Search Results (1,318)

Background: Thoracic endovascular aortic repair (TEVAR) has evolved the management of descending thoracic aortic disease, but neurological complications—particularly spinal cord ischemia (SCI), stroke, and postoperative delirium—remain among the most feared adverse events, adversely affecting survival, quality of life, and functional independence. Objectives: The aim of this study was to provide a contemporary narrative synthesis (2000–2025) of the incidence, mechanisms, risk factors, prevention, and management of neurological complications after TEVAR, emphasizing how current evidence supports individualized and risk-adapted strategies for prevention and management. Methods: A narrative, non-systematic search (PubMed/MEDLINE, Scopus, Cochrane Library; 2000–2025) was conducted using terms related to TEVAR, SCI, cerebrovascular events, delirium, and cognitive dysfunction. Priority was given to large registries, cohort studies, and systematic reviews in adult TEVAR populations. Results: Perioperative stroke occurs in ~2–6% of TEVAR cases, with higher rates in arch/zone 0–2 procedures and when the left subclavian artery (LSA) is covered without revascularization. SCI incidence ranges from ~2–9%, influenced by aortic extent and urgency; Vascular Quality Initiative data report SCI in 3.7% of procedures, with markedly reduced 1-year survival. Major SCI risk factors include extensive thoracic coverage, prior aortic repair, vertebral or hypogastric occlusion, emergency presentation, low perioperative mean arterial pressure, anemia, and chronic kidney disease. Postoperative delirium occurs in ~13% of TEVAR-treated type B dissections and correlates with longer hospitalization and early complications. Emerging nomograms for SCI and delirium enable individualized risk stratification. Conclusions: Neurological complications after TEVAR remain clinically significant. Contemporary evidence supports personalized prevention—selective cerebrospinal fluid (CSF) drainage, LSA revascularization, staging, neuromonitoring, and tailored hemodynamic targets—guided by anatomical complexity, comorbidities, collateral network integrity, and prior aortic history. Further research should refine prediction tools, standardize definitions, and evaluate individualized neuroprotective bundles. Full article

Background: Cefiderocol, a siderophore cephalosporin, is approved for the treatment of infections caused by multi-drug-resistant Gram-negative bacteria (MRGN). At present, few data are available on the pharmacokinetics of this substance in critically ill patients, particularly for the treatment of central nervous system infections. Patients and Methods: Here, we reported on a 22-year-old male patient after severe open head trauma. Initial screening revealed colonization with 4MRGN A. baumannii (OXA-23) (perianal) and 4MRGN K. pneumoniae (KPC) (tracheal). Unfortunately, he developed ventriculitis (4MRGN A. baumannii). According to microbiological testing, the patient with normal renal function received 3 × 2 g/d i.v. cefiderocol as a prolonged infusion (3 h) and colistin 3 × 3 Mio. IU/d i.v. for 2 weeks. In addition to serum trough levels, drug monitoring was performed in the cerebrospinal fluid (CSF) via external ventricular drainage (24 h aliquots). Results: Serum and CSF specimens analyzed by liquid chromatography–mass spectroscopy (LC-MS) in the presence of severe meningeal inflammation yielded average CSF concentrations of cefiderocol from 5.48 to 8.40 (median 6.98) μg/mL and a concentration ratio C_{CSF mean}/C_{serum trough} from 0.38 to 0.76 (median 0.48). The cefiderocol levels in the CSF were sufficient for eradication of A. baumannii. A subsequent CSF infection with K. pneumoniae (found initially in screening and resistant to cefiderocol) after completed treatment with cefiderocol was successfully treated with gentamicin (intrathecally) and ceftazidime/avibactam (i.v.). However, the patient died due to a Candida tropicalis infection detected in the CSF on day 71. Conclusions: Our results indicate that standard dosages of cefiderocol are sufficient for treatment of CNS infections in the presence of a severe disruption of the blood–CSF barrier. Full article

