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
{"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}
Anujit Saha, Wen Shi, Mohamad N Elsharydah, Jeff Schaffert, Jack Kaufman, Jennine Leary, Alison Jin, Jaime P Almandoz, Hanzhang Lu, Binu P Thomas
{"title":"Blood-brain barrier water permeability is elevated in type 2 diabetes and obesity: associations with cognitive function and metabolic markers.","authors":"Anujit Saha, Wen Shi, Mohamad N Elsharydah, Jeff Schaffert, Jack Kaufman, Jennine Leary, Alison Jin, Jaime P Almandoz, Hanzhang Lu, Binu P Thomas","doi":"10.1186/s12987-026-00843-0","DOIUrl":"10.1186/s12987-026-00843-0","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes (T2D) and obesity are established risk factors for Alzheimer's disease and related dementias, yet the cerebrovascular mechanisms linking metabolic dysfunction to cognitive decline remain poorly understood. This study aims to assess BBB water permeability-surface area product in older adults with T2D and obesity using non-contrast WEPCAST MRI, and to evaluate associations between BBB integrity, metabolic markers, and cognitive function.</p><p><strong>Methods: </strong>Twenty-eight older adults - 12 with T2D and obesity (BMI ≥ 30 kg/m²) and 16 age- and sex- matched controls - underwent WEPCAST MRI to quantify the BBB water permeability measures: permeability-surface area product (PS), water extraction fraction (E) and global cerebral blood flow (CBF), along with T1-Weighted structural MRI acquisition. Cognitive function and fasting blood biomarkers were assessed in all participants. Associations between PS versus metabolic and cognitive function were examined using linear regression adjusted for age and sex. An additional adjustment for statin use was made for hemoglobin A1c (HbA1c) and lipid markers.</p><p><strong>Results: </strong>T2D participants exhibited significantly elevated BBB water permeability-surface area product (PS: P = 0.001, Hedges' g = 1.10). Specifically, higher PS was associated with HbA1c (f² = 0.28, P = 0.016) and lower circulating cholesterol (total cholesterol: f² = 0.49, P = 0.003; LDL: f² = 0.45, P = 0.004; HDL: f² = 0.18, P = 0.053). The T2D group demonstrated lower scores across multiple domains including memory, attention, learning, executive function, and processing speed (g = 0.80-1.42). Higher PS was associated with poorer measures of executive function (P-values < 0.05).</p><p><strong>Conclusions: </strong>Older adults with T2D and obesity exhibit elevated PS, detectable by non-contrast WEPCAST MRI. Higher PS was associated with higher glycemic burden and lower executive function, providing preliminary evidence that PS may serve as a novel imaging biomarker linking metabolic dysregulation to early cognitive vulnerability in T2D that follows a traditional \"frontal-subcortical\" pattern.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817662","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":"Cerebral venous outflow disturbance exacerbates ischemic stroke via an endothelium-initiated inflammatory cascade: an integrated single-cell transcriptomic analysis.","authors":"Shiyan Qian, Ying Zhang, Guoqian Cui, Muzi Li, Lixiang Wang, Wenbo Guo, Xin Shao, Jie Liao, Qinghua Feng, Shengshuang Chen, Xiao-Hui Fan, Guoqing Zheng","doi":"10.1186/s12987-026-00842-1","DOIUrl":"10.1186/s12987-026-00842-1","url":null,"abstract":"<p><strong>Background: </strong>Unfavorable cerebral venous outflow (VO) critically worsens ischemic stroke (IS) prognosis, yet the underlying cellular mechanisms driving this aggravation remain obscure. This study aimed to explore the impact of VO disturbance on ischemic brain injury.</p><p><strong>Methods: </strong>We superimposed the left internal jugular vein occlusion (LIJVO) onto a rat model of ischemia/reperfusion (I/R). Key pathological indices were assessed and the transcriptomic landscape of the injury using the integrated single-cell and single-nucleus RNA sequencing approach, followed by immunofluorescence validation.