A Randomized, Placebo-Controlled, Phase II Trial of Intravenous Allogeneic Non-HLA Matched, Unrelated Donor, Cord Blood Infusion for Ischemic Stroke.

Stroke remains a leading cause of death and disability in the US, and time-limited reperfusion strategies remain the only approved treatment options. To address this unmet clinical need, we conducted a phase II randomized clinical trial to determine whether intravenous infusion of banked, non-HLA matched unrelated donor umbilical cord blood (UCB) improved functional outcome after stroke. Participants were randomized 2:1 to UCB or placebo within strata of National Institutes of Health Stroke Scale Score (NIHSS) and study center. Study product was infused 3-10 days following index stroke. The primary endpoint was change in modified Rankin Scale (mRS) from baseline to day 90. Key secondary outcomes included functional independence, NIHSS, the Barthel Index, and assessment of adverse events. The trial was terminated early due to slow accrual and logistical concerns associated with the COVID-19 pandemic, and a total of 73 of a planned 100 participants were included in primary analyses. The median (range) of the change in mRS was 1 point (-2, 3) in UCB and 1 point (-1,4) in Placebo (P = 0.72). A shift analysis comparing the mRS at day 90 utilizing proportional odds modeling showed a common odds ratio of 0.9 (95% CI: 0.4, 2.3) after adjustment for baseline NIHSS and randomization strata. The distribution of adverse events was similar between arms. Although this study did not suggest any safety concerns related to UCB in ischemic stroke, we did not show a clinical benefit in the reduced sample size evaluated.

Robot-Assisted Transcranial Doppler Versus Transthoracic Echocardiography for Right to Left Shunt Detection.

BACKGROUND: Right to left shunt (RLS), including patent foramen ovale, is a recognized risk factor for stroke. RLS/patent foramen ovale diagnosis is made by transthoracic echocardiography (TTE), which is insensitive, transesophageal echocardiography, which is invasive, and transcranial Doppler (TCD), which is noninvasive and accurate but scarce. METHODS: We conducted a prospective, single-arm device clinical trial of robot-assisted TCD (raTCD) versus TTE for RLS diagnosis at 6 clinical sites in patients who presented with an event suspicious for embolic cerebrovascular ischemia from October 6, 2020 to October 20, 2021. raTCD was performed with standard TCD bubble study technique. TTE bubble study was performed per local standards. The primary outcome was rate of RLS detection by raTCD versus TTE. RESULTS: A total of 154 patients were enrolled, 129 evaluable (intent to scan) and 121 subjects had complete data per protocol. In the intent to scan cohort, mean age was 60±15 years, 47% were women, and all qualifying events were diagnosed as ischemic stroke or transient ischemic attack. raTCD was positive for RLS in 82 subjects (64%) and TTE was positive in 26 (20%; absolute difference 43.4% [95% CI, 35.2%-52.0%]; P<0.001). On prespecified secondary analysis, large RLS was detected by raTCD in 35 subjects (27%) versus 13 (10%) by TTE (absolute difference 17.0% [95% CI, 11.5%-24.5%]; P<0.001). There were no serious adverse events. CONCLUSIONS: raTCD was safe and ≈3 times more likely to diagnose RLS than TTE. TTE completely missed or underdiagnosed two thirds of large shunts diagnosed by raTCD. The raTCD device, used by health professionals with no prior TCD training, may allow providers to achieve the known sensitivity of TCD for RLS and patent foramen ovale detection without the need for an experienced operator to perform the test. Pending confirmatory studies, TCD appears to be the superior screen for RLS compared with TTE (funded by NeuraSignal). REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04604015.

Reliability of the National Institutes of Health (NIH) Stroke Scale Between Emergency Room and Neurology Physicians for Initial Stroke Severity Scoring.

