The new Global Multiple Sclerosis Severity Score (MSSS) correlates with axonal but not glial biomarkers

Abstract

This study investigated whether the new Global Multiple Sclerosis Severity Scale (MSSS) correlated with cerebrospinal fluid biomarkers for axonal and glial pathology. The MSSS correlated with the phosphorylated neurofilament heavy chain (NfH-SMI35, R=0.44, P=0.016). The degree of neurofilament phosphorylation (ratio NfH-SMI34 to NfH-SMI35) was 8-fold higher in severely (median MSSS 6.5) versus mildly (MSSS 3.2) disabled patients (7.3 versus 0.9, P=0.03). The MSSS may provide a statistically powerful tool for comparing overall disease severity and be useful for validating the biomarker concept in MS.

Keywords

biomarker MSSS multiple sclerosis

Get full access to this article

View all access options for this article.

References

Roxburgh RHSR , Seaman SR , Masterman T , Hensiek AE , Sawcer SJ , Vukusic S et al. Multiple Sclerosis Severity Score. Using disability and disease duration to rate disease severity . Neurology 2005; 64: 1144-1151 .

Petzold A. Neurofilament phosphoforms: surrogate markers for axonal injury, degeneration & loss . J Neurol Sci 2005; 233: 183-198 .

Petzold A , Eikelenboom MJ , Gveric D , Keir G , Chapman M , Lazeron RH et al. Markers for different glial cell responses in multiple sclerosis: clinical and pathological correlations . Brain 2002; 125: 1462-1473 .

Rosengren LE , Lycke J , Andersen O. Glial fibrillary acidic protein in CSF of multiple sclerosis patients-relation to neurological deficit . J Neurol Sci 1995; 133: 61-65 .

Malmestrom C , Haghighi S , Rosengren L , Andersen O , Lycke J. Neuro-filament light protein and glial fibrillary acidic protein as biological markers in MS . Neurology 2003; 61: 1720-1725 .

Lycke JN , Karlsson JE , Andersen O , Rosengren LE. Neurofilament protein in cerebrospinal fluid: a potential marker of activity in multiple sclerosis . J Neurol Neurosurg Psychiatry 1998; 64: 402-404 .

Petzold A , Baker D , Pryce G , Keir G , Thompson EJ , Giovannoni G. Quantification of neurodegeneration by measurement of brain-specific proteins . J Neuroimmunol 2003; 138: 45-48 .

G Pryce , Z Ahmed , DJ Hankey , Jackson SJ , Croxford JL , Pocock JM et al. Cannabinoids inhibit neurodegeneration in models of multiple sclerosis . Brain 2003; 127: 2191-2202 .

Jackson SJ , Baker D , Cuzner ML , Diemel LT. Cannabinoid-mediated neuroprotection following inter-feron-gamma treatment in a three-dimensional mouse brain aggregate cell culture . Eur J Neurosci 2004; 20: 2267-2275 .

10.

Petzold A , Eikelenboom MJ , Keir G , Grant D , Lazeron RH , Polman CH et al. Axonal damage accumulates in the progressive phase of multiple sclerosis: a 3-year follow-up study . J Neurol Neurosurg Psychiatry 2005; 76: 206-211 .

11.

Kurtzke JF. Rating neurological impairment in multiple sclerosis: an expanded disability status scale (EDSS) . Neurology 1983; 33: 1444-1452 .

12.

Rejdak K , Eikelenboom MJ , Petzold A , Thompson EJ , Stelmasiak Z , Lazeron RH et al. CSF nitric oxide metabolites are associated with activity and progression of multiple sclerosis . Neurology 2004; 63: 1439-1445 .

13.

Lublin FD , Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis . Neurology 1996; 46: 907-911 .