Permeability of the blood-CSF barrier in MOGAD: clinical correlation based on the 2023 diagnostic criteria

Abstract

Background: The pathogenesis of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is associated with damage to the blood-cerebrospinal fluid (CSF) barrier (BCB), but a specific correlation remains unclear. We used the newly proposed diagnostic criteria in 2023 with the aim to evaluate the permeability of the BCB in MOGAD.

Methods: We retrospectively analyzed data from 48 eligible patients with MOGAD. Serum and CSF samples were collected simultaneously prior to initiation of immunotherapies at admission. Elevated CSF/serum albumin quotient (QAlb) and indicators of intrathecal immunoglobulin G (IgG) synthesis were calculated as indicators of BCB damage. The relationship between the parameters and clinical features, disease severity, and prognosis were analyzed.

Results: Elevated QAlb levels were detected in 50% of patients, but only a small proportion of patients met the corresponding classifications of intrathecal IgG synthesis, namely IgG index >0.7 (10.4%), IgG synthesis rate >10 (6.2%), and local IgG synthesis rate >0 (8.1%). Elevated QAlb was significantly more common in patients with myelitis than in those with optic neuritis (p = 0.049). It was identified as an independent predictor of moderate-severe disease at admission (modified Rankin Scale [mRS]/Expanded Disability Status Scale [EDSS] ≥ 4). Moreover, elevated QAlb emerged as an independent risk factor for a poor long-term prognosis (mRS/EDSS ≥3 at the last follow-up).

Conclusions: BCB damage was common in MOGAD. Elevated QAlb could serve as a biomarker for evaluating disease severity at admission and predicting long-term prognosis.

Keywords: Blood-cerebrospinal fluid barrier; albumin quotient; disease severity; myelin oligodendrocyte glycoprotein antibody-associated disease; prognosis.

Figure 1.

Study flowchart. *Referred to Ref. [1]. Abbreviations: BCB, blood-cerebrospinal fluid barrier; CBA, cell-based assay; CNS, central nervous system; CSF, cerebrospinal fluid; IgG, immunoglobulin G; IgG loc, immunoglobulin G local synthesis; IgG SR, immunoglobulin G synthesis rate; MOG-IgG, myelin oligodendrocyte glycoprotein immunoglobulin G; MOGAD, myelin oligodendrocyte glycoprotein antibody-associated disease; QAlb, albumin quotient; QIgG, immunoglobulin G quotient.

Figure 2.

Reibergram displays QAlb and QIgG values for different patients (A). Indicators of BCB permeability in each demyelinating phenotype of MOGAD (B-F). The points with different colours and shapes correspond to different features listed in the box below. Points located above the QLim IgG curve (red) indicate the presence of intrathecal IgG synthesis. *Post-hoc analysis based on the Bonferroni method revealed statistically significant differences (p = 0.013, p = 0.001). Abbreviations: BCB, blood-cerebrospinal fluid barrier; IgG, immunoglobulin G; IgG loc, immunoglobulin G local synthesis; IgG SR, immunoglobulin G synthesis rate; MOGAD, myelin oligodendrocyte glycoprotein antibody-associated disease; QAlb, albumin quotient; QIgG, immunoglobulin G quotient.

Figure 3.

Correlogram of different indicators in MOGAD. The bottom left of the plot indicates the correlation value between the corresponding variables. The circle size at the top right represents the magnitude of the correlation coefficient, which corresponds to the colour value in the chart notes of the correlation coefficient on the right. Abbreviations: EDSS, Expanded Disability Status Scale; IgG, immunoglobulin G; IgG loc, immunoglobulin G local synthesis; IgG SR, immunoglobulin G synthesis rate; mRS, modified Rankin Scale; MOG-IgG, myelin oligodendrocyte glycoprotein immunoglobulin G; MOGAD, myelin oligodendrocyte glycoprotein antibody-associated disease; QAlb, albumin quotient; QIgG, immunoglobulin G quotient.

Figure 4.

Distribution of normal and elevated QAlb groups among different outcomes classified by mRS (A-C) and EDSS (D-F). The asterisk (*) indicates that elevated QAlb shows significant differences in the Chi-square analysis (p < 0.05), it is also identified as an independent risk factor for moderate-severe disease and poor long-term prognosis in multivariate analysis. Abbreviations: EDSS, Expanded Disability Status Scale; mRS, modified Rankin Scale; QAlb, albumin quotient.