Inflammatory markers in cerebrospinal fluid: independent prognostic biomarkers in amyotrophic lateral sclerosis?. Issue 12 (7th June 2019)

• Record Type: Journal Article
• Authors: Gille, Benjamin; De Schaepdryver, Maxim; Dedeene, Lieselot; Goossens, Janne; Claeys, Kristl G; Van Den Bosch, Ludo; Tournoy, Jos; Van Damme, Philip; Poesen, Koen
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 90:Issue 12(2019)
• Page Start: 1338
• Page End: 1346
• Publication Date: 2019-06-07
• Subjects: amyotrophic lateral sclerosis -- inflammation -- biomarker -- survival; Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2018-319586
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : Objective: Inflammation is a key pathological hallmark in amyotrophic lateral sclerosis (ALS), which seems to be linked to the disease progression. It is not clear what the added diagnostic and prognostic value are of inflammatory markers in the cerebrospinal fluid (CSF) of patients with ALS. Methods: Chitotriosidase-1 (CHIT1), chitinase-3-like protein 1 (YKL-40) and monocyte chemoattractant protein-1 (MCP-1) were measured in CSF and serum of patients with ALS (n=105), disease controls (n=102) and patients with a disease mimicking ALS (n=16). The discriminatory performance was evaluated by means of a receiver operating characteristic curve analysis. CSF and serum levels were correlated with several clinical parameters. A multivariate Cox regression analysis, including eight other established prognostic markers, was used to evaluate survival in ALS. Results: In CSF, CHIT1, YKL-40 and MCP-1 showed a weak discriminatory performance between ALS and ALS mimics (area under the curve: 0.79, p<0.0001; 0.72, p=0.001; 0.75, p=0.001, respectively). CHIT1 and YKL-40 correlated with the disease progression rate (ρ=0.28, p=0.009; ρ=0.34, p=0.002, respectively). CHIT1 levels were elevated in patients with a higher number of regions displaying motor neuron degeneration (one vs three regions: 4248 vs 13 518 pg/mL, p = 0.0075). In CSF, YKL-40 and MCP-1 were independently associated with survival (HR: 29.7, p=0.0003; 6.14, p=0.001, respectively). Conclusions: Our findings show that inflammation in patients with ALS reflects the disease progression as an independent predictor of survival. Our data encourage the use of inflammatory markers in patient stratification and as surrogate markers of therapy response in clinical trials.