autoregulation (CA; Mx-index) were calculated. Results: CA was similar off and on treatment, in the MCA (p = 0.42) and PCA (p = 0.72). CVR was also unaffected by treatment, in the MCA (p = 0.38) and PCA (p = 0.92). CBFv and blood pressure were also unaffected. The subgroup of clinical responders (>50% reduction in migraine frequency) exhibited a small reduction in MCA-CBFv (6.0 cm/s; IQR: 1.1-12.4; p = 0.007) and PCA-CBFv (8.9 cm/s; IQR: 6.9-10.3; p = 0.04). Discussion: Dynamic measures of cerebrovascular physiology were preserved after 3 months of CGRP-mAb therapy, but a small reduction in CBFv was observed in patients who responded to treatment. Subgroup findings should be interpreted cautiously, but further investigation may clarify if CBFv is dependent on the degree of CGRP inhibition or may serve as a biomarker of drug sensitivity.

Validation of the Openwater wearable optical system: cerebral hemodynamic monitoring during a breath-hold maneuver.

Significance: Bedside cerebral blood flow (CBF) monitoring has the potential to inform and improve care for acute neurologic diseases, but technical challenges limit the use of existing techniques in clinical practice. Aim: Here, we validate the Openwater optical system, a novel wearable headset that uses laser speckle contrast to monitor microvascular hemodynamics. Approach: We monitored 25 healthy adults with the Openwater system and concurrent transcranial Doppler (TCD) while performing a breath-hold maneuver to increase CBF. Relative blood flow (rBF) was derived from changes in speckle contrast, and relative blood volume (rBV) was derived from changes in speckle average intensity. Results: A strong correlation was observed between beat-to-beat optical rBF and TCD-measured cerebral blood flow velocity (CBFv), R=0.79; the slope of the linear fit indicates good agreement, 0.87 (95% CI: 0.83 -0.92). Beat-to-beat rBV and CBFv were also strongly correlated, R=0.72, but as expected the two variables were not proportional; changes in rBV were smaller than CBFv changes, with linear fit slope of 0.18 (95% CI: 0.17 to 0.19). Further, strong agreement was found between rBF and CBFv waveform morphology and related metrics. Conclusions: This first in vivo validation of the Openwater optical system highlights its potential as a cerebral hemodynamic monitor, but additional validation is needed in disease states.

Portable cerebral blood flow monitor to detect large vessel occlusion in patients with suspected stroke.

BACKGROUND: Early detection of large vessel occlusion (LVO) facilitates triage to an appropriate stroke center to reduce treatment times and improve outcomes. Prehospital stroke scales are not sufficiently sensitive, so we investigated the ability of the portable Openwater optical blood flow monitor to detect LVO. METHODS: Patients were prospectively enrolled at two comprehensive stroke centers during stroke alert evaluation within 24 hours of onset with National Institutes of Health Stroke Scale (NIHSS) score ≥2. A 70 s bedside optical blood flow scan generated cerebral blood flow waveforms based on relative changes in speckle contrast. Anterior circulation LVO was determined by CT angiography. A deep learning model trained on all patient data using fivefold cross-validation and learned discriminative representations from the raw speckle contrast waveform data. Receiver operating characteristic (ROC) analysis compared the Openwater diagnostic performance (ie, LVO detection) with prehospital stroke scales. RESULTS: Among 135 patients, 52 (39%) had an anterior circulation LVO. The median NIHSS score was 8 (IQR 4-14). The Openwater instrument had 79% sensitivity and 84% specificity for the detection of LVO. The rapid arterial occlusion evaluation (RACE) scale had 60% sensitivity and 81% specificity and the Los Angeles motor scale (LAMS) had 50% sensitivity and 81% specificity. The binary Openwater classification (high-likelihood vs low-likelihood) had an area under the ROC (AUROC) of 0.82 (95% CI 0.75 to 0.88), which outperformed RACE (AUC 0.70; 95% CI 0.62 to 0.78; P=0.04) and LAMS (AUC 0.65; 95% CI 0.57 to 0.73; P=0.002). CONCLUSIONS: The Openwater optical blood flow monitor outperformed prehospital stroke scales for the detection of LVO in patients undergoing acute stroke evaluation in the emergency department. These encouraging findings need to be validated in an independent test set and the prehospital environment.

