Work

Transthyretin variant cerebral amyloid angiopathy fulfilling the modified Boston criteria: Retrospective data from the Bicêtre hospital cohort

Year: 2025

Type: article

Abstract: • Hereditary transthyretin amyloidosis (ATTRv) is a cause of cerebral amyloid angiopathy. • Transthyretin-associated cerebral amyloid angiopathy should be suspected in case of leptomenigeal enhancement, when other organs are involved or in case of suggestive familial history. • Transthyretin-associated cerebral amyloid angiopathy prevalence is expected to rise, as treatments exist for peripheral nerve and cardiac involvement, increasing life expectancy, but with no effect on transthyretin production in the central nervous system. • ATTRv patients should probably be clinically screened for CNS involvement and, if present, a brain MRI should probably be performed to adapt cardiovascular follow-up. Hereditary transthyretin amyloidosis (ATTRv) is the most common hereditary amyloidosis, affecting mainly the peripheral nervous system and the heart. Central nervous system (CNS) involvement is regarded as rare, apart in some TTR variants, although leptomeningeal amyloid deposit had been described in the frequent Val30Met variant. Cerebral amyloid angiopathy (CAA) is a neurovascular disease characterized by amyloid deposits in brain vasculature, leading to ischemic and hemorrhagic events. The main cause is sporadic CAA with β-amyloid deposits but hereditary causes are possible. We analyzed a cohort of ATTRv symptomatic patients treated at Bicêtre university hospital who underwent brain magnetic resonance imaging (MRI) regardless of indication. Twenty out of 64 ATTRv patients (31%) fulfilled radiological criteria of possible or probable CAA (suspected CAA) according to the modified Boston criteria with an unusually high 77% (10/13) frequency of leptomeningeal enhancement. Clinically, suspected CAA patients tended to have more focal central neurological symptoms, seizures and memory complaints than ATTRv patients without those MRI features. ATTRv-related CAA should be considered in case of CAA with suggestive systemic features or familial history, as specific treatments and genetic counseling now exist for ATTRv. Conversely, CNS symptoms and brain MRI abnormalities should be sought in ATTRv patients.

Source: Revue Neurologique

DOI: 10.1016/j.neurol.2025.07.012