Abstract

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.

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

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

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

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 AND PURPOSE The computed tomography angiography or contrast-enhanced computed tomography based spot sign has been proposed as a biomarker for identifying on-going hematoma expansion in patients with acute intracerebral hemorrhage. We investigated, if spot-sign positive participants benefit more from tranexamic acid versus placebo as compared to spot-sign negative participants. METHODS TICH-2 trial (Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage) was a randomized, placebo-controlled clinical trial recruiting acutely hospitalized participants with intracerebral hemorrhage within 8 hours after symptom onset. Local investigators randomized participants to 2 grams of intravenous tranexamic acid or matching placebo (1:1). All participants underwent computed tomography scan on admission and on day 2 (24±12 hours) after randomization. In this sub group analysis, we included all participants from the main trial population with imaging allowing adjudication of spot sign status. RESULTS Of the 2325 TICH-2 participants, 254 (10.9%) had imaging allowing for spot-sign adjudication. Of these participants, 64 (25.2%) were spot-sign positive. Median (interquartile range) time from symptom onset to administration of the intervention was 225.0 (169.0 to 310.0) minutes. The adjusted percent difference in absolute day-2 hematoma volume between participants allocated to tranexamic versus placebo was 3.7% (95% CI, -12.8% to 23.4%) for spot-sign positive and 1.7% (95% CI, -8.4% to 12.8%) for spot-sign negative participants (P(heterogenity)=0.85). No difference was observed in significant hematoma progression (dichotomous composite outcome) between participants allocated to tranexamic versus placebo among spot-sign positive (odds ratio, 0.85 [95% CI, 0.29 to 2.46]) and negative (odds ratio, 0.77 [95% CI, 0.41 to 1.45]) participants (P(heterogenity)=0.88). CONCLUSIONS Data from the TICH-2 trial do not support that admission spot sign status modifies the treatment effect of tranexamic acid versus placebo in patients with acute intracerebral hemorrhage. The results might have been affected by low statistical power as well as treatment delay. REGISTRATION URL: http://www.controlled-trials.com; Unique identifier: ISRCTN93732214.

Abstract

OBJECTIVE This study explored and analyzed the effects of butylphthalide injection on the cognitive function and on the TLRs/NF-κB pathway in hypertensive intracerebral hemorrhage patients. METHODS A total of 115 patients admitted to our hospital with hypertensive intracerebral hemorrhages were recruited as the study cohort and randomly placed in the observation group (n=60) or the control group (n=55). In addition to the routine treatment administered in both groups, the control group was additionally administered oral nimodipine tablets, and the observation group was administered intravenous butylphthalide injections. Both groups were treated continuously for 14 days. Subsequently, the changes in the clinical efficacy, the NIHSS scores, the extremity motor function, the Fugl-Meyer scores, the blood-brain barrier (BBB) and the peripheral blood mononuclear cells (PBMCs), the TLR2, TLR9, and the NF-κB mRNA levels in the two groups before and after the treatment were compared, and any adverse reactions were observed. RESULTS The total effective rate in the observation group was significantly superior to the total effective rate in the control group (P<0.05). The post-treatment NIHSS scores in the two groups were dramatically lower (P<0.05), and the post-treatment scores in the observation group were significantly lower than they were in the control group (P<0.05). The post-treatment cerebral spinal fluid (CSF) albumin and BBB indexes in the two groups were decreased significantly compared to their pre-treatment levels (P<0.05), and the post-treatment indexes in the observation group were significantly lower than the post-treatment indexes in the control group (P<0.05). The post-treatment relative TLR2, TLR9, and NF-κB mRNA expressions in the two groups were apparently lower than their in pre-treatment levels (P<0.05), and the relative expressions in the observation group after the treatment were clearly lower than they were in the control group (P<0.05). CONCLUSION Butylphthalide injection has a high clinical efficacy in treating hypertensive intracerebral hemorrhages. The drug can effectively improve patients' cognitive functions, extremity motor functions, and BBB indexes, and its mechanism may connect with the expressive suppression of the TLRs/NF-κB signaling pathway. The treatment is safe and effective, so it is worthy of clinical promotion.

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

BACKGROUND Early out-of-bed mobilization may improve acute post-intracerebral hemorrhage (ICH) outcomes, but hemodynamic instability may be a concern. Some recent studies have showed that an increase in mean systolic blood pressure (SBP) and high blood pressure variability (BPV), high standard deviation of SBP, may lead to negative ICH outcomes. Therefore, we investigated the impact of an early mobilization (EM) protocol on mean SBP and BPV during the acute phase. METHODS The study was an assessor-blinded, randomized controlled non-inferiority study. The participants were in An Early Mobilization for Acute Cerebral Hemorrhage trial and were randomly assigned to undergo EM or a standard early rehabilitation (SER) protocol within 24 to 72 hour after ICH onset at the stroke center. The EM and SER groups each had 30 patients. 24-measurement SBP were recorded on days 2 and 3 after onset, and SBP were recorded three times daily and during rehabilitation on days 4 through 7. The two groups' mean SBP and BPV under three different time frames (days 2 and 3 during the acute phase, and days 4 through 7 during the late acute phase) were calculated and compared. RESULTS At baseline, the two groups' results were similar, with the exception being that the mean time to first out-of-bed mobilization after symptom onset was 51.60 hours (SD 14.15) and 135.02 hours (SD 33.05) for the EM group and SER group, respectively (P < .001). There were no significant differences in mean SBP and BPV during the acute and late acute phase between the two groups for the three analyses (days 2, 3, and 4 through 7) (P > .05). CONCLUSIONS It is safe to implement the EM protocol within 24 to 72 hour of onset for mild-moderate ICH patients during the acute phase.

Abstract

OBJECTIVE To explore the clinical efficacy of comprehensive rehabilitation nursing (CRN) intervention in patients with cerebral hemorrhagic hemiplegia (CHH). METHODS A total of 102 patients with CHH admitted to our hospital were selected for the prospective study. The patients were randomly divided into the control group (n=51) and the observation group (n=51) according to the random number table method. Routine nursing was performed in the control group, while CRN was conducted in the observation group. Fugl-Meyer motor function assessment scale, activity of daily living scale (Barthel index), self-rating anxiety scale (SAS), complications and muscle strength improvement (Brunnstrom assessment) were compared between the two groups. RESULTS Compared with those before nursing, Fugl-Meyer score, Barthel index and SAS score in the two groups after nursing were significantly improved (P<0.01). Fugl-Meyer score and Barthel index of the observation group were significantly higher than those of the control group after nursing, while SAS score showed the opposite change (P<0.001). The incidence of complications in the control group was 49.02%, and that in the observation group was 29.41% (P<0.05). The rate of muscle strength improvement in the observation group was 80.39% after nursing, which was significantly higher than that in the control group (60.78%; P<0.05). CONCLUSION CRN intervention has a positive clinical efficacy in patients with CHH. It can enhance motor ability, improve the ability of daily life, amend psychological mood and reduce the incidence of complications.