{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:54:29Z","timestamp":1790834069544,"version":"4.1.0"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T00:00:00Z","timestamp":1571788800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T00:00:00Z","timestamp":1571788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100009397","name":"Medizinischen Fakult\u00e4t, Eberhard Karls Universit\u00e4t T\u00fcbingen","doi-asserted-by":"publisher","award":["#386-0-0"],"award-info":[{"award-number":["#386-0-0"]}],"id":[{"id":"10.13039\/501100009397","id-type":"DOI","asserted-by":"publisher"}]},{"name":"HSP Selbsthilfegruppe","award":["Grant recipient LS&TWR"],"award-info":[{"award-number":["Grant recipient LS&TWR"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2020,2]]},"DOI":"10.1007\/s00415-019-09573-w","type":"journal-article","created":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T13:17:49Z","timestamp":1571836669000},"page":"369-379","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Non-motor symptoms are relevant and possibly treatable in hereditary spastic paraplegia type 4 (SPG4)"],"prefix":"10.1007","volume":"267","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5456-7761","authenticated-orcid":false,"given":"Tim W.","family":"Rattay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Boldt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"V\u00f6lker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Wiethoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Hengel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Sch\u00fcle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludger","family":"Sch\u00f6ls","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,10,23]]},"reference":[{"key":"9573_CR1","doi-asserted-by":"publisher","first-page":"958","DOI":"10.3389\/fneur.2018.00958","volume":"9","author":"DM Bis-Brewer","year":"2018","unstructured":"Bis-Brewer DM, Zuchner S (2018) Perspectives on the genomics of HSP beyond Mendelian inheritance. Front Neurol 9:958","journal-title":"Front Neurol"},{"key":"9573_CR2","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1002\/ana.24611","volume":"79","author":"R Schule","year":"2016","unstructured":"Schule R, Wiethoff S, Martus P, Karle KN, Otto S, Klebe S, Klimpe S, Gallenmuller C, Kurzwelly D, Henkel D, Rimmele F, Stolze H, Kohl Z, Kassubek J, Klockgether T, Vielhaber S, Kamm C, Klopstock T, Bauer P, Zuchner S, Liepelt-Scarfone I, Schols L (2016) Hereditary spastic paraplegia: clinicogenetic lessons from 608 patients. Ann Neurol 79:646\u2013658","journal-title":"Ann Neurol"},{"key":"9573_CR3","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3389\/fneur.2019.00003","volume":"10","author":"M Bellofatto","year":"2019","unstructured":"Bellofatto M, De Michele G, Iovino A, Filla A, Santorelli FM (2019) Management of hereditary spastic paraplegia: a systematic review of the literature. Front Neurol 10:3","journal-title":"Front Neurol"},{"key":"9573_CR4","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1177\/0269215509337186","volume":"23","author":"L Vahter","year":"2009","unstructured":"Vahter L, Braschinsky M, Haldre S, Gross-Paju K (2009) The prevalence of depression in hereditary spastic paraplegia. Clin Rehabil 23:857\u2013861","journal-title":"Clin Rehabil"},{"key":"9573_CR5","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1159\/000097007","volume":"57","author":"AD Sperfeld","year":"2007","unstructured":"Sperfeld AD, Unrath A, Kassubek J (2007) Restless legs syndrome in hereditary spastic paraparesis. Eur Neurol 57:31\u201335","journal-title":"Eur Neurol"},{"key":"9573_CR6","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1111\/ene.12839","volume":"23","author":"K Servelhere","year":"2016","unstructured":"Servelhere K, Faber I, Saute J, Moscovich M, D'Abreu A, Jardim L, Teive H, Lopes-Cendes I, Franca M (2016) Non-motor symptoms in patients with hereditary spastic paraplegia caused by SPG4 mutations. Eur J Neurol 23:408\u2013411","journal-title":"Eur J Neurol"},{"key":"9573_CR7","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1136\/jnnp-2017-315796","volume":"88","author":"V Chelban","year":"2017","unstructured":"Chelban V, Tucci A, Lynch DS, Polke JM, Santos L, Jonvik H, Groppa S, Wood NW, Houlden HJJNNP (2017) Truncating mutations in SPAST patients are associated with a high rate of psychiatric comorbidities in hereditary spastic paraplegia. J Neurol Neurosurg Psychiatry 