Search Results (105)

Meningitis and encephalitis necessitate rapid pathogen identification to guide therapy, as conventional methods are time-consuming. This study evaluated both the wet-lab analytical performance and the clinical performance evaluation of the Bioeksen Meningitis/Encephalitis Panel (BS-MEP) integrated onto the fully automated, high-throughput Sigmoida Lab platform. Analytical limits of detection (LoD) were defined via Probit analysis (95% threshold) by spiking negative cerebrospinal fluid (CSF) matrices. Target detection was verified using characterized reference materials for all 14 analytes, and in silico primer/probe coverage was assessed against taxon-specific sequence databases. Cross-reactivity was evaluated using high-prevalence non-target organisms. Clinical performance was evaluated retrospectively using 500 archived, anonymized CSF specimens from a single-center repository, with analyte-specific classifications compared with prespecified routine comparator methods. The automated platform provided an 80-min sample-to-result turnaround for up to 23 samples. Verified LoDs ranged from 472 to 2118 genome copies/mL. All inclusivity strains were successfully detected in 5/5 replicates. In silico coverage exceeded 98% combined, and zero wet-lab cross-reactivity was observed. Precision coefficients of variation (CVs) were consistently ≤1.38%. In the clinical evaluation, the pooled clinical agreement was high, with PPA ranging from 90.9% to 100% and NPA of 100% across the evaluated analytes. Analyte-level clinical sensitivity ranged from 90.9% to 100%, with zero false-positive results across all targets. The fully automated molecular system demonstrates excellent analytical robustness and strong clinical agreement for syndromic detection of major CNS pathogens. The automated workflow combines broad pathogen coverage with an approximately 80-min sample-to-result turnaround and warrants further prospective evaluation in routine clinical settings. Full article

Background: Herpes simplex encephalitis (HSE) is a rare but life-threatening infection of the central nervous system associated with high mortality and severe neurological sequelae. The diagnosis may be particularly challenging in patients presenting with atypical clinical or laboratory findings. Case presentation: An 85-year-old woman presented with progressive impairment of consciousness and generalized neurological deterioration. Initial neuroimaging suggested an acute ischemic stroke, whereas subsequent brain magnetic resonance imaging (MRI) demonstrated bilateral temporal and insular cortical abnormalities suggestive of encephalitis. Cerebrospinal fluid (CSF) analysis revealed no pleocytosis, and blood tests showed no markers of systemic inflammation during admission, which initially lowered the suspicion of infectious encephalitis. Although no inflammatory cells were detected in the routine CSF examination, polymerase chain reaction (PCR) testing confirmed infection with herpes simplex virus type 1 (HSV-1). Despite the prompt initiation of acyclovir after suspicion of encephalitis with MRI, together with corticosteroid therapy, anticonvulsants, and supportive treatment, the clinical course was fatal. Conclusions: This case highlights the diagnostic challenges associated with HSE, particularly in patients with normocellular CSF and radiological findings that may mimic other neurological conditions, including ischemic stroke. The absence of CSF pleocytosis does not exclude HSE, although the timing of CSF sampling should be considered when interpreting this finding. Early MRI and molecular CSF diagnostics remain essential for establishing an accurate diagnosis and ensuring timely treatment. Full article

