Contributions
Abstract: EP1598
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: Analysis of cerebrospinal fluid (CSF) biomarkers has the potential of clarifying the interplay between the inflammatory and degenerative components of multiple sclerosis (MS). The main goal of the study was to determine whether CSF concentration of neurofilament light chain (Nf-L), C-X-C ligand motif 13 (CXCL13), and chitinase-3-like protein 1 (CHI3L1) were associated with MRI measures of disease activity and grey matter pathology.
Methods: Consecutive patients with clinically isolated syndrome (CIS) or MS according to 2010 McDonald criteria, and a CSF sample stored at Verona Laboratory of Neuropathology were eligible for the study. All cases had a brain MRI performed at the time of lumbar puncture with a 1.5 Tesla scanner and a standardized protocol, including Double Inversion Recovery sequences. Brain volume analysis was performed using SIENAX software. CSF standard analysis, including IgG index and oligoclonal bands (OBs), was done at the time of sample collection. Commercial ELISA kits were used to determine Nf-L, CXCL13 and CHI3L1 levels on stored CSF samples. The distribution of CSF biomarker levels according to presence of enhancing and cortical lesions on brain MRI and the correlation between biomarkers CSF concentration, brain volumes and number of cortical lesions were analysed.
Results: As of May 2017, 78 patients (50 females) have been included in the study, with mean age at CSF collection of 38.3±12.5 years. 48 patients had relapsing-remitting MS, 15 a CIS, and 15 progressive forms of MS. Median disease duration at inclusion was 0.6 years (range 0-31). Mean Nf-L concentration was 4215 ng/L in patients with at least one enhancing lesion on MRI compared to 2043 ng/L in patients with no enhancing lesions (p=0.002). Mean Nf-L concentration was greater in patients with OBs or increased IgG index in CSF compared to cases without such findings (3795 vs. 1856 ng/L, p=0.002). Mean concentration of CXCL13 was 53.4 pg/mL in patients with OBs or increased IgG index in CSF, compared to 11.4 pg/mL in patients with no such evidence (p< 0.001). Finally, CHI3L1 level was inversely correlated to total cerebral volume (r= -0.317, p=0.018) and white matter volume (r= -0.279, p=0.039).
Conclusions: Nf-L and CXCL13 levels in the CSF of MS patients are associated with MRI and CSF measures of inflammatory activity, while CHI3L1 CSF concentration is correlated to brain volume loss. Implications for prognosis and treatment deserve further investigation.
Disclosure:
Dr. Zanoni: nothing to disclose;
Dr. Bongianni: nothing to disclose;
Dr. Poletto: nothing to disclose;
Dr. Turatti: nothing to disclose;
Dr. Marangi: nothing to disclose;
Dr. Gobbin: nothing to disclose;
Dr. Monaco: nothing to disclose;
Dr. Benedetti: nothing to disclose;
Dr. Calabrese received payment for development of educational presentations including service on speakers bureaus by Biogen-Elan, Genzyme, TEVA, Bayer-Schering, he received travel/accomodation expenses by Novartis Pharma, Genzyme, Biogen idec, Merck Serono, Bayer-Schering, TEVA, and Advisory Board membership by Bayer-Shering, Genzyme, Biogen Idec.
Dr. Gajofatto received speaker honoraria from Merck.
The study was supported by Cariverona Foundation and Merck.
Abstract: EP1598
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: Analysis of cerebrospinal fluid (CSF) biomarkers has the potential of clarifying the interplay between the inflammatory and degenerative components of multiple sclerosis (MS). The main goal of the study was to determine whether CSF concentration of neurofilament light chain (Nf-L), C-X-C ligand motif 13 (CXCL13), and chitinase-3-like protein 1 (CHI3L1) were associated with MRI measures of disease activity and grey matter pathology.
Methods: Consecutive patients with clinically isolated syndrome (CIS) or MS according to 2010 McDonald criteria, and a CSF sample stored at Verona Laboratory of Neuropathology were eligible for the study. All cases had a brain MRI performed at the time of lumbar puncture with a 1.5 Tesla scanner and a standardized protocol, including Double Inversion Recovery sequences. Brain volume analysis was performed using SIENAX software. CSF standard analysis, including IgG index and oligoclonal bands (OBs), was done at the time of sample collection. Commercial ELISA kits were used to determine Nf-L, CXCL13 and CHI3L1 levels on stored CSF samples. The distribution of CSF biomarker levels according to presence of enhancing and cortical lesions on brain MRI and the correlation between biomarkers CSF concentration, brain volumes and number of cortical lesions were analysed.
Results: As of May 2017, 78 patients (50 females) have been included in the study, with mean age at CSF collection of 38.3±12.5 years. 48 patients had relapsing-remitting MS, 15 a CIS, and 15 progressive forms of MS. Median disease duration at inclusion was 0.6 years (range 0-31). Mean Nf-L concentration was 4215 ng/L in patients with at least one enhancing lesion on MRI compared to 2043 ng/L in patients with no enhancing lesions (p=0.002). Mean Nf-L concentration was greater in patients with OBs or increased IgG index in CSF compared to cases without such findings (3795 vs. 1856 ng/L, p=0.002). Mean concentration of CXCL13 was 53.4 pg/mL in patients with OBs or increased IgG index in CSF, compared to 11.4 pg/mL in patients with no such evidence (p< 0.001). Finally, CHI3L1 level was inversely correlated to total cerebral volume (r= -0.317, p=0.018) and white matter volume (r= -0.279, p=0.039).
Conclusions: Nf-L and CXCL13 levels in the CSF of MS patients are associated with MRI and CSF measures of inflammatory activity, while CHI3L1 CSF concentration is correlated to brain volume loss. Implications for prognosis and treatment deserve further investigation.
Disclosure:
Dr. Zanoni: nothing to disclose;
Dr. Bongianni: nothing to disclose;
Dr. Poletto: nothing to disclose;
Dr. Turatti: nothing to disclose;
Dr. Marangi: nothing to disclose;
Dr. Gobbin: nothing to disclose;
Dr. Monaco: nothing to disclose;
Dr. Benedetti: nothing to disclose;
Dr. Calabrese received payment for development of educational presentations including service on speakers bureaus by Biogen-Elan, Genzyme, TEVA, Bayer-Schering, he received travel/accomodation expenses by Novartis Pharma, Genzyme, Biogen idec, Merck Serono, Bayer-Schering, TEVA, and Advisory Board membership by Bayer-Shering, Genzyme, Biogen Idec.
Dr. Gajofatto received speaker honoraria from Merck.
The study was supported by Cariverona Foundation and Merck.