{"title":"Response to Comment on \"Dynamic Impact of Leptomeningeal Collateral Status for Hemorrhagic Transformation in Patients with Acute Ischemic Stroke with Endovascular Treatment\".","authors":"Xin Jiang, Jian Guo","doi":"10.1007/s12028-025-02370-6","DOIUrl":"https://doi.org/10.1007/s12028-025-02370-6","url":null,"abstract":"","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stefan Yu Bögli, Ihsane Olakorede, Claudia Ann Smith, Peter Hutchinson, Marek Czosnyka, Peter Smielewski, Shruti Agrawal
{"title":"Exploring the Upper Limits of Cerebral Perfusion Pressure in Pediatric Traumatic Brain Injury: A STARSHIP Analysis.","authors":"Stefan Yu Bögli, Ihsane Olakorede, Claudia Ann Smith, Peter Hutchinson, Marek Czosnyka, Peter Smielewski, Shruti Agrawal","doi":"10.1007/s12028-025-02358-2","DOIUrl":"https://doi.org/10.1007/s12028-025-02358-2","url":null,"abstract":"<p><strong>Background: </strong>Low cerebral perfusion pressure (CPP) has previously been identified as a key prognostic marker after pediatric traumatic brain injury (TBI). Cerebrovascular autoregulation supports stabilization of cerebral blood flow within the autoregulation range. Beyond the upper limit of this range, cerebral blood flow increases with increasing CPP, leading to increased risk of intracranial hypertension and blood-brain barrier disruptions. Based on the hypothesis that children are less sensitive to high CPP, we aimed to characterize the pediatric upper limit of autoregulation and the association between high CPP and outcome.</p><p><strong>Methods: </strong>Data acquired as part of the \"Studying Trends of Autoregulation in Severe Head Injury in Paediatrics\" (STARSHIP) study (a prospective, multicenter, observational study that enrolled 135 children with TBI from July 2018 to March 2023) were explored. The association between different levels of CPP and the autoregulation proxy measure, the pressure reactivity index (PRx), were explored visually. The prognostic value of CPP was assessed by exploring overall averages, overall dose, hourly dose, and percentage time spent above specific thresholds. We employed univariable/multivariable (χ<sup>2</sup> tests, logistic regression, sliding dichotomy) and visual (heatmap) methods.</p><p><strong>Results: </strong>No clear upper limit of autoregulation could be identified with PRx increasing beyond 0.2 only with CPP values beyond 100 mm Hg. Using iterative χ<sup>2</sup> testing and logistic regression analyses, similarly, only hourly dose and percentage time beyond CPP of 90 mm Hg displayed a trend toward worse outcome. Using heatmap analyses, regions of CPP with differing risk stratifications could be identified. No difference in CPP could be identified between patients with and without acute respiratory distress syndrome or secondary hemorrhages.</p><p><strong>Conclusions: </strong>In contrast to the well-established association between low CPP and poor outcome, our findings suggest that exposure to CPP values above those recommended by the Brain Trauma Foundation guidelines may not be associated with worse outcomes in this cohort. However, given the observational nature of the study and potential confounding factors, these results highlight the need for prospective trials to assess the safety and efficacy of targeting higher CPP in pediatric TBI.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comment on \"Dynamic Impact of Leptomeningeal Collateral Status for Hemorrhagic Transformation in Patients with Acute Ischemic Stroke with Endovascular Treatment\".","authors":"Songsong Luo, Xiaoyuan Shen","doi":"10.1007/s12028-025-02369-z","DOIUrl":"https://doi.org/10.1007/s12028-025-02369-z","url":null,"abstract":"","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comment on \"Effect of Ketamine Analgosedation on Neurological Outcome in Patients with Severe Traumatic Brain Injury: A Randomized Controlled Pilot Study\".","authors":"Haneen Asma, Muhammad Shayan Khan","doi":"10.1007/s12028-025-02367-1","DOIUrl":"https://doi.org/10.1007/s12028-025-02367-1","url":null,"abstract":"","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transcranial Ultrasonography: A New World of Images Using the Linear Probe.","authors":"Vasiliki Tsolaki, Theofilos Amanatidis, Kyriaki Parisi, Demosthenes Makris, Epaminondas Zakynthinos","doi":"10.1007/s12028-025-02365-3","DOIUrl":"https://doi.org/10.1007/s12028-025-02365-3","url":null,"abstract":"","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Vagus Nerve Stimulation Attenuates Cognitive Impairment in Traumatic Brain Injury via the mtDNA/cGAS-STING/NLRP3 