{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,14]],"date-time":"2026-11-14T01:36:40Z","timestamp":1794620200241,"version":"4.9.1"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T00:00:00Z","timestamp":1687737600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T00:00:00Z","timestamp":1687737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100007195","name":"Universit\u00e0 degli Studi di Napoli Federico II","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007195","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Among non-motor symptoms, autonomic disturbances have been described in amyotrophic lateral sclerosis (ALS) and reported as mild to moderate in up to 75% of patients. However, no study has systematically investigated autonomic symptoms as prognostic factors.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Objectives<\/jats:title>\n                <jats:p>The main aim of this longitudinal study was to examine the association of autonomic dysfunction with disease progression and survival in ALS.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We enrolled newly diagnosed ALS patients and a healthy control group (HC). Time from disease onset to disease milestone (King\u2019s stage 4) and death were calculated to assess disease progression and survival. Autonomic symptoms were assessed by a dedicated questionnaire. Longitudinal evaluation of parasympathetic cardiovascular activity was performed by the heart rate variability (HRV). Multivariable Cox proportional hazards regression models on the risk of the disease milestone and death were used. A mixed-effect linear regression model was used to compare autonomic dysfunction with a HC group as well as its impairment over time.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>A total of 102 patients and 41 HC were studied. ALS patients, compared with HC, complained of more autonomic symptoms, especially in bulbar onset patients. Autonomic symptoms occurred in 69 (68%) patients at diagnosis and progressed over time (post-6: <jats:italic>p<\/jats:italic>\u2009=\u20090.015 and post-12: <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). A higher autonomic symptom burden was an independent marker of faster development of King\u2019s stage 4 (HR 1.05; 95% CI 1.00\u20131.11; <jats:italic>p<\/jats:italic>\u2009=\u20090.022); whereas, urinary complaints were independent factors of a shorter survival (HR 3.12; 95% CI 1.22\u20137.97; <jats:italic>p<\/jats:italic>\u2009=\u20090.018). Moreover, HRV in ALS patients was lower than in HC (<jats:italic>p<\/jats:italic>\u2009=\u20090.018) and further decreased over time (<jats:italic>p<\/jats:italic>\u2009=\u20090.003), implying a parasympathetic hypofunction that progressed over time.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Autonomic symptoms occur in most of the ALS patients at diagnosis and progress over time, implying that autonomic dysfunction represents an intrinsic non-motor feature of the disease. A higher autonomic burden is a poor prognostic factor, associated with a more rapid development of disease milestones and shorter survival.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00415-023-11832-w","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T05:01:43Z","timestamp":1687755703000},"page":"4968-4977","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Autonomic dysfunction is associated with disease progression and survival in amyotrophic lateral sclerosis: a prospective longitudinal cohort study"],"prefix":"10.1007","volume":"270","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2487-4741","authenticated-orcid":false,"given":"Raffaele","family":"Dubbioso","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Provitera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Pacella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucio","family":"Santoro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiore","family":"Manganelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Nolano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,6,26]]},"reference":[{"key":"11832_CR1","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1007\/s40263-021-00820-1","volume":"35","author":"CJ Mahoney","year":"2021","unstructured":"Mahoney CJ, Ahmed RM, Huynh W et al (2021) Pathophysiology and treatment of non-motor dysfunction in amyotrophic lateral sclerosis. CNS Drugs 35:483\u2013505. https:\/\/doi.org\/10.1007\/s40263-021-00820-1","journal-title":"CNS Drugs"},{"key":"11832_CR2","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1212\/WNL.0b013e318214359f","volume":"76","author":"M Elamin","year":"2011","unstructured":"Elamin M, Phukan J, Bede P et al (2011) Executive dysfunction is a negative prognostic indicator in patients with ALS without dementia. Neurology 76:1263\u20131269. https:\/\/doi.org\/10.1212\/WNL.0b013e318214359f","journal-title":"Neurology"},{"key":"11832_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.bandc.2021.105710","volume":"150","author":"C Nguyen","year":"2021","unstructured":"Nguyen C, Caga J, Mahoney CJ et al (2021) Behavioural changes predict poorer survival in amyotrophic lateral sclerosis. Brain Cogn 150:105710. https:\/\/doi.org\/10.1016\/j.bandc.2021.105710","journal-title":"Brain Cogn"},{"key":"11832_CR4","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1002\/mus.24457","volume":"51","author":"EA Piccione","year":"2015","unstructured":"Piccione EA, Sletten DM, Staff NP, Low PA (2015) Autonomic system and amyotrophic lateral sclerosis. Muscle Nerve 51:676\u2013679. https:\/\/doi.org\/10.1002\/mus.24457","journal-title":"Muscle Nerve"},{"key":"11832_CR5","doi-asserted-by":"publisher","first-page":"352","DOI":"10.3109\/17482968.2011.574141","volume":"12","author":"MLL De Carvalho","year":"2011","unstructured":"De Carvalho MLL, Motta R, Battaglia MA, Brichetto G (2011) Urinary disorders in amyotrophic lateral sclerosis subjects. Amyotroph Lateral Scler 12:352\u2013355. https:\/\/doi.org\/10.3109\/17482968.2011.574141","journal-title":"Amyotroph Lateral Scler"},{"key":"11832_CR6","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1002\/nau.22976","volume":"36","author":"S Arlandis","year":"2017","unstructured":"Arlandis S, V\u00e1zquez-Costa JF, Mart\u00ednez-Cuenca E et al (2017) Urodynamic findings in amyotrophic lateral sclerosis patients with lower urinary tract symptoms: results from a pilot study. Neurourol Urodyn 36:626\u2013631. https:\/\/doi.org\/10.1002\/nau.22976","journal-title":"Neurourol Urodyn"},{"key":"11832_CR7","doi-asserted-by":"publisher","first-page":"174","DOI":"10.3109\/21678421.2013.868001","volume":"15","author":"GS N\u00fcbling","year":"2014","unstructured":"N\u00fcbling GS, Mie E, Bauer RM et al (2014) Increased prevalence of bladder and intestinal dysfunction in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 15:174\u2013179. https:\/\/doi.org\/10.3109\/21678421.2013.868001","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"key":"11832_CR8","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1111\/nan.12332","volume":"43","author":"M Nolano","year":"2017","unstructured":"Nolano M, Provitera V, Manganelli F et al (2017) Non-motor involvement in amyotrophic lateral sclerosis: new insight from nerve and vessel analysis in skin biopsy. Neuropathol Appl Neurobiol 43:119\u2013132. https:\/\/doi.org\/10.1111\/nan.12332","journal-title":"Neuropathol Appl Neurobiol"},{"key":"11832_CR9","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1002\/mus.880181103","volume":"18","author":"F Pisano","year":"1995","unstructured":"Pisano F, Miscio G, Mazzuero G et al (1995) Decreased heart rate variability in amyotrophic lateral sclerosis. Muscle Nerve 18:1225\u20131231. https:\/\/doi.org\/10.1002\/mus.880181103","journal-title":"Muscle Nerve"},{"key":"11832_CR10","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1097\/01.wco.0000183114.76056.0e","volume":"18","author":"R Baltadzhieva","year":"2005","unstructured":"Baltadzhieva R, Gurevich T, Korczyn AD (2005) Autonomic impairment in amyotrophic lateral sclerosis. Curr Opin Neurol 