{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T06:32:18Z","timestamp":1788330738486,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T00:00:00Z","timestamp":1692144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006400","name":"Alnylam Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006400","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Peripheral Nervous Sys"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Hereditary transthyretin amyloidosis polyneuropathy (ATTRv\u2010PN) presymptomatic carriers often show preclinical abnormalities at small fiber\u2010related diagnostic tests. However, no validated biomarker is currently available to use for presymptomatic carriers' follow\u2010up, thus helping therapeutic decision making. Our study aimed at assessing nerve conduction study (NCS), quantitative sensory testing (QST), and skin biopsy parameters in a large cohort of late\u2010onset ATTRv presymptomatic carriers and to evaluate whether they correlated with predicted age of disease onset (PADO).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Late\u2010onset ATTRv presymptomatic carriers were consecutively enrolled and underwent NCS, QST, and skin biopsy with intraepidermal nerve fiber density (IENFD) evaluation from a distal and a proximal site. <jats:italic>Douleur Neuropathique\u20104<\/jats:italic> (DN4) and Small Fiber Neuropathy\u2010Symptoms Inventory (SFN\u2010SIQ) were used to assess painful and small fiber neuropathy\u2010related symptoms. PADO and time\u2010to\u2010PADO (delta\u2010PADO) were estimated for each carrier, and correlations with diagnostic test measures were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Forty presymptomatic ATTRv subjects were enrolled. Twenty carriers (50%) had distal IENFD reduction, with a non\u2010length\u2010dependent distribution in 73% of cases. Eleven subjects (27.5%) had cold and\/or warm detection threshold (CDT and\/or WDT) abnormalities at QST. Delta\u2010PADO positively correlated with sural sensory nerve action potential (SNAP) amplitude (<jats:italic>r<\/jats:italic>\u2009=\u2009.416, <jats:italic>p<\/jats:italic>\u2009=\u2009.004), and z\u2010values of QST parameters like CDT (<jats:italic>r<\/jats:italic>\u2009=\u2009.314, <jats:italic>p<\/jats:italic>\u2009=\u2009.028), WDT (<jats:italic>r<\/jats:italic>\u2009=\u2009\u2212.294, <jats:italic>p<\/jats:italic>\u2009=\u2009.034), and mechanical detection threshold (MDT; <jats:italic>r<\/jats:italic>\u2009=\u2009\u2212.382, <jats:italic>p<\/jats:italic>\u2009=\u2009.012). Simple linear regression models showed a linear relation between delta\u2010PADO and sural SAP, CDT, and MDT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings confirm that IENFD reduction and QST abnormalities may occur early in ATTRv presymptomatic carriers, often with a non\u2010length\u2010dependent pattern. However, only sural SAP amplitude and QST parameters correlated with delta\u2010PADO, suggesting that serial combined QST and NCS evaluation could be useful in ATTRv presymptomatic carriers' follow\u2010up.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jns.12586","type":"journal-article","created":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T15:48:44Z","timestamp":1691077724000},"page":"390-397","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Quantitative sensory testing and skin biopsy findings in late\u2010onset ATTRv presymptomatic carriers: Relationships with predicted time of disease onset (PADO)"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1267-864X","authenticated-orcid":false,"given":"Luca","family":"Leonardi","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Mental Health and Sensory Organs (NESMOS) Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocco","family":"Costanzo","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mental Health and Sensory Organs (NESMOS) Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Forcina","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mental Health and Sensory Organs (NESMOS) Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Morino","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mental Health and Sensory Organs (NESMOS) Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Antonini","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mental Health and Sensory Organs (NESMOS) Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Salvetti","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mental Health and Sensory Organs (NESMOS) Sapienza University of Rome  Rome Italy"},{"name":"Neuromed Institute IRCCS  Pozzilli Isernia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7539-505X","authenticated-orcid":false,"given":"Marco","family":"Luigetti","sequence":"additional","affiliation":[{"name":"UOC Neurologia Fondazione Policlinico Universitario A. 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Sede di Roma  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8813-2272","authenticated-orcid":false,"given":"Laura","family":"Fionda","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mental Health and Sensory Organs (NESMOS) Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Garibaldi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mental Health and Sensory Organs (NESMOS) Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Lauletta","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mental Health and Sensory Organs (NESMOS) Sapienza University of Rome  Rome 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