</p><p><strong>Results: </strong>Superimposed LIJVO significantly exacerbated neurological deficits and infarction, precipitating malignant brain edema and blood-brain barrier breakdown (P < 0.05). The pathological expansion of pro-inflammatory Endothelial0 and Microglia1 subpopulations were identified. We traced these deteriorations to an endothelial-initiated inflammatory cascade: a specific Endothelial0 emerged to recruit leukocytes and trigger a feed-forward loop with hyper-reactive Microglia1. This crosstalk may drive a cytokine storm and tight junction collapse, ultimately leading to severe perivascular infiltration and accelerated neuronal injury.</p><p><strong>Conclusion: </strong>Collectively, this study elucidates that unfavorable VO functions as a critical aggravator in IS via an endothelial-initiated inflammatory cascade. Targeting upstream endothelial activation represents a promising therapeutic strategy for the IS patients with compromised venous drainage.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535696","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}
Olivia C Milam, Cullen P Wolford, Geoffrey L Pecar, Joshua J Applegate, Maxine E Casto, Dominic J Gabriele, Austin S Nestor, Paul R Lockman
{"title":"Correction: Characterization of blood-brain barrier L-arginine uptake using in situ brain perfusions in a female mouse model.","authors":"Olivia C Milam, Cullen P Wolford, Geoffrey L Pecar, Joshua J Applegate, Maxine E Casto, Dominic J Gabriele, Austin S Nestor, Paul R Lockman","doi":"10.1186/s12987-026-00839-w","DOIUrl":"10.1186/s12987-026-00839-w","url":null,"abstract":"","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13383510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520028","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}
Yichao Ou, Mengjie Che, Guangsen Wu, Mingfeng Zhou, Xufan Ling, Junjie Peng, Ken Kin Lam Yung, Yongjia Wang, Kai Li, Rongjun Chen, Xichun Yan, Yihan Wang, Kairui Huang, Jia Wu, Le Yang, Yiyang Chen, Xi'an Zhang, Songtao Qi, Zhanpeng Feng
{"title":"Spatial heterogeneity of the ventricular interface between the median eminence and arcuate nucleus revealed by an unfolded whole-mount view.","authors":"Yichao Ou, Mengjie Che, Guangsen Wu, Mingfeng Zhou, Xufan Ling, Junjie Peng, Ken Kin Lam Yung, Yongjia Wang, Kai Li, Rongjun Chen, Xichun Yan, Yihan Wang, Kairui Huang, Jia Wu, Le Yang, Yiyang Chen, Xi'an Zhang, Songtao Qi, Zhanpeng Feng","doi":"10.1186/s12987-026-00841-2","DOIUrl":"10.1186/s12987-026-00841-2","url":null,"abstract":"<p><strong>Background: </strong>The median eminence (ME) and adjacent arcuate nucleus (ARC) sit at a unique interface where blood, cerebrospinal fluid (CSF), and hypothalamic circuits meet. However, its continuous organization, postnatal maturation, and aging-related remodeling remain incompletely defined because conventional sections capture only limited spatial fragments.</p><p><strong>Methods: </strong>A topological unfolding method was established to open and flatten the third ventricle floor for whole-mount view imaging. Whole-mount immunostaining, reporter-based anatomical mapping, coronal section validation, and tracer assays were combined to examine apical specializations, junctional architecture, vascular organization, and regional permeability along the rostrocaudal axis. Evans Blue was delivered intraventricularly or intracardially at 1, 3, and 8 weeks and at 14 months of age. WGA was delivered intraventricularly and analyzed at 4 h and 24 h after injection.</p><p><strong>Results: </strong>The unfolded whole-mount view preserved the continuous surface anatomy of the third ventricle floor and enabled direct registration of ventricular and hypothalamic landmarks. A clear rostrocaudal heterogeneity was identified around the ME, including regional differences in tanycyte organization, Ki67-positive cells, vascular patterning, neuroendocrine axonal networks, ciliation, and ZO-1 junctional domains. Enlarged and more heterogeneous ZO-1 polygons were enriched toward the caudal ME and infundibular region. Tracer assays showed stronger Evans Blue access toward the caudal ME and infundibular region. WGA analysis further revealed region-dependent differences in macromolecular uptake and redistribution along the third ventricle wall. Among the ages examined, intraventricular Evans Blue permeability was greater at 1 week than at 3 and 8 weeks, became restricted by 3 weeks, and increased again in aged mice, accompanied by junctional disorganization.</p><p><strong>Conclusions: </strong>The third ventricle floor is organized as a continuous spatial gradient rather than a uniform barrier. The caudal ME and infundibular region form a more permissive CSF-facing exchange territory. Aging disrupts this regional junctional organization and is associated with increased intraventricular permeability in the ME and ARC.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148455108","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}
