Significance of aberrant nerve conduction in hereditary transthyretin amyloidosis

In hereditary transthyretin (ATTRv) amyloidosis, axonal neuropathy is the main pathologic basis of polyneuropathy. However, whether nerve conduction slowing resembling chronic inflammatory demyelinating polyneuropathy (CIDP), observed in some patients, reflects primary demyelination or secondary changes related to axonal damage remains unclear. Electrophysiologic findings were compared between 96 patients with V30M ATTRv amyloidosis from nonendemic areas and 175 patients with nutritional or alcoholic axonal neuropathies. Myelinated fiber density was assessed in sural nerve biopsy specimens from 66 and 133 patients, respectively. Motor nerve conduction velocity (MCV) was reduced and distal motor latency (DML) was prolonged in both groups compared with normal controls, with more marked changes in ATTRv amyloidosis. Compound muscle action potential (CMAP) amplitude and myelinated fiber density were significantly lower in ATTRv amyloidosis than in nutritional/alcoholic neuropathies (p < 0.001). Conduction slowing fulfilling EAN/PNS CIDP criteria was observed only in patients with severe axonal loss. After adjusting for age, disease duration, and CMAP amplitude, only MCV slowing and DML prolongation in median nerve remained more pronounced in ATTRv amyloidosis. CIDP-like conduction slowing in ATTRv amyloidosis largely represents secondary changes caused by axonal degeneration, although additional mechanisms may contribute to slowing in the median nerve.