Predictors of motor complications in early Parkinson's disease: A prospective cohort study

Abstract

Objective The objective of this study was to identify clinical predictors of motor complications (dyskinesia and motor fluctuations) of levodopa in a prospectively recruited PD cohort using longitudinal analysis. Methods An inception cohort (Oxford Discovery) of 734 patients was followed to a maximum of 10 years from diagnosis using a discrete‐time survival analysis. A subset analysis was used to validate an online dyskinesia‐risk calculator developed from the results of the Stalevo Reduction in Dyskinesia Evaluation PD trial. Results A total of 186 cases of dyskinesia and 254 cases of motor fluctuations were observed. Dyskinesia incidence increased with time (risk per 100 participants [95% confidence interval] 13 [11–16] <3.5 years, 16 [13–21] 3.5–5.0 years, 19 [14–26] 5–6.5 years, and 23 [16–33] >6.5 years from diagnosis). Motor complication predictors were grouped as medication predictors, disease predictors and patient predictors. Baseline nonmotor feature severity, low mood, anxiety, and age at symptom onset were associated with motor complications among a number of previously identified predictors. Replication of the Stalevo Reduction in Dyskinesia Evaluation PD calculator was reasonable with the area under the curve for dyskinesia risk score as a predictor of dyskinesia being 0.68 (95% confidence interval, 0.55–0.81). Conclusions This study quantifies risk of motor complications, finds consistent predictors, and demonstrates the novel finding that nonmotor features of PD, particularly low mood and anxiety, are significant risk factors for motor complications. Further validation of dyskinesia risk scores are required as well as evidence to determine if the routine use of such scores can be clinically valuable in enhancing patient care and quality of life. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Predictors of Motor Complications in Early Parkinson's Disease

“…Female sex and Unified Parkinson's Disease Rating Scale part III were associated with levodopa‐induced dyskinesias in 2 studies . Anxiety and Unified Parkinson's Disease Rating Scale part I were the only nonmotor symptoms associated with levodopa‐induced dyskinesias in these studies …”

“…We read with great interest the article published in Movement Disorders by Kelly and colleagues about the predictors associated with motor complications in Parkinson's disease (PD), mainly levodopa‐induced dyskinesias. Indeed, it is the largest observational prospective study about this theme at moment (n = 734), and their results help us to understand the risk of levodopa‐induced dyskinesias onset as data that may change throughout the disease evolution, probably as a result of time‐varying variables, as levodopa dose and disease severity.…”

“…In all 4 studies, there were differences about the predictors associated with levodopa‐induced dyskinesias without a common predictor. Only levodopa‐equivalent daily dose or levodopa daily dose was associated with levodopa‐induced dyskinesias onset in 3 studies . Female sex and Unified Parkinson's Disease Rating Scale part III were associated with levodopa‐induced dyskinesias in 2 studies .…”

“…However, these studies have issues on their strategy to detect levodopa‐induced dyskinesia onset. For example, the article from Kelly and colleagues reevaluated patients at each 18 months, a long interval to detect prospectively the exact moment of levodopa‐induced dyskinesias onset, considering a cumulative incidence of 6.3% at each 12 months described by Bjornestad and colleagues . PD cohorts should adopt more short reevaluation intervals, dyskinesia‐monitoring wearable devices, or methods to educate patients to detect new abnormal involuntary movements themselves as soon as possible.…”

“…Kelly and colleagues also tested a levodopa‐induced dyskinesia onset risk‐prediction strategy using a former dyskinesia risk calculator based on a clinical trial (STalevo Reduction In Dyskinesia Evaluation – Parkinson's Disease). Considering the problems already cited by the authors in this approach (time of data extraction, missing data, study design), it would be advisable for the authors the development of a predictive model based on their own final multivariate model, with further internal and external validations .…”