Amyloid neuropathy: a retrospective study of 35 peripheral nerve biopsies
ABSTRACT We performed a retrospective study of 35 peripheral nerve biopsies (PNBs) with amyloid deposits in the endoneurium. In every case, nerve lesions were studied on paraffin-embedded fragments (PEFs) and by ultrastructural examination (USE). In addition, muscle fragments were taken and embedded in paraffin. Immunohistochemistry was performed with anti-transthyretin (TTR) serum on 19 nerve and 15 muscle PEFs. Direct immunofluorescence with anti-light-chain sera was performed on frozen nerve fragments in 19 cases. Endoneurial amyloid deposits were easily identified on routine PEF in 26 cases, after Congo red or thioflavine staining in three, and by USE in six. A dramatic myelinated fiber loss was evidenced in 34 cases (77-2970 per mm2), and features of axonal degeneration were present in every case. Segmental demyelination was observed in 10 cases. A mutation in the TTR gene was present in 14 cases, with Met30 mutation in 10 and Ala49 in four members of the same family. Amyloid deposits were strongly marked by the anti-TTR serum in 11 other cases, twice in the endoneurium, five around muscle fibers, and four in both locations. In eight patients, light-chain positivity was evidenced in endoneurial deposits, lambda in six and kappa in two. Two other patients with monoclonal gammopathy did not present any light-chain fixation. In 17 cases, amyloidosis was disclosed by PNB and 13 had a TTR pathology; eight of them, over 65 years old, correspond to a late-onset form of familial amyloid polyneuropathy which is an underdiagnosed condition.
- SourceAvailable from: Ilaria Cabrini[Show abstract] [Hide abstract]
ABSTRACT: Autosomal-dominant transthyretin (TTR)-related amyloidosis usually manifests in the second to fourth decade with a length-dependent axonal neuropathy with prominent involvement of the small fibers and multi-organ systemic failure. We retrospectively analyzed seventeen probands, including thirteen apparently isolated cases, carrying eight mutations of TTR gene (age of onset = 60.4 ± 13.5 years). Thirteen patients were initially un/misdiagnosed; interval from onset to definite diagnosis was 3.3 ± 2.3 years. Inaugural syndromes were a length-dependent motor-sensory neuropathy in seven cases, a sensory neuropathy in four, an isolated carpal tunnel syndrome in three, a pure dysautonomia in two, and a painful neuropathy in one. Atypical presentations included demyelinating nerve conduction changes with increased cerebrospinal fluid proteins resembling chronic inflammatory demyelinating polyradiculoneuropathy and a predominantly motor involvement resembling a motor neuron disorder. Misleading findings also included amyloid-negative abdominal fat aspirate/biopsy, biclonal gammopathy, and hepatitis C virus (HCV) seropositivity. Sural nerve biopsy detected amyloid deposits in thirteen of fifteen patients, including one case with a previous negative biopsy. TTR-immunohistochemistry was necessary to complete the diagnosis of primary amyloidosis light chain in a patient with biclonal gammopathy. A recurrent p.Phe64Leu mutation manifested in the seventh decade with painful motor-sensory polyneuropathy, dysautonomia, bulbar palsies, and fasciculations. TTR should be tested in a wide clinical spectrum of cryptogenetic, progressive, and motor-sensory neuropathies even manifesting with a very late onset.Journal of the Peripheral Nervous System 06/2011; 16(2):119-29. DOI:10.1111/j.1529-8027.2011.00331.x
Article: European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of paraproteinaemic demyelinating neuropathies: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society* R. D. M. Haddena, E. Nobile-Oraziob, C. Sommerc, A. Hahnd, I. Illae, E. Morraf, J. Pollardg, R. A. C. Hughesh, P. Bouchei, D. Cornblathj, E. Eversk, C. L. Koskil ,J. M. Legerm, P. Van den Berghn, P. van Doorno and I. N. van Schaikp
Chapter: Primary Systemic Amyloid Neuropathy[Show abstract] [Hide abstract]
ABSTRACT: Primary systemic amyloidosis (PSA) is a plasma cell dyscrasia. Organ damage is caused by deposition of amyloid, derived from monoclonal light chains, in tissues including nerves. PSA damages tissues and leads to combinations of neuropathy and renal, cardiac, and liver failure. The neuropathy of PSA is relatively stereotyped with damage to small and autonomic nerve fibers and superimposed carpal tunnel syndrome. The disease is progressive and mortality is high, especially when there is early involvement of vital organs. Treatment in the past was relatively ineffective. However, with the advent of peripheral blood stem cell transplantation and chemotherapy in selected patients, prolonged survival is possible if the weight of organ damage at onset of treatment is not too high. Thus, early detection is paramount. KeywordsAmyloid-Peripheral neuropathy-Amyloidosis-Primary systemic amyloid-Primary systemic amyloid neuropathy-Familial amyloid neuropathy01/1970: pages 145-154;