{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T13:31:48Z","timestamp":1776951108302,"version":"3.51.4"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004047","name":"Karolinska Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurol Sci"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background\n<\/jats:title>\n                <jats:p>Hereditary spastic paraplegia (HSP) is a rare genetic disorder associated with mutations in\u2009&gt;\u200980 loci designated <jats:italic>SPG<\/jats:italic> (SPastic parapleGia). The phenotypic spectrum of HSP can extend to include other neurologic features, including movement disorders. Our aim was to investigate genotype\u2013phenotype associations in HSP with a focus on movement disorders.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We performed a systematic review and individual participant data (IPD)-level meta-analysis by retrieving publications from Medline\/EMBASE\/Web of Science on HSP with a SPG genotype. Studies were included only if individual-level information was accessible and at least one patient with a movement disorder was reported for that genotype. Out of 21,957 hits, 192 manuscripts with a total of 1413 HSP cases were eligible. Data were compared between two HSP groups: manifested with (HSP-MD, <jats:italic>n<\/jats:italic>\u2009=\u2009767) or without (HSP-nMD, <jats:italic>n<\/jats:italic>\u2009=\u2009646) a movement disorder.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The HSP-MD group had an older age of onset (20.5\u2009\u00b1\u200916.0 vs. 17.1\u2009\u00b1\u200914.2\u00a0yr, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and less frequent autosomal dominant inheritance (7.6% vs. 30.1%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) compared to HSP-nMD. SPG7 (31.2%) and SPG11 (23.8%) were the most frequent genotypes in the HSP-MD group. HSP-MD with SPG7 had higher frequency of later onset during adulthood (82.9% vs. 8.5%), ataxia (OR\u2009=\u200912.6), extraocular movement disturbances (OR\u2009=\u20093.4) and seizure (OR\u2009=\u20093.7) compared to HSP-MD with SPG11. Conversely, SPG11 mutations were more frequently associated with consanguinity (OR\u2009=\u20094.1), parkinsonism (OR\u2009=\u20097.8), dystonia (OR\u2009=\u20095.4), peripheral neuropathy (OR\u2009=\u200926.9), and cognitive dysfunction (OR\u2009=\u200934.5).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>This systematic IPD-level meta-analysis provides the largest data on genotype\u2013phenotype associations in HSP-MD. Several clinically relevant phenotypic differences were found between various genotypes, which can possibly facilitate diagnosis in resource-limited settings.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10072-022-06516-8","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T14:03:00Z","timestamp":1669644180000},"page":"947-959","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Movement disorders in hereditary spastic paraplegia (HSP): a systematic review and individual participant data meta-analysis"],"prefix":"10.1007","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9255-9351","authenticated-orcid":false,"given":"Seyed-Mohammad","family":"Fereshtehnejad","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip A.","family":"Saleh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lais M.","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neha","family":"Patel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suvorit","family":"Bhowmick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard","family":"Saranza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorraine V.","family":"Kalia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,11,28]]},"reference":[{"issue":"8334","key":"6516_CR1","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(8334):1151\u20131155. https:\/\/doi.org\/10.1016\/s0140-6736(83)92879-9","journal-title":"Lancet"},{"issue":"Pt 7","key":"6516_CR2","doi-asserted-by":"publisher","first-page":"1904","DOI":"10.1093\/brain\/aww111","volume":"139","author":"E Kara","year":"2016","unstructured":"Kara E, Tucci A, Manzoni C, Lynch DS, Elpidorou M, Bettencourt C, Chelban V, Manole A, Hamed SA, Haridy NA, Federoff M, Preza E, Hughes D, Pittman A, Jaunmuktane Z, Brandner S, Xiromerisiou G, Wiethoff S, Schottlaender L, Proukakis C, Morris H, Warner T, Bhatia KP, Korlipara LV, Singleton AB, Hardy J, Wood NW, Lewis PA, Houlden H (2016) Genetic and phenotypic characterization of complex hereditary spastic paraplegia. Brain 139(Pt 7):1904\u20131918. https:\/\/doi.org\/10.1093\/brain\/aww111","journal-title":"Brain"},{"issue":"2","key":"6516_CR3","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1007\/s12311-016-0803-z","volume":"16","author":"PVS de Souza","year":"2017","unstructured":"de Souza PVS, de Rezende Pinto WBV, de Rezende Batistella GN, Bortholin T, Oliveira ASB (2017) Hereditary spastic paraplegia: clinical and genetic hallmarks. Cerebellum 16(2):525\u2013551. https:\/\/doi.org\/10.1007\/s12311-016-0803-z","journal-title":"Cerebellum"},{"issue":"4","key":"6516_CR4","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1007\/s12311-019-01038-0","volume":"18","author":"A Kim","year":"2019","unstructured":"Kim A, Kumar KR, Davis RL, Mallawaarachchi AC, Gayevskiy V, Minoche AE, Walls Z, Kim HJ, Jang M, Cowley MJ, Choi JH, Shin C, Sue CM, Jeon B (2019) Increased diagnostic yield of spastic paraplegia with or without cerebellar ataxia through whole-genome sequencing. Cerebellum 18(4):781\u2013790. https:\/\/doi.org\/10.1007\/s12311-019-01038-0","journal-title":"Cerebellum"},{"issue":"3","key":"6516_CR5","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1002\/mds.26944","volume":"32","author":"M Synofzik","year":"2017","unstructured":"Synofzik M, Schule R (2017) Overcoming the divide between ataxias and spastic paraplegias: Shared phenotypes, genes, and pathways. Mov Disord 32(3):332\u2013345. https:\/\/doi.org\/10.1002\/mds.26944","journal-title":"Mov Disord"},{"issue":"6","key":"6516_CR6","doi-asserted-by":"publisher","first-page":"e279","DOI":"10.1212\/NXG.0000000000000279","volume":"4","author":"CA Hewamadduma","year":"2018","unstructured":"Hewamadduma CA, Hoggard N, O\u2019Malley R, Robinson MK, Beauchamp NJ, Segamogaite R, Martindale J, Rodgers T, Rao G, Sarrigiannis P, Shanmugarajah P, Zis P, Sharrack B, McDermott CJ, Shaw PJ, Hadjivassiliou M (2018) Novel genotype-phenotype and MRI correlations in a large cohort of patients with SPG7 mutations. Neurol Genet 4(6):e279. https:\/\/doi.org\/10.1212\/NXG.0000000000000279","journal-title":"Neurol Genet"},{"issue":"2","key":"6516_CR7","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1002\/mdc3.12711","volume":"6","author":"P Salgado","year":"2019","unstructured":"Salgado P, Latorre A, Del Gamba C, Menozzi E, Balint B, Bhatia KP (2019) SPG7: the great imitator of MSA-C within the ILOCAs. Mov Disord Clin Pract 6(2):174\u2013175. https:\/\/doi.org\/10.1002\/mdc3.12711","journal-title":"Mov Disord Clin Pract"},{"issue":"1","key":"6516_CR8","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1007\/s00415-009-0083-3","volume":"256","author":"M Anheim","year":"2009","unstructured":"Anheim M, Lagier-Tourenne C, Stevanin G, Fleury M, Durr A, Namer IJ, Denora P, Brice A, Mandel JL, Koenig M, Tranchant C (2009) SPG11 spastic