18:487\u2013493. https:\/\/doi.org\/10.1097\/01.wco.0000183114.76056.0e","journal-title":"Curr Opin Neurol"},{"key":"11832_CR11","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1016\/S1474-4422(15)00058-7","volume":"14","author":"PA Low","year":"2015","unstructured":"Low PA, Reich SG, Jankovic J et al (2015) Natural history of multiple system atrophy in the USA: a prospective cohort study. Lancet Neurol 14:710\u2013719. https:\/\/doi.org\/10.1016\/S1474-4422(15)00058-7","journal-title":"Lancet Neurol"},{"key":"11832_CR12","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1001\/jamaneurol.2017.1125","volume":"74","author":"E De Pablo-Fernandez","year":"2017","unstructured":"De Pablo-Fernandez E, Tur C, Revesz T et al (2017) Association of autonomic dysfunction with disease progression and survival in Parkinson disease. JAMA Neurol 74:970\u2013976. https:\/\/doi.org\/10.1001\/jamaneurol.2017.1125","journal-title":"JAMA Neurol"},{"key":"11832_CR13","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1371\/journal.pone.0045451","volume":"7","author":"K Stubendorff","year":"2012","unstructured":"Stubendorff K, Aarsland D, Minthon L, Londos E (2012) The impact of autonomic dysfunction on survival in patients with dementia with Lewy bodies and Parkinson\u2019s disease with dementia. PLoS\u00a0One 7:3\u20138. https:\/\/doi.org\/10.1371\/journal.pone.0045451","journal-title":"PLoS\u00a0One"},{"key":"11832_CR14","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1136\/jnnp-2018-319374","volume":"90","author":"MCB Oliveira","year":"2019","unstructured":"Oliveira MCB, Ling H, Lees AJ et al (2019) Association of autonomic symptoms with disease progression and survival in progressive supranuclear palsy. J Neurol Neurosurg Psychiatry 90:555\u2013561. https:\/\/doi.org\/10.1136\/jnnp-2018-319374","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"11832_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fpubh.2017.00258","volume":"5","author":"F Shaffer","year":"2017","unstructured":"Shaffer F, Ginsberg JP (2017) An overview of heart rate variability metrics and norms. Front Public Health 5:1\u201317. https:\/\/doi.org\/10.3389\/fpubh.2017.00258","journal-title":"Front Public Health"},{"key":"11832_CR16","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1080\/146608200300079536","volume":"1","author":"BR Brooks","year":"2000","unstructured":"Brooks BR, Miller RG, Swash M, Munsat TL (2000) El Escorial revisited: revised criteria for the diagnosis of ALS. Amyotroph Lateral Scler Other Motor Neuron Disord 1:293\u2013299","journal-title":"Amyotroph Lateral Scler Other Motor Neuron Disord"},{"key":"11832_CR17","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1136\/jnnp.2005.072660","volume":"77","author":"A Czaplinski","year":"2006","unstructured":"Czaplinski A, Yen AA, Appel SH (2006) Forced vital capacity (FVC) as an indicator of survival and disease progression in an ALS clinic population. J Neurol Neurosurg Psychiatry 77:390\u2013392. https:\/\/doi.org\/10.1136\/jnnp.2005.072660","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"11832_CR18","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1136\/jnnp-2015-310998","volume":"87","author":"J Labra","year":"2016","unstructured":"Labra J, Menon P, Byth K et al (2016) Rate of disease progression: a prognostic biomarker in ALS. J Neurol Neurosurg Psychiatry 87:628\u2013632. https:\/\/doi.org\/10.1136\/jnnp-2015-310998","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"11832_CR19","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1212\/WNL.0000000000002912","volume":"87","author":"K Shibuya","year":"2016","unstructured":"Shibuya K, Park SB, Geevasinga N et al (2016) Motor cortical function determines prognosis in sporadic ALS. Neurology 87:513\u2013520. https:\/\/doi.org\/10.1212\/WNL.0000000000002912","journal-title":"Neurology"},{"key":"11832_CR20","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1093\/brain\/awr351","volume":"135","author":"JC Roche","year":"2012","unstructured":"Roche JC, Rojas-Garcia R, Scott