Fluids and Barriers of the CNS最新文献

{"title":"CSF stroke volume measured in pediatric Chiari type 1 Malformation subjects before and after posterior fossa decompression surgery compared with healthy subjects.","authors":"Brice Williams, Bliss Uribe, Francis Loth, Samir Sarda, Nilesh Desai, Joshua Chern, John Oshinski","doi":"10.1186/s12987-026-00849-8","DOIUrl":"10.1186/s12987-026-00849-8","url":null,"abstract":"<p><strong>Background: </strong>Chiari Malformation Type 1 (CM-1) is characterized radiologically by > 5 mm herniation of the cerebellar tonsils below the foramen magnum (FM). Tonsillar descent below the FM does not correlate well with symptom severity nor does it predict outcomes following posterior-fossa-decompression surgery. Using 2D phase-contrast magnetic resonance imaging (MRI) it is possible to measure cerebrospinal fluid (CSF) hydrodynamics non-invasively in CM-1 patients. The volume of fluid moved each heartbeat, or stroke volume, has shown promise as a new metric to characterize CM-1 malformation in adults, but has been relatively underexplored in the pediatric population. We measured CSF stroke volume in a pediatric CM-1 cohort before and after posterior fossa decompression surgery and in age-matched controls.</p><p><strong>Materials and methods: </strong>24 pediatric CM-1 patients (age 9.3 ± 4.5, 7 M, 17 F) underwent posterior fossa decompression surgery to treat CM-1 symptoms and received an MRI pre-operatively and 6 months post-operatively. 8 additional healthy volunteers (age 7.8 ± 5.7, 5 F) were used as control subjects. ECG-gated 2D phase-contrast magnetic resonance (PCMR) scans were acquired in the axial orientation at the foramen magnum (FM). CSF stroke volume was calculated from flow by separately integrating positive and negative flow, then averaging the absolute values.</p><p><strong>Results: </strong>The CSF stroke volumes in the pre-surgical CM-1 subjects (0.26 ml ± 0.21) were lower than control subjects (0.55 ± 0.2, p < 0.01). Post-surgical stroke volumes in CM-1 subjects (0.44 ± 0.3) were not different than controls (p = 0.18). Pre-surgical stroke volumes were lower than post-surgical stroke volumes across all patients (p = 0.03), and in paired patients who had both pre- and post-surgical scans (p = 0.03). There was no difference in peak velocity pre-surgical and control (p = 0.7) or pre- and post-surgical subjects (p = 0.2). Pre-surgical patients with syrinx (10/15) showed no difference in stroke volume to patients without syrinx (p = 0.6).</p><p><strong>Conclusion: </strong>Healthy pediatric control subjects had higher CSF stroke flow volume than CM-1 patients. Surgery increased CSF stroke volume in CM-1 patients to values equal to healthy control subjects, and post-surgical stroke volumes were significantly greater than pre-surgical volumes. CSF stroke volume shows potential for use as a flow metric in assessing pediatric CM-1 patients.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13445750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neonatal blood biomarkers related to development of hydrocephalus.","authors":"Nicolas Hernandez Norager, Man-Hung Eric Tang, Michael Christiansen, Tina N Munch, Nis Borbye-Lorenzen","doi":"10.1186/s12987-026-00852-z","DOIUrl":"10.1186/s12987-026-00852-z","url":null,"abstract":"<p><strong>Background: </strong>Infantile hydrocephalus is a challenging condition with variable timing of clinical recognition. Early identification of newborns at increased risk could enable closer surveillance and earlier intervention. Neonatal blood samples collected routinely for newborn screening allow us to test whether specific blood biomarkers are associated to hydrocephalus.</p><p><strong>Methods: </strong>We used the data from an established nationwide Danish cohort study of 14,866 infants born from March 2009 to March 2011, with blood samples collected 2-8 days after birth and linked to longitudinal health registry data. The data included ten protein biomarkers spanning from inflammatory, cellular stress, growth, and neurotrophic pathways. Associations between neonatal biomarker concentrations and hydrocephalus were investigated using multivariable regression models adjusting for gestational age, age at sampling, and neonatal anthropometrics.</p><p><strong>Results: </strong>Among 14,866 infants, 41 were diagnosed with hydrocephalus (approximately 3 per 1,000 births). The primary biomarker analyses included 30 hydrocephalus cases diagnosed no later than the age of 2 years and 14,577 controls. Neonatal heat-shock protein 70 (HSP70) concentrations were significantly higher in infants who developed hydrocephalus. No significant differences were found for the remaining biomarkers, and subgroup analyses related to intraventricular hemorrhage did not show distinct biomarker profiles.