Risk and course of motor complications in a population-based incident Parkinson's disease cohort

https://doi.org/10.1016/j.parkreldis.2015.11.007Get rights and content

Highlights

  • Motor complications affected over 50% in the first 5 years of Parkinson's disease.

  • Dopamine depletion is indicated as an important cause.

  • Early levodopa treatment was not associated with motor complications.

  • Motor complications were mild in the majority and reversible in more than 35%.

  • No patients required advanced treatment during the first 5 years after diagnosis.

Abstract

Background

Motor complications may become major challenges in the management of patients with Parkinson's disease. In this study, we sought to determine the incidence, risk factors, evolution, and treatment of motor fluctuations and dyskinesias in a population-representative, incident Parkinson's disease cohort.

Methods

In this prospective population-based 5-year longitudinal study, we followed 189 incident and initially drug-naïve Parkinson's disease patients biannually for detailed examination of dyskinesias and motor fluctuations as defined by the Unified Parkinson's disease Rating Scale. We performed Kaplan–Meier survival and Cox regression analyses to assess cumulative incidence and risk factors of these motor complications.

Results

The 5-year cumulative incidence of motor complications was 52.4%. Motor fluctuations occurred in 42.9% and dyskinesias in 24.3%. Besides higher motor severity predicting both motor fluctuations (p = 0.016) and dyskinesias (p < 0.001), lower age at diagnosis predicted motor fluctuations (p = 0.001), whereas female gender predicted dyskinesias (p = 0.001). Actual levodopa dose at onset of motor fluctuations (p = 0.037) or dyskinesias (p < 0.001) rather than initial treatment with levodopa (p > 0.1) independently predicted development of motor complications. Motor fluctuations reversed in 37% and dyskinesias in 49% of patients on oral treatment and remained generally mild in those with persistent complications. No patients received device-aided therapies during the study.

Conclusions

More than 50% in the general Parkinson's disease population develop motor complications within 5 years of diagnosis. However, they remain mild in the vast majority and are reversible in a substantial proportion of patients.

Introduction

Parkinson disease (PD) is a relentlessly progressive movement disorder of unknown etiology [1]. With PD progression, the efficacy of pharmacotherapy deteriorates [2] and patients may develop motor complications, which can be broadly subdivided into motor fluctuations and dyskinesias. The risk for and time to emergence of these motor complications vary substantially among patients for reasons that are probably complex, including both disease- and drug-related factors, particularly treatment with levodopa [3], [4].

Although motor fluctuations and dyskinesias may compromise quality of life [5], their evolution and prognosis are still incompletely investigated, as most previous studies assessed cross-sectional cohorts with established disease [6] or followed patients recruited from movement disorders centers or clinical trials [7]. This may result in both under- and overestimation of the risk of these motor complications. In addition, as treatment options have changed during the last decades, previous estimates might no longer be accurate. Finally, device-aided therapies have emerged as second-line treatments in patients with otherwise intractable motor complications [8], [9]. Recent studies promote early initiation of these advanced therapies [9], [10], which – however – are costly and may cause serious adverse events. Therefore, precise information on the evolution and potential reversal of motor fluctuations and dyskinesias using conventional pharmacotherapy is crucial for optimal patient selection to and timing of second-line treatment in PD.

To gain this important knowledge, we recruited a large, population-based, and initially drug-naive PD cohort that we monitored closely for emergence of motor complications for five years from diagnosis.

Section snippets

Subjects

All subjects participate in the Norwegian ParkWest project, a prospective, population-based, multicenter, longitudinal cohort study investigating the incidence, neurobiology and prognosis of PD. In order to establish a population-representative, incident PD cohort, we recruited patients with newly-diagnosed and untreated PD from the general population between November, 2004, and August, 2006, using multiple recruitment strategies, as previously described [11]. Briefly, all patients were

Baseline characteristics and subject flow

Baseline characteristics are given in Table 1 and the flow of subjects in Fig. 1. Of the 189 patients included at baseline, 183 (97%) completed 1 year, 173 (92%) 3 years and 158 (84%) 5 years of biannual follow-up, generating 1911 observations in total. Few subjects (7/189, 4%) withdrew from the study, whereas remaining loss to follow-up (24/189, 13%) was due to death. Median follow-up time was 5.0 (interquartile range 4.9–5.1) years.

Frequency of motor complications

Point prevalence rates increased progressively, reaching

Discussion

Our study highlights a high risk of early motor complications in the general PD population and also provides important insights into their evolution and associated risk factors, with implications for both understanding and management of motor fluctuations and dyskinesias in PD.

We are aware of only two previous longitudinal studies of dyskinesias [16] or motor complications [17] in patients with early PD derived from the community. Our study differs importantly from these in several ways,

Funding

This study was supported by the Research Council of Norway (grant# 177966), the Western Norway Regional Health Authority (grant# 911218 and 911949), and the Norwegian Parkinson's disease Association. Sponsors had no role in study design; the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.

Financial disclosures

Anders Bjornestad reports no disclosures.

Elin Bjelland Forsaa reports no disclosures.

Kenn Freddy Pedersen reports no disclosures.

Ole-Bjørn Tysnes reports no disclosures.

Jan Petter Larsen reports no disclosures.

Guido Alves has received payment for lecturing from AbbVie and research support from the Norwegian Parkinson's Disease Association.

Author’s roles

Study concept and design: Drs. Bjornestad, Tysnes, Larsen, Alves.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Dr. Bjornestad.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Drs. Bjornestad, Alves.

Obtained funding: Dr. Larsen

Administrative, technical, or material support: Drs. Tysnes, Larsen.

Study supervision: Drs. Tysnes, Larsen.

Dr. Bjornestad takes responsibility for the integrity of the data

Acknowledgments

We are grateful to all patients for their participation in this study and thank the members of the Norwegian ParkWest study group and all other personnel involved in this study for their contributions.

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