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. 2005 Feb;76(2):206–211. doi: 10.1136/jnnp.2004.043315

Axonal damage accumulates in the progressive phase of multiple sclerosis: three year follow up study

A Petzold 1, M Eikelenboom 1, G Keir 1, D Grant 1, R Lazeron 1, C Polman 1, B Uitdehaag 1, E Thompson 1, G Giovannoni 1
PMCID: PMC1739484  PMID: 15654034

Abstract

Background: Neurofilament phosphoforms (Nf) are principal components of the axoskeleton released during axonal injury. Cerebrospinal fluid (CSF) levels of Nf phosphoforms might be useful surrogate markers for disability in multiple sclerosis (MS), aid in distinguishing clinical subtypes, and provide valuable prognostic information.

Method: Thirty four patients with MS were included in a three year follow up study along with 318 controls with other non-inflammatory neurological diseases. CSF levels of two Nf heavy chain (NfH) phosphoforms (NfHSMI35, NfHSMI34) were quantified at baseline and three year follow up using new ELISA techniques. Levels of NfH phosphoforms, the degree of phosphorylation (NfHSMI34:NfHSMI35 ratio), and changes in NfH levels between baseline and follow up (ΔNfH) were related to the clinical phenotype (RR or SP/PP), to three clinical scales (Kurtzke's EDSS, ambulation index (AI), and nine hole peg test (9HPT)), and to progression of disability.

Results: A significantly higher proportion (59%) of patients with SP/PPMS experienced an increase in NfHSMI35 levels between baseline and follow up compared with those with RRMS (14%, p<0.05). CSF NfHSMI34 levels at baseline were higher in patients with SP/PP (11 pg/ml) compared with RR (7 pg/ml, p<0.05) and NfHSMI35 levels were higher at follow up in SP/PP (129 pg/ml) compared with levels below assay sensitivity in RR (p<0.05). NfHSMI35 correlated with the EDSS (rs = 0.54, p<0.01), the AI (rs = 0.42, p<0.05), and the 9HPT (rs = 0.59, p<0.01) at follow up.

Conclusion: The increase in NfH during the progressive phase of the disease together with the correlation of NfHSMI35 with all clinical scales at follow up suggests that cumulative axonal loss is responsible for sustained disability and that high NfHSMI35 levels are a poor prognostic sign.

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Selected References

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