Clinical and neurophysiological features of neuropathic pain in hereditary transthyretin amyloidosis associated polyneuropathy.

Background: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is often associated with neuropathic pain (NP), involving developing mechanisms across different nerve fibres. This study aimed to explore the relationship between NP intensity and clinical/neurophysiological measures in symptomatic ATTR V30M (p.V50M)-PN patients.

Methods: We included 106 symptomatic patients (46 males; mean age 47.5 ± 13.2 years). NP severity was classified using three pain-related items from the Norfolk QOL-DN, generating three groups: no pain, mild pain, and moderate-to-severe pain. Clinical and neurophysiological assessments included the Neuropathy Impairment Score (NIS), nerve conduction studies (sural SNAP, peroneal CMAP), electrochemical skin conductance (ESC), sympathetic skin response (SSR), and Quantitative Sensory Testing (QST). Statistical analyses included non-parametric tests and ordinal logistic regression.

Results: Patients with NP had significantly higher NIS scores and reduced sural/peroneal amplitudes and ESC values. However, only NIS was significantly associated with NP intensity (OR = 1.062, 95% CI: 1.008-1.119, p = .024). Subscore analysis showed the sensory component as the main driver (OR = 1.205, p = .015). QST variables differed by pain presence but not intensity.

Conclusion: NIS, especially its sensory subscore, is a robust predictor of NP severity in ATTRv-PN. These findings support its utility in monitoring disease burden and guiding management.