BACKGROUND: This study aims to investigate the efficacy and safety of glibenclamide treatment in patients with acute aneurysmal subarachnoid hemorrhage (aSAH).
METHODS: The randomized controlled trial was conducted from October 2021 to May 2023 at two university-affiliated hospitals in Beijing, China. The study included patients with aSAH within 48 h of onset, of whom were divided into the intervention group and the control group according to the random number table method. Patients in the intervention group received glibenclamide tablet 3.75 mg/day for 7 days. The primary end points were the levels of serum neuron-specific enolase (NSE) and soluble protein 100B (S100B) between the two groups. Secondary end points included evaluating changes in the midline shift and the gray matter-white matter ratio, as well as assessing the modified Rankin Scale scores during follow-up. The trial was registered at ClinicalTrials.gov (identifier NCT05137678).
RESULTS: A total of 111 study participants completed the study. The median age was 55 years, and 52% were women. The mean admission Glasgow Coma Scale was 10, and 58% of the Hunt-Hess grades were no less than grade III. The baseline characteristics of the two groups were similar. On days 3 and 7, there were no statistically significant differences observed in serum NSE and S100B levels between the two groups (P > 0.05). The computer tomography (CT) values of gray matter and white matter in the basal ganglia were low on admission, indicating early brain edema. However, there were no significant differences found in midline shift and gray matter-white matter ratio (P > 0.05) between the two groups. More than half of the patients had a beneficial outcome (modified Rankin Scale scores 0-2), and there were no statistically significant differences between the two groups. The incidence of hypoglycemia in the two groups were 4% and 9%, respectively (P = 0.439).
CONCLUSIONS: Treating patients with early aSAH with oral glibenclamide did not decrease levels of serum NSE and S100B and did not improve the poor 90-day neurological outcome. In the intervention group, there was a visible decreasing trend in cases of delayed cerebral ischemia, but no statistically significant difference was observed. The incidence of hypoglycemia did not differ significantly between the two groups.

UNASSIGNED: Brain edema is a life-threatening complication that occurs after glioma surgery. There are no noninvasive and specific treatment methods for brain edema. Hydrogen is an anti-inflammatory and antioxidant gas that has demonstrated therapeutic and preventative effects on several diseases, particularly in the nervous system. This study aimed to determine the therapeutic effects of hydrogen administration on brain edema following glioma surgery and elucidate its mechanism.
UNASSIGNED: A single-center, randomized controlled clinical trial of hydrogen inhalation was conducted (China Clinical Trial Registry [ChiCTR-2300074362]). Participants in hydrogen (H) group that inhaled hydrogen experienced quicker alleviation of postoperative brain edema compared with participants in control (C) group that inhaled oxygen.
UNASSIGNED: The volume of brain edema before discharge was significantly lower in the H group (p < 0.05). Additionally, the regression rate of brain edema was higher in the H group than in the C group, which was statistically significant (p < 0.05). Furthermore, 3 days after surgery, the H group had longer total sleep duration, improved sleep efficiency, shorter sleep latency, and lower numerical rating scale (NRS) scores (p < 0.05).
UNASSIGNED: In conclusion, hydrogen/oxygen inhalation effectively reduced postoperative brain edema in glioma patients. Further research is necessary to understand the underlying mechanisms of hydrogen\'s therapeutic effects. Hydrogen is expected to become a new target for future adjuvant therapy for brain edema.

Although diabetes mellitus negatively affects post-ischaemic stroke injury and recovery, its impact on intracerebral haemorrhage (ICH) remains uncertain. This study aimed to investigate the effect of experimental diabetes (ED) on ICH-induced injury and neurological impairment. Sprague-Dawley rats were induced with ED 2 weeks before ICH induction. Animals were randomly assigned to four groups: 1)Healthy; 2)ICH; 3)ED; 4)ED-ICH. ICH and ED-ICH groups showed similar functional assessment. The ED-ICH group exhibited significantly lower haemorrhage volume compared with the ICH group, except at 1 mo. The oedema/ICH volume ratio and cistern displacement ratio were significantly higher in the ED-ICH group. Vascular markers revealed greater expression of α-SMA in the ED groups (ED and ED-ICH) compared with ICH. Conversely, the ICH groups (ED-ICH and ICH) exhibited higher levels of VEGF compared to the healthy and ED groups. An assessment of myelin tract integrity showed an increase in fractional anisotropy in the ED and ED-ICH groups compared with ICH. The ED group showed higher cryomyelin expression than the ED-ICH and ICH groups. Additionally, the ED groups (ED and ED-ICH) displayed higher expression of MOG and Olig-2 than ICH. As for inflammation, MCP-1 levels were significantly lower in the ED-ICH groups compared with the ICH group. Notably, ED did not aggravate the neurological outcome; however, it results in greater ICH-related brain oedema, greater brain structure displacement and lower haemorrhage volume. ED influences the cerebral vascularisation with an increase in vascular thickness, limits the inflammatory response and attenuates the deleterious effect of ICH on white matter integrity.

