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Comparison of dyskinesia profiles after L-DOPA dose challenges with or without dopamine agonist coadministration

Grigoriou, Sotirios LU orcid ; Espa, Elena LU ; Odin, Per LU orcid ; Timpka, Jonathan LU ; von Grothusen, Gustaf ; Jakobsson, Andreas LU orcid and Cenci, M. Angela LU orcid (2023) In Neuropharmacology 237.
Abstract

Many patients with Parkinson's disease (PD) experiencing L-DOPA-induced dyskinesia (LID) receive adjunct treatment with dopamine agonists, whose functional impact on LID is unknown. We set out to compare temporal and topographic profiles of abnormal involuntary movements (AIMs) after L-DOPA dose challenges including or not the dopamine agonist ropinirole. Twenty-five patients with PD and a history of dyskinesias were sequentially administered either L-DOPA alone (150% of usual morning dose) or an equipotent combination of L-DOPA and ropinirole in random order. Involuntary movements were assessed by two blinded raters prior and every 30 min after drug dosing using the Clinical Dyskinesia Rating Scale (CDRS). A sensor-recording smartphone... (More)

Many patients with Parkinson's disease (PD) experiencing L-DOPA-induced dyskinesia (LID) receive adjunct treatment with dopamine agonists, whose functional impact on LID is unknown. We set out to compare temporal and topographic profiles of abnormal involuntary movements (AIMs) after L-DOPA dose challenges including or not the dopamine agonist ropinirole. Twenty-five patients with PD and a history of dyskinesias were sequentially administered either L-DOPA alone (150% of usual morning dose) or an equipotent combination of L-DOPA and ropinirole in random order. Involuntary movements were assessed by two blinded raters prior and every 30 min after drug dosing using the Clinical Dyskinesia Rating Scale (CDRS). A sensor-recording smartphone was secured to the patients' abdomen during the test sessions. The two raters’ CDRS scores were highly reliable and concordant with models of hyperkinesia presence and severity trained on accelerometer data. The dyskinesia time curves differed between treatments as the L-DOPA-ropinirole combination resulted in lower peak severity but longer duration of the AIMs compared with L-DOPA alone. At the peak of the AIMs curve (60–120 min), L-DOPA induced a significantly higher total hyperkinesia score, whereas in the end phase (240–270 min), both hyperkinesia and dystonia tended to be more severe after the L-DOPA-ropinirole combination (though reaching statistical significance only for the item, arm dystonia). Our results pave the way for the introduction of a combined L-DOPA-ropinirole challenge test in the early clinical evaluation of antidyskinetic treatments. Furthermore, we propose a machine-learning method to predict CDRS hyperkinesia severity using accelerometer data.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Dyskinesia, Dystonia, Hyperkinesia, Movement disorders, Parkinson's disease
in
Neuropharmacology
volume
237
article number
109630
publisher
Elsevier
external identifiers
  • pmid:37315840
  • scopus:85162927575
ISSN
0028-3908
DOI
10.1016/j.neuropharm.2023.109630
language
English
LU publication?
yes
id
a1b3553b-6cab-4174-b417-e5a62e52c2d2
date added to LUP
2023-09-05 10:09:15
date last changed
2024-04-20 02:33:07
@article{a1b3553b-6cab-4174-b417-e5a62e52c2d2,
  abstract     = {{<p>Many patients with Parkinson's disease (PD) experiencing L-DOPA-induced dyskinesia (LID) receive adjunct treatment with dopamine agonists, whose functional impact on LID is unknown. We set out to compare temporal and topographic profiles of abnormal involuntary movements (AIMs) after L-DOPA dose challenges including or not the dopamine agonist ropinirole. Twenty-five patients with PD and a history of dyskinesias were sequentially administered either L-DOPA alone (150% of usual morning dose) or an equipotent combination of L-DOPA and ropinirole in random order. Involuntary movements were assessed by two blinded raters prior and every 30 min after drug dosing using the Clinical Dyskinesia Rating Scale (CDRS). A sensor-recording smartphone was secured to the patients' abdomen during the test sessions. The two raters’ CDRS scores were highly reliable and concordant with models of hyperkinesia presence and severity trained on accelerometer data. The dyskinesia time curves differed between treatments as the L-DOPA-ropinirole combination resulted in lower peak severity but longer duration of the AIMs compared with L-DOPA alone. At the peak of the AIMs curve (60–120 min), L-DOPA induced a significantly higher total hyperkinesia score, whereas in the end phase (240–270 min), both hyperkinesia and dystonia tended to be more severe after the L-DOPA-ropinirole combination (though reaching statistical significance only for the item, arm dystonia). Our results pave the way for the introduction of a combined L-DOPA-ropinirole challenge test in the early clinical evaluation of antidyskinetic treatments. Furthermore, we propose a machine-learning method to predict CDRS hyperkinesia severity using accelerometer data.</p>}},
  author       = {{Grigoriou, Sotirios and Espa, Elena and Odin, Per and Timpka, Jonathan and von Grothusen, Gustaf and Jakobsson, Andreas and Cenci, M. Angela}},
  issn         = {{0028-3908}},
  keywords     = {{Dyskinesia; Dystonia; Hyperkinesia; Movement disorders; Parkinson's disease}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Neuropharmacology}},
  title        = {{Comparison of dyskinesia profiles after L-DOPA dose challenges with or without dopamine agonist coadministration}},
  url          = {{http://dx.doi.org/10.1016/j.neuropharm.2023.109630}},
  doi          = {{10.1016/j.neuropharm.2023.109630}},
  volume       = {{237}},
  year         = {{2023}},
}