Early Detection of Central Nervous System Involvement in ATTRv Using Multimodal MRI and Cognitive Assessments

Hereditary Transthyretin Amyloidosis with polyneuropathy (ATTRv-PN) is an autosomal dominant disorder characterized by TTR gene mutations, causing amyloid fibril deposition in peripheral nerves. Significant CNS involvement has been noted, emphasizing the necessity for advanced neuroimaging tools for early detection of CNS damage in ATTRv.

Comprehensive clinical assessments and multimodal MRI techniques, including FreeSurfer, TBSS and microbleed analysis, were utilized. The cohorts comprised 30 symptomatic patients (ATTRv-PN), 19 presymptomatic patients (pre-ATTRv-PN), classified based on neuropathic signs, and 44 age- and sex-matched controls. For cognitive assessment, we utilized the Addenbrooke's Cognitive Examination-Revised.

The ATTRv-PN group had an average age of 51 years, while the pre-ATTRv-PN group averaged 41 years, with a sex ratio of 35% men to 65% women. Symptomatic patients experienced an average disease duration of 5 years, predominantly featuring the p.Val50Met genotype (73%). Brain imaging showed diffuse subcortical white matter alterations in ATTRv-PN, while cortical thinning and microbleeds were infrequent. Cognitive assessments revealed significant differences, with symptomatic scoring lower in memory and verbal fluency than presymptomatic.

ATTRv-PN involves cerebral white matter microstructural damage from early stages. Multimodal MRI serves as an accurate, non-invasive tool for detecting CNS damage, improving our understanding of the disease spectrum.