Sex Differences in Perihematomal Edema Volume and Outcome After Intracerebral Hemorrhage.

BACKGROUND: Although larger hematoma volume is associated with worse outcome after intracerebral hemorrhage (ICH), the association between perihematomal edema (PHE) volume and outcome remains uncertain, as does the impact of sex on PHE and outcome. Here we aimed to determine whether larger PHE volume is associated with worse outcome and whether PHE volume trajectories differ by sex. METHODS: We conducted a post hoc analysis of the Factor VIIa for Acute Hemorrhagic Stroke Treatment (FAST) trial, which randomized patients with ICH to receive recombinant activated factor VIIa or placebo. Computerized planimetry calculated PHE and ICH volumes on serial computed tomography (CT) scans (at baseline [within 3 h of onset], at 24 h, and at 72 h). Generalized estimating equations examined interactions between sex, CT time points, and FAST treatment arm on PHE and ICH volumes. Mixed and multivariable logistic models examined associations between sex, PHE, and outcomes. RESULTS: A total of 781 patients with supratentorial ICH (mean age 65 years) were included. Compared to women (n = 296), men (n = 485) had similar median ICH (14.9 vs. 13.6 mL, p = 0.053) and PHE volumes (11.1 vs. 10.5 mL, p = 0.56) at baseline but larger ICH and PHE volumes at 24 h (19.0 vs. 14.0 mL, p < 0.001; 22.2 vs. 15.7 mL, p < 0.001) and 72 h (16.0 vs. 11.8 mL, p < 0.001; 28.7 vs. 19.9 mL, p < 0.001). Men had higher absolute early PHE expansion (p < 0.001) and more hematoma expansion (growth ≥ 33% or 6 mL at 24 h, 33% vs. 22%, p < 0.001). An interaction between sex and CT time points on PHE volume (p < 0.001), but not on ICH volume, confirmed a steeper PHE trajectory in men. PHE expansion (per 5 mL, odds radio 1.19, 95% confidence interval 1.10-1.28), but not sex, was associated with poor outcome. CONCLUSIONS: Early PHE expansion and trajectory in men were significantly higher. PHE expansion was associated with poor outcomes independent of sex. Mechanisms leading to sex differences in PHE trajectories merit further investigation.

Priorities for Advancements in Neuroimaging in the Diagnostic Workup of Acute Stroke.

STAIR XII (12th Stroke Treatment Academy Industry Roundtable) included a workshop to discuss the priorities for advancements in neuroimaging in the diagnostic workup of acute ischemic stroke. The workshop brought together representatives from academia, industry, and government. The participants identified 10 critical areas of priority for the advancement of acute stroke imaging. These include enhancing imaging capabilities at primary and comprehensive stroke centers, refining the analysis and characterization of clots, establishing imaging criteria that can predict the response to reperfusion, optimizing the Thrombolysis in Cerebral Infarction scale, predicting first-pass reperfusion outcomes, improving imaging techniques post-reperfusion therapy, detecting early ischemia on noncontrast computed tomography, enhancing cone beam computed tomography, advancing mobile stroke units, and leveraging high-resolution vessel wall imaging to gain deeper insights into pathology. Imaging in acute ischemic stroke treatment has advanced significantly, but important challenges remain that need to be addressed. A combined effort from academic investigators, industry, and regulators is needed to improve imaging technologies and, ultimately, patient outcomes.

Sex differences in perihematomal edema volume and outcome after intracerebral hemorrhage.

