Vladimir Han

Relationship between the non-motor items of the MDS-UPDRS and Quality of Life in patients with Parkinson's disease

The Movement Disorder Society-Unified Parkinsons Disease Rating Scale (MDS-UPDRS) is a newly developed comprehensive tool to assess Parkinsons disease (PD), which covers a wider range of non-motor PD manifestations than the original UPDRS scale. The aim of this study was to assess the relationship between the MDS-UPDRS and Quality of Life (QoL) and to analyze the relationship between individual MDS-UPDRS non-motor items and QoL. A total of 291 PD patients were examined in a multicenter Slovak study. Patients were assessed by the MDS-UPDRS, HY scale and PDQ39. Data were analyzed using the multiple regression analyses. The mean participant age was 68.0 ± 9.0 years, 53.5% were men, mean disease duration was 8.3 ± 5.3 years and mean HY was 2.7 ± 1.0. In a multiple regression analysis model the PDQ39 summary index was related to MDS-UPDRS parts II, I and IV respectively, but not to part III. Individual MDS-UPDRS non-motor items related to the PDQ39 summary index in the summary group and in the non-fluctuating patients subgroup were pain, fatigue and features of dopamine dysregulation syndrome (DDS). In the fluctuating PD patient subgroup, PDQ39 was related to pain and Depressed mood items. Other MDS-UPDRS non-motor items e.g. Anxious mood, Apathy, Cognitive impairment, Hallucinations and psychosis, Sleep problems, Daytime sleepiness and Urinary problems were related to some PDQ39 domains. The overall burden of NMS in PD is more important in terms of QoL than motor symptoms. Individual MDS-UPDRS non-motor items related to worse QoL are especially pain and other sensations, fatigue and features of DDS.

Paroxysmal exercise-induced dystonia within the phenotypic spectrum of ECHS1 deficiency

ECHS1 encodes a mitochondrial enzyme involved in the degradation of essential amino acids and fatty acids. Recently, ECHS1 mutations were shown to cause a new severe metabolic disorder presenting as Leigh or Leigh‐like syndromes. The objective of this study was to describe a family with 2 siblings affected by different dystonic disorders as a resulting phenotype of ECHS1 mutations.

The Clinical Syndrome of Paroxysmal Exercise‐Induced Dystonia: Diagnostic Outcomes and an Algorithm

Paroxysmal exercise‐induced dyskinesia (PED) is characterized by recurrent episodes of involuntary movement disorders usually precipitated by sustained walking or running. Recently, mutations in the gene encoding for glucose transporter type 1 (GLUT‐1) were described in a number of families with autosomal dominant PED. However, the underlying etiology of PED is quite heterogeneous. We describe a large series of patients presenting with PED. Of 16 patients, we reached a conclusive diagnosis for 11 (4 patients with GLUT‐1 mutations, 4 patients with early Parkinsons disease, 2 with dopa‐responsive dystonia, and one with a psychogenic/functional movement disorder). For the remaining 5 patients, the final diagnosis remained descriptive. Although certain clinical features might allow etiological distinction between cases, clinical examination alone is not always conclusive. Based on our series, we propose a diagnostic algorithm to aid the differential diagnosis of PED.

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.

Prevalence of Prodromal Parkinson’s Disease as Defined by MDS Research Criteria among Elderly Patients Undergoing Colonoscopy

BACKGROUND Gastrointestinal symptoms are a well-recognized and common premotor feature of Parkinsons disease (PD). Moreover, multiple studies have assessed the value of colonic α-synuclein as a potential marker of prodromal PD. Recently, the International Parkinson and Movement Disorders Society (MDS) defined research criteria for prodromal PD. OBJECTIVE The aim of our study was to test the MDS research criteria in patients undergoing diagnostic colonoscopies as potential candidates for inclusion in prospective trials evaluating colonic biopsies as a potential biomarker of prodromal PD. METHODS We evaluated elderly patients without manifest parkinsonism undergoing diagnostic colonoscopies. During the study we assessed all risks and prodromal markers of the MDS research criteria, excluding radiotracer imaging and genetic testing. RESULTS The mean age of the 100 enrolled patients was 61.6±9.7 years; 42 were men. The most common prodromal marker in our cohort was constipation (40%), followed by MDS-UPDRS part III scores of >6 points, excluding action tremor items (39%) and hyposmia (37%). Substantia nigra hyperechogenicity was identified in 9%, and polysomnography confirmed REM sleep behavior disorder in 2% of the patients. Five of the 100 enrolled patients (5%) fulfilled the criteria for probable prodromal PD, while another 3 patients met the 50% probability threshold. CONCLUSIONS Our findings suggest, that the prevalence of prodromal PD in patients undergoing diagnostic colonoscopies may be higher compared to the general elderly population, although this should be confirmed in further studies including also matched controls not undergoing colonoscopy. The real prevalence of prodromal PD in this cohort will have to be confirmed in longitudinal follow-up. Patients undergoing diagnostic colonoscopies may be good candidates for multistep screening and inclusion in prospective trials.

