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Author Notes:

Corresponding author: Stewart A. Factor, Email: sfactor@emory.edu

See publication for full list of author contributions.

J.L.M. has no competing interests, F.C.G. has no competing interests, B.S. has no competing interests, D.B. has no competing interests, S.P.P. has no competing interests, S.A.F. has the following competing interests: Honoraria: Lundbeck, Teva, Sunovion, Biogen, Acadia, Neuroderm, Acorda, CereSpire.

Grants: Ipsen, Medtronics, Boston Scientific, Teva, US World Meds, Sunovion Therapeutics, Vaccinex, Voyager, Jazz Pharmaceuticals, Lilly, CHDI Foundation, Michael J. Fox Foundation, NIH, Royalties: Demos, Blackwell Futura for textbooks, Uptodate, Other Bracket Global LLC, CNS Ratings LLC.

The content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health.


Research Funding:

Additional gait assessments were completed by Garrett Alexander M.D., Ph.D. Serum levodopa levels were completed by the Emory HPLC Bioanalytical Core (EHBC), which was supported by the Department of Pharmacology, Emory University School of Medicine and the Georgia Clinical & Translational Science Alliance of the National Institutes of Health under Award Number UL1TR002378.

The study was funded by Curtis Family Fund, Sartain Lanier Family Foundation (S.A.F.), NIH K25HD086276 (J.L.M.), and Parkinson Foundation Fellowship (S.P.P.)


  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology

Freezing of Gait can persist after an acute levodopa challenge in Parkinson's disease


Journal Title:

npj Parkinson's Disease


Volume 5


, Pages 25-25

Type of Work:

Article | Final Publisher PDF


Study objectives included testing whether presumed levodopa-unresponsive freezing of gait (FOG) in Parkinson's disease (PD) actually persists in the presence of adequate dopaminergic dosing and to investigate whether the presence of other parkinsonian features and their responsiveness to therapy varies across patients without FOG (NO-FOG), with levodopa-responsive FOG (OFF-FOG), and with levodopa-unresponsive FOG (ONOFF-FOG). Fifty-five PD patients completed levodopa challenges after >12-h OFF with supratherapeutic doses of dopaminergic medications. Observed responses in FOG, measured with MDS-UPDRS-III during the patient reported full "ON", were used to classify them as NO-FOG, OFF-FOG, or ONOFF-FOG. Serum levodopa levels were measured. Only those with ≥20% improvement in MDS-UPDRS-III score were included in analyses. Levodopa challenge was sufficient to bring about a full "ON" state with ≥20% improvement in 45 patients. Levodopa-equivalent-dose utilized was 142 ± 56% of patients' typical morning doses. Overall, 19/45 patients exhibited FOG in the full "ON" state (ONOFF-FOG), 11 were classified as OFF-FOG, and 15 NO-FOG. Linear mixed models revealed a highly significant association between serum levodopa level and total MDS-UPDRS-III score that was similar across groups. The ONOFF-FOG group exhibited significantly higher New-FOG-questionnaire and MDS-UPDRS-II scores compared to the OFF-FOG group. Among MDS-UPDRS-III subdomains significant effects of group (highest in ONOFF-FOG) were identified for other axial parkinsonian features. We found that FOG can persist in the full "ON" state brought about by ample dopaminergic dosing in PD. Other axial measures can also be levodopa-unresponsive among those with ONOFF-FOG only. These data provide evidence that ONOFF-FOG is distinct from responsive freezing.

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© The Author(s) 2019

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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