Search Results (78)

The insulin-like growth factor binding protein, acid-labile subunit (IGFALS), plays a crucial role in glucose metabolism and immune regulation, key processes in recovery from surgery. Here, we studied the perioperative serum IGFALS dynamics and explored potential clinical implications. A total of 79 patients undergoing elective cardiac surgery with implementation of cardiopulmonary bypass had their serum isolated at baseline, 24 h, seven days, and three months postoperatively to assess serum concentrations of IGFALS and insulin growth factor 1 (IGF-1). Markers of perioperative injury included troponin I (TnI), high-mobility group box 1 (HMGB-1), and heat shock protein 60 (Hsp-60). Inflammatory status was assessed via interleukin-6 (IL-6) and interleukin-8 (IL-8). Additionally, we measured in vitro cytokine production to viral stimulation of whole blood and monocytes. Surrogates of neuronal distress included neurofilament light chain (NF-L), total tau (τ), phosphorylated tau at threonine 181 (τp181), and amyloid β40 and β42. Renal impairment was defined by RIFLE criteria. Cardiac dysfunction was denoted by serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Serum IGFALS levels declined significantly after surgery and remained depressed even at 3 months. Administration of acetaminophen and acetylsalicylic acid differentiated IGFALS levels at the 24 h postoperatively. Serum IGFALS 24 h post-operatively correlated with production of cytokines by leukocytes after in vitro viral stimulation. Serum amyloid-β1-42 was significantly associated with IGFALS at baseline and 24 h post-surgery Patients discharged home had higher IGFALS levels at 28 days and 3 months than those discharged to healthcare facilities or who died. These findings suggest that IGFALS may serve as a prognostic biomarker for recovery trajectory and postoperative outcomes in cardiac surgery patients. Full article

The combined use of serum and CSF biomarkers for prognostic stratification in multiple sclerosis (MS) remains underexplored. This multicenter observational study investigated associations between serum neurofilament light chain (sNfL), glial fibrillary acidic protein (sGFAP), and CSF lipid-specific IgM oligoclonal bands (LS-OCMB) with different forms of disability worsening, such as relapse-associated worsening (RAW), active progression independent of relapse activity (aPIRA), and non-active PIRA (naPIRA). A total of 535 patients with MS were included, all sampled within one year of disease onset. Biomarkers were quantified using single-molecule array and immunoblotting techniques, and CSF cell subsets were analyzed by flow cytometry. High sNfL z-scores and LS-OCMB positivity were independently associated with increased risk of RAW and aPIRA, collectively termed inflammatory-associated worsening (IAW), while elevated sGFAP levels predicted naPIRA. Patients with both high sNfL and LS-OCMB positivity had the highest risk of IAW. Among LS-OCMB–positive patients, higher regulatory T cell percentages were associated with lower sNfL levels, suggesting a protective role. Conversely, in LS-OCMB–negative patients, sNfL levels correlated with CSF C3 concentrations. These findings support the complementary role of sNfL, sGFAP, and LS-OCMB in identifying distinct mechanisms of disease worsening and may inform early personalized management strategies in MS. Full article

