Objective:
To characterize the longitudinal progression of mobility impairment in familial dysautonomia (FD) using wearable sensor-based assessments and to identify sensitive functional markers of sensory ataxia progression.
Background:
FD, also known as hereditary sensory and autonomic neuropathy type III (HSAN III), is an autosomal recessive neurodevelopmental disorder marked by severe sensory and autonomic dysfunction with relative preservation of motor pathways. Despite preserved strength, patients develop progressive gait and balance impairment driven by proprioceptive loss. Traditional clinical scales lack sensitivity to early or subtle mobility decline. Wearable inertial sensors allow objective quantification of gait and postural control and may provide sensitive markers of disease progression.
Design/Methods:
This prospective longitudinal cohort study included 24 patients with genetically confirmed FD evaluated at the NYU Dysautonomia center. Mobility was assessed using APDM Mobility Lab™ at baseline and at approximately 12- and 24-month follow-up visits. Outcomes included gait temporal parameters (cadence, gait cycle duration, step duration) and postural sway metrics during eyes-closed standing (sway area, sagittal, and coronal root-mean-square [RMS] sway).
Results:
Postural sway measures demonstrated the earliest sensitivity to change. At 12 months, significant increases were observed in RMS sway (0.39 ± 0.73°, P = 0.02) and sagittal RMS sway (0.56 ± 0.56°, P = 0.01), while sway area showed a non-significant upward trend (9.0 ± 79.9°², P = 0.34). At 24 months, sway area increased significantly (21.3 ± 38.5°², P = 0.02), with progression in both coronal (0.71 ± 1.07°, P = 0.01) and sagittal RMS sway (0.41 ± 0.66°, P = 0.01). Gait parameters remained stable at 12 months but deteriorated at 24 months, with reduced cadence (−6.24 ± 12.2 steps/min, P = 0.034) and prolonged gait cycle (0.09 ± 0.18 s, P = 0.036) and step duration (0.41 ± 0.80 s, P = 0.032).
Conclusions:
Patients with FD exhibit progressive mobility impairment that is detectable using wearable sensor technology. Balance instability during eyes-closed standing emerges earlier than gait deterioration, highlighting postural sway as a sensitive functional marker of sensory ataxia progression and a promising outcome measure for future therapeutic trials.
Acknowledgements: Authors of this Project from NYU Langone's Dysautonomia Center: Beatriz Tijero-Merino, MD, PhD; Patricio Millar-Vernetti, MD; Andreana Barnett, NP, FNP-BC; Horacio Kaufmann, MD, FAAN; Alejandra González-Duarte, MD, PhD