Objective: To determine whether in patients with intracerebral hemorrhage (ICH) perihematomal edema (PHE) volume trajectories differ by sex. Methods: We conducted a post-hoc analysis of the Factor-VII-for-Acute-Hemorrhagic-Stroke-Treatment (FAST) trial that randomized patients with ICH to receive recombinant activated Factor VIIa or placebo. Computerized planimetry calculated PHE and ICH volumes on serial CT scans (at baseline [within 3 hours of onset], at 24, and at 72 hours). Generalized estimating equations examined interactions between sex, CT-timepoints, and FAST treatment-arm on PHE and ICH volumes. Mixed and multivariate logistic models examined associations between sex, PHE, and outcomes. Results: 781 with supratentorial ICH (mean age 65 years) were included. Compared to women (n=296), men (n=485) had similar median ICH (14.9 versus 13.6 ml, p=0.053), and PHE volumes (11.1 versus 10.5 ml, p=0.56) at baseline but larger ICH and PHE at 24 hours (19.0 versus 14.0, p<0.001; 22.2 versus 15.7, p<0.001) and 72 hours (16.0 versus 11.8, p<0.001; 28.7 versus 19.9, p<0.001). Men had higher absolute PHE expansion (p<0.001), and more hematoma expansion (growth ≥33% or 6 mL at 24 hours, 33% versus 22%, p<0.001). An interaction between sex and CT-timepoints on PHE (p<0.001) but not on ICH volumes confirmed a steeper PHE trajectory in men. PHE expansion (per 5mL, odds radio, 1.19, 95%-confidence interval 1.10-1.28), but not sex, was associated with poor outcome. Conclusions: PHE expansion and trajectory in men were significantly higher. PHE expansion was associated with poor outcomes independent of sex. Mechanisms leading to sex differences in PHE trajectories merit further investigation. What is already known on this topic: Prior research has reported sex differences in intracerebral hemorrhage (ICH) characteristics and some studies suggest worse outcome after ICH in women. However, we do not have a good understanding whether there are sex differences in perihematomal edema (PHE) volume trajectories, or whether sex, independent of confounders, is associated with poor after ICH. What this study adds: In this post-hoc analysis of 781 patients with supratentorial ICH from the Factor-VII-for-Acute-Hemorrhagic-Stroke-Treatment (FAST) trial in which patients underwent brain CT imaging time-locked to symptom onset (within 3 hours of symptom onset, at 24 hours, and at 72 hours), men compared to women had similar ICH and PHE volumes at baseline, but larger ICH expansion and PHE expansion on follow up imaging. The PHE but not the ICH volume trajectory across scans was significantly higher in men than in women. While PHE expansion was associated with poor outcome at 90 days, outcome between the sexes was similar at 90 days, and sex was not associated with outcome. How this study might affect research practice or policy: The finding of heightened early PHE and ICH expansion in men may inform study design, patient recruitment strategies, and pre-specification of subgroup analyses in future interventional trials. The findings of this study also suggest that focusing on sex-specific factors may allow novel mechanistic insight into PHE, a major cause of secondary injury and poor outcome after ICH.

Validation of the Openwater wearable optical system: cerebral hemodynamic monitoring during a breath hold maneuver.

Bedside cerebral blood flow (CBF) monitoring has the potential to inform and improve care for acute neurologic diseases, but technical challenges limit the use of existing techniques in clinical practice. Here we validate the Openwater optical system, a novel wearable headset that uses laser speckle contrast to monitor microvascular hemodynamics. We monitored 25 healthy adults with the Openwater system and concurrent transcranial Doppler (TCD) while performing a breath-hold maneuver to increase CBF. Relative blood flow (rBF) was derived from the changes in speckle contrast, and relative blood volume (rBV) was derived from the changes in speckle average intensity. A strong correlation was observed between beat-to-beat optical rBF and TCD-measured cerebral blood flow velocity (CBFv), R=0.79; the slope of the linear fit indicates good agreement, 0.87 (95% CI:0.83-0.92). Beat-to-beat rBV and CBFv were strongly correlated, R=0.72, but as expected the two variables were not proportional; changes in rBV were smaller than CBFv changes, with linear fit slope of 0.18 (95% CI:0.17-0.19). Further, strong agreement was found between rBF and CBFv waveform morphology and related metrics. This first in vivo validation of the Openwater optical system highlights its potential as a cerebral hemodynamic monitor, but additional validation is needed in disease states.

