Rate of neuropathic progression in hereditary transthyretin amyloidosis with polyneuropathy and other peripheral neuropathies: a systematic review and meta-analysis

Xiaochen Lin,Chafic Karam,Nishtha Baranwal,Duncan Brown,Montserrat Vera-Llonch,Aaron Yarlas,Braden Vogt,Josh Biber

doi:10.1186/s12883-021-02094-y

Abstract

BackgroundWe aimed to compare neuropathic progression rate between hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) and other peripheral neuropathies, including diabetic peripheral neuropathy (DPN) and Charcot-Marie-Tooth disease (CMT).MethodsLiterature searches identified studies reporting neuropathic progression, measured by Neuropathy Impairment Score (NIS) or NIS-Lower Limbs (NIS-LL). Our study also included unpublished data from a clinical registry of patients who were diagnosed with different peripheral neuropathies and seen at the Oregon Health & Science University (OHSU) during 2016–2020. Meta-analysis and meta-regression models examined and compared annual progression rates, calculated from extracted data, between studies of ATTRv-PN and other peripheral neuropathies.ResultsData were synthesized from 15 studies in which NIS and/or NIS-LL total scores were assessed at least twice, with ≥12 weeks between assessments, among untreated patients with ATTRv-PN or other peripheral neuropathies. Meta-analysis models yielded that the annual progression rate in NIS total scores was significantly different from zero for studies in ATTRv-PN and CMT (11.77 and 1.41; both P < 0.001), but not DPN (− 1.96; P = 0.147). Meta-regression models showed significantly faster annual progression in studies in ATTRv-PN, which statistically exceeded that in other peripheral neuropathies by 12.45 points/year for NIS, and 6.96 for NIS-LL (both P < 0.001).ConclusionsPeripheral nervous function deteriorates more rapidly in patients with ATTRv-PN than for other peripheral neuropathies. These findings may improve understanding of the natural history of neuropathy in ATTRv-PN, facilitate early diagnosis, and guide the development of assessment tools and therapies specifically targeting neuropathic progression in this debilitating disease.

Highlights

We aimed to compare neuropathic progression rate between hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) and other peripheral neuropathies, including diabetic peripheral neuropathy (DPN) and Charcot-Marie-Tooth disease (CMT)
The Neuropathy Impairment Score (NIS) was originally developed for assessing neuropathic progression and response to treatment in DPN, but this instrument and its related measures have been utilized in other types of peripheral neuropathy [7, 17,18,19]
The NIS can be used to compare the rate of neuropathic progression between ATTRv-PN and other disease types manifesting in peripheral neuropathy

Summary

Introduction

We aimed to compare neuropathic progression rate between hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) and other peripheral neuropathies, including diabetic peripheral neuropathy (DPN) and Charcot-Marie-Tooth disease (CMT). Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a rare disease characterized by progressive sensory, motor, and autonomic neuropathy [1]. Patients with ATTRv-PN experience rapid neuropathic progression [11]. Indirect comparison suggests a substantially faster rate of progression in patients with ATTRv-PN than in patients with other peripheral neuropathies, such as diabetic peripheral neuropathy (DPN) [12]. There have been no direct empirical comparisons of the rates of neuropathic progression between patients with ATTRv-PN and patients with other peripheral neuropathies. ATTRv-PN may be difficult to differentiate from idiopathic peripheral neuropathy (IPN) or DPN in early stages of disease [13,14,15,16]

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