Rapid Intravenous Glyceryl Trinitrate in Ischemic Damage (RIGID): A potential neuroprotection strategy for acute ischemic stroke (AIS) patients.

Despite advances in intravenous thrombolysis and endovascular thrombectomy, numerous acute ischemic stroke survivors continue to experience various disability levels. The nitric oxide (NO) donor, Glyceryl Trinitrate (GTN), has been identified as a potential neuroprotective agent against ischemic damage. We evaluated the safety and feasibility of intravenous GTN in AIS patients. Subsequently, we conducted a secondary analysis to assess for possible efficacy of GTN as a neuroprotectant. We conducted a prospective, double-blind, randomized controlled trial in the Stroke Intervention & Translational Center (SITC) in Beijing Luhe Hospital, Capital Medical University (ChiCTR2100046271). AIS patients within 24 h of stroke onset were evenly divided into GTN or control groups (n = 20 each). The GTN group received intravenous GTN (5 mg in 50 ml saline at a rate of 0.4 mg/h for 12.5 h/day over 2 days), while controls were administered an equivalent volume of 0.9% saline. Both groups followed standard Stroke Guidelines for treatment. Safety measures focused on SBP<110 mmHg and headache occurrence. Efficacy was assessed via the 90-day modified rankin score (mRS) and the national institutes of health stroke score (NIHSS). Of the 40 AIS patients, baseline characteristics such as age, gender, risk factors, and pre-mRS scores showed no significant difference between the groups. Safety measures of SBP<110 mmHg and headache occurrence were comparable. Overall, 90-day mRS (1 vs. 1) and NIHSS (1 vs. 1) did not significantly differ between groups. However, the GTN-treated group had a benefit in enhancing NIHSS recovery (△NIHSS 4.5 vs. 3, p = 0.028), indicating that GTN may augment recovery. Subgroup analyses revealed a benefit in the GTN group at the 90-day NIHSS score and △NIHSS follow up for non-thrombolysis patients (1 vs. 2, p = 0.016; 5 vs. 2, p = 0.001). Moreover, the GTN group may benefit mild stroke patients in NIHSS score at 90 day and △NIHSS observed at 90 days (1 vs. 1, p = 0.025; 3 vs. 2 p = 0.002). Overall, while preliminary data suggest GTN might aid recovery in NIHSS improvement, the evidence is tempered due to sample size limitations. The RIGID study confirms the safety and feasibility of intravenous GTN administration for AIS patients. Preliminary data also suggest that the GTN group may provide improvement in NIHSS recovery compared to the control group. Furthermore, a potential benefit for non-thrombolysis patients and those with mild stroke symptoms was identified, suggesting a possible potential role as a tailored intervention in specific AIS subgroups. Due to the limited sample size, further larger RCT will be necessary to replicate these results. TRIAL REGISTRATION: www.chictr.org.cn, identifier: ChiCTR2100046271.

Arterial Glyceryl Trinitrate in Acute Ischemic Stroke After Thrombectomy for Neuroprotection (AGAIN): A Pilot Randomized Controlled Trial.

Although endovascular therapy demonstrates robust clinical efficacy in acute ischemic stroke (AIS), not all stroke patients benefit from successful reperfusion. This study aimed to evaluate the safety, feasibility, and preliminary efficacy of intra-arterial administration of glyceryl trinitrate (GTN) after endovascular recanalization for neuroprotection. This is a prospective randomized controlled study. Eligible patients were randomized to receive 800 µg GTN or the same volume of normal saline through the catheter after recanalization. The primary outcome was symptomatic intracranial hemorrhage (ICH), while secondary outcomes included mortality, functional outcome, infarction volume, complications, and blood nitrate index (NOx). A total of 40 patients were enrolled and randomized with no participants being lost to follow-up. There was no significant difference in the proportion of sICH between GTN and control groups. Additionally, no significant difference was observed in mortality or rates of neurological deterioration and other complications. Favorable trends, while non-significant, were noted in both outcome and imaging for functional independence at 90 days and reduction in final infarct volume (75.0% vs 65.0%; 33.2 vs 38.9 ml) for the GTN group. Moreover, the concentration of blood NOx in the GTN group was significantly higher than in the control group at 2 h after GTN administration (26.2 vs 18.0 µmol/l, p < 0.05). The AGAIN study suggests intra-arterial administration of GTN post-endovascular therapy is safe and feasible and GTN successfully raised NOx levels over controls at 2 h. A multi-center randomized controlled trial with a larger sample size is warranted to determine GTN neoadjuvant efficacy.

Unilateral Minimally Invasive Across-Midline Vertebral Column Resection Partially Corrects Thoracolumbar Kyphosis - A Case Series.

