Liis Kadastik-Eerme

Differences in MDS‐UPDRS Scores Based on Hoehn and Yahr Stage and Disease Duration

The Movement Disorder Society Unified Parkinsons Disease Rating Scale (MDS‐UPDRS) is a newly developed tool to assess Parkinsons disease (PD). Changes in scores on the scale over the course of PD, including increasing disease duration and Hoehn and Yahr (HY) stages, have not been described. The objectives of this study were to analyze MDS‐UPDRS scores on Parts I through IV and their differences based on HY stage and disease duration in a large cohort of patients with PD.

Looking beyond the brain to improve the pathogenic understanding of Parkinson’s disease: implications of whole transcriptome profiling of Patients’ skin

BackgroundParkinson’s Disease is a progressive neurodegenerative disease, characterized by symptoms of motor impairment, resulting from the loss of dopaminergic neurons in the midbrain, however non-neuronal symptoms are also common. Although great advances have been made in the pathogenic understanding of Parkinson’s Disease in the nervous system, little is known about the molecular alterations occurring in other non-neuronal organ systems. In addition, a higher rate of melanoma and non-melanoma skin cancer has been observed in the Parkinson’s Disease population, indicating crosstalk between these diseases.MethodsTo understand the molecular pathogenesis and gene expression alterations of Parkinson’s Disease in peripheral tissues, and in order to explore the possible link between skin cancer and neurodegeneration, whole transcriptomic profiling of patients’ skin was performed. Skin biopsies from 12 patients and matched controls were collected, and processed with high-throughput RNA-sequencing analysis.ResultsThis analysis resulted in a large collection of over 1000 differentially expressed genes, among which clear biological and functional networks could be distinguished. The central functional processes altered in patients skin can be grouped into six broad categories: impaired cellular metabolism and mitochondrial dysfunction, defective protein metabolism, disturbed skin homeostasis, dysfunctional nuclear processes, altered signalling and tumour pathways, as well as disordered immune regulation.ConclusionsThese results demonstrate that the molecular alterations leading to neurodegeneration in the CNS are systemic and manifest also in peripheral tissues, thereby indicating the presence of “skin-brain” crosstalk in Parkinson’s Disease. In addition, the extensive homeostatic imbalance and basal stress can lead to increased susceptibility to external and internal mutagenic hazards in these patients, and thus provide a possible molecular link for the crosstalk between skin cancer and Parkinson’s Disease.

Substantia Nigra Hyperechogenicity Validation of Transcranial Sonography for Parkinson Disease Diagnosis in a Large Estonian Cohort

Substantia nigra hyperechogenicity is a promising biomarker for Parkinson disease (PD). Substantia nigra hyperechogenicity has previously been established as a useful diagnostic criterion in several European and Asian patient cohorts. However, diagnostic cutoff values for substantia nigra hyperechogenicity remain unknown for most patient populations. This study validated the diagnostic accuracy of substantia nigra hyperechogenicity in a large cohort of patients with PD in Estonia.

Relationship between the MDS-UPDRS and Quality of Life: A large multicenter study of 3206 patients

BACKGROUND The relationship between Health-Related Quality of Life (HRQoL) and MDS-UPDRS has not been fully studied so far. The aim of this study was to evaluate the relationship between all MDS-UPDRS components and HRQoL in a representative international cohort of PD patients. METHODS We collected demographic and disease-related data as well as MDS-UPDRS and PDQ8 scales. Data were analyzed using correlations between PDQ8 and all MDS-UPDRS items, subsequently two hierarchical multiple regressions were performed, first between the scores of the MDS-UPDRS Parts and PDQ8 and second between individual items from those Parts demonstrating significant relationship to PDQ8 scores in the first regression. LASSO regression analyses were performed to evaluate the relationship between PDQ8 and all individual MDS-UPDRS items. RESULTS A total of 3206 PD patients were included in the study. In the first regression analysis, PDQ8 was significantly related to MDS-UPDRS parts I and II, but not to III and IV. In the second regression model, significant contributions to PDQ8 were found for Part I items Fatigue, Pain, Depressed mood, Apathy; and Part II items Dressing, Doing hobbies, Freezing, Speech and Tremor. In the LASSO analysis, six Part I, seven Part II, three Part III and one Part IV items contributed to PDQ8 scores. The five items most significantly related to the model were Depressed mood, Dressing, Apathy, Pain and Fatigue. CONCLUSIONS This is so far the largest study related to HRQoL issues in PD. Restrictions in activities of daily living and non-motor symptoms significantly contribute to HRQoL in PD.

The increasing prevalence of Parkinson's disease in Estonia

A previous epidemiological study of Parkinsons disease (PD) in the county of Tartu, Estonia, found an adjusted prevalence rate of 152/100 000 persons. We aimed to determine PD prevalence almost 20 years later, as well as evaluate any dynamic changes in disease frequency compared to the first study.

