Epub: Romme Christensen et al. CSF inflammation and axonal damage are increased and correlate in progressive multiple sclerosis. Mult Scler. 2012 Nov.
BACKGROUND: The mechanism underlying disease progression in progressive MSers is uncertain. Pathological studies find widespread inflammation in progressive MS brains correlating with disease progression and axonal damage.
OBJECTIVES: To study cerebrospinal fluid (CSF) biomarkers and clarify whether inflammation and axonal damage are associated in progressive MS.
METHODS: Using enzyme-linked immunosorbent assay (ELISA), they analysed CSF from 40 secondary progressive (SPMS), 21 primary progressive (PPMS), and 36 relapsing-remitting (RRMS) MSers and 20 non-inflammatory neurological disease (NIND) controls. Twenty-two of the SPMSers participated in an MBP8298 peptide clinical trial and had CSF follow-up after one year.
RESULTS: Compared to NIND patients, inflammatory biomarkers osteopontin and matrix metalloproteinase-9 (MMP9) were increased in all MSers while CXCL13 was increased in RR and SP MSers. Biomarkers of axonal damage (NFL) and demyelination (MBP) were increased in all MSers. In progressive MSers CSF levels of osteopontin and CXCL13 correlated with NFL while osteopontin and MMP9 correlated with MBP. MBP8298 treatment did not affect the levels of the biomarkers after one year of treatment. All biomarkers were continuously increased after one year of follow-up except MBP, which decreased.
CONCLUSION: CSF biomarkers of inflammation, axonal damage and demyelination are continuously increased in progressive MSers and correlate. These findings parallel pathology studies, emphasise a relationship between inflammation, axonal damage and demyelination and support the use of CSF biomarkers in progressive MS clinical trials.