This study evaluated clinical characteristics, treatment outcomes, and CNS relapse patterns in patients with breast-involved diffuse large B-cell lymphoma (DLBCL), a rare extranodal presentation with limited real-world data. We conducted a retrospective study on 33 consecutive patients with newly diagnosed breast-involved DLBCL treated from 2019 to 2024. All patients received R-CHOP. Baseline CNS screening—including neurological examination, fundoscopy, brain magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) analysis—was routinely performed. High-dose methotrexate (HD-MTX) was offered as CNS prophylaxis after completion of systemic therapy based on multidisciplinary team evaluation and clinician–patient shared decision-making according to institutional treatment protocols. Median age was 52.6 years; 84.8% had ECOG 0. Non-GCB subtype predominated (84.8%), and Ki-67 >70% was present in 69.7%. The overall response rate was 90.9%, with 84.8% complete responses. At a median follow-up of 44 months, 5-year Overall Survival (OS) and Progression-Free Survival (PFS) were 84.8% and 66.7%. CNS relapse occurred in 4 of 6 patients (66.7%) without prophylaxis, all within 5–11 months after R-CHOP, whereas no CNS relapses were observed among prophylaxis recipients (p < 0.001), although this observation should be interpreted with extreme caution given the very small non-prophylaxis subgroup (n = 6), limited statistical power, and non-randomized treatment allocation. Exploratory analyses suggested that bulky disease was associated with inferior OS. R-CHOP achieved high response rates and favorable long-term outcomes in breast-involved DLBCL. The absence of CNS relapse among HD-MTX prophylaxis recipients, contrasted with a high relapse rate in those without prophylaxis, provides only a hypothesis-generating observation that requires confirmation in larger prospective studies; this warrants further investigation of the role of systemic CNS prophylaxis. Full article

Depression is defined by clinical symptoms, but its biology varies considerably among patients. In this review, dietary tryptophan allocation describes the routes taken by tryptophan after intestinal absorption. Some is incorporated into proteins. Some enters serotonin and melatonin synthesis or the kynurenine pathway, while gut bacteria convert another fraction into indole compounds. Brain availability also depends on the circulating free pool and competition with other large neutral amino acids. This term does not imply a new biochemical pathway. It allows these known processes to be considered in relation to inflammation, metabolism, the gut microbiota, medication use, and current disease state. Recent meta-analyses indicate that peripheral tryptophan is lower in depression. They do not show a consistent increase in the kynurenine-to-tryptophan ratio, and findings from cerebrospinal fluid vary between studies. Human multiomics studies have associated microbial and metabolite profiles with cognition and response to treatment, although the evidence remains largely correlational. Changes in kynurenine, 3-hydroxykynurenine, and quinolinic acid are more apparent in inflammatory subgroups than in unselected samples. Modern evidence for L-tryptophan monotherapy is sparse. Trials of 5-hydroxytryptophan and interventions directed at the gut microbiota have also produced mixed results. Studies should characterize participants and sampling conditions more carefully. Diet and competition among amino acids need to be recorded. Albumin concentration, medication exposure, and disease state also affect interpretation. Considering these variables together may improve biomarker analyses and support trials in more biologically homogeneous groups. Dietary tryptophan allocation is proposed for these research purposes, not for clinical diagnosis or routine supplementation. Full article

Objective: Axonal injury is a key determinant in irreversible disability in multiple sclerosis (MS). Reliable biomarkers of neuroaxonal damage are essential for improving diagnosis, monitoring disease progression, and evaluating treatment response. This study investigated the relationship between phosphorylated neurofilament heavy chain (pNF-H), clinical characteristics, and conventional cerebrospinal fluid (CSF) and serum biomarkers in Algerian patients with MS. Methods: A total of 102 participants were enrolled. Clinical, immunological, and biochemical parameters were assessed, including the Expanded Disability Status Scale (EDSS), oligoclonal bands (OCBs), IgG index, albumin quotient, and pNF-H concentrations in paired CSF and serum samples. Results: OCBs were detected in 85.5% of patients, and 65.21% exhibited intrathecal immunoglobulin synthesis, with a median IgG index of 0.87. Patients with progressive MS were significantly older and more disabled than those with relapsing–remitting MS (age: p = 0.01; EDSS: p = 0.0007). OCB-positive patients had significantly higher IgG index values (p = 0.0004), but OCB status was not associated with age, EDSS, or albumin quotient. EDSS correlated positively with age (p = 0.0007), albumin quotient (p = 0.01), and IgG index (p = 0.001). Both CSF and serum pNF-H levels were significantly elevated in MS patients compared with NSDs group (p < 0.001). Increased pNF-H concentrations were associated with progressive disease and greater disability (EDSS ≥ 5). Conclusions: Elevated pNF-H levels in CSF and serum are associated with disease severity and progressive MS, supporting their potential as complementary biomarkers of neuroaxonal damage and clinical disability in routine MS assessment. Full article

