Effects of Continuous Dopaminergic Stimulation on Parkinson’s Disease Gait: A Longitudinal Prospective Study with Levodopa Intestinal Gel Infusion

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Abstract

Background:

Gait issues, including reduced speed, stride length and freezing of gait (FoG), are disabling in advanced phases of Parkinson’s disease (PD), and their treatment is challenging. Levodopa/carbidopa intestinal gel (LCIG) can improve these symptoms in PD patients with suboptimal control of motor fluctuations, but it is unclear if continuous dopaminergic stimulation can further improve gait issues, independently from reducing Off-time.

Objective:

To analyze before (T0) and after 3 (T1) and 6 (T2) months of LCIG initiation: a) the objective improvement of gait and balance; b) the improvement of FoG severity; c) the improvement of motor complications and their correlation with changes in gait parameters and FoG severity.

Methods:

This prospective, longitudinal 6-months study analyzed quantitative gait parameters using wearable inertial sensors, FoG with the New Freezing of Gait Questionnaire (NFoG-Q), and motor complications, as per the MDS-UPDRS part IV scores.

Results:

Gait speed and stride length increased and duration of Timed up and Go and of sit-to-stand transition was significantly reduced comparing T0 with T2, but not between T0-T1. NFoG-Q score decreased significantly from 19.3±4.6 (T0) to 11.8±7.9 (T1) and 8.4±7.6 (T2) (T1-T0 p = 0.018; T2-T0 p < 0.001). Improvement of MDS-UPDRS-IV (T0-T2, p = 0.002, T0-T1 p = 0.024) was not correlated with improvement of gait parameters and NFoG-Q from T0 to T2. LEDD did not change significantly after LCIG initiation.

Conclusion:

Continuous dopaminergic stimulation provided by LCIG infusion progressively ameliorates gait and alleviates FoG in PD patients over time, independently from improvement of motor fluctuations and without increase of daily dosage of dopaminergic therapy.

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Most cited references 44

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MDS clinical diagnostic criteria for Parkinson's disease.

Ronald Postuma, Daniela Berg, Matthew Stern … (2015)

This document presents the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease (PD). The Movement Disorder Society PD Criteria are intended for use in clinical research but also may be used to guide clinical diagnosis. The benchmark for these criteria is expert clinical diagnosis; the criteria aim to systematize the diagnostic process, to make it reproducible across centers and applicable by clinicians with less expertise in PD diagnosis. Although motor abnormalities remain central, increasing recognition has been given to nonmotor manifestations; these are incorporated into both the current criteria and particularly into separate criteria for prodromal PD. Similar to previous criteria, the Movement Disorder Society PD Criteria retain motor parkinsonism as the core feature of the disease, defined as bradykinesia plus rest tremor or rigidity. Explicit instructions for defining these cardinal features are included. After documentation of parkinsonism, determination of PD as the cause of parkinsonism relies on three categories of diagnostic features: absolute exclusion criteria (which rule out PD), red flags (which must be counterbalanced by additional supportive criteria to allow diagnosis of PD), and supportive criteria (positive features that increase confidence of the PD diagnosis). Two levels of certainty are delineated: clinically established PD (maximizing specificity at the expense of reduced sensitivity) and probable PD (which balances sensitivity and specificity). The Movement Disorder Society criteria retain elements proven valuable in previous criteria and omit aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of PD expands, the Movement Disorder Society criteria will need continuous revision to accommodate these advances.

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Parkinsonism: onset, progression, and mortality

M Hoehn, M Yahr (1967)

Neurology, 17(5), 427-427

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The MoCA: well-suited screen for cognitive impairment in Parkinson disease.

J. Dalrymple-Alford, M. R. MacAskill, C. T. Nakas … (2010)

To establish the diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) when screening externally validated cognition in Parkinson disease (PD), by comparison with a PD-focused test (Scales for Outcomes in Parkinson disease-Cognition [SCOPA-COG]) and the standardized Mini-Mental State Examination (S-MMSE) as benchmarks. A convenience sample of 114 patients with idiopathic PD and 47 healthy controls was examined in a movement disorders center. The 21 patients with dementia (PD-D) were diagnosed using Movement Disorders Society criteria, externally validated by detailed independent functional and neuropsychological tests. The 21 patients with mild cognitive impairment (PD-MCI) scored 1.5 SD or more below normative data in at least 2 measures in 1 of 4 cognitive domains. Other patients had normal cognition (PD-N). Primary outcomes using receiver operating characteristic (ROC) curve analyses showed that all 3 mental status tests produced excellent discrimination of PD-D from patients without dementia (area under the curve [AUC], 87%-91%) and PD-MCI from PD-N patients (AUC, 78%-90%), but the MoCA was generally better suited across both assessments. The optimal MoCA screening cutoffs were <21/30 for PD-D (sensitivity 81%; specificity 95%; negative predictive value [NPV] 92%) and <26/30 for PD-MCI (sensitivity 90%; specificity 75%; NPV 95%). Further support that the MoCA is at least equivalent to the SCOPA-COG, and superior to the S-MMSE, came from the simultaneous classification of the 3 PD patient groups (volumes under a 3-dimensional ROC surface, chance = 17%: MoCA 79%, confidence interval [CI] 70%-89%; SCOPA-COG 74%, CI 62%-86%; MMSE-Sevens item 56%, CI 44%-68%; MMSE-World item 62%, CI 50%-73%). The MoCA is a suitably accurate, brief test when screening all levels of cognition in PD.

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Author and article information

Journal

Journal ID (nlm-ta): J Parkinsons Dis

Journal ID (iso-abbrev): J Parkinsons Dis

Journal ID (publisher-id): JPD

Title: Journal of Parkinson's Disease

Publisher: IOS Press (Nieuwe Hemweg 6B, 1013 BG Amsterdam, The Netherlands )

ISSN (Print): 1877-7171

ISSN (Electronic): 1877-718X

Publication date (Electronic, preprint): 08 May 2024

Publication date (Electronic, pub): 04 June 2024

Publication date (Electronic, collection): 2024

Volume: 14

Issue: 4

Pages: 843-853

Affiliations

[a ] Department of Neuroscience “Rita Levi Montalcini”, University of Torino , Torino, Italy

[b ]SC Neurologia 2U, AOU Città della Salute e della Scienza, Torino, Italy

Author notes

[ 1 ]

These authors contributed equally as first author to this work.

[ 2 ]

These authors contributed equally as last author to this work.

[* ]Correspondence to: Prof. Maurizio Zibetti, MD, PhD, Department of Neuroscience “Rita Levi Montalcini”, University of Torino, Via Cherasco 15, 10126, Torino, Italy. Tel.: +39 0116709366; E-mail: maurizio.zibetti@ 123456unito.it .

Article

Publisher ID: JPD240003

DOI: 10.3233/JPD-240003

PMC ID: 11191481

PubMed ID: 38728203

SO-VID: 0580b048-f81c-4ec3-9170-48e368a64e67

License:

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date accepted : 27 March 2024

Effects of Continuous Dopaminergic Stimulation on Parkinson’s Disease Gait: A Longitudinal Prospective Study with Levodopa Intestinal Gel Infusion

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Abstract

Background:

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Methods:

Results:

Conclusion:

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Most cited references 44

MDS clinical diagnostic criteria for Parkinson's disease.

Parkinsonism: onset, progression, and mortality

The MoCA: well-suited screen for cognitive impairment in Parkinson disease.

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