Patients transferred within a telestroke network for large-vessel occlusion.

INTRODUCTION: In a telestroke network, patients at a referring hospital (RH) with large-vessel occlusion (LVO) are transferred to a comprehensive stroke centre (CSC) for endovascular thrombectomy (EVT). However, a significant number of patients do not ultimately undergo thrombectomy after CSC arrival. METHODS: Within a 17-hospital telestroke network, we retrospectively analysed patients with suspected or confirmed LVO transferred to a CSC, and characterized the reasons why these patients did not undergo EVT based on the 2019 American Heart Association guidelines. RESULTS: Of 400 patients transferred to our hub, 68 (17%) were based on vascular imaging at RH. Time from RH arrival to neuroimaging was significantly longer in patients that underwent both computed tomography (CT) and CT angiography of the brain and neck compared to only CT of the brain (53 vs 13 minutes, p < 0.05). Accuracy of anterior circulation LVO (ACLVO) detection based on clinical suspicion was 62% (205 of 332 patients). Among 234 ACLVO patients, overall, 175 (74%) (early window group: 123 (73%) patients and late window group: 52 (80%) patients) met at least one EVT ineligibility criterion. The reasons for EVT ineligibility varied from large core infarct (aspects <6 or core volume >70 cc on perfusion imaging in late window), low National Institutes of Health Stroke Scale (<6), distal occlusion, and poor baseline modified Rankin Scale score (>1). DISCUSSION: Instituting rapid acquisition and interpretation of vascular imaging at RHs for LVO detection and establishing benchmarks for door to vascular imaging is urgently needed for RHs.

A meta-analysis of the global impact of the COVID-19 pandemic on stroke care & the Houston Experience.

OBJECTIVE: To review the global impact of the COVID-19 pandemic on stroke care-metrics and report data from a health system in Houston. METHODS: We performed a meta-analysis of the published literature reporting stroke admissions, intracerebral hemorrhage (ICH) cases, number of thrombolysis (tPA) and thrombectomy (MT) cases, and time metrics (door to needle, DTN; and door to groin time, DTG) during the pandemic compared to prepandemic period. Within our hospital system, between January-June 2019 and January-June 2020, we compared the proportion of stroke admissions and door to tPA and MT times. RESULTS: A total of 32,640 stroke admissions from 29 studies were assessed. Compared to prepandemic period, the mean ratio of stroke admissions during the pandemic was 70.78% [95% CI, 65.02%, 76.54%], ICH cases was 83.10% [95% CI, 71.01%, 95.17%], tPA cases was 81.74% [95% CI, 72.33%, 91.16%], and MT cases was 88.63% [95% CI, 74.12%, 103.13%], whereas DTN time was 104.48% [95% CI, 95.52%, 113.44%] and DTG was 104.30% [95% CI, 81.99%, 126.61%]. In Houston, a total of 4808 cases were assessed. There was an initial drop of ~30% in cases at the pandemic onset. Compared to 2019, there was a significant reduction in mild strokes (NIHSS 1-5) [N (%), 891 (43) vs 635 (40), P = 0.02]. There were similar mean (SD) (mins) DTN [44 (17) vs 42 (17), P = 0.14] but significantly prolonged DTG times [94 (15) vs 85 (20), P = 0.005] in 2020. INTERPRETATION: The COVID-19 pandemic led to a global reduction in stroke admissions and treatment interventions and prolonged treatment time metrics.

Routine surveillance of pelvic and lower extremity deep vein thrombosis in stroke patients with patent foramen ovale.

Patent foramen ovale (PFO) is a potential conduit for paradoxical embolization to the systemic atrial circulation of a thrombus originating in the venous system. In a selected group of subjects, the prevalence of deep vein thrombosis (DVT) was assessed. Subjects were identified if they underwent magnetic resonance venography (MRV) pelvis and lower extremity doppler (LE-VDU) for assessment of DVT with PFO. The primary outcome measure was to report the number of patients with paradoxical embolization as their suspected etiology of stroke due to the presence of DVT, which then will be considered as determined stroke. Others with determined stroke diagnosis were reported using Treatment of Acute Stroke Trial (TOAST) criteria. At discharge, those without etiology of their stroke were grouped under embolic stroke of undetermined source (ESUS). We further analyzed the prevalence of DVT by age group, ≤ 60 years vs > 60 years to describe if the prevalence is higher with younger age and to evaluate if higher Risk of Paradoxical Embolism (ROPE) score will have higher number of DVTs compared to lower ROPE scores. Of the 293, 19 (7%) were strokes due to paradoxical embolism. At discharge, determined stroke were 54% vs ESUS were 46%. The overall prevalence of DVT was 19 (7%); MRV-pelvis 13 (4%), and LE-VDU was 9 (3%). No significant difference was noted using both modalities. However, in multivariable regression analysis, a trend suggested an association between pelvic thrombi and high ROPE score as the etiology of stroke; OR 3.56 (0.98, 12.93); p = 0.054. Detection of DVT was not associated with PFO, high ROPE scores or young age. Our data indicate an over-reliance of testing for DVT, particularly MRV pelvis with contrast, in patients with PFO. Clinical studies are needed to identify other factors predictive of DVT in patients with ischemic stroke and PFO.

