Abstract
Individuals carrying the amyloidogenic transthyretin (TTR) mutation are predisposed to develop familial amyloid polyneuropathy (FAP). The first clinical manifestations are often subjective sensory symptoms and, therefore, objective markers are needed to confirm the onset of TTR-FAP. The purpose of this study was to evaluate the usefulness of a comprehensive battery of neurophysiological tests to provide early markers of FAP in TTR-mutation carriers. Twenty patients with documented pathogenic TTR mutation were enrolled, including eight clinically asymptomatic carriers and 12 paucisymptomatic carriers who had subjective sensory symptoms or doubtful sensory signs but no firm clinical deficit at clinical examination. Neurophysiological assessment of large fibres consisted of conventional nerve conduction studies. Small-fibre tests included laser evoked potentials, sympathetic skin responses and the measurement of cold and warm detection thresholds and heart-rate variability. Abnormalities in small-fibre tests were found in two of the eight asymptomatic carriers and nine of the 12 paucisymptomatic carriers. In contrast, conventional conduction studies did not show any sign of polyneuropathy. Early neuropathic involvement in TTR-mutation carriers can be detected or confirmed by neurophysiological tests specifically assessing small nerve fibres. These tests did not show any redundancy or difference in their sensitivity, emphasizing the value of combining them for TTR-FAP diagnosis.
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This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Conflicts of interest
Dr. Lefaucheur has received speaker honoraria from Pfizer-Synergy and LFB and serves on the editorial board of the journals Clinical Neurophysiology and Neurophysiologie Clinique/Clinical Neurophysiology. Dr. Ng Wing Tin reports no disclosures. Dr. Kerschen reports no disclosures. Dr. Damy has received speaker honoraria from Pfizer-Synergy. Dr. Planté-Bordeneuve has received speaker honoraria from Pfizer-Synergy and as clinical investigator in Fx1A-301 study.
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Lefaucheur, JP., Ng Wing Tin, S., Kerschen, P. et al. Neurophysiological markers of small fibre neuropathy in TTR-FAP mutation carriers. J Neurol 260, 1497–1503 (2013). https://doi.org/10.1007/s00415-012-6816-8
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DOI: https://doi.org/10.1007/s00415-012-6816-8