The cerebral biomarkers, neurofilament light chain (NfL), amyloid-β, tau, and neuron specific enolase (NSE) reflect a wide spectrum of neurological damage in the brain and spinal cord. With this study, we aimed to assess whether these biomarkers hold any potential diagnostic value for the three most common canine neurological diseases. Canines suffering from meningoencephalitis of unknown origin (MUO), brain tumors, and selected non-infectious myelopathies were included. For each diagnosis, we analyzed these biomarkers in the cerebrospinal fluid collected via cranial puncture from the cisterna magna. Elevated levels of CSF tau, NfL, and NSE were observed in MUO, with all three biomarkers being intercorrelated. Tau and NSE were increased while amyloid-β was decreased in dogs suffering from tumors. In contrast, no biomarker changes were observed in dogs with myelopathies. Covariates such as age, sex, or castration had minimal impact. CSF biomarkers may reflect molecular changes related to MUO and tumors, but not to non-infectious myelopathies. The combination of NfL, tau, and NSE may represent useful biomarkers for MUO as they reflect the same pathology and are not influenced by age.
- MeSH
- amyloidní beta-protein mozkomíšní mok MeSH
- biologické markery * mozkomíšní mok MeSH
- fosfopyruváthydratasa mozkomíšní mok MeSH
- meningoencefalitida mozkomíšní mok veterinární diagnóza MeSH
- nádory mozku mozkomíšní mok veterinární MeSH
- nemoci nervového systému mozkomíšní mok veterinární diagnóza MeSH
- nemoci psů * mozkomíšní mok diagnóza MeSH
- neurofilamentové proteiny * mozkomíšní mok MeSH
- proteiny tau * mozkomíšní mok MeSH
- psi MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- psi MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
AIMS: The aim of this study was to evaluate the association of serum neurofilament heavy chain (sNfH) and chitinase 3-like 1 (sCHI3L1) with treatment response and disease activity in multiple sclerosis (MS). METHODS: This single-center, prospective, observational cohort study was conducted at the MS Centre, University Hospital Ostrava, Czech Republic, from May 2020 to August 2023. sNfH and sCHI3L1 were determined using ELISA. A mixed-effects linear model with a log-transformed outcome variable was applied. RESULTS: We analyzed 459 samples from 57 people with MS. Patients were sampled an average of 8.05 times during 21.9 months of follow-up. Those experiencing a relapse at sampling had a sNfH concentration 50 % higher than those in remission (exp(β) 1.5, 95 % CI 1.15-1.96). A longer duration of treatment was associated with lower sNfH (exp(β) 0.95, 95 % CI 0.94-0.96). Patients switched from low- to high-efficacy disease-modifying therapies (DMTs) had higher sNfH than patients treated with low-efficacy DMTs only (exp(β) 1.95, 95 % CI 1.35-2.81). Higher sCHI3L1 was associated with older age (exp(β) 1.01, 95 % CI 1.00-1.02) and longer DMT use (exp(β) 1.01, 95 % CI 1.00-1.02). sCHI3L1 values were not associated with relapse at the time of sampling, renal function, sex, or type of DMT. CONCLUSION: In contrast to sCHI3L1, sNfH may be a potential biomarker for monitoring treatment response and confirming clinical relapse in MS. Further research is needed to determine the long-term dynamics of sNfH and develop related treatment strategies.
