Cerebrospinal fluid/serum gradient of IgG is associated with disability at acute attacks of neuromyelitis optica

Increased blood-brain barrier (BBB) disruption can be found in patients with neuromyelitis optica (NMO); however, its clinical implication and association with disability at acute attack remains obscure. The purpose of the study was to evaluate the clinical significance of BBB disruption and the subsequent cerebrospinal fluid (CSF)/serum IgG gradient in NMO. Retrospective analysis was made of acute-stage CSF samples from NMO (n = 40) and multiple sclerosis (MS; n = 26) patients. The CSF/serum IgG gradient (QIgG), albumin ratio (Qalb), and IgG index were calculated. Multivariate regression analysis was used to identify clinical and CSF variables associated with disability at acute attacks (extended disability scale score, EDSS) in both groups. The EDSS was significantly associated with the QIgG (p < 0.001), Qalb (p = 0.012), and number of cumulative attacks (p = 0.012) in NMO but not in MS with univariate analysis. Length of spinal cord involvement was also associated with EDSS in NMO (p = 0.030). However, multivariate analysis revealed that the QIgG was only significantly associated with EDSS in NMO (0.580; 95% CI -0.257, 0.961; p = 0.002). The QIgG was also highly associated with the Qalb in NMO (p < 0.001). The QIgG may reflect systemic IgG leakage into the CNS and is strongly associated with disability at acute attacks in NMO, suggesting that BBB disruption can aggravate disease activity by facilitating systemic IgG infiltration into the CNS.