{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T23:45:39Z","timestamp":1784763939409,"version":"3.55.0"},"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T00:00:00Z","timestamp":1654128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008519","name":"University of Arkansas for Medical Sciences","doi-asserted-by":"crossref","award":["Clinician Scientist Program"],"award-info":[{"award-number":["Clinician Scientist Program"]}],"id":[{"id":"10.13039\/100008519","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100013301","name":"Parkinson's Foundation","doi-asserted-by":"crossref","award":["PF-JFA-1935"],"award-info":[{"award-number":["PF-JFA-1935"]}],"id":[{"id":"10.13039\/100013301","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM110702"],"award-info":[{"award-number":["GM110702"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Freezing in the levodopa-medicated-state (ON-state) is a debilitating feature of Parkinson\u2019s disease without treatment options. Studies detailing the distinguishing features between people with freezing of gait that improves with levodopa and those whose freezing continues even on levodopa are lacking.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objective<\/jats:title>\n<jats:p>To characterize the gross motor, gait, and non-motor features of this phenotype.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Instrumented continuous gait was collected in the levodopa-medicated-state in 105 patients: 43 non-freezers (no-FOG), 36 with freezing only OFF-levodopa (OFF-FOG) and 26 with freezing both ON- and OFF-levodopa (ONOFF-FOG). Evaluation of motor and non-motor disease features was undertaken using validated scales. A linear mixed model with age, sex, disease duration, and motor UPDRS scores as covariates was used to determine differences in spatiotemporal gait and non-motor disease features among the groups.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>Compared to OFF-FOG, the ONOFF-FOG group had greater disease severity (on the Unified Parkinson\u2019s disease Rating Scale) and worse cognition (on the Montreal Cognitive Assessment, Frontal Assessment Battery and Scales for Outcome in Parkinson\u2019s disease-Cognition scales) and quality of life (on the PDQ-39), but similar mood (on the Hamilton depression and anxiety scales) and sleep quality (on Epworth sleepiness scale and RBD questionnaire). For several gait features, differences between the ONOFF-OFF groups were at least as large and in the opposite direction as differences between OFF-no groups, controlling for disease severity. Variability in ONOFF-FOG was greater than in other groups. Using results from our study and others, a power analysis for a potential future study reveals sample sizes of at least 80 ONOFF and 80 OFF-FOG patients would be needed to detect clinically meaningful differences.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Intra-patient variability in spatiotemporal gait features was much greater in ONOFF-FOG than in the other two groups. Our results suggest that multifactorial deficits may lead to ONOFF-FOG development.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0269227","type":"journal-article","created":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T17:35:44Z","timestamp":1654191344000},"page":"e0269227","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":21,"title":["Levodopa ONOFF-state freezing of gait: Defining the gait and non-motor phenotype"],"prefix":"10.1371","volume":"17","author":[{"given":"Reid D.","family":"Landes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliyah","family":"Glover","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshmi","family":"Pillai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Doerhoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1826-2020","authenticated-orcid":true,"given":"Tuhin","family":"Virmani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,6,2]]},"reference":[{"issue":"12","key":"pone.0269227.ref001","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1212\/WNL.56.12.1712","article-title":"Freezing of gait in PD: prospective assessment in the DATATOP cohort","volume":"56","author":"N Giladi","year":"2001","journal-title":"Neurology"},{"issue":"14","key":"pone.0269227.ref002","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1002\/mds.26346","article-title":"Clinicopathological characteristics of freezing of gait in autopsy-confirmed Parkinson\u2019s disease","volume":"30","author":"T Virmani","year":"2015","journal-title":"Movement disorders: official journal of the Movement Disorder Society"},{"issue":"6","key":"pone.0269227.ref003","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.parkreldis.2015.03.028","article-title":"Prevalence and associated features of self-reported freezing of gait in Parkinson disease: The DEEP FOG study","volume":"21","author":"M Amboni","year":"2015","journal-title":"Parkinsonism & related disorders"},{"key":"pone.0269227.ref004","author":"T. 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