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

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...

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Autores principales: Zanazzi, George, Arshad, Muhammad, Maurer, Mathew S., Brannagan, Thomas H., Tanji, Kurenai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Journal of Clinical Neuromuscular Disease 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392216/
https://www.ncbi.nlm.nih.gov/pubmed/30801482
http://dx.doi.org/10.1097/CND.0000000000000242
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author Zanazzi, George
Arshad, Muhammad
Maurer, Mathew S.
Brannagan, Thomas H.
Tanji, Kurenai
author_facet Zanazzi, George
Arshad, Muhammad
Maurer, Mathew S.
Brannagan, Thomas H.
Tanji, Kurenai
author_sort Zanazzi, George
collection PubMed
description 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.
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spelling pubmed-63922162019-03-16 Demyelinating Neuropathy in a Patient Treated With Revusiran for Transthyretin (Thr60Ala) Amyloidosis Zanazzi, George Arshad, Muhammad Maurer, Mathew S. Brannagan, Thomas H. Tanji, Kurenai J Clin Neuromuscul Dis Case Review 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. Journal of Clinical Neuromuscular Disease 2019-03 2019-02-20 /pmc/articles/PMC6392216/ /pubmed/30801482 http://dx.doi.org/10.1097/CND.0000000000000242 Text en Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Case Review
Zanazzi, George
Arshad, Muhammad
Maurer, Mathew S.
Brannagan, Thomas H.
Tanji, Kurenai
Demyelinating Neuropathy in a Patient Treated With Revusiran for Transthyretin (Thr60Ala) Amyloidosis
title Demyelinating Neuropathy in a Patient Treated With Revusiran for Transthyretin (Thr60Ala) Amyloidosis
title_full Demyelinating Neuropathy in a Patient Treated With Revusiran for Transthyretin (Thr60Ala) Amyloidosis
title_fullStr Demyelinating Neuropathy in a Patient Treated With Revusiran for Transthyretin (Thr60Ala) Amyloidosis
title_full_unstemmed Demyelinating Neuropathy in a Patient Treated With Revusiran for Transthyretin (Thr60Ala) Amyloidosis
title_short Demyelinating Neuropathy in a Patient Treated With Revusiran for Transthyretin (Thr60Ala) Amyloidosis
title_sort demyelinating neuropathy in a patient treated with revusiran for transthyretin (thr60ala) amyloidosis
topic Case Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392216/
https://www.ncbi.nlm.nih.gov/pubmed/30801482
http://dx.doi.org/10.1097/CND.0000000000000242
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