</p><p><strong>Conclusions: </strong>In this nationwide cohort, elevated HSP70 in neonatal blood samples was associated with development of infantile hydrocephalus. No other of the inflammatory and neurotrophic biomarkers we investigated were significantly associated with hydrocephalus. These findings support further mechanistic investigation of HSP70 as a potential component of multifactorial early-life risk models of hydrocephalus.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13520248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148826648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TNFα-induced endothelial extracellular vesicles regulate astrocyte function: an integrated transcriptomic and proteomic study.","authors":"Le Wang, Li Luo, Zhaoyang Zhang, Xueqin Li, Yi Xu, Han Luo, Qiang Lyu, Fei-Fei Shang","doi":"10.1186/s12987-026-00851-0","DOIUrl":"10.1186/s12987-026-00851-0","url":null,"abstract":"<p><p>Endothelial cells and astrocytes are critical structural and functional components of the blood-brain barrier. In many neuroinflammatory diseases, endothelial cells are among the first to respond to inflammatory stimuli and release extracellular vesicles (EVs). However, whether inflammatory stimulation alters EV RNA cargo and subsequently regulates astrocyte function remains unclear. In this study, we performed integrated RNA sequencing and proteomic analyses to investigate the effects of TNFα-stimulated endothelial EVs on astrocytes. RNA profiling revealed significant alterations in EV cargo after TNFα stimulation, including 867 upregulated and 577 downregulated mRNAs, 317 upregulated and 15 downregulated lncRNAs, and 88 upregulated and 62 downregulated miRNAs. The results of functional enrichment analysis suggested that altered EV RNAs may primarily promote inflammatory responses, cell migration, and RNA splicing in astrocytes while reducing their regulatory effects on neuronal projection and calcium homeostasis. Further integrative analysis of EV RNAs and astrocytic proteomics revealed key overlapping targets, including upregulated expression of ICAM1, SOD2, TFPI2, and TNFAIP8, whereas NFKBIA expression was consistently decreased. Network analysis revealed NF-κB as the central regulatory node. Reduced levels of EV-derived NFKBIA mRNA were associated with decreased IκBα protein levels in astrocytes, which promoted NF-κB activation and inflammatory cytokine release. Finally, overexpression of IκBα in astrocytes significantly attenuated TNFα EV-induced IL-1β and IL-6 secretion. Collectively, these findings demonstrate that TNFα-stimulated endothelial EVs coordinately regulate astrocyte function through mRNA, lncRNA, and miRNA cargo and that the IκBα/NF-κB axis may be a key mechanism underlying endothelial EV-mediated inflammatory disruption of the blood-brain barrier.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13576280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring and translating novel approaches targeting the choroid plexus for the treatment of hydrocephalus: a literature review.","authors":"Olivier J J Sluijters, John R Pooley, William G B Singleton","doi":"10.1186/s12987-026-00779-5","DOIUrl":"10.1186/s12987-026-00779-5","url":null,"abstract":"<p><p>Hydrocephalus is common with a mixed phenotype and aetiology. Its treatment is predominantly surgical, with temporary or permanent cerebrospinal fluid (CSF) diversion, which does not address the underlying disease mechanism. The choroid plexus (ChP), a secretory epithelium found in all four ventricles of the brain, produces most CSF within the central nervous system and has been investigated extensively over the past century to understand its function and potential role as a therapeutic target. Past attempts at either medically or surgically controlling its rate of secretion have not significantly altered our approach to the treatment of hydrocephalus, with CSF diversion remaining the main intervention. Rodent models of post-haemorrhagic hydrocephalus (PHH) have advanced our understanding of choroid plexus function in health and disease. Pre-clinical experiments have demonstrated a hypersecretory response in the ChP that may contribute to PHH. Targeting the choroid plexus directly may therefore present a novel therapeutic method. These findings have led to a significant increase in pre-clinical studies exploring this hypersecretory response and how to modulate it. Translating these promising results to clinical practice will rely on the development of large animal hydrocephalus models, which thus far has been limited. This literature review discusses the recent advances in targeting the ChP as a treatment for hydrocephalus, both surgically and non-surgically, and the current barriers to further advancement of this approach.