Alzheimer’s disease (AD) is the most common neurodegenerative disorder and a leading cause of dementia worldwide. Current diagnostic methods, including cerebrospinal fluid analysis and neuroimaging, are often invasive, expensive, and not suitable for large-scale screening. Therefore, increasing attention has been directed toward the identification of non-invasive biomarkers. Saliva has emerged as a promising diagnostic biofluid containing proteins, metabolites, inflammatory mediators, exosomes, and nucleic acids potentially associated with neurodegenerative processes. This review aimed to summarize current evidence regarding salivary biomarkers in Alzheimer’s disease and to discuss their diagnostic potential, limitations, and association with periodontal disease within the framework of the oral–brain axis. A literature search was conducted using PubMed, Scopus, and Google Scholar databases for studies published between 2018 and 2026. Relevant English-language articles focusing on salivary biomarkers, Alzheimer’s disease, periodontitis, and oral–brain axis interactions were included. Current evidence suggests that salivary biomarkers such as amyloid-beta, tau protein, lactoferrin, exosomes, oxidative stress markers, metabolites, and nucleic acid-based biomarkers may reflect the pathological mechanisms associated with Alzheimer’s disease. In addition, increasing evidence supports a relationship between chronic periodontal inflammation, oral pathogens, and neurodegenerative processes. However, substantial heterogeneity among studies, methodological variability, and a lack of standardized protocols currently limit the reproducibility and clinical applicability of saliva-based diagnostics. Salivary biomarkers represent a promising non-invasive approach for the early detection and monitoring of Alzheimer’s disease. Nevertheless, further large-scale, longitudinal, and standardized studies are necessary to validate their diagnostic utility and support their implementation in routine clinical practice. Full article

Background: Rapid etiological diagnosis of bacterial meningitis is crucial in children, as delays can lead to neurological sequelae. The BioFire FilmArray Meningitis/Encephalitis (ME) panel is widely used on cerebrospinal fluid (CSF), but its target spectrum may miss healthcare-associated or multidrug-resistant pathogens. We evaluated the diagnostic performance and stewardship-oriented clinical impact of off-label BioFire FilmArray Blood Culture Identification 2 (BCID2) testing on CSF from pediatric patients with suspected bacterial CNS infection and negative ME results. Methods: We retrospectively analyzed CSF samples collected between January 2023 and March 2025 at a tertiary pediatric hospital. In ME-negative cases with persistent suspicion and abnormal CSF parameters, BCID2 was performed off-label on residual CSF aliquots after routine testing, without additional sampling. We assessed pathogen detection, agreement with culture, resistance-gene identification, and documented stewardship actions. Results: Among 76 ME-negative CSF samples tested with BCID2, 23 (30.3%) were positive, all involving organisms not included in the ME panel. BCID2 was concordant with culture in 19/23 cases (82.6%); 4/23 (17.4%) were BCID2-positive/culture-negative, consistent with reduced culture sensitivity in frequently pretreated cases. Resistance genes (VIM, vanA/B, CTX-M) were detected in 30.4% of BCID2-positive samples. Overall agreement with culture was 94.7% (PPA 100%, NPA 93.0%). Escalation was documented in 13/23 episodes (56.5%), discontinuation in 2/23 (8.7%), and confirmation in 9/23 (39.1%), with no de-escalation events; clinical outcomes were not systematically available. Conclusions: In selected ME-negative pediatric cases with abnormal CSF profiles, BCID2 testing on residual CSF provided rapid, clinically meaningful microbiological information that may support antimicrobial optimization. Full article

