The range and nature of non-motor symptoms in drug-naive Parkinson's disease patients: a state-of-the-art systematic review.

Panagiotis Zis,Panagiotis Zis,Kallol Ray Chaudhuri,Courtney C Walton,Roberto Erro,Roberto Erro,Anna Sauerbier,Anna Sauerbier

doi:10.1038/npjparkd.2015.13

Abstract

Non-motor symptoms (NMS) are a key component of Parkinson’s disease (PD). A range of NMS, most notably impaired sense of smell, sleep dysfunction, and dysautonomia are present from the ‘pre-motor’ phase to the final palliative stage. Theories as to the pathogenesis of PD such as those proposed by Braak and others also support the occurrence of NMS in PD years before motor symptoms start. However, research addressing the range and nature of NMS in PD has been confounded by the fact that many NMS arise as part of drug-related side effects. Thus, drug-naive PD (DNPD) patients provide an ideal population to study the differences in the presentation of NMS. The aim of this paper is therefore to systematically review all the available studies of NMS in DNPD patients. We believe this is the first review of its kind. The current review confirms the increasing research being conducted into NMS in DNPD patients as well as the necessity for further investigation into less-studied NMS, such as pain. Moreover, the data confirms non-motor heterogeneity among PD patients, and, therefore, further research into the concept of non-motor subtyping is encouraged. The review suggests that the clinical assessment of NMS should be integral to any assessment of PD in clinical and research settings.

Highlights

Non-motor symptoms (NMS) are a key component of Parkinson’s disease (PD)[1] and a major determinant of quality of life and phenotypic expression.[1,2] there is growing evidence that the overall burden of NMS may have a greater impact on quality of life than motor symptoms, not just in advanced motor disease as commonly perceived and in early motor PD.[2,3]A number of NMS are present from the ‘pre-motor’ stage[4] to the final palliative stages of PD.[5]
Drug-naive PD (DNPD) patients are an ideal population to study to study the differences in presentation of NMS at the early, or even pre-motor stages of PD and some controlled studies have reported on the burden of NMS in drug-naive PD (DNPD).[7,8]
The aim of this review is to systematically review all the available studies of NMS in DNPD patients and we believe this is the first review of its kind

Summary

Introduction

A number of NMS are present from the ‘pre-motor’ stage[4] to the final palliative stages of PD.[5] The involvement of multiple neurotransmitters from the onset of PD, extra-striatal dopaminergic pathways, as well as early involvement of brainstem and olfactory areas in PD further augment the importance of NMS in PD.[6]. The fact that a range of NMS may arise as part of drugrelated side effects confounds this issue further.[3] drug-naive PD (DNPD) patients are an ideal population to study to study the differences in presentation of NMS at the early, or even pre-motor stages of PD and some controlled studies have reported on the burden of NMS in DNPD.[7,8] Yet, it is difficult to obtain large case series of DNPD patients as often patients referred to PD specialist centers or clinical research-orientated neurology departments are already on anti-parkinsonian medication. The aim of this review is to systematically review all the available studies of NMS in DNPD patients and we believe this is the first review of its kind

Objectives

Methods

Results

Conclusion