How resistant are levodopa-resistant axial symptoms? Response of freezing, posture, and voice to increasing levodopa intestinal infusion rates in Parkinson disease.


Journal

European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311

Informations de publication

Date de publication:
01 2023
Historique:
revised: 23 08 2022
received: 09 07 2022
accepted: 01 09 2022
pubmed: 13 9 2022
medline: 17 12 2022
entrez: 12 9 2022
Statut: ppublish

Résumé

Treatment of freezing of gait (FoG) and other Parkinson disease (PD) axial symptoms is challenging. Systematic assessments of axial symptoms at progressively increasing levodopa doses are lacking. We sought to analyze the resistance to high levodopa doses of FoG, posture, speech, and altered gait features presenting in daily-ON therapeutic condition. We performed a pre-/postinterventional study including patients treated with levodopa/carbidopa intestinal gel infusion (LCIG) with disabling FoG in daily-ON condition. Patients were evaluated at their usual LCIG infusion rate (T1), and 1 h after 1.5× (T2) and 2× (T3) increase of the LCIG infusion rate by quantitative outcome measures. The number of FoG episodes (primary outcome), posture, speech, and gait features were objectively quantified during a standardized test by a blinded rater. Changes in motor symptoms, dyskinesia, and plasma levodopa concentrations were also analyzed. We evaluated 16 patients with a mean age of 69 ± 9.4 years and treated with LCIG for a mean of 2.2 ± 2.1 years. FoG improved in 83.3% of patients by increasing the levodopa doses. The number of FoG episodes significantly decreased (mean = 2.3 at T1, 1.7 at T2, 1.2 at T3; p = 0.013). Posture and speech features did not show significant changes, whereas stride length (p = 0.049), turn duration (p = 0.001), and turn velocity (p = 0.024) significantly improved on doubling the levodopa infusion rate. In a short-term evaluation, the increase of LCIG dose can improve "dopa-resistant" FoG and gait issues in most advanced PD patients with overall good control of motor symptoms in the absence of clinically significant dyskinesia.

Sections du résumé

BACKGROUND AND PURPOSE
Treatment of freezing of gait (FoG) and other Parkinson disease (PD) axial symptoms is challenging. Systematic assessments of axial symptoms at progressively increasing levodopa doses are lacking. We sought to analyze the resistance to high levodopa doses of FoG, posture, speech, and altered gait features presenting in daily-ON therapeutic condition.
METHODS
We performed a pre-/postinterventional study including patients treated with levodopa/carbidopa intestinal gel infusion (LCIG) with disabling FoG in daily-ON condition. Patients were evaluated at their usual LCIG infusion rate (T1), and 1 h after 1.5× (T2) and 2× (T3) increase of the LCIG infusion rate by quantitative outcome measures. The number of FoG episodes (primary outcome), posture, speech, and gait features were objectively quantified during a standardized test by a blinded rater. Changes in motor symptoms, dyskinesia, and plasma levodopa concentrations were also analyzed.
RESULTS
We evaluated 16 patients with a mean age of 69 ± 9.4 years and treated with LCIG for a mean of 2.2 ± 2.1 years. FoG improved in 83.3% of patients by increasing the levodopa doses. The number of FoG episodes significantly decreased (mean = 2.3 at T1, 1.7 at T2, 1.2 at T3; p = 0.013). Posture and speech features did not show significant changes, whereas stride length (p = 0.049), turn duration (p = 0.001), and turn velocity (p = 0.024) significantly improved on doubling the levodopa infusion rate.
CONCLUSIONS
In a short-term evaluation, the increase of LCIG dose can improve "dopa-resistant" FoG and gait issues in most advanced PD patients with overall good control of motor symptoms in the absence of clinically significant dyskinesia.

Identifiants

pubmed: 36093563
doi: 10.1111/ene.15558
pmc: PMC10092343
doi:

Substances chimiques

Levodopa 46627O600J
Antiparkinson Agents 0
Carbidopa MNX7R8C5VO
Gels 0
Drug Combinations 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

96-106

Informations de copyright

© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

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Auteurs

Gabriele Imbalzano (G)

Department of Neuroscience "Rita Levi Montalcini", University of Turin, Turin, Italy.
SC Neurologia 2U, AOU City of Health and Science, Turin, Italy.

Domiziana Rinaldi (D)

Department of Neuroscience, Mental Health, and Sense Organs, Sapienza University of Rome, Rome, Italy.

Giovanna Calandra-Buonaura (G)

Scientific Institute for Research and Health Care, Institute of Neurological Sciences of Bologna, Bologna, Italy.
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.

Manuela Contin (M)

Scientific Institute for Research and Health Care, Institute of Neurological Sciences of Bologna, Bologna, Italy.
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.

Federica Amato (F)

Department of Control and Computer Engineering, Polytechnic University of Turin, Turin, Italy.

Giulia Giannini (G)

Scientific Institute for Research and Health Care, Institute of Neurological Sciences of Bologna, Bologna, Italy.
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.

Luisa Sambati (L)

Scientific Institute for Research and Health Care, Institute of Neurological Sciences of Bologna, Bologna, Italy.
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.

Claudia Ledda (C)

Department of Neuroscience "Rita Levi Montalcini", University of Turin, Turin, Italy.
SC Neurologia 2U, AOU City of Health and Science, Turin, Italy.

Alberto Romagnolo (A)

Department of Neuroscience "Rita Levi Montalcini", University of Turin, Turin, Italy.
SC Neurologia 2U, AOU City of Health and Science, Turin, Italy.

Gabriella Olmo (G)

Department of Control and Computer Engineering, Polytechnic University of Turin, Turin, Italy.

Pietro Cortelli (P)

Scientific Institute for Research and Health Care, Institute of Neurological Sciences of Bologna, Bologna, Italy.
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.

Maurizio Zibetti (M)

Department of Neuroscience "Rita Levi Montalcini", University of Turin, Turin, Italy.
SC Neurologia 2U, AOU City of Health and Science, Turin, Italy.

Leonardo Lopiano (L)

Department of Neuroscience "Rita Levi Montalcini", University of Turin, Turin, Italy.
SC Neurologia 2U, AOU City of Health and Science, Turin, Italy.

Carlo Alberto Artusi (CA)

Department of Neuroscience "Rita Levi Montalcini", University of Turin, Turin, Italy.
SC Neurologia 2U, AOU City of Health and Science, Turin, Italy.

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