OBJECTIVE: The goal of this study was to describe the indirect and partial correction of spine kyphotic deformities (secondary to various pathologies) achieved by minimally invasive posterolateral extracavitary approach (MIS PLECA) for corpectomy. METHODS: The authors retrospectively reviewed a consecutive case series of 12 patients undergoing MIS PLECA in a single institution. Perioperative data were collected and follow-up computed tomographies and radiographs were reviewed to assess for interbody arthrodesis. RESULTS: The mean age was 60.7 ± 20.8 years (58.4% males). The etiologies of deformity included pathological fracture (41.6%), acute trauma (30%), and infection. An expandable cage was used in 66.7% of patients for anterior reconstruction. The mean total estimated blood loss was 764.1 ± 332.9 ml. The mean operative time was 413.3 ± 98.8 minutes. The average length of hospital stay was 5.8 ± 2.5 days. A consistent degree of focal correction of sagittal alignment was seen in all patients with a mean correction of sagittal angle of 7.4 ± 4.3° (P < 0.0001). The mean duration of rehabilitation was 8.5 ± 6.7 days. All patients remained neurologically stable at the last follow-up with a mean follow-up period of 20.1 ± 12.8 months. Successful fusion was achieved in 91.7% at the last follow-up. CONCLUSIONS: MIS PLECA for corpectomy appears to be a feasible, safe, and effective MIS technique for select patients, particularly those who cannot tolerate the traditional open approach. Additionally, a focal sagittal deformity correction can be achieved using MIS corpectomy.

Patch Technique for Primary Treatment of Type A Carotid Cavernous Fistula: A Case Series and Technical Notes.

BACKGROUND: The utilization of flow diverters (FDs) in the treatment of high-flow Type A carotid cavernous fistulas (CCFs) has been described before mainly as an adjunct to the traditional endovascular techniques and rarely as a stand-alone treatment. In this study, we retrospectively evaluated our experience with FDs as the solo nonadjunctive treatment of Type A CCF with severe cortical venous reflux (CVR). METHODS: A retrospective review was performed of patients with Type A CCFs who were treated using FDs' patch technique (PT). Patients' demographics, clinical data, and preoperative and postoperative ocular examination were recorded. The procedure technique, pipeline embolization device (PED) diameters, and immediate and late procedure outcomes were described. RESULTS: Three patients were included in this case series. All patients had history of trauma and presented with decreased visual acuity, cranial nerve II deficit, limited extraocular muscles' movement, and increased intraocular pressure (IOP). Diagnostic angiography was performed, which confirmed high-flow Type A CCF. Endovascular treatment was performed through distal radial access in 2 patients and femoral access in 1 patient by deploying 4 sequentially enlarging PEDs with immediate resolution of the ocular symptoms. Follow-up angiography confirmed complete resolution of CCF in 2 patients. One patient was lost to follow-up; however, angiogram at 4 months demonstrated residual small CCF with significant improvement from postprocedure angiogram. CONCLUSIONS: The patch technique using sequentially enlarging FDs is a reasonable alternative solo technique for the treatment of direct CCF symptoms and results in immediate resolution of CVR while preserving the cavernous sinus anatomy.

Vertebrobasilar artery cooling infusion in acute ischemic stroke for posterior circulation following thrombectomy: Rationale, design and protocol for a prospective randomized controlled trial.

Background: Although endovascular mechanical thrombectomy demonstrates clinical efficacy in posterior circulation acute ischemic stroke (AIS), only one third of these patients attain functional independence with a third of patients' expiring despite vascular recanalization. Neuroprotection strategies, such as therapeutic hypothermia (TH) have been considered a promising adjunctive treatment in AIS. We propose the following rationale, design and protocol for a prospective randomized controlled trial (RCT) aimed to determine whether Vertebrobasilar Artery Cooling Infusion (VACI) improves functional outcomes in posterior circulation AIS patients post mechanical thrombectomy. Methods: Subjects in the study will be assigned randomly to either the cooling infusion or the control group in a 1:1 ratio (n = 40). Patients allocated to the cooling infusion group will receive 300 ml cool saline at 4C through the catheter (30 ml/min) into vertebral artery after thrombectomy. The control group will receive the same volume of 37C saline. All patients enrolled will receive standard care according to current guidelines for stroke management. The primary outcome is symptomatic intracranial hemorrhage (ICH), whereas the secondary outcomes include functional outcome score, infarction volume, mortality, ICH, fatal ICH, cerebral vasospasm, coagulation abnormality, pneumonia and urinary infection. Discussions: This study will determine the preliminary safety, feasibility, and neuroprotective benefits of VACI in posterior circulation AIS patients with reperfusion therapy. The results of this study may provide evidence for VACI as a new therapy in posterior circulation AIS. Clinical Trial Registration: www.chictr.org.cn, ChiCTR2200065806, registered on November 15, 2022.

Large vessel occlusion stroke outcomes in diabetic vs. non-diabetic patients with acute stress hyperglycemia.

