Quantitative Sensory Testing in Late-Onset ATTRv Presymptomatic Subjects: A Single Center Experience

Abstract

Backgrounds Hereditary transthyretin amyloidosis (ATTRv) presymptomatic subjects undergo multidisciplinary evaluation to detect, as early as possible, a subclinical involvement of multisystem disease. Quantitative sensory testing (QST) that investigates and discriminates the function of C, Aδ and Aβ fibers is included as an instrumental test to monitor nerve fiber function. The purpose of this study was to evaluate the role of QST in the context of the multidisciplinary evaluation in late onset carriers. Methods Four-teen presymptomatic (namely carriers) were enrolled. Subjects underwent thermal [cold and warm detection threshold (CDT, WDT), cold and heat pain (CP and HP)] and tactile QST in four body sites: foot dorsum, distal lateral leg, distal thigh, hand dorsum. Results Overall, presymptomatic subject showed a significant difference in all thermal QST findings compared to the control group. All subjects had at least one altered thermal QST finding; the sites more frequently altered were foot and leg, whilst the thermal modalities which were more frequently abnormal were CDT, WDT and CP. Conclusions Our study highlights the importance of performing thermal QST in subjects carrying TTR mutation, given the high frequency of abnormal findings. Notably, performing both innocuous and painful stimulation in foot and/or leg increases the chance of detecting nerve fiber dysfunction. Moreover, the investigation of the hand may provide useful information in monitoring disease progression before the Predicted Age of Disease Onset (PADO).

Keywords: ATTRv; TTR; amyloidosis; carrier; quantitative sensory testing.

Figure 1

Radar representation of thermal QST at leg site. In the figure was represented the z-score value of all thermal modalities for each patient (each radius of the wheel). The red dotted circle lines represent the abnormal z-score value cut-off (the outer line is the +2 z-score, and the inner one is the −2 z-score).

Figure 2

Comparison of QST finding between groups. Each panel represents a single stimulation site (foot, leg, thigh, hand). On the y-axis is reported the absolute temperature (°C) and on the x-axis is reported the different type of sensory stimulation (CDT = cold detection threshold; WDT = warm detection threshold; CP = cold pain; HP = heat pain). Different color denotes different group (in blue the group of patients with a time-to-PADO ≤10 years; in red the group of patients with a time-to-PADO > 10 years; in green the group of healthy controls). Asterisks (*) indicates significant p-value between groups (p < 0.05).