Microvascular reperfusion during endovascular therapy: the balance of supply and demand.

BACKGROUND: Endovascular therapy (EVT) has revolutionized the treatment of acute stroke, but large vessel recanalization does not always result in tissue-level reperfusion. Cerebral blood flow (CBF) is not routinely monitored during EVT. We aimed to leverage diffuse correlation spectroscopy (DCS), a novel transcranial optical imaging technique, to assess the relationship between microvascular CBF and post-EVT outcomes. METHODS: Frontal lobe CBF was monitored by DCS in 40 patients undergoing EVT. Baseline CBF deficit was calculated as the percentage of CBF impairment on pre-EVT CT perfusion. Microvascular reperfusion was calculated as the percentage increase in DCS-derived CBF that occurred with recanalization. The adequacy of reperfusion was defined by persistent CBF deficit, calculated as: baseline CBF deficit - microvascular reperfusion. A good functional outcome was defined as 90-day modified Rankin Scale score ≤2. RESULTS: Thirty-six of 40 patients achieved successful recanalization, in whom microvascular reperfusion in itself was not associated with infarct volume or functional outcome. However, patients with good functional outcomes had a smaller persistent CBF deficit (median 1% (IQR -11%-16%)) than patients with poor outcomes (median 28% (IQR 2-50%)) (p=0.02). Smaller persistent CBF deficit was also associated with smaller infarct volume (p=0.004). Multivariate models confirmed that persistent CBF deficit was independently associated with infarct volume and functional outcome. CONCLUSIONS: CBF augmentation alone does not predict post-EVT outcomes, but when microvascular reperfusion closely matches the baseline CBF deficit, patients experience favorable clinical and radiographic outcomes. By recognizing inadequate reperfusion, bedside CBF monitoring may provide opportunities to personalize post-EVT care aimed at CBF optimization.

Management of Patients With Patent Foramen Ovale and Stroke: A National Survey of Interventional Cardiologists and Vascular Neurologists.

Background Results from multiple clinical trials support patent foramen ovale closure after cryptogenic stroke in select patients, but it remains unclear how new data and updated professional society guidelines have impacted clinical practice. Here, we aimed to compare how stroke neurologists and interventional cardiologists approach patients with cryptogenic stroke with patent foramen ovale and how critical anatomic and clinical factors influence decision making. Methods and Results An electronic survey was administered to 1556 vascular neurologists and 1057 interventional cardiologists throughout the United States. The survey addressed factors such as patient age, preclosure workup, and postclosure antithrombotics. Clinical vignettes highlighted critical variables and used a 5-point Likert scale to assess the providers' level of support for closure. There were 491 survey responses received from 301 (of 1556) vascular neurologists and 190 (of 1057) interventional cardiologists, with an overall response rate of 19%. Vascular neurologists were more likely to recommend against closure on the basis of older age (P<0.001). Interventional cardiologists are more supportive of closure across a range of clinical vignettes, including a very carefully selected patient with cryptogenic stroke (P<0.001), a patient with a high-risk alternative stroke cause (P<0.001), and a range of cases highlighting clinical variables where data are lacking. The majority of interventionalists (88%) seek neurology consultation before pursuing patent foramen ovale closure. Conclusions lnterventional cardiologists are more likely than vascular neurologists to support patent foramen ovale closure across a range of situations. This emphasizes the importance of collaboration and shared decision making, but also reveals an opportunity for professional society educational outreach.

Noninvasive finger plethysmography for continuous blood pressure monitoring in patients with left ventricular assist device.