Inflammasome Axis.","authors":"Bingkai Ren, Junwei Kang, Xiaoyang Dong, Lianghua Huang, Xiao Wu, Yunliang Tang","doi":"10.1007/s12028-025-02351-9","DOIUrl":"https://doi.org/10.1007/s12028-025-02351-9","url":null,"abstract":"<p><strong>Background: </strong>Traumatic brain injury (TBI) is a major life-threatening event. In addition to neurological deficits, it can lead to long-term impairments of cognitive function. The vagus nerve (VN) provides a direct communication conduit between the central nervous system and the periphery, and modulation of the inflammatory reflex via electrical stimulation of the vagus nerve (VNS) shows efficacy in ameliorating pathology in neurodegenerative diseases. Our objective was to investigate the impact and underlying mechanism of VNS for cognitive impairment in a rat model of TBI.</p><p><strong>Methods: </strong>Male rats were implanted with VNS electrodes on the left VN 1 week prior to controlled cortical impact. Mitochondrial permeability transition pore blocker cyclosporin A (CsA) and stimulator of interferon genes (STING) agonist 2'3'-cGAMP were delivered by intranasal administration or intraventricular injection. Post-VNS assessments included Morris water maze, Nissl staining, hematoxylin and eosin staining, Western blotting, quantitative polymerase chain reaction, mitochondrial membrane potential, and enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>We found that VNS treatment significantly improved cognitive impairment, increased mitochondrial membrane potential, reduced accumulation of cytosolic mitochondrial DNA, attenuated cyclic GMP-AMP synthase (cGAS)-STING pathway, suppressed nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome activation, and partially reversed hippocampus neuronal damage and loss caused by TBI. However, 2'3'-cGAMP delivery significantly abrogated these effects of VNS. In addition, CsA also showed neuroprotective effects, including improved cognitive impairment, decreased levels of cGAS, phosphorylated STING, and suppressed the expressions of NLRP3 inflammasome and pyroptosis-pertinent components containing cleaved Caspase-1, ASC, and N-terminal Gasdermin D. CsA also inhibited interleukin-1β and interleukin-18 proinflammatory cytokine concentration.</p><p><strong>Conclusions: </strong>Stimulation of the VN attenuates the pyroptosis and neuroinflammatory cascades in the rat of the TBI model by regulating the mitochondrial DNA/cGAS/STING /NLRP3 pathway.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Involvement of Periostin in Acute Neuronal Apoptosis Induced by Subarachnoid Hemorrhage in Mice and its Suppression by Clarithromycin.","authors":"Hiroki Oinaka, Hideki Kanamaru, Fumihiro Kawakita, Yume Suzuki, Hideki Nakajima, Mai Nampei, Hidenori Suzuki","doi":"10.1007/s12028-025-02348-4","DOIUrl":"https://doi.org/10.1007/s12028-025-02348-4","url":null,"abstract":"<p><strong>Background: </strong>Periostin is an inflammation-related matricellular protein that has been reported to increase in the acute phase after subarachnoid hemorrhage (SAH) in clinical settings. However, its relationship with neuronal apoptosis, a characteristic of early brain injury, remains unknown. The purpose of this study was to investigate the involvement of periostin in SAH-induced acute neuronal apoptosis and to determine whether clarithromycin (CAM), a macrolide antibiotic known to suppress periostin expression, prevents acute neuronal apoptosis after SAH in mice.</p><p><strong>Methods: </strong>In 141 male C57BL/6 mice undergoing endovascular perforation SAH or sham operation, vehicle or CAM (50 mg/kg) was administered subcutaneously 5 min after surgery, followed by intracerebroventricular administration of vehicle or recombinant mouse periostin (R-periostin) 30 min after surgery. The intervention effects were assessed 24 h after surgery by neurological score, Western blotting, and double immunostaining.</p><p><strong>Results: </strong>After induction of SAH, neurological scores worsened, and caspase-3-dependent neuronal apoptosis was increased, which was associated with upregulation of periostin expression in the left (perforation side) cerebral hemisphere compared with sham-operated animals (p < 0.01 vs. sham + vehicle group, respectively). Administration of CAM improved neurological scores and reduced caspase-3-dependent neuronal apoptosis as well as periostin expression in SAH mice (p < 0.05, p < 0.01, p < 0.01 vs. SAH + vehicle group, respectively). The protective effects of CAM on neurological scores and neuronal apoptosis after SAH were counteracted by administration of R-periostin (SAH + CAM + vehicle group vs. SAH + CAM + R-periostin group, p < 0.05 and p < 0.001, respectively). Immunohistochemical analysis confirmed overexpression of periostin in neurons after SAH, which was attenuated by CAM treatment but re-increased by administration of R-periostin.