title: Assessment of a multiple biomarker panel for diagnosis of amyotrophic lateral sclerosis.
abstract: BACKGROUND
  The aim of the study was to assess a panel of promising biomarkers for their ability to improve diagnosis of sporadic amyotrophic lateral sclerosis (ALS).
  
  
  METHODS
  Forty patients with sporadic ALS and 40 controls with other neurological diseases were evaluated. Levels of phosphorylated neurofilament heavy chain (pNfH), S100-β, cystatin C, and chitotriosidase (CHIT) in cerebrospinal fluid were assayed using two-site solid-phase sandwich ELISA.
  
  
  RESULTS
  Patients with sporadic ALS showed higher levels of pNfH and CHIT than controls, but lower levels of cystatin C. Multivariate logistic regression that adjusted for patient age and sex identified significant associations between sporadic ALS and levels of pNfH, CHIT and cystatin C. Levels of pNfH correlated positively with rate of progression and decline based on the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised. Based on receiver operating curve analysis, a pNfH cut-off of 437 ng/L discriminated patients from controls with a sensitivity of 97.3 % and specificity of 83.8 %. A CHIT cut-off of 1593.779 ng/L discriminated patients from controls with a sensitivity of 83.8 % and specificity of 81.1 %. Combining the two biomarkers gave a sensitivity of 83.8 % and specificity of 91.9 %.
  
  
  CONCLUSIONS
  Levels of pNfH in cerebrospinal fluid may be a reliable biomarker for diagnosing ALS, and combining this biomarker with levels of CHIT may improve diagnostic accuracy.
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Xueping
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Ruwei
authors.initials: R
authors.lastname: Ou
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Cao
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Bi
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China. hfshang2002@126.com.
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Shang
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D055316:Cystatin C / Q000134:cerebrospinal fluid*; D018450:Disease Progression; D005260:Female; D006596:Hexosaminidases / Q000134:cerebrospinal fluid*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D011237:Predictive Value of Tests; D064568:S100 Calcium Binding Protein beta Subunit / Q000134:cerebrospinal fluid*; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D055316:Cystatin C; D016900:Neurofilament Proteins; D064568:S100 Calcium Binding Protein beta Subunit; C051774:neurofilament protein H; D006596:Hexosaminidases; C086400:chitotriosidase
keywords: Amyotrophic lateral sclerosis; Biomarker; CHIT; S100-β; cystatin C; pNfH