BACKGROUND: Accurate blood pressure (BP) measurement remains challenging in patients with HeartMate 3™ left ventricular assist devices (HM3 LVADs). The Finapres® NOVA is a promising non-invasive continuous BP monitor that uses the volume clamp method via a finger cuff, so here we aimed to validate the instrument in HM3 patients. METHODS: In a single-center cohort, BP was monitored in 15 patients within 72 h following HM3 implantation. A radial artery catheter quantified arterial blood pressure (ABP), while the NOVA measured finger arterial pressure (fiAP) and reconstructed brachial artery pressure (reBAP). Waveforms were recorded for 10 min, and mean values were calculated in 15-s intervals. RESUTS: fiAP and ABP were moderately correlated during both the first (ICC 0.61, p = 0.04) and final measurements (ICC 0.66, p = 0.03). reBAP and ABP were strongly correlated during both the first (ICC 0.81, p = 0.002) and final measurements (ICC 0.83, p = 0.001). Both NOVA-derived values may underestimate low BP values while overestimating relatively high BP values. The reBAP was within 5 mm Hg of the ABP in 40% of patients (and within 10 mm Hg in 67%). CONCLUSIONS: This pilot represents the first evidence in support of the Finapres® NOVA for non-invasive BP measurement in select patients with HM3 LVADs. The instrument may provide useful data during BP medication adjustments or pump titration, but despite the correlation between the non-invasive reBAP and invasive ABP, individual-level inaccuracy may be clinically meaningful. Further investigation is needed to clarify these limitations and optimize accuracy before widespread adoption in this unique patient population.

Always Look on the Bright Side: Associations of Optimism With Functional Outcomes After Stroke.

Background Psychological health is as an important contributor to recovery after cardiovascular disease, but the roles of both optimism and depression in stroke recovery are not well characterized. Methods and Results A total of 879 participants in the SRUP (Stroke Recovery in Underserved Populations) 2005 to 2006 Study, aged ≥50 years, with incident stroke admitted to a rehabilitation facility were included. Optimism was assessed by the question: "Are you optimistic about the future?" Depression was defined by Center for Epidemiologic Studies Depression scale score >16. Participants were categorized into 4 groups: optimistic/without depression (n=581), optimistic/with depression (n=197), nonoptimistic/without depression (n=36), and nonoptimistic/with depression (n=65). Functional Independence Measure scores were used to assess stroke outcomes at discharge, 3 months after discharge, and 1 year after discharge with adjusted linear mixed models to estimate score trajectories. Participants were a mean age of 68 years (SD, 13 years), 52% were women, and 74% were White race. The optimistic/without depression group experienced the most recovery of total Functional Independence Measure scores in the first 3 months, 24.0 (95% CI, 22.5-25.4), followed by no change in the following 9 months, -0.3 (95% CI, -2.3 to 1.7), similar to the optimistic/with depression group with rapid recovery in 0 to 3 months, 21.1 (95% CI, 18.6-23.6) followed by minimal change in 3 to 12 months, 0.7 (95% CI, -2.8 to 4.1). The nonoptimistic groups demonstrated slow but continued recovery throughout the 12-month period, with overall change, 25.4 (95% CI, 17.6-33.2) in the nonoptimistic/without depression group and 17.6 (95% CI, 12.0-23.1) in the nonoptimistic/with depression group. There was robust effect modification between optimism and depression (Pinteraction<0.001). Conclusions In this longitudinal cohort, optimism and depression are synergistically associated with functional recovery after stroke. Measuring optimism status may help identify individuals at risk for worse poststroke recovery.

Anticoagulation under-utilization in atrial fibrillation patients is responsible for a large proportion of strokes requiring endovascular therapy.

