Abstract

Background. The latest Movement Disorder Society (MDS) diagnostic criteria require a good and sustained response to medication to get a diagnosis of Parkinson’s disease, PD. Objective. The aim of this study was to evaluate levodopa response in a group of patients with probable PD, diagnosed by movement disorder specialists. Methods. An acute levodopa challenge test (LDCT) was performed after pausing the dopaminergic medication for 6 half-times. The motor part of the Unified Parkinson’s Disease Rating Scale was performed in the OFF-state and after LDCT (ON). A good effect was defined as >30% improvement. A video-protocol was used to secure standardized motor examination with blinded assessments of the UPDRS-III OFF and ON. An age-matched group of control subjects (CS) was included but did not go through LDCT. All participants were evaluated with Montreal Cognitive Assessment (MoCA) and Beck’s Depression Inventory (BDI). Results. In the statistical analysis, 37 patients were included. Twenty-one patients showed an improvement ≤۳۰%, while 16 patients showed an improvement >30%. LDCT showed an overall mean improvement of 27.3% of motor UPDRS. In 43.2%, there was a discrepancy between the effect seen with the LDCT and the patients’ self-perceived medicine evaluation. Patients with PD had a significantly lower MoCA score and more depressive symptoms compared to CS. Conclusions. We showed an acute effect of levodopa using LDCT that was around 30% improvement. While it lends support to the use of this limit in the MDS diagnostic criteria, an acute effect of less than 30% should be considered acceptable in some patients. Our study highlights a discrepancy in the objective measure of medicine effect on motor symptoms and the patient’s subjective evaluation.

Introduction

Parkinson’s disease (PD) is the second most common neurodegenerative disease, causing severe disability with increasing prevalence. A diagnosis of PD is based on the motor manifestations: bradykinesia, rigidity, and tremor, and clinical symptoms related to the loss of dopamine. In PD, these symptoms of parkinsonism are related to a neurodegenerative pathological process involving misfolding and aggregation of α-synuclein and formation of inclusion bodies, Lewy bodies, primarily in dopaminergic neurons. A diagnosis of PD is clinicopathological and requires both this pathological hallmark as well as the clinical phenomenology. In 2015, the Movement Disorder Society (MDS) put forward updated clinical diagnostic criteria for PD to increase early diagnostic accuracy in patients with Lewy body pathology Parkinson’s disease [1]. Dopaminergic neuronal loss in addition to Lewy body formation is central in the pathology of PD. In the diagnostic criteria from 2015, the importance of this pathological hallmark is emphasized even more than in earlier diagnostic criteria [2], through suggestion of operational criteria including (i) support by objective measurement of effect on motor symptoms showing a >30% improvement with dopaminergic medication in the motor part of the Unified Parkinson’s Disease Rating Scale (UPDRS-III), (ii) a clearly documented history of marked changes with medication from the patient or the caregiver, and also that (iii) lack of sufficient motor improvement should be an exclusion criterion [3].

While the diagnostic criteria of PD from MDS have been validated against expert clinical diagnosis and the United Kingdom Brain Bank criteria from 1988 [4], the clinical importance of having this definition of the effect of medication in a movement disorder clinic may still be more thoroughly evaluated.

Treatment with levodopa (L-dopa) is the most efficient dopaminergic therapy and the golden standard treatment for PD [1]. An evaluation of dopaminergic effect is therefore necessarily based on treatment with L-dopa. To evaluate the treatment effect in an objective manner, the standardized acute levodopa challenge test (LDCT) can be used to assess motor symptoms both OFF and ON medication to evaluate the L-dopa response. Besides using LDCT in a diagnostic approach, the acute LDCT protocol has been described and used in the measurement of disease progression [5]. In addition, it has been widely accepted as an evaluation of levodopa effect as a preoperative evaluation before deep brain stimulation of the subthalamic nucleus (STN-DBS) [6].

Conclusion

We have performed a clinically relevant evaluation of levodopa response in a group of patients with PD with both a self-reported good and poor L-dopa response. An acute LDCT was performed as an objective measure, but a surprisingly large discrepancy was found between the subjectively reported usual response and the acute effect. As patients all otherwise had a diagnosis of PD, a good effect should be found for both the subjective and objective evaluation in accordance with diagnostic criteria. Our study sheds light on the importance of questioning the reported effect when making a diagnosis. The mean LCDT was close to 30% in most cases, but our study indicates that an acute effect of less than 30% should sometimes be expected.

In conclusion, this study showed that the LCDT can be used as a diagnostic support and that it is a valuable tool in addition to the self-reported effect from the patient. But also, that conclusions based on an acute effect of less than 30% should be evaluated with caution, as this was the case in 56.8% of the patients with PD in our study.