Two distinct mechanisms of neuropathy in immunoglobulin light chain (AL) amyloidosis

Abstract Introduction Although polyneuropathy in patients with immunoglobulin light chain (AL) amyloidosis has been considered to be attributable to axonal degeneration resulting from amyloid deposition, patients with nerve conduction parameters indicating demyelination that mimics chronic inflammatory demyelinating polyneuropathy (CIDP) have also been reported anecdotally. Methods We evaluated the electrophysiological and pathological features of 8 consecutive patients with AL amyloidosis who were referred for sural nerve biopsy. Results Although findings of axonal neuropathy predominantly in the lower limbs were the cardinal feature, all patients showed one or more abnormalities of nerve conduction velocities or distal motor latencies. In particular, 2 of these patients fulfilled the definite electrophysiological for CIDP defined by the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS). On electron microscopic examination of sural nerve biopsy specimens, Schwann cells apposed to amyloid fibrils became atrophic in all patients, suggesting that amyloid deposits directly affect neighboring tissues. Additionally, detachment of the neurilemma from the outermost compacted myelin lamella was seen where amyloid fibrils were absent in 4 patients. Electrophysiological findings suggestive of demyelination were more conspicuous in these patients compared with the other patients. The detachment of the neurilemma from the outermost compacted myelin lamella was particularly conspicuous in patients who fulfilled the definite EFNS/PNS electrophysiological criteria for CIDP. Conclusion Abnormalities of myelinated fibers unrelated to amyloid deposition may frequently occur in AL amyloidosis. Disjunction between myelin and the neurilemma may induce nerve conduction abnormalities suggestive of demyelination.