Inflammatory-associated proteomic predictors of cognitive outcome in subjects with ELVO treated by mechanical thrombectomy.

BACKGROUND: Emergent Large Vessel Occlusion (ELVO) stroke causes devastating vascular events which can lead to significant cognitive decline and dementia. In the subset of ELVO subjects treated with mechanical thrombectomy (MT) at our institution, we aimed to identify systemic and intracranial proteins predictive of cognitive function at time of discharge and at 90-days. These proteomic biomarkers may serve as prognostic indicators of recovery, as well as potential targets for novel/existing therapeutics to be delivered during the subacute stage of stroke recovery. METHODS: At the University of Kentucky Center for Advanced Translational Stroke Sciences, the BACTRAC tissue registry (clinicaltrials.gov; NCT03153683) of human biospecimens acquired during ELVO stroke by MT is utilized for research. Clinical data are collected on each enrolled subject who meets inclusion criteria. Blood samples obtained during thrombectomy were sent to Olink Proteomics for proteomic expression values. Montreal Cognitive Assessments (MoCA) were evaluated with categorical variables using ANOVA and t-tests, and continuous variables using Pearson correlations. RESULTS: There were n = 52 subjects with discharge MoCA scores and n = 28 subjects with 90-day MoCA scores. Several systemic and intracranial proteins were identified as having significant correlations to discharge MoCA scores as well as 90-day MoCA scores. Highlighted proteins included s-DPP4, CCL11, IGFBP3, DNER, NRP1, MCP1, and COMP. CONCLUSION: We set out to identify proteomic predictors and potential therapeutic targets related to cognitive outcomes in ELVO subjects undergoing MT. Here, we identify several proteins which predicted MoCA after MT, which may serve as therapeutic targets to lessen post-stroke cognitive decline.

Simultaneous transarterial and transvenous contrast injection to reveal the fistulous point in carotid cavernous fistula: illustrative case.

BACKGROUND: Access of the cavernous sinus (CS) via venous route from the inferior petrosal sinus (IPS) can sometimes be challenging during the treatment of carotid cavernous fistulas (CCF), largely because of anatomical variations, tortuosity, and/or difficult visualization of IPS given high retrograde flow through the fistulous connection. OBSERVATIONS: A 58-year-old male was transferred to our university hospital center after suspected diagnosis of CCF at another hospital by head computerized tomography-angiogram. His symptoms included three weeks of right eye pain that was later complicated by redness, diplopia, and blurry vision. In a diagnostic angiogram, separate contrast injections from the arterial side via internal carotid artery (ICA) and from the venous side via IPS did not reveal a connection point. Injecting contrast simultaneously from both arterial and venous ends resulted in visualization of a connection point allowing entry into the CS. LESSONS: Technique of simultaneous contrast injection from ICA and internal jugular vein is comparatively simple and saves an operator prolonged time and complexity of approach. In our case, it revealed fistulous point allowing navigation and completing the coiling.

Use of Surpass Streamline Flow Diverter for the Endovascular Treatment of Craniocervical Aneurysms: A Single-Institution Experience.

BACKGROUND: Flow diversion has revolutionized endovascular treatment for cerebral aneurysms. The Surpass Streamline flow diverter (SSFD) has shown promise for expanding flow diversion device options for aneurysm treatment. SSFD differs from earlier stents by maintaining high porosity with increased pore density to ensure appropriate flow disruption. Given the delivery system's increased dimension options and potential greater flow-diverting properties, SSFD is poised to extend the anatomic and pathologic reaches of flow diversion therapy. METHODS: Data pertaining to SSFD-treated aneurysms were gathered retrospectively between 2019 and 2020, including aneurysm location, size, symptoms, complications, and occlusions rates at follow-up. Size was categorized as small (<10 mm), large (10-25 mm), and giant (>25 mm) according to SCENT (Surpass Intracranial Aneurysm Embolization System Pivotal Trial to Treat Large or Giant Wide Neck Aneurysms) criteria. Aneurysm occlusion on follow-up imaging was characterized by Simple Measurement of Aneurysm Residual after Treatment (SMART) grading with adequate occlusion defined as grades 3 and 4. Imaging was performed at time of treatment and 6-month and 1-year follow-up. RESULTS: There were 42 aneurysms treated with SSFD throughout the cerebrovascular system: 3 cervical, 4 posterior, and 35 intracranial anterior circulation. Complete occlusion rates at 6 months and 1 year were 48% and 57% with adequate occlusion achieved in 89.6% and 85.7%, respectively. Rates of complete occlusion were higher for small (69%) compared with large (38%) aneurysms. CONCLUSIONS: Our data suggest comparable complete occlusion rates compared with SCENT (66.1% vs. 57% in our center) and adequate occlusion rates. Similar occlusion rates to prior studies despite broadened inclusion criteria and diversity of treated aneurysms demonstrate favorable generalizability of flow-diverting technology to a wide array of aneurysmal pathology.

