Progressive leptomeningeal involvement on gadolinium-enhanced FLAIR MRI in hereditary transthyretin amyloidosis with the V30M (p.V50M) mutation

Background Advances in disease-modifying therapies for hereditary transthyretin (ATTRv) amyloidosis have improved long-term survival. As a result, central nervous system (CNS) involvement, particularly leptomeningeal amyloidosis and cerebral amyloid angiopathy, is increasingly encountered in V30M (p.V50M) patients. However, the frequency, distribution, and progression of CNS involvement on MRI remain unclear.Methods We retrospectively analyzed patients with ATTR V30M amyloidosis who underwent brain MRI with gadolinium-enhanced FLAIR (Gd-FLAIR) or susceptibility-weighted imaging (SWI) between 2010 and 2025. Associations between leptomeningeal enhancement, cerebral microbleeds, and clinical parameters were evaluated.Results Leptomeningeal enhancement on Gd-FLAIR was observed in 13/44 patients (29.5%); disease duration was longer in patients with enhancement than in those without (15.0 [8.9–22.8] vs. 5.2 [2.4–10.5] years, p < 0.001). The semiquantitative Gd-FLAIR score correlated with disease duration (rs = 0.56, p < 0.001). In contrast, cerebral microbleeds were not associated with disease duration or progression. Leptomeningeal enhancement appeared as focal surface lesions in early stages and became diffuse in advanced stages, predominantly involving the posterior fossa.Conclusions Leptomeningeal enhancement on Gd-FLAIR MRI is a frequent and progressive finding associated with disease duration and may precede cerebral microbleeds, supporting its role as an early and sensitive marker in ATTR V30M amyloidosis.