Formation of neutrophil extracellular traps worsens cerebrovascular outcomes after traumatic brain injury.

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.

Y selected patients. Patients should be stratified for future stroke risk based on both the degree of stenosis and the presence of symptoms referable to the culprit lesion. Carotid stenting is also useful in reducing stroke risk, again in carefully selected patients. Because of the publication of significant data regarding both carotid endarterectomy and carotid artery stenting in the last several years, selection can be far more personalized and refined for individual patients based on demographics, sex, patient preference, and medical comorbidities. Routine extracranial-intracranial bypass surgery remains unproven as a therapeutic option for large vessel occlusion in reducing the incidence of ischemic stroke although some carefully screened patient populations remaining at high risk may benefit; procedural risks and pathology related to alterations in blood flow dynamics are challenges to overcome. Indirect revascularization remains an appropriate solution for carefully selected patients with cerebral large vessel steno-occlusive disease, and multiple variations of surgical technique are patient specific. Indirect revascularization may benefit from clinical trials with larger patient populations for validation in specific pathologies and offers the advantages of lower surgical complication rates and reduced risk of pathologic responses to altered cerebral flow dynamics. SUMMARY Surgical solutions to reduce stroke risk provide important alternatives in appropriately selected patients and should be considered in addition to medical management and lifestyle modification for optimizing patient outcomes....

Neutrophil extracellular traps formation (NETosis) facilitates thrombosis and contributes to reperfusion resistance - a major challenge encountered during the treatment of acute ischemic stroke. The effect of acute stroke on plasma NETosis biomarkers remains unclear. In this study, young adult C57BL/6 wildtype (WT) mice were subjected to acute brain ischemia-reperfusion (IR) injury. The IR-subjected mice exhibited a drastic increase in plasma citrullinated histone 3 (CitH3) and neutrophil elastase (NE) on day 1 (p < 0.05) while deoxyribonucleic acid (DNA) and myeloperoxidase (MPO) reached their peak levels on day 3. IR-subjected mice also showed a significant increase in peripheral neutrophils and decline in peripheral leukocytes, lymphocytes, and monocytes on day 1 and day 2 (p < 0.05). The ratios of neutrophil to lymphocyte, neutrophil to leukocyte, and lymphocyte to monocyte dramatically increased on day 1 (p < 0.05). Plasma NE, CitH3 and MPO were positively correlated with peripheral neutrophil and the ratio of neutrophil to lymphocyte, but inversely correlated with peripheral lymphocyte (p < 0.05). Our data suggest that there are time dependent changes in plasma NETosis biomarkers. Therefore, targeting these biomarkers before their peak may offer potential therapeutic options to reduce cerebral infarction and prevent functional deterioration after acute ischemic stroke.