- MeSH
- biologické markery * krev MeSH
- dospělí MeSH
- hodnocení výsledků zdravotní péče MeSH
- imunologické faktory aplikace a dávkování farmakologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- neurofilamentové proteiny * krev MeSH
- prospektivní studie MeSH
- protein CHI3L1 * krev MeSH
- roztroušená skleróza krev farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
INTRODUCTION: The gold standard for serum neurofilament light chain (sNfL) determination is the single molecule array (SIMOA), the use of which is limited by availability and cost. The VEUS method is a fully automated, user-friendly diagnostic system requiring no sample preparation, with high reported sensitivity, multiplexing capability, and rapid diagnostics. The aim of this study was to compare the SIMOA and VEUS methods for determining sNfL levels in patients with multiple sclerosis (MS). METHODOLOGY: A single-centre cross-sectional study was conducted at the MS Centre of University Hospital Ostrava. Patients were enrolled in the study from January 18 to January 31, 2024. Inclusion criteria were: 1) diagnosis of MS according to the revised 2017 McDonald criteria, 2) age ≥18 years, and 3) signed informed consent. The NF-light V2 diagnostic kit (SIMOA, Quanterix) and the Singleplex Neurology assay kit (VEUDx, EZDiatech) were used to determine sNfL concentrations. The two methods were compared by use of Spearman correlation, Passing-Bablok regression, and Bland-Altman analysis. RESULTS: A total of 49 patients were included in the study, of whom 39 (79.6 %) were female. The median sNfL concentration was 7.73 (IQR 5.80-9.93) ng/L determined by SIMOA and 1.31 (IQR 1.18-1.65) ng/L by VEUS. We did not find a correlation between SIMOA and VEUS (rs = 0.025, p = 0.866). Passing-Bablok regression demonstrated a systematic and proportional difference between the two methods. A significant disagreement between them was also confirmed by the Bland-Altman plots. On average, sNfL values measured by SIMOA were 3.56 ng/L (95 % CI 0.78 to 6.34) higher than those measured by VEUS. CONCLUSION: Our investigation uncovered noteworthy disparities between the SIMOA and VEUS techniques in determining sNfL levels. Specifically, the VEUS technique systematically produces lower estimates of sNFL levels. This substantial variance emphasizes the importance of carefully evaluating assay methods when quantifying sNfL.
- MeSH
- biologické markery krev MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- neurofilamentové proteiny * krev MeSH
- průřezové studie MeSH
- roztroušená skleróza * krev diagnóza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
BACKGROUND AND OBJECTIVES: Serum neurofilament light chain (sNfL) levels correlate with multiple sclerosis (MS) disease activity, but the dynamics of this correlation are unknown. We evaluated the relationship between sNfL levels and radiologic MS disease activity through monthly assessments during the 24-week natalizumab treatment interruption period in RESTORE (NCT01071083). METHODS: In the RESTORE trial, participants with relapsing forms of MS who had received natalizumab for ≥12 months were randomized to either continue or stop natalizumab and followed with MRI and blood draws every 4 weeks to week 28 and again at week 52 The sNfL was measured, and its dynamics were correlated with the development of gadolinium-enhancing (Gd+) lesions. Log-linear trend in sNfL levels were modeled longitudinally using generalized estimating equations with robust variance estimator from baseline to week 28. RESULTS: Of 175 patients enrolled in RESTORE, 166 had serum samples for analysis. Participants with Gd+ lesions were younger (37.7 vs 43.1, p = 0.001) and had lower Expanded Disability Status Scale scores at baseline (2.7 vs 3.4, p = 0.017) than participants without Gd+ lesions. sNfL levels increased in participants with Gd+ lesions (n = 65) compared with those without (n = 101, mean change from baseline to maximum sNfL value, 12.1 vs 3.2 pg/mL, respectively; p = 0.003). As the number of Gd+ lesions increased, peak median sNfL change also increased by 1.4, 3.0, 4.3, and 19.6 pg/mL in the Gd+ lesion groups of 1 (n = 12), 2-3 (n = 18), 4-9 (n = 21), and ≥10 (n = 14) lesions, respectively. However, 46 of 65 (71%) participants with Gd+ lesions did not increase above the 95th percentile threshold of the group without Gd+ lesions. The initial increase of sNfL typically trailed the first observation of Gd+ lesions, and the peak increase in sNfL was a median [interquartile range] of 8 [0, 12] weeks after the first appearance of the Gd+ lesion. DISCUSSION: Although sNfL correlated with the presence of Gd+ lesions, most participants with Gd+ lesions did not have elevations in sNfL levels. These observations have implications for the use and interpretation of sNfL as a biomarker for monitoring MS disease activity in controlled trials and clinical practice.
