Fifty-nine patients with p-NBS, identified based on the International Consensus Recommendation (ICR) criteria, and 57 healthy controls matched for age, sex, and educational level were included in this prospective study. Exclusion criteria were (i) presence of any comorbid neurological and/or psychiatric disease, drug, and/or alcohol abuse, (ii) p-NBS patients in the acute attack stage, (iii) NBS patients with a history of cerebral venous thrombosis or ischemic stroke, (iv) illiteracy, severe intellectual disability, visual and/or hearing impairment, and (v) individuals with prior intracranial surgery that could confound the structural analyses. The current systemic disease activity was evaluated with Behcet's Disease Current Activity Form (BDCAF), while cumulative systemic disease burden was assessed with Behcet's Syndrome Overall Damage Index (BODI). A modified version of the Kurtzke's Expanded Disability Status Scale (EDSS) for BS was used to determine physical disability rating and disease severity [7]. General cognitive performance was measured using the Montreal Cognitive Assessment (MoCA) questionnaire. Diffusion tensor imaging on 3T scanner was acquired in transverse plane with single-shot, spin-echo echo-planar sequence (TR: 2561 ms, TE: 97 ms, 2 mm isotropic resolution, multi-band factor of 2, NSA: 2, phase-encoding direction: AP, b=1000 s/mm2, and 64 diffusion-sensitizing directions).
Whole-brain FBA analysis was performed using the MRtrix3 pipeline to compare inter-group differences in white matter connectivity, represented by fixel-wise metrics (fibre density (FD), fibre bundle cross-section (FC), and combined FD and FC (FDC)). Group-wise comparisons were performed using general linear models (GLMs) adjusted for age, sex, and intracranial volume. Subsequently, for tract-of-interest analyses, all fixels that exhibited statistically significant decreases in the p-NBS group upon whole-brain FBA were identified and categorized into 16 white matter tracts, using anatomical DTI atlases to guide categorization [8,9,10]. Mean fixel-wise metrics were computed across the fixels in each defined tract—namely, bilateral corticospinal tracts, fornix, anterior thalamic radiation, superior thalamic radiation, superior longitudinal fasciculus, superior cerebellar peduncles, middle cerebellar peduncle, forceps minor, anterior commissure, and corpus callosum—and correlations between fixel-derived parameters of white matter tracts, neurocognitive test scores, physical disability status and disease activity measures were examined. Pearson correlation coefficients were computed to assess relationships between white matter integrity and clinical outcomes, with statistical significance set at p < 0.05. Degree of correlation relationship was considered very weak if r<0.2, weak if 0.2≤r<0.4, moderate if 0.4≤r<0.6, high if 0.6≤r<0.8, and very high if r≥0.8.