KM et al (2012) A proposed staging system for amyotrophic lateral sclerosis. Brain 135:847\u2013852. https:\/\/doi.org\/10.1093\/brain\/awr351","journal-title":"Brain"},{"key":"11832_CR21","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1080\/21678421.2016.1267768","volume":"18","author":"MJ Strong","year":"2017","unstructured":"Strong MJ, Abrahams S, Goldstein LH et al (2017) Amyotrophic lateral sclerosis\u2014frontotemporal spectrum disorder (ALS-FTSD): revised diagnostic criteria. Amyotroph Lateral Scler Frontotemporal Degener 18:153\u2013174. https:\/\/doi.org\/10.1080\/21678421.2016.1267768","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"key":"11832_CR22","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2019-321153","author":"U Manera","year":"2019","unstructured":"Manera U, Calvo A, Daviddi M et al (2019) Regional spreading of symptoms at diagnosis as a prognostic marker in amyotrophic lateral sclerosis: a population-based study. J Neurol Neurosurg Psychiatry. https:\/\/doi.org\/10.1136\/jnnp-2019-321153","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"11832_CR23","doi-asserted-by":"publisher","DOI":"10.1111\/ene.15936","author":"R Dubbioso","year":"2023","unstructured":"Dubbioso R, Spisto M, Hausdorff JM, Aceto G, Iuzzolino VV, Senerchia G, De Marco S, Marcuccio L, Femiano C, Iodice R, Salvatore E, Santangelo G, Trojano L, Moretta P. Cognitive impairment is associated with gait variability and fall risk in Amyotrophic Lateral Sclerosis. Eur J Neurol. 2023. https:\/\/doi.org\/10.1111\/ene.15936","journal-title":"Eur J Neurol"},{"key":"11832_CR24","doi-asserted-by":"publisher","first-page":"5403","DOI":"10.1007\/s10072-022-06231-4","volume":"43","author":"P Moretta","year":"2022","unstructured":"Moretta P, Spisto M, Ausiello FP et al (2022) Alteration of interoceptive sensitivity: expanding the spectrum of behavioural disorders in amyotrophic lateral sclerosis. Neurol Sci 43:5403\u20135410. https:\/\/doi.org\/10.1007\/s10072-022-06231-4","journal-title":"Neurol Sci"},{"key":"11832_CR25","doi-asserted-by":"publisher","first-page":"2339","DOI":"10.1007\/s10072-020-04592-2","volume":"41","author":"N De Lucia","year":"2020","unstructured":"De Lucia N, Ausiello FP, Spisto M et al (2020) The emotional impact of COVID-19 outbreak in amyotrophic lateral sclerosis patients: evaluation of depression, anxiety and interoceptive awareness. Neurol Sci 41:2339\u20132341. https:\/\/doi.org\/10.1007\/s10072-020-04592-2","journal-title":"Neurol Sci"},{"key":"11832_CR26","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1002\/mds.20153","volume":"19","author":"M Visser","year":"2004","unstructured":"Visser M, Marinus J, Stiggelbout AM, van Hilten JJ (2004) Assessment of autonomic dysfunction in Parkinson\u2019s disease: the SCOPA-AUT. Mov Disord 19:306\u2013312. https:\/\/doi.org\/10.1002\/mds.20153","journal-title":"Mov Disord"},{"key":"11832_CR27","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1016\/j.parkreldis.2011.12.009","volume":"18","author":"N Damon-Perri\u00e8re","year":"2012","unstructured":"Damon-Perri\u00e8re N, Foubert-Samier A, De Cock VC et al (2012) Assessment of the Scopa-Aut questionnaire in multiple system atrophy: relation to UMSARS scores and progression over time. Parkinsonism Relat Disord 18:612\u2013615. https:\/\/doi.org\/10.1016\/j.parkreldis.2011.12.009","journal-title":"Parkinsonism Relat Disord"},{"key":"11832_CR28","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12692","author":"R Dubbioso","year":"2021","unstructured":"Dubbioso R, Provitera V, Vitale F et al (2021) Cutaneous sensory and autonomic denervation in progressive supranuclear palsy. Neuropathol Appl Neurobiol. https:\/\/doi.org\/10.1111\/nan.12692","journal-title":"Neuropathol Appl Neurobiol"},{"key":"11832_CR29","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1136\/jnnp.48.11.1103","volume":"48","author":"PGE Kennedy","year":"1985","unstructured":"Kennedy PGE, Duchen LW (1985) A quantitative study of intermediolateral column cells in motor neuron disease and