A Quantitative Assessment of Upper Limb Motor Function Across Disease Stages in Hereditary Transthyretin Amyloidosis

Hereditary transthyretin amyloidosis (ATTRv) is a multisystemic disease where early neuropathy signs are challenging to detect conventionally. This study aimed to evaluate hand motor performance in ATTRv using the Hand Test System (HTS) across disease stages and examine correlations with standard measures.

A total of 113 individuals were enrolled: 74 patients with ATTRv (divided according to Familial Amyloid Polyneuropathy [FAP] stage into FAP0: pre-symptomatic with confirmed TTR mutations, n = 16; FAP1: mild sensory/motor symptoms, n = 40; FAP2: ambulatory with assistance, n = 18) and 39 healthy controls. All participants underwent HTS evaluation; 9-Hole Peg Test (9HPT); handgrip and tripod pinch strength testing; Thumb Opposition Test (TOT); Neuropathy Impairment Score (NIS); Disabilities of the Arm, Shoulder and Hand questionnaire (DASH); and Quality of Life Diabetic Neuropathy (Norfolk QoL-DN) questionnaire. Group differences were analyzed with analysis of covariance and correlations with Pearson's coefficients.

HTS parameters (Touch Duration, Inter-Tapping Interval, Movement Rate) significantly differed across stages between the FAP2 and all other groups, with some parameters distinguishing the FAP1 from the control and FAP0 groups. 9HPT impairment was observed only in the FAP2 group. Grip strength showed subtle changes, especially in the right hands of the FAP1 group, while tripod pinch strength declined during advanced stages. Several HTS parameters were correlated with NIS, DASH, Norfolk QoL-DN, and hand strength. Subclinical carpal tunnel syndrome possibly influenced early-stage results.

HTS detected stage-related motor differences in ATTRv and correlated them with standard measures, offering increased sensitivity to early neuropathic changes.