OBJECTIVES: Atrial fibrillation (AF) is responsible for 30-50% of large strokes requiring endovascular thrombectomy (EVT). Anticoagulation (AC) underutilization is a common source of AF-related stroke. We compared antithrombotic medications among stroke patients with AF that did or did not undergo EVT to determine if AC underutilization disproportionately results in strokes requiring EVT, while quantifying the proportion of likely preventable thrombectomies. METHODS: This retrospective single-center cohort included consecutive patients admitted with acute ischemic stroke between 2016 and 2021. Patients were categorized based on the presence of AF, and pre-admission antithrombotic medications were compared between those who underwent EVT and those who didn't. The reason for not being on AC was abstracted from the medical record, and patients were categorized as either AC eligible or AC contraindicated. RESULTS: Of 3092 acute ischemic stroke patients, 644 had a history of AF, 213 of whom underwent EVT. Patients who required EVT were more likely to not be taking any antithrombotics prior to admission (34% vs 24%, p=0.007) or have subtherapeutic INR on admission if taking warfarin (83% vs 63%; p = 0.046). Among the AF-EVT patients, 44% were taking AC, and only 31% were adequately anticoagulated. Only 8% of AF-EVT patients who were not on pre-admission AC had a clear contraindication, and 94% were ultimately discharged on AC. CONCLUSIONS: Lack of antithrombotic therapy in AF patients disproportionately contributes to strokes requiring EVT. A small minority of AF patients have contraindications to AC, so adequate anticoagulation can prevent a remarkable number of strokes requiring EVT.

Dynamic cerebral autoregulation measured by diffuse correlation spectroscopy.

Dynamic cerebral autoregulation (dCA) can be derived from spontaneous oscillations in arterial blood pressure (ABP) and cerebral blood flow (CBF). Transcranial Doppler (TCD) measures CBF-velocity and is commonly used to assess dCA. Diffuse correlation spectroscopy (DCS) is a promising optical technique for non-invasive CBF monitoring, so here we aimed to validate DCS as a tool for quantifying dCA. In 33 healthy adults and 17 acute ischemic stroke patients, resting-state hemodynamic were monitored simultaneously with high-speed (20 Hz) DCS and TCD. dCA parameters were calcaulated by a transfer function analysis using a Fourier decomposition of ABP and CBF (or CBF-velocity). Strong correlation was found between DCS and TCD measured gain (magnitude of regulation) in healthy volunteers (r = 0.73, p < 0.001) and stroke patients (r = 0.76, p = 0.003). DCS-gain retained strong test-retest reliability in both groups (ICC 0.87 and 0.82, respectively). DCS and TCD-derived phase (latency of regulation) did not significantly correlate in healthy volunteers (r = 0.12, p = 0.50) but moderately correlated in stroke patients (r = 0.65, p = 0.006). DCS-derived phase was reproducible in both groups (ICC 0.88 and 0.90, respectively). High-frequency DCS is a promising non-invasive bedside technique that can be leveraged to quantify dCA from resting-state data, but the discrepancy between TCD and DCS-derived phase requires further investigation.

Clinicians' Approach to Patent Foramen Ovale Closure after Stroke: Comparing Cardiologists and Neurologists.

Background Evidence from randomized trials and updated professional society guidelines supports patent foramen ovale (PFO) closure after cryptogenic stroke in select patients. It is unclear how this has been integrated into real-world practice, so we aimed to compare practice patterns between cardiologists and neurologists. Methods and Results In March of 2021, a survey of cardiologists and neurologists who work or previously trained at the University of Pennsylvania Health System assessed practice preferences with respect to PFO closure after stroke. Clinical vignettes isolated specific variables of interest and used a 5-point Likert scale to assess the level of support for PFO closure. Stroke neurologists and interventional cardiologists were compared by Wilcoxon-Mann-Whitney tests. Secondarily, Kruskal-Wallis tests compared stroke neurologists, general neurologists, interventional cardiologists, and general cardiologists. We received 106 responses from 182 survey recipients (31/31 stroke neurologists, 38/46 interventional cardiologists, 20/30 general neurologists, and 17/77 general cardiologists). A similar proportion of stroke neurologists and interventional cardiologists favored PFO closure in a young patient with cryptogenic stroke, 88% and 87%, respectively (P=0.54). Interventionalists were more likely than stroke neurologists to support closure in the context of an alternative high-risk stroke mechanism, 14% and 0%, respectively (P=0.003). Stroke neurologists were more likely to oppose closure on the basis of older age (P=0.01). Conclusions There are key differences between how neurologists and cardiologists approach PFO closure after stroke, particularly when interpreting the stroke etiology and when considering closure beyond the scope of prior trials; this underscores the importance of collaboration between cardiologists and neurologists.

