Abstract

BACKGROUND The objective of this study was to evaluate factors associated with intraventricular hemorrhage (IVH) expansion and its association with long-term outcomes. METHODS We performed a post hoc analysis of the international, multi-center CLEAR III trial (Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage) which enrolled IVH patients between September 1, 2009, and January 31, 2015. The exposure was IVH expansion, defined as >1 mL increase in volume between baseline and stability computed tomography scans, before treatment randomization. We assessed factors associated with IVH expansion and secondarily assessed the relationship of IVH expansion with clinical outcomes: composite of death or major disability (modified Rankin Scale score, >3), and mortality alone at 6 months. The relationship of IVH expansion on ventriculoperitoneal shunt placement was additionally explored. Multivariable logistic regression was used for all analyses. RESULTS Of 500 IVH patients analyzed, the mean age was 59 (±11) years old, 44% were female and 135 (27%) had IVH expansion. In multivariable regression models, factors associated with IVH expansion were baseline parenchymal intracerebral hemorrhage (ICH) volume (adjusted odds ratio [OR], 1.04 per 1 mL increase [95% CI, 1.01-1.08]), presence of parenchymal hematoma expansion: >33% (adjusted OR, 6.63 [95% CI, 3.92-11.24]), time to stability head CT (adjusted OR, 0.71 per 1 hour increase [95% CI, 0.54-0.94]), and thalamic hematoma location (adjusted OR, 1.68 [95% CI, 1.01-2.79]) while additionally adjusting for age, sex, and race. In secondary analyses, IVH expansion was associated with higher odds of poor 6-month outcomes (adjusted OR, 1.84 [95% CI, 1.12-3.02]) but not mortality (OR, 1.40 [95% CI, 0.78-2.50]) after adjusting for baseline ICH volume, thalamic ICH location, age, anticoagulant use, Glasgow Coma Scale score, any withdrawal of care order, and treatment randomization arm. However, there were no relationships of IVH expansion on subsequent ventriculoperitoneal shunt placement (adjusted OR, 1.02 [95% CI, 0.58-1.80]) after adjusting for similar covariates. CONCLUSIONS In a clinical trial cohort of patients with large IVH, acute hematoma characteristics, specifically larger parenchymal volume, hematoma expansion, and thalamic ICH location were associated with IVH expansion. Given that IVH expansion resulted in poor functional outcomes, exploration of treatment approaches to optimize hemostasis and prevent IVH expansion, particularly in patients with thalamic ICH, require further study. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT00784134.

Abstract

OBJECTIVES To explore the clinical value of minimally invasive aspiration and drainage of intracranial hematoma in the treatment of cerebral hemorrhage. METHODS Seventy-eight patients with cerebral hemorrhage who were treated in the Taian City Central Hospital and the Second Affiliated Hospital of Shandong First Medical University between June 2018 and December 2019 were selected. The patients were randomly numbered and divided into two groups by drawing lots, 39 in each group. The control group was treated with the traditional internal medicine conservative therapy, and the observation group was treated with minimally invasive intracranial hematoma aspiration and drainage. The indexes of the two groups were compared. RESULTS The efficacy rate of the observation group was significantly higher than that of the control group, and the difference was statistically significant (P<0.05). The National Institutes of Health Stroke Scale (NIHSS) score of the observation group was lower than that of the control group after treatment, and the difference was statistically significant (P<0.05). After treatment, the good recovery rate of the observation group was higher compared to the control group, and the difference had statistical significance (P<0.05). The incidence of complications in the observation group was lower than that of the control group, with a statistically significant difference (P<0.05). CONCLUSION In the treatment of cerebral hemorrhage, minimally invasive intracranial hematoma aspiration and drainage facilitates the recovery of patients, promotes the improvement of neurological function, and has a high safety profile and an ideal prognostic quality.