- MeSH
- biologické markery krev MeSH
- časové faktory MeSH
- dospělí MeSH
- gadolinium MeSH
- imunologické faktory terapeutické užití krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie * MeSH
- mozek diagnostické zobrazování patologie MeSH
- natalizumab * terapeutické užití MeSH
- neurofilamentové proteiny * krev MeSH
- posuzování pracovní neschopnosti MeSH
- progrese nemoci MeSH
- relabující-remitující roztroušená skleróza krev farmakoterapie diagnostické zobrazování MeSH
- roztroušená skleróza krev diagnostické zobrazování farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
Misdiagnosis is frequent in early motor neuron disease (MND), typically compressive radiculopathy, or in patients with restricted MND phenotype. In this retrospective, single tertiary centre study, we measured levels of neurofilament light (NfL) and phosphorylated neurofilament heavy (p-NfH) chain in cerebrospinal fluid (CSF) and of p-NfH in serum with commercially available ELISA kits and assessed their respective diagnostic performance as a marker of MND. The entire study population (n = 164) comprised 71 MND patients, 30 patients with compressive myelo- or radiculopathy, and 63 disease controls (DC). Among MND patients, we specified subgroups with only lower motoneuron involvement (MND-LMN, n = 15) and with confounding nerve roots or spinal cord compression (MND-C, n = 18), representing clinical diagnostic pitfalls. MND-LMN displayed significantly lower CSF NfL (p = 0.003) and p-NFH (p = 0.017), but not serum p-NfH (p = 0.347) levels compared to other MND patients (n = 56). The discriminative ability (area under the curve-AUC) of both CSF Nfs towards all MND patients was comparable to each other but significantly higher than that of p-NfH in serum (ps < 0.001). AUC of both CSF Nfs between MND-LMN and DC and also between MND-C and myelo-/radiculopathies were reduced, as compared to AUC between other MND and DC or myelo-/radiculopathies, respectively. Our results suggest that both Nfs in CSF represent a reliable diagnostic marker in a general MND population, fulfilling Awaji criteria. As for diagnostic pitfalls, and also for p-NfH in serum, their discriminative ability and, therefore, clinical utility appears to be limited.
Multiple sclerosis is a highly heterogeneous disease, and the detection of neuroaxonal damage as well as its quantification is a critical step for patients. Blood-based serum neurofilament light chain (sNfL) is currently under close investigation as an easily accessible biomarker of prognosis and treatment response in patients with multiple sclerosis. There is abundant evidence that sNfL levels reflect ongoing inflammatory-driven neuroaxonal damage (e.g. relapses or MRI disease activity) and that sNfL levels predict disease activity over the next few years. In contrast, the association of sNfL with long-term clinical outcomes or its ability to reflect slow, diffuse neurodegenerative damage in multiple sclerosis is less clear. However, early results from real-world cohorts and clinical trials using sNfL as a marker of treatment response in multiple sclerosis are encouraging. Importantly, clinical algorithms should now be developed that incorporate the routine use of sNfL to guide individualized clinical decision-making in people with multiple sclerosis, together with additional fluid biomarkers and clinical and MRI measures. Here, we propose specific clinical scenarios where implementing sNfL measures may be of utility, including, among others: initial diagnosis, first treatment choice, surveillance of subclinical disease activity and guidance of therapy selection.
- MeSH
- biologické markery krev MeSH
- lidé MeSH
- longitudinální studie MeSH
- magnetická rezonanční tomografie metody trendy MeSH
- neurofilamentové proteiny krev MeSH
- prognóza MeSH
- roztroušená skleróza krev diagnostické zobrazování MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
BACKGROUND The added value of neurofilament light chain levels in serum sNfL to the concept of no evidence of disease activity 3 NEDA 3 has not yet been investigated in detail OBJECTIVE To assess whether combination of sNfL with NEDA 3 status improves identification of patients at higher risk of disease activity during the following year METHODS We analyzed 369 blood samples from 155 ear
Various proteins play a decisive role in the pathology of different neurodegenerative diseases. Nonetheless, most of these proteins can only be detected during a neuropathological assessment, although some non-specific biomarkers are routinely tested for in the cerebrospinal fluid (CSF) as a part of the differential diagnosis of dementia. In antemortem CSF samples from 117 patients with different types of neuropathologically confirmed neurodegenerative disease with dementia, we assessed total-tau (t-tau), phosphorylated-tau (181P) (p-tau), amyloid-beta (1-42) (Aβ42), TAR DNA binding protein (TDP)-43, progranulin (PGRN), and neurofilament light (NfL) chain levels, and positivity of protein 14-3-3. We found t-tau levels and the t-tau/p-tau ratios were significantly higher in prion diseases compared to the other neurodegenerative diseases. Statistically significant differences in the t-tau/Aβ42 ratio predominantly corresponded to t-tau levels in prion diseases and Aβ42 levels in AD. TDP-43 levels were significantly lower in prion diseases. Additionally, the TDP-43/Aβ42 ratio was better able to distinguish Alzheimer's disease from other neurodegenerative diseases compared to using Aβ42 alone. In frontotemporal lobar degeneration, PRGN levels were significantly higher in comparison to other neurodegenerative diseases. There is an increasing need for biomarkers suitable for diagnostic workups for neurodegenerative diseases. It appears that adding TDP-43 and PGRN to the testing panel for neurodegenerative diseases could improve the resolution of differential diagnoses.
