Electrophysiological Monitoring of Asymptomatic Transthyretin Mutation Carriers

• Published in: Muscle & nerve 2025-02, Vol.71 (2), p.208-215
• Main Authors: Berard, Nicolas, Verschueren, Annie, Fortanier, Etienne, Grapperon, Aude‐Marie, Kouton, Ludivine, Rebouh, Hadia, Gallard, Julien, Salort‐Campana, Emmanuelle, Attarian, Shahram, Delmont, Emilien
• Format: Article
• Language: English
• Subjects: Action potential; Action Potentials - physiology; Adult; Amyloid Neuropathies, Familial - diagnosis; Amyloid Neuropathies, Familial - genetics; Amyloid Neuropathies, Familial - physiopathology; Assessments; Asymptomatic; asymptomatic carriers; Autonomic nervous system; Biomarkers; Clinical; Electrochemistry; Electrodiagnosis - methods; electrophysiological monitoring; familial amyloid polyneuropathy; Female; Heart rate; Heterozygote; Humans; Latency; Male; Median nerve; Medical records; Middle Aged; Mutation; Nerve conduction; Neural Conduction - physiology; Neuropathy; Parameter sensitivity; Prealbumin - genetics; Retrospective Studies; Sensory neurons; Skin; small fiber testing; Standardization; Sympathetic nervous system; Transthyretin
• ISSN: 0148-639X; 1097-4598; 1097-4598
• DOI: 10.1002/mus.28318

ABSTRACT Introduction/Aims It is imperative to screen asymptomatic carriers of transthyretin (TTR) mutations to initiate treatment early. The protocol for repeated electrodiagnostic (EDX) assessments over time lacks standardization. Our aim was to report the electrophysiological evolution of a cohort of asymptomatic carriers and to determine which biomarkers were most sensitive to change. Methods We performed a retrospective review of medical records of asymptomatic carriers identified by screening families with amyloid neuropathy. Carriers who underwent two EDX assessments with a minimum 1‐year interval between studies were selected. EDX included analysis of median, ulnar, tibial, fibular and sural nerves, motor unit number index (MUNIX), electrochemical skin conductance, sympathetic skin response, and heart rate variability on deep breathing. Measurements were compared at first and second examinations. Results Twenty‐three carriers were included with a median age of 49 years (interquartile range 37–58). Median time between examinations was 3 years (2–4). Compound muscle and sensory nerve action potential (CMAP and SNAP) amplitudes, nerve conduction velocities, autonomic small fiber testing and MUNIX remained stable except for motor distal latency of the median nerve (+0.07 ms/year) and CMAP duration of the ulnar (+0.10 ms/year) and fibular (+0.12 ms/year) nerves. The CMAP duration of the ulnar nerve was the most sensitive biomarker to change when performed within 10 years preceding the age of the youngest case in the family, with a standardized response mean of 0.91. Discussion Nerve conduction parameters remain relatively stable in asymptomatic TTR carriers. Changes can only be detected using multimodal and extensive electrophysiological tests.