Influence of BMI on adenosine deaminase and stroke outcomes in mechanical thrombectomy subjects.

BACKGROUND: Emergent Large Vessel Occlusion (ELVO) strokes are ischemic vascular events for which novel biomarkers and therapies are needed. The purpose of this study is to investigate the role of Body Mass Index (BMI) on protein expression and signaling at the time of ELVO intervention. Additionally, we highlight the protein adenosine deaminase (ADA), which is a deaminating enzyme that degrades adenosine, which has been shown to be neuroprotective in ischemia. We investigate the relationship between ADA and BMI, stroke outcomes, and associated proteomic networks which might aid in personalizing prognosis and future treatment of ELVO stroke. METHODS: The Blood And Clot Thrombectomy And Collaboration (BACTRAC) study is a continually enrolling tissue bank (clinicaltrials.gov NCT03153683) and registry from stroke patients undergoing mechanical thrombectomy (MT). N â€‹= â€‹61 human carotid plasma samples were analyzed for inflammatory and cardiometabolic protein expression by Olink Proteomics. Statistical analyses used t-tests, linear, logistic, and robust regressions, to assess the relationship between BMI, proteomic expression, and stroke-related outcomes. RESULTS: The 61 subjects studied were broken into three categories: normal weight (BMI 18.5-24.9) which contained 19 subjects, overweight (BMI 25-30) which contained 25 subjects, and obese (BMI ≥30) which contained 17 subjects. Normal BMI group was a significantly older population (mean 76 years) when compared to overweight (mean 66 years) and obese (mean 61 years) with significance of p â€‹= â€‹0.041 and p â€‹= â€‹0.005, respectively. When compared to normal weight and overweight categories, the obese category had significantly higher levels of adenosine deaminase (ADA) expression (p â€‹= â€‹0.01 and p â€‹= â€‹0.039, respectively). Elevated levels of ADA were found to have a significant positive correlation with both infarct volume and edema volume (p â€‹= â€‹0.013 and p â€‹= â€‹0.041, respectively), and were associated with a more severe stroke (NIHSS on discharge) and greater stroke related disability (mRS on discharge) with significance of p â€‹= â€‹0.053 and p â€‹= â€‹0.032, respectively. CONCLUSIONS: When examined according to BMI, subjects undergoing MT for ELVO demonstrate significant differences in the expression of certain plasma proteins, including ADA. Levels of ADA were found to be significantly higher in the obese population when compared to normal or overweight groups. Increased levels of ADA in the obese group were predictive of increased infarct volume, edema volume, and worse NIHSS scores and mRS at discharge. These data provide novel biomarker candidates as well as treatment targets while increasing the personalization of stroke prognosis and treatment.

Alterations in Local Peri-Infarct Blood Gases in Stroke Patients Undergoing Thrombectomy.

BACKGROUND: Ischemic stroke is a prevalent, devastating disease with high morbidity and mortality. Despite extensive research using animal models, significant gaps remain in understanding the pathological processes in human stroke. We previously developed a tissue bank to analyze the blood immediately proximal and distal to an intracranial thrombus in patients undergoing mechanical thrombectomy (ClinicalTrials.gov identifier, NCT03153683). Our goal for the present project was to evaluate the blood gas changes and acid/base balance during stroke and determine how vascular collateralization affects these changes. METHODS: We analyzed the blood samples and computed tomography angiography collateral scores from the first 62 patients in the BACTRAC (Blood and Clot Thrombectomy Registry and Collaboration) registry. The bicarbonate, partial pressure of oxygen, and partial pressure of carbon dioxide (pCO2) values of the intracranial (distal) and systemic (proximal) arterial blood relative to the occlusive thrombus were analyzed. Analysis of the group differences in systemic and intracranial blood gas values was also performed. RESULTS: The partial pressure of oxygen, pCO2, and bicarbonate levels were all significantly higher in the systemic blood than in the intracranial blood (P < 0.001 for all) at thrombectomy. Collateralization did not significantly affect the distal blood gas values. Compared with the female patients, the male patients had had higher systemic pCO2 values (39.8 vs. 36.6 mm Hg; P = 0.0065) and lower systemic and intracranial pH values (7.351 vs. 7.392; P = 0.0047). CONCLUSIONS: The arterial blood gases differed immediately proximal and distal to thrombi in large vessel occlusive stroke. Although vascular collateralization did not appear to affect the blood gas changes, some blood gas values differed between men and women. The changes in bicarbonate and pCO2 suggested a compensatory acid-base process occurring at the time of infarction.

Early post-Humanitarian Device Exemption experience with the Neuroform Atlas stent.

