Thalamic nuclei volumes and structural covariance network in patients with Anti-N-methyl-D-aspartate receptor...

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis (anti-NMDAR encephalitis) is one of the most common types of autoimmune encephalitis in children, characterized by neuropsychiatric syndromes such as memory deficits, verbal apraxia and complex movement disorders. Evidence indicates thalamic abnormalities in anti-NMDAR encephalitis, yet existing studies have predominantly examined the thalamus only as an undifferentiated whole, particularly within the pediatric population. This study specifically characterized thalamic abnormalities in pediatric anti-NMDAR encephalitis at subnuclear scale, quantifying (1) nuclei-specific volumetric changes and (2) structural covariance network reorganization in pediatric patients versus age-matched healthy controls (HCs).

Thirty pediatric patients with anti-NMDAR encephalitis and 32 age- and sex-matched HCs who underwent structural MRI were recruited. Total thalamic volumes (bilateral) and individual thalamic nuclei volumes were obtained using FreeSurfer. For network analysis, group-level thalamic structural covariance matrices were generated in BRAPH by computing inter-regional partial correlations of nuclei volumes (covarying for age and sex) across participants, from which graph theory metrics were subsequently derived.

While no intergroup differences were observed in total thalamic volumes (left and right), pediatric patients with anti-NMDAR encephalitis exhibited significant volumetric reductions in specific thalamic subnuclei, including the right anteroventral (AV) nucleus, left lateral dorsal (LD) nuclei, and left lateral posterior (LP) nuclei (p < 0.001, Bonferroni corrected). Furthermore, the graph theory analysis revealed that pediatric patients with anti-NMDAR encephalitis showed a significant decrease in global efficiency (p < 0.05, permutation test) compared to HCs within the thalamic structural covariance network.

Our findings demonstrate that pediatric patients with anti-NMDAR encephalitis suffer from nuclei-specific structural damage and disrupted global integration within the thalamic structural covariance network. These subnuclear and network alterations highlight the critical role of the thalamus in the pathophysiology of cognitive dysfunction in childhood anti-NMDAR encephalitis, offering refined neuromorphological insights into the disease.