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13425997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distribution of transgene in the rodent choroid plexus after intracerebroventricular injection of adeno-associated virus.","authors":"John R Pooley, Ali S Bienemann, Alison Young, Owen Hollings, Jiahui Wu, Eddie Mayo, Colin J Chu, Will G B Singleton","doi":"10.1186/s12987-026-00831-4","DOIUrl":"10.1186/s12987-026-00831-4","url":null,"abstract":"<p><p>Using adeno-associated virus to transfer genetic information to the choroid plexus has emerged as a promising route for long-term gene therapy in the brain for a variety of conditions. Overexpression of proteins has proved effective in small animal models but few attempts have been made to translate this technology to clinic, suppress the activity of a protein of interest, or further expand the limited capsid serotypes known to have choroid plexus tropism. We utilise transfer of green fluorescent protein to show choroid plexus epithelium tropism for novel AAV6 derived capsid ShH10^Y445F in mouse, rat and porcine tissue explant cultures. In vivo tropism is shown in the mouse following stereotactic intracerebroventricular injection. We examined the distribution of viral transduction across the choroid plexus in all four ventricles following a single unilateral intracerebroventricular injection using both green fluorescent protein as a transgene, but also the CRISPR/Cas9 system to deliver permanent knockdown of apical water channel aquaporin-1. Quantitative immunofluorescence and SURVEYOR assay were used to statistically assess the magnitude and extent of choroid plexus knockdown across the ventricular system. We conclude that serotype ShH10^Y445F targets choroid plexus epithelium in mouse, rat and pig; and when carrying the CRISPR/Cas9 system can reduce target protein expression in these cells. Transduced choroid plexus epithelial cells distribute unevenly with a bias toward the lateral ventricle on the injected side and a preferential infection of choroid plexus in the lateral over the third and fourth ventricles. Overcoming irregular distribution represents a challenge for clinical translation of this technology where clinical efficacy may require manipulation of the entire choroid plexus.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13428447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ascorbic acid transport via choroid plexus measured with 6-deoxy-6-[¹⁸F]fluoro-L-ascorbic acid PET.","authors":"Yuying Zhang, Xiaofeng Lin, Haoyue Deng, Yali Long, Tianhong Yang, Kunyuan Jiang, Songhan Ge, Qiao He, Bing Zhang, Ningyi Jiang, Zhihao Zha, Xiangsong Zhang","doi":"10.1186/s12987-026-00847-w","DOIUrl":"https://doi.org/10.1186/s12987-026-00847-w","url":null,"abstract":"<p><strong>Background: </strong>Ascorbic acid, a crucial antioxidant, is transported from blood to cerebrospinal fluid (CSF) via the choroid plexus (ChP). A noninvasive tool to visualize and quantify ascorbic acid transport process in the human brain is currently lacking. We aimed to determine whether 6-deoxy-6-[¹⁸F]fluoro-L-ascorbic acid ([¹⁸F]FAA) PET can visualize and quantify ascorbic acid transport from blood to CSF via the ChP in humans.</p><p><strong>Methods: </strong>This prospective secondary analysis evaluated participants between May 2024 and September 2024. Eight participants underwent a 45-minute dynamic brain [¹⁸F]FAA PET/CT scan; 153 participants underwent a static [¹⁸F]FAA PET/CT scan. Tracer accumulation in ChP and CSF were measured in the lateral and fourth ventricles. Univariable and multivariable linear regression models were used to investigate the associated factors of [¹⁸F]FAA PET metrics.</p><p><strong>Results: </strong>One hundred sixty-one participants (mean age, 48.0 years ± 15.7 [SD]; 90 women) were evaluated. Dynamic [¹⁸F]FAA PET showed rapid ChP tracer accumulation in the lateral and fourth ventricles, peaking at about 5 min post-injection followed by declining, while CSF [¹⁸F]FAA standardized uptake value progressively increased. The area under the curve of the time-activity curves from 0 to 40 min was significantly higher in the young group (<60 years, n = 4) than in the elderly group (≥ 60 years, n = 4) in the ChP. Multiple linear regression analyses showed age was independently and negatively associated with [¹⁸F]FAA accumulation in the ChP and CSF.</p><p><strong>Conclusions: </strong>[¹⁸F]FAA PET is a non-invasive tool for visualizing and assessing choroid plexus ascorbic acid transport in humans.</p><p><strong>Clinical trial number: </strong>(ChiCTR2300076126: http://www.chictr.org.cn/ ) with the Clinical Trial Registry (2023-09-25).