INTRODUCTION: The low-profile Neuroform Atlas stent received FDA Humanitarian Device Exemption status (HDE) in January 2018 for stent-assisted coil embolization of wide-necked saccular aneurysms. We review and report our results with the Atlas stent in our institution within the first year after its HDE approval. METHODS: Our retrospective chart review identified patients treated with the Atlas stent. We analyzed the patient demographics, aneurysm characteristics, stent parameters and configuration, complications, angiographic, and clinical outcomes at discharge. RESULTS: From January to December 2018, 76 Atlas stents were deployed in 58 patients (average 1.3 stents/patient). Median patient age was 63.5 (IQR 56-71) years. Fifty-six (96.6%) patients had elective embolization of unruptured aneurysms, while two (3.4%) patients underwent embolization of a ruptured aneurysm within 2 weeks of subarachnoid hemorrhage. Forty (69.0%) patients were treated with a single stent, 15 (25.9%) with a Y-stent, and three (5.2%) with X-stent configuration. All stent deployments were technically successful. Most stents (82.9%) were the smallest 3 mm diameter devices. Procedural complications included transient stent-associated thrombosis in three (5.2%) patients and aneurysm rupture in one (1.7%). None had distal embolization, associated cerebral infarction, or permanent neurological deficits. Immediate Raymond-Roy 1 occlusion was achieved in 41 (70.7%) patients. Median hospital length of stay for elective aneurysm embolization was 1 day. Excellent outcomes with median National Institute of Health Stroke Scale score 0 (IQR 0-0) and modified Rankin Score 0 (IQR 0-1) were seen for elective patients at discharge. CONCLUSION: The Neuroform Atlas stent provided a reliable technical and safety profile for the treatment of intracranial wide-neck aneurysms. Further experience is needed to determine long-term durability and safety of this device.

Reduction in time to treatment in prehospital telemedicine evaluation and thrombolysis.

OBJECTIVE: To compare the times to evaluation and thrombolytic treatment of patients treated with a telemedicine-enabled mobile stroke treatment unit (MSTU) vs those among patients brought to the emergency department (ED) via a traditional ambulance. METHODS: We implemented a MSTU with telemedicine at our institution starting July 18, 2014. A vascular neurologist evaluated each patient via telemedicine and a neuroradiologist and vascular neurologist remotely assessed images obtained by the MSTU CT. Data were entered in a prospective registry. The evaluation and treatment of the first 100 MSTU patients (July 18, 2014-November 1, 2014) was compared to a control group of 53 patients brought to the ED via a traditional ambulance in 2014. Times were expressed as medians with their interquartile ranges. RESULTS: Patient and stroke severity characteristics were similar between 100 MSTU and 53 ED control patients (initial NIH Stroke Scale score 6 vs 7, p = 0.679). There was a significant reduction of median alarm-to-CT scan completion times (33 minutes MSTU vs 56 minutes controls, p < 0.0001), median alarm-to-thrombolysis times (55.5 minutes MSTU vs 94 minutes controls, p < 0.0001), median door-to-thrombolysis times (31.5 minutes MSTU vs 58 minutes controls, p = 0.0012), and symptom-onset-to-thrombolysis times (97 minutes MSTU vs 122.5 minutes controls, p = 0.0485). Sixteen patients evaluated on MSTU received thrombolysis, 25% of whom received it within 60 minutes of symptom onset. CONCLUSION: Compared with the traditional ambulance model, telemedicine-enabled ambulance-based thrombolysis resulted in significantly decreased time to imaging and treatment.

A Mobile Stroke Treatment Unit for Field Triage of Patients for Intraarterial Revascularization Therapy.

INTRODUCTION: Favorable outcomes in intraarterial therapy (IAT) for acute ischemic stroke (AIS) are related to early vessel recanalization. The mobile stroke treatment unit (MSTU) is an on-site, prehospital, treatment team, laboratory, and CT scanner that reduces time to treatment for intravenous thrombolysis and may also shorten time to IAT. METHODS: Using our MSTU database, we identified patients that underwent IAT for AIS. We compared the key time metrics to historical controls, which included patients that underwent IAT at our institution six months prior to implementation of the MSTU. We further divided the controls into two groups: (1) transferred to our institution for IAT and (2) directly presented to our emergency room and underwent IAT. RESULTS: After 164 days of service, the MSTU transported 155 patients of which 5 underwent IAT. We identified 5 historical controls that were transferred to our center for IAT. Substantial reduction in times including median door to initial CT (12 minute vs. 32 minute), CT to IAT (82 minute vs. 165 minute), and door to MSTU/primary stroke center departure (37 minute vs. 106 minute) were noted among the two groups. Compared to the 6 patients who presented to our institution directly, the MSTU process times were also shorter. CONCLUSION: Our initial experience shows that MSTU may help in early triage and shorten the time to IAT for AIS.