Reliability of Past Medical History in a Single Hospital Participating in Get With The Guidelines-Stroke Registry.

Background The GWTG (Get With The Guidelines)-Stroke registry supports clinical research and quality improvement projects that often rely on past medical history elements, the reliability of which remains largely unknown. Here, we evaluated the reliability of specific past medical history elements in a local GWTG-Stroke data set, with particular attention to calculating the CHA2DS2-VASc score. Methods and Results A single-center cohort was identified by querying the Hospital of the University of Pennsylvania's GWTG IQVIA Registry Platform for patients admitted with acute ischemic stroke between January 2017 and December 2020, with a previously known history of atrial fibrillation. Demographics and previously known medical history elements were retrieved from the registry to calculate the CHA2DS2-VASc score. Five neurologists abstracted the same medical history elements from the health records. The κ statistics quantified the reliability of medical history elements and CHA2DS2-VASc score. Four hundred fifty-three patients with acute ischemic stroke and previously known atrial fibrillation were included in the cohort. In comparison with manual reabstraction, registry-based medical history elements were only moderately reliable: congestive heart failure (κ=0.53), hypertension (κ=0.42), diabetes (κ=0.80), prior stroke (κ=0.45), and vascular disease (κ=0.48). However, leveraging these variables to calculate the CHA2DS2-VASc score was more reliable (κ=0.73). Conclusions Previously known medical history elements in the GWTG-Stroke registry were only modestly reliable in this single-center study, suggesting caution should be exercised when relying on any individual history elements in registry-based research. Combining these variables to calculate the CHA2DS2-VASc score was somewhat more reliable. Multicenter data are needed before assuming generalizability.

Highly Visible Wall-Timer to Reduce Endovascular Treatment Time for Stroke.

BACKGROUND: Endovascular therapy for acute ischemic stroke has revolutionized clinical care for patients with stroke and large vessel occlusion, but treatment remains time sensitive. At our stroke center, up to half of the door-to-groin time is accounted for after the patient arrives in the angio-suite. Here, we apply the concept of a highly visible timer in the angio-suite to quantify the impact on endovascular treatment time. METHODS: This was a single-center prospective pseudorandomized study conducted over a 32-week period. Pseudorandomization was achieved by turning the timer on and off in 2-week intervals. The primary outcome was angio-suite-to-groin time, and secondary outcomes were angio-suite-to-intubation time, groin-to-recanalization time, and 90-day modified Rankin scale. A stratified analysis was performed based on type of anesthesia (ie, endotracheal intubation versus not). RESULTS: During the 32-week study period, 97 mechanical thrombectomies were performed. The timer was on and off for 38 and 59 cases, respectively. The timer resulted in faster angio-suite-to-groin time (28 versus 33 minutes; P=0.02). The 5-minute reduction in angio-suite-to-groin was maintained after adjusting for intubation status in a multivariate regression (P=0.02). There was no difference in the 90-day modified Rankin scale between groups. The timer impact was consistent across the 32-week study period. CONCLUSIONS: A highly visible timer in the angio-suite achieved a meaningful, albeit modest, reduction in endovascular treatment time for patients with stroke. Given the lack of risk and low cost, it is reasonable for stroke centers to consider a highly visible timer in the angio-suite to improve treatment times.

Dual-Antiplatelet Therapy May Not Be Associated With an Increased Risk of In-hospital Bleeding in Patients With Moderate or Severe Ischemic Stroke.

