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Compromised Long Association Fiber Architecture in Patients with Anti-Nmdar Encephalitis
16 Pages Posted: 14 Nov 2023
More...Abstract
Background: Previous study demonstrates widespread superficial white matter (U-fiber) damage in non-recovered anti-NMDAR encephalitis patients. However, the microstructural integrity of long association fibers and the contributing factors have yet to be determined.
Methods: Thirty-two patients diagnosed with anti-NMDAR encephalitis were consecutively recruited, along with 30 healthy controls matched for age and sex. Patient cohort was categorized into early immunotherapy subgroup and delayed immunotherapy subgroup according to the timing of immunotherapy initiation. Diffusion MRI scans was acquired for all subjects. Automated fiber quantification pipeline was employed to compute the diffusion properties of the major long association fibers based on the deterministic tractography algorithms. The diffusion properties of long association fibers were compared at bundle-wise and node-wise levels. Correlation analysis was performed to assess the relationship between mean diffusivity (MD) alterations of affected long association fibers and the time to initiate immunotherapy as well as cognitive performance.
Findings: Compared with healthy controls, patients with anti-NMDAR encephalitis showed widespread impaired microstructural integrity in major long association fibers, characterized by decreased fractional anisotropy and elevated MD tract profiles (FDR-corrected p＜0.05). Based on the distinguishable diffusion features identified by principal component analysis, a support vector machine classifier achieved a high accuracy (81%) in discriminating patients from healthy controls. Partial correlation analysis revealed a linear positive correlation between the time to initiate immunotherapy and mean MD of major long association fiber tracts, including the right inferior fronto-occipital fasciculus (r=0.3667, p= 0.0462), left inferior longitudinal fasciculus (r=0.4119, p= 0.0237), left uncinate fasciculus (r=0.3841, p= 0.0361), and right arcuate fasciculus (r=0.4161, p= 0.0222) at bundle-wise level. The delayed immunotherapy subgroup exhibited more prominent microstructural impairments within long association fibers at both bundle-wise and node-wise levels (FDR-corrected p <0.05). Furthermore, the MD properties of affected segments in delayed immunotherapy subgroup were negatively correlated with MMSE performance (FDR-corrected p <0.05).
Interpretation: Patients with anti-NMDAR encephalitis exhibited substantial microstructural damage in major long association fibers, with this damage being more pronounced in delayed immunotherapy subgroup. Our findings highlighted a compromised long association fiber architecture in the pathophysiology of anti-NMDAR encephalitis, and underscored the critical importance of initiating immunotherapy promptly after symptom onset.
Funding: This work was supported by grants from the National Natural Science Foundation of China (82271377), Guangdong Basic and Applied Basic Research Foundation (2022B1515120042), National Key Research and Development Program of China (2022YFC3600600), Technology Innovation 2030-"Brain Science and Brain-like Research Major Project(2022ZD0208900), National Natural Science Foundation of China (82071343, 82371354, 81701188), Guangdong Basic and Applied Basic Research Foundation (2021A1515010393) and Guangzhou Science and Technology Key R&D Plan (2023B03J1347), Guangzhou Municipal School (Hospital) Joint Funding (202201020415).
Declaration of Interest: The authors have no conflicts of interest to declare.
Ethical Approval: Ethical approval was granted by the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University in Guangdong Province, China [(2019)2-637]. The study protocol was carried out in accordance with the principles described in the Declaration of Helsinki. Written informed consent was obtained from all participants.
Keywords: anti-N-methyl-d-aspartate receptor encephalitis, diffusion tensor imaging, long association fiber, mean diffusivity, cognition
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