(1) Background: Multiple sclerosis (MS) is a biologically highly heterogeneous disease and has poor predictability at diagnosis. Moreover, robust data indicate that early disease activity strongly correlates with future disability. Therefore, there is a need for strong and reliable biomarkers from diagnosis to characterize and identify patients who require highly effective disease-modifying treatments (DMTs). Several biomarkers are promising, particularly neurofilament light chains (NFLs), but the relevance of others is less consolidated. (2) Methods: We evaluated a panel of axonal damage and inflammatory biomarkers in cerebrospinal fluid (CSF) and matched serum obtained from a cohort of 60 newly diagnosed MS patients. Disability at diagnosis, negative prognostic factors, and the initial DMT prescribed were carefully recorded. (3) Results: We observed correlations between different axonal biomarkers: CSF and serum NFL versus CSF total tau; and between the inflammatory marker osteopontin (OPN) and axonal biomarkers CSF p-Tau, CSF total tau, and serum NFL. CSF and serum NFL and total tau, as well as CSF OPN, positively correlated with EDSS at diagnosis. Moreover, CSF and serum NFL levels were increased in patients with gadolinium-enhancing lesions (p = 0.01 and p = 0.04, respectively) and in those treated with highly effective DMT (p = 0.049). Furthermore, CSF OPN and both CSF and serum NFL levels significantly differentiated patients based on EDSS, with a combined ROC AUC of 0.88. We calculated and internally validated biomarker (in particular serum NFL) thresholds that significantly identified patients with higher disability. Finally, CSF OPN levels and dissemination in the spinal cord were significant predictors of EDSS at diagnosis. (4) Conclusions: These preliminary exploratory data confirm the pathological interconnection between inflammation and axonal damage from early disease stages, contributing to early disability. Follow-up data, such as longitudinal disability scores, repeated serum measurements, a healthy control group, and external validation of our results, are needed. We suggest that combining several fluid biomarkers may improve the clinical characterization of patients. Full article

Canine cognitive dysfunction syndrome (CDS) is a progressive neurodegenerative disorder in aging dogs and serves as a natural model for Alzheimer’s disease in humans. This study evaluated blood biomarkers—amyloid-beta (Aβ40, Aβ42), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP)—for diagnosing and staging CDS and assessed whether combining biomarkers with behavioral questionnaires improves diagnostic reliability. Seventy-seven dogs, including healthy controls and CDS cases, were assessed using the Canine Cognitive Dysfunction Rating Scale (CCDR), Canine Dementia Scale (CADES), and Canine Cognitive Assessment Scale (CCAS). Plasma Aβ40, Aβ42, GFAP, and serum NfL levels were measured via ELISA. While Aβ40, Aβ42, and GFAP were not significantly associated with CDS stage, serum NfL levels were elevated (p < 0.05) across all questionnaires. Receiver operating characteristic (ROC) analyses showed areas under the curve (AUCs) of 0.763 (CCDR), 0.722 (CADES), and 0.777 (CCAS), with cut-off values around 18.28–43.13 pg/mL. NfL shows promise as a blood biomarker correlated with CDS severity. Combining serum NfL measurements with questionnaire assessments may enhance diagnostic accuracy for CDS in veterinary practice. Full article

Background: Primary angiitis of the central nervous system (PACNS) is a rare vasculitis affecting CNS blood vessels, posing diagnostic challenges due to the limited specificity of the established diagnostic tools. Neurofilament light chain (NfL) might be a promising biomarker in PACNS. Methods: NfL in serum and CSF was measured in 33 PACNS patients (25 active [aPACNS], 8 in remission [rPACNS]) enrolled between 2014 and 2022 and compared to controls (serum: n = 303; CSF: n = 68); Results: Serum NfL was significantly elevated in aPACNS (median: 45.77 pg/mL) versus rPACNS (6.68 pg/mL; p < 0.001) and healthy controls (6.05 pg/mL; p < 0.001). Similarly, CSF NfL was significantly elevated in aPACNS (median: 4914.58 pg/mL) compared to rPACNS (301.19 pg/mL; p = 0.002) and controls (262.83 pg/mL; p < 0.001). Serum and CSF NfL were significantly correlated (r = 0.90, p < 0.001). Additionally, an association between elevated NfL and ischemic lesions was observed (serum: r = 0.59, p = 0.006; CSF: r = 0.43, p = 0.032). A subgroup analysis excluding stroke patients still revealed elevated NfL in 90% (CSF) and 50% (serum), with diminishing discriminatory power with older age. Conclusions: NfL holds potential as a biomarker for PACNS, in particular in younger patients. Full article