Abstract

BACKGROUND AND PURPOSE Patients with intracerebral hemorrhage (ICH) have oxidative stress. Oxidative stress contributes to the development and progression of perihematomal edema (PHE) in brain hemorrhage patients. We hypothesized that reactive oxygen species (ROS) scavengers might have a neuroprotective role in the acute period of patients with ICH. METHODS This prospective, multicenter, single-blind, randomized study was conducted between June 2017 and October 2019. Intracranial bleeding, including spontaneous ICH, secondary ICH due to vascular anomalies, venous thrombosis, neoplasms, or hemorrhagic infarction, were included in our study. These ROS scavengers were given for 14 days with a dose of N-acetylcysteine 2000 mg/d and selenium 1600 µg/d intravenously. Other patients received a placebo. The primary outcome was hemorrhage and PHE volume changes in 2-week follow-up computed tomography between ROS scavenger versus placebo groups. RESULTS In total, 448 patients were enrolled with 123 patients remaining after applying the inclusion and exclusion criteria. There were no significant differences in baseline characteristics between the ROS scavenger (n=57) and placebo (n=66) groups. No significant differences in baseline hematoma and PHE volumes were observed but 2 weeks follow-up computed tomography showed significant differences in PHE volume (21.90±17.63 versus 30.66±32.35, P<0.01) and PHE ratio (1.19±0.73 versus 2.05±1.27, P<0.01). Among clinical factors, time to reach target Richmond Agitation Sedation Scale (5.98 hours [95% CI, 4.82-7.241 versus 8.42 hours], [95% CI, 6.57-10.77], P<0.01) and the length of intensive care unit stays (6.46 days [95% CI, 2.38-10.55 versus 12.66 days], [95% CI, 8.47-16.85], P<0.01) were significantly shortened among patients who received ROS scavengers than among patients who did not receive ROS scavenger. CONCLUSIONS ROS scavenger showed a significantly reduced PHE volume, time to reach target Richmond Agitation Sedation Scale, and shortened length of intensive care unit stay in patients with acute ICH. Early and high doses of ROS scavengers in a combination regimen may have played a key role in obtaining a favorable outcome in our study.

Abstract

BACKGROUND Reliable prediction models of intracerebral hemorrhage (ICH) outcomes are needed for decision-making of the treatment. Statistically making such prediction models needs a large number of samples and time-consuming statistical analysis. Deep learning (DL), one of the artificial intelligence, is attractive, but there were no reports on DL-based functional outcome prediction models for ICH outcomes after surgery. We herein made a functional outcome prediction model using DLframework, Prediction One (Sony Network Communications Inc., Tokyo, Japan), and compared it to original ICH score, ICH Grading Scale, and FUNC score. METHODS We used 140 consecutive hypertensive ICH patients' data in our hospital between 2012 and 2019. All patients were surgically treated. Modified Rankin Scale 0-3 at 6 months was defined as a favorable outcome. We randomly divided them into 100 patients training dataset and 40 patients validation dataset. Prediction One made the prediction model using the training dataset with 5-fold cross-validation. We calculated area under the curves (AUCs) regarding the outcome using the DL-based model, ICH score, ICH Grading Scale, and FUNC score. The AUCs were compared. RESULTS The model made by Prediction One using 64 variables had AUC of 0.997 in the training dataset and that of 0.884 in the validation dataset. These AUCs were superior to those derived from ICH score, ICH Grading Scale, and FUNC score. CONCLUSION We easily and quickly made prediction models using Prediction One, even with a small single-center dataset. The accuracy of the DL-based model was superior to those of previous statistically calculated models.

Abstract

Introduction: We investigated the effect of hematoma volume reduction with minimally invasive surgery (MIS) on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in patients with large spontaneous intracerebral hemorrhage (ICH). Methods: Post-hoc analysis of the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation (MISTIE III) study, a clinical trial with blinded outcome assessments. The primary outcome was the proportion of ICP readings ≥20 and 30 mmHg, and CPP readings <70 and 60 mm Hg. Secondary outcomes included major disability (modified Rankin scale >3) and mortality at 30 and 365 days. We assessed the relationship between proportion of high ICP and low CPP events and MIS using binomial generalized linear models, and outcomes using multiple logistic regression. Results: Of 499 patients enrolled in MISTIE III, 72 patients had guideline based ICP monitors placed, 34 in the MIS group and 38 in control (no surgery) group. Threshold ICP and CPP events ≥20/ <70 mmHg occurred in 31 (43.1%) and 52 (72.2%) patients respectively. On adjusted analyses, proportion of ICP readings ≥20 and 30 mmHg were significantly lower in the MIS group vs. control group [Odds Ratio (OR) 0.27, 95% Confidence Interval [CI] 0.11-0.63 (p = 0.002); OR = 0.18, 0.04-0.75, p = 0.02], respectively. Proportion of CPP readings <70 and 60 mm Hg were also significantly lower in MIS patients [OR 0.31, 95% CI 0.15-0.63 (p = 0.001); OR 0.30, 95% CI 0.11-0.83 (p = 0.02)], respectively. Higher proportions of CPP readings <70 and 60 mm were significantly associated with short term mortality (p = 0.04), and (p = 0.006), respectively. Long term mortality was significantly associated with higher proportion of time with ICP ≥ 20 (p = 0.04), ICP ≥ 30 (p = 0.04), and CPP <70 mmHg (p = 0.01). Conclusion: Our results are consistent with the hypothesis that surgical reduction of ICH volume decreases proportion of high ICP and low CPP events and that these variables are associated with short- and long-term mortality.

