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There are few studies about non\u2010motor manifestations in this disease and none about autonomic involvement. Therefore, the aim was to\u00a0determine the frequency and pattern of autonomic complaints in patients with <jats:styled-content style=\"fixed-case\">SPG<\/jats:styled-content>4\u2010<jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content>, as well as to determine the clinical relevance and the possible factors associated with these manifestations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty\u2010four molecularly confirmed <jats:styled-content style=\"fixed-case\">SPG<\/jats:styled-content>4 patients were recruited in a multicenter cross\u2010sectional study, of whom 26 underwent detailed neurophysiological testing (heart rate variability, sympathetic skin response and the Quantitative Sudomotor Axonal Reflex Test). The Scales for Outcomes in Parkinson's Disease \u2013 Autonomic Questionnaire (<jats:styled-content style=\"fixed-case\">SCOPA<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">AUT<\/jats:styled-content>) was applied to quantify the severity of autonomic symptoms. Results were compared with 44 age\u2010 and gender\u2010matched healthy controls using non\u2010parametric tests. <jats:italic>P<\/jats:italic> values &lt;0.05 were considered significant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the <jats:styled-content style=\"fixed-case\">SPG<\/jats:styled-content>4\u2010<jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content> group, there were 18 men with a mean age of 47.7\u00a0\u00b1\u00a012.6\u00a0years. <jats:styled-content style=\"fixed-case\">SCOPA<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">AUT<\/jats:styled-content> scores were similar between patients and controls (<jats:italic>P\u00a0=\u00a0<\/jats:italic>0.238). Only the urinary domain subscore was significantly higher amongst patients (4 vs. 2.5, <jats:italic>P\u00a0=\u00a0<\/jats:italic>0.05).\u00a0Absent sympathetic skin response in the hands and feet was more frequent amongst patients (20% vs. 0%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001, and 64% vs. 0%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.006, respectively). Quantitative Sudomotor Axonal Reflex Test responses were also smaller throughout all recording regions in the <jats:styled-content style=\"fixed-case\">SPG<\/jats:styled-content>4\u2010<jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content> group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results indicate that <jats:styled-content style=\"fixed-case\">SPG<\/jats:styled-content>4\u2010<jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content> patients have sudomotor dysfunction caused by damaged small post\u2010ganglionic cholinergic fibers. Damage in <jats:styled-content style=\"fixed-case\">SPG<\/jats:styled-content>4\u2010<jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content> extends to the peripheral nervous system.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.13878","type":"journal-article","created":{"date-parts":[[2018,11,29]],"date-time":"2018-11-29T17:03:34Z","timestamp":1543511014000},"page":"687-693","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Autonomic dysfunction in hereditary spastic paraplegia type 4"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2300-682X","authenticated-orcid":false,"given":"C.","family":"Gonz\u00e1lez\u2010Salazar","sequence":"first","affiliation":[{"name":"Department of Neurology School of Medical Sciences University of Campinas (UNICAMP) Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. A. G.","family":"Takazaki","sequence":"additional","affiliation":[{"name":"Department of Neurology School of Medical Sciences University of Campinas (UNICAMP) Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7160-0853","authenticated-orcid":false,"given":"A. R. M.","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Neurology School of Medical Sciences University of Campinas (UNICAMP) Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. R.","family":"Pimentel\u2010Silva","sequence":"additional","affiliation":[{"name":"Department of Neurology School of Medical Sciences University of Campinas (UNICAMP) Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. A.","family":"Jacinto\u2010Scudeiro","sequence":"additional","affiliation":[{"name":"Medical Genetics and Neurology Services Hospital de Cl\u00ednicas de Porto Alegre Porto Alegre Brazil"},{"name":"Department of Internal Medicine and Sciences Universidade Federal do Rio Grande do Sul (UFRGS) Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9. Y.","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Neurology Service Universidade Federal do Paran\u00e1 Curitiba Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. E.","family":"Fujiwara Murakami","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Neurology Service Universidade Federal do Paran\u00e1 Curitiba Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. A. 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