Search Results (2,377)

Tethered cord syndrome (TCS) is a disease caused by pathological fixation of the spinal cord, most commonly due to a thickened filum terminale, postoperative adhesions, or congenital dysraphism. Progressive neurological, urological, and orthopedic manifestations result from chronic cord traction and impaired vascular supply. Surgical detethering remains the standard treatment, with the classic intradural sectioning of the filum terminale being the most widely used technique. Recent developments, however, include minimally invasive tubular and endoscopic approaches, spinal column shortening procedures for recurrent or complex cases, and extradural detethering strategies. Each technique aims to reduce cord tension while minimizing postoperative complications, particularly cerebrospinal fluid leakage and retethering. This review summarizes the anatomical background, pathophysiology, and operative strategies for TCS, highlighting current evidence, technical nuances, and limitations of emerging minimally invasive and alternative approaches. Full article

Candida dubliniensis is an opportunistic yeast closely related to Candida albicans and an uncommon cause of central nervous system (CNS) infection. While isolates are often susceptible to azoles, reduced susceptibility or acquired resistance may occur, making species identification and antifungal susceptibility testing clinically relevant. We report a 3-year-old boy with Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia (ALL) in hematologic remission who developed chronic meningitis during maintenance chemotherapy. The initial presentation was non-specific (marked somnolence without fever or meningeal signs) and lumbar puncture performed to exclude CNS relapse revealed neutrophil-predominant pleocytosis and elevated protein; the cerebrospinal fluid (CSF) culture grew C. dubliniensis. Treatment with intravenous liposomal amphotericin B followed by prolonged fluconazole led to clinical improvement and sterile CSF. Six months later, progressive gait disturbance, limb pain, and episodic severe headaches recurred; repeat CSF cultures again yielded C. dubliniensis, with a changed susceptibility profile. Spine MRI demonstrated leptomeningeal enhancement involving the cauda equina nerve roots. Intravenous voriconazole with therapeutic drug monitoring was initiated and combined with intrathecal liposomal amphotericin B (seven doses, dose-escalated up to 3 mg), which was well tolerated and associated with rapid neurologic improvement, CSF sterilization, and radiologic resolution. At 12 months of follow-up, the patient remained infection-free and in leukemia remission. This case highlights that C. dubliniensis chronic meningitis may present subtly yet progress, requiring repeated CSF cultures with susceptibility testing; intrathecal liposomal amphotericin B can be a safe and effective adjunct to systemic therapy in refractory or recurrent disease. Full article

Creutzfeldt–Jakob disease (CJD) is a rare and still fatal neurodegenerative disorder caused by prion protein misfolding in the central nervous system. Accumulation of the pathogenic isoform leads to neuronal damage, spongiform degeneration, and rapidly progressive dementia. The disease is divided into sporadic, familial, iatrogenic, and variant forms, with sporadic cases accounting for the majority of cases. Diagnosis remains challenging and relies on a combination of clinical assessment, neuroimaging, and laboratory biomarkers. Key diagnostic methods include electroencephalography, Magnetic Resonance Imaging, and cerebrospinal fluid analysis for proteins as well as advanced amplification tests that improve diagnostic accuracy. Despite these advances, early detection remains challenging and misdiagnosis can occur. Currently, there is no effective disease-modifying therapy, and treatment is primarily supportive, focusing on symptom control and palliative care. Ongoing research aims to better understand the molecular mechanisms underlying prion propagation and develop targeted therapeutic strategies. This review summarizes current diagnostic methods and therapeutic approaches, focusing on molecular applications and their potential clinical implications. Full article

Ceftobiprole is a fifth-generation beta-cephalosporin with high inter-individual pharmacokinetic variability in critically ill patients. However, data on its pharmacokinetics and central nervous system (CNS) penetration are limited. This study developed and validated a rapid LC-MS/MS method for quantifying ceftobiprole in human plasma and CSF. Sample preparation involved protein precipitation of 50 µL aliquots. Analysis used gradient elution on an ACQUITY UPLC^® HSS T3 column (2.1 × 100 mm, 1.8 µm) with 0.2% formic acid and acetonitrile and was detected by positive ion electrospray, achieving a 3.5 min run time. The method was linear from 0.100 to 25.0 mg/L in plasma and 0.0500 to 15.0 mg/L in CSF. Intra- and inter-run precision and accuracy were within ±15% at all quality control levels. All validation parameters, including selectivity, matrix effects, recovery, and stability under various conditions, met acceptance criteria. Potential interference from the prodrug ceftobiprole medocaril was evaluated and found to be negligible. The method was successfully applied to samples from three patients, revealing a CSF penetration range of 11.9% to 36.5%. This validated LC-MS/MS method enables simple and rapid quantification of ceftobiprole in plasma and cerebrospinal fluid, filling the gap in data on its CNS penetration and supporting routine drug concentration monitoring in critically ill patients. Full article

