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Background: Intraventricular hemorrhage (IVH) refers to bleeding within the brain's ventricular system, and hydrocephalus is a life-threatening complication of IVH characterized by increased cerebrospinal fluid accumulation in the ventricles resulting in elevated intracranial pressure. IVH poses significant challenges for healthcare providers due to the complexity of the underlying pathophysiology and lack of standardized treatment guidelines. Herein, we performed a systematic review of the treatment strategies for hydrocephalus secondary to IVH. Methods: This systematic review was prospectively registered with PROSPERO (CRD42023450786). The search was conducted in PubMed, Cochrane Library, and Web of Science on July 15, 2023. We included original studies containing valid information on therapy management and outcome of hydrocephalus secondary to primary, spontaneous, and subarachnoid or intracranial hemorrhage following IVH in adults that were published between 2000 and 2023. Glasgow Outcome Scale (GOS) or modified Ranking Scale (mRS) scores during follow-up were extracted as primary outcomes. The risk of bias was assessed using the Newcastle–Ottawa Scale for Cohort Studies or Cochrane Risk of Bias 2.0 Tool. Results: Two hundred and seven patients from nine published papers, including two randomized controlled trials, were included in the analysis. The GOS was used in five studies, while the mRS was used in four. Seven interventions were applied, including craniotomy for removal of hematoma, endoscopic removal of hematoma with/without endoscopic third ventriculostomy (ETV), traditional external ventricular drainage (EVD), and various combinations of EVD, lumbar drainage (LD), and intraventricular fibrinolysis (IVF). Endoscopic removal of hematoma was performed in five of nine studies. Traditional EVD had no obvious benefit compared with new management strategies. Three different combinations of EVD, LD, and IVF demonstrated satisfactory outcomes, although more studies are required to confirm their reliability. Removal of hematoma through craniotomy generated reliable result. Generally, endoscopic removal of hematoma with ETV, removal of hematoma through craniotomy, EVD with IVF, and EVD with early continuous LD were useful. Conclusion: EVD is still crucial for the management of IVH and hydrocephalus. Despite a more reliable result from the removal of hematoma through craniotomy, a trend toward endoscopic approach was observed due to a less invasive profile. [ABSTRACT FROM AUTHOR]

Background: The management of patients with disorders of consciousness (DOC) presents substantial challenges in clinical practice. Deep brain stimulation (DBS) has emerged as a potential therapeutic approach, but the lack of standardized regulatory parameters for DBS in DOC hinders definitive conclusions. Objective: This comprehensive review aims to provide a detailed summary of the current issues concerning patient selection, target setting, and modulation parameters in clinical studies investigating the application of DBS for DOC patients. Methods: A meticulous systematic analysis of the literatures was conducted, encompassing articles published from 1968 to April 2023, retrieved from reputable databases (PubMed, Embase, Medline, and Web of Science). Results: The systematic analysis of 21 eligible articles, involving 146 patients with DOC resulting from acquired brain injury or other disorders, revealed significant insights. The most frequently targeted regions were the Centromedian‐parafascicular complex (CM‐pf) nuclei and central thalamus (CT), both recognized for their role in regulating consciousness. However, other targets have also been explored in different studies. The stimulation frequency was predominantly set at 25 or 100 Hz, with pulse width of 120 μs, and voltages ranged from 0 to 4 V. These parameters were customized based on individual patient responses and evaluations. The overall clinical efficacy rate in all included studies was 39.7%, indicating a positive effect of DBS in a subset of DOC patients. Nonetheless, the assessment methods, follow‐up durations, and outcome measures varied across studies, potentially contributing to the variability in reported efficacy rates. Conclusion: Despite the challenges arising from the lack of standardized parameters, DBS shows promising potential as a therapeutic option for patients with DOC. However, there still remains the need for standardized protocols and assessment methods, which are crucial to deepen the understanding and optimizing the therapeutic potential of DBS in this specific patient population. [ABSTRACT FROM AUTHOR]

Growing evidence suggests that systemic immune and inflammatory responses may play a critical role in the formation and development of aneurysms. Exploring the differences between single intracranial aneurysm (SIA) and multiple IAs (MIAs) could provide insights for targeted therapies. However, there is a lack of comprehensive and detailed characterization of changes in circulating immune cells in MIAs. Peripheral blood mononuclear cell (PBMC) samples from patients with SIA (n = 16) or MIAs (n = 6) were analyzed using high-dimensional mass cytometry to evaluate the frequency and phenotype of immune cell subtypes. A total of 25 cell clusters were identified, revealing that the immune signature of MIAs included cluster changes. Compared to patients with SIA, patients with MIAs exhibited immune dysfunction and regulatory imbalance in T-cell clusters. They also had reduced numbers of CD8+ T cells and their subgroups CD8+ Te and CD8+ Tem cells, as well as reduced