Amyloid neuropathy. A retrospective study of 35 nerve biopsies
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.
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- "From more than 35-year experience of combined nerve and muscle biopsy, we are convinced that this procedure significantly improves the diagnosis of systemic diseases with peripheral nerve involvement [11, 12, 13, 14, 15, 16, 17, 18, 19]. Among these diseases, vasculitides are certainly the most frequently diagnosed on neuro-muscular biopsies, but this procedure is also well advised to assess the diagnosis of sarcoidosis or amyloidosis. "
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ABSTRACT: Simultaneous combined superficial peroneal nerve and peroneous brevis muscle biopsy, via the same cutaneous incision, allows examination of several tissue specimens and significantly improves the diagnosis of systemic diseases with peripheral nerve involvement. Vasculitides are certainly the most frequently diagnosed on neuro-muscular biopsies, but this procedure is also well advised to asses a diagnosis of sarcoidosis or amyloidosis. More occasionally, combined nerve and muscle biopsy may reveal an unpredicted diagnosis of cholesterol embolism, intra-vascular lymphoma, or enables complementary diagnosis investigations on mitochondrial cytopathy or storage disease.
Clinical neuropathology 03/2014; 33(05). DOI:10.5414/NP300740 · 1.53 Impact Factor
Available from: Bo Goran Ericzon
- "To confirm amyloidosis, the demonstration of amyloid deposits via tissue biopsy is essential. Deposition of amyloid in the tissue can be demonstrated by Congo red staining of biopsy specimens . With Congo red staining, amyloid deposits show a characteristic green birefringence under polarized light. "
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ABSTRACT: Transthyretin amyloidosis is a progressive and eventually fatal disease primarily characterized by sensory, motor, and autonomic neuropathy and/or cardiomyopathy. Given its phenotypic unpredictability and variability, transthyretin amyloidosis can be difficult to recognize and manage. Misdiagnosis is common, and patients may wait several years before accurate diagnosis, risking additional significant irreversible deterioration. This article aims to help physicians better understand transthyretin amyloidosis-and, specifically, familial amyloidotic polyneuropathy-so they can recognize and manage the disease more easily and discuss it with their patients. We provide guidance on making a definitive diagnosis, explain methods for disease staging and evaluation of disease progression, and discuss symptom mitigation and treatment strategies, including liver transplant and several pharmacotherapies that have shown promise in clinical trials.
Orphanet Journal of Rare Diseases 02/2013; 8(1):31. DOI:10.1186/1750-1172-8-31 · 3.36 Impact Factor
Available from: Ilaria Cabrini
- "Patient 5, indeed, an isolated case with progressive polyneuropathy and biclonal gammopathy, had been initially diagnosed as AL because of the detection of κ-light-chain reactive amyloid deposits in the nerve biopsy; TTR-FAP was correctly diagnosed upon positive TTR-IHC performed only after severe progression despite chemotherapy. Because co-existence of monoclonal gammopathy and TTR-related amyloidoses have been already reported representing a diagnostic challenge (Lachmann et al., 2002; Vital et al., 2004; Comenzo et al., 2006; Dattilo, 2009), the nerve biopsy analysis should include a complete IHC panel to characterize the biochemical subtypes of amyloid deposits. "
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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 · 2.76 Impact Factor
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