paraplegia. A new cause of juvenile parkinsonism. J Neurol 256(1):104\u2013108. https:\/\/doi.org\/10.1007\/s00415-009-0083-3","journal-title":"J Neurol"},{"issue":"3","key":"6516_CR9","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1002\/mds.23552","volume":"26","author":"A Guidubaldi","year":"2011","unstructured":"Guidubaldi A, Piano C, Santorelli FM, Silvestri G, Petracca M, Tessa A, Bentivoglio AR (2011) Novel mutations in SPG11 cause hereditary spastic paraplegia associated with early-onset levodopa-responsive Parkinsonism. Mov Disord 26(3):553\u2013556. https:\/\/doi.org\/10.1002\/mds.23552","journal-title":"Mov Disord"},{"issue":"1","key":"6516_CR10","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1001\/jamaneurol.2016.4297","volume":"74","author":"A Ramirez-Zamora","year":"2017","unstructured":"Ramirez-Zamora A, Gee L, Youn Y, Shin DS, Pilitsis JG (2017) Pallidal deep brain stimulation for the treatment of levodopa-responsive juvenile dystonia and parkinsonism secondary to SPG11 mutation. JAMA Neurol 74(1):127\u2013128. https:\/\/doi.org\/10.1001\/jamaneurol.2016.4297","journal-title":"JAMA Neurol"},{"issue":"2","key":"6516_CR11","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1002\/mdc3.12144","volume":"2","author":"S Wijemanne","year":"2015","unstructured":"Wijemanne S, Shulman JM, Jimenez-Shahed J, Curry D, Jankovic J (2015) SPG11 mutations associated with a complex phenotype resembling dopa-responsive dystonia. Mov Disord Clin Pract 2(2):149\u2013154. https:\/\/doi.org\/10.1002\/mdc3.12144","journal-title":"Mov Disord Clin Pract"},{"issue":"3","key":"6516_CR12","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1002\/mds.23472","volume":"26","author":"J Schicks","year":"2011","unstructured":"Schicks J, Synofzik M, Petursson H, Huttenlocher J, Reimold M, Schols L, Bauer P (2011) Atypical juvenile parkinsonism in a consanguineous SPG15 family. Mov Disord 26(3):564\u2013566. https:\/\/doi.org\/10.1002\/mds.23472","journal-title":"Mov Disord"},{"issue":"2","key":"6516_CR13","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1007\/s00415-013-7216-4","volume":"261","author":"M Mallaret","year":"2014","unstructured":"Mallaret M, Lagha-Boukbiza O, Biskup S, Namer IJ, Rudolf G, Anheim M, Tranchant C (2014) SPG15: a cause of juvenile atypical levodopa responsive parkinsonism. J Neurol 261(2):435\u2013437. https:\/\/doi.org\/10.1007\/s00415-013-7216-4","journal-title":"J Neurol"},{"issue":"6","key":"6516_CR14","doi-asserted-by":"publisher","first-page":"e49","DOI":"10.1212\/CPJ.0000000000000552","volume":"8","author":"SM Schaefer","year":"2018","unstructured":"Schaefer SM, Szekely AM, Moeller JJ, Tinaz S (2018) Hereditary spastic paraplegia presenting as limb dystonia with a rare SPG7 mutation. Neurol Clin Pract 8(6):e49\u2013e50. https:\/\/doi.org\/10.1212\/CPJ.0000000000000552","journal-title":"Neurol Clin Pract"},{"issue":"Pt 10","key":"6516_CR15","doi-asserted-by":"publisher","first-page":"2994","DOI":"10.1093\/brain\/aws224","volume":"135","author":"KL van Gassen","year":"2012","unstructured":"van Gassen KL, van der Heijden CD, de Bot ST, den Dunnen WF, van den Berg LH, Verschuuren-Bemelmans CC, Kremer HP, Veldink JH, Kamsteeg EJ, Scheffer H, van de Warrenburg BP (2012) Genotype-phenotype correlations in spastic paraplegia type 7: a study in a large Dutch cohort. Brain 135(Pt 10):2994\u20133004. https:\/\/doi.org\/10.1093\/brain\/aws224","journal-title":"Brain"},{"issue":"2","key":"6516_CR16","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1002\/mdc3.12580","volume":"5","author":"D Hall","year":"2018","unstructured":"Hall D, Stong N, Lippa N, Pitman MJ, Pullman SL, Levy