numbers of the CD4+ T-cell subgroup CD27-CD4+ Tem cells. Furthermore, compared to SIA, MIAs were associated with enhanced T-cell immune activation, with elevated expression levels of CD3, CD25, CD27, CCR7, GP130, and interleukin 10. This study provides insights into the circulating immune cell profiles in patients with MIAs, highlighting the similarities and differences between patients with SIA and those with MIAs. Furthermore, the study suggests that circulating immune dysfunction may contribute to development of MIAs., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Disorders of consciousness (DoC) represent a spectrum of neurological conditions that pose significant treatment challenges. Percutaneous short-term spinal cord stimulation (SCS) has emerged as a promising experimental diagnostic treatment to assess and potentially improve consciousness levels. However, the effectiveness of this intervention is frequently compromised by the shift of electrodes, particularly in the cervical region, which can negatively affect therapeutic outcomes., Methods: This retrospective study aimed to study if electrodes shift in percutaneous short-term SCS in patients with DoC would affect the outcome. We analyzed the relationship between electrode shift length and patient outcome, as well as the correlation with various anatomical parameters, including the actual length of the cervical spine, linear length, spinal canal transverse diameter, spinal canal diameter, and C2 cone height, in a cohort of patients undergoing the procedure., Results: Our findings revealed that in patients with better outcome, there are significant less patient with electrode shift ( p  = 0.019). Further, a linear correlation was found between the length of electrode shift and patients' outcome (Rho = 0.583, p  = 0.002), with longer shift lengths associated with poorer outcomes. Contrary to our expectations, there was no significant association between the measured anatomical parameters and the extent of electrode shift. However, a trend was found between the actual length of the cervical spine and the shift of the electrode ( p  = 0.098). Notably, the shorter spinal canal transverse diameter was found to be significantly associated with better outcome in patients with DoC receiving percutaneous short-term SCS ( p  = 0.033)., Conclusion: These results highlight the clinical importance of electrode stability in the cervical region during SCS treatment for patients with DoC. Ensuring secure placement of electrodes may play a crucial role in enhancing patients' outcome and minimize postoperative complications. Given the lack of association with expected anatomical parameters, future research should investigate other factors that could impact electrode stability to optimize this therapeutic intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Yang, Xu, Niu, Wu, Huang, Chai, Cao, Wang, Wong, He, Yang and Zhao.)

A brain-computer interface (BCI) serves as a direct communication channel between brain activity and external devices, typically a computer or robotic limb. Advances in technology have led to the increasing use of intracranial electrical recording or stimulation in the treatment of conditions such as epilepsy, depression, and movement disorders. This indicates that BCIs can offer clinical neurological rehabilitation for patients with disabilities and functional impairments. They also provide a means to restore consciousness and functionality for patients with sequelae from major brain diseases. Whether invasive or non-invasive, the collected cortical or deep signals can be decoded and translated for communication. This review aims to provide an overview of the advantages of endovascular BCIs compared with conventional BCIs, along with insights into the specific anatomical regions under study. Given the rapid progress, we also provide updates on ongoing clinical trials and the prospects for current research involving endovascular electrodes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: Initial shunt failure following ventriculoperitoneal (VP) shunt surgery has a significant impact on the working time of the shunt. However, there are few studies regarding factors affecting VP shunt longevity. Hence, in this study, we aimed to build a nomogram to predict the longevity of the replacement VP shunt in patients with initial shunt failure., Methods: From 2011 to 2021, 142 patients with initial VP failure who underwent VP shunt revision were enrolled and relevant clinical and demographic factors were analyzed. Univariate and multivariate Cox proportional hazard regression models were used to choose predictors, and a nomogram was constructed using nine independent prognostic variables: sex, age, hydrocephalus type, intensive care unit admission, tracheostomy, decompressive craniectomy, craniotomy, lumbar cisterna drainage, and ventricular drainage. The prediction models' discrimination, accuracy, calibration, and clinical value were evaluated using Harrell's C-index, a calibration plot, and decision curve analysis., Results: At 1 month, 3 months, and 5 years, the nomogram's C-index was 0.680, 0.708, and 0.694, respectively. The nomogram's calibration plot provided a good fit for the overall prediction over the course of 1 year. Decision curve analysis predicted that 1-3 months after surgery will yield good net benefits between 30 and 50% probability thresholds., Conclusion: A preoperative nomogram may be an effective tool for assessing VP shunt longevity after initial VP shunt placement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, He, Niu, Li, Geng, Cao, Wang, Lv, He, Zhao, Chen and Yang.)