BACKGROUND: Early assessment and management of cerebral edema and hematoma following aneurysmal subarachnoid hemorrhage (a-SAH) can significantly impact clinical cognitive outcomes. However, current clinical practices lack predictive models to identify early structural brain abnormalities affecting cognition. To address this gap, the authors propose the development of a predictive model termed the a-SAH Early Brain Edema/Hematoma Compression Neural (Structural Brain) Networks Score System (SEBE-HCNNSS).
METHODS: In this study, 202 consecutive patients with spontaneous a-SAH underwent initial computed tomography (CT) or MRI scans within 24 h of ictus with follow-up 2 months after discharge. Using logistic regression analysis (univariate and multivariate), the authors evaluated the association of clinically relevant factors and various traditional scale ratings with cognitive impairment (CI). Risk factors with the highest area under the curve (AUC) values were included in the multivariate analysis and least absolute shrinkage and selection operator (LASSO) analysis or Cox regression analysis.
RESULTS: A total of 177 patients were enrolled in the study, and 43 patients were classified with a high SEBE-HCNNSS grade (3-5). After a mean follow-up of 2 months, 121 individuals (68.36%) with a-SAH and three control subjects developed incident CI. The CT interobserver reliability of the SEBE-HCNNSS scale was high, with a Kappa value of 1. Furthermore, ROC analysis identified the SEBE-HCNNSS scale (OR 3.322, 95% CI: 2.312-7.237, P =0.00025) as an independent predictor of edema, CI, and unfavorable prognosis. These results were also replicated in a validation cohort.
CONCLUSIONS: Overall, the SEBE-HCNNSS scale represents a simple assessment tool with promising predictive value for CI and clinical outcomes post-a-SAH. Our findings indicate its practical utility as a prognostic instrument for risk evaluation after a-SAH, potentially facilitating early intervention and treatment.

UNASSIGNED: Mortality in pediatric cerebral malaria (CM) in low- and middle-income countries (LMICs) is associated with brain swelling on magnetic resonance imaging (MRI); however, MRI is unavailable in most LMICs. Optic nerve sheath diameter (ONSD) measurement is an inexpensive method of detecting increased intracranial pressure compared with the invasive opening pressure (OP). Our primary objective was to determine if increased ONSD correlated with brain swelling on MRI in pediatric CM. Our secondary objective was to determine if increased ONSD correlated with increased OP and/or poor neurological outcome in pediatric CM. We hypothesized that increased ONSD would correlate with brain swelling on MRI and increased OP and that ONSD would be higher in survivors with sequelae and non-survivors.
UNASSIGNED: We performed a retrospective chart review of children aged 0-12 years in Blantyre, Malawi, from 2013 to 2022 with CM as defined by the World Health Organization. Brain swelling on admission MRI was characterized by brain volume scores (BVS); severe swelling was scored as 7-8, mild-to-moderate as 4-6, normal as 3. The admission ONSD was measured via ultrasound; it was defined as abnormal if it was >4.5 mm in children >1 year and >4 mm in children <1 year. Favorable outcome was defined as a normal neurological exam on discharge in survivors. The primary and secondary objectives were evaluated using Spearman\'s correlation; and the demographics were compared using chi-square and the Kruskal-Wallis test (Stata, College Station, TX, USA).
UNASSIGNED: Median age of the 207-patients cohort was 50 months [interquartile range (IQR) 35-75]; 49% (n = 102) were female. Of those, 73% (n = 152) had a favorable outcome, and 14% (n = 30) died. Twenty-nine (14%) had a normal BVS, 134 (65%) had mild-to-moderate swelling, and 44 (21%) had severe swelling. ONSD was elevated in 86% (n = 178) of patients, while 12% of patients had increased OP. There was a weakly positive correlation between BVS and ONSD (r = 0.14, p = 0.05). The median ONSD was not significantly different compared by discharge outcome (p = 0.11) or by BVS (p = 0.18).
UNASSIGNED: ONSD was not a reliable tool to correlate with BVS, neurological outcome, or OP in children with CM. Future studies to identify alternative methods of early identification of CM patients at highest risk for morbidity and mortality are urgently needed.