Background: Streptococcus pneumoniae, also referred to as pneumococcus, is of immense public health significance. In particular, it causes severe invasive diseases among children. This has led to the recommendation of anti-pneumococcal prophylaxis, including the administration of penicillin and pneumococcal conjugate vaccines (PCVs), which have become available in about 90% of the countries in sub-Saharan Africa. Nonetheless, breakthrough disease still occurs. Also, PCVs can cause a shift in the distribution of pneumococcal serotypes, usually towards non-vaccine types. However, in many sub-Saharan African countries where PCVs have been introduced, there are hardly any comprehensive post-vaccination surveillance data on pneumococcus. Aim: To describe the post-vaccination epidemiology of invasive pneumococcal disease (IPD) in Ghana, including the prevalence, serotype distribution and antibiotic resistance. Methods: The study was cross-sectional and involved 14,597 patients recruited at the Korle Bu Teaching Hospital, Greater Accra Regional Hospital, Princess Marie Louise Children’s Hospital, Ho Regional Hospital, Eastern Regional Hospital, and Zonal Public Health and Reference Laboratory, Tamale. Specimens of cerebrospinal fluid (obtained by lumbar puncture) and blood were collected routinely from meningitis patients, while blood specimens were taken from pneumonia patients. These were cultured for S. pneumoniae following standard microbiological methods and subjected to antimicrobial susceptibility testing. The isolates were serotyped by the pneumotest latex agglutination kit, and the results confirmed by Quellung reaction, using serotype-specific antisera. Results: The overall prevalence of IPD was 0.66% (n = 97), varying across syndromes: bloodstream infections (0.53%, n = 38), meningitis (2.45%, n = 43), and pneumonia (0.28%, n = 16). The majority of the cases (56.70%, n = 55) occurred in the 11–20-year-old group. Ten pneumococcal serotypes were identified, with Serotype 1 being predominant (58.76%), followed by Serotypes 23B (11.34%), 33F (9.28%), and 12F (8.24%). Vaccine serotypes accounted for 81.44% of the isolates, while 18.56% were non-vaccine serotypes (23A, 23B, and 38). Antimicrobial resistance was highest against sulphamethoxazole-trimethoprim (52%), ampicillin (51%), and penicillin (46%). No resistance was observed against ciprofloxacin, levofloxacin, and vancomycin. The multidrug resistance proportion was 42.3% (n = 41). Conclusions: Even in the post-vaccination era, vaccine-type IPD remains a significant public health issue in Ghana. The observed serotype distribution and antimicrobial resistance patterns warrant sustained surveillance, more adaptive vaccination policies, and rigorous antibiotic stewardship to effectively mitigate IPD burden. Full article

Autoimmune encephalitis is an increasingly recognized cause of encephalitis. Detection of disease-specific antibodies is the cornerstone of diagnosis. Despite growing clinical awareness and the routine availability of antibody assays in most centers, diagnosis remains challenging due to diverse clinical presentations, the low diagnostic yield of commercial antibody kits, difficulties in interpreting antibody results, and a substantial proportion of paraclinically silent patients. This narrative review summarizes current diagnostic approaches to autoimmune encephalitis, with particular emphasis on antibody detection strategies, the diagnostic yield of different techniques, serum vs. cerebrospinal fluid testing, and the diagnostic value of supportive cerebrospinal fluid biomarkers. In addition, we discuss patients with seronegative or paraclinically silent disease, in whom diagnosis relies primarily on clinical criteria and the exclusion of alternative etiologies. Finally, we outline future perspectives, including advanced immunological techniques and machine learning-based diagnostic models, which may facilitate earlier identification and more accurate classification of autoimmune encephalitis. Improved integration of clinical assessment with cerebrospinal fluid biomarkers and novel analytical tools may reduce diagnostic delay and support the timely initiation of immunotherapy, ultimately improving neurological outcomes. Full article