Background and Objectives: Visual evoked potentials (VEPs) are a simple, noninvasive method for detecting subclinical visual pathway involvement in multiple sclerosis. This study investigated the frequency of VEP abnormalities and their associations with baseline clinical, radiological, and cerebrospinal fluid (CSF) features in treatment-naïve patients with clinically isolated syndrome (CIS) or early relapsing-remitting multiple sclerosis (RRMS) without prior optic neuritis. Materials and Methods: We retrospectively reviewed newly diagnosed, treatment-naïve CIS/early RRMS patients evaluated between January 2022 and July 2024 who underwent CSF analysis. Pattern-reversal VEPs were recorded under standardized conditions. VEP abnormalities were analyzed as any or bilateral, and associations were assessed using group comparisons and multivariable logistic regression. Results: In 101 patients (mean age 31.8 ± 9.7 years; 72% female; median EDSS 1.0), latency prolongation occurred in 69 (42 any,27 bilateral) and amplitude reduction in 33 (22 any, 11 bilateral). Among patients with latency prolongation, both the number of OCB bands and the IgG index were higher (bilateral p = 0.032; any p = 0.007). In multivariable analysis, male sex (p = 0.032) and pyramidal/brainstem-onset presentation (p = 0.006) were independently associated with any amplitude reduction; neither was associated with latency abnormalities. Conclusions: VEP abnormalities are common early in the disease, even without a history of optic neuritis. Male sex and pyramidal/brainstem-onset presentation were associated with reduced amplitude, suggesting that amplitude decrease may reflect early tissue dysfunction and may be related to adverse baseline clinical features. Associations between intrathecal immune activation and prolonged latency may indicate subclinical demyelination of the visual pathways related to inflammatory activity. Larger longitudinal studies are needed to clarify the clinical significance of VEP abnormalities in early RRMS. Full article

Introduction: The majority of progressive multifocal leukoencephalopathy (PML) cases is still represented by patients affected by acquired immunodeficiency syndrome (AIDS). Diagnosis of PML relies on histopathological findings or by the combination of clinical signs, radiological evidence, and molecular positivity of the JC virus in cerebrospinal fluid. However, AIDS status predisposes to various diseases involving the brain, testing the diagnostic ability of the clinician. Case description: We describe a PML case in a patient with AIDS, in whom lumbar puncture was initially impossible for severe thrombocytopenia and magnetic resonance showed an hyperintense lesion and was unable to distinguish between PML and lymphoma. In this case, [¹⁸F]-fluorodeoxyglucose (FDG)-PET imaging showing a hypometabolism of the lesion helped to initially orient toward PML, as diagnosis was later confirmed by lumbar puncture. We collected 21 cases in the literature in which [¹⁸F]-FDG-PET was helpful in cases of PML. Discussion and Conclusions: PET imaging is not considered a standard diagnostic tool for PML. However, in selected cases, it may provide valuable information to direct the diagnosis towards PML. Full article

Frontal sinus fractures typically reflect high-energy trauma and must be evaluated and treated carefully to avoid long-term problems including contour deformity, sinus dysfunction, cerebrospinal fluid (CSF) leakage, chronic sinusitis, and mucocele formation. This article outlines frontal sinus anatomy, diagnostic pathways, and evolving treatment concepts in detail. An anatomically driven treatment algorithm is emphasized, with a focus on preservation of sinus function whenever possible and preference for conservative management. Advanced procedures, such as endoscopic sinus surgery and cranialization, are reviewed in the context of managing more severe injuries. Key points: (1) Clinical decision-making in the management of frontal sinus fractures is best guided by evaluating the status of the anterior table, posterior table, and nasofrontal outflow tract, with treatment options ranging from nonoperative care to open or endoscopic surgery. (2) Improvements in endoscopic techniques, combined with evidence supporting less aggressive strategies, have shifted management toward more conservative approaches, reserving open procedures for higher-grade injuries. (3) Extended follow-up is essential to identify delayed problems such as mucoceles, chronic sinusitis, frontal bone osteomyelitis, and contour irregularities. Full article