INTRODUCTION: In patients with acute ischemic stroke (AIS), the National Institutes of Health Stroke Scale (NIHSS) is essential to establishing a patient's initial stroke severity. While previous research has validated NIHSS scoring reliability between neurologists and other clinicians, it has not specifically evaluated NIHSS scoring reliability between emergency room (ER) and neurology physicians within the same clinical scenario and timeframe in a large cohort of patients. This study specifically addresses the key question: does an ER physician's NIHSS score agree with the neurologist's NIHSS score in the same patient at the same time in a real-world context? METHODS: Data was retrospectively collected from 1,946 patients being evaluated for AIS at Houston Methodist Hospital from 05/2016 - 04/2018. Triage NIHSS scores assessed by both the ER and neurology providers within one hour of each other under the same clinical context were evaluated for comparison. Ultimately, 129 patients were included in the analysis. All providers in this study were NIHSS rater-certified. RESULTS: The distribution of the NIHSS score differences (ER score - neurology score) had a mean of -0.46 and a standard deviation of 2.11. The score difference between provider teams ranged ±5 points. The intraclass correlation coefficient (ICC) for the NIHSS scores between the ER and neurology teams was 0.95 (95% CI, 0.93 - 0.97) with an F-test of 42.41 and a p-value of 4.43E-69. Overall reliability was excellent between the ER and neurology teams. CONCLUSION: We evaluated triage NIHSS scores performed by ER and neurology providers under matching time and treatment conditions and found excellent interrater reliability. The excellent score agreement has important implications for treatment decision-making during patient handoff and further in stroke modeling, prediction, and clinical trial registries where missing NIHSS scores may be equivalently substituted from either provider team.

Readmission in patients undergoing percutaneous patent foramen ovale closure in the United States.

Current estimates suggest that a patent foramen ovale (PFO) may exist in up to 25% of the general population and is a potential risk factor for embolic, ischemic stroke. PFO closure complications include bleeding, need for procedure-related surgical intervention, pulmonary emboli, device malpositioning, new onset atrial arrhythmias, and transient atrioventricular block. Rates of PFO closure complications at a national level in the Unites States remain unknown. To address this, we performed a contemporary nationwide study using the 2016 and 2017 Nationwide Readmissions Database (NRD) to identify patterns of readmissions after percutaneous PFO closure. In conclusion, our study showed that following PFO closure, the most common complications were atrial fibrillation/atrial flutter followed by acute heart failure syndrome, supraventricular tachycardia and acute myocardial infarction.

Automatic Segmentation in Acute Ischemic Stroke: Prognostic Significance of Topological Stroke Volumes on Stroke Outcome.

BACKGROUND: Stroke infarct volume predicts patient disability and has utility for clinical trial outcomes. Accurate infarct volume measurement requires manual segmentation of stroke boundaries in diffusion-weighted magnetic resonance imaging scans which is time-consuming and subject to variability. Automatic infarct segmentation should be robust to rotation and reflection; however, prior work has not encoded this property into deep learning architecture. Here, we use rotation-reflection equivariance and train a deep learning model to segment stroke volumes in a large cohort of well-characterized patients with acute ischemic stroke in different vascular territories. METHODS: In this retrospective study, patients were selected from a stroke registry at Houston Methodist Hospital. Eight hundred seventy-five patients with acute ischemic stroke in any brain area who had magnetic resonance imaging with diffusion-weighted imaging were included for analysis and split 80/20 for training/testing. Infarct volumes were manually segmented by consensus of 3 independent clinical experts and cross-referenced against radiology reports. A rotation-reflection equivariant model was developed based on U-Net and grouped convolutions. Segmentation performance was evaluated using Dice score, precision, and recall. Ninety-day modified Rankin Scale outcome prediction was also evaluated using clinical variables and segmented stroke volumes in different brain regions. RESULTS: Segmentation model Dice scores are 0.88 (95% CI, 0.87-0.89; training) and 0.85 (0.82-0.88; testing). The modified Rankin Scale outcome prediction AUC using stroke volume in 30 refined brain regions based upon modified Rankin Scale-relevance areas adjusted for clinical variables was 0.80 (0.76-0.83) with an accuracy of 0.75 (0.72-0.78). CONCLUSIONS: We trained a deep learning model with encoded rotation-reflection equivariance to segment acute ischemic stroke lesions in diffusion- weighted imaging using a large data set from the Houston Methodist stroke center. The model achieved competitive performance in 175 well-balanced hold-out testing cases that include strokes from different vascular territories. Furthermore, the location specific stroke volume segmentations from the deep learning model combined with clinical factors demonstrated high AUC and accuracy for 90-day modified Rankin Scale in an outcome prediction model.

