ArticleJournal of neurology2026
Central nervous system manifestations in hereditary transthyretin amyloidosis: a cross-sectional study with 151 patients.
Article in Journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundCentral nervous system (CNS) dysfunction is increasingly recognized in hereditary transthyretin (ATTRv) amyloidosis. We aimed to characterize CNS manifestations and assess associations with clinical variables and plasma neurofilament light chain (NfL), using history of transient focal neurological episodes (TFNEs) as the main outcome.
methodsWe conducted a cross-sectional study at Unidade Corino de Andrade in Porto (January 2021-April 2023), including patients with ATTRv amyloidosis caused by the V30M mutation. History of TFNEs, stroke, seizures, headaches and symptoms/signs of cranial nerve dysfunction were assessed through patient interview and neurological examination. Plasma NfL was analyzed cross-sectionally and longitudinally (0-6-12 months).
results151 patients were included (56.3% male, median age 48 [IQR 44-53], with a median disease duration of 15 years [IQR 11-20]. Most had early-onset disease (94.7%). TFNE history occurred in 29.1%, headaches in 23.8%, seizures in 6.6% and stroke in 1.3%. Patients with past TFNEs had longer disease duration than those without. No other robust differences were identified. Longitudinally, pNfL levels showed an overall effect of time (p=0.013), driven by a decrease between 6 and 12 months, with no significant differences between baseline and either follow-up timepoint. There were no differences in pNfL trajectories according to TFNEs history (time-by-TFNE interaction, p=0.416).
conclusionsThe high frequency of CNS symptoms in this sample supports including CNS assessment in routine follow-up of patients with ATTRv amyloidosis with longstanding disease. Further longitudinal studies are needed to clarify determinants of CNS involvement.
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