Objective: This study assesses whether stress-induced hyperglycemia is a predictor of poor outcome at 3 months for patients with acute ischemic stroke (AIS) treated by endovascular treatment (EVT) and impacted by their previous blood glucose status. Methods: This retrospective study collected data from 576 patients with AIS due to large vessel occlusion (LVO) treated by EVT from March 2019 to June 2022. The sample was composed of 230 and 346 patients with and without diabetes mellitus (DM), respectively, based on their premorbid diabetic status. Prognosis was assessed with modified Rankin Scale (mRS) at 3-month after AIS. Poor prognosis was defined as mRS>2. Stress-induced hyperglycemia was assessed by fasting glucose-to-glycated hemoglobin ratio (GAR). Each group was stratified into four groups by quartiles of GAR (Q1-Q4). Binary logistic regression analysis was used to identify relationship between different GAR quartiles and clinical outcome after EVT. Results: In DM group, a poor prognosis was seen in 122 (53%) patients and GAR level was 1.27 ± 0.44. These variables were higher than non-DM group and the differences were statistically significant (p < 0.05, respectively). Patients with severe stress-induced hyperglycemia demonstrated greater incidence of 3-month poor prognosis (DM: Q1, 39.7%; Q2, 45.6%; Q3, 58.6%; Q4, 68.4%; p = 0.009. Non-DM: Q1, 31%; Q2, 32.6%; Q3, 42.5%; Q4, 64%; p < 0.001). However, the highest quartile of GAR was independently associated with poor prognosis at 3 months (OR 3.39, 95% CI 1.66-6.96, p = 0.001), compared to the lowest quartile in non-DM patients after logistic regression. This association was not observed from DM patients. Conclusion: The outcome of patients with acute LVO stroke treated with EVT appears to be influenced by premorbid diabetes status. However, the poor prognosis at 3-month in patients with DM is not independently correlated with stress-induced hyperglycemia. This could be due to the long-term damage of persistent hyperglycemia and diabetic patients' adaptive response to stress following acute ischemic damage to the brain.

Arterial Glyceryl Trinitrate in Acute Ischemic Stroke after Thrombectomy for Neuroprotection (AGAIN): Rationale, design and protocol for a prospective randomized controlled trial.

BACKGROUND: Although endovascular recanalization therapy demonstrates robust clinical efficacy in acute ischemic stroke (AIS), not all victims of these cerebrovascular accidents can benefit from it and achieve a favorable prognosis after successful reperfusion. Therefore, alternative neuroprotective strategies are urgently needed for AIS patients after vessel recanalization. Nitric oxide (NO) levels are low after AIS and NO donor drugs may be neuroprotective against cerebral ischemia-reperfusion injury. Glyceryl trinitrate (GTN), often used in the clinic as a NO donor, may provide a novel neuroprotective strategy. This rationale, design, and protocol for a prospective pilot study plans to explore the preliminary safety, feasibility, and neuroprotective benefits of Arterial Glyceryl Trinitrate in Acute Ischemic Stroke after Thrombectomy for Neuroprotection (AGAIN). METHODS: AGAIN, a prospective RCT, is proposed for AIS patients after mechanical thrombectomy. Subjects will be randomly assigned in a 1:1 fashion (n = 40) to either the control group or the intervention group. Participants assigned to the intervention group will be administered 800 µg GTN in the catheter immediately after recanalization, whereas those in the control group will be administered the same volume of normal saline. All participants from either group will be given concurrent treatment with standard of care therapies in accordance with the current guidelines for stroke management. The primary outcome is safety [symptomatic intracranial hemorrhage (ICH), hypotension, neurological deterioration, ICH, fatal ICH, as well as headache, tachycardia, emesis, and seizures], whereas secondary outcomes included changes in poststroke functional outcomes, infarction volumes, and blood nitrate index detection. DISCUSSIONS: This study is a prospective randomized controlled trial to test the safety and efficacy of intra-arterial GTN in AIS patients after endovascular therapy. The results from this study will give insight for future GTN studies and new neuroprotective strategies for future AIS treatment strategies. TRIAL REGISTRATION NUMBER: ChiCTR2100045254. Registered on March 21, 2021.

Endovascular Therapy vs Medical Management for Patients With Acute Stroke With Medium Vessel Occlusion in the Anterior Circulation.