Background: The optimal timing of cranioplasty (CP) after decompressive craniectomy (DC) remains debated. Early reconstruction may enhance neurological recovery through restoration of cerebral perfusion and cerebrospinal fluid dynamics, yet concerns persist regarding postoperative complications. Objective: To evaluate the impact of early versus delayed cranioplasty on neurological outcomes and postoperative complications in adults following decompressive craniectomy. Methods: A systematic review was conducted in accordance with PRISMA guidelines (PROSPERO ID: CRD420251123808). PubMed, OVID, and Web of Science were searched for studies published between January 2017 and December 2025. Eligible studies compared early and delayed CP in adults and reported neurological outcomes and/or complications. Results: Twenty-one retrospective cohort studies including 8462 patients were analyzed. Neurological improvement was observed in both groups across multiple validated scales (GOSE, GOS, GCS, mRS, BI, FIM, NIHSS, MMSE). Early CP was consistently associated with superior recovery, including higher one-year Barthel Index improvement (74.1% vs. 54.8%), greater FIM gains (7.31% vs. 4.66%), and higher composite recovery rates (95.6% vs. 80.0%). No study demonstrated superior recovery with delayed CP. Infection, hydrocephalus, and seizure rates were comparable between groups. However, hematoma (21% vs. 10.4%) and hygroma (7.49% vs. 4.73%) were more frequent after early CP, although hematoma rates were influenced by a large database study. Bone flap resorption was less frequent with early CP (1.44% vs. 6.26%). Conclusions: Early cranioplasty is associated with improved neurological recovery but carries an increased risk of select complications, particularly hematoma and hygroma, representing a clinically relevant trade-off. Delayed CP does not demonstrate overall superior safety due to higher bone flap resorption. Timing should be individualized, and prospective multicenter studies with standardized definitions are needed. Full article

Background/Objectives: Healthcare-associated ventriculitis and meningitis (HAVM) is a life-threatening complication of neurosurgical procedures. Conventional cerebrospinal fluid (CSF) indices cannot reliably distinguish bacterial infection from sterile postoperative inflammation, and cultures are frequently delayed or negative. We conducted the first systematic review and meta-analysis to determine the pooled diagnostic accuracy of CSF heparin-binding protein (HBP) for HAVM and to establish clinically actionable decision thresholds. Methods: PubMed, Embase, the Cochrane Library, and China National Knowledge Infrastructure were searched from inception to 15 February 2026. Risk of bias was assessed using QUADAS-3. Sensitivity and specificity were pooled with a bivariate random-effects model, and heterogeneity was explored through subgroup analyses and metaregression. Thresholds were derived using likelihood ratio (LR)-based and diagmeta cutoff modeling. Results: Twelve studies (n = 1761) were included. Pooled sensitivity was 0.861 (95% confidence interval [CI]: 0.777–0.917) and specificity was 0.848 (95% CI: 0.781–0.897), with a positive LR (LR+) of 5.65 and a negative LR (LR−) of 0.164. At a 50% pretest probability, post-test probability was increased to 85% by a positive result and reduced to 14% by a negative result. Intracerebral hemorrhage cohorts showed lower accuracy (sensitivity: 0.675, specificity: 0.755), whereas brain tumor-predominant cohorts demonstrated the highest performance (sensitivity: 0.935, specificity: 0.922; p = 0.017). Thresholds of ≥41.3 (rule-in; LR+ ≥10) and ≤30.1 ng/mL (rule-out; LR− ≤0.1) defined clinically actionable decision zones. Conclusions: CSF HBP provides quantitatively defined rule-in and rule-out thresholds that meaningfully shift the post-test probability and may support antimicrobial decision-making in suspected HAVM. Prospective multicenter validation is warranted. Full article