Early-onset infection caused by Streptococcus agalactiae (Group B Streptococcus, GBS) may occur during gestation or delivery and can lead to severe neonatal sepsis, meningitis, or pneumonia. Discordant GBS infections in twin gestations are rare. We report a fatal case of early-onset GBS infection in dichorionic–diamniotic twins conceived via IVF and delivered by caesarean section at 32 weeks’ gestation due to discordant fetal growth and abnormal Doppler indices in Twin A (Umbilical Artery PI = 1.4; Middle Cerebral Artery PI = 1.5). Twin A had Apgar scores of 3, 5, and 5 and rapidly developed tachycardia, respiratory distress, and systemic infection, while Twin B, with Apgar scores of 7, 8, and 9, remained clinically stable. Both infants were admitted to the NICU and underwent routine blood, urine, and cerebrospinal fluid testing. Despite the prompt initiation of parenteral ceftriaxone and respiratory support, Twin A deteriorated rapidly and died within 28 h. GBS was isolated from Twin A’s blood culture, and maternal placental tissue and high vaginal samples collected before antibiotic administration also grew GBS, with all isolates demonstrating identical antimicrobial resistance profiles. Molecular analysis revealed matching rib1 and alp2/3 gene patterns in isolates from the mother and Twin A. Maternal anovaginal immunochromatography at delivery was positive, whereas screening cultures obtained at 29 weeks’ gestation were negative. This case highlights the limitations of culture-based GBS screening in high-risk pregnancies and preterm deliveries and underscores the potential value of molecular assays and point-of-care testing to improve detection of S. agalactiae throughout pregnancy and the peripartum period. Emerging preventive strategies, including modulation of the genital microbiome and maternal vaccination aligned with WHO recommendations, may further reduce the burden of neonatal GBS disease. Full article

Meningovascular syphilis, a type of neurosyphilis, causes stroke and various types of myelopathy. In recent years, there has been an increase in the incidence of neurosyphilis. However, diagnosing neurosyphilis remains challenging due to the reliance on serum and cerebrospinal fluid (CSF) testing, which has low specificity and sensitivity. Magnetic resonance vessel wall imaging (MR-VWI), recently developed to identify vessel wall pathologies, may aid in diagnosing neurosyphilis. In this cross-sectional study, we performed systematic screening for syphilis in all 366 patients with acute ischemic stroke or transient ischemic attack admitted to our stroke unit. Further CSF analysis and MR-VWI were specifically conducted only on those with reactive serum venereal disease research laboratory (VDRL) or treponema pallidum particle hemagglutination assay (TPHA) tests to evaluate neurosyphilis. Serum screening was reactive in 5.7% (21/366) of patients; among these, the prevalence of likely neurosyphilis (defined by abnormal CSF pleocytosis or protein levels) was 2.2% (8/366). Within this group of eight patients, MR-VWI was technically feasible and thus performed in six cases. Although all CSF-VDRL tests were non-reactive, MR-VWI identified diagnostic evidence of meningovascular syphilis (concentric wall thickening and enhancement) in 33.3% (2/6) of symptomatic patients who underwent the scan. Neurosyphilis remains a critical, treatable cause of stroke that can affect older patients with established vascular risk factors. Our findings demonstrate that routine serum screening is essential, as traditional CSF-VDRL tests may yield false-negative results. MR-VWI serves as a valuable adjunct tool to provide objective evidence of active vasculitis, guiding the initiation of appropriate antibiotic therapy when laboratory results are inconclusive. Full article

