scholarly journals Diagnostic and prognostic value of serum NfL and p-Tau181 in frontotemporal lobar degeneration

2020 ◽  
Vol 91 (9) ◽  
pp. 960-967 ◽  
Author(s):  
Alberto Benussi ◽  
Thomas K Karikari ◽  
Nicholas Ashton ◽  
Stefano Gazzina ◽  
Enrico Premi ◽  
...  

ObjectiveTo assess the diagnostic and prognostic value of serum neurofilament light (NfL) and serum phospho-Tau181 (p-Tau181) in a large cohort of patients with frontotemporal lobar degeneration (FTLD).MethodsIn this retrospective study, performed on 417 participants, we analysed serum NfL and p-Tau181 concentrations with an ultrasensitive single molecule array (Simoa) approach. We assessed the diagnostic values of serum biomarkers in the differential diagnosis between FTLD, Alzheimer’s disease (AD) and healthy ageing; their role as markers of disease severity assessing the correlation with clinical variables, cross-sectional brain imaging and neurophysiological data; their role as prognostic markers, considering their ability to predict survival probability in FTLD.ResultsWe observed significantly higher levels of serum NfL in patients with FTLD syndromes, compared with healthy controls, and lower levels of p-Tau181 compared with patients with AD. Serum NfL concentrations showed a high accuracy in discriminating between FTLD and healthy controls (area under the curve (AUC): 0.86, p<0.001), while serum p-Tau181 showed high accuracy in differentiating FTLD from patients with AD (AUC: 0.93, p<0.001). In FTLD, serum NfL levels correlated with measures of cognitive function, disease severity and behavioural disturbances and were associated with frontotemporal atrophy and indirect measures of GABAergic deficit. Moreover, serum NfL concentrations were identified as the best predictors of survival probability.ConclusionsThe assessment of serum NfL and p-Tau181 may provide a comprehensive view of FTLD, aiding in the differential diagnosis, in staging disease severity and in defining survival probability.

2020 ◽  
Vol 77 (3) ◽  
pp. 1129-1141 ◽  
Author(s):  
Alberto Benussi ◽  
Nicholas J. Ashton ◽  
Thomas K. Karikari ◽  
Stefano Gazzina ◽  
Enrico Premi ◽  
...  

Background: It is still unknown if serum glial fibrillary acidic protein (GFAP) is a useful marker in frontotemporal lobar degeneration (FTLD). Objective: To assess the diagnostic and prognostic value of serum GFAP in a large cohort of patients with FTLD. Methods: In this retrospective study, performed on 406 participants, we measured serum GFAP concentration with an ultrasensitive Single molecule array (Simoa) method in patients with FTLD, Alzheimer’s disease (AD), and in cognitively unimpaired elderly controls. We assessed the role of GFAP as marker of disease severity by analyzing the correlation with clinical variables, neurophysiological data, and cross-sectional brain imaging. Moreover, we evaluated the role of serum GFAP as a prognostic marker of disease survival. Results: We observed significantly higher levels of serum GFAP in patients with FTLD syndromes, except progressive supranuclear palsy, compared with healthy controls, but not compared with AD patients. In FTLD, serum GFAP levels correlated with measures of cognitive dysfunction and disease severity, and were associated with indirect measures of GABAergic deficit. Serum GFAP concentration was not a significant predictor of survival. Conclusion: Serum GFAP is increased in FTLD, correlates with cognition and GABAergic deficits, and thus shows promise as a biomarker of disease severity in FTLD.


