Biomarkers of Progression and Nerve loss

Martínez MA, Olsson B, Bau L, Matas E, Calvo ÁC, Andreasson U, Blennow K, Romero-Pinel L, Martínez-Yélamos S, Zetterberg H. Glial and neuronal markers in cerebrospinal fluid predict progression in multiple sclerosis. Mult Scler. 2015. pii: 1352458514549397. [Epub ahead of print]

OBJECTIVE: To investigate glial and neuronal biomarkers in cerebrospinal fluid (CSF) samples from patients with relapsing-remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS), and to evaluate their ability to predict conversion from CIS to clinically definite MS (CDMS) and also disability progression in MS.

METHODS: CSF levels of neurofilament light protein (NFL), t-tau, p-tau, glial fibrillary acidic protein (GFAP), S-100B, human chitinase 3-like 1 protein (YKL-40), monocyte chemoattractant protein-1 (MCP-1), α-sAPP and β-sAPP; and Aβ38, Aβ40 and Aβ42, were analyzed in 109 CIS patients and 192 RRMS patients. The mean follow-up time of these 301 patients was 11.7 ± 6.4 years.

RESULTS: High levels of NFL were associated with early conversion from CIS to CDMS (hazard ratio (HR) with 95% confidence interval (CI): 2.69 (1.75 – 4.15); p < 0.0001). High levels of YKL-40 and GFAP were associated with earlier progression in the Expanded Disability Status Scale (EDSS), score 3: YKL-40 (HR (95% CI): 2.78 (1.48 – 5.23); p = 0.001) and GFAP (HR (95% CI): 1.83 (1.01 – 3.35); p = 0.04). High levels of YKL-40 were associated with earlier progression to EDSS 6 (HR (95% CI): 4.57 (1.01 – 20.83); p = 0.05).

CONCLUSIONS: CSF levels of NFL in CIS patients are an independent prognostic marker for conversion to CDMS. Whereas, CSF levels of YKL-40 and GFAP are independent prognostic markers for disability progression in MS.

A few days ago profG and friends reported that high blood levels of neurofilament levels during the first symptom were indicators of who would convert to MS. 

They said that “If replicated in future studies, serum NfL may represent a reliable and easily accessible biomarker of early axonal damage in CIS and MS”. They didn’t have to wait long for a replication….i.e. about a week.

They also found that CHI3L1 produced by activated macrophages and GFAP, produced by activated astrocytes are markers of progression. These cells are common in MS lesions.

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  • I have been reading about neurofilament markers for about 4 years now – on this blog and from Australia – my question:

    since it's pretty sure that it's a solid proof WHEN will it be available for us MSers at the doctor's office?

    We need it as a measure of progression e.g. for applying for benefits it's very useful to have solid test results to get some money granted otherwise people tend to disbelieve us.

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