Quantitative sensation and autonomic test abnormalities in transthyretin amyloidosis polyneuropathy

This study assesses the value of standard quantitative autonomic (QAT) and sensation (QST) tests in detecting, characterizing, and quantitating the severity of transthyretin amyloid polyneuropathy (TTR-A-PN). This information is needed for prospective therapeutic trials, epidemiologic surveys, and medical practice. We reviewed 36 patients with TTR-A-PN who were evaluated between 1997 and 2007. They had neurologic, genetic, electrodiagnostic, and autonomic reflex screen evaluations and allowed their medical records and test results to be evaluated for research purposes. Of these, 22 patients had also been tested by quantitative sensation tests (QSTs). The median symptom duration was 4 years (range 1-30 years). Among quantitative nerve tests evaluated, composite scores of nerve conduction (Sigma5 NC nds), a composite score of QSTs (Sigma3 QST nds), and quantitative autonomic tests (QSART, HR(db), and CASS) gave high frequencies of abnormality. The results show that peripheral autonomic and small-fiber sensory dysfunction was prominent and characteristic of most of the patients we studied. However, this involvement was not selective for small-diameter sensory and autonomic nerve fibers; large motor and sensory fibers were also shown to be dysfunctional. Dysfunction of large fibers was approximately as frequent as that of small fibers. This study provides a rationale for the use of QAT, QST, and Sigma5 NC nds as standard, objective, and quantitative measures for assessing the severity of TTR-A-PN in epidemiologic surveys, therapeutic trials, and medical practice.