Importance: Randomized clinical trials have shown the efficacy of endovascular therapy (EVT) for acute large vessel occlusion strokes. The benefit of EVT in acute stroke with distal, medium vessel occlusion (DMVO) remains unclear. Objective: To examine the efficacy and safety outcomes associated with EVT in patients with primary DMVO stroke when compared with a control cohort treated with medical management (MM) alone. Design, Setting, and Participants: This multicenter, retrospective cohort study pooled data from patients who had an acute stroke and a primary anterior circulation emergency DMVO, defined as any segment of the anterior cerebral artery (ACA) or distal middle cerebral artery, between January 1, 2015, and December 31, 2019. Those with a concomitant proximal occlusion were excluded. Outcomes were compared between the 2 treatment groups using propensity score methods. Data analysis was performed from March to June 2021. Exposures: Patients were divided into EVT and MM groups. Main Outcomes and Measures: Main efficacy outcomes included 3-month functional independence (modified Rankin Scale [mRS] scores, 0-2) and 3-month excellent outcome (mRS scores, 0-1). Safety outcomes included 3-month mortality and symptomatic intracranial hemorrhage. Results: A total of 286 patients with DMVO were evaluated, including 156 treated with EVT (mean [SD] age, 66.7 [13.7] years; 90 men [57.6%]; median National Institute of Health Stroke Scale [NIHSS] score, 13.5 [IQR, 8.5-18.5]; intravenous tissue plasminogen activator [IV tPA] use, 75 [49.7%]; ACA involvement, 49 [31.4%]) and 130 treated with medical management (mean [SD] age, 69.8 [14.9] years; 62 men [47.7%]; median NIHSS score, 7.0 [IQR, 4.0-14.0], IV tPA use, 58 [44.6%]; ACA involvement, 31 [24.0%]). There was no difference in the unadjusted rate of 3-month functional independence in the EVT vs MM groups (151 [51.7%] vs 124 [50.0%]; P = .78), excellent outcome (151 [38.4%] vs 123 [31.7%]; P = .25), or mortality (139 [18.7%] vs 106 [11.3%]; P = .15). The rate of symptomatic intracranial hemorrhage was similar in the EVT vs MM groups (weighted: 4.0% vs 3.1%; P = .90). In inverse probability of treatment weighting propensity analyses, there was no significant difference between groups for functional independence (adjusted odds ratio [aOR], 1.36; 95% CI, 0.84-2.19; P = .20) or mortality (aOR, 1.24; 95% CI, 0.63-2.43; P = .53), whereas the EVT group had higher odds of an excellent outcome (mRS scores, 0-1) at 3 months (aOR, 1.71; 95% CI, 1.02-2.87; P = .04). Conclusions and Relevance: The findings of this multicenter cohort study suggest that EVT may be considered for selected patients with ACA or distal middle cerebral artery strokes. Further larger randomized investigation regarding the risk-benefit ratio for DMVO treatment is indicated.

Adjuvant high-flow normobaric oxygen after mechanical thrombectomy for posterior circulation stroke: A randomized clinical trial.

BACKGROUND: Recent studies suggest only a third of posterior circulation stroke patients have a good functional outcome with a high mortality after mechanical thrombectomy. To mitigate mortality rates and increase functional outcomes, we investigated the safety and efficacy of high-flow, normobaric oxygen (NBO) after endovascular recanalization in posterior circulation stroke. METHODS: This is a prospective randomized controlled study. Eligible patients were randomized to receive high-flow NBO by a Venturi mask (FiO2 50%, flow 15 L/min) or routine low-flow oxygen supplementation by nasal cannula (flow 3 L/min) after vessel recanalization for 6 h. Patient demographics, procedural metrics, complications, functional outcomes, symptomatic intracranial hemorrhage (sICH), and infarct volume were assessed. RESULTS: While we assessed 122 patients for eligibility, 87 patients were randomly assigned (44 patients to the NBO group). Post operatively there was no significant difference in distribution of global disability scores on the mRS at 90 days or functional independence between the two groups. We did observe a trend suggesting reduced mortality at 90 days with reduced infarct volume in the NBO group, however this was not statistically significant. No significant differences were seen in the rate of sICH, pneumonia or urinary infection between the two groups. When comparing our results with the BASICS and BEST study, our study did reveal a significantly better prognosis after endovascular therapy. CONCLUSION: Our results indicate that high-flow adjuvant NBO therapy was safe. However, the current study does not provide evidence for a significant neuroprotection effect in posterior circulation stroke patients after endovascular recanalization.

Imaging features of adult moyamoya disease patients with anterior intracerebral hemorrhage based on high-resolution magnetic resonance imaging.