Clara Ciampi, Samuele Trisolini, Lorenzo Di Cesare Mannelli, Elena Ferri, Carla Ghelardini, Flavio Giordano, Laura Micheli
{"title":"Hydrocephalus-associated persistent pain: a preclinical investigation correlating brain fluid imbalance and sensory alterations.","authors":"Clara Ciampi, Samuele Trisolini, Lorenzo Di Cesare Mannelli, Elena Ferri, Carla Ghelardini, Flavio Giordano, Laura Micheli","doi":"10.1186/s12987-026-00838-x","DOIUrl":"10.1186/s12987-026-00838-x","url":null,"abstract":"<p><strong>Background: </strong>Hydrocephalus is a neurological disorder characterized by ventricular enlargement, elevated intracranial pressure and long-term complications, including cognitive dysfunction, motor deficits and pain. Despite the relevance of hydrocephalus-associated pain (characterized by peripheral sensory disturbances and central sensitization) this aspect is neglected both in clinical practice and animal studies.</p><p><strong>Methods: </strong>We characterized persistent pain in a rat model of kaolin-induced hydrocephalus, investigating behavioural, pharmacological, molecular, and cellular aspects, to improve translational relevance. A particular focus was placed on the role of glial cells in the underlying pathophysiology: astrocytes and astrocytic protein aquaporin-4 (AQP4) and microglia. Analyses were conducted separately in male and female rats as an exploratory approach to examine potential sex-related differences in hydrocephalus-associated pain, an aspect that has been largely overlooked in previous preclinical studies.</p><p><strong>Results: </strong>Induction of hydrocephalus resulted in a significant reduction in pain threshold, as evidenced by the development of peripheral and cephalic hypersensitivity, and spontaneous pain. This pain phenotype is of mixed origin, encompassing both nociceptive and neuropathic components, and shows limited responsiveness to conventional pain therapy. Histological analysis revealed activation of ependymal cells, likely triggered by increased intraventricular pressure. In brain regions implicated in pain processing, particularly the periaqueductal gray (PAG), astrocytes are altered in terms of quantity, simplified morphology, and diminished AQP4 expression, while microglial cells switched to an activated phenotype, suggesting primary mechanical compression damage leading to cellular distress. In downstream areas, in the dorsal horns of the spinal cord, both astrocytes and microglia displayed overt activation, suggestive of secondary reactive changes at spinal level, in line with the hypothesis of central sensitization.</p><p><strong>Conclusions: </strong>The regional specificity of these alterations underscores the complexity of hydrocephalus-related pain mechanisms and emphasizes the urgent need for novel therapeutic options to manage pain in hydrocephalus, a clinical challenge that remains inadequately addressed.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13629091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148404171","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}
Rafael T Holmgren, Andreas Eleftheriou, Johanna Rydja, Fredrik Lundin, Peter Zsigmond, Charalampos Georgiopoulos