OBJECTIVE: Percutaneous 3-mm twist-drill trephination (TDT) under local anesthesia as a bedside operative technique is an alternative to the conventional open surgical trephination in the operating theatre. The aim of this study was to verify the efficacy and safety of this minimal invasive procedure.
METHODS: This retrospective study comprises 1000 patients who were treated with TDT under local anesthesia at bedside due to chronic subdural hematoma (cSDH), intracerebral hemorrhage (ICH), and hydrocephalus (HYD) as a result of subarachnoid hemorrhage or non-hemorrhagic causes, increased intracranial pressure (IIP) in traumatic brain injury or non-traumatic brain edema, and other pathologies (OP) requiring drainage. Medical records, clinical outcome, and results of pre- and postoperative computed tomography (CT) and/or magnetic resonance tomography (MRT) were analyzed.
RESULTS: Indications for TDT were cSDH (n = 275; 27.5%), ICH (n = 291; 29.1%), HYD (n = 316; 31.6%), IIP (n = 112; 11.2%), and OP (n = 6; 0.6%). Overall, primary catheter placement was sufficient in 93.8% of trephinations. Complication rate was 14.1% and mainly related to primary catheter malposition (6.2%), infections (5.2%), and secondary hemorrhage (2.7%); the majority of which were clinically inapparent puncture channel bleedings not requiring surgical intervention. The revision rate was 13%.
CONCLUSIONS: Bedside TDT under local anesthesia has proven to be an effective and safe alternative to the conventional burr-hole operative technique as usually performed under general anesthesia in the operation theatre, and may be particularly useful in emergency cases as well as in elderly and multimorbid patients.

BACKGROUND: This pilot study in post-stroke patients evaluated the effects of supplementation with Pycnogenol® on alterations in cognitive functions (COFU) over a period of 6 months, starting 4 weeks after the stroke.
METHODS: The effects of supplementation - possibly acting on residual brain edema, on global cognitive function, attention and on mental performance - were studied. A control group used standard management (SM) and the other group added Pycnogenol®, 150 mg daily to SM.
RESULTS: 38 post-stroke patients completed the 6-month-study, 20 in the Pycnogenol® group and 18 in the control group. No side effects were observed with the supplement. The tolerability was very good. The patients included into the two groups were comparable for age, sex and clinical distribution. There were 2 dropouts in the control group, due to non-medical problems. Main COFU parameters (assessed by a cognitive questionnaire) were significantly improved (all single items) with the supplement compared to controls (P<0.05). Additional observations indicate that Pycnogenol® patients experienced significantly less mini-accidents (including falls) than controls (P<0.05). The incidences of (minor) psychotic episodes or conflicts and distress and other problems including rare occurrence of minor hallucinations, were lower with the supplementation than in controls (P<0.05). Single observations concerning daily tasks indicated a better effect of Pycnogenol® compared to controls (P<0.05). Plasma free radicals also decreased significantly with the supplement in comparison to controls (P<0.05). Globally, supplemented subjects had a better recovery than controls.
CONCLUSIONS: In post-stroke subjects, Pycnogenol® supplementation resulted in better recovery outcome and faster COFU \'normalization\' after the stroke in comparison with SM; it can be considered a safe, manageable post-stroke, adjuvant management possibly reducing local brain edema. Nevertheless, more patients and a longer period of evaluation are needed to confirm these results.

BACKGROUND: We retrospectively analyzed the effects of low-dose bevacizumab (BEV) combined with temozolomide (TMZ) on health-related quality of life (HRQL) in patients with recurrent high-grade glioma (rHGG).
METHODS: A total of 129 patients with rHGG were included in this study. Patients were divided into a combination group and TMZ group based on the treatment they received. The Quality of Life Questionnaire Core 30 (QLQ-C30) and EORTC Brain Cancer Module (QLQ-BN20) were used to evaluate HRQL in all patients before and after treatment. Categorical variables were compared using the chi-squared test. The data for all continuous variables were first tested for a normal distribution. If the data conformed to a normal distribution, a T test was used for comparison. If the data did not conform to a normal distribution, the rank-sum test was used.
RESULTS: There were differences in PFS and PFS-6 between the BEV + TMZ and TMZ groups (P＜0.05). However, there was no difference in the OS between the two groups (P＞0.05). The BEV + TMZ group performed better than the TMZ group in both the QLQ-C30 and QLQ-BN20. In addition, the KPS score was higher in the BEV + TMZ group than in the TMZ group. Steroid doses given were lower in the BEV + TMZ group than in the TMZ group (P < 0.05).
CONCLUSIONS: Low-dose BEV + TMZ can relieve the clinical symptoms of rHGG patients, reduce their steroid dose, improve HRQL, and prolong PFS, but does not bear any benefit on OS.

