Assessment of a multiple biomarker panel for diagnosis of amyotrophic lateral sclerosis.

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-ß, 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.

Assessment of outcome predictors in first-episode acute myelitis: a retrospective study of 53 cases.

OBJECTIVE: To identify predictors of short- and long-term outcomes in acute myelitis (AM). DESIGN: First episodes of AM were retrospectively identified in a single institution. Information regarding demographics, clinical status, laboratory workup, magnetic resonance imaging of the spine and brain, and electrophysiological assessment was collected. Tau, 14-3-3 protein, and cystatin C levels were assessed de novo in stored cerebrospinal fluid samples. SETTING: A neurological department database. Patients Fifty-three patients with a first episode of AM. MAIN OUTCOME MEASURES: The prognostic value of all variables was analyzed for the following outcomes: recovery from the initial event, symptom recurrence, conversion to multiple sclerosis (MS), and long-term disability. RESULTS: Median follow-up was 6.2 years. Six patients (11%) remained monophasic; 5 (9%) developed recurrent myelitis; and 42 (79%) underwent conversion to MS. Sensory level absence, no sphincter involvement, abnormal magnetic resonance imaging findings in the brain, spinal cord lesions shorter than 3 vertebral segments, and abnormal somatosensory evoked potentials predicted MS conversion. Fifteen of 32 patients with pyramidal dysfunction at onset (47%) and 17 of 43 with relapses during follow-up (40%) had significant disability at the last visit compared with 2 of 21 patients without pyramidal manifestations (10%) and none of the patients without exacerbations (P = .006 and P = .02, respectively). In 11 patients with exacerbations, we observed a significant correlation between cerebrospinal fluid levels of cystatin C and the degree of neurological disability at the last visit (Spearman rho = 0.69; P = .03). CONCLUSIONS: For patients with first-episode AM, the conversion rate to MS is high. Motor dysfunction at onset and relapse occurrence are associated with worse outcome. Cerebrospinal fluid levels of cystatin C may prove useful for predicting the prognosis of such patients.

The assessment of beta amyloid, tau protein and cystatin C in the cerebrospinal fluid: laboratory markers of neurodegenerative diseases.

To assess the role of tau protein, beta-amyloid(1-42) and cystatin C in the diagnostics of Alzheimer dementia (AD) and other neurodegenerative diseases (ND) by comparing to the control groups (CG). The levels of tau protein, beta-amyloid(1-42) and cystatin C were assessed in the set of 69 patients (AD + ND, 33 males, 36 females, aged 22-90, mean 60.5 + 16.1 years), and in a control group of 69 subjects without the affection of the central nervous system (CGAD + CGND, 33 males, 36 females, aged 20-91, mean 60.5 + 16.0 years). Statistically significant increased tau protein levels (P = 0.0001) and index tau/beta-amyloid(1-42) levels (P = 0.0002) were shown in the group of AD patients, compared to the group of ND patients. One-way ANOVA analysis with Bonferonni post hoc test did not show any significant differences of the cystatin C values between any of the compared groups. ROC analysis showed at least one tie between the positive actual state group (AD) and the negative actual state group (ND) by CSF cystatin C and at least one tie between the positive actual state group and the negative actual state group by CSF tau protein. Our study confirmed previously reported results only in part. While tau protein seems to be quite a reliable marker of AD, the role of beta-amyloid(1-42) and cystatin C in AD diagnosis remains at least questionable.