No evidence of cerebral microangiopathy in hereditary transthyretin amyloidosis: An MRI case-control study from an Italian Center.

Hereditary transthyretin amyloidosis (ATTRv) is a rare, progressive, and life-threatening disorder characterized by the accumulation of misfolded transthyretin proteins in various organs and tissues. While peripheral neuropathy and cardiomyopathy are well-recognized manifestations of ATTRv, cerebral involvement has been increasingly recognized as a significant aspect of the disease. However, the full extent of cerebral involvement, its clinical implications, and its impact on disease progression remain areas of ongoing research and clinical interest in the field of amyloidosis. In particular, gene silencers do not pass through blood-brain barrier thus possibly leading to a shift in clinical phenotype in the next future with a wider involvement of central nervous system. In this study we enrolled 32 ATTRv subjects (mean age 66.0 ± 13.0 years, range 28-85; eight women), including patients and carriers, and gender and age matched healthy controls (HC). 3 T brain MRI was performed to assess microvascular involvement. Number of microbleeds at susceptivity weighted imaging (SWI) sequences and Fazekas score were quantified and compared between the groups. No differences were found in SWI microbleeds and Fezekas score between groups. No significant correlations between the number of SWI microbleeds and FAP stage, years from disease onset and age were found. These findings suggest unexpectedly that brain involvement in ATTRv, as evaluated with standard MRI markers of small-vessel disease, is scarce and clinically limited.