Objective: Extra-axial cavernous hemangiomas (ECHs) are sporadic and rare intracranial occupational lesions that usually occur within the cavernous sinus. The aetiology of ECHs remains unknown., Methods: Whole-exome sequencing was performed on ECH lesions from 12 patients (discovery cohort) and droplet digital polymerase-chain-reaction (ddPCR) was used to confirm the identified mutation in 46 additional cases (validation cohort). Laser capture microdissection (LCM) was carried out to capture and characterise subgroups of tissue cells. Mechanistic and functional investigations were carried out in human umbilical vein endothelial cells and a newly established mouse model., Results: We detected somatic GJA4 mutation (c.121G>T, p.G41C) in 5/12 patients with ECH in the discovery cohort and confirmed the finding in the validation cohort (16/46). LCM followed by ddPCR revealed that the mutation was enriched in lesional endothelium. In vitro experiments in endothelial cells demonstrated that the GJA4 mutation activated SGK-1 signalling that in turn upregulated key genes involved in cell hyperproliferation and the loss of arterial specification. Compared with wild-type littermates, mice overexpressing the GJA4 mutation developed ECH-like pathological morphological characteristics (dilated venous lumen and elevated vascular density) in the retinal superficial vascular plexus at the postnatal 3 weeks, which were reversed by an SGK1 inhibitor, EMD638683., Conclusions: We identified a somatic GJA4 mutation that presents in over one-third of ECH lesions and proposed that ECHs are vascular malformations due to GJA4 -induced activation of the SGK1 signalling pathway in brain endothelial cells., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Somatic KRAS mutations have been identified in the majority of brain arteriovenous malformations (bAVMs), and subsequent in vivo experiments have confirmed that KRAS mutation in endothelial cells (ECs) causes AVMs in mouse and zebrafish models. Our previous study demonstrated that the KRAS G12D mutant independently induced the endothelial-mesenchymal transition (EndMT), which was reversed by treatment with the lipid-lowering drug lovastatin. However, the underlying mechanisms of action were unclear., Methods: We used human umbilical vein ECs (HUVECs) overexpressing the KRAS G12D mutant for Western blotting, quantitative real-time PCR, and immunofluorescence and wound healing assays to evaluate the EndMT and determine the activation of downstream pathways. Knockdown of SMAD4 by RNA interference was performed to explore the role of SMAD4 in regulating the EndMT. BAVM ECs expressing the KRAS G12D mutant were obtained to verify the SMAD4 function. Finally, we performed a coimmunoprecipitation assay to probe the mechanism by which lovastatin affects SMAD4., Results: HUVECs infected with KRAS G12D adenovirus underwent the EndMT. Transforming growth factor beta (TGF-β) and bone morphogenetic protein (BMP) signalling pathways were activated in the KRAS G12D -mutant HUVECs and ECs in bAVM tissue. Knocking down SMAD4 expression in both KRAS G12D -mutant HUVECs and ECs in bAVM tissues inhibited the EndMT. Lovastatin attenuated the EndMT by downregulating p-SMAD2/3, p-SMAD1/5 and acetylated SMAD4 expression in KRAS G12D -mutant HUVECs., Conclusions: Our findings suggest that the KRAS G12D mutant induces the EndMT by activating the ERK-TGF-β/BMP-SMAD4 signalling pathway and that lovastatin inhibits the EndMT by suppressing TGF-β/BMP pathway activation and SMAD4 acetylation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To compare the clinical outcomes of hybrid microsurgery and embolization with multi-staged procedure for patients harboring brain arteriovenous malformations (bAVMs)., Methods: We retrospectively reviewed bAVM patients from a multicenter, prospectively collected database (NCT03774017) between June 2016 and June 2020. Patients were divided into single-staged hybrid operation (HO) group and multi-staged operation (MO) group according to the received treatment, in which microsurgeries were performed with embolization in a single setting or with multi-stage procedure, respectively. Cases were 1:1 matched between the two groups. Outcomes were compared between groups, which included neurological deficits (NDs), perioperative rupture, and proportion of complete resection. Variables associated with NDs were analyzed., Results: In total, 198 out of 544 cases were identified, including 120 in the HO group and 78 in the MO group. Sixty-six cases were matched in each group resulting in a total of 132 patients in this case-controlled study. Mean age was 29.2 years old, with 82 (62.1%) being male. No significant difference was observed in baseline demographics and clinical characteristics between the two groups. There were 7 ruptures occurred in the interval between embolization and microsurgery for MO group while none in the HO group (P=0.023). This yielded a rupture risk of 4.1% per year for the MO group. Duration of surgical resection was significantly reduced in HO group (P=0.001). Compared to MO, HO was more favorable to avoid short-term NDs (3.0% vs. 15.2%, P=0.021), but long-term outcomes were similar. The HO modality (OR, 0.110; 95% CI: 0.017-0.737; P=0.023) was confirmed as the protective factor for short-term NDs., Conclusions: HO is an effective setup to treat complex bAVMs with avoiding interval hemorrhage risk and reducing surgical risk. We also observed overall similar obliteration rate and resulting clinical outcomes between HO and MO., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-811/coif). All authors report that this study was supported by National Key Technologies Research and Development Program of China (2016YFC1301800), Beijing Science and Technology Supporting Plan (D161100003816005), Beijing Municipal Administration of Hospitals’ Mission Plan (SML20150501), Project of China Postdoctoral Science Foundation (2019M660921), and Science Foundation for Postdoctorate Research of Beijing (2017-ZZ-123). The authors have no other conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)