This study aimed to identify the high-resolution magnetic resonance imaging (HRMRI) features of moyamoya disease (MMD) patients with anterior intracerebral hemorrhage (ICH) and attempted to reveal potential mechanisms of anterior ICH. Eligible adult MMD patients were consecutively included, and the morphological features of lenticulostriate arteries (LSAs), vessel wall structure of terminal internal carotid artery (ICA) and periventricular anastomosis were evaluated by HRMRI. 78 MMD patients containing 21 patients with anterior ICH, 31 ischemic patients and 26 asymptomatic patients were included. The mean value of total length of LSAs in anterior ICH group (90.79 ± 37.00 mm) was distinctively lower (p < 0.001) compared with either ischemic group (138.04 ± 46.01 mm) or asymptomatic group (170.50 ± 39.18 mm). Lumen area of terminal ICA was significantly larger (p < 0.001) in hemorrhagic group (4.33 ± 2.02 mm2) compared with ischemic group (2.29 ± 1.17 mm2) or asymptomatic group (3.00 ± 1.34 mm2). Multivariate analysis revealed the total length of LSAs (OR 0.689, 95%CI, 0.565-0.840; p < 0.001) and lumen area of terminal ICA (OR 2.085, 95%, 1.214-3.582; p = 0.008) were significantly associated with anterior ICH. Coexistence of reduced LSAs and relatively preserved lumen area of terminal ICA with an AUC of 0.901 (95%CI, 0.812-0.990) could be a potential predictor of anterior ICH in MMD patients.

Learning curves for transradial access versus transfemoral access in diagnostic cerebral angiography: a case series.

BACKGROUND: The perception of a steep learning curve associated with transradial access has resulted in its limited adoption in neurointervention despite the demonstrated benefits, including decreased access-site complications. OBJECTIVE: To compare learning curves of transradial versus transfemoral diagnostic cerebral angiograms obtained by five neurovascular fellows as primary operator. METHODS: The first 100-150 consecutive transradial and transfemoral angiographic scans performed by each fellow between July 2017 and March 2020 were identified. Mean fluoroscopy time per artery injected (angiographic efficiency) was calculated as a marker of technical proficiency and compared for every 25 consecutive procedures performed (eg, 1-25, 26-50, 51-75). RESULTS: We identified 1242 diagnostic angiograms, 607 transradial and 635 transfemoral. The radial cohort was older (64.3 years vs 62.3 years, p=0.01) and demonstrated better angiographic efficiency (3.4 min/vessel vs 3.7 min/vessel, p=0.03). For three fellows without previous endovascular experience, proficiency was obtained between 25 and 50 transfemoral angiograms. One fellow achieved proficiency after performing 25-50 transradial angiograms; and the two other fellows, in <25 transradial angiograms. The two fellows with previous experience had flattened learning curves for both access types. Two patients experienced transient neurologic symptoms postprocedure. Transradial angiograms were associated with significantly fewer access-site complications (3/607, 0.5% vs 22/635, 3.5%, p<0.01). Radial-to-femoral conversion occurred in 1.2% (7/607); femoral-to-radial conversion occurred in 0.3% (2/635). Over time, the proportion of transradial angiographic procedures increased. CONCLUSION: Technical proficiency improved significantly over time for both access types, typically requiring between 25 and 50 diagnostic angiograms to achieve asymptomatic improvement in efficiency. Reduced access-site complications and decreased fluoroscopy time were benefits associated with transradial angiography.

Passing Extracranial Artery Occlusion by Intermediate Catheter With Expanding Microballoon (PEACE): A Novel Endovascular Therapy in Acute Tandem Occlusion Stroke.

PURPOSE: Endovascular treatment of atherosclerotic tandem occlusions in acute ischemic stroke (AIS) is a matter of debate. This article reports a single-center experience using an intermediate catheter with microballoon for treatment of tandem occlusions. METHODS: A total of 151 AIS patients with large vessel occlusion received endovascular therapy and a consecutive series of patients (n = 26) who suffered from tandem cervical intracranial occlusions were treated using the Passing Extracranial Artery Occlusion by Intermediate Catheter with Expanding Microballoon (PEACE) technique. Intracranial recanalization was achieved by aspiration or stent retriever and then emergency stenting was performed for extracranial internal carotid artery (ICA) lesion. Demographic, clinical characteristics, procedural details of endovascular therapy, and prognosis outcome were assessed. The outcomes of tandem occlusion group were compared with isolated intracranial occlusion group (n = 122) and previous studies. RESULTS: As compared to isolated intracranial occlusion groups, only a few patients suffered from atrial fibrillation (7.7% vs 38.5%, p<0.01) in tandem occlusions group. A larger proportion of patients (61.5% vs 29.5%) had tandem occlusions in which extracranial ICA occlusion was combined with intracranial terminus occlusion in ICA (p<0.01). 46.2% of tandem occlusions patients achieved intracranial recanalization by aspiration alone versus 15.6% in patients with isolated intracranial occlusion (p<0.01). In tandem occlusion patients treated with PEACE, 92.3% achieved successful reperfusion (thrombolysis in cerebral infarct [TICI] ≥2b). The median time from puncture to recanalization was 51 minutes (interquartile range [IQR], 41-66). 67.6% favorable functional prognosis (modified Rankin score [mRS], 0-2) was seen, with 11.5% mortality and 3.8% of symptomatic intracerebral hemorrhage (sICH) at 90 days. These outcomes are all consistent or better than previously reported studies performed for tandem occlusion. CONCLUSIONS: Endovascular therapy using the PEACE technique with intermediate catheter and lined expanding microballoon is safe, efficient, and fast in the treatment of atherosclerotic tandem occlusion patients.