OA (2018) Spasmodic dysphonia in hereditary spastic paraplegia type 7. Mov Disord Clin Pract 5(2):221\u2013222. https:\/\/doi.org\/10.1002\/mdc3.12580","journal-title":"Mov Disord Clin Pract"},{"issue":"5","key":"6516_CR17","doi-asserted-by":"publisher","first-page":"e98","DOI":"10.1212\/NXG.0000000000000098","volume":"2","author":"J Hirst","year":"2016","unstructured":"Hirst J, Madeo M, Smets K, Edgar JR, Schols L, Li J, Yarrow A, Deconinck T, Baets J, Van Aken E, De Bleecker J, Datiles MB 3rd, Roda RH, Liepert J, Zuchner S, Mariotti C, De Jonghe P, Blackstone C, Kruer MC (2016) Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48). Neurol Genet 2(5):e98. https:\/\/doi.org\/10.1212\/NXG.0000000000000098","journal-title":"Neurol Genet"},{"issue":"16","key":"6516_CR18","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.1001\/jama.2015.3656","volume":"313","author":"LA Stewart","year":"2015","unstructured":"Stewart LA, Clarke M, Rovers M, Riley RD, Simmonds M, Stewart G, Tierney JF, Group P-ID (2015) Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data: the PRISMA-IPD Statement. JAMA 313(16):1657\u20131665. https:\/\/doi.org\/10.1001\/jama.2015.3656","journal-title":"JAMA"},{"key":"6516_CR19","doi-asserted-by":"publisher","unstructured":"Amberger J, Bocchini CA, Scott AF, Hamosh A (2009) McKusick\u2019s Online Mendelian Inheritance in Man (OMIM). Nucleic Acids Res 37 (Database issue):D793\u2013796. https:\/\/doi.org\/10.1093\/nar\/gkn665","DOI":"10.1093\/nar\/gkn665"},{"issue":"6","key":"6516_CR20","doi-asserted-by":"publisher","first-page":"2065","DOI":"10.1007\/s00415-019-09633-1","volume":"268","author":"M Erfanian Omidvar","year":"2021","unstructured":"Erfanian Omidvar M, Torkamandi S, Rezaei S, Alipoor B, Omrani MD, Darvish H, Ghaedi H (2021) Genotype-phenotype associations in hereditary spastic paraplegia: a systematic review and meta-analysis on 13,570 patients. J Neurol 268(6):2065\u20132082. https:\/\/doi.org\/10.1007\/s00415-019-09633-1","journal-title":"J Neurol"},{"issue":"4","key":"6516_CR21","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(4):646\u2013658. https:\/\/doi.org\/10.1002\/ana.24611","journal-title":"Ann Neurol"},{"issue":"5","key":"6516_CR22","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1016\/j.neurol.2020.07.001","volume":"177","author":"P Lallemant-Dudek","year":"2021","unstructured":"Lallemant-Dudek P, Durr A (2021) Clinical and genetic update of hereditary spastic paraparesis. Rev Neurol (Paris) 177(5):550\u2013556. https:\/\/doi.org\/10.1016\/j.neurol.2020.07.001","journal-title":"Rev Neurol (Paris)"},{"issue":"1","key":"6516_CR23","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1212\/01.wnl.0000191390.20564.8e","volume":"66","author":"M Namekawa","year":"2006","unstructured":"Namekawa M, Ribai P, Nelson I, Forlani S, Fellmann F, Goizet C, Depienne C, Stevanin G, Ruberg M, Durr A, Brice A (2006) SPG3A is the most frequent cause of hereditary spastic paraplegia with onset before age 10 years. Neurology 66(1):112\u2013114. https:\/\/doi.org\/10.1212\/01.wnl.0000191390.20564.8e","journal-title":"Neurology"},{"issue":"12","key":"6516_CR24","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1016\/S1474-4422(19)30235-2","volume":"18","author":"S Shribman","year":"2019","unstructured":"Shribman S, Reid E, Crosby AH, Houlden H, Warner TT (2019) Hereditary spastic paraplegia: from diagnosis to emerging therapeutic approaches. Lancet Neurol 18(12):1136\u20131146. https:\/\/doi.org\/10.1016\/S1474-4422(19)30235-2","journal-title":"Lancet Neurol"},{"issue":"10","key":"6516_CR25","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1002\/mds.27812","volume":"34","author":"B