Abstract

OBJECTIVE To investigate the clinical effect of mild hypothermia therapy (MHT) combined with minimally invasive debridement (MID) in patients with severe hypertensive intracranial hemorrhage (HICH). METHODS A total of 120 patients with severe HICH who received clinical intervention in our hospital were enrolled as study subjects. In this randomized, controlled, double-blind trial, they were divided into a study group (SG, n=70) and a control group (CNG, n=50). The CNG was treated with MID, and the SG was treated with MID combined with MHT. The general surgical indices, short-term postoperative outcomes, postoperative neurological and recovery in activities of daily living, and complications were compared between the two groups. Patients' Glasgow prognosis (Glasgow Outcome Scale, GOS) scores at 1 year after surgery were analyzed. RESULTS The operative time, intraoperative blood loss and intensive care unit (ICU) admission were shorter/lower in the SG than in the CNG (P<0.05). The SG had higher hematoma clearance rate at 1 d and 3 d postoperatively, and lower residual hematoma volume at 3 d and 7 d postoperatively than the CNG (P<0.05). Patients in the SG had higher Barthel scores and lower National Institutes of Health Stroke Scale (NIHSS) scores than the CNG at 1-12 months after intervention (P<0.05). The incidence of complications in the SG was lower than that in the CNG (P<0.05). The percentage of GOS grade IV and V was significantly higher in the SG than in the CNG 1 year after surgery (P<0.05). CONCLUSION The combination of MID and MHT in patients with severe HICH has better clinical results in the short and long term, and improves the postoperative outcomes and quality of life. It can also reduce the incidence of perioperative complications.

Abstract

Background Remote ischemic conditioning (RIC) can promote hematoma resolution, attenuate brain edema, and improve neurological recovery in animal models of intracerebral hemorrhage (ICH). Aims This study aimed to evaluate the safety and preliminary efficacy of RIC in patients with ICH.Methods In this multicenter, randomized, controlled trial, 40 subjects with supratentorial ICH presenting within 24-48 hours of onset were randomly assigned to receive medical therapy plus RIC for consecutive 7 days or medical therapy alone. The primary safety outcome was neurological deterioration within 7 days of enrollment, and the primary efficacy outcome was the changes of hematoma volume on CT images. Other outcomes included hematoma resolution rate at 7 d ([hematoma volume at 7 d â hematoma volume at baseline]/hematoma volume at baseline), perihematomal edema (PHE), and functional outcome at 90 days. Results The mean age was 59.3±11.7 years and hematoma volume was 13.9±4.5 mL. No subjects experienced neurological deterioration within 7 days of enrollment, and no subject died or experienced RIC-associated adverse events during the study period. At baseline, the hematoma volumes were 14.19±5.07 mL in the control group and 13.55±3.99 mL in the RIC group, and they were 8.54±3.99 mL and 6.95±2.71 mL at 7 days after enrollment, respectively, not a significant difference (p>0.05 each). The hematoma resolution rate in the RIC group (49.25±9.17%) was significantly higher than in the control group (41.92±9.14%; MD, 7.3%; 95% CI, 1.51% to 13.16%; p=0.015). The absolute PHE volume was 17.27±8.34 mL in the control group and 12.92±7.30 mL in the RIC group at 7 days after enrollment, not a significant between-group difference (p=0.087), but the relative PHE in the RIC group (1.77±0.39) was significantly lower than in the control group (2.02±0.27; MD, 0.25; 95% CI, 0.39-0.47; p=0.023). At 90-day follow-up, 13 subjects (65%) in the RIC group and 12 subjects (60%) in the control group achieved favorable functional outcomes (mRS scoreâ¤3), not a significant between-group difference (p=0.744).Conclusions Repeated daily RIC for consecutive 7 days was safe and well-tolerated in patients with ICH, and it may be able to improve hematoma resolution rate and reduce relative PHE. However, effects RIC on the absolute hematoma and PHE volume and functional outcomes in this patient population need further investigations.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03930940.

Abstract

A role of iron as a target to prevent stroke-induced neurodegeneration has been recently revisited due to new evidence showing that ferroptosis inhibitors are protective in experimental ischemic stroke and might be therapeutic in other neurodegenerative brain pathologies. Ferroptosis is a new form of programmed cell death attributed to an overwhelming lipidic peroxidation due to excessive free iron and reactive oxygen species (ROS). This study aims to evaluate the safety and tolerability and to explore the therapeutic efficacy of the iron chelator and antioxidant deferoxamine mesylate (DFO) in ischemic stroke patients. Administration of placebo or a single DFO bolus followed by a 72 h continuous infusion of three escalating doses was initiated during the tPA infusion, and the impact on blood transferrin iron was determined. Primary endpoint was safety and tolerability, and secondary endpoint was good clinical outcome (clinicalTrials.gov NCT00777140). DFO was found safe as adverse effects were not different between placebo and DFO arms. DFO (40-60 mg/Kg/day) reduced the iron saturation of blood transferrin. A trend to efficacy was observed in patients with moderate-severe ischemic stroke (NIHSS > 7) treated with DFO 40-60 mg/Kg/day. A good outcome was observed at day 90 in 31% of placebo vs. 50-58% of the 40-60 mg/Kg/day DFO-treated patients.