2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Axel Petzold ◽  
Gordon T. Plant

Background. Loss of visual function differs between immune-mediated optic neuropathies and is related to axonal loss in the optic nerve. This study investigated the diagnostic and prognostic value of a biomarker for neurodegeneration, the neurofilament heavy chain (NfH) in three immune-mediated optic neuropathies.Methods. A prospective, longitudinal study including patients with optic neuritis due to multiple sclerosis (MSON,n=20), chronic relapsing inflammatory optic neuritis (CRION,n=19), neuromyelitis optica (NMO,n=9), and healthy controls (n=28). Serum NfH-SMI35 levels were quantified by ELISA.Findings. Serum NfH-SMI35 levels were highest in patients with NMO (mean0.79±1.51 ng/mL) compared to patients with CRION (0.13±0.16 ng/mL,P=0.007), MSON (0.09±0.09,P=0.008), and healthy controls (0.01±0.02 ng/mL,P=0.001). High serum NfH-SMI35 levels were related to poor visual outcome.Conclusions. Blood NfH-SMI35 levels are of moderate diagnostic and more important prognostic value in immune-mediated optic neuropathies. We speculate that longitudinal blood NfH levels may help to identify particular disabling events in relapsing conditions.


2021 ◽  
Vol 8 (1) ◽  
pp. e000827 ◽  
Author(s):  
Carlos Machahua ◽  
Sabina A. Guler ◽  
Michael P. Horn ◽  
Lurdes Planas-Cerezales ◽  
Ana Montes-Worboys ◽  
...  

BackgroundNon-invasive biomarkers for the assessment of disease severity in idiopathic pulmonary fibrosis (IPF) are urgently needed. Calprotectin belongs to the S-100 proteins produced by neutrophils, which likely contribute to IPF pathogenesis. Calprotectin is a well-established biomarker in inflammatory bowel diseases. In this cross-sectional study, we aimed to establish the potential role of calprotectin as a biomarker in IPF. Specifically, we hypothesised that patients with IPF have higher serum calprotectin levels compared with healthy controls, and that calprotectin levels are associated with disease severity.MethodsBlood samples were obtained from healthy volunteers (n=26) and from two independent IPF cohorts (derivation cohort n=26, validation cohort n=66). Serum calprotectin levels were measured with a commercial kit adapted for that purpose and compared between healthy controls and patients with IPF. Clinical parameters, including forced vital capacity, diffusing capacity for carbon monoxide (DLCO) and the Composite Physiologic Index (CPI), were correlated with calprotectin serum levels.ResultsThe IPF derivation cohort showed increased serum calprotectin levels compared with healthy controls (2.47±1.67 vs 0.97±0.53 µg/mL, p<0.001). In addition, serum calprotectin levels correlated with DLCO% predicted (r=−0.53, p=0.007) and with CPI (r=0.66, p=0.007). These findings were confirmed in an independent IPF validation cohort.ConclusionSerum calprotectin levels are significantly increased in patients with IPF compared with healthy controls and correlate with DLCO and CPI. Calprotectin might be a potential new biomarker for disease severity in IPF.


Neurology ◽  
2018 ◽  
Vol 90 (6) ◽  
pp. e518-e524 ◽  
Author(s):  
Åsa Sandelius ◽  
Henrik Zetterberg ◽  
Kaj Blennow ◽  
Rocco Adiutori ◽  
Andrea Malaspina ◽  
...  

ObjectiveTo perform a cross-sectional study to determine whether plasma neurofilament light chain (NfL) concentration is elevated in patients with Charcot-Marie-Tooth disease (CMT) and if it correlates with disease severity.MethodsBlood samples were collected from 75 patients with CMT and 67 age-matched healthy controls over a 1-year period. Disease severity was measured using the Rasch modified CMT Examination and neuropathy scores. Plasma NfL concentration was measured using an in-house-developed Simoa assay.ResultsPlasma NfL concentration was significantly higher in patients with CMT (median 26.0 pg/mL) compared to healthy controls (median 14.6 pg/mL, p < 0.0001) and correlated with disease severity as measured using the Rasch modified CMT examination (r = 0.43, p < 0.0001) and neuropathy (r = 0.37, p = 0.044) scores. Concentrations were also significantly higher when subdividing patients by genetic subtype (CMT1A, SPTLC1, and GJB1) or into demyelinating or axonal forms compared to healthy controls.ConclusionThere are currently no validated blood biomarkers for peripheral neuropathy. The significantly raised plasma NfL concentration in patients with CMT and its correlation with disease severity suggest that plasma NfL holds promise as a biomarker of disease activity, not only for inherited neuropathies but for peripheral neuropathy in general.