Background/Objectives: Relapsed and refractory (rr) primary large B-cell lymphoma of the central nervous system (PCNSL) has a dismal prognosis, and the standard of care is not established. The most common genetic imbalance includes the B-cell lymphoma 2 (BCL-2) locus. Methods: We planned a bi-centric phase Ib dose-escalation study with the chemotherapy-free combination of the BCL-2 inhibitor venetoclax and CD20 antibody obinutuzumab for rrPCNSL patients in Germany. The intended treatment consisted of 6 cycles of fixed-dose obinutuzumab at 1000 mg intravenously every 3 weeks, and an oral daily dose of 600, 800, or 1000 mg venetoclax, depending on the planned dosing group, followed by a 12-month venetoclax maintenance period. The primary endpoint was the pharmacokinetics of venetoclax and obinutuzumab in cerebrospinal fluid (CSF). Results: This study was prematurely terminated after registration of 5/15 (33%) patients in dosing group 1 (600 mg oral daily dose of venetoclax) between May 2020 and November 2021. The mean ratio of the concentration of venetoclax in CSF over peripheral blood was 0.55% (±0.28 standard deviation (SD)) and 0.25% (±0.23 SD) for obinutuzumab. Two of five patients achieved complete remission, and each one patient achieved partial remission and stable disease as best response. The median duration of response was 6.5 months (range 0.7–47). Conclusions: Venetoclax and obinutuzumab can penetrate into the central nervous system, but the CSF concentration did not correlate with the outcome. The combination is feasible, tolerable, and may lead to durable responses in selected rrPCNSL patients. Full article

Subarachnoid hemorrhage (SAH) due to ruptured cerebral aneurysms is the most severe form of stroke, and treatment outcomes remain poor. Brain damage after SAH can be broadly divided into early brain injury (EBI) and delayed cerebral ischemia (DCI). Although the causes of these events are multifactorial, free hemoglobin generated after hemolysis in the subarachnoid space is believed to be one of the most important causative factors. Recently, cerebral lymphatic vessels, previously thought to be non-existent, have been identified, suggesting their involvement not only in maintaining homeostasis but also in brain injury. Furthermore, new findings have been reported regarding cerebrospinal fluid (CSF) circulation. Because intracranial CSF circulation and lymphatic drainage to the extracranial blood and lymphatic vessels affect free hemoglobin metabolism in the CSF, these factors are likely to affect EBI and DCI. In addition, matricellular protein tenascin-C, which we have reported to be involved in the pathogenesis of EBI and DCI, has been reported to inhibit lymphatic vessel proliferation in non-central nervous system pathologies. However, the relationship between post-SAH brain injury and intracranial lymphatics remains unknown. This review aimed to summarize recent findings regarding intracranial lymphatics and CSF circulation and to discuss how they may affect post-SAH pathology. Full article

The flow behavior of fluids can be characterized by rheology and is especially used in the field of polymeric materials. This study focused on characterizing cerebrospinal fluid (CSF) of patients who developed hydrocephalus after subarachnoid hemorrhage (SAH) with rheology. Samples were drawn from an external ventricular drainage (EVD) at four pre-defined time points after the initial hemorrhage. The CSF samples were analyzed using a rotational rheometer with a double gap geometry. In addition to the characterization of viscoelastic parameters, the cumulative storage factor was calculated to determine the interactions in the fluid. In order to investigate the temperature dependence of the CSF properties, the oscillatory measurements were implemented at certain temperatures that simulated specific conditions, such as 5 °C, at which temperature the CSF samples were stored; 35 °C for hypothermic conditions; 37 °C for physiologic conditions; and 40 °C for elevated body temperature. The overall goal was to evaluate whether rheology-based parameters may help in the prediction of shunt dependence for post-hemorrhagic hydrocephalus patients. For this aim, rheological parameters were correlated to certain laboratory parameters, such as erythrocyte and leukocyte count, glucose, lactate, and total protein concentration. Full article

Objectives: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis that can lead to severe neurological impairments, particularly in pediatric patients. Effective biomarkers for diagnosis and prognosis are crucial for improved treatment outcomes. To evaluate the potential of soluble Triggering Receptor Expressed on Myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) and serum as diagnostic and prognostic biomarkers in pediatric patients with anti-NMDAR encephalitis. Methods: The study included 21 children diagnosed with anti-NMDAR encephalitis and 27 children with non-inflammatory neurological disorders (OND) as controls. CSF and serum samples were collected from each patient. sTREM2 levels were measured using enzyme-linked immunosorbent assay (ELISA). Statistical analyses, including Mann–Whitney U test and ROC curve analysis, were performed to assess the diagnostic and prognostic value of sTREM2. Results: sTREM2 levels in CSF and serum were significantly higher in children with anti-NMDAR encephalitis compared to the OND group (p < 0.001). CSF sTREM2 levels showed a positive correlation with modified Rankin Scale (mRS) scores and a negative correlation with Glasgow Coma Scale (GCS) scores, suggesting an association with disease severity. ROC curve analysis demonstrated that CSF sTREM2 had a high diagnostic accuracy (AUC = 0.887, p < 0.001), while serum sTREM2 showed a slightly lower diagnostic accuracy (AUC = 0.848, p < 0.001). Patients with better prognoses had significantly lower CSF sTREM2 levels than those with poorer outcomes (p = 0.029). Conclusions: Elevated CSF sTREM2 levels were associated with increased neuroinflammation and poorer clinical outcomes in children with anti-NMDAR encephalitis. These findings suggest that CSF sTREM2 may serve as a valuable biomarker for the diagnosis and prognosis of pediatric anti-NMDAR encephalitis. Full article