{"title":"Ventricular volumetry in relation to clinical response and overdrainage after shunt surgery in idiopathic normal-pressure hydrocephalus: a three-year prospective study.","authors":"Rafael T Holmgren, Andreas Eleftheriou, Johanna Rydja, Fredrik Lundin, Peter Zsigmond, Charalampos Georgiopoulos","doi":"10.1186/s12987-026-00835-0","DOIUrl":"10.1186/s12987-026-00835-0","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic normal pressure hydrocephalus (iNPH) is treated with shunt surgery, but long-term monitoring of shunt function and complications remains challenging. Traditional radiological measures such as the Evans index lack sensitivity for detecting subtle longitudinal ventricular changes. Ventricular volumetry may provide a more precise method, but prospective long-term data are scarce.</p><p><strong>Objective: </strong>To evaluate ventricular volumetry in relation to clinical outcome, overdrainage, and valve adjustments during a structured three-year follow-up after shunting for iNPH.</p><p><strong>Methods: </strong>Fifty patients who fulfilled the diagnostic criteria for iNPH and who underwent shunt surgery with an adjustable Codman Certas Plus® valve without an antisiphoning device (ASD) were enrolled in this prospective single-center study. Clinical outcomes were assessed with the Hellstrom iNPH scale and Mini-Mental State Examination (MMSE) at baseline and at 3, 12, and 36 months. Ventricular volumes were measured via quantitative magnetic resonance imaging (qMRI) and automated segmentation. Overdrainage was defined clinically and/or radiologically.</p><p><strong>Results: </strong>Forty-two patients completed the 3-month follow-up, 86% of whom were classified as clinical responders. Gait improvement was sustained at 12 months, whereas cognitive gains were transient. The ventricular volume decreased significantly from baseline by a mean of 20% at 3 months (p < 0.001), with a further decreasing trend up to 36 months. The responders demonstrated greater relative ventricular reduction (21%) than the nonresponders did (10%) at 3 months, while ventricular reduction was equal at later timepoints. Overdrainage symptoms and events occurred in 12 out of 50 patients, including 7% with subdural collections. Patients with overdrainage symptoms showed markedly greater reductions in ventricular volume (35%) than asymptomatic patients did (16%; <0.001). Valve adjustments resulted in detectable volumetric changes, supporting volumetry as a noninvasive marker of shunt function.</p><p><strong>Conclusion: </strong>Ventricular volumetry is a sensitive tool for longitudinal follow-up after shunting in iNPH patients. A reduction of ventricular volume of approximately 20% is associated with clinical improvement, whereas a reduction exceeding 30% increases the risk of overdrainage symptoms. Routine baseline volumetry, early intensive follow-up and the routine use of ASDs could be used to optimize outcomes and minimize complications.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360270","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}
Christopher W Roberts, Brandon G Rocque, Leopold Arko Iv, Neena I Marupudi, Sandeep Sood, Andrew Jea, Elliot Widd, Bryn A Martin, Carolyn A Harris
{"title":"Catheter architecture as a determinant of cerebrospinal fluid flow in pediatric hydrocephalus.","authors":"Christopher W Roberts, Brandon G Rocque, Leopold Arko Iv, Neena I Marupudi, Sandeep Sood, Andrew Jea, Elliot Widd, Bryn A Martin, Carolyn A Harris","doi":"10.1186/s12987-026-00834-1","DOIUrl":"10.1186/s12987-026-00834-1","url":null,"abstract":"<p><p>Cerebral ventricular catheters (VCs) remain the critical but failure-prone component of cerebrospinal fluid (CSF) shunt systems for pediatric hydrocephalus, with proximal obstruction accounting for most malfunctions. Several catheter geometries have been introduced to the market in the US alone, yet none demonstrate long-term reliability. This study investigates how catheter design interacts with patient-specific ventricular anatomy and surgical placement to influence CSF drainage patterns. Three patient-specific hydrocephalic ventricles were modeled from MRI scans, with FOHR values of 0.45, 0.30, and 0.29 and corresponding ventricular volumes of 167.5 (enlarged), 12.5 (moderate), and 20.6 mL (small). Four ventricular catheters with varying architectures from our institutional biobank were reverse engineered using confocal microscopy. Catheters were virtually implanted into the lateral ventricles under frontal, parietal, and occipital placements. Computational fluid dynamic simulations were performed, and mass flow rates were quantified across drainage holes grouped into longitudinal segments. Boundary conditions consisted of a constant CSF efflux rate of 0.35 mL/min applied uniformly across all configurations and a continuous pressure