the Shy\u2013Drager syndrome. J Neurol Neurosurg Psychiatry 48:1103\u20131106. https:\/\/doi.org\/10.1136\/jnnp.48.11.1103","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"11832_CR30","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1007\/BF00334889","volume":"86","author":"H Takahashi","year":"1993","unstructured":"Takahashi H, Oyanagi K, Ikuta F (1993) The intermediolateral nucleus in sporadic amyotrophic lateral sclerosis. Acta Neuropathol 86:190\u2013192. https:\/\/doi.org\/10.1007\/BF00334889","journal-title":"Acta Neuropathol"},{"key":"11832_CR31","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/0022-510X(86)90130-9","volume":"73","author":"H Konno","year":"1986","unstructured":"Konno H, Yamamoto T, Iwasaki Y, Iizuka H (1986) Shy-Drager syndrome and amyotrophic lateral sclerosis. Cytoarchitectonic and morphometric studies of sacral autonomic neurons. J Neurol Sci 73:193\u2013204. https:\/\/doi.org\/10.1016\/0022-510X(86)90130-9","journal-title":"J Neurol Sci"},{"key":"11832_CR32","doi-asserted-by":"publisher","first-page":"2024","DOI":"10.1212\/WNL.0b013e31821e553a","volume":"76","author":"J Weis","year":"2011","unstructured":"Weis J, Katona I, M\u00fcller-Newen G et al (2011) Small-fiber neuropathy in patients with ALS. Neurology 76:2024\u20132029. https:\/\/doi.org\/10.1212\/WNL.0b013e31821e553a","journal-title":"Neurology"},{"key":"11832_CR33","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1007\/s00415-015-7672-0","volume":"262","author":"A Truini","year":"2015","unstructured":"Truini A, Biasiotta A, Onesti E et al (2015) Small-fibre neuropathy related to bulbar and spinal-onset in patients with ALS. J Neurol 262:1014\u20131018. https:\/\/doi.org\/10.1007\/s00415-015-7672-0","journal-title":"J Neurol"},{"key":"11832_CR34","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1111\/ene.12936","volume":"23","author":"E Dalla Bella","year":"2016","unstructured":"Dalla Bella E, Lombardi R, Porretta-Serapiglia C et al (2016) Amyotrophic lateral sclerosis causes small fiber pathology. Eur J Neurol 23:416\u2013420. https:\/\/doi.org\/10.1111\/ene.12936","journal-title":"Eur J Neurol"},{"key":"11832_CR35","volume-title":"Primer on the autonomic nervous system","author":"DW Robertson","year":"2012","unstructured":"Robertson DW, Biaggioni I, Burnstock G et al (2012) Primer on the autonomic nervous system. Elsevier"},{"key":"11832_CR36","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1212\/WNL.54.7.1534","volume":"54","author":"T Shimizu","year":"2000","unstructured":"Shimizu T, Kawata A, Kato S et al (2000) Autonomic failure in ALS with a novel SOD1 gene mutation. Neurology 54:1534\u20131537. https:\/\/doi.org\/10.1212\/WNL.54.7.1534","journal-title":"Neurology"},{"key":"11832_CR37","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1159\/000517613","volume":"21","author":"C Parra-Cantu","year":"2021","unstructured":"Parra-Cantu C, Zaldivar-Ruenes A, Martinez-Vazquez M, Martinez HR (2021) Prevalence of gastrointestinal symptoms, severity of dysphagia, and their correlation with severity of amyotrophic lateral sclerosis in a Mexican cohort. Neurodegener Dis 21:42\u201347. https:\/\/doi.org\/10.1159\/000517613","journal-title":"Neurodegener Dis"},{"key":"11832_CR38","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1159\/000007708","volume":"60","author":"M Toepfer","year":"1999","unstructured":"Toepfer M, Folwaczny C, Lochm\u00fcller H et al (1999) Noninvasive 13C-octanoic acid breath test shows delayed gastric emptying in patients with amyotrophic lateral sclerosis. Digestion 60:567\u2013571. https:\/\/doi.org\/10.1159\/000007708","journal-title":"Digestion"},{"key":"11832_CR39","first-page":"473","volume":"2","author":"M Toepfer","year":"1997","unstructured":"Toepfer M, Schroeder M, Klause R et al (1997) Delayed colonic transit times in amyotrophic lateral sclerosis assessed with radio-opaque markers. Eur J Med Res 2:473\u2013476","journal-title":"Eur J Med Res"},{"key":"11832_CR40","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.jns.2017.04.053","volume":"378","author":"JF