Retrospective study of deep learning to reduce noise in non-contrast head CT images.

PURPOSE: Presented herein is a novel CT denoising method uses a skip residual encoder-decoder framework with group convolutions and a novel loss function to improve the subjective and objective image quality for improved disease detection in patients with acute ischemic stroke (AIS). MATERIALS AND METHODS: In this retrospective study, confirmed AIS patients with full-dose NCCT head scans were randomly selected from a stroke registry between 2016 and 2020. 325 patients (67 ± 15 years, 176 men) were included. 18 patients each with 4-7 NCCTs performed within 5-day timeframe (83 total scans) were used for model training; 307 patients each with 1-4 NCCTs performed within 5-day timeframe (380 total scans) were used for hold-out testing. In the training group, a mean CT was created from the patient's co-registered scans for each input CT to train a rotation-reflection equivariant U-Net with skip and residual connections, as well as a group convolutional neural network (SRED-GCNN) using a custom loss function to remove image noise. Denoising performance was compared to the standard Block-matching and 3D filtering (BM3D) method and RED-CNN quantitatively and visually. Signal-to-noise ratio (SNR) and contrast-to-noise (CNR) were measured in manually drawn regions-of-interest in grey matter (GM), white matter (WM) and deep grey matter (DG). Visual comparison and impact on spatial resolution were assessed through phantom images. RESULTS: SRED-GCNN reduced the original CT image noise significantly better than BM3D, with SNR improvements in GM, WM, and DG by 2.47x, 2.83x, and 2.64x respectively and CNR improvements in DG/WM and GM/WM by 2.30x and 2.16x respectively. Compared to the proposed SRED-GCNN, RED-CNN reduces noise effectively though the results are visibly blurred. Scans denoised by the SRED-GCNN are shown to be visually clearer with preserved anatomy. CONCLUSION: The proposed SRED-GCNN model significantly reduces image noise and improves signal-to-noise and contrast-to-noise ratios in 380 unseen head NCCT cases.

Transcranial Doppler and magnetic resonance angiography assessment of intracranial stenosis: An analysis of screening modalities.

BACKGROUND: Time-of-flight (TOF) magnetic resonance angiography (MRA) of the head and transcranial Doppler (TCD) are used to diagnose intracranial stenosis, an important cause of ischemic stroke. We aimed to compare TCD findings with TOF-MRA results in a population of patients with symptoms of cerebrovascular disease in whom both tests were done within a short intervening period of each other. METHODS: This is a retrospective, single-center study. Among adult patients referred for symptoms of cerebrovascular disease in both outpatient and inpatient settings, those who received a TCD with adequate insonation of all intracranial arteries and underwent MRA within 3 months intervals of TCD were included in this study. We evaluated the agreement between the results of these two modalities, and also assessed sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of TCD through receiver-operating characteristic (ROC) curve analysis, while MRA considered as a comparator. RESULTS: Among eighty included patients, 720 arteries were examined. An overall significant agreement of 96.5% was observed between TCD and MRA (Kappa = 0.377, P < 0.001). Compared to MRA, TCD had sensitivity of 42.1%, specificity of 99.6%, PPV of 72.7%, and NPV of 98.4% (ROC area: 0.708 [0.594-0.822]). TCD is specifically accurate in evaluating middle cerebral artery (MCA) (ROC area = 0.83). CONCLUSIONS: The high NPV of TCD in our study indicates the utility of TCD as a diagnostic test to exclude the presence of intracranial stenosis. This study supports TCD as a convenient, safe, and reproducible imaging modality applicable in the screening of intracranial stenosis, especially to evaluate MCA.

