Objective Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis often causes cognitive impairment, yet conventional MRI lacks sensitivity to detect related microstructural changes. This study aimed to investigate T1-weighted/T2-weighted (T1w/T2w) ratios alterations in normal-appearing white matter (NAWM) and their relationship with cognitive function in patients with anti-NMDAR encephalitis, including a 12-month longitudinal follow-up. Methods Fifty-nine patients with anti-NMDAR encephalitis (31 with mild cognitive impairment (MCI), 28 with no cognitive impairment (NCI)) and 34 healthy controls (HCs) underwent 3.0T whole-brain MRI and comprehensive neuropsychological assessments, including the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), and domain-specific tests for attention-executive function, memory, and visuospatial reasoning. T1w/T2w ratios were calculated for globel NAWM and multiple major white matter (WM) tracts. Eighteen MCI patients were followed longitudinally for 12 months to evaluate changes in T1w/T2w ratios and cognitive performance over time. Results Compared with NCI patients and HCs, MCI patients exhibited significantly reduced T1w/T2w ratios in global NAWM ( P 0.001) and multiple WM tracts, including the corpus callosum, fornix, left hippocampal cingulum, and right hippocampal cingulum (all P 0.05). Lower ratios were significantly associated with worse global cognition (r = 0.364, P = 0.023), memory (r = 0.336, P = 0.023), and visuospatial reasoning performance (r = 0.397, P = 0.005). In the 18 MCI patients with 12-month follow-up, increased T1w/T2w ratios in the fornix and hippocampal cingulum (both P = 0.009) were accompanied by significant improvements in visuospatial reasoning and memory functions. Conclusion T1w/T2w ratios derived from routine MRI provide a sensitive, clinically feasible biomarker for detecting NAWM microstructural damage in anti-NMDAR encephalitis. Longitudinal changes in these ratios may parallel cognitive improvement, and these preliminary findings support further investigation of this metric as an imaging biomarker, independent cohorts.
Tao et al. (Wed,) studied this question.