Value of multi-modality small fiber assessments in a genotypically diverse cohort of transthyretin-related amyloidosis in the early stages of disease

Monica Alcantara; Shabber Mannan; James de la Cruz; Vera Bril

doi:10.1016/j.medcli.2024.02.012

Value of multi-modality small fiber assessments in a genotypically diverse cohort of transthyretin-related amyloidosis in the early stages of disease

Med Clin (Barc). 2024 Apr 13:S0025-7753(24)00159-3. doi: 10.1016/j.medcli.2024.02.012. Online ahead of print.

[Article in English, Spanish]

Authors

Monica Alcantara¹, Shabber Mannan¹, James de la Cruz¹, Vera Bril²

Affiliations

¹ Prosserman Family Neuromuscular Clinic, Department of Medicine, Division of Neurology, University of Toronto, Toronto, Ontario, Canada.
² Prosserman Family Neuromuscular Clinic, Department of Medicine, Division of Neurology, University of Toronto, Toronto, Ontario, Canada. Electronic address: vera.bril@utoronto.ca.

PMID: 38616431
DOI: 10.1016/j.medcli.2024.02.012

Abstract

Introduction: Transthyretin-related amyloidosis (ATTRv) is a progressive multisystem disorder, predominantly involving the peripheral nerve system (PNS) and heart. Quantification of small fiber damage may help guide treatment decisions, as amyloid deposits frequently affect those fibers early in disease course. Corneal confocal microscopy (CCM) is a promising method to monitor patients with ATTRv, due to similarities between corneal nerves and PNS, as the cornea is innervated by Aδ and C fibers.

Methods: We compared CCM measures from ATTRv patients to a group of healthy individuals, matched by age and gender. We then investigated the correlations between small fiber tests (SFT): CCM, LDI-Flare and CDT, COMPASS-31 and disability scales (RODS and ONLS) in patients.

Results: Of 20 patients (6 with V30M), mean age 50.3±15.3Y, 7 female (35%), six (30%) had polyneuropathy and 10 (50%) carpal tunnel syndrome. CDT was abnormal in 9 and LDI-flare in 6 patients. CCM was abnormal in 19 tested patients and significantly reduced when compared to controls (CNFL: 6.31±0.31 vs. 15.21±1.02mm/mm², p<0.001). Mean COMPASS-31-scores were 22.27±22.84; RODS and ONLS were 38.15±12.33 and 2.05±2.3, with no significant differences between sub-group scores. Disease duration was significantly correlated with ONLS (0.43, p=0.05) and RODS (0.46, p=0.03). There were no significant correlations between measures of disability and SFT.

Conclusions: In a diverse cohort of ATTRv patients, CCM was the most frequent abnormal measurement. CCM can be a useful test to triage patients in the early disease stages and with few or equivocal symptoms.

Keywords: Amiloidosis por transtiretina; Corneal confocal microscopy; Microscopia confocal corneal; Polineuropatía; Polyneuropathy; Pruebas de fibras pequeñas; Small fiber tests; TTR amyloidosis.