Multifocal transcranial stimulation in chronic ischemic stroke: A phase 1/2a randomized trial.

BACKGROUND AND PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) may promote recovery of motor function after stroke by inducing functional reorganization of cortical circuits. The objective of this study was to examine whether multifocal cortical stimulation using a new wearable transcranial rotating permanent magnet stimulator (TRPMS) can promote recovery of motor function after stroke by inducing functional reorganization of cortical circuits. METHODS: Thirty30 patients with chronic ischemic stroke and stable unilateral weakness were enrolled in a Phase 1/2a randomized double-blind sham-controlled clinical trial to evaluate safety and preliminary efficacy. Bilateral hemispheric stimulation was administered for 20 sessions 40 min each over 4 weeks. The primary efficacy endpoint was the change in functional MRI BOLD activation immediately after end of treatment. Secondary efficacy endpoints were clinical scales of motor function, including the Fugl-Meyer motor arm score, ARAT, grip strength, pinch strength, gait velocity, and NIHSS. RESULTS: TRPMS treatment was well-tolerated with no device-related adverse effects. Active treatment produced a significantly greater increase in the number of active voxels on fMRI than sham treatment (median +48.5 vs -30, p = 0.038). The median active voxel number after active treatment was 8.8-fold greater than after sham (227.5 vs 26, p = 0.016). Although the statistical power was inadequate to establish clinical endpoint benefits, numerical improvements were demonstrated in 5 of 6 clinical scales of motor function. The treatment effects persisted over a 3-month duration of follow-up. CONCLUSIONS: Multifocal bilateral TRPMS was safe and showed significant fMRI changes suggestive of functional reorganization of cortical circuits in patients with chronic ischemic stroke. A larger randomized clinical trial is warranted to verify recovery of motor function.

Thrombectomy in DAWN- and DEFUSE-3-Ineligible Patients: A Subgroup Analysis From the BEST Prospective Cohort Study.

BACKGROUND: Because of the overwhelming benefit of thrombectomy for highly selected trial patients with large vessel occlusion (LVO), some trial-ineligible patients are being treated in practice. OBJECTIVE: To determine the safety and efficacy of thrombectomy in DAWN/DEFUSE-3-ineligible patients. METHODS: Using a multicenter prospective observational study of consecutive patients with anterior circulation LVO who underwent late thrombectomy, we compared symptomatic intracerebral hemorrhage (sICH) and good outcome (90-d mRS 0-2) among DAWN/DEFUSE-3-ineligible patients to trial-eligible patients and to untreated DAWN/DEFUSE-3 controls. RESULTS: Ninety-eight patients had perfusion imaging and underwent thrombectomy >6 h; 46 (47%) were trial ineligible (41% M2 occlusions, 39% mild deficits, 28% ASPECTS <6). In multivariable regression, the odds of a good outcome (aOR 0.76, 95% CI 0.49-1.19) and sICH (aOR 3.33, 95% CI 0.42-26.12) were not different among trial-ineligible vs eligible patients. Patients with mild deficits were more likely to achieve a good outcome (aOR 3.62, 95% CI 1.48-8.86) and less sICH (0% vs 10%, P = .16), whereas patients with ASPECTS <6 had poorer outcomes (aOR 0.14, 95% CI 0.05-0.44) and more sICH (aOR 24, 95% CI 5.7-103). Compared to untreated DAWN/DEFUSE-3 controls, trial-ineligible patients had more sICH (13%BEST vs 3%DAWN [P = .02] vs 4%DEFUSE [P = .05]), but were more likely to achieve a good outcome at 90 d (36%BEST vs 13%DAWN [P < .01] vs 17%DEFUSE [P = .01]). CONCLUSION: Thrombectomy is used in practice for some patients ineligible for the DAWN/DEFUSE-3 trials with potentially favorable outcomes. Additional trials are needed to confirm the safety and efficacy of thrombectomy in broader populations, such as large core infarction and M2 occlusions.