88:681\u2013687","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"9573_CR8","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1212\/WNL.0b013e3181b04c6c","volume":"73","author":"S Murphy","year":"2009","unstructured":"Murphy S, Gorman G, Beetz C, Byrne P, Dytko M, McMonagle P, Kinsella K, Farrell M, Hutchinson M (2009) Dementia in SPG4 hereditary spastic paraplegia clinical, genetic, and neuropathologic evidence. Neurology 73:378\u2013384","journal-title":"Neurology"},{"key":"9573_CR9","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1212\/01.WNL.0000108629.04434.05","volume":"62","author":"P McMonagle","year":"2004","unstructured":"McMonagle P, Byrne P, Hutchinson M (2004) Further evidence of dementia in SPG4-linked autosomal dominant hereditary spastic paraplegia. Neurology 62:407\u2013410","journal-title":"Neurology"},{"key":"9573_CR10","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1001\/archneur.60.8.1113","volume":"60","author":"CE Tallaksen","year":"2003","unstructured":"Tallaksen CE, Guichart-Gomez E, Verpillat P et al (2003) Subtle cognitive impairment but no dementia in patients with spastin mutations. Arch Neurol 60:1113\u20131118","journal-title":"Arch Neurol"},{"key":"9573_CR11","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/6423461","author":"L Chamard","year":"2016","unstructured":"Chamard L, Ferreira S, Pijoff A, Silvestre M, Berger E, Magnin E (2016) Cognitive impairment involving social cognition in SPG4 hereditary spastic paraplegia. Behav Neurol. \nhttps:\/\/doi.org\/10.1155\/2016\/6423461","journal-title":"Behav Neurol"},{"key":"9573_CR12","doi-asserted-by":"publisher","first-page":"1961","DOI":"10.1007\/s00415-015-7791-7","volume":"261","author":"T Lindig","year":"2015","unstructured":"Lindig T, Bender B, Hauser T-K, Mang S, Schweikardt D, Klose U, Karle KN, Sch\u00fcle R, Sch\u00f6ls L, Rattay TW (2015) Gray and white matter alterations in hereditary spastic paraplegia type SPG4 and clinical correlations. J Neurol 261:1961\u20131971","journal-title":"J Neurol"},{"key":"9573_CR13","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1212\/01.wnl.0000228242.53336.90","volume":"67","author":"R Schule","year":"2006","unstructured":"Schule R, Holland-Letz T, Klimpe S, Kassubek J, Klopstock T, Mall V, Otto S, Winner B, Schols L (2006) The spastic paraplegia rating scale (SPRS): a reliable and valid measure of disease severity. Neurology 67:430\u2013434","journal-title":"Neurology"},{"key":"9573_CR14","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1007\/s00415-015-7707-6","volume":"262","author":"M B\u00e9reau","year":"2015","unstructured":"B\u00e9reau M, Anheim M, Chanson J-B, Tio G, Echaniz-Laguna A, Depienne C, Collongues N, de S\u00e8ze J (2015) Dalfampridine in hereditary spastic paraplegia: a prospective, open study. J Neurol 262:1285\u20131288","journal-title":"J Neurol"},{"key":"9573_CR15","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1055\/s-2005-867061","volume":"56","author":"A Hinz","year":"2006","unstructured":"Hinz A, Klaiberg A, Brahler E, Konig HH (2006) The quality of life questionnaire EQ-5D: Modelling and norm values for the general population. Psychother Psychosom Med Psychol 56:42\u201348","journal-title":"Psychother Psychosom Med Psychol"},{"key":"9573_CR16","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/0168-8510(90)90421-9","volume":"16","author":"EuroQol-Group","year":"1990","unstructured":"EuroQol-Group (1990) EuroQol-a new facility for the measurement of health-related quality of life. J Health policy 16:199\u2013208","journal-title":"J Health policy"},{"key":"9573_CR17","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1016\/j.sleep.2014.03.025","volume":"15","author":"RP Allen","year":"2014","unstructured":"Allen RP, Picchietti DL, Garcia-Borreguero D, Ondo WG, Walters AS, Winkelman JW, Zucconi M, Ferri R, Trenkwalder C, Lee HB (2014) Restless legs syndrome\/Willis\u2013Ekbom disease diagnostic criteria: updated international restless legs syndrome Study Group (IRLSSG) consensus criteria\u2014history, rationale, description, and significance. Sleep Med 15:860\u2013873","journal-title":"Sleep Med"},{"issue":"2","key":"9573_CR18","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1026\/0012-1924.52.2.51","volume":"52","author":"Manfred Schmitt","year":"2006","unstructured":"Schmitt M, Altst\u00f6tter-Gleich C, Hinz A, Maes J, Br\u00e4hler EJD (2006) Normwerte f\u00fcr das vereinfachte Beck-Depressions-Inventar (BDI-V) in der Allgemeinbev\u00f6lkerung. 