Influence of Intraoperative Microelectrode Recording in Deep Brain Stimulation.

BACKGROUND: There is considerable debate regarding the use of intraoperative microelectrode recording (MER) in deep brain stimulation (DBS). OBJECTIVE: To determine if the use of intraoperative MER impacts the final position of the lead implant in DBS of the subthalamic nucleus (STN) and globus pallidus (GPi) and to evaluate the incidence of complications. METHODS: The authors conducted a retrospective chart review of all patients who underwent STN and GPi DBS with MER, at the University of Texas Health Science Center in Houston from June 1, 2009 to October 1, 2013 to compare initial and final coordinates. Hemorrhagic and infectious complications were reviewed. RESULTS: A total of 90 lead implants on 46 patients implanted at the center during this time period were reviewed and included in the study. A statistically significant difference between the initial and final coordinates was observed in the superior-inferior direction with a mean difference of 0.40 mm inferiorly (±0.96 mm, P<0.05) and 0.96 mm inferiorly (±1.32 mm, P<0.05) in the STN and GPi locations, respectively. A nonstatistically significant difference was also observed in the anterior-posterior direction in both locations. There were no intraparenchymal hemorrhages on postoperative computed tomography. Two patients developed postoperative seizures (7.4%). One STN electrode (1.1%) required revision because of a suboptimal response. CONCLUSIONS: Intraoperative MER in STN and GPi DBS implant does not seem to have a higher rate of surgical complications compared with historical series not using MER and might also be useful in determining the final lead location.

Immune profiling of uveal melanoma identifies a potential signature associated with response to immunotherapy.

BACKGROUND: To date, no systemic therapy, including immunotherapy, exists to improve clinical outcomes in metastatic uveal melanoma (UM) patients. To understand the role of immune infiltrates in the genesis, metastasis, and response to treatment for UM, we systematically characterized immune profiles of UM primary and metastatic tumors, as well as samples from UM patients treated with immunotherapies. METHODS: Relevant immune markers (CD3, CD8, FoxP3, CD68, PD-1, and PD-L1) were analyzed by immunohistochemistry on 27 primary and 31 metastatic tumors from 47 patients with UM. Immune gene expression profiling was conducted by NanoString analysis on pre-treatment and post-treatment tumors from patients (n=6) receiving immune checkpoint blockade or 4-1BB and OX40 dual costimulation. The immune signature of UM tumors responding to immunotherapy was further characterized by Ingenuity Pathways Analysis and validated in The Cancer Genome Atlas data set. RESULTS: Both primary and metastatic UM tumors showed detectable infiltrating lymphocytes. Compared with primary tumors, treatment-naïve metastatic UM showed significantly higher levels of CD3+, CD8+, FoxP3+ T cells, and CD68+ macrophages. Notably, levels of PD-1+ infiltrates and PD-L1+ tumor cells were low to absent in primary and metastatic UM tumors. No metastatic organ-specific differences were seen in immune infiltrates. Our NanoString analysis revealed significant differences in a set of immune markers between responders and non-responders. A group of genes relevant to the interferon-γ signature was differentially up-expressed in the pre-treatment tumors of responders. Among these genes, suppressor of cytokine signaling 1 was identified as a marker potentially contributing to the response to immunotherapy. A panel of genes that encoded pro-inflammatory cytokines and molecules were expressed significantly higher in pre-treatment tumors of non-responders compared with responders. CONCLUSION: Our study provides critical insight into immune profiles of UM primary and metastatic tumors, which suggests a baseline tumor immune signature predictive of response and resistance to immunotherapy in UM.

Hypertension-Related Cerebral Microbleeds.

Hypertension and cerebral amyloid angiopathy are the most common causes of cerebral microbleeds. The pattern of microbleeds on T2*-weighted gradient echo sequence of magnetic resonance imaging of the brain can be indicative of the etiology of intracerebral hemorrhage. We describe a case of cerebellar hemorrhage with cerebral microbleeds secondary to chronic hypertension.

