Neuropathic involvement in wild-type transthyretin amyloidosis

Wild-type transthyretin amyloidosis (ATTRwt amyloidosis) has traditionally been considered a purely cardiological condition. However, recent studies suggest that neurological involvement in ATTRwt amyloidosis is more significant than previously believed. We conducted a comprehensive neurological study aiming to contribute to a better clinical and functional characterization of the neuropathy in this disease.

Fourteen patients with ATTRwt amyloidosis were recruited at Hospital Clínico San Carlos (Madrid, Spain). Participants completed various clinical questionnaires and underwent neurological examination, functional tests, and measurement of electrochemical skin conductance. Additionally, their laboratory analysis results and electrophysiological data were reviewed.

The cohort included 14 men with an average age of 83.07 years (standard deviation: 6.39). Overall, 92.9% presented objective signs of neuropathy, with 71.4% showing electrophysiological evidence of neuropathy, which was predominantly axonal and sensorimotor. Patients scored a median of 8 (interquartile range: 8) on the Neuropathy Impairment Score, and 1 on the Familial Amyloid Polyneuropathy and Polyneuropathy Disability stages. Electrochemical skin conductance was altered in 64.3%, although there was limited impact on the Composite Autonomic Symptom Score-31 (median: 12) and Survey of Autonomic Symptoms (median: 7.5) scales. A decrease in quality of life, according to the Norfolk scale, was reported by 69.2% of patients.

Large- and small-fiber neuropathy are highly prevalent in ATTRwt amyloidosis. Although their clinical and functional impact is mild to moderate, they reduce the patients' quality of life. This finding sheds light on the disease and paves the way for new therapeutic alternatives.