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline, synaptic dysfunction, and the accumulation of amyloid plaques and neurofibrillary tangles. While prior research has focused mainly on protein aggregation and neuroinflammation, emerging evidence suggests that ionic imbalances, particularly involving sodium (Na⁺) and potassium (K⁺), may contribute to AD progression. Na⁺ and K⁺ are critical for maintaining neuronal membrane potential, regulating action potential firing, and supporting neurotransmitter function. Although studies primarily focused on absolute Na⁺ concentrations, the Na⁺/K⁺ ratio may provide a more sensitive marker of ionic dysregulation. Given that the Na⁺/K⁺ gradient is actively maintained by the Na⁺/K⁺-ATPase pump—a target known to be vulnerable in AD—we hypothesized that the Na⁺/K⁺ ratio is altered in AD. We analyzed postmortem tissue from the prefrontal cortex, thalamus, and cerebrospinal fluid (CSF) of 97 human subjects (67 AD, 30 controls). AD cases exhibited a significant increase in the Na⁺/K⁺ ratio in the thalamus and CSF, driven primarily by elevated Na⁺ levels. The Na⁺/K⁺ ratio positively correlated with Braak tangle stage, suggesting an association with AD progression. These findings provide novel insights into ionic dysregulation in AD and suggest that the Na⁺/K⁺ ratio in the CSF may serve as a valuable biomarker for disease severity and progression. Future research should explore the potential of targeting ionic homeostasis as a therapeutic strategy in AD. Full article

Background/Objectives: Speech difficulties are an early and disabling manifestation of Parkinson’s disease (PD), affecting communication and quality of life. This study aimed to examine demographic, clinical, dopaminergic imaging and cerebrospinal fluid (CSF) correlates of speech difficulties in early PD, comparing treatment-naïve and levodopa-treated patients. Methods: A cross-sectional analysis was conducted using data from the Parkinson’s Progression Markers Initiative (PPMI). The sample included 376 treatment-naïve and 133 levodopa-treated early PD participants. Speech difficulties were defined by Movement Disorder Society—Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III, with Item 3.1 ≥ 1. Group comparisons and binary logistic regression identified predictors among demographic, clinical, dopaminergic and CSF biomarker variables, including [¹²³I]FP-CIT specific binding ratios (SBRs). All analyses were cross-sectional, and findings reflect associative relationships rather than treatment effects or causal mechanisms. Results: Speech difficulties were present in 44% of treatment-naïve and 57% of levodopa-treated participants. In both cohorts, higher MDS-UPDRS Part III ON scores—reflecting greater motor severity—and lower mean putamen SBR values were significant independent predictors of speech impairment. Age was an additional predictor in the treatment-naïve group. No significant differences were found in CSF biomarkers (α-synuclein, amyloid-β, tau, phosphorylated tau). These findings indicate that striatal dopaminergic loss, particularly in the putamen, and motor dysfunction relate to early PD-related speech difficulties, whereas CSF neurodegeneration markers do not differentiate affected patients. Conclusions: Speech difficulties in early PD are primarily linked to dopaminergic and motor dysfunction rather than global neurodegenerative biomarker changes. Longitudinal and multimodal studies integrating acoustic, neuroimaging, and cognitive measures are warranted to elucidate the neural basis of speech decline and inform targeted interventions. Full article

