Dataset Information

Demyelinating Neuropathy in a Patient Treated With Revusiran for Transthyretin (Thr60Ala) Amyloidosis.

ABSTRACT: Transthyretin amyloidosis patients develop length-dependent peripheral neuropathy, autonomic dysfunction, and restrictive cardiomyopathy associated with deposition of amyloid fibrils in these tissues. Despite advances in management over the past decade, this disorder causes profound debilitation and ultimately proves fatal. In this report, we describe a man with late-onset cardiac amyloidosis due to a transthyretin Thr60Ala mutation who was treated with an investigational RNAi therapeutic, revusiran, which targets hepatic transthyretin production. Sixteen months into treatment, he developed bilateral lower-extremity weakness and numbness, worsening balance, difficulty manipulating objects with his hands, and finger numbness. Nerve conduction studies were consistent with multifocal demyelinating neuropathy. Intravenous immunoglobulin therapy improved sensation in his hands and feet, and improved hand dexterity. A sural nerve biopsy demonstrated demyelination with substantial axonal loss in the absence of histologically detectable endoneurial amyloid deposition. This case expands the clinicopathologic spectrum of transthyretin amyloidosis and may represent complex disease and treatment effects.

SUBMITTER: Zanazzi G

PROVIDER: S-EPMC6392216 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Demyelinating Neuropathy in a Patient Treated With Revusiran for Transthyretin (Thr60Ala) Amyloidosis.

Zanazzi George G Arshad Muhammad M Maurer Mathew S MS Brannagan Thomas H TH Tanji Kurenai K

Journal of clinical neuromuscular disease 20190301 3

Transthyretin amyloidosis patients develop length-dependent peripheral neuropathy, autonomic dysfunction, and restrictive cardiomyopathy associated with deposition of amyloid fibrils in these tissues. Despite advances in management over the past decade, this disorder causes profound debilitation and ultimately proves fatal. In this report, we describe a man with late-onset cardiac amyloidosis due to a transthyretin Thr60Ala mutation who was treated with an investigational RNAi therapeutic, revus ...[more]

PMID: 30801482

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Project description:AimsCardiac transthyretin amyloidosis (ATTR-CM) is a progressive and fatal condition. Prognosis can be determined at diagnosis according to the National Amyloidosis Centre (NAC) transthyretin amyloidosis (ATTR) stage. We sought to examine how NAC ATTR stage changes during follow-up and whether it maintains its prognostic value throughout the disease course.Methods and resultsWe performed a retrospective study of 945 patients with wild-type ATTR-CM (wtATTR-CM) or hereditary ATTR-CM associated with the V122I variant (V122I-hATTR-CM) who were diagnosed and serially evaluated at the UK NAC. Patients who commenced any disease-modifying therapy for amyloidosis were censored at the time of doing so. Landmark Kaplan-Meier survival analyses were performed at diagnosis (n = 945) and at 6 ± 1 (n = 432), 12 ± 3 (n = 562), and 24 ± 3 (n = 316) months and stratified by recalculated NAC ATTR stage at the relevant time point. Cox regression analyses were performed to assess the prognostic significance during follow-up of an increase in NAC ATTR stage from Stage I at diagnosis. Mortality in ATTR-CM was predicted by NAC ATTR stage at each time point [Stage II vs. I, hazard ratios (HRs) 1.95-2.67; P < 0.001; Stage III vs. II, HRs 1.64-2.25; P < 0.001-0.013]. An increase from NAC ATTR Stage I, which occurred in 21%, 32%, and 44% of evaluable patients at 6, 12, and 24 months of follow-up respectively, was highly predictive of ongoing mortality at each time point (HRs 2.58-3.22; P < 0.001) and in each genotypic subgroup (HRs 1.86-4.38; P < 0.05). Increase in NAC ATTR stage occurred earlier in V122I-hATTR-CM than in wtATTR-CM (43% vs. 27% at 12 months of follow-up; P = 0.003).ConclusionsNational Amyloidosis Centre ATTR stage predicts ongoing survival throughout the disease natural history in ATTR-CM, and an increase from NAC ATTR Stage I at diagnosis to a higher NAC ATTR stage predicts mortality throughout follow-up. Serial calculation of NAC ATTR stage suggests a more aggressive phenotype in V122I-hATTR-CM than in wtATTR-CM.

Dataset Information

Demyelinating Neuropathy in a Patient Treated With Revusiran for Transthyretin (Thr60Ala) Amyloidosis.

Publications

Demyelinating Neuropathy in a Patient Treated With Revusiran for Transthyretin (Thr60Ala) Amyloidosis.

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