Multimodal Brain MRI and Cognitive Changes in the Post-Acute Stage of Anti-NMDA Receptor Encephalitis
Mar Guasp1, Francesc Vivo2, Eloy Martínez-Heras2, Elisabeth Solana2, Eugenia Martinez-Hernandez3, Amaia Muñoz-Lopetegi2, Thais Armangue4, Laia Prades5, Elianet Fonseca5, Gisela Sugranyes6, Josefina Castro-Fornieles6, Albert Compte2, Josep Dalmau5, Sara Llufriu7
1Neurology, Hospital Clínic Barcelona - IDIBAPS/CaixaResearch Institute, 2IDIBAPS, 3Hospital Clinic Barcelona, 4IDIBAPS-HClinic, 5IDIBAPS/CaixaResearch Institute, 6Child and Adolescent Psychiatry, Hospital Clínic Barcelona, 7Neurology, Hospital Clínic Barcelona - IDIBAPS
Objective:
We aimed to characterize the course of alterations in brain grey matter (GM) volumetry and diffusion-based white matter (WM) connectivity, and their association with cognitive performance during the post-acute stage of anti-NMDAR encephalitis (NMDARe).
Background:
NMDARe has a characteristic post-acute symptomatic stage. Previous studies suggested varying degrees of accompanying brain MRI alterations, but did not prospectively assess the longitudinal evolution of these changes and potential associations with cognitive outcomes.
Design/Methods:
In this prospective longitudinal cohort study, adult NMDARe patients and age-matched healthy participants (HP) were prospectively examined at 4, 8, 12 and 12-24 months from disease onset with paired cognitive and multimodal MRI assessments including whole brain and regional grey matter (GM) volumetry, and diffusion-based WM connectivity quantified with fractional anisotropy. Differences between NMDARe and HP were analyzed using multilevel linear mixed-effect models.
Results:
Twenty-one post-acute NMDARe and 19 HP were included. Compared with HP, patients showed similar global brain volume, but specific regional changes that included atrophy of the middle frontal cortex and enlargement of bilateral hippocampus and right amygdala, mainly during the first 8 months from disease onset, which improved over time. NMDARe patients showed differences in 76/2020 (3.8%; p<0.05, family-wise error rate) WM connections, following two distinct dynamic patterns: reduced connectivity in 63/76 (83%) connections, involving bilateral cingulate, parietal cortex and deep GM, which improved rapidly (first 8 months), and increased connectivity in 13/76 (17%) connections, mainly subcortical areas, which stabilized over time. Regional atrophy and decreased WM connectivity largely explained variability in working memory (87%) and learning and memory (86%) outcomes.
Conclusions:
In post-acute NMDARe there is an early phase (first 8 months of symptoms) characterized by rapid improvement of volumetric changes and alterations of WM connectivity, followed by stagnation of these MRI alterations (8-24 months after symptom onset). These alterations occur in association with protracted cognitive deficits.
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