Effect of different operation time on surgical effect and quality of life in patients with severe hypertensive intracerebral hemorrhage
American journal of translational research. 2021;13(8):9538-9545
OBJECTIVE To investigate the effect of different operation time on the surgery effect and quality of life of patients with severe hypertensive cerebral hemorrhage. METHODS A total of 98 patients with severe hypertensive cerebral hemorrhage were selected in this prospective study. According to the random number table, 98 patients were divided into group A and group B. About 47 patients in group A received surgical treatment within 6 hours after onset of a cerebral hemorrhage and 51 patients in group B received surgical treatment within 6-24 hours after onset of a cerebral hemorrhage. The effect of the operation, quality of life (the World Health Organization Quality of Life Scale Brief Version, WHOQOL-BREF) score, neuro function (National Institute of Health stroke scale, NIHSS), the ability of daily living (Barthel index), athletic ability (Fugl-Meyer motor function score), complications and prognosis (GOS) were compared between the two groups. RESULTS The total effective rate of operation in group A (91.49%) was higher than that in group B (76.47%), and the incidence of complications (8.70%) was lower than that in group B (27.08%; all P<0.05). NIHSS score of group A was lower than that of group B, and the WHOQOL-BREF score was higher than that of group B three months after the operation (all P<0.05). Barthel Index and Fugl-Meyer motor function scores of group A were higher than those of group B three months after the operation (all P<0.05). The prognosis of group A was better than group B three months after the operation (P<0.05). CONCLUSION Operation performed within 6 hours after the onset of cerebral hemorrhage is useful in the treatment of severe hypertensive intracerebral hemorrhage. It can effectively improve patients' neurological function, the ability of daily living and motor function without increasing complications and, the quality of life, as well as the prognosis of patients.
Intracranial Pressure and Cerebral Perfusion Pressure in Large Spontaneous Intracranial Hemorrhage and Impact of Minimally Invasive Surgery
Frontiers in neurology. 2021;12:729831
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.
Hypertension management in elderly with severe intracerebral hemorrhage
Annals of clinical and translational neurology. 2021
OBJECTIVE To explore the effect of individualized blood pressure (BP)-lowering treatment on the outcomes of elderly patients with severe intracerebral hemorrhage (ICH). METHODS We performed an exploratory analysis of Controlling Hypertension After Severe Cerebrovascular Event (CHASE) trial, which was a multicenter, randomized, controlled clinical trial. Patients with severe ischemic or hemorrhagic stroke (defined as GCS ≤ 12 or NIHSS ≥ 11) were randomized into individualized versus standard BP-lowering treatment in CHASE trial. In this exploratory analysis, patients with severe ICH were included. The primary outcome was the percentage of patients with 90-day functional independence defined as modified Rankin Scale (mRS) ≤2. RESULTS We included 242 patients with severe ICH in the present analysis, consisting of 142 patients aged <65 years and 100 patients aged ≥65 years. There were significant differences between patients aged ≥65 years and <65 years in the proportion of functional independence (47.9% vs. 15.0%, P < 0.001) and good outcome (73.9% vs. 50.0%, P < 0.001) at day 90. In patients aged ≥65 years, the adjusted individualized BP-lowering treatment had an unequivocal effect on the functional independence at day 90 (21.6% vs. 8.2%, odds ratio [OR]: 4.309, 95% confidence interval [CI]: 1.040-17.859, P = 0.044) and improved the neurological deficits at discharge (∆ NIHSS ≥ 4: 64.7% vs. 34.7%, OR: 4.300, 95% CI: 1.599-11.563, P = 0.004). INTERPRETATION Compared with the younger counterparts, the elderly patients (≥65 years) with acute severe ICH might benefit more from individualized BP-lowering treatment.
Safety and efficacy of intensive blood pressure lowering after successful endovascular therapy in acute ischaemic stroke (BP-TARGET): a multicentre, open-label, randomised controlled trial
The Lancet. Neurology. 2021
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.
Targeting Pro-Oxidant Iron with Deferoxamine as a Treatment for Ischemic Stroke: Safety and Optimal Dose Selection in a Randomized Clinical Trial
Antioxidants (Basel, Switzerland). 2021;10(8)
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.
Reactive Oxygen Species Scavenger in Acute Intracerebral Hemorrhage Patients: A Multicenter, Randomized Controlled Trial
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.
Postsurgical functional outcome prediction model using deep learning framework (Prediction One, Sony Network Communications Inc.) for hypertensive intracerebral hemorrhage
Surgical neurology international. 2021;12:203
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.
Effects of mild hypothermia therapy combined with minimally invasive debridement in patients with hypertensive intracranial hemorrhage: a randomized controlled study
American journal of translational research. 2021;13(7):7997-8003
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.
Beneficial Effect of Sodium Nitrite on EEG Ischaemic Markers in Patients with Subarachnoid Haemorrhage
Translational stroke research. 2021
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.
Prognostic significance of early pyrexia in acute intracerebral haemorrhage: The INTERACT2 study
Journal of the neurological sciences. 2021;423:117364
INTRODUCTION Uncertainty exists over the prognostic significance of pyrexia in acute intracerebral haemorrhage (ICH). We aimed to determine the association of elevated body temperature with clinical and imaging outcomes among participants of the main Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT2). METHODS Post-hoc analyses of INTERACT2, an international open, blinded outcome assessed, randomised trial of 2839 patients with spontaneous ICH (<6 h of onset) and elevated systolic blood pressure (SBP, 150-220 mmHg) randomly assigned to intensive (SBP target <140 mmHg) or guideline-recommended (SBP target < 180 mmHg) BP management. Multivariable logistic regression was used to determine associations of elevated baseline body temperature (<37.5 vs. ≥37.5 °C) and 90-day clinical outcome defined on the modified Rankin scale (mRS). Analysis of covariance determined relations of body temperature and haematoma and perihaematomal oedema (PHE) volumes, at baseline and 24 h post-randomisation. RESULTS Of 2792 participants with data available at admission, 39 (1.4%) patients had elevated body temperature ≥ 37.5 °C. Elevated body temperature was significantly associated with 90-day mortality (adjusted odds ratio 2.44; 95% confidence interval 1.02-5.82; P = .044) but not with major disability alone (mRS scores 3-5) and combination death or major disability (mRS scores 3-6). Elevated body temperature was also associated with larger PHE volume at baseline (10.89 vs. 3.14 cm(3), P < .001;) and 24 h (12.43 vs 5.76 cm(3), P = .018) but not with haematoma volumes at these time points. CONCLUSION Early pyrexia in mild to moderate ICH is associated with greater mortality and larger PHE volume, suggesting an early inflammatory-mediated reaction. CLINICAL TRIAL REGISTRATION www.clinicaltrials.gov (NCT00716079).