</p><p><strong>Conclusions: </strong>These findings indicate that periostin-driven signaling contributes to caspase-dependent neuronal apoptosis during early brain injury after SAH. This study highlights periostin as a potential therapeutic target to attenuate SAH-induced acute neuronal apoptosis and demonstrates that CAM holds promise as an antiapoptotic agent through periostin inhibition.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maged Kharouba, Aaron M Cook, Melissa L Thompson Bastin, Demetrios J Kutsogiannis, Sherif Hanafy Mahmoud
{"title":"Levetiracetam Dosing Optimization in Neurocritical Care Population: Neuro-ARC Study.","authors":"Maged Kharouba, Aaron M Cook, Melissa L Thompson Bastin, Demetrios J Kutsogiannis, Sherif Hanafy Mahmoud","doi":"10.1007/s12028-025-02347-5","DOIUrl":"https://doi.org/10.1007/s12028-025-02347-5","url":null,"abstract":"<p><strong>Background: </strong>Levetiracetam, a first-line antiseizure medication, is primarily eliminated through the kidneys, with approximately 66% renal elimination. Consequently, its pharmacokinetics are significantly influenced by kidney function. Augmented renal clearance (ARC), a condition characterized by renal hyperfiltration, is frequently observed in critical care settings and can profoundly impact the disposition of renally eliminated drugs such as levetiracetam. Our objectives were to characterize levetiracetam pharmacokinetics in neurocritical care patients, identify covariates significantly influencing drug clearance, and provide clinicians with optimal dosage recommendations in those with and without ARC.</p><p><strong>Methods: </strong>This was a multicenter, prospective, observational study involving patients admitted to the participating centers with life-threatening neurological illnesses. Each participant had up to four plasma samples collected, and the samples were analyzed using a validated high-performance liquid chromatography method. The creatinine clearance (CL<sub>CR</sub>) of enrolled participants was measured using the 8-h urine collection method (measured CL<sub>CR</sub> [mCL<sub>CR</sub>]). Population pharmacokinetic modeling was performed using Monolix software. Monte Carlo simulations were performed to explore various dosage strategies and to suggest optimal levetiracetam regimens.</p><p><strong>Results: </strong>Our study included 50 patients, with 35 patients (70%) experiencing ARC. Trough levetiracetam levels were significantly lower in the ARC group compared with the no-ARC group (median [interquartile range] 4.4 [11.5] vs. 11.8 [19] mg/L, p value = 0.039, respectively). Population pharmacokinetic modeling showed levetiracetam clearance at 4.6 ± 2.97 L/h and volume of distribution at 0.56 ± 0.63 L/kg, following a one-compartment model. The mCL<sub>CR</sub> significantly affected levetiracetam clearance. Simulations indicated that an initial 500 mg twice daily (BID) dosage is insufficient. Patients with mCL<sub>CR</sub> ≥ 90 mL/min/1.73 m<sup>2</sup>, including patients with ARC, may need at least 1500 mg BID, whereas those with mCL<sub>CR</sub> 60-89 mL/min/1.73 m<sup>2</sup> may require an initial dosage of 1250 mg BID.</p><p><strong>Conclusions: </strong>Augmented renal clearance significantly impacts the pharmacokinetics of levetiracetam by enhancing clearance. Dosing simulations revealed the inadequacy of the initial 500 mg BID regimen, indicating a minimum dosage of 1500 mg BID is necessary for patients experiencing ARC to achieve reference range concentrations.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ravi Garg, Gabriel Torrealba-Acosta, Pitchaiah Mandava