Background and Purpose: Dual antiplatelet therapy (DAPT), compared to single antiplatelet therapy (SAPT), lowers the risk of stroke or death early after TIA and minor ischemic stroke. Prior trials excluded moderate to severe strokes, due to a potential increased risk of bleeding. We aimed to compare in-hospital bleeding rates in SAPT and DAPT patients with moderate or severe stroke (defined by NIHSS ≥4). Methods: We performed a retrospective cohort study of ischemic stroke over a 2-year period with admission NIHSS ≥4. The primary outcome was symptomatic intracranial hemorrhage (ICH) with any change in NIHSS. Secondary outcomes included systemic bleeding and major bleeding, a composite of serious systemic bleeding and symptomatic ICH. We performed analyses stratified by stroke severity (NIHSS 4-7 vs. 8+) and by preceding use of tPA and/or thrombectomy. Univariate followed by multivariate logistic regression evaluated whether DAPT was independently associated with bleeding. Results: Of 377 patients who met our inclusion criteria, 148 received DAPT (39%). Symptomatic ICH was less common with DAPT compared to SAPT (0.7 vs. 6.4%, p < 0.01), as was the composite of major bleeding (2.1 vs. 7.6%, p = 0.03). Symptomatic ICH was numerically less frequent in the DAPT group, but not statistically significant, when stratified by stroke severity (NIHSS 4-7: 0 vs. 5.9%, p = 0.06; NIHSS 8+: 1.5 vs. 6.6%, p = 0.18) and by treatment with tPA and/or thrombectomy (Yes: 2.6 vs. 9.1%, p = 0.30; No: 0 vs. 2.9%, p = 0.25). DAPT was not associated with major bleeding in either the univariate or the multivariate regression. Conclusions: In this single center cohort, symptomatic ICH and the composite of serious systemic bleeding and symptomatic ICH was rare in patients on DAPT. Relative to single antiplatelet therapy DAPT was not associated with an increased risk of in-hospital bleeding in patients with moderate and severe ischemic stroke.

Blood flow response to orthostatic challenge identifies signatures of the failure of static cerebral autoregulation in patients with cerebrovascular disease.

BACKGROUND: The cortical microvascular cerebral blood flow response (CBF) to different changes in head-of-bed (HOB) position has been shown to be altered in acute ischemic stroke (AIS) by diffuse correlation spectroscopy (DCS) technique. However, the relationship between these relative ΔCBF changes and associated systemic blood pressure changes has not been studied, even though blood pressure is a major driver of cerebral blood flow. METHODS: Transcranial DCS data from four studies measuring bilateral frontal microvascular cerebral blood flow in healthy controls (n = 15), patients with asymptomatic severe internal carotid artery stenosis (ICA, n = 27), and patients with acute ischemic stroke (AIS, n = 72) were aggregated. DCS-measured CBF was measured in response to a short head-of-bed (HOB) position manipulation protocol (supine/elevated/supine, 5 min at each position). In a sub-group (AIS, n = 26; ICA, n = 14; control, n = 15), mean arterial pressure (MAP) was measured dynamically during the protocol. RESULTS: After elevated positioning, DCS CBF returned to baseline supine values in controls (p = 0.890) but not in patients with AIS (9.6% [6.0,13.3], mean 95% CI, p < 0.001) or ICA stenosis (8.6% [3.1,14.0], p = 0.003)). MAP in AIS patients did not return to baseline values (2.6 mmHg [0.5, 4.7], p = 0.018), but in ICA stenosis patients and controls did. Instead ipsilesional but not contralesional CBF was correlated with MAP (AIS 6.0%/mmHg [- 2.4,14.3], p = 0.038; ICA stenosis 11.0%/mmHg [2.4,19.5], p < 0.001). CONCLUSIONS: The observed associations between ipsilateral CBF and MAP suggest that short HOB position changes may elicit deficits in cerebral autoregulation in cerebrovascular disorders. Additional research is required to further characterize this phenomenon.