Polyneuropathy in Wild-Type Transthyretin Amyloidosis

Transthyretin amyloidosis (ATTR) is a systemic disorder characterized by the extracellular accumulation of amyloid fibrils, classified as either mutant (ATTRv, v for variant) or wild-type (ATTRwt), based on the genetic sequence of the transthyretin (TTR) protein. ATTRwt primarily manifests with cardiac and osteo-articular involvement. Nevertheless, evidence of peripheral neuropathy, besides carpal tunnel syndrome (CTS), can be found in ATTRwt patients. Although neurological complications of ATTRv have been extensively studied, to date information on peripheral nervous system (PNS) involvement in ATTRwt remains limited.

Patients with a confirmed diagnosis of ATTRwt underwent neurological examination and nerve conduction studies (NCS). In patients with confirmed polyneuropathy, we suggested a sural nerve biopsy to detect amyloid deposits.

We examined 30 patients with a mean age of 81.1 years (range 60-96). The absence of lower-limb distal tendon reflexes was shown in 53% of cases. CTS was present in 70% of cases. NCS revealed a sensory polyneuropathy in 18 patients (60%). Among the patients with neuropathy, four agreed to undergo sural nerve biopsy: in two patients, histological examination showed the presence of Congo red-positive amyloid deposits.

We observed a sensory neuropathy in more than half of the enrolled ATTRwt patients, supporting the systemic nature of the disease. However, the unclear pathogenesis of sensory polyneuropathy, considering the various comorbidities in the elderly population, highlights the need for further investigation. Histological confirmation of amyloid deposition in nerve tissue may provide a causal link between amyloidosis and PNS involvement.