1981 ◽  
Author(s):  
M Monreal ◽  
R Rodriguez ◽  
P Vañentin ◽  
J Monasterio

AT-III activity has been evaluated in 675 patients with different kinds of hepatic disease.In 300 patients with hepatic chronic disease, AT-III levels showed a good correlation with prothrombin time as well as same diagnostic value. Survival in this group of patients was directly related to AT-III values.In 75 patients with acute liver disease, persistent low AT-III values correlated with clinical evolution of fulminans hepatitis.In 200 patients with cholestatic syndrome, evaluation of AT-III levels had no value for differential diagnosis of neither obstacle’s localization nor benign or neoplastic process.In 100 patients, suffering from cancer, without and with hepatic metastasis, AT-III values decreased in terminal states only.


2019 ◽  
Author(s):  
Dwi Ratna Adisty ◽  
Iskandar Zulkarnain ◽  
Diah Mira Indramaya

Melatonin an important immunomodulatory molecule in allergic diseases. Melatonin also plays a role in several body systems including to regulate circadian rhythms because of its role to cause drowsiness. Research shows in the case of atopic dermatitis (AD) circadian production of melatonin is reduced compared to healthy controls. This study aimed to investigate the differences of urinary melatonin levels between children with AD and healthy controls, and its relationship with disease severity. A cross sectional study was conducted in pediatric dermatology division of our outpatient clinic. Severity of AD was determined by using the instruments Scoring Atopic Dermatitis (SCORAD). Urinary melatonin levels were measured by Enzyme-linked immunosorbent assay (ELISA). The urinary melatonin levels in AD group were not significantly lower than in healthy controls (P =0.98 P<0.05) but the means show lower levels of urinary melatonin levels in AD group (486.73 ± 292.13 pg/ml , 611.51 ± 280.45 pg/ml, respectively). There were no significant association between urinary melatonin levels and disease severity (P > 0.05) but there’s a tendency of decreased urinary melatonin with increased the severity of AD.


Neurology ◽  
2018 ◽  
Vol 91 (14) ◽  
pp. e1338-e1347 ◽  
Author(s):  
Steffen Tiedt ◽  
Marco Duering ◽  
Christian Barro ◽  
Asli Gizem Kaya ◽  
Julia Boeck ◽  
...  

ObjectiveTo explore the utility of serum neurofilament light chain (NfL) as a biomarker for primary and secondary neuroaxonal injury after ischemic stroke (IS) and study its value for the prediction of clinical outcome.MethodsWe used an ultrasensitive single-molecule array assay to measure serum NfL levels in healthy controls (n = 30) and 2 independent cohorts of patients with IS: (1) with serial serum sampling at hospital arrival (n = 196), at days 2, 3, and 7 (n = 89), and up to 6 months post stroke; and (2) with standardized MRI at baseline and at 6 months post stroke, and with cross-sectional serum sampling at 6 months (n = 95). We determined the temporal profile of serum NfL levels, their association with imaging markers of neuroaxonal injury, and with clinical outcome.ResultsPatients with IS had higher serum NfL levels compared with healthy controls starting from admission until 6 months post stroke. Serum NfL levels peaked at day 7 (211.2 pg/mL [104.7–442.6], median [IQR]) and correlated with infarct volumes (day 7: partial r = 0.736, p = 1.5 × 10−15). Six months post stroke, patients with recurrent ischemic lesions on MRI (n = 19) had higher serum NfL levels compared to those without new lesions (n = 76, p = 0.002). Serum NfL levels 6 months post stroke further correlated with a quantitative measure of secondary neurodegeneration obtained from diffusion tensor imaging MRI (r = 0.361, p = 0.001). Serum NfL levels 7 days post stroke independently predicted modified Rankin Scale scores 3 months post stroke (cumulative odds ratio [95% confidence interval] = 2.35 [1.60–3.45]; p = 1.24 × 10−05).ConclusionSerum NfL holds promise as a biomarker for monitoring primary and secondary neuroaxonal injury after IS and for predicting functional outcome.


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