Neurofilament light chain (NfL), an abundant cytoskeletal protein in neurons, has emerged as a promising serum biomarker that indicates non-specific neuronal damage secondary to various neurologic diseases, including multiple sclerosis (MS). Emerging evidence suggests that serum NfL levels correlate with future disability, brain atrophy, predict new disease activity, and decrease in response to various disease-modifying therapies. As research continues to validate NfL’s potential role in clinical practice, the need for a practical model to conceptualize and visualize its relevance to MS pathology becomes evident—not only for healthcare providers but also for patients. To address this, we propose the Neurofoundational Model (NFM), which likens a neuron to a home, with various parts of the home representing distinct regions of the central nervous system (CNS). In this model, the home (neuron) experiences scenarios such as a fire, an earthquake, and a slow flood, representing distinct MS disease states. A fire illustrates an MS relapse with good recovery, where serum NfL levels rise during the relapse and subsequently return near baseline. An earthquake represents an MS relapse with poor recovery, where NfL levels increase and remain elevated above baseline. Finally, a slow flood depicts MS in progressive stages, characterized by sustained and gradually increasing serum NfL levels without abrupt clinical changes. This approach offers a clear and relatable visualization for clinicians and patients alike, illustrating the dynamics of serum NfL levels during CNS damage caused by demyelination. By integrating this model into clinical practice, we aim to enhance understanding and communication regarding the role of NfL in MS pathology and its potential utility as a biomarker. Full article

Objectives: The aim of the present study was to assess the clinical value of measuring the concentration of neurofilament light chains (NF-Ls) in the diagnosis of taxane-induced neuropathy (CIPN) during neoadjuvant chemotherapy (NAC) in breast cancer patients. Methods: This study included a total of 94 patients who qualified for NAC with taxanes. Serum samples were collected before starting NAC, after three and six cycles, and 3–6 months after NAC. The NF-L concentration was determined using the Ella technology. The assessment of CIPN was based on the clinical symptoms included in the EORTC QLQ-CIPN20 scores. Results: The median NF-L concentrations increased during NAT monitoring. After the end of therapy, a significant decrease in NF-L concentrations was observed (p = 0.001, R = 0.37). We established a cut-off point of 29.5 pg/mL to distinguish between the control group and patients with early symptoms of neuropathy (CIPN G1) (p = 0.001; AUC = 0.982). We showed that NF-L concentrations, regardless of the stage of therapy, increased with the severity of neuropathy symptoms (CIPG1 vs. G2 vs. G3) (p = 0.0189, R = 0.33). According to the established cut-off points, serum NF-L concentrations above 196 pg/mL in patients undergoing therapy likely indicate the presence of low-grade neuropathy (p = 0.0076), while values above 218 pg/mL may indicate advanced CIPN (p = 0.0008). Conclusions: In this study, we demonstrated the usefulness of NF-L levels to confirm neuropathy early in the course of treatment, which is important as the questionnaire-based assessment of neuropathy currently used in practice remains subjective. Ultimately, serum NF-L levels are helpful in determining the severity of NAC-induced neuropathy among breast cancer patients. Full article

We aimed to determine whether transient global amnesia (TGA) is associated with alterations in central nervous system (CNS) injury biomarkers—serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP). In a prospective cohort of TGA patients, blood samples were obtained within 24–48 h of TGA onset (t0) and 6 weeks thereafter (t1). We assessed sNfL and sGFAP levels using the highly sensitive single-molecule array assay and calculated Z-scores adjusted for age, gender, and body mass index (BMI). Demographics, electroencephalography (EEG), and cerebral magnetic resonance imaging (cMRI) findings were also collected. A total of 20 patients were included (median age: 66 years, 70% women). No significant changes in sNfL or sGFAP levels associated with TGA at t0 and t1 were observed. Median sNfL Z-scores were 0.45 (interquartile range [IQR] −0.09, 1.19) at t0 and 0.60 (IQR −0.61, 1.19) at t1. Median sGFAP Z-scores were 0.27 (IQR −0.45, 0.76) at t0 and 0.44 (IQR −0.27, 0.75) at t1. Similarly, in the subgroup of patients with diffusion-weighted imaging (DWI)-positive hippocampal lesions (n = 5/20[25%]), no elevations in blood biomarkers were detected. Our pilot study on neurological blood biomarkers supports the benign nature of TGA, indicating that no CNS tissue damage occurs. Full article