Intracranial microembolic signals might be a potential risk factor for cognitive impairment.

Objective: We aimed to explore the relationship between microembolic signals (MES) and cognitive impairment in patients with neurological disorders using a 30-minute MES monitoring test.Methods: We retrospectively reviewed patients who visited outpatient departments and underwent a 30-minute MES monitoring session using dual-channel transcranial doppler (TCD) at Beijing Tiantan hospital between July 2016 and December 2018. All patients completed the Montreal Cognitive Assessment (MoCA) and underwent magnetic resonance imaging (MRI). Cognitive impairment was defined as a MoCA score of less than 26. MES were identified according to the criteria of the International Consensus Group on Microembolus Detection.Results: Of the 1356 subjects who underwent MES monitoring, 159 patients (including 50 cases of MES positive and 109 cases of MES negative) had both analyzable MES monitoring recording and cognition evaluation data, of which 72 had cognitive impairment. Compared with the group with no deficits in cognitive function, the proportion of MES positive was significantly higher in patients with impaired cognitive function - that is, 47% (34/72) versus 18.4% (16/87), respectively, with p < 0.05. In multivariate logistic regression analysis, MES were independently associated with lower MoCA score (odd ratios (OR), 7.36; 95% confidence intervals (CI), 2.72-19.85, P < 0.0001).Conclusions: In this retrospective study, we found a possible correlation and relationship between MES and cognitive impairment. Further studies are required to determine whether continuous cerebral microembolization to the brain will lead to progressive cognitive impairment.

Rapid Intravenous Glyceryl Trinitrate in Ischemic Damage (RIGID) After Stroke: Rationale, Design and Protocol for a Prospective Randomized Controlled Trial.

Background: Despite intravenous thrombolysis and endovascular therapy for acute ischemic stroke (AIS), many survivors still have varying degrees of disability. Glyceryl trinitrate (GTN), a nitric oxide (NO) donor, has been previously reported to induce neuroprotection after AIS. The use of GTN to reduce brain damage after stroke remains yet to be elucidated. This study was designed to explore the safety, feasibility, and preliminary efficacy of intravenous administration of GTN after AIS. Methods: A prospective randomized controlled trial is proposed with AIS patients. Participants will be randomly allocated to GTN group and control group with a 1:1 ratio (n = 40). Both groups will be treated with standard therapies according to the current stroke guidelines. Participants allocated to the GTN group will receive intravenous administration of GTN (5 mg GTN in 50 ml saline at a rate of 0.4 mg/h that is continued for 12.5 h/day for 2 days) within 24 h of symptom onset. Participants allocated to the control group will receive intravenous administration at equal capacity of 0.9% normal saline (NS) (total 50 ml/day at 4 ml/h that is continued for 12.5 h/day for 2 days). The primary outcome is safety [systolic blood pressure (SBP) <110 mmHg, headache], while the secondary outcomes include changes in functional outcome and infarction volume. Discussion: Rapid Intravenous Glyceryl Trinitrate in Ischemic Damage (RIGID) is a prospective randomized controlled trial that aims to ascertain the safety, feasibility, and preliminary efficacy of intravenous GTN as a neuroprotection strategy after AIS. These results will provide parameters for future studies as well as provide insights into treatment effects. Any possible neuroprotective qualities of GTN in AIS will also be elucidated. Trial Registration:www.chictr.org.cn, identifier: ChiCTR2100046271.

Normobaric oxygen may correct chronic cerebral ischemia-mediated EEG anomalies.

AIMS: To explore the safety and efficacy of normobaric oxygen (NBO) on correcting chronic cerebral ischemia (CCI) and related EEG anomalies. METHODS: This prospective randomized trial (NCT03745092) enrolled 50 cases of CCI patients, which were divided into NBO (8 L/min of oxygen supplement) group and control group (room air) randomly, and also enrolled 21 healthy volunteers. Two times of 30-min EEG recordings with the interval of 45min of NBO or room air were analyzed quantitatively. RESULTS: The CCI-mediated EEG presented with two patterns of electrical activities: high-power oscillations (high-power EEG, n = 26) and paroxysmal slow activities under the normal-power background (normal-power EEG, n = 24). The fronto-central absolute power (AP) of the beta, alpha, theta, and delta in the high-power EEG was higher than that in healthy EEG (p < 0.05). The fronto-central theta/alpha, delta/alpha and (delta + theta)/(alpha + beta) ratios in the normal-power EEG were higher than those in healthy EEG (p < 0.05). The high-power EEG in NBO group had higher fronto-central AP reduction rates than those in control group (p < 0.05). NBO remarkably reduced the fronto-central theta/alpha, delta/alpha, and (delta + theta)/(alpha + beta) ratios in the normal-power EEG (p < 0.05). CONCLUSIONS: NBO rapidly ameliorates CCI-mediated EEG anomalies, including attenuation of the abnormal high-power oscillations and the paroxysmal slow activities associated with CCI.

