Cerebrospinal fluid measures of disease activity in patients with multiple sclerosis

Abstract

The potential of magnetic resonance imaging to serve as a surrogate marker of disease activity in patients with multiple sclerosis (MS) is increasingly recognised. In contrast, the use of cerebrospinal fluid analysis has received less attention. We analysed the correlation between clinical data and cerebrospinal fluid parameters in 75 patients with acute optic neuritis (ON) as a possible first symptom of MS, as a symptom of clinically definite MS, and in patients with an attack of MS other than ON. The samples were obtained within 30 days from the onset of an exacerbation. The concentration of myelin basic protein (MBP) in cerebrospinal fluid was significantly correlated with the visual acuity in patients with ON and the Kurtzke EDSS score in patients with MS. The concentration of MBP in CSF also correlated positively with the CSF leukocyte count, intrathecal IgG synthesis, and the CSF-serum albumin concentration quotient. The concentration of MBP in CSF correlated negatively with intrathecal IgA synthesis. The results support the use of the concentration of MBP in CSF as a surrogate marker of disease activity during acute exacerbations of MS; the data also link the presence of MBP in CSF to neuroimmunological parameters.

Relationship between Cerebrospinal Fluid Biomarkers for Inflammation, Demyelination and Neurodegeneration in Acute Optic Neuritis

“…MBP, previously shown to be weakly correlated with the severity of ON [33], did not associate to the ON severity or temporal course in our material, but was strongly associated with dissemination in space on MRI. CSF levels of MBP could represent both the damage from the ongoing attack and a more widespread breakdown of myelin, including that of subclinical lesions on MRI, providing one explanation for the lack of association to severity of the acute optic nerve demyelination.…”

Optic neuritis in multiple sclerosis

“…Elevated T cell-mediated cytotoxicity against the encephalitogenic peptide is a highly specific marker for demyelination in MS. Optic neuritis patients who test positive for this antigen have a greater risk of developing clinically definite MS. 115 The increased CSF MBP-and MBPreactive B cells in patients who had optic neuritis could correlate with the process of early myelin breakdown or restoration. 116 Although magnetic resonance imaging (MRI) generally has been accepted as the marker of disease activity in patients who have MS, the concentration of MBP in CSF also has been useful as a marker during acute exacerbations of MS.…”

CSF inflammation and axonal damage are increased and correlate in progressive multiple sclerosis

“…MBP has been established as a biomarker of demyelination in clinically isolated syndromes and RRMS, where there is a close relationship between concentrations of MBP and disease activity. 33 Furthermore, MBP in CSF is a response biomarker of the effect of treatment with methylprednisolone, and patients with high CSF concentrations of MBP have a better response to methylprednisolone. 34,35 It is tempting to speculate that the decreases in MBP concentrations could reflect the pathological observation of a shift from a white matter demyelinating pathology to a cortical-based pathology, where demyelination is present but less intense than in the white matter, but this hypothesis must be addressed in future studies.…”