Background: Cognitive impairment has an impact upon the function and quality of life of patients with multiple sclerosis (MS). High-serum neurofilament light-chain (sNfL) levels predict disease progression and are also associated with impaired cognitive performance. This study aimed to assess the attitudes of neurologists toward sNfL testing as regards making therapeutic decisions in clinically and radiologically stable patients experiencing cognitive decline. Methods: A web-based observational study was conducted among neurologists caring for patients with MS. The role of sNfL in therapeutic decisions was assessed through a simulated case scenario describing a 31-year-old woman with relapsing–remitting MS for four years on glatiramer acetate. Her partner reported increased distractibility and difficulties in organizing daily activities over the past 18 months. There was no history of new relapses, and a follow-up brain MRI scan showed no new lesions. Her performance in the Symbol Digit Modalities Test decreased by 8 points from the previous year, with 46 correct answers. The patient had an sNfL level of 21 pg/mL, with no other identified factors that could have altered this value. The participants were tasked with deciding to either escalate treatment or to continue the current treatment and schedule the patient for reassessment in 6–12 months (defined as decisions misaligned with emerging evidence [DMEE]). Multivariate regression analysis was conducted to determine factors associated with DMEE. Results: One hundred and sixteen neurologists participated in the study. Almost 50% of the participants (n = 57) opted not to escalate treatment despite high sNfL levels. This was more common among neurologists not fully dedicated to MS care (60.5% vs. 43.6%). The multivariate analysis showed that being a neurologist not fully dedicated to MS (odds ratio [OR] = 2.35, 95% confidence interval [CI] 1.01–5.50; p = 0.04) and having a poor perception of sNfL benefits (OR = 1.02, 95% CI 1.00–1.04; p = 0.01) were associated with DMEE. Conclusions: Neurologists’ lack of full dedication to MS care and limited perception of sNfL’s clinical utility were key factors associated with suboptimal therapeutic decisions in a simulated case of cognitive decline with elevated sNfL. These findings underscore the need for increased education on the role of sNfL to improve evidence-based decision-making in MS management. Full article

Background/Objectives: Fabry disease (FD) is an inborn error of the glycosphingolipid metabolism with variable kidney, heart, and central nervous system (CNS) involvement. CNS-related FD manifestations include early ischemic stroke and white matter lesions (WMLs) related to cerebral small-vessel disease (CSVD), possibly resulting in cognitive impairment. We studied 40 adult FD patients (17 male) to assess: (i) prevalence of cerebrovascular and cognitive manifestations in FD and their correlation with heart and renal involvement; and (ii) the potential value of serum neurofilament light chain (NfL) levels as an indicator of WMLs in FD. Methods: Patients underwent detailed diagnostic assessment related to FD, also including Mainz Severity Score Index (MSSI), neuropsychological tests, brain MRI to assess WMLs by the modified Fazekas score (mFS), and NfL determination by single-molecule array (SiMoA) (n = 22 FD patients vs. 15 healthy controls). Results: Overall, 4 FD patients had a history of ischemic stroke and 13/32 patients (40.6%) had an mFS ≥ 1. Almost two-thirds of FD patients (27/39, 69.2%) showed impairment on at least one cognitive test. On univariate analysis, only a reduction in estimated glomerular filtration rate was associated with an increased likelihood of having WMLs on brain MRI. Serum NfL levels were higher in FD patients vs. controls, with a trend toward significance (p = 0.08). Conclusions: Mild-to-moderate CSVD is a characteristic brain “signature” in FD patients. Both cardiac and renal involvement correlate with WML load, but only renal involvement appears to be predictive of CNS damage. Brain microvascular damage is associated with mild cognitive impairment in FD, and serum NfL might represent a potential biomarker of CSVD in FD. Full article