Noncontrast CT versus Perfusion-Based Core Estimation in Large Vessel Occlusion: The Blood Pressure after Endovascular Stroke Therapy Study.

BACKGROUND AND PURPOSE: The 2018 AHA guidelines recommend perfusion imaging to select patients with acute large vessel occlusion (LVO) for thrombectomy in the extended window. However, the relationship between noncontrast CT and CT perfusion imaging has not been sufficiently characterized >6 hours after last known normal (LKN). METHODS: From a multicenter prospective cohort of consecutive adults who underwent thrombectomy for anterior LVO 0-24 hours after LKN, we correlated baseline core volume (rCBF < 30%) and the Alberta Stroke Program Early CT Scale (ASPECTS) score. We compared perfusion findings between patients with an unfavorable ASPECTS (<6) against those with a favorable ASPECTS (≥6), and assessed findings over time. RESULTS: Of 485 enrolled patients, 177 met inclusion criteria (median age: 69 years, interquartile range [IQR: 57-81], 49% female, median ASPECTS 8 [IQR: 6-9], median core 10 cc [IQR: 0-30]). ASPECTS and core volume moderately correlated (r = -.37). A 0 cc core was observed in 54 (31%) patients, 70% of whom had ASPECTS <10. Of the 28 patients with ASPECTS <6, 3 (11%) had a 0 cc core. After adjustment for age and stroke severity, there was a lower ASPECTS for every 1 hour delay from LKN (cOR: 0.95, 95% confidence of interval [CI]: 0.91-1.00, P = .04). There was no difference in core (P = .51) or penumbra volumes (P = .87) across patients over time. CONCLUSIONS: In this multicenter prospective cohort of patients who underwent thrombectomy, one-third of patients had normal CTP core volumes despite nearly three quarters of patients showing ischemic changes on CT. This finding emphasizes the need to carefully assess both noncontrast and perfusion imaging when considering thrombectomy eligibility.

Blood Pressure after Endovascular Therapy for Ischemic Stroke (BEST): A Multicenter Prospective Cohort Study.

Background and Purpose- To identify the specific post-endovascular stroke therapy (EVT) peak systolic blood pressure (SBP) threshold that best discriminates good from bad functional outcomes (a priori hypothesized to be 160 mm Hg), we conducted a prospective, multicenter, cohort study with a prespecified analysis plan. Methods- Consecutive adult patients treated with EVT for an anterior ischemic stroke were enrolled from November 2017 to July 2018 at 12 comprehensive stroke centers accross the United States. All SBP values within 24 hours post-EVT were recorded. Using Youden index, the threshold of peak SBP that best discriminated primary outcome of dichotomized 90-day modified Rankin Scale score (0-2 versus 3-6) was identified. Association of this SBP threshold with the outcomes was quantified using multiple logistic regression. Results- Among 485 enrolled patients (median age, 69 [interquartile range, 57-79] years; 51% females), a peak SBP of 158 mm Hg was associated with the largest difference in the dichotomous modified Rankin Scale score (absolute risk reduction of 19%). Having a peak SBP >158 mm Hg resulted in an increased likelihood of modified Rankin Scale score 3 to 6 (odds ratio, 2.24 [1.52-3.29], P<0.01; adjusted odds ratio, 1.29 [0.81-2.06], P=0.28, after adjustment for prespecified variables). Conclusions- A peak post-EVT SBP of 158 mm Hg was prospectively identified to best discriminate good from bad functional outcome. Those with a peak SBP >158 had an increased likelihood of having a bad outcome in unadjusted, but not in adjusted analysis. The observed effect size was similar to prior studies. This finding should undergo further testing in a future randomized trial of goal-targeted post-EVT antihypertensive treatment.

Cost-effectiveness of percutaneous closure of a patent foramen ovale compared with medical management in patients with a cryptogenic stroke: from the US payer perspective.