Glioblastoma (GBM) remains one of the most treatment-resistant human malignancies, largely due to the interplay between disrupted fluid dynamics, immune evasion, and the structural complexity of the tumor microenvironment; in addition to these, treatment resistance is also driven by intratumoral heterogeneity, glioma stem cell persistence, hypoxia-induced metabolic and epigenetic plasticity, adaptive oncogenic signaling, and profound immunosuppression within the tumor microenvironment. Emerging evidence shows that dysfunction of the glymphatic system, mislocalization of aquaporin-4, and increased intracranial pressure compromise cerebrospinal fluid–interstitial fluid exchange and impair antigen drainage to meningeal lymphatics, thereby weakening immunosurveillance. GBM simultaneously remodels the blood–brain barrier into a heterogeneous and permeable blood–tumor barrier that restricts uniform drug penetration yet enables tumor progression. These alterations intersect with profound immunosuppression mediated by pericytes, tumor-associated macrophages, and hypoxic niches. Advances in imaging, including DCE-MRI, DTI-ALPS, CSF-tracing PET, and elastography, now allow in vivo characterization of glymphatic function and interstitial flow. Therapeutic strategies targeting the fluid-immune interface are rapidly expanding, including convection-enhanced delivery, intrathecal and intranasal approaches, focused ultrasound, nanoparticle systems, and lymphatic-modulating immunotherapies such as VEGF-C and STING agonists. Integrating barrier modulation with immunotherapy and nanomedicine holds promise for overcoming treatment resistance. Our review synthesizes the mechanistic, microenvironmental, and translational advances that position the glymphatic–immune axis as a new frontier in glioblastoma research. Full article

Objective: Alzheimer’s disease (AD) and other forms of dementia are a heterogeneous group of neurodegenerative diseases characterized by progressive cognitive decline. Differential diagnosis between AD and other dementias is crucial for choosing the optimal treatment strategy. Currently, cerebrospinal fluid (CSF) analysis remains the most accurate diagnostic method, but its invasiveness limits its use. In this regard, the search for reliable biomarkers in the blood is an urgent task. Methods: The study included 31 dementia patients (23 women and 8 men) diagnosed via interdisciplinary consultations and neuropsychological testing (MMSE ≤ 24). CSF and blood plasma samples were collected and analyzed using Luminex technology. Biomarker concentrations were measured, and statistical analyses (ANOVA, Kruskal–Wallis, and Pearson correlation) were performed to compare groups and assess correlations. Results: Levels of Aβ40 and Aβ42 in CSF were significantly lower in patients with AD compared with non-AD dementia (p = 0.02 and p < 0.001, respectively). The Aβ42/40 ratio in CSF was higher in patients with non-AD dementia (p = 0.048). The concentration of Aβ42 in blood plasma was increased in patients with AD (p = 0.001). Positive correlations were found between Aβ42 in CSF and TDP-43 in plasma in non-AD dementia (r = 0.97, p < 0.001), as well as between neurogranin and TDP-43 in plasma in AD (r = 0.845, p < 0.001). Conclusions: The study demonstrates the potential of blood biomarkers, in particular Aβ42, for the differential diagnosis of AD and other forms of dementia. The discovered correlations between CSF and plasma biomarkers deepen the understanding of neurodegenerative processes and contribute to the development of noninvasive diagnostic methods. Full article

Neurogenesis is tightly regulated by complex interactions among neural stem and progenitor cells (NSCs/NPCs), blood vessels, microglia, and extracellular matrix components within the neurogenic niche. In the embryonic brain, NSCs reside along the ventricular surface, where cerebrospinal fluid (CSF) directly regulates their proliferation. Here, we identify Akhirin (AKH) as a critical regulator that preserves the integrity of the NSC niche during mouse brain development. At embryonic day 14.5, AKH is secreted and enriched at the apical surface of choroid plexus epithelial cells and the ventricular lining. Loss of AKH leads to increases the inflammatory cytokine expression in the CSF and disrupts NSC niche homeostasis. Furthermore, AKH is cleaved upon inflammatory stimulation, and its LCCL domain directly binds bacteria, thereby preventing their spread. These findings reveal that AKH functions as a protective barrier molecule within the developing neurogenic niche, providing immune protection and preserving NSC niche homeostasis during periods when the innate immune defenses are still immature. Full article