Diagnosis of atypical parkinsonian syndromes (APS), including progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), rely on clinical criteria that often result in misclassification or delayed confirmation. Cerebrospinal fluid (CSF) metabolomics offers the potential to identify disease-specific biochemical “fingerprints”. The aim of the study is to identify CSF metabolomic biomarkers that distinguish PSP and MSA from each other and from non-neurodegenerative controls. Targeted mass spectrometry-based metabolomics was performed on CSF samples from 30 patients with MSA, 41 with PSP, and 30 age- and sex-matched non-neurodegenerative controls. Global metabolomic profiles showed no clear group separation. Both PSP and MSA showed elevated gut-derived metabolites p-cresyl sulfate and deoxycholic acid versus controls. In PSP, decreased cortisone and increased hexosylceramide d18:1/24:1 were observed, whereas in MSA, dihydroxyphenylalanine was elevated alongside homoarginine and creatinine. In the direct comparison of APS, levels of α-aminoadipic acid were increased in PSP compared to MSA. Pathway analysis highlighted disrupted glycerophospholipid metabolism in both APS disorders. Distinct metabolite panels mainly combining membrane-associated lipids, gut-derived and neurotransmitter-related metabolites demonstrated high diagnostic accuracy for distinguishing PSP and MSA from control groups (AUC = 0.95 for PSP and AUC = 0.98 for MSA), while a separate panel showed moderate performance in differentiating PSP from MSA (AUC = 0.85). Distinct but partially overlapping CSF metabolomic profiles characterize PSP and MSA. These metabolomic fingerprints highlight gut–brain axis involvement, alterations in cell membrane-related lipid metabolism, and disease-specific changes in neurotransmitter-related metabolites. Further, a panel of these metabolites showed strong potential as diagnostic biomarkers. Full article

Alzheimer’s disease (AD) is the most common form of dementia marked by cognitive decline and memory loss. Early detection is essential for timely intervention; however, traditional biomarkers, including cerebrospinal fluid (CSF) assays, neuroimaging, and cognitive assessments, are limited by cost, invasiveness, and accessibility. Digital biomarkers, obtained from wearable sensors, smartphone applications, speech analysis, and other passive monitoring technologies, represent a promising alternative for scalable, non-invasive, and continuous assessment of early cognitive decline. This paper provides a comprehensive review of the current landscape of digital biomarkers for AD diagnosis, emphasizing their potential application in the preclinical and prodromal stages of the disease. In addition, a bibliometric analysis demonstrates the rapid expansion of digital biomarker research, highlighting key trends in publication volume, influential authors, institutions, and interdisciplinary collaborations. Despite the significant promise of digital biomarkers, challenges remain regarding validation, regulatory approval, data privacy, and integration into clinical practice. The results indicate that future research should prioritize standardization, multimodal biomarker integration, and large-scale longitudinal studies to fully realize the potential of digital technologies in AD detection. Full article

Aim: This study investigates how Buyang Huanwu Decoction (BHD) protects against cerebral ischemic damage by targeting the NLRP3/Caspase-1 pathway. Methods: The fingerprint of BHD was analyzed by HPLC-UV. Migratory chemicals in BHD-containing cerebrospinal fluid (BHD-CCSF) were analyzed by ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS). The effects of BHD on the NLRP3/Caspase-1 pathway, IL-18 and IL-1β levels in oxygen and glucose deprivation/reperfusion (OGD/R) cells were assessed by Western blot and ELISA. Cerebral infarction severity in permanent middle cerebral artery occlusion (pMCAO) mice was assessed by mNSS scores and staining. Protein and mRNA levels of the NLRP3/Caspase-1 pathway and inflammatory factors (IL-18, IL-1β) were measured. Results: BHD-containing serum (BHD-CS), BHD-CCSF, and Calycosin (Cal) reduced NLRP3, Caspase-1, ASC, GSDMD proteins, IL-18 and IL-1β in OGD/R cells. In pMCAO mice, BHD decreased pathway-related proteins and mRNA and inflammatory factors and alleviated brain injury. Conclusions: BHD ameliorates cerebral ischemia by inhibiting the NLRP3/Caspase-1 pathway, thereby suppressing pyroptosis and inflammation. Full article

Circulating tumour DNA (ctDNA) assays are increasingly applied in haematological malignancies for non-invasive genotyping, quantitative response assessment, measurable residual disease (MRD) detection, and relapse surveillance, often complementing bone marrow-based testing and, in selected scenarios, potentially reducing its frequency. Yet, translating ctDNA results into comparable clinical decisions across laboratories, platforms, and time remains challenging because ctDNA measurements are influenced by the definition of the measurand (for example, variant allele fraction versus mutant molecules per mL), pre-analytical variables, end-to-end workflow losses, and lineage-specific confounders such as clonal haematopoiesis of indeterminate potential (CHIP), therapy-related clonal haematopoiesis, and compartmental disease (marrow, plasma, cerebrospinal fluid, extramedullary sites). This review proposes a harmonisation framework for haematological ctDNA based on three linked concepts—metrological traceability, which connects reported values to reference systems with stated uncertainty, commutability, which ensures that reference materials behave like patient specimens across diverse workflows and fit-for-purpose reference materials that support calibration, and quality control, external quality assessment, and cut-off setting for intended uses such as early molecular response in large B-cell lymphoma, molecular MRD in acute myeloid leukaemia, and deep response monitoring in multiple myeloma. This framework is accompanied by harmonised CHIP-aware reporting rules for settings without matched cellular DNA and practical change-control/bridging strategies to preserve clinical decision thresholds when platforms or bioinformatic pipelines evolve. Full article