Rapid Intervention of Chlorpromazine and Promethazine for Hibernation-Like Effect in Stroke: Rationale, Design, and Protocol for a Prospective Randomized Controlled Trial.

Background: Following an acute ischemic stroke (AIS), rapidly initiated reperfusion therapies [i. e., intravenous thrombolysis (IVT) and endovascular treatment (EVT)] demonstrate robust clinical efficacy. However, only a subset of these patients can benefit from these therapies due to their short treatment windows and potential complications. In addition, many patients despite successful reperfusion still have unfavorable outcomes. Thus, neuroprotection strategies are urgently needed for AIS patients. Chlorpromazine and promethazine (C+P) have been employed in clinical practice for antipsychotic and sedative purposes. A clinical study has also shown a neuroprotective effect of C+P on patients with cerebral hemorrhage and subarachnoid hemorrhage. The safety, feasibility, and preliminary efficacy of intravenous administration of C+P in AIS patients within 24 h of onset will be elucidated. Methods: A prospective randomized controlled trial is proposed with AIS patients. Participants will be randomly allocated to an intervention group and a control group with a 1:1 ratio (n = 30) and will be treated with standard therapies according to the current stroke guidelines. Participants allocated to the intervention group will receive intravenous administration of C+P (chlorpromazine 50 mg and promethazine 50 mg) within 24 h of symptom onset. The primary outcome is safety (mainly hypotension), while the secondary outcomes include changes in functional outcome and infarction volume. Discussions: This study on Rapid Intervention of Chlorpromazine and Promethazine for Hibernation-like Effect in Stroke (RICHES) will be the first prospective randomized controlled trial to ascertain the safety, feasibility, and preliminary efficacy of intravenous C+P as a neuroprotection strategy in AIS patients. These results will provide parameters for future studies, provide insights into treatment effects, and neuroprotection with phenothiazine in AIS. Clinical Trial Registration: www.chictr.org.cn, identifier: ChiCTR2000038727.

Outcomes in Endovascular Therapy for Basilar Artery Occlusion: Intracranial Atherosclerotic Disease vs. Embolism.

Acute ischemic stroke due to basilar artery occlusion (BAO) carries a very poor prognosis. Functional outcomes in BAO patients undergoing endovascular therapy (EVT) may differ according to the specific pathological mechanisms. We aimed to explore the impact of the underlying pathological mechanisms on prognosis at 90-days and long-term follow-up in BAO patients treated with EVT. We analyzed consecutive BAO patients undergoing EVT from December 2012 to December 2018 at a single center (Xuanwu Hospital). Patients were classified into either an intracranial atherosclerotic disease (ICAD) group or an embolic group according to the corresponding angiographic findings. The baseline characteristics and functional outcomes were compared between the two groups. Multivariable logistic regression analysis was performed. Among the 167 patients enrolled, 78 patients (46.7%) were in the ICAD group and 89 patients (53.3%) were assigned to the embolic group. Overall, 149 patients (89.2%) achieved successful reperfusion post-EVT. There were no significant differences in functional outcomes at 90-days and long-term follow-up between the two groups. Similarly, a Kaplan-Meier survival analysis showed similar long-term survival probabilities (P = 0.438). The pathological mechanism was not associated with functional independence (OR, 1.818; 95% CI, 0.694-4.761; P = 0.224), favorable outcome (OR, 1.476; 95% CI, 0.592-3.681; P = 0.403), or mortality (OR, 1.249; 95% CI, 0.483-3.226; P = 0.646). However, based on subgroup analysis, embolic BAO versus ICAD was significantly associated with better functional independence in those aged 60 years and younger (OR, 4.513; 95% CI, 1.138-17.902). In this study, no differences in either 90-days or long-term functional outcomes between ICAD-related BAO and embolic BAO patients undergoing EVT were observed. However, in BAO patients aged ≤ 60 years, the pathological mechanism of embolism was associated with better functional independence.

NIHSS Consciousness Score Combined with ASPECTS is a Favorable Predictor of Functional Outcome post Endovascular Recanalization in Stroke Patients.