Aims: To evaluate the cost-effectiveness of percutaneous patent foramen ovale (PFO) closure, from a US payer perspective. Lower rates of recurrent ischemic stroke have been documented following percutaneous PFO closure in properly selected patients. Stroke in patients aged <60 years is particularly interesting because this population is typically at peak economic productivity and vulnerable to prolonged disability. Materials and methods: A Markov model comprising six health states (Stable after index stroke, Transient ischemic attack, Post-Transient Ischemic Attack, Clinical ischemic stroke, Post-clinical ischemic stroke, and Death) was constructed to evaluate the cost-effectiveness of PFO closure in combination with medical management versus medical management alone. The base-case model employed a 5-year time-horizon, with transition probabilities, clinical inputs, costs, and utility values ascertained from published and national costing sources. Incremental cost-effectiveness ratio (ICER) was evaluated per US guidelines, utilizing a discount rate of 3.0%. Results: At 5 years, overall costs and quality-adjusted life-years (QALYs) obtained from PFO closure compared with medical management were $16,323 vs $7,670 and 4.18 vs 3.77, respectively. At 5 years, PFO closure achieved an ICER of $21,049, beneficially lower than the conventional threshold of $50,000. PFO closure reached cost-effectiveness at 2.3 years (ICER = $47,145). Applying discount rates of 0% and 6% had a negligible impact on base-case model findings. Furthermore, PFO closure was 95.4% likely to be cost-effective, with a willingness-to-pay (WTP) threshold of $50,000 and a 5-year time horizon. Limitations: From a cost perspective, our economic model employed a US patient sub-population, so cost data may not extrapolate to other non-US stroke populations. Conclusion: Percutaneous PFO closure plus medical management represents a cost-effective approach for lowering the risk of recurrent stroke compared with medical management alone.

Human tissue kallikrein in the treatment of acute ischemic stroke.

Acute ischemic stroke (AIS) remains a major cause of death and disability throughout the world. The most severe form of stroke results from large vessel occlusion of the major branches of the Circle of Willis. The treatment strategies currently available in western countries for large vessel occlusion involve rapid restoration of blood flow through removal of the offending blood clot using mechanical or pharmacological means (e.g. tissue plasma activator; tPA). This review assesses prospects for a novel pharmacological approach to enhance the availability of the natural enzyme tissue kallikrein (KLK1), an important regulator of local blood flow. KLK1 is responsible for the generation of kinins (bradykinin and kallidin), which promote local vasodilation and long-term vascularization. Moreover, KLK1 has been used clinically as a direct treatment for multiple diseases associated with impaired local blood flow including AIS. A form of human KLK1 isolated from human urine is approved in the People's Republic of China for subacute treatment of AIS. Here we review the rationale for using KLK1 as an additional pharmacological treatment for AIS by providing the biochemical mechanism as well as the human clinical data that support this approach.

Patent Foramen Ovale in Cryptogenic Stroke and Migraine with Aura: Does Size Matter?

INTRODUCTION: There is an association between cryptogenic strokes and patent foramen ovale (PFO), as well as between migraines with aura and PFO. The purpose of the current study was to compare shunt characteristics in the stroke and migraine populations. METHODS: We retrospectively evaluated the degree of the shunt in 68 consecutive patients with cryptogenic stroke (n=33) or migraines with aura (n=35) evaluated in a single transcranial Doppler laboratory. All patients underwent an intravenous injection of agitated saline, followed by the insonation of the middle cerebral artery to determine the degree of the right-to-left shunt. We graded the shunt size according to the number of emboli: Grade I, none; Grade II, 1-10; Grade III, 11-100; and Grade IV, >100. Grades I and II were considered low-grade shunts, and Grades III and IV were considered high-grade. RESULTS: In the 14-month study period, we found 31 high-grade shunts and 37 low-grade shunts. Among migraines with aura patients, 27 (77%) had high-grade shunts, whereas only 4 patients (12%) with cryptogenic stroke had high-grade shunts. These percentages were significantly different between groups (Fisher's exact test, p<0.0001). CONCLUSIONS: In a standardized laboratory using uniform methods, we found a significant difference in shunt size associated with PFO between cryptogenic stroke and migraine with aura patients. We hypothesize that in migraines with aura, venous admixture with arterial blood is the main mechanism by which PFO contributes to the condition. In contrast, cryptogenic strokes associated with PFO are more likely to arise from an atrial septal clot within the PFO space.