The discovery of the glymphatic system (GS) transformed understanding of central nervous system homeostasis by revealing a brain-wide network that facilitates cerebrospinal and interstitial fluid exchange along perivascular pathways. This system clears metabolic waste and maintains the precise ionic environment required for neuronal function through the coordinated action of astrocytic aquaporin-4 channels and intact perivascular architecture. Glioblastoma multiforme (GBM), the most aggressive primary brain tumor in adults, alters physiological barriers through pathological angiogenesis, compression of perivascular spaces, depolarization of aquaporin-4 at astrocytic endfeet, and obstruction of venous and lymphatic drainage. This narrative review synthesizes current experimental and clinical literature identified through targeted searches of PubMed and Scopus to examine interactions between glioblastoma, glymphatic system dysfunction, and tumor microenvironmental changes. To minimize selection bias, studies were categorized according to evidence source and experimental design. Evidence from rodent models and advanced imaging demonstrates as tumor growth impairs glymphatic function, the resulting dysfunction promotes tumor progression by enabling accumulation of pro-tumorigenic growth factors, inflammatory mediators, and acidic metabolites, while elevated interstitial fluid pressure limits drug delivery. Impaired antigen drainage further diminishes immune surveillance, contributing to the immunosuppressive microenvironment that limits immunotherapy efficacy. A critical evaluation of these mechanisms highlights how the glymphatic system influences disease progression and suggests novel avenues for diagnostic imaging and therapeutic intervention. Although significant challenges remain in modeling human fluid dynamics, understanding these hidden networks offers a promising frontier for strategies aimed at restoring cerebral clearance and improving clinical outcomes. Full article

Background/Objectives: Alzheimer’s disease (AD) is a leading cause of dementia globally, yet standard diagnostic markers like cerebrospinal fluid (CSF) analysis and molecular imaging are invasive and resource-intensive. While artificial intelligence (AI)-based volumetric magnetic resonance imaging (MRI) offers a scalable and non-invasive alternative, data correlating these structural metrics with fluid biomarkers and cognitive status in Southeast Asian populations are scarce. This study addresses this critical gap by examining the within-cohort relationship between CSF biomarkers and regional brain volumes derived from AI-assisted MRI in Indonesian patients with clinically diagnosed AD, providing novel data for an underrepresented population. Methods: Twenty-one AD patients from three national referral hospitals in Indonesia underwent lumbar puncture for CSF biomarker analysis and 3 Tesla structural brain MRI. Brain volumes were analyzed using United Imaging Intelligence software, focusing on AD-relevant regions (hippocampus, entorhinal cortex, parahippocampus, precuneus, and posterior cingulate cortex [PCC]). Results: Spearman’s correlation revealed significant positive associations between CSF Aβ42 levels and several brain regions. Strong correlations were found with the right entorhinal volume indexed to intracranial volume (VICV) (r = 0.601, p = 0.004), right PCC VICV (r = 0.603, p = 0.004), right entorhinal volume (r = 0.533, p = 0.013), and right hippocampus VICV (r = 0.503, p = 0.020). Furthermore, MoCA-InA scores demonstrated highly significant positive correlations with CSF Aβ42 concentrations (r = 0.720, p < 0.001), right Hippocampus VICV (r = 0.703, p < 0.001), and right PCC VICV (r = 0.695, p < 0.001). No significant correlations were found between CSF pTau or the pTau/Aβ42 ratio and regional volumes. Conclusions: These results highlight the entorhinal cortex and PCC as early affected regions where CSF Aβ42 correlates with preserved volume, supporting their role as structural markers in early AD. The absence of pTau associations may reflect early-stage pathology or limitations of cross-sectional volumetry. In resource-limited settings, AI-assisted volumetric MRI demonstrates potential utility as a non-invasive tool for stratifying amyloid-associated brain atrophy and staging disease severity. Full article