UNASSIGNED: Glibenclamide alleviates brain edema and improves neurological outcomes in experimental models of stroke. We aimed to assess whether glibenclamide improves functional outcomes in patients with acute ischemic stroke treated with recombinant tissue plasminogen activator (rtPA).
UNASSIGNED: In this randomized, double-blind, placebo-controlled trial, patients with acute ischemic stroke were recruited to eight academic hospitals in China. Patients were eligible if they were aged 18-74 years, presented with a symptomatic anterior circulation occlusion with a deficit on the NIHSS of 4-25, and had been treated with rtPA within 4.5 h of symptom onset. We used web-based randomization (1:1) to allocate eligible participants to the glibenclamide or placebo group, stratified according to endovascular treatment and baseline stroke severity. Glibenclamide or placebo was taken orally or via tube feeding at a loading dose of 1.25 mg within 10 h after symptom onset, followed by 0.625 mg every 8 h for 5 days. The primary outcome was the proportion of patients with good outcomes (modified Rankin Scale of 0-2) at 90 days, assessed in all randomly assigned patients who had been correctly diagnosed and had begun study medication. The study is registered with ClinicalTrials.gov, NCT03284463, and is closed to new participants.
UNASSIGNED: Between January 1, 2018, and May 28, 2022, 305 patients were randomly assigned, of whom 272 (142 received glibenclamide and 130 received placebo) were included in the primary efficacy analysis. 103 (73%) patients in the glibenclamide group and 94 (72%) in the placebo group had a good outcome (adjusted risk difference 0.002, 95% CI -0.098 to 0.103; p = 0.96). 12 (8%) patients allocated to glibenclamide and seven (5%) patients allocated to placebo died from any cause at 90 days (p = 0.35). The number and type of adverse events were similar between the two groups. There were no drug-related adverse events and no drug-related deaths.
UNASSIGNED: The addition of glibenclamide to thrombolytic therapy did not increase the proportion of patients who achieved good outcomes after stroke compared with placebo, but it did not lead to any safety concerns.
UNASSIGNED: Southern Medical University and Nanfang Hospital.

Patients with acute spontaneous intracerebral hemorrhage (ICH) develop secondary neuroinflammation and cerebral edema that can further damage the brain and lead to increased risk of neurologic complications. Preclinical studies in animal models of acute brain injury have shown that a novel small-molecule drug candidate, MW01-6-189WH (MW189), decreases neuroinflammation and cerebral edema and improves functional outcomes. MW189 was also safe and well tolerated in phase 1 studies in healthy adults. The proof-of-concept phase 2a Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) clinical trial is a first-in-patient, multicenter, randomized, double-blind, placebo-controlled trial. It is designed to determine the safety and tolerability of MW189 in patients with acute ICH, identify trends in potential mitigation of neuroinflammation and cerebral edema, and assess effects on functional outcomes. A total of 120 participants with nontraumatic ICH will be randomly assigned 1:1 to receive intravenous MW189 (0.25 mg/kg) or placebo (saline) within 24 h of symptom onset and every 12 h for up to 5 days or until hospital discharge. The 120-participant sample size (60 per group) will allow testing of the null hypothesis of noninferiority with a tolerance limit of 12% and assuming a \"worst-case\" safety assumption of 10% rate of death in each arm with 10% significance and 80% power. The primary outcome is all-cause mortality at 7 days post randomization between treatment arms. Secondary end points include all-cause mortality at 30 days, perihematomal edema volume after symptom onset, adverse events, vital signs, pharmacokinetics of MW189, and inflammatory cytokine concentrations in plasma (and cerebrospinal fluid if available). Other exploratory end points are functional outcomes collected on days 30, 90, and 180. BEACH will provide important information about the utility of targeting neuroinflammation in ICH and will inform the design of future larger trials of acute central nervous system injury.