</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149264953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood-brain barrier and blood-tumoral barrier formation in glioblastoma: endothelial cells and glioblastoma stem cells at the immune-brain crossroad.","authors":"Maria Rosito, Ruth Lyck, Britta Engelhardt, Cristina Limatola","doi":"10.1186/s12987-026-00850-1","DOIUrl":"https://doi.org/10.1186/s12987-026-00850-1","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most aggressive primary brain tumor characterized by significant cellular and molecular complexity. Central to this complexity are glioma stem cells (GSCs) and the perivascular niche, a specialized microenvironment that integrates signals from the systemic circulation with cues arising from tumor development. Acting as a regulatory hub, the perivascular niche influences GSC proliferation, migration, and resistance to therapy through multiple interactions among vascular, immune, and tumor cell populations. In this review, we focus on GSCs and examine the cellular composition and molecular mechanisms operating within the perivascular niche, highlighting key modes of crosstalk that sustain tumor progression. We furthermore critically evaluate experimental strategies used to study this compartment, including 2D and 3D cell cultures, organoids, and in vivo models, discussing their respective strengths and limitations for testing intercellular interactions and therapeutic approaches. A comprehensive understanding of tumor heterogeneity and the interactions between different tumor cell populations, combined with well-characterized experimental models, is essential for deriving mechanistic insights and informing the development of more effective targeted therapies for GBM, ultimately advancing our knowledge of how tumor-microenvironment interactions drive GBM progression.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149243896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ischemic stroke: molecular mechanisms of blood-brain barrier dysfunction and opportunities for drug development.","authors":"Patrick T Ronaldson, Thomas P Davis","doi":"10.1186/s12987-026-00848-9","DOIUrl":"https://doi.org/10.1186/s12987-026-00848-9","url":null,"abstract":"<p><p>Ischemic stroke remains a leading cause of disability and death, yet decades of therapeutic development have yielded remarkably little clinical progress. The limited progress in improving stroke outcomes is closely linked to dysfunction of the blood-brain barrier (BBB), which undergoes profound structural and functional disruption during ischemic injury. Barrier injury under ischemic conditions is driven, in part, by glutamate dysregulation, neuroinflammation, and oxidative stress, which act in concert to destabilize endothelial integrity and exacerbate BBB permeability. Targeting these interconnected mechanisms represents a promising approach to preserve BBB function and limit secondary injury following stroke. Interventions aimed at modulating excitotoxic signaling, inflammatory cascades, and redox imbalance can protect the BBB and the larger neurovascular unit (NVU); however, aging further compromises BBB integrity and resilience, compounding these pathological processes and posing additional challenges for therapeutic development, particularly given the higher incidence of stroke in older individuals. This review highlights current understanding of BBB physiology in health and under ischemic conditions with an emphasis on how excitotoxicity, neuroinflammation, and oxidative stress compromise BBB functional integrity. Additionally, we evaluate therapeutic strategies aimed at preserving or restoring BBB homeostasis. By integrating insights into BBB biology with advances in neurovascular therapeutics, this review provides a forward-thinking assessment on the future of therapeutic development for ischemic stroke.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149243907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatiotemporal arising of molecular and functional blood-brain barrier properties in the developing Gallus gallus optic tectum.","authors":"Jesús Juárez-Balarezo, María Jesús Garrido-Muñoz, Benjamín Reuse-Benavente, Ignacio Casanova-Maldonado, Verónica Palma","doi":"10.1186/s12987-026-00840-3","DOIUrl":"10.1186/s12987-026-00840-3","url":null,"abstract":"<p><strong>Background: </strong>The cerebrovascular endothelium possesses unique properties that strictly regulate the neural microenvironment. While mammalian Blood Brain Barrier (BBB) development is well-characterized, the avian embryo (Gallus gallus) offers a unique, highly accessible model for real-time developmental imaging and manipulation. However, the precise molecular and functional timeline of BBB maturation in the avian brain remains poorly explored. Here, we provide the first comprehensive spatiotemporal characterization of BBB development in the Gallus gallus optic tectum (OT).