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Integrated evaluation of a panel of neurochemical biomarkers to optimize diagnosis and prognosis in amyotrophic lateral sclerosis
Author(s) -
Falzone Yuri Matteo,
Domi Teuta,
Mandelli Alessandra,
Pozzi Laura,
Schito Paride,
Russo Tommaso,
Barbieri Alessandra,
Fazio Raffaella,
Volontè Maria Antonietta,
Magnani Giuseppe,
Del Carro Ubaldo,
Carrera Paola,
Malaspina Andrea,
Agosta Federica,
Quattrini Angelo,
Furlan Roberto,
Filippi Massimo,
Riva Nilo
Publication year - 2022
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.15321
Subject(s) - amyotrophic lateral sclerosis , medicine , biomarker , glial fibrillary acidic protein , cohort , gastroenterology , area under the curve , pathology , oncology , disease , immunohistochemistry , biochemistry , chemistry
Background and purpose This study was undertaken to determine the diagnostic and prognostic value of a panel of serum biomarkers and to correlate their concentrations with several clinical parameters in a large cohort of patients with amyotrophic lateral sclerosis (ALS). Methods One hundred forty‐three consecutive patients with ALS and a control cohort consisting of 70 patients with other neurodegenerative disorders (DEG), 70 patients with ALS mimic disorders (ALSmd), and 45 healthy controls (HC) were included. Serum neurofilament light chain (NfL), ubiquitin carboxyl‐terminal hydrolase isozyme L1 (UCHL1), glial fibrillary acidic protein (GFAP), and total tau protein levels were measured using ultrasensitive single molecule array. Results NfL correlated with disease progression rate ( p < 0.001) and with the measures of upper motor neuron burden ( p < 0.001). NfL was higher in the ALS patients with classic and pyramidal phenotype. GFAP was raised in ALS with cognitive–behavioral impairment compared with ALS with normal cognition. NfL displayed the best diagnostic performance in discriminating ALS from HC (area under the curve [AUC] = 0.990), DEG (AUC = 0.946), and ALSmd (AUC = 0.850). UCHL1 performed well in distinguishing ALS from HC (AUC = 0.761), whereas it was not helpful in differentiating ALS from DEG and ALSmd. In multivariate analysis, NfL ( p < 0.001) and UCHL1 ( p = 0.038) were independent prognostic factors. Survival analysis combining NfL and UCHL1 effectively stratified patients with lower NfL levels ( p < 0.001). Conclusions NfL is a useful biomarker for the diagnosis of ALS and the strongest predictor of survival. UCHL1 is an independent prognostic factor helpful in stratifying survival in patients with low NfL levels, likely to have slowly progressive disease. GFAP reflects extramotor involvement, namely cognitive impairment or frontotemporal dementia.