De la Casa-Fages","year":"2019","unstructured":"De la Casa-Fages B, Fernandez-Eulate G, Gamez J, Barahona-Hernando R, Moris G, Garcia-Barcina M, Infante J, Zulaica M, Fernandez-Pelayo U, Munoz-Oreja M, Urtasun M, Olaskoaga A, Zelaya V, Jerico I, Saez-Villaverde R, Catalina I, Sola E, Martinez-Saez E, Pujol A, Ruiz M, Schluter A, Spinazzola A, Munoz-Blanco JL, Grandas F, Holt I, Alvarez V, Lopez de Munain A (2019) Parkinsonism and spastic paraplegia type 7: expanding the spectrum of mitochondrial parkinsonism. Mov Disord 34(10):1547\u20131561. https:\/\/doi.org\/10.1002\/mds.27812","journal-title":"Mov Disord"},{"key":"6516_CR26","doi-asserted-by":"publisher","first-page":"c221","DOI":"10.1136\/bmj.c221","volume":"340","author":"RD Riley","year":"2010","unstructured":"Riley RD, Lambert PC, Abo-Zaid G (2010) Meta-analysis of individual participant data: rationale, conduct, and reporting. BMJ 340:c221. https:\/\/doi.org\/10.1136\/bmj.c221","journal-title":"BMJ"},{"issue":"2","key":"6516_CR27","doi-asserted-by":"publisher","first-page":"e664","DOI":"10.1212\/NXG.0000000000000664","volume":"8","author":"S Rossi","year":"2022","unstructured":"Rossi S, Rubegni A, Riso V, Barghigiani M, Bassi MT, Battini R, Bertini E, Cereda C, Cioffi E, Criscuolo C, Dal Fabbro B, Dato C, D\u2019Angelo MG, Di Muzio A, Diamanti L, Dotti MT, Filla A, Gioiosa V, Liguori R, Martinuzzi A, Massa R, Mignarri A, Moroni R, Musumeci O, Nicita F, Orologio I, Orsi L, Pegoraro E, Petrucci A, Plumari M, Ricca I, Rizzo G, Romano S, Rumore R, Sampaolo S, Scarlato M, Seri M, Stefan C, Straccia G, Tessa A, Travaglini L, Trovato R, Ulgheri L, Vazza G, Orlacchio A, Silvestri G, Santorelli FM, Melone MAB, Casali C (2022) Clinical-genetic features influencing disability in spastic paraplegia type 4: a cross-sectional study by the Italian DAISY Network. Neurol Genet 8(2):e664. https:\/\/doi.org\/10.1212\/NXG.0000000000000664","journal-title":"Neurol Genet"}],"container-title":["Neurological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10072-022-06516-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10072-022-06516-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10072-022-06516-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T23:41:10Z","timestamp":1676331670000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10072-022-06516-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,28]]},"references-count":27,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["6516"],"URL":"https:\/\/doi.org\/10.1007\/s10072-022-06516-8","relation":{},"ISSN":["1590-1874","1590-3478"],"issn-type":[{"value":"1590-1874","type":"print"},{"value":"1590-3478","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,28]]},"assertion":[{"value":"19 September 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 November 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 November 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"None.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"In the past year, S. M. F. has received honoraria from the European Science Foundation. L. V. K. has received research support from Canadian Health Institutes of Research (CIHR), Michael J. Fox Foundation for Parkinson\u2019s Research, Natural Sciences and Engineering Research Council of Canada (NSERC), Ontario Brain Institute, Parkinson Canada, and Toronto General and Western Hospital Foundation; held contracts with ApoPharma and UCB; and received honoraria from National Institutes of Health (NIH) and Takeda. Other authors (P. A. S., L. M. O., N. P., S. B., and G. S.) reported no financial disclosure.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}