Prevalence of depressive symptoms and their association with brainstem raphe echogenicity in patients with Parkinson's disease and non-PD controls

Despite advances in diagnostics and clinical recognition, depressive symptoms in Parkinsons disease (PD) exceeding normal limits remain effectively untreated. In this study, we report on the prevalence and severity of depressive symptoms as well as their association with brainstem raphe echogenicity in patients with PD and non-PD controls. The study included 266 Estonian PD patients and 168 age- and education-matched controls. Demographic and clinical data was documented. Brainstem raphe (BR) was visualized by transcranial sonography (TCS). The prevalence of depressive symptoms in the patient sample was found to be significantly higher than in controls. BR echogenicity in both patients and controls was directly related to their total BDI score, although we found a significantly greater reduction of BR echogenicity in patients with PD and depressive symptoms compared to depressed non-PD controls. The present results corroborate the hypothesis that morphological alteration of the BR is involved in the pathogenesis of depressive disorders. TCS of BR could be used as a non-invasive biomarker to improve detection of depressive symptoms in early PD stages where clinicians may not recognize affective disturbances in the context of PD phenomena.

Factors associated with motor complications in Parkinson's disease

Levodopa is the most effective therapy for treating Parkinsons disease (PD); however, side effects such as dyskinesias and motor fluctuations may occur after some years of its usage. The aims of this study were to assess the frequency of and factors associated with motor complications among PD patients on levodopa treatment.

Effect of Age on Substantia Nigra Hyper-echogenicity in Parkinson's Disease Patients and Healthy Controls

Substantia nigra (SN) hyper-echogenicity (SN+) describes an enlargement (>90th percentile) of the area of echogenicity at the anatomic site of the SN in the midbrain detected by transcranial sonography. This ultrasound sign has proven to be a valuable marker supporting the clinical diagnosis of Parkinsons disease (PD). Although there is considerable variation in the extent of echogenic signals at the anatomic site of the SN among PD patients, previous work suggests that SN+ is a stable marker throughout the course of the disease. The present study focused on two aspects: (i) determining whether SN+ values differ between the sides, mirroring the asymmetric character of the disease; and (ii) determining whether age has an influence on SN echogenicity. This cross-sectional study included 300 PD patients and 200 healthy controls. SN+ was measured planimetrically by transcranial sonography. Echogenicity was analyzed separately for onset and non-onset sides, with onset side defined as the SN contralateral to the side of the body that first manifested PD-related motor impairment. Age of the patients and healthy controls at study time was used for correlation. We found that the onset SN+ contralateral to the side of initial motor symptoms was on average 17.6% larger than its counterpart. However, we also found that contrary to the control group, where an increase in age was associated with an increase in size of SN+, age of PD patients was associated with a decline in size of the onset SN+. Furthermore, SN measured at the onset side of PD patients correlated significantly with patient age and Hoehn and Yahr stage, a scale that grades PD severity, although this was not the case for the non-onset side. The present study indicates that changes in SN echogenicity have a different dynamic depending on the onset side of the disease. The age at study time had a significantly negative effect on the size of onset SN+, the effect on the non-onset side was non-significant. We conclude that for appropriate PD analysis, onset SN+ is a more important marker than the average of both sides of SN. Furthermore, we found that among healthy controls, the size of SN+ increases with age.

Response to the letter by Scorza et al

To the Editor, We appreciate the letter from Dr Scorza and his colleagues regarding our recently published article “The increasing prevalence of Parkinson’s disease (PD) in Estonia.”1 We read with great interest the papers cited in this letter that investigate the comorbidity and mortality of PD, paying a special attention to the cardiac abnormalities, in particular, the sudden unexpected death in PD (SUDPAR). Based on the World Health Organization reports, the increase in mean life expectancy at birth for Estonian people has been remarkable, rising from 70.8 years in 2000 to 77.6 years in 2015. The shift towards longer life expectancy has increased more rapidly in Estonia than in the European region in general where the abovementioned indicator has risen from 73 years in 2000 to 77.1 years in 2015.2 As already discussed in our recent article on PD prevalence in Estonia, the moderately higher frequency of PD at present compared to the demographic situation 20 years ago might be significantly influenced by the higher proportion of elderly people. Our epidemiological study on PD in Estonia encompasses the prevalence, incidence and mortality of the disease. The yet unpublished data show that the incidence has not significantly changed over two decades supporting the influence of longer survival of people to the increased prevalence of the disease. With increasing proportion of elderly population, the disease burden of morbidities associated with ageing is going to rise as well. Older age is associated not only with the higher prevalence of PD, but also with other diseases including cardiovascular, gastrointestinal and oncological disorders.3,4 Our earlier crosssectional study on the healthrelated quality of life of patients with PD showed that women have statistically higher load of comorbidities compared to men, including a significantly higher rate of cardiovascular diseases.5 Although the causes of morbidity and mortality are shown to be similar in the general population and in the PD population, it has been shown that the survival is shorter among PD patients.6 Higher burden of comorbidities has shown to be a predictor of death in PD patients.7 Our study analysing the death certificate data of 168 PD patients in the period of 20102017 showed that the three most common primary causes of death were cardiovascular diseases (61%), cerebrovascular disorders (14%) and malignant neoplasms (12%). Surprisingly, sudden cardiac death was not registered in any of the death records.