outlet at the proximal catheter outlet, representing valveless drainage. Occipital placement consistently produced valve adjacent dominant inflow across catheter designs, whereas frontal and parietal placements exhibited design-specific flow behaviors when segmental inflow through the catheter drainage holes was measured. In most configurations, segments nearest the catheter valve captured the majority of inflow, accounting for 65-82% of total CSF entry. In frontal placements, smaller ventricular geometries caused valve-adjacent segments in several catheter designs to extend outside the ventricular cavity. As a result, inflow was redistributed toward the remaining tip-adjacent segments, with up to 99.5% of total flow entering through these segments when valve-adjacent holes were excluded. Catheter designs with shorter perforated lengths and more closely spaced drainage holes maintained a greater number of functionally active segments across ventricular geometries, whereas longer perforated spans were more susceptible to anatomical exclusion. These findings demonstrate that ventricular catheter drainage is governed not by catheter geometry alone, but by the interaction between catheter architecture, ventricular morphology, and surgical placement.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360313","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}
Severina Leu, Tim Hallenberger, Jonathan Rychen, Lea Pacan, Evangelia Christodoulou, Kristine Blackham, Ladina Greuter, Florian Samuel Halbeisen, Ethan Taub, Birgit Westermann, Raphael Guzman, Luigi Mariani, Jehuda Soleman
{"title":"Ultrasound-guided versus stereotactically navigated ventriculoperitoneal shunt placement: a randomized clinical trial.","authors":"Severina Leu, Tim Hallenberger, Jonathan Rychen, Lea Pacan, Evangelia Christodoulou, Kristine Blackham, Ladina Greuter, Florian Samuel Halbeisen, Ethan Taub, Birgit Westermann, Raphael Guzman, Luigi Mariani, Jehuda Soleman","doi":"10.1186/s12987-026-00833-2","DOIUrl":"10.1186/s12987-026-00833-2","url":null,"abstract":"<p><strong>Background: </strong>Accurate catheter positioning is essential for optimal outcomes in ventriculoperitoneal shunt (VPS) surgery, while shorter operative times lower infection risk and costs. Navigated VPS placement, using either intraoperative ultrasound-guided (US-G) or stereotactically guided (ST-G) navigation, enhances catheter accuracy and reduces revision rates. However, high-quality studies comparing the two navigation methods are lacking. We aim to compare surgical intervention time, accuracy, and safety of US-G to ST-G VPS placement.</p><p><strong>Methods: </strong>The Navigated VPS (NAVPS) trial was an investigator-initiated, randomized trial conducted from February 2020 to June 2024 in the Neurosurgical Department of the University Hospital of Basel. Consecutive adults undergoing VPS placement were included. Out of 153 screened participants, 134 participants were included. Participants were randomized 1:1 to receive either US-G or ST-G insertion of the ventricular catheter. The primary outcome was surgical intervention time. An intention to treat analysis was performed calculating surgical intervention time differences. Secondary outcomes were accuracy of catheter positioning, number of ventricular puncture attempts, and VPS dysfunction and complication rates. The study follow-up lasted 6 months.</p><p><strong>Results: </strong>Of 134 participants, 66 were assigned to US-G and 68 to ST-G. The mean (SD) age was 73 (55.3 to 78) and 66 (54.5 to 73) years for the US-G and ST-G, respectively, and 58 participants (45.7%) were female. The US-G group had significantly shorter surgical intervention times compared to the ST-G group (-11.5 min; 95% CI -18.5 to -4.5; P = 0.002). The number of ventricular puncture attempts was significantly higher in the US-G group, while accuracy of catheter placement, and VPS dysfunction and complications rates were comparable in both groups.</p><p><strong>Conclusions: </strong>The NAVPS trial shows US-G VPS placement to be more time-efficient, while accuracy of catheter placement and complication rates seem to be comparable to ST-G placement. US-G can be efficiently and safely used in clinical practice.</p><p><strong>Trial registration: </strong>clinicalTrials.gov Identifier: NCT04450797, date of registration: 22.06.2020.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13309968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338451","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}
