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

Journal of Clinical Neuromuscular Disease
George ZanazziKurenai Tanji

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.

References

Dec 1, 1991·Brain : a Journal of Neurology·H StauntonA E Harding
Oct 1, 1987·Brain : a Journal of Neurology·H StauntonP Kelly
Nov 1, 1985·Muscle & Nerve·A H KoeppenR O Bailey
May 24, 2003·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Toshiyuki YamadaBarbara Kluve-Beckerman
Feb 3, 2004·Muscle & Nerve·Hannah R Briemberg, Anthony A Amato
Jun 7, 2005·Seminars in Neurology·Robert W Pratt, Louis H Weimer
Apr 15, 2008·Neuroscience Letters·Tatsufumi MurakamiYoshihide Sunada
Mar 1, 2002·Journal of Clinical Neuromuscular Disease·Uma PulipakaBennet Omalu
Jun 16, 2010·Brain Research·Tatsufumi MurakamiYoshihide Sunada
May 31, 2011·Journal of the Neurological Sciences·Joerg-Patrick Stübgen
Jun 23, 2011·Journal of the Peripheral Nervous System : JPNS·Manuel CappellariGian Maria Fabrizi
Dec 23, 2011·Muscle & Nerve·Stephane MathisJean-Michel Vallat
Aug 13, 2013·Handbook of Clinical Neurology·V Planté-Bordeneuve, P Kerschen
Aug 13, 2013·Handbook of Clinical Neurology·Hadi Manji
Apr 3, 2014·Practical Neurology·Malick GibaniCarolyn M Gabriel
May 3, 2014·Basic & Clinical Pharmacology & Toxicology·Ole Jakob VilholmMustapha Itani
May 23, 2015·Journal of Clinical Neuromuscular Disease·Sujata P ThawaniThomas H Brannagan
Aug 6, 2015·Journal of Neurology, Neurosurgery, and Psychiatry·A S CarrM M Reilly
Sep 16, 2015·Annals of Neurology·Louise-Laure MarianiUNKNOWN French Familial Amyloid Polyneuropathies Network (CORNAMYL) Study Group
Jan 7, 2016·Current Opinion in Neurology·David AdamsUNKNOWN from the European Network for TTR-FAP (ATTReuNET)
Jan 28, 2017·Molecular Therapy : the Journal of the American Society of Gene Therapy·Tracy S ZimmermannJared Gollob
Jul 5, 2018·The New England Journal of Medicine·David AdamsOle B Suhr
Jul 5, 2018·The New England Journal of Medicine·Merrill D BensonTeresa Coelho

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BETA
biopsies
biopsy

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