Disease progression and brain atrophy in NMDAR encephalitis: Associated factor & clinical implication.

OBJECTIVE

We investigated the longitudinal pattern, determining factors, and clinical implications of brain volume changes in N-methyl d-aspartate receptor-antibody (NMDAR) encephalitis.

METHODS

Baseline clinical profiles, treatment profiles, and outcome measured using the Clinical Assessment Scale in Autoimmune Encephalitis (CASE) and modified Rankin scale (mRS) were obtained from a long-term clinical database documenting an NMDAR encephalitis cohort. In serial MRI, the change in the normalized volume of different brain regions from the baseline evaluation was measured. At each MRI evaluation time point, the cumulative disease burden (CASE score × months) and the cumulative duration of status epilepticus were also evaluated.

RESULTS

Thirty-six patients were followed-up for 28.5 months (range 12-63 months). The volume ratio at last MRI to baseline was the lowest in the cerebellum (94.4 ± 5.7%, p < 0.001). Once developed, cerebellar volume reduction followed a progressive course until 2 years from disease onset. The degree of cerebellar volume reduction was positively correlated with mRS and total CASE scores (all, p < 0.001), and CASE scores in the domains of memory, language, and psychiatric problems, gait instability/ataxia, and weakness (all, p < 0.01). In linear mixed model analyses, the degree of cerebellar volume reduction was associated with cumulative disease burden up to 2 years (p < 0.001) and duration of status epilepticus (p < 0.001), and delayed removal of teratoma for ≥1 month (p = 0.006).

INTERPRETATION: In NMDAR encephalitis, cerebellar volume reduction was progressive once developed. Cerebellar volume reduction might reflect disease burden and extent of progression and be associated with poor outcomes in multiple functional domains.