Changes in Transcranial Sonographic Measurement of the Optic Nerve Sheath Diameter in Non-concussed Collegiate Soccer Players Across a Single Season.

Introduction Bedside ultrasound measurement of the optic nerve sheath diameter (ONSD) is emerging as a non-invasive technique to evaluate and predict raised intracranial pressure (ICP) in both children and adults. The prognostic value of increased ONSD on brain computed tomography (CT) scan has previously been correlated with increased intensive care unit (ICU) mortality in patients with severe traumatic brain injury (TBI). Previous studies have also evaluated the association between high-contact sports, such as soccer, and TBI; however, the related changes in ONSD are still unknown. The aim of this study was to evaluate for the natural evolution of changes in ONSD in athletes who participate in high-contact sports. Methods In this prospective observational study, volunteers from a collegiate women's soccer team underwent the measurement of ONSD with transcranial Doppler (TCD). ONSDs were measured during the initial visit during the pre-season period and again at the three-month follow-up. A single experienced neuro-sonographer performed all measurements to eliminate any operator bias. Results Twenty-four female college soccer players between the ages of 18 and 23 were included in this analysis. Mean ONSD during the initial pre-season clinic visit and the three-month follow-up were 4.14±0.6 mm and 5.02±0.72 mm, respectively (P < 0.0001). A two-tailed t-test analysis was performed, which resulted in a t-value of 4.76 and P < 0.00001. The average ONSD measured during the post-season follow-up showed a 21.3% increase compared to the baseline. Conclusion The evaluation of high-contact sports athletes is limited due to the lack of objective radiologic and diagnostic tools. Moreover, in an athlete suffering a concussion, return-to-play decisions are heavily dependent on the symptoms reported by the athletes. In our analysis of collegiate women's soccer players, active participation in soccer competitions and practice may be associated with an increase in ONSD, independent of concussions. Further studies are underway to evaluate the clinical significance of these findings as well as possible correlations between concussions and changes in ONSD.

Allogeneic Umbilical Cord Blood Infusion for Adults with Ischemic Stroke: Clinical Outcomes from a Phase I Safety Study.

Stroke is a major cause of death and long-term disability, affecting one in six people worldwide. The only currently available approved pharmacological treatment for ischemic stroke is tissue plasminogen activator; however, relatively few patients are eligible for this therapy. We hypothesized that intravenous (IV) infusion of banked unrelated allogeneic umbilical cord blood (UCB) would improve functional outcomes in patients with ischemic stroke. To investigate this, we conducted a phase I open-label trial to assess the safety and feasibility of a single IV infusion of non-human leukocyte antigen (HLA) matched, ABO matched, unrelated allogeneic UCB into adult stroke patients. Ten participants with acute middle cerebral artery ischemic stroke were enrolled. UCB units were matched for blood group antigens and race but not HLA, and infused 3-9 days post-stroke. The adverse event (AE) profile over a 12 month postinfusion period indicated that the treatment was well-tolerated in these stroke patients, with no serious AEs directly related to the study product. Study participants were also assessed using neurological and functional evaluations, including the modified Rankin Score (mRS) and National Institute of Health Stroke Scale (NIHSS). At 3 months post-treatment, all participants had improved by at least one grade in mRS (mean 2.8 ± 0.9) and by at least 4 points in NIHSS (mean 5.9 ± 1.4), relative to baseline. Together, these data suggest that a single i.v. dose of allogeneic non-HLA matched human UCB cells is safe in adults with ischemic stroke, and support the conduct of a randomized, placebo-controlled phase 2 study. Stem Cells Translational Medicine 2018;7:521-529.

