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.

A Case of Atypical Amyloid Polyneuropathy with Predominant Upper-limb Involvement with the Diagnosis Unexpectedly Found at Lung Operation

“…distal portion of the nerve), the cause of the neuropathy in the present patient might be ascribed to possible deposition of amyloid in the more proximal region of the peripheral nerve (18). With regard to biopsy of the distal portion of the nerve, a retrospective study demonstrated that six of the 35 peripheral nerve biopsies obtained from patients with amyloid neuropathy required electron microscopy to detect an amyloid deposit, although 4 of the six reinvestigations of the specimen using light microscope could reveal it (19). Another study demonstrated that TTR IHC could reveal amyloid deposits in the sural nerve that could not be detected by Congo red staining, supporting increased sensitivity of TTR IHC (20).…”

“…Amyloid deposits are usually found in the endoneurium, but in our case they were restricted to the vascular walls of the epineurium. Although several studies have shown epineurial amyloid deposition (19,21), its frequency is as low as two out of 40 (21). The two cases, in which epineurial amyloid deposition was noted, were elderly (68 and 73 years old) and showed amyloid deposits only around the capillaries as in our patient.…”

Polyneuropathy associated with a monoclonal gammopathy

“…The sensitivity of nerve biopsy for the diagnosis of systemic amyloidosis is said to be around 85% [59]. On paraffin-embedded sections, amyloid deposits appear round, are scattered in the endoneurium and sometimes attached to thickened capillary walls [60]. AL amyloidosis results from the transformation of an immunoglobulin light chain, which may be identified on frozen specimens with a specific antibody.…”

Familial and Senile Amyloidosis Caused by Transthyretin

“…The presence of amyloid deposits in peripheral nerves results in axonal degeneration and demyelination [30]. Fibers near amyloid deposits demonstrate distortion of the myelin sheath, segmental demyelination, and Wallerian degeneration [31].…”