Abstract

BACKGROUND High systolic blood pressure after successful endovascular therapy for acute ischaemic stroke is associated with increased risk of intraparenchymal haemorrhage. However, no randomised controlled trials are available to guide optimal management. We therefore aimed to assess whether an intensive systolic blood pressure target resulted in reduced rates of intraparenchymal haemorrhage compared with a standard systolic blood pressure target. METHODS We did a multicentre, open-label, randomised controlled trial at four academic hospital centres in France. Eligible individuals were adults (aged ≥18 years) with an acute ischaemic stroke due to a large-vessel occlusion that was successfully treated with endovascular therapy. Patients were randomly assigned (1:1) to either an intensive systolic blood pressure target group (100-129 mm Hg) or a standard care systolic blood pressure target group (130-185 mm Hg), by means of a central web-based procedure, stratified by centre and intravenous thrombolysis use before endovascular therapy. In both groups, the target systolic blood pressure had to be achieved within 1 h after randomisation and maintained for 24 h with intravenous blood pressure lowering treatments. The primary outcome was the rate of radiographic intraparenchymal haemorrhage at 24-36 h and the primary safety outcome was the occurrence of hypotension. Analyses were done on an intention-to-treat basis. BP-TARGET is registered with ClinicalTrials.gov, number NCT03160677, and the trial is closed at all participating sites. FINDINGS Between June 21, 2017, and Sept 27, 2019, 324 patients were enrolled in the four participating stroke centres: 162 patients were randomly assigned to the intensive target group and 162 to the standard target group. Four (2%) of 162 patients were excluded from the intensive target group and two (1%) of 162 from the standard target group for withdrawal of consent or legal reasons. The mean systolic blood pressure during the first 24 h after reperfusion was 128 mm Hg (SD 11) in the intensive target group and 138 mm Hg (17) in the standard target group. The primary outcome was observed in 65 (42%) of 154 patients in the intensive target group and 68 (43%) of 157 in the standard target group on brain CT within 24-36 h after reperfusion] (adjusted odds ratio 0·96, 95% CI 0·60-1·51; p=0·84). Hypotensive events were not significantly different between both groups and occurred in 12 (8%) of 158 patients in the intensive target and five (3%) of 160 in the standard target group. Mortality within the first week after randomisation occurred in 11 (7%) of 158 patients in the intensive target group and in seven (4%) of 160 in the standard target group. INTERPRETATION An intensive systolic blood pressure target of 100-129 mm Hg after successful endovascular therapy did not reduce radiographic intraparenchymal haemorrhage rates at 24-36 h as compared with a standard care systolic blood pressure target of 130-185 mm Hg. Notably, these results are applicable to patients with successful reperfusion and systolic blood pressures of more than 130 mm Hg at the end of procedure. Further studies are needed to understand the association between blood pressure and outcomes after reperfusion. FUNDING French Health Ministry.

Abstract

Subarachnoid haemorrhage (SAH) is associated with long-term disability, serious reduction in quality of life and significant mortality. Early brain injury (EBI) refers to the pathological changes in cerebral metabolism and blood flow that happen in the first few days after ictus and may lead on to delayed cerebral ischaemia (DCI). A disruption of the nitric oxide (NO) pathway is hypothesised as a key mechanism underlying EBI. A decrease in the alpha-delta power ratio (ADR) of the electroencephalogram has been related to cerebral ischaemia. In an experimental medicine study, we tested the hypothesis that intravenous sodium nitrite, an NO donor, would lead to increases in ADR. We studied 33 patients with acute aneurysmal SAH in the EBI phase. Participants were randomised to either sodium nitrite or saline infusion for 1 h. EEG measurements were taken before the start of and during the infusion. Twenty-eight patients did not develop DCI and five patients developed DCI. In the patients who did not develop DCI, we found an increase in ADR during sodium nitrite versus saline infusion. In the five patients who developed DCI, we did not observe a consistent pattern of ADR changes. We suggest that ADR power changes in response to nitrite infusion reflect a NO-mediated reduction in cerebral ischaemia and increase in perfusion, adding further evidence to the role of the NO pathway in EBI after SAH. Our findings provide the basis for future clinical trials employing NO donors after SAH.