Background: Mild cognitive impairment is increasingly recognized as a precursor to more severe neurodegenerative conditions, particularly in the context of aging. Recent studies have highlighted the intersection of hearing loss and cognitive decline, suggesting that auditory deficits may exacerbate cognitive impairments in older adults, proposing the use of hearing aids to mitigate cognitive decline, and indicating that early intervention in hearing loss could be crucial for preserving cognitive function. The underlying mechanisms of the relationship between hearing and cognitive impairment may involve neuroinflammatory processes and neurodegeneration. Recent studies have evidenced the role of tau proteins and neurofilaments as biomarkers in the onset and progression of neurodegenerative diseases. Methods: We selected 30 subjects with age-related hearing loss, and we evaluated their cognitive status through the administration of screening tests, which also measured neurofilament light chain and phospho-tau 181 serum levels as biomarkers of neurodegeneration. The subjects were re-evaluated six months after the hearing aid fitting. Results: Patients with hearing impairment presented slightly altered results on cognitive tests, typical of a mild cognitive impairment. At the same time, serum levels of neurofilament light chain and phospho-tau 181 were significantly increased compared to the matched control group. After the hearing aids fitting, auditory, cognitive, and serum values results improved. Conclusions: The results of the study highlight the cognitive involvement in patients with hearing impairment and identify neurofilament light chain and phospho-tau 181 as serum biomarkers of neurodegeneration useful in monitoring the pathology. Full article

Impaired renal function can influence biomarker levels through mechanisms involving blood–brain barrier integrity and clearance pathways; however, the impact of variations within normal renal function remains unclear. The main aim of this study was to determine whether adjustment for the specific level of renal function is necessary when renal function remains within physiological levels. We studied n = 183 patients (NID n = 122; other neurological diseases n = 39; somatoform controls n = 22) who underwent lumbar puncture at University Hospital Frankfurt. Serum and cerebrospinal fluid (CSF) levels of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), total tau protein (tTAU), and ubiquitin C-terminal hydrolase-L1 (UCHL1) were measured using the single molecule array (SIMOA) technique. Estimated glomerular filtration rate (eGFR) correlated negatively with CSF GFAP (r = −0.217, p = 0.004) and serum NfL (r = −0.164, p = 0.032). Patients with impaired renal function exhibited higher CSF NfL (p = 0.036) and CSF GFAP (p = 0.026) levels. However, these findings did not remain significant after adjusting for BMI and age. Importantly, in patients with normal renal function, no significant correlations with eGFR and biomarker levels were observed after adjustment. Our findings indicate that serum and CSF concentrations of NfL, GFAP, tTAU, and UCHL1 are not significantly affected by fluctuations in physiological kidney function but emphasize the importance of considering comorbidities in impaired renal function when interpreting biomarker levels. Full article

Prion diseases, including Creutzfeldt–Jakob disease (CJD), are deadly neurodegenerative disorders characterized by the buildup of abnormal prion proteins in the brain. This accumulation disrupts neuronal functions, leading to the rapid onset of psychiatric symptoms, ataxia, and cognitive decline. The urgency of timely diagnosis for effective treatment necessitates the identification of strongly correlated biomarkers in bodily fluids, which makes our research crucial. In this study, we employed a fully automated multiplex ELISA (Ella^®) to measure the concentrations of 14-3-3 protein, total tau protein, and neurofilament light chain (NF-L) in cerebrospinal fluid (CSF) and serum samples from patients with prion disease and analyzed their link to disease prognosis. However, in North American and European cases, we did not confirm a correlation between NF-L levels and survival time. This discrepancy is believed to stem from differences in treatment policies and measurement methods between Japan and the United States. Nonetheless, our findings suggest that NF-L concentrations could be an early diagnostic marker for CJD patients with further enhancements. The potential impact of our findings on the early diagnosis of CJD patients is significant. Future research should focus on increasing the number of sCJD cases studied in Japan and gathering additional evidence using next-generation measurement techniques. Full article

