The Relations Between Non-motor Symptoms and Motor Symptoms in Parkinson Disease

OANA CRICIOTOIU1, DIANA IULIA STANCA2*, DANIELA GABRIELA GLAVAN3, SIMONA BONDARI4, RAMONA DENISE MALIN5, MIRCEA SORIN CIOLOFAN5, MARIUS GABRIEL BUNESCU6, FLORIN MARIUS ROMANESCU7, MICHAEL SCHENKER8, OVIDIU STEFAN GEORGESCU1, MANUELA IULIANA DRAGOMIR9, VICTOR GHEORMAN10, VERONICA GHEORMAN11, DAN IONUT GHEONEA12 1University of Medicine and Pharmacy of Craiova, Doctoral School, 2 Petru Rares Str., 200349, Craiova, Romania 2University of Medicine and Pharmacy of Craiova, Faculty of Medicine, Department of Neurology, 2 Petru Rares Str., 200349, Craiova, Romania 3University of Medicine and Pharmacy of Craiova, Faculty of Medicine, Department of Psychiatry, 2 Petru Rares Str., 200349, Craiova, Romania 4University of Medicine and Pharmacy of Craiova, Department of Radiology and Medical Imaging,, County Hospital of Craiova, 1 Tabaci Str.,200642, Craiova, Romania 5University of Medicine and Pharmacy of Craiova, Faculty of Medicine, Department of ORL, 2 Petru Rares Str., 200349, Craiova, Romania 6University of Medicine and Pharmacy of Craiova, Faculty of Medicine, Occupational Medicine Department, 2 Petru Rares Str., 200349, Craiova, Romania 7University of Medicine and Pharmacy of Craiova, Department of Physiology, 2 Petru Rares Str.,200349, Craiova, Romania 8University of Medicine and Pharmacy of Craiova, Oncology Department, 2 Petru Rares Str., 200349, Craiova, Romania 9University of Medicine and Pharmacy of Craiova, Department of Public Health and Healthcare Management, 2 Petru Rares Str.,200349, Craiova, Romania 10University of Medicine and Pharmacy of Craiova, Psychiatry Department, Neuropsychiatry Hospital of Craiova, 24 Aleea Potelu Str., 200473, Craiova, Romania 11University of Medicine and Pharmacy of Craiova, Department of Cardiology, 2 Petru Rares Str.,200349, Craiova, Romania 12University of Medicine and Pharmacy of Craiova, County Hospital of Craiova, Gastroenterology Department, 1 Tabaci Str.,200642, Craiova, Romania

Parkinson disease (PD), one of the most common neurodegenerative disease, is classified as a movement disorder, but non-motor symptoms (NMS) also occur [1].
Traditionally, PD is characterized by its motor symptoms: bradykinesia, resting tremor and rigidity, but, in last decades, this concept has changed and now the disease is regarded as much a non-motor disorder as a motor disorder. Several studies showed that NMS are a real burden in PD which may appear even before the diagnosis of PD and that these NMS reflect a key determinant of the patient and career's quality of life [2].
Increasing data showed that PD is a multisystem disease rather than a disease and this is due to it's multi-focal and multi-neurotransmitter driven pathology. The clinical phenotypic variations of PD are variable, and this is, in part, the consequence of a wide range of NMS which can include sleep dysfunction, psychiatric disorders, gastrointestinal dysfunction or autonomic dysfunction. But the change that underlie the NMS is still poor understand and they are not treated effectively well with dopamine-based drug therapy [3][4][5].
It is well known that motor symptoms affect quality of life in PD patients, but many reports have suggested that NMS can have a greater influence on the patient's life than the motor symptoms. It is important to assess the presence of motor and non-motor symptoms and to evaluate the impact of these symptoms on quality of life [6][7].
The purpose of our study was to evaluate the distribution and correlations of the two types of symptoms.

