Abstract
IntroductionHereditary transthyretin (ATTRv) amyloidosis caused by the V30M (p. V50M) mutation is a fatal, neuropathic systemic amyloidosis. Liver transplantation has prolonged the survival of patients and central nervous system (CNS) complications, attributed to amyloid angiopathy caused by CNS synthesis of variant transthyretin, have emerged. The study aimed to ascertain amyloid deposition within the brain in long-term ATTRv amyloidosis survivors with neurological symptoms from the CNS.MethodsA total of 20 patients with ATTR V30M having symptoms from the CNS and a median disease duration of 16 years (8–25 years) were included in this study. The cognitive and peripheral nervous functions were determined for 18 patients cross-sectionally at the time of the investigation. Amyloid brain deposits were examined by [18F]flutemetamol PET/CT. Five patients with Alzheimer's disease (AD) served as positive controls.Result60% of the patients with ATTRv had a pathological Z-score in the cerebellum, compared to only 20% in the patients with AD. 75% of the patients with transient focal neurological episodes (TFNEs) displayed a pathological uptake only in the cerebellum. Increased cerebellar uptake was related to an early age of onset of the ATTRv disease. 55% of the patients with ATTRv had a pathological Z-score in the global cerebral region compared to 100% of the patients with AD.ConclusionAmyloid deposition within the brain after long-standing ATTRv amyloidosis is common, especially in the cerebellum. A cerebellar amyloid uptake profile seems to be related to TFNE symptoms.
Highlights
Hereditary transthyretin (ATTRv) amyloidosis caused by the V30M
It has been suggested that the combination of low serum levels of mutant relative to wild type TTR together with a mutation that produces a low kinetic and thermodynamic stability of the TTR tetramer predispose to central nervous system (CNS) complication
All 11 the patients, who had had their ATTR fibril type determined had type B fibrils, and their [18F]flutemetamol uptake was not different from that of the remaining 9 patients; we believe that we have a homogeneous group of mostly type B patients
Summary
Hereditary transthyretin (ATTRv) amyloidosis caused by the V30M (p. V50M) mutation is a fatal, neuropathic systemic amyloidosis. The study aimed to ascertain amyloid deposition within the brain in long-term ATTRv amyloidosis survivors with neurological symptoms from the CNS. ATTRv is a fatal systemic amyloidosis caused by mutations in the transthyretin (TTR) gene. It has been suggested that the combination of low serum levels of mutant relative to wild type TTR together with a mutation that produces a low kinetic and thermodynamic stability of the TTR tetramer predispose to CNS complication. This has been shown for the D18G (pD38G) and A25T (p.A45T) TTR mutations [6, 7]. Since this is not the case for the V30M (p.V50M) mutation, this may explain the low occurrence of CNS complications in the natural history of patients with ATTR V30M
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