</p><p><strong>Methods: </strong>We performed a multi-modal analysis between developmental stages HH32 and HH44, combining transcriptional analysis of BBB-associated genes, confocal and lightsheet microscopy, and quantitative functional assays for permeability and efflux activity.</p><p><strong>Results: </strong>We identified a critical developmental window between stages HH36 and HH40 that marks the transition to a specialized barrier. This period is characterized by the significant upregulation of tight junction proteins (CLDN5, OCLN) and efflux transporters (ABCB1), accompanied by the downregulation of fenestration markers (PLVAP). Also, tight junction assembly protein ZO-1 undergoes a progressive redistribution from a discontinuous pattern to continuous linear expression along the vessel walls during this period. Functionally, we demonstrate that paracellular restriction to 10 kDa dextran develops in a region-dependent manner, while quantitative assays reveal a sharp reduction in Evans Blue permeability starting at HH38. Lastly, we detected the onset of P-glycoprotein efflux activity from HH36 onwards.</p><p><strong>Conclusions: </strong>Altogether, our findings redefine the chicken embryo as a tractable model for barrier genesis research, pinpointing the HH36-40 developmental window as the discrete period where the molecular and functional BBB properties are acquired. This establishes a robust baseline for future mechanistic investigations into neurovascular development and pathology.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13463485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Motor network neurophysiological (TMS-EEG) markers as predictors of outcomes of ventriculoperitoneal shunt sustained for over a year in normal pressure hydrocephalus.","authors":"Tal Davidy, Alexandra Suminski, Yakov Zauberman, Tsvia Fay-Karmon, Saar Anis, Adi Saar, Noa Zifman, Hilla Fogel, Ofri Levy-Lamdan, Orit Lesman-Segev, Sharon Hassin-Baer","doi":"10.1186/s12987-026-00844-z","DOIUrl":"10.1186/s12987-026-00844-z","url":null,"abstract":"<p><strong>Background and objectives: </strong>Current practice for normal pressure hydrocephalus (NPH) relies on clinical presentation, imaging, and various clinical procedures to determine the need for neurosurgical intervention, specifically the installation of a ventriculoperitoneal shunt (VPS). This study aimed to evaluate the utility of a TMS-evoked potential (TEP)-based assessment (Delphi-MD) for predicting sustained response (over one year) to VPS, serving as an ancillary test to the cerebrospinal fluid tap test (CTT).</p><p><strong>Methods: </strong>Forty-one patients with possible iNPH underwent Delphi-MD evaluation of wave form adherence (WFA), a composite measure assessing how closely their TEPs resembled an ideal benchmark TEP. Of these, 18 patients received VPS treatment following a multidisciplinary team decision based on standard practice, blinded to the TEP results. Response to the intervention was evaluated over a period of more than one year using the clinical global impression of change (CGIC) scale, in addition to assessments with a 10-meter timed up and go test and the modified Rankin scale.</p><p><strong>Results: </strong>Responders had higher M1L WFA values at baseline (prior to VPS) than non-responders (median 0.51 [95% CI 0.36-0.76], median 0.14 [95% CI -0.02-0.38], respectively p = 0.012). M1L WFA was successful in distinguishing responders (11/18) from non-responders (7/18) with an ROC-AUC of 0.935 [bootstrap 95% CI 0.792-1.00], p < 0.0001. M1L WFA cutoff was established with LOOCV and produced 90.9% sensitivity, 85.7% specificity and 88.9% accuracy. In contrast the CTT result was unsuccessful in predicting shunt responsiveness.</p><p><strong>Conclusion: </strong>This study indicates that higher M1L WFA obtained through Delphi-MD (TMS-EEG), signifies better preservation and functional integrity of the motor network in patients with probable iNPH that had a sustained response to VPS than those that did not. Given replication of results in future independent cohorts, Delphi-MD shows promise as an objective, accurate, and accessible ancillary screening tool for iNPH candidates, prior to referral for VPS treatment.</p><p><strong>Trial registration: </strong>Registration number: MOH_2021-12-08_010449. Registration date: 11.09.2021. https://clinicaltrial.health.gov.il/clinicaltrials/?sort=experimentapproveddate_tdt+desc&page=1&searchQuery=MOH_2021-12-08_010449 .</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13685369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}