Methods and Materials
We included in our study 72 patients (28 females and 44 males), mean age 67.56±7.74 (range between 49 and 80 years, diagnosed with Parkinson Disease in according with United Kingdom Society Brain Bank criteria [8]. For each patient we recorded details of demographic data, age at onset, disease duration, symptoms at onset, medications, motor fluctuations and family history. The patients were assessed using United Parkinson Disease Rating Scalemotor section (UPDRS part III) [9]. This scale is an instrument with 27 items which assessed motor function related to tremor, rigidity, posture and bodily movement. Scores range from 0 to 108 points and higher scores indicate lower motor functioning.
The Hoehn and Yahr Scale was used for disease staging [10].
Both scale (UPDRS and Hoehn and Yahr scale) were evaluated while the patients were in best on state.
To evaluate the non-motor symptoms, each patient was assessed by Non-motor Symptoms Questionnaire for Parkinson Disease (NMS Quest) [11]. It is a self-assessing tool that includes 30 questions covering 10 different domains ranging from gastrointestinal to miscellaneous. This questionnaire must be completed by the patient, checking the no or yes box. We rated 0 point if the patient's answer was no and 1 point if the patient's answer was yes.
To evaluate sleep dysfunction the patients took the Parkinson Disease Sleep Scale(PDSS) [14].
The statistical analysis was made using IBM SPSS Statistics V20.
We performed both descriptive and exploratory data analysis. For comparations we used one tailed student Ttest and for correlation -Pearson R test, with the statistically significance established at 95%, p<0.05.

Results and discussions
The present study evaluated PD patients that preformed our protocol from 2017 to 2019. There were included 34 from rural environment and 38 urban. When evaluated the disease progression there were included patients from stage 1 to stage 5 H&Y with an medium distribution around stage 3.
The aim of this study was to analyze the relation between the two types of symptomatology in PD, motor and non-motor.
In the figure 1 we can observe that there was a positive correlation between the motor and non-motor state of our patients. This means that as the motor symptomatology accentuate the non-motor one follows the same trend.
In the table above we observe that there was an correlation with an statistical significance with p=0.008 (table 1).
Given the literature data that not all non-motor features correlate with the motor ones, we went further to analyze the different domains of NMSQ to compare it with the motor state of our patients.
There was no surprise to realize that not al NMSQ domains correlated with the motor UPDRS.
In the table below we can observe an positive correlation when it comes to digestive, cardiovascular, sleep and miscellaneous domains. On the other side the urinary, memory, hallucination, depression and sexual function domain did not correlate. On the positive correlation we had an statistical significance established with p<0.05 (table 2).
We went further and considered that for the memory and sleep we can better analyze it with the validated questionnaires for each one.
We observed that for the sleep dysfunction there was an negative correlation with the motor UPDRS, with p value of 0.03. This negative correlation can be explained by the fact that the PDSS questionnaire has an decrease of the score as the dysfunction accentuate and the UPDRS part III score increases as the motor symptoms progresses. This significate that there is an relation between the sleep and motor dysfunction (table 3, fig. 2).
When it comes to memory there was no correlation with the motor UPDRS. This shows that the memory domain evaluated with the NMSQ showed the same correlation status as the validated questionnaire for memory (MMSE), showing that MNSQ domains can proper evaluate the non-motor state(table 4, fig. 3).   This study shows that the incomplete discovery of the pathophysiology process of PD has an impact on those patients disease management. It is important that we treat both motor and non-motor symptoms to offer our patients the best quality of life possible in their stage of the disease.
As in our study, other findings showed that there is a correlation between the motor and non-motor symptoms [15][16].
When it comes to sleep the literature is mentioned that even if the patients report an improve of motor function when the sleep dysfunction diminuates, there is no objective improvement of the motor function [17][18][19]. In our study there was an correlation between those two [20].
The memory impairment is linked in other studies to the progression of the motor state but in this study there was no statistical correlation between those two [21].
This shows that both motor and non-motor symptoms affect the quality of life of PD patients and the case management should be made by an multidisciplinary team.

Conclusions
Patients with PD have an variety of symptoms that should be recognized and treated. In this study we headlighted that some of the non-motor symptoms correlate with the motor state of our patients, amoung them there are digestive, cardiovascular, sleep and miscellaneous domains. On the other side some of the symptoms does not present an interdependence with the motor symptoms as urinary, memory, hallucination, depression and sexual function domain, and it should be treated separately.