Although revascularization rates after endovascular thrombectomy for large vessel acute ischemic stroke (AIS) are high (71%), only 46% of patients achieve functional independence at 90 days. The present study was designed to explore a new method for predicting the functional prognosis of AIS patients after endovascular recanalization. A total of 200 anterior circulation stroke patients who received endovascular therapy were enrolled. Logistic regression analysis of clinical characteristics on functional independence were performed. The predictive power of sub-items in National Institute of Health stroke scale (NIHSS) and the combination of NIHSS consciousness and Alberta Stroke Program Early CT Score (ASPECTS) on functional independence were assessed by Receiver Operating Characteristic (ROC) curves and the latter was compared with 3 previously published prediction models by AUC (the area under ROC curve). The AUC for the NIHSS consciousness score to predict functional independence was higher than whole NIHSS and other sub-items (0.716 v 0.705, 0.586, 0.573, 0.552 and 0.559). Low NIHSS consciousness score, high ASPECTS score, short time from onset to recanalization, and high rate of successful recanalization were demonstrated to be significantly associated with the functional independence (OR 0.697, 2.226, 0.994 and 28.643). The prediction power of the combination was significantly better than NIHSS and ASPECTS alone (AUC 0.793 v 0.705 and 0.752). Compared with 3 other prediction models, the combination was found to be the strongest predictor for functional independence (AUC 0.793 v 0.791, 0.671 and 0.564). NIHSS which has been shown to be a strong predictor of functional outcomes after endovascular recanalization is largely dependent on the consciousness component. NIHSS consciousness score combined with ASPECTS appears to be a favorable predictor of functional independence. These findings may have broad reaching effects for isolated centers around the world without advanced imaging for triage and prognostication.

Identifying Biomarkers Associated with Venous Infarction in Acute/Subacute Cerebral Venous Thrombosis.

Among cerebral venous thrombosis (CVT) patients, those with venous infarction have more severe clinical presentations and worse outcomes. Identifying biomarkers associated with venous infarction in CVT may help understand the pathogenesis and provide potentially useful therapeutic markers. Fifty-two CVT patients were prospectively recruited and divided into three groups: acute/subacute CVT with venous infarction (ASVI, n=30), without venous infarction (ASOVI, n=13), and chronic CVT (n=9). Blood brain barrier (BBB) permeability-related proteins, including claudin-5, occludin, matrix metalloproteinase-9, glial fibrillary acidic protein, and S100B, and inflammation-related factor high-sensitivity C-reactive protein (hs-CRP), were tested in serum and/or cerebrospinal fluid upon admission. We compared these biomarkers between the three groups and investigated their associations with venous infarction and clinical symptom severity in acute/subacute CVT patients on admission using the NIH Stroke Scale (NIHSS). Serum hs-CRP was significantly higher in acute/subacute CVT patients than chronic CVT patients. For acute/subacute CVT patients, levels were significantly higher in the ASVI group than the ASOVI group for serum claudin-5 (medians 2.80 vs. 2.50 mg/I, respectively, P = 0.039) and hs-CRP (medians 17.25 vs. 2.27 mg/l, respectively, P = 0.003). Both these biomarkers, analyzed as categorical or continuous variables, were also significantly associated with venous infarction in acute/subacute CVT patients after logistic regression analysis. Additionally, hs-CRP was positively correlated with the NIHSS (r = 0.710, P < 0.001) on admission in acute/subacute CVT patients. In CVT patients, venous infarction was associated with BBB disruption and potentially inflammation. Hs-CRP might serve as a biomarker reflecting the clinical severity of CVT in the acute/subacute stages.

Complete flow control using transient concurrent rapid ventricular pacing or intravenous adenosine and afferent arterial balloon occlusion during transvenous embolization of cerebral arteriovenous malformations: case series.

BACKGROUND: There are no reports that describe complete flow control using concurrent transient rapid ventricular pacing or intravenous (IV) adenosine and afferent arterial balloon flow arrest to aid transvenous embolization of cerebral arteriovenous malformations (AVM). We describe our experience with the use of this technique in patients undergoing transvenous AVM embolization. METHODS: Consecutive patients in whom transvenous embolization was attempted at our institute between January 2017 and July 2019 were included. Anatomical AVM features, number of embolization stages, technique of concurrent transient rapid ventricular pacing and afferent arterial balloon flow arrest, complications, and clinical and radiological outcomes were recorded and tabulated. RESULTS: Transvenous AVM embolization was attempted in 12 patients but abandoned in two patients for technical reasons. Complete embolization was achieved in 10 patients, five of whom had infratentorial AVMs. All 10 had a single primary draining vein. Rapid ventricular pacing was used in nine cases; IV adenosine injection was used in one case to achieve cardiac standstill. Complete AVM nidus obliteration was achieved with excellent neurologic outcome in nine cases, with transvenous embolization alone in two cases, and with staged transarterial followed by transvenous embolization in the others. Two patients developed hemorrhagic complications intraprocedurally. One patient was managed conservatively and the other operatively with AVM excision and hematoma evacuation; both made an excellent recovery without any neurologic deficits at 3 months. CONCLUSION: Complete flow control using concurrent transient rapid ventricular pacing with afferent arterial balloon flow arrest technique is safe and feasible for transvenous embolization of select AVMs.