Background/Objectives: The latest National Comprehensive Cancer Network (NCCN) Central Nervous System (CNS) Guidelines recommend utilizing next-generation sequencing (NGS) to enable comprehensive genomic profiling (CGP) as the preferred approach for molecular characterization of central nervous system (CNS) malignancies. CNS malignancies present distinct challenges due to the infeasibility of tissue-based testing for many patients and the restrictive nature of the blood–brain barrier (BBB) making plasma-based liquid biopsy an ineffective alternative. Recent advances in liquid biopsy have extended molecular testing beyond plasma to include cerebrospinal fluid (CSF), which serves as a valuable source for tumor-derived nucleic acids. Methods: The Belay Summit™ 2.0 is a high-throughput CGP assay capable of detecting multiple variant types, including single nucleotide variants (SNVs) and small insertion and deletions (Indels), copy number variations (CNVs), gene fusions, splice variants, and immunotherapy biomarkers such as microsatellite instability (MSI) and tumor mutational burden (TMB). This study details the analytical and clinical validation of Summit™ 2.0 to assess its technical performance and clinical sensitivity. Analytical validation was conducted using 68 specimens, demonstrating robust and reproducible detection of all variant types with 15 ng of CSF-derived total nucleic acid (tNA). Results: The analytical sensitivity of the Belay Summit™ 2.0 assay for SNVs and Indels was determined to be 96.7% with a 100% limit of detection (LoD) at a variant allele frequency of 0.3%. Clinical validity was evaluated across a cohort of 118 CSF specimens, including both primary and metastatic CNS tumors, demonstrating 96% sensitivity and 98% specificity. Conclusions: These findings support the use of the Belay Summit™ 2.0 assay for accurate and reproducible genomic profiling of CNS tumors using tumor-derived nucleic acids from CSF in patients for whom tissue-based testing is considered infeasible, unsafe, or not deemed by the prescribing physician to be clinically appropriate. Full article

Preeclampsia (PE) is the onset of hypertension in pregnancy with systemic involvement; PE poses significant risks of cerebral complications, including eclampsia and long-term cognitive impairment. This review explores the potential of neurological biomarkers—neurofilament light chain (NfL), neuron-specific enolase (NSE), S100 Calcium Binding Protein B (S100B), and tau—as indicators of cerebral injury in PE. A literature search identified studies comparing biomarker levels in preeclamptic and healthy pregnancies. Findings reveal elevated plasma levels of NfL, NSE, S100B, and Tau in PE, with NfL showing the strongest association with blood–brain barrier dysfunction, cognitive symptoms, and disease severity. Variations between plasma and cerebrospinal fluid levels suggest impaired BBB integrity rather than increased central nervous system production. Despite promising correlations, limitations include small sample sizes, lack of standardized thresholds, and limited CSF data. While NfL emerges as a particularly promising marker for risk stratification, further research is needed to validate the clinical utility of these biomarkers in routine PE management. Full article

Background and Clinical Significance: Cerebral candidiasis (Candida albicans meningoencephalitis) is a rare but severe central nervous system (CNS) infection, usually associated with neurosurgical procedures or indwelling devices. Diagnosis is challenging due to frequent negativity of cerebrospinal fluid (CSF) cultures, and mortality remains high despite antifungal therapy. Case Presentation: We describe a 64-year-old woman who underwent retrosigmoid resection of a left vestibular schwannoma. The early postoperative course was complicated by fever, neurological deterioration, and hydrocephalus requiring external CSF drainage. Multiple lumbar punctures revealed inflammatory CSF profiles but persistently negative cultures. One month post-surgery, intraoperative samples from mastoid repair material grew Candida albicans, prompting antifungal therapy. Despite treatment, the patient experienced fluctuating neurological status and required multiple external ventricular drains. Three months after surgery, she clinically deteriorated and died. Autopsy showed diffuse meningeal thickening and purulent exudates at the brain base and posterior fossa. Histopathology confirmed chronic lympho-histiocytic meningitis with necrotizing foci containing Candida albicans. Conclusions: This case underscores the diagnostic and therapeutic challenges of post-neurosurgical Candida CNS infections. Repeatedly negative CSF cultures delayed diagnosis, emphasizing the value of ancillary tests such as β-d-glucan and molecular assays. Even with antifungal therapy, prognosis is poor. Autopsy remains essential for uncovering fatal healthcare-associated fungal infections and informing clinical vigilance and medico-legal assessment. Full article

Cerebrospinal fluid (CSF) is a key biological matrix that reflects the physiological and pathological states of the central nervous system (CNS). It supports brain function by regulating ionic balance, facilitating molecular transport, and clearing metabolic waste. In this article, we present a standardized protocol for CSF collection along with an integrative multiplatform metabolomic workflow that combines proton nuclear magnetic resonance spectroscopy (¹H-NMRS) and high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS). Integrating these complementary analytical modalities enhances metabolite coverage and improves analytical robustness, enabling a more comprehensive and reliable characterization of the CSF metabolome. This workflow supports the discovery of potential biomarkers and advances our understanding of neurochemical alterations within the CNS. Full article