{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T13:41:16Z","timestamp":1776519676262,"version":"3.51.2"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T00:00:00Z","timestamp":1637107200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Hereditary amyloidosis related to transthyretin (ATTR) is a rare and progressive disease that, despite the phenotypic heterogeneity, a length\u2010dependent sensorimotor axonal neuropathy (ATTR\u2010PN) is the classic hallmark. Timely diagnosis is paramount for early treatment implementation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sixty\u2010nine asymptomatic gene carriers (Val30Met) were assessed during a 4\u2010year period to identify those remaining asymptomatic versus those converting to ATTRV30M\u2010PN. Conversion to symptomatic was defined as presenting with two definite symptoms of ATTRV30M\u2010PN. Composite neurophysiological scores of sensory (SNS), motor (MNS), and sympathetic skin response (SSRS) amplitudes were used to assess neuropathy progression. We used mixed\u2010effects modeling and ordinal logistic regression to assess neurophysiological evolution over time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of all asymptomatic gene carriers, 55.1% (<jats:italic>n<\/jats:italic>\u00a0=\u00a038\/69) converted over the period of this analysis. The progression of the SNS relative to baseline was different between groups (asymptomatic gene carriers vs. converters), the decline being greater in the converter group (time \u00d7 group interaction <jats:italic>p<\/jats:italic>\u00a0=\u00a00.040), starting about 2\u00a0years before symptom onset. No significant change occurred regarding MNS or SSRS. Moreover, the percentage of cases with an annual decline on the SNS of at least 25%, gradually and significantly increased in the converter group, representing a 1.92 increase in risk of developing symptoms for those with such reduction on the last evaluation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A simple composite neurophysiological sum score can predict the onset of ATTRV30M\u2010PN symptoms by as much as 2\u00a0years, highlighting the importance of a systematic follow\u2010up of asymptomatic gene carriers, allowing a timely diagnosis, and management of symptomatic disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.15176","type":"journal-article","created":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T17:47:47Z","timestamp":1636480067000},"page":"826-832","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Changes in nerve conduction studies predate clinical symptoms onset in early onset Val30Met hereditary ATTR amyloidosis"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8984-475X","authenticated-orcid":false,"given":"Jos\u00e9","family":"Castro","sequence":"first","affiliation":[{"name":"Department of Neurosciences and Mental Health Centro Hospitalar Universit\u00e1rio de Lisboa Central Lisbon Portugal"},{"name":"Faculdade de Medicina Instituto de Fisiologia Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes Universidade de Lisboa Lisbon Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4660-6051","authenticated-orcid":false,"given":"Bruno","family":"Miranda","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina Instituto de Fisiologia Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes Universidade de Lisboa Lisbon Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"de Castro","sequence":"additional","affiliation":[{"name":"Department of Neurosciences and Mental Health Centro Hospitalar Universit\u00e1rio de Lisboa Central Lisbon Portugal"},{"name":"Faculdade de Medicina Instituto de Fisiologia Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes Universidade de Lisboa Lisbon Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Concei\u00e7\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Neurosciences and Mental Health Centro Hospitalar Universit\u00e1rio de Lisboa Central Lisbon Portugal"},{"name":"Faculdade de Medicina Instituto de Fisiologia Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes Universidade de Lisboa Lisbon Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,11,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.34.8.1025"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/13506129.2018.1549825"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-8-31"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-017-0726-x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jns.12153"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0210-4"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1716153"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1716793"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(11)70246-0"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.41.9.847"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001870"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13724"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr383"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-014-7373-0"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1991.tb03085.x"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182661eb1"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30368-9"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.14285"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/13506129.2018.1556156"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.23901"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-012-6816-8"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2016.02.013"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/13506129.2019.1708716"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu344"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/med\/9780199738687.001.0001"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000092307.98347.CB"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/75.3.408"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/123.7.1495"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.3109\/13506120208995245"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.2147\/TCRM.S219979"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004016"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.51.2.165"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pmr.2008.02.006"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-003-0107-5"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-019-09688-0"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.2147\/TCRM.S185677"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.15176","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ene.15176","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.15176","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T08:38:15Z","timestamp":1692866295000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.15176"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,17]]},"references-count":36,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1111\/ene.15176"],"URL":"https:\/\/doi.org\/10.1111\/ene.15176","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"value":"1351-5101","type":"print"},{"value":"1468-1331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,17]]},"assertion":[{"value":"2021-07-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}