Mechanical Thrombectomy Outcomes With and Without Intravenous Thrombolysis in Stroke Patients: A Meta-Analysis.

BACKGROUND AND PURPOSE: Whether prior intravenous thrombolysis provides any additional benefits to the patients undergoing mechanical thrombectomy for large vessel, acute ischemic stroke remains unclear. METHODS: We conducted a meta-analysis of 13 studies obtained through PubMed and EMBASE database searches to determine whether functional outcome (modified Rankin Scale) at 90 days, successful recanalization rate, and symptomatic intracerebral hemorrhage rate differed between patients who underwent mechanical thrombectomy with (MT+IVT) and without (MT-IVT) pre-treatment with intravenous thrombolysis. RESULTS: MT+IVT patients compared with MT-IVT patients had better functional outcomes (modified Rankin Scale score, 0-2; summary odds ratio [OR], 1.27 [95% confidence interval (CI), 1.05-1.55]; P=0.02; n=1769/1174), lower mortality (OR, 0.71 [95% CI, 0.55-0.91]; P=0.006; n=1774/1202), and higher rate of successful recanalization (OR, 1.46 [95% CI, 1.09-1.96]; P=0.01; n=1652/1216) without having increased odds of symptomatic intracerebral hemorrhage (OR, 1.11 [95% CI, 0.69-1.77]; P=0.67; n=1471/1143). A greater number of MT+IVT patients required ≤2 passes with a neurothrombectomy device to achieve successful recanalization (OR, 2.06 [95% CI, 1.37-3.10]; P=0.0005; n=316/231). CONCLUSIONS: Our results demonstrated that MT+IVT patients had better functional outcomes, lower mortality, higher rate of successful recanalization, requiring lower number of device passes, and equal odds of symptomatic intracerebral hemorrhage compared with MT-IVT patients. The results support the current guidelines of offering intravenous thrombolysis to eligible patients even if they are being considered for mechanical thrombectomy. Because the data are compiled from studies where the 2 groups differed based on eligibility for intravenous thrombolysis, randomized trials are necessary to accurately evaluate the added value of intravenous thrombolysis in patients treated with mechanical thrombectomy.

Systolic Blood Pressure Within 24 Hours After Thrombectomy for Acute Ischemic Stroke Correlates With Outcome.

BACKGROUND: Current guidelines suggest treating blood pressure above 180/105 mm Hg during the first 24 hours in patients with acute ischemic stroke undergoing any form of recanalization therapy. Currently, no studies exist to guide blood pressure management in patients with stroke treated specifically with mechanical thrombectomy. We aimed to determine the association between blood pressure parameters within the first 24 hours after mechanical thrombectomy and patient outcomes. METHODS AND RESULTS: We retrospectively studied a consecutive sample of adult patients who underwent mechanical thrombectomy for acute ischemic stroke of the anterior cerebral circulation at 3 institutions from March 2015 to October 2016. We collected the values of maximum, minimum, and average values of systolic blood pressure, diastolic blood pressure, and mean arterial pressures in the first 24 hours after mechanical thrombectomy. Primary and secondary outcomes were patients' functional status at 90 days measured on the modified Rankin scale and the incidence and severity of intracranial hemorrhages within 48 hours. Associations were explored using an ordered multivariable logistic regression analyses. A total of 228 patients were included (mean age 65.8±14.3; 104 males, 45.6%). Maximum systolic blood pressure independently correlated with a worse 90-day modified Rankin scale and hemorrhagic complications within 48 hours (adjusted odds ratio=1.02 [1.01-1.03], P=0.004; 1.02 [1.01-1.04], P=0.002; respectively) in multivariable analyses, after adjusting for several possible confounders. CONCLUSIONS: Higher peak values of systolic blood pressure independently correlated with worse 90-day modified Rankin scale and a higher rate of hemorrhagic complications. Further prospective studies are warranted to identify whether systolic blood pressure is a therapeutic target to improve outcomes.