V\u00e1zquez-Costa","year":"2017","unstructured":"V\u00e1zquez-Costa JF, Arlandis S, Hervas D et al (2017) Clinical profile of motor neuron disease patients with lower urinary tract symptoms and neurogenic bladder. J Neurol Sci 378:130\u2013136. https:\/\/doi.org\/10.1016\/j.jns.2017.04.053","journal-title":"J Neurol Sci"},{"key":"11832_CR41","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1093\/brain\/116.1.203","volume":"116","author":"HAJ Kiernan","year":"1993","unstructured":"Kiernan HAJ (1993) Changes in shapes of surviving motor neurons in amyotrophic lateral sclerosis. Brain 116:203\u2013215. https:\/\/doi.org\/10.1093\/brain\/116.1.203","journal-title":"Brain"},{"key":"11832_CR42","doi-asserted-by":"publisher","first-page":"272","DOI":"10.3109\/17482960903390855","volume":"11","author":"S Pavlovic","year":"2010","unstructured":"Pavlovic S, Stevic Z, Milovanovic B et al (2010) Impairment of cardiac autonomic control in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler 11:272\u2013276. https:\/\/doi.org\/10.3109\/17482960903390855","journal-title":"Amyotroph Lateral Scler"},{"key":"11832_CR43","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1088\/0967-3334\/36\/4\/659","volume":"36","author":"L Dalla Vecchia","year":"2015","unstructured":"Dalla Vecchia L, De Maria B, Marinou K et al (2015) Cardiovascular neural regulation is impaired in amyotrophic lateral sclerosis patients. A study by spectral and complexity analysis of cardiovascular oscillations. Physiol Meas 36:659\u2013670. https:\/\/doi.org\/10.1088\/0967-3334\/36\/4\/659","journal-title":"Physiol Meas"},{"key":"11832_CR44","doi-asserted-by":"publisher","unstructured":"De Maria B, Bari V, Marchi A, et al (2015) Cardiovascular control indexes in amyotrophic lateral sclerosis patients and their relation with clinical markers. Proceedings of the annual international conference of the IEEE engineering in medicine and biology society, EMBS 2015-November:2055\u20132058. https:\/\/doi.org\/10.1109\/EMBC.2015.7318791","DOI":"10.1109\/EMBC.2015.7318791"},{"key":"11832_CR45","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1007\/s10286-003-0100-z","volume":"13","author":"A Lipp","year":"2003","unstructured":"Lipp A, Tank J, Stoffels M et al (2003) Riluzole and blood pressure in multiple system atrophy. Clin Auton Res 13:271\u2013274. https:\/\/doi.org\/10.1007\/s10286-003-0100-z","journal-title":"Clin Auton Res"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-023-11832-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-023-11832-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-023-11832-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T04:05:14Z","timestamp":1695182714000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-023-11832-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,26]]},"references-count":45,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["11832"],"URL":"https:\/\/doi.org\/10.1007\/s00415-023-11832-w","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,26]]},"assertion":[{"value":"26 April 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 June 2023","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 June 2023","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 June 2023","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no relevant financial or non-financial interests to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"The study was approved by the ethics committee of the University Federico II of Naples (N. 100\/17). All procedures were performed in accordance with the ethical outlines in the 1964 Helsinki Declaration and its later amendments.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"All patients or their parents\/legal representatives provided written informed consent for to participate in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All patients or their parents\/legal representatives provided written informed consent for publication.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}