Cardinal Motor Features of Parkinson's Disease Coexist with Peak-Dose Choreic-Type Drug-Induced Dyskinesia

Abstract

Background: Clinical and anecdotal observations propose that patients with Parkinson's disease (PD) may show drug-induced dyskinesia (DID) concomitantly with cardinal motor features. However, the extent of the concomitant presence of DID and cardinal features remains to be determined.

Objectives: This cross-sectional study measured peak-dose choreic-type DID in a quantitative manner in patients diagnosed with PD, and determined whether symptoms such as tremor, bradykinesia, rigidity, postural instability or freezing of gait (FoG) were still detectable in these patients.

Methods: 89 patients diagnosed with PD were recruited and assessed using a combination of quantitative measures using inertial measurement units to capture DID, tremor, bradykinesia, and FoG. Clinical evaluations were also used to assess rigidity and postural instability. Motor symptoms of PD were assessed 3 times during the testing period, and a series of activities of daily living were repeated twice, in between clinical tests, during which the level of DID was quantified. Peak-dose was identified as the period during which patients had the highest levels of DID. Levels of tremor, rigidity, bradykinesia, postural instability, and FoG were used to determine the percentage of patients showing these motor symptoms simultaneously with DID.

Results: 72.4% of patients tested presented with measurable DID during the experiment. Rest, postural and kinetic tremor (12.7% , 38.1% , and 15.9% respectively), bradykinesia (28.6% ), rigidity (55.6% ), postural instability (71.4% ) and FoG (9.5% ) were detected simultaneously with DID.

Conclusions: PD symptomatology remains present in patients showing peak-dose choreic-type DID, illustrating the challenge facing physicians when trying to avoid dyskinesia while attempting to alleviate motor symptoms.

Keywords: Chorea; Parkinson disease; drug-induced; dyskinesia; hypokinesia; movement disorders; tremor.

Fig.1

Pattern of motor response to levodopa during the progression of PD. Early in the disease, levodopa response is optimal, reaching the therapeutic window. As the disease progresses, this therapeutic window decreases due to changes in exogenous dopamine management by remaining neurons. After approximately seven to ten years, this therapeutic window becomes less attainable, leaving the patient in either an OFF or ON with dyskinesia condition. Inspired by Cenci [11] and Jankovic [12].

Fig.2

Dyskinesia amplitude of controls and participants with PD. Dyskinesia detection in patients (black) based on the behavior of healthy controls (grey). Mean plus two standard deviations of data from controls are illustrated in gray. Individual data points from patients are illustrated in black.

Fig.3

Level of cardinal motor symptoms in the 63 patients with PD who presented with DID (black), compared to normative values obtained from the control group (grey). Mean plus two standard deviations of data from controls are Illustrated in gray. Individual data points from patients are illustrated in black.

Fig.4

Proposed pattern of motor response to levodopa over the time. This pattern suggests that some residual cardinal motor features of PD (i.e., bradykinesia, rigidity, postural instability and tremors) remain present in the therapeutic window, and could even overlap with dyskinesia.