Rapid Infarct Progression in Anterior Circulation Large Vessel Occlusion Ischemic Stroke Patients During Inter-Facility Transfer.

INTRODUCTION: We aimed to identify factors associated with rapid infarct progression during inter-facility transfer for endovascular thrombectomy evaluation and its impact on clinical outcomes. METHODS: Patients with anterior circulation large artery occlusion within 24 h of onset transferred within our 17 hospital tele-stroke network were retrospectively analyzed. Patients were divided into fast progressors and slow progressors. Fast progressors were defined as CT ASPECTS score of ≥6 at the referring hospital (RH) and <6 at the hub hospital. Good clinical outcomes were defined as modified Rankin Scale score (mRS) 0-2 at 90 days. Demographic, clinical and radiologic variables associated with fast progressors and good clinical outcomes were identified using multivariable regression models. RESULTS: Among the 190 patients, 44 (23%) patients underwent rapid infarct progression. Higher stroke severity at presentation [aOR, 1.096, 95% CI,1.023, 1.174; p = 0.009], presence of early ischemic changes (CT ASPECT 6-9) at the RH [aOR, 2.721, 95% CI, 1.22, 6.071; p = 0.014] were positively associated, whereas prior ischemic stroke [aOR, 0.272, 95% CI, 0.078, 0.948; p = 0.04] and higher collateral score (2,3,4) [aOR, 0.138, 95%CI, 0.059, 0.324, p=<0.0001] were negatively associated with rapid infarct progression. Fifty-eight (31%) transferred patients had good outcomes. After adjusting for reperfusion status, age [aOR, 0.96, 95% CI, 0.93, 0.98; p=<0.001], initial stroke severity [aOR, 0.87, 95% CI, 0.81, 0.93; p=<0.001], absolute rate of decrease in CT ASPECTS [aOR, 0.38, 95% CI, 0.19, 0.77; p = 0.007] and internal carotid artery (ICA) occlusion [aOR, 0.34, 95 %CI, 0.12, 0.94; p = 0.038] were negatively associated with good outcome. CONCLUSION: Higher stroke severity, presence of early ischemic changes at the referring facility, absence of prior stroke, and poor collateral scores (CS 0-1) are the factors associated with rapid infarct progression in the telemedicine transfer cohort. Increasing age, higher stroke severity, higher absolute decrease in CT ASPECTS and ICA occlusion determine poor clinical outcomes.

Cerebrovascular Disease in Patients with COVID-19: A Review of the Literature and Case Series.

COVID-19 has been associated with a hypercoagulable state causing cardiovascular and neurovascular complications. To further characterize cerebrovascular disease (CVD) in COVID-19, we review the current literature of published cases and additionally report the clinical presentation, laboratory and diagnostic testing results of 12 cases with COVID-19 infection and concurrent CVD from two academic medical centers in Houston, TX, USA, between March 1 and May 10, 2020. To date, there are 12 case studies reporting 47 cases of CVD in COVID-19. However, only 4 small case series have described the clinical and laboratory findings in patients with COVID-19 and concurrent stroke. Viral neurotropism, endothelial dysfunction, coagulopathy and inflammation are plausible proposed mechanisms of CVD in COVID-19 patients. In our case series of 12 patients, 10 patients had an ischemic stroke, of which 1 suffered hemorrhagic transformation and two had intracerebral hemorrhage. Etiology was determined to be embolic without a clear cause identified in 6 ischemic stroke patients, while the remaining had an identifiable source of stroke. The majority of the patients had elevated inflammatory markers such as D-dimer and interleukin-6. In patients with embolic stroke of unclear etiology, COVID-19 may have played a direct or indirect role in the processes that eventually led to the strokes while in the remaining cases, it is unclear if infection contributed partially or was an incidental finding.

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

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

Non-Vitamin K Oral Anticoagulants (NOACs) and Their Reversal.

PURPOSE OF REVIEW: An 80-year-old man presents with an acute right hemiparesis and National Institutes of Health Stroke Scale (NIHSS) of 25, 14 h after taking dabigatran. Activated partial thromboplastin time (aPTT) is 42.8 s. Arteriogram demonstrates left internal carotid artery thrombosis. What is the appropriate management of this patient with acute ischemic stroke while on a NOAC? RECENT FINDINGS: Idarucizumab is a reversal agent approved for dabigatran, and two more reversal agents, andexanet alfa and aripazine, are currently in development for NOACs. In this article, we review currently available NOACs, their laboratory monitoring, and reversal agents.