{"title":"Assessing the Clinical Relevance of Blood Pressure Measures in Spontaneous Intracerebral Hemorrhage: A Post Hoc Analysis of ATACH-2.","authors":"Ravi Garg, Gabriel Torrealba-Acosta, Pitchaiah Mandava","doi":"10.1007/s12028-025-02350-w","DOIUrl":"https://doi.org/10.1007/s12028-025-02350-w","url":null,"abstract":"<p><strong>Background: </strong>Recent American Heart Association guidelines have relied on post hoc subgroup analyses to identify summary blood pressure measures for targets in early management of acute intracerebral hemorrhage. To our knowledge, measurement error has not been considered when determining the impact of these summary measures. Our objective was to determine whether statistically significant differences in three systolic blood pressure (SBP) measures (achieved SBP, SBP variability, and magnitude of SBP reduction) in patients with intracerebral hemorrhage from the antihypertensive treatment of acute cerebral hemorrhage II (ATACH-2) randomized clinical trial are clinically meaningful by comparing them to a minimally detectable difference (MDD) of 10 mm Hg.</p><p><strong>Methods: </strong>We performed a post hoc analysis of individual patient data from the ATACH-2 randomized clinical trial, evaluating the differences in achieved SBP, SBP variability, and magnitude of SBP reduction between patients with favorable (modified Rankin scale score 0-3) and unfavorable (modified Rankin scale score 4-6) outcomes. We used the empirical cumulative distribution functions and Kolmogorov-Smirnov tests to compare distributions, and we considered differences clinically meaningful if they exceeded the MDD of 10 mm Hg. We also performed a propensity score matched analysis to understand the nature of the association between these measures and outcomes.</p><p><strong>Results: </strong>Although SBP variability in the first 24 h differed statistically between outcome groups, the mean difference (95% confidence interval) did not exceed the MDD threshold. Achieved SBP and magnitude of SBP reduction showed no significant differences between groups. In the propensity score matched analysis, there were no statistical differences between any blood pressure measurements and outcomes.</p><p><strong>Conclusions: </strong>Our findings suggest that although there are statistically significant differences in SBP variability between patients with good and poor outcomes in ATACH-2, these differences do not meet the threshold for clinical relevance because they were within the range of measurement noise. The propensity score matched analysis suggested that the association between summary blood pressure measurements and outcomes is not robust to analytical method. These findings emphasize the need for caution in interpreting post hoc findings for clinical decision-making.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aman Elwadhi, Prateek Kumar Panda, Amit Kumar Tyagi, Osama Neyaz, Amanjot Kaur, Lokesh Kumar Tiwari, Indar Kumar Sharawat
{"title":"Early Protocolized Rehabilitation Versus Usual Care in Improving Functional Outcomes in Pediatric Neurocritical Patients: A Randomized Controlled Trial.","authors":"Aman Elwadhi, Prateek Kumar Panda, Amit Kumar Tyagi, Osama Neyaz, Amanjot Kaur, Lokesh Kumar Tiwari, Indar Kumar Sharawat","doi":"10.1007/s12028-025-02357-3","DOIUrl":"https://doi.org/10.1007/s12028-025-02357-3","url":null,"abstract":"<p><strong>Background: </strong>An early protocolized rehabilitation (EPR) program has the potential to improve functional outcomes in pediatric neurocritical care patients in the pediatric intensive care unit over standard care alone. However, this requires validation through a randomized controlled trial (RCT).</p><p><strong>Methods: </strong>This single-blind, parallel-design, two-arm RCT evaluated the efficacy of EPR in improving functional outcomes at 24 weeks in pediatric neurocritical patients aged 1-18 years compared to usual care. The study also aimed to compare adaptive function, gross motor function, language skills, cognition, behavioral issues, sleep patterns, quality of life, and family functional outcomes between the two groups. EPR was initiated within 72 h of mechanical ventilation and was customized for each patient by a team of specialists in pediatric neurology, physical medicine and rehabilitation, and speech and language pathology. Rehabilitation sessions were conducted daily for one week, then three times a week for one month, and monthly after discharge, supplemented with weekly teleconsultations.</p><p><strong>Results: </strong>A total of 196 patients were enrolled (98 in each arm). At 24 weeks, the Pediatric Cerebral Performance Category score was significantly better in the intervention arm (mean difference 0.133 [95% confidence interval 0.055-0.205], p < 0.001). Additionally, improvements were noted in the EPR arm across Child Behavior Checklist, Vineland Adaptive Behavior Scale, Children's Sleep Habits Questionnaire, Pediatric Quality of Life Inventory, and Family Assessment Device scores (p < 0.001 for all).</p><p><strong>Conclusions: </strong>EPR in pediatric neurocritical patients significantly improves functional outcomes and quality of life at 24 weeks compared to usual care.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}