Clinical and immunological correlates of elevated age-adjusted QAlb in anti-NMDAR encephalitis

Anti-NMDAR encephalitis is a common form of autoimmune encephalitis with marked clinical heterogeneity. The cerebrospinal fluid (CSF)/serum albumin quotient (QAlb) is a clinically accessible marker reflecting blood-CSF barrier (BCB) function. However, the clinical significance of elevated age-adjusted QAlb in anti-NMDAR encephalitis remains unclear.

We retrospectively enrolled 103 patients with anti-NMDAR encephalitis and classified them into Elevated QAlb and Normal QAlb groups according to whether measured QAlb exceeded its age-adjusted upper reference limit (Qlim). Clinical features, paired serum-CSF findings, quantitative indices of intrathecal IgG synthesis, MRI/EEG findings, disease severity, and discharge outcomes were compared. Logistic regression, sensitivity analyses, Reibergram, and Spearman correlation analyses were performed.

Elevated age-adjusted QAlb was identified in 36 patients (35.0%). Compared with the Normal QAlb group, the Elevated QAlb group had higher proportions of male patients and prodromal headache, and showed higher CSF protein, CSF albumin, CSF IgG, IgG index (IgGI), and 24-h intrathecal IgG synthesis rate. Reibergram analysis showed that a higher proportion of patients in the Elevated QAlb group were above the Qlim(IgG) curve than in the Normal QAlb group [9/36 (25.0%) vs. 4/67 (6.0%), p = 0.010], supporting increased total intrathecal IgG synthesis beyond passive blood-derived transfer in a subset of patients. In contrast, CSF anti-NMDAR antibody titers, CSF pleocytosis, peak mRS and CASE scores, ICU admission, and discharge outcomes were comparable between groups. Male sex and prodromal headache remained associated with elevated QAlb after multivariable adjustment. Hippocampal MRI abnormalities were more frequent in the Elevated QAlb group, but this finding was based on only nine affected patients and should be considered exploratory.

Elevated age-adjusted QAlb was associated with increased quantitative markers of total intrathecal IgG synthesis, but not with CSF anti-NMDAR antibody titers, acute disease severity, or short-term discharge outcomes. These findings support interpreting QAlb as an accessible CSF marker related to BCB function rather than as a standalone acute prognostic marker. The observed association with hippocampal MRI abnormalities was exploratory and requires independent validation.