52:51\u201359","journal-title":"Diagnostica"},{"key":"9573_CR19","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/0022-3999(94)00125-O","volume":"39","author":"E Smets","year":"1995","unstructured":"Smets E, Garssen B, Bonke Bd, De Haes J (1995) The multidimensional fatigue inventory (MFI) psychometric qualities of an instrument to assess fatigue. J Psychosom Res 39:315\u2013325","journal-title":"J Psychosom Res"},{"key":"9573_CR20","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/S0885-3924(99)00064-0","volume":"18","author":"L Radbruch","year":"1999","unstructured":"Radbruch L, Loick G, Kiencke P, Lindena G, Sabatowski R, Grond S, Lehmann KA, Cleeland CS (1999) Validation of the German version of the brief pain inventory. J Pain Symptom Manag 18:180\u2013187","journal-title":"J Pain Symptom Manag"},{"key":"9573_CR21","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1111\/j.1532-5415.2005.53221.x","volume":"53","author":"ZS Nasreddine","year":"2005","unstructured":"Nasreddine ZS, Phillips NA, B\u00e9dirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow HJ (2005) The montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53:695\u2013699","journal-title":"J Am Geriatr Soc"},{"key":"9573_CR22","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1016\/S0140-6736(83)92879-9","volume":"1","author":"AE Harding","year":"1983","unstructured":"Harding AE (1983) Classification of the hereditary ataxias and paraplegias. Lancet 1:1151\u20131155","journal-title":"Lancet"},{"key":"9573_CR23","doi-asserted-by":"publisher","first-page":"3331","DOI":"10.1093\/brain\/awy285","volume":"141","author":"L Parodi","year":"2018","unstructured":"Parodi L, Fenu S, Barbier M, Banneau G, Duyckaerts C, Tezenas du Montcel S, Monin M-L, Ait Said S, Guegan J, Tallaksen CME, Sablonniere B, Brice A, Stevanin G, Depienne C, Dur Network AS (2018) Spastic paraplegia due to SPAST mutations is modified by the underlying mutation and sex. Brain 141:3331\u20133342","journal-title":"Brain"},{"key":"9573_CR24","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1186\/1750-1172-8-158","volume":"8","author":"KN Karle","year":"2013","unstructured":"Karle KN, Schule R, Klebe S, Otto S, Frischholz C, Liepelt-Scarfone I, Schols L (2013) Electrophysiological characterisation of motor and sensory tracts in patients with hereditary spastic paraplegia (HSP). Orphanet J Rare Dis 8:158","journal-title":"Orphanet J Rare Dis"},{"key":"9573_CR25","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.expneurol.2003.08.005","volume":"184","author":"JK Fink","year":"2003","unstructured":"Fink JK (2003) Advances in the hereditary spastic paraplegias. Exp Neurol 184:106\u2013110","journal-title":"Exp Neurol"},{"key":"9573_CR26","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1007\/s00415-012-6780-3","volume":"260","author":"G Guthrie","year":"2013","unstructured":"Guthrie G, Pfeffer G, Bailie M, Bradshaw K, Browning AC, Horvath R, Chinnery PF (2013) The neurological and ophthalmological manifestations of SPG4-related hereditary spastic paraplegia. J Neurol 260:906","journal-title":"J Neurol"},{"key":"9573_CR27","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1186\/1471-2377-12-143","volume":"12","author":"S Wiethoff","year":"2012","unstructured":"Wiethoff, S., Zhour, A., Schols, L., et al., Retinal nerve fibre layer loss in hereditary spastic paraplegias is restricted to complex phenotypes. BMC Neurol, 2012. 12: p. 143","journal-title":"BMC Neurol"},{"key":"9573_CR28","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1111\/j.1468-1331.2011.03443.x","volume":"19","author":"S Klimpe","year":"2012","unstructured":"Klimpe S, Sch\u00fcle R, Kassubek J, Otto S, Kohl Z, Klebe S, Klopstock T, Ratzka S, Karle K, Sch\u00f6ls L (2012) Disease severity affects quality of life of hereditary spastic paraplegia patients. Eur J Neurol 19:168\u2013171","journal-title":"Eur J Neurol"},{"key":"9573_CR29","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1038\/sc.2010.61","volume":"49","author":"M Braschinsky","year":"2011","unstructured":"Braschinsky M, Rannikm\u00e4e K, Krikmann \u00dc, L\u00fc\u00fcs S, Raidvee A, Gross-Paju K, Haldre S (2011) Health-related quality of life in patients with hereditary spastic paraplegia in Estonia. Spinal Cord 49:175","journal-title":"Spinal Cord"},{"key":"9573_CR30","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1038\/ajg.2014.190","volume":"109","author":"A Wald","year":"2014","unstructured":"Wald A, Bharucha AE, Cosman BC, Whitehead WE (2014) ACG clinical guideline: management of benign anorectal disorders. Am J Gastroenterol 109:1141","journal-title":"Am J Gastroenterol"},{"key":"9573_CR31","doi-asserted-by":"publisher","first-page":"S14","DOI":"10.1053\/j.gastro.2003.10.013","volume":"126","author":"SSC Rao","year":"2004","unstructured":"Rao SSC (2004) Pathophysiology of adult fecal incontinence. Gastroenterology 126:S14\u2013S22","journal-title":"Gastroenterology"},{"key":"9573_CR32","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1097\/00042737-200104000-00025","volume":"13","author":"PH Wiesel","year":"2001","unstructured":"Wiesel PH, Norton C, Glickman S, Kamm MA (2001) Pathophysiology and management of bowel dysfunction in multiple sclerosis. Eur J Gastroenterol Hepatol 13:441\u2013448","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"9573_CR33","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1037\/hea0000598","volume":"37","author":"J Menting","year":"2018","unstructured":"Menting J, Tack CJ, Bleijenberg G, Donders R, Droogleever Fortuyn HA, Fransen J, Goedendorp MM, Kalkman JS, Strik-Albers R, van Alfen N, van der Werf SP, Voermans NC, van Engelen BG, Knoop H (2018) Is fatigue a disease-specific or generic symptom in chronic medical conditions? Health Psychol 37:530\u2013543","journal-title":"Health Psychol"},{"key":"9573_CR34","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/S1389-9457(03)00010-8","volume":"4","author":"RP Allen","year":"2003","unstructured":"Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J (2003) Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology: a report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 4:101\u2013119","journal-title":"Sleep Med"},{"key":"9573_CR35","first-page":"279175","volume":"2014","author":"R Bhimani","year":"2014","unstructured":"Bhimani R, Anderson L (2014) Clinical understanding of spasticity: implications for practice. Rehabil Res Pract 2014:279175","journal-title":"Rehabil Res Pract"},{"key":"9573_CR36","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1093\/brain\/awz102","volume":"142","author":"TW Rattay","year":"2019","unstructured":"Rattay TW, Lindig T, Baets J, Smets K, Deconinck T, S\u00f6hn AS, H\u00f6rtnagel K, Eckstein KN, Wiethoff S, Reichbauer J, D\u00f6bler-Neumann M, Kr\u00e4geloh-Mann I, Auer-Grumbach M, Plecko B, M\u00fcnchau A, Wilken B, Janauschek M, Giese A-K, De Bleecker JL, Ortibus E, Debyser M, Lopez de Munain A, Pujol A, Bassi MT, D\u2019Angelo MG, De Jonghe P, Z\u00fcchner S, Bauer P, Sch\u00f6ls L, Sch\u00fcle R (2019) FAHN\/SPG35: a narrow phenotypic spectrum across disease classifications. Brain 142:1561\u20131572","journal-title":"Brain"},{"key":"9573_CR37","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1016\/S0140-6736(07)61415-9","volume":"370","author":"S Moussavi","year":"2007","unstructured":"Moussavi S, Chatterji S, Verdes E, Tandon A, Patel V, Ustun B (2007) Depression, chronic diseases, and decrements in health: results from the World health surveys. Lancet 370:851\u2013858","journal-title":"Lancet"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-019-09573-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00415-019-09573-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-019-09573-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T19:22:05Z","timestamp":1603308125000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00415-019-09573-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,23]]},"references-count":37,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["9573"],"URL":"https:\/\/doi.org\/10.1007\/s00415-019-09573-w","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.736800605.793582725","asserted-by":"object"}]},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,23]]},"assertion":[{"value":"31 July 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 2019","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 October 2019","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 October 2019","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of Interest"}},{"value":"The data sets for this manuscript are not publicly available, because raw data regarding human subjects (e.g., genetic raw data, personal data) are not shared freely to protect the privacy of the human subjects involved in this study; no consent for open sharing has been obtained. Requests to access the data sets should be directed to Dr. Tim W. Rattay.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability statement"}}]}}