Background and Objectives: Vascular dementia (VaD) and mixed dementia (MD) represent prevalent causes of cognitive decline in the elderly, as they share similar pathological pathways and clinical features. Distinguishing between these two conditions remains a challenge, due to their frequent clinical and neuroimaging overlap. Nevertheless, it is important from a prognostic perspective. Materials and Methods: The study comprised 114 participants, including patients with VaD (n = 33), MD (n = 26), Alzheimer’s disease (AD; n = 26), and 29 cognitively healthy controls (C). We evaluated routinely used cerebrospinal fluid (CSF) biomarkers (total tau, p-tau181, Aβ_1–42) and their ratios to assess inter-group differences, diagnostic accuracy, and correlations with cognitive score. Results: Patients with MD demonstrated significantly higher levels of t-tau and p-tau181, and lower levels of Aβ_1–42, compared to VaD (p < 0.004 for all analyses). With the exception of p-tau181/t-tau, all calculated ratios enabled differentiation between these groups. ROC analysis confirmed the high diagnostic accuracy of CSF Aβ_1–42 and t-tau (AUC 0.82 and 0.79 respectively) for detecting AD pathology in dementia patients. Furthermore, the t-tau/Aβ_1–42, p-tau181/Aβ_1–42 ratios were the most effective in differentiating AD-related from vascular pathologies (AUC 0.78 and 0.80 respectively), and in differentiating MD from VaD (AUC 0.79 and 0.77 respectively). A significant correlation was observed between CSF biomarkers (especially tau markers) and cognitive impairment severity. Conclusions: CSF biomarkers effectively differentiate mixed from vascular dementia by identifying underlying AD pathology independent of the clinical phenotype. This supports the use of CSF biomarkers in clinical practice to reveal the neurodegenerative component in patients with cerebrovascular disease, which is of fundamental importance for emerging disease-modifying treatment strategies in mixed neuropathologies. Full article

Cerebrospinal fluid (CSF) biomarkers for neurodegenerative diseases have been extensively studied over the years. However, CSF samples are routinely centrifuged, and the resulting sediment or pellet is typically discarded to remove cellular debris and high-density particles. This standard practice raises a critical question: Could these discarded sediments harbour potential biomarkers? The aim of the present study is to demonstrate that CSF sediments contain specific brain-derived components and thus to substantiate the possible presence of biomarkers within these sediments. To this end, we analysed post-mortem CSF samples of one patient with neuropathologically confirmed Alzheimer’s disease (AD) and one patient with confirmed progressive supranuclear palsy (PSP). CSF pellets were studied using transmission and scanning electron microscopy techniques (TEM and SEM, respectively), along with compositional analysis through SEM combined with energy-dispersive X-ray spectroscopy (SEM-EDX), as well as immunofluorescence and histochemical analyses on semithin pellet sections. We observed that, among others, CSF pellets contain brain-derived structures such as wasteosomes and psammoma bodies. Furthermore, we also found disease-relevant proteins, including tau and Aβ42 in the AD sediment and tau in the PSP sediment. Although further studies are required, the study of CSF pellets could open new avenues for biomarker discovery in neurodegenerative diseases. 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

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and one of the leading causes of dementia worldwide. With the increasing prevalence driven by population aging, there is a growing demand for early, accurate, and biologically grounded diagnostic approaches. Advances in molecular diagnostics have created new opportunities for early disease detection, staging, and monitoring of therapeutic responses, reshaping contemporary diagnostic workflows. Validated cerebrospinal fluid biomarkers—amyloid-β, total tau, and phosphorylated tau—form the core of current biologically based diagnostic criteria, while blood-based biomarkers such as plasma p-tau and neurofilament light chain are gaining prominence due to their minimally invasive nature and scalability. Advanced imaging techniques, including amyloid and tau positron emission tomography, further enhance diagnostic accuracy and support differentiation of AD from other neurodegenerative disorders. Despite these advances, the clinical implementation of molecular diagnostics remains limited by methodological heterogeneity, biological variability, and the lack of standardized analytical and clinical frameworks. Addressing these translational challenges is essential for integrating molecular biomarkers into routine clinical practice and for enabling reliable, large-scale screening and early diagnosis of AD. Full article