Background: A limited number of studies have investigated the role of environmental chemicals in the etiology of mild cognitive impairment (MCI). We performed a cross-sectional study of the association between exposure to selected trace elements and the biomarkers of cognitive decline. Methods: During 2019–2021, we recruited 128 newly diagnosed patients with MCI from two Neurology Clinics in Northern Italy, i.e., Modena and Reggio Emilia. At baseline, we measured serum and cerebrospinal fluid (CSF) concentrations of cadmium, copper, iron, manganese, and zinc using inductively coupled plasma mass spectrometry. With immuno-enzymatic assays, we estimated concentrations of β-amyloid 1-40, β-amyloid 1-42, Total Tau and phosphorylated Tau181 proteins, neurofilament light chain (NfL), and the mini-mental state examination (MMSE) to assess cognitive status. We used spline regression to explore the shape of the association between exposure and each endpoint, adjusted for age at diagnosis, educational attainment, MMSE, and sex. Results: In analyses between the serum and CSF concentrations of trace metals, we found monotonic positive correlations between copper and zinc, while an inverse association was observed for cadmium. Serum cadmium concentrations were inversely associated with amyloid ratio and positively associated with Tau proteins. Serum iron concentrations showed the opposite trend, while copper, manganese, and zinc displayed heterogeneous non-linear associations with amyloid ratio and Tau biomarkers. Regarding CSF exposure biomarkers, only cadmium consistently showed an inverse association with amyloid ratio, while iron was positively associated with Tau. Cadmium concentrations in CSF were not appreciably associated with serum NfL levels, while we observed an inverted U-shaped association with CSF NfL, similar to that observed for copper. In CSF, zinc was the only trace element positively associated with NfL at high concentrations. Conclusions: In this cross-sectional study, high serum cadmium concentrations were associated with selected biomarkers of cognitive impairment. Findings for the other trace elements were difficult to interpret, showing complex and inconsistent associations with the neurodegenerative endpoints examined. Full article

Background/Objectives: Millions of individuals worldwide continue to experience symptoms following SARS-CoV-2 infection. This study aimed to assess the prevalence and phenotype of multi-system symptoms attributed to Long COVID—including fatigue, pain, cognitive-emotional disturbances, headache, cardiopulmonary issues, and alterations in taste and smell—that have persisted for at least two years after acute infection, which we define as “persistent Long COVID”. Additionally, the study aimed to identify clinical features and blood biomarkers associated with persistent Long COVID symptoms. Methods: We sent a detailed long COVID symptoms questionnaire to an existing cohort of 1258 vaccinated adults (age 18–79 years) who had mild infection (e.g., non-hospitalized) SARS-CoV-2 Delta variant 2 years earlier. These individuals had comprehensive datasets, including blood samples, available for further analysis. We estimated prevalence of persistent long COVID two years post-infection using weighted adjustment (Horvitz–Thompson estimator) to overcome reporting bias. Multivariable logistic regression models were used to determine association of clinical features and blood biomarkers (pre-infection SARS-CoV-2 RBD-IgG, SARS-CoV-2 neutralizing antibodies, and pre-infection and post-infection neurofilament light) with prevalence of persistent long COVID. Results: N = 323 participants responded to the survey, of whom N = 74 (23%) reported at least one long COVID symptom that had persisted for two years after the acute infection. Weighted prevalence of persistent long COVID symptoms was 21.5% (95% CI = 16.7–26.3%). Female gender, smoking, and severity of acute COVID-19 infection were significantly associated with persistent Long COVID. The blood biomarkers assessed were not significantly associated with persistent Long COVID. Conclusions: Among vaccinated adults two years after mild infection with Delta variant SARS-CoV-2, persistent symptoms attributed to Long COVID are extremely common, certain subgroups are at higher risk, and further research into biological mechanisms and potential treatment targets is needed. Full article