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Early changes of nerve integrity in preclinical carriers of hereditary transthyretin Ala117Ser amyloidosis with polyneuropathy
Author(s) -
Chiang MingChang,
Yeh TiYen,
Sung JiaYing,
Hsueh HsuehWen,
Kao YiHui,
Hsueh SungJu,
Chang KaiChieh,
Feng FangPing,
Lin YeaHuey,
Chao ChiChao,
Hsieh SungTsang
Publication year - 2021
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.14698
Subject(s) - medicine , polyneuropathy , asymptomatic , nerve fiber , asymptomatic carrier , nerve conduction study , motor nerve , nerve conduction velocity , diabetes mellitus , pathology , cardiology , endocrinology , nerve conduction , anatomy
Background and purpose Disease‐modifying therapies provide new horizons for hereditary transthyretin amyloidosis with polyneuropathy (ATTRv‐PN) to slow neuropathic progression. Initiating treatment at the earliest time requires biomarkers reflecting both small‐ and large‐fiber degeneration in carriers. Methods This study included examinations of pathology (intraepidermal nerve fiber [IENF] density), physiology (nerve conduction studies, autonomic function test, and nerve excitability), and psychophysics (thermal thresholds) in carriers to compare to healthy controls and asymptomatic diabetic patients. Results There were 43 carriers (44.2 ± 11.4 years, p.Ala117Ser in 42 carriers), 43 controls (43.4 ± 12.7 years) including 26 noncarrier families, and 50 asymptomatic diabetic patients (58.1 ± 9.5 years). Carriers had lower IENF densities than controls and similar densities as diabetic patients. Median nerve conduction parameters, especially distal motor latency, were the most frequent neurophysiological abnormality in carriers, could differentiate carriers from controls and diabetic patients, were correlated with IENF densities in carriers but not in controls and diabetic patients, and were correlated with nerve excitability parameters in carriers but not in controls. Fifteen carriers (34.9%) with electrophysiological evidence of median nerve entrapment at the wrist had lower IENF densities and more abnormal conduction parameters than carriers without. We defined nerve dysfunction index—the ratio of median distal motor latency to IENF density—which differentiated carriers from controls. Conclusions In late‐onset ATTRv‐PN carriers with predominant p.Ala117Ser, median conduction parameters were the most common neurophysiological abnormalities and served as surrogate signatures of small‐ and large‐fiber impairment. Combination of median distal motor latency and IENF density can reflect early neuropathy in carriers.