Chiara Riccietti, Luisa Sambati, Corrado Zenesini, Simone Baiardi, Maria Sasca Criante, Antonella D'Apolito, David Milletti, Luca Albini-Riccioli, Barbara Polischi, Giovanna Calandra-Buonaura, Elena Magelli, Davide Mascarella, Liliana Mazza, Luca Baldelli, Michelangelo Stanzani-Maserati, Pietro Cortelli, Sabina Cevoli, Giorgio Palandri, Piero Parchi, Giulia Giannini
{"title":"Alzheimer's disease core biomarkers are associated with worse baseline and postoperative cognitive profiles in idiopathic normal pressure hydrocephalus: findings from the Bologna PRO-Hydro study.","authors":"Chiara Riccietti, Luisa Sambati, Corrado Zenesini, Simone Baiardi, Maria Sasca Criante, Antonella D'Apolito, David Milletti, Luca Albini-Riccioli, Barbara Polischi, Giovanna Calandra-Buonaura, Elena Magelli, Davide Mascarella, Liliana Mazza, Luca Baldelli, Michelangelo Stanzani-Maserati, Pietro Cortelli, Sabina Cevoli, Giorgio Palandri, Piero Parchi, Giulia Giannini","doi":"10.1186/s12987-026-00836-z","DOIUrl":"10.1186/s12987-026-00836-z","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic normal pressure hydrocephalus (iNPH) is a clinico-radiological syndrome affecting the elderly. Recent studies have reported a high prevalence of neurodegenerative copathologies in iNPH, particularly Alzheimer's disease (AD). Neuropsychological studies in iNPH sample revealed variable and heterogeneous cognitive profile. Few studies have examined cognitive differences according to neurodegenerative copathology, and none has systematically applied a comprehensive neuropsychological battery while stratifying patients by AD biomarkers both before and after surgery. The main objective of this study was to assess baseline differences in the neuropsychological profile of iNPH patients with and without AD core biomarkers, using a comprehensive neuropsychological battery. The secondary aim was to investigate changes in neuropsychological functions from baseline to short-term postoperative outcomes in the overall sample and in subgroups with and without AD biomarkers.</p><p><strong>Methods: </strong>Patients underwent a standardized inpatient work-up including clinical evaluation, comprehensive neuropsychological assessment, and cerebrospinal fluid (CSF) biomarkers analysis. A multidisciplinary team selected candidates for surgery. An extensive clinical and neuropsychological reassessment was performed six months after surgery.</p><p><strong>Results: </strong>From 2015 to 2025, 226 (97 females) consecutive iNPH patients completed the baseline evaluation. Among these, 102 shunted iNPH patients (46 females) underwent six-month postoperative neuropsychological assessment. The cognitive profile in all individuals revealed deficits in attentive-executive functions with a significant improvement after surgery. Overall, 24.3% of iNPH participants showed a pathological phosphorylated tau/beta-amyloid 1-42 ratio (pTau/Aβ42+). At baseline, pTau/Aβ42+ (n = 53) patients revealed worse neuropsychological performances than those (n = 165) with normal pTau/Aβ ratio (pTau/Aβ42-), with more pronounced memory impairment. At six-month follow-up, the pTau/Aβ42 + group exhibited poorer cognitive outcomes compared to pTau/Aβ42- one, particularly in general cognition, short- and long-term verbal and visuo-spatial memory, and executive functions.</p><p><strong>Conclusions: </strong>Nearly one-quarter of patients exhibited AD core biomarkers positivity. iNPH patients with AD core biomarkers copathology showed an earlier cognitive onset and worse neuropsychological performances at baseline. At follow-up, the pTau/Aβ42 + group demonstrated poorer cognitive outcomes in specific cognitive domains compared to the pTau/Aβ42 - group. These differences in cognitive profiles at baseline and six months after surgery in iNPH patients with AD core biomarker positivity may have clinical relevance.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307527","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}