PMID- 31175169
OWN - NLM
STAT- MEDLINE
DCOM- 20200611
LR  - 20200611
IS  - 1468-330X (Electronic)
IS  - 0022-3050 (Linking)
VI  - 90
IP  - 12
DP  - 2019 Dec
TI  - Inflammatory markers in cerebrospinal fluid: independent prognostic biomarkers in 
      amyotrophic lateral sclerosis?
PG  - 1338-1346
LID - 10.1136/jnnp-2018-319586 [doi]
AB  - 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 (rho=0.28, p=0.009; rho=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.
CI  - (c) Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and 
      permissions. Published by BMJ.
FAU - Gille, Benjamin
AU  - Gille B
AD  - Department of Neurosciences, Laboratory for Molecular Neurobiomarker Research, KU 
      Leuven, Leuven, Belgium.
AD  - Department of Chronic Disease, Metabolism and Ageing, KU Leuven, Leuven, Belgium.
FAU - De Schaepdryver, Maxim
AU  - De Schaepdryver M
AD  - Department of Neurosciences, Laboratory for Molecular Neurobiomarker Research, KU 
      Leuven, Leuven, Belgium.
AD  - Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.
FAU - Dedeene, Lieselot
AU  - Dedeene L
AD  - Department of Neurosciences, Laboratory for Molecular Neurobiomarker Research, KU 
      Leuven, Leuven, Belgium.
AD  - Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.
FAU - Goossens, Janne
AU  - Goossens J
AD  - Department of Neurosciences, Laboratory for Molecular Neurobiomarker Research, KU 
      Leuven, Leuven, Belgium.
FAU - Claeys, Kristl G
AU  - Claeys KG
AD  - Department of Neurology, Neuromuscular Reference Centre, University Hospitals 
      Leuven, Leuven, Belgium.
AD  - Department of Neurosciences, Laboratory for Muscle Diseases and Neuropathies, KU 
      Leuven, Leuven, Belgium.
FAU - Van Den Bosch, Ludo
AU  - Van Den Bosch L
AD  - Department of Neurosciences, Laboratory of Neurobiology, KU Leuven, Leuven, 
      Belgium.
AD  - VIB, Center for Brain & Disease Research, KU Leuven, Leuven, Belgium.
FAU - Tournoy, Jos
AU  - Tournoy J
AD  - Department of Chronic Disease, Metabolism and Ageing, KU Leuven, Leuven, Belgium.
AD  - Department of Geriatric Medicine, University Hospitals Leuven, Leuven, Belgium.
FAU - Van Damme, Philip
AU  - Van Damme P
AUID- ORCID: 0000-0002-4010-2357
AD  - Department of Neurology, Neuromuscular Reference Centre, University Hospitals 
      Leuven, Leuven, Belgium.
AD  - VIB, Center for Brain & Disease Research, KU Leuven, Leuven, Belgium.
FAU - Poesen, Koen
AU  - Poesen K
AUID- ORCID: 0000-0001-5290-9476
AD  - Department of Neurosciences, Laboratory for Molecular Neurobiomarker Research, KU 
      Leuven, Leuven, Belgium koen.poesen@uzleuven.be.
AD  - Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190607
PL  - England
TA  - J Neurol Neurosurg Psychiatry
JT  - Journal of neurology, neurosurgery, and psychiatry
JID - 2985191R
RN  - 0 (Biomarkers)
SB  - IM
CIN - J Neurol Neurosurg Psychiatry. 2019 Dec;90(12):1303-1304. PMID: 31296587
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Amyotrophic Lateral Sclerosis/*cerebrospinal fluid
MH  - Biomarkers/*cerebrospinal fluid
MH  - Case-Control Studies
MH  - Diagnosis, Differential
MH  - Disease Progression
MH  - Female
MH  - Humans
MH  - Inflammation/*cerebrospinal fluid
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Middle Aged
MH  - Predictive Value of Tests
MH  - Prognosis
MH  - ROC Curve
MH  - Survival Analysis
OTO - NOTNLM
OT  - amyotrophic lateral sclerosis
OT  - biomarker
OT  - inflammation
OT  - survival
COIS- Competing interests: None declared.
EDAT- 2019/06/09 06:00
MHDA- 2020/06/12 06:00
CRDT- 2019/06/09 06:00
PHST- 2018/09/06 00:00 [received]
PHST- 2019/04/11 00:00 [revised]
PHST- 2019/05/20 00:00 [accepted]
PHST- 2019/06/09 06:00 [pubmed]
PHST- 2020/06/12 06:00 [medline]
PHST- 2019/06/09 06:00 [entrez]
AID - jnnp-2018-319586 [pii]
AID - 10.1136/jnnp-2018-319586 [doi]
PST - ppublish
SO  - J Neurol Neurosurg Psychiatry. 2019 Dec;90(12):1338-1346. doi: 
      10.1136/jnnp-2018-319586. Epub 2019 Jun 7.