- MeSH
- amyloidní beta-protein mozkomíšní mok MeSH
- biologické markery mozkomíšní mok MeSH
- demence mozkomíšní mok klasifikace diagnóza MeSH
- diferenciální diagnóza MeSH
- DNA vazebné proteiny mozkomíšní mok MeSH
- lidé středního věku MeSH
- lidé MeSH
- neurofilamentové proteiny mozkomíšní mok MeSH
- peptidové fragmenty mozkomíšní mok MeSH
- pitva MeSH
- progranuliny mozkomíšní mok MeSH
- proteiny 14-3-3 mozkomíšní mok MeSH
- proteiny tau mozkomíšní mok MeSH
- proteiny v mozkomíšním moku mozkomíšní mok MeSH
- regulace genové exprese MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Increased blood brain barrier (BBB) permeability, CNS inflammation and neuroaxonal damage are pathological hallmarks in early multiple sclerosis (MS). OBJECTIVE: To investigate the associations of neurofilament light chain (NfL) levels with measures of BBB integrity and central nervous system (CNS) inflammation in MS during the first demyelinating event. METHODS: Blood and cerebrospinal fluid (CSF) were obtained from 142 MS (McDonald 2017) treatment-naive patients from the SET study (63% female; age: 29.7 ± 7.9 years) following the disease onset. NfL, albumin, immunoglobulin G (IgG), and immunoglobulin M (IgM) levels were measured in CSF and blood samples. Albumin quotient was computed as a marker of BBB integrity. Immune cell subset counts in CSF were measured using flow cytometry. MS risk factors, such as Human leukocyte antigen DRB1 locus gene (HLA DRB1)*1501, anti-Epstein-Barr virus (EBV) antibodies, and 25-hydroxy vitamin D3, were also measured. RESULTS: Higher serum NfL (sNfL) levels were associated with higher albumin quotient (p < 0.001), CSF CD80+ (p = 0.012), and CD80+ CD19+ (p = 0.015) cell frequency. sNfL levels were also associated with contrast-enhancing and T2 lesions on brain magnetic resonance imaging (MRI; all p ⩽ 0.001). Albumin quotient was not associated with any of the MS risk factors assessed. sNfL levels were associated with anti-EBV viral capsid antigen (VCA) IgG levels (p = 0.0026). CONCLUSION: sNfL levels during the first demyelinating event of MS are associated with greater impairment of BBB integrity, immune cell extravasation, and brain lesion activity on MRI.
- MeSH
- biologické markery MeSH
- dospělí MeSH
- hematoencefalická bariéra * MeSH
- intermediární filamenta MeSH
- lidé MeSH
- lymfocyty MeSH
- mladý dospělý MeSH
- neurofilamentové proteiny MeSH
- rizikové faktory MeSH
- roztroušená skleróza * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Serum neurofilament light chain (sNfL) is a marker of neuroaxonal injury. There is a lack of studies investigating the dynamics of relationships between sNfL levels and radiological disease activity over long-term follow-up in multiple sclerosis (MS). OBJECTIVES: To investigate the relationship among repeated measures of sNfL, lesion burden accumulation, brain volume loss and clinical measures. METHODS: We investigated 172 patients in the early stages of MS (McDonald 2017 criteria). Clinical exams were performed every 3 months and brain magnetic resonance imaging (MRI) scans were collected annually over 48 months. sNfL levels were measured in serum by Simoa assay at the time of treatment initiation and then annually over 36 months. RESULTS: In repeated-measures analysis, considering all time points, we found a strong relationship between percentage changes of sNfL and lesion burden accumulation assessed by T1 lesion volume (p < 0.001) and T2 lesion number (p < 0.001). There was no relationship between percentage changes of sNfL and brain volume loss over 36 months (p > 0.1). Early sNfL levels were associated with delayed brain volume loss after 48 months (p < 0.001). Patients with No Evidence of Disease Activity (NEDA-3) status showed lower sNfL levels compared with active MS patients. CONCLUSIONS: sNfL is associated with ongoing neuroinflammation and predictive of future neurodegeneration in early MS.
- MeSH
- biologické markery MeSH
- intermediární filamenta MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mozek diagnostické zobrazování MeSH
- neurofilamentové proteiny MeSH
- roztroušená skleróza * diagnostické zobrazování MeSH
- zánět diagnostické zobrazování MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
