{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:28:21Z","timestamp":1790875701765,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The objective of this study was to provide clinical and pathological characterization, and evaluation of the diagnostic and prognostic implications of levodopa response in Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Long\u2010duration levodopa response in patients with pathology\u2010confirmed PD, MSA, and PSP was collated from medical records. Associations between definite levodopa response (&gt;50% motor improvement sustained &gt;2\u2009years) with clinical and pathological features were reported. Risk of disease milestones using multivariate Cox regression and diagnostic accuracy parameters were estimated for several measures of levodopa response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fourteen percent of 132 patients with PD (57.1% men, age at onset 60.0\u2009\u00b1\u200911.8\u2009years) did not have a definite levodopa response associated with older age and postural\u2010instability and gait\u2010difficulty subtype without global or nigral pathological differences. Definite levodopa responders had 55% lower falls, 69% lower dementia risk, and 69% increased survival. Eight percent of 115 patients with MSA (55.7% men, age at onset 57.9\u2009\u00b1\u200910.4\u2009years) showed a definite levodopa response without distinctive clinical or pathological features, and no impact on disease milestones. Two percent of 191 patients with PSP (64.4% men, age of onset 67.6\u2009\u00b1\u20097.6\u2009years) showed a definite levodopa response associated with a PSP\u2010parkinsonism subtype, and more frequent and severe Lewy copathology. Definite levodopa response showed excellent diagnostic accuracy (sensitivity 86.4% and specificity 95.8%) to distinguish PD from MSA and PSP. Short\u2010duration (acute dopaminergic drug challenge) response had suboptimal diagnostic value and modest correlation with long\u2010duration response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Levodopa response in PD, MSA, and PSP has important clinical, pathological, diagnostic, and prognostic implications. ANN NEUROL 2026;100:305\u2013318<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.78257","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T04:40:36Z","timestamp":1778820036000},"page":"305-318","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Diagnostic, Prognostic Value, and Pathological Associations of Levodopa Responsiveness in Parkinson's Disease, Multiple System Atrophy, and Progressive Supranuclear Palsy"],"prefix":"10.1002","volume":"100","author":[{"given":"Vitor Maia","family":"Arca","sequence":"first","affiliation":[{"name":"Queen Square Brain Bank for Neurological Disorders University College London Queen Square Institute of Neurology  London UK"},{"name":"Neurology Department Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo (HC\u2010FMUSP)  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justina","family":"Jurkeviciene","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank for Neurological Disorders University College London Queen Square Institute of Neurology  London UK"},{"name":"Reta Lila Weston Institute of Neurological Studies UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Cullinane","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank for Neurological Disorders University College London Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Wrigley","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank for Neurological Disorders University College London Queen Square Institute of Neurology  London UK"},{"name":"Reta Lila Weston Institute of Neurological Studies UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3565-5328","authenticated-orcid":false,"given":"Jacy Bezerra","family":"Parmera","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank for Neurological Disorders University College London Queen Square Institute of Neurology  London UK"},{"name":"Neurology Department Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo (HC\u2010FMUSP)  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zannatul","family":"Farin","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank for Neurological Disorders University College London Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samarth","family":"Pimparkar","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank for Neurological Disorders University College London Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yau Mun","family":"Lim","sequence":"additional","affiliation":[{"name":"Division of Neuropathology National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Trust  London UK"},{"name":"Department of Neurodegenerative Disease UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamas","family":"Revesz","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank for Neurological Disorders University College London Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zane","family":"Jaunmuktane","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank for Neurological Disorders University College London Queen Square Institute of Neurology  London UK"},{"name":"Division of Neuropathology National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6195-6995","authenticated-orcid":false,"given":"Thomas","family":"Warner","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank for Neurological Disorders University College London Queen Square Institute of Neurology  London UK"},{"name":"Reta Lila Weston Institute of Neurological Studies UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2834-2515","authenticated-orcid":false,"given":"Eduardo","family":"de Pablo\u2010Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank for Neurological Disorders University College London Queen Square Institute of Neurology  London UK"},{"name":"Reta Lila Weston Institute of Neurological Studies UCL Queen Square Institute of Neurology  London UK"},{"name":"Centre for Preventive Neurology Wolfson Institute of Population Health. Queen Mary University London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26424"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2011.03.014"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.12885"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28406"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2018.4377"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/17582024.2025.2493465"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-022-02540-2"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29304"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29317"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.30261"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29005"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26987"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-020-09810-7"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.1069"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)91531-E"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23429"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2017.1125"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.1989.tb01147.x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn065"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70238-8"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2007.00907.x"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.47.1.1"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004058"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(02)00065-9"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0523-2"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-006-0127-z"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2008.00147.x"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-00934-2_30"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870100303"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa181"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-223433"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1809983"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29796"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm142"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-008-0344-8"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2019.05.022"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.68.4.434"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002826-199012000-00007"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh303"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29670"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh488"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22977"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.55.8.1099"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm104"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02158-2"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28011"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.30019"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000209818"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12022"},{"key":"e_1_2_9_52_1","unstructured":"National Institute for Health and Care Excellence.Parkinson's disease in adults. NICE clinical guideline NG71. London: National Institute for Health and Care Excellence 2017. Available at:https:\/\/www.nice.org.uk\/guidance\/NG71."},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.69.5.590"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.78257","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ana.78257","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.78257","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:33:38Z","timestamp":1787837618000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.78257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,14]]},"references-count":52,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/ana.78257"],"URL":"https:\/\/doi.org\/10.1002\/ana.78257","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,14]]},"assertion":[{"value":"2025-10-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}