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.

Fatigue, Sleep Disturbances, and Their Influence on Quality of Life in Cervical Dystonia Patients

Nonmotor symptoms (NMS) are highly prevalent in cervical dystonia (CD). In general, fatigue and sleep are important NMS that determine a decreased health‐related quality of life (HR‐QoL), but their influence in CD is unknown. The authors systematically investigated fatigue, excessive daytime sleepiness (EDS), and sleep quality in patients with CD and controls and assessed the influence of psychiatric comorbidity, pain, and dystonia motor severity. They also examined the predictors of HR‐QoL.

Validation of the Official Slovak Version of the Unified Dyskinesia Rating Scale (UDysRS).

After successful clinimetric testing of the Unified Dyskinesia Rating Scale (UDysRS), a program for translation and validation of non-English versions of the UDysRS was initiated. The aim of this study was to validate and confirm the factor structure of the Slovak translation of the UDysRS. We examined 251 patients with Parkinsons disease and dyskinesia using the Slovak version of the UDysRS. The average age of our sample was 65.2 ± 9.2 years and average disease duration was 10.9 ± 5.0 years. Slovak data were compared using confirmatory factor analysis with the Spanish data. To be designated as the official Slovak UDysRS translation, the comparative fit index (CFI) had to be ≥0.90 relative to the Spanish language version. Exploratory factor analysis was performed to explore the underlying factor structure without the constraint of a prespecified factor structure. For all four parts of the Slovak UDysRS, the CFI, in comparison with the Spanish language factor structure, was ≥0.98. Isolated differences in the factor structure of the Slovak UDysRS were identified by exploratory factor analysis compared with the Spanish version. The Slovak version of the UDysRS was designated as an official non-English translation and can be downloaded from the website of the International Parkinson and Movement Disorder Society.

α-Synuclein antibody 5G4 identifies manifest and prodromal Parkinson's disease in colonic mucosa: LETTERS: NEWOBSERVATIONS

α-Synuclein Antibody 5G4 Identifies Manifest and Prodromal Parkinson’s Disease in Colonic Mucosa The presence of colonic α-synuclein or phosphorylated α-synuclein immunoreactivity, several years preceding onset of first motor symptoms of Parkinson’s disease (PD), has been reported. Nevertheless, none of the colonic immunohistochemical methods have been shown sufficiently sensitive and specific to distinguish manifest or prodromal PD cases from healthy controls (HCs) in vivo so far. Recently, a monoclonal α-synuclein antibody (clone 5G4) has been reported to show high reactivity for disease-associated forms, including oligomers, of α-synuclein, with superior results in comparative immunohistochemical studies in the central nervous system. The aim of this study was to evaluate colonic mucosa staining using the 5G4 antibody, specific only for the diseaseassociated form of α-synuclein, in a deeply phenotyped cohort of clinically manifest PD patients, patients meeting International Parkinson and Movement Disorder Society (MDS) research criteria for prodromal PD (pPD), and HCs not meeting the pPD criteria. Patients undergoing diagnostic colonoscopies were screened for risk and prodromal markers from the MDS research criteria for prodromal PD as reported previously (see Supporting Materials, Supporting Fig. 1). Immunoreactivity for 5G4 antibody (α-syn; 1:4’000, clone 5G4; Roboscreen, Leipzig, Germany) was performed in formalin-fixed in vivo biopsy samples of the colonic mucosa of patients with manifest PD (n = 6), pPD (n = 7), and HCs (n = 17) and were evaluated by two independent and blinded raters (G.G.K., E.G.; see Supporting Materials). The criteria to consider 5G4 immunoreactivity as specific for the presence of pathological aggregates of α-synuclein in the colonic mucosa were defined after agreement as follows: (1) confirmation of the presence of neurofilament staining depicting mucosal nerve fibers and/or submucosal ganglion cells (Fig. 1A) and (2) dot-like, globular, or thread-like dark brown stained structures independent from an overlap with a cell nucleus (Fig. 1B,D). Immunoreactivity observed in mast cells or other diffuse-cell-associated 5G4 immunoreactivities (Fig. 1E) were considered as nonspecific findings. Special care was taken not to misinterpret accumulations of yellowish lipopigment as specific immunoreactivity (Fig. 1F). For detailed characteristics of our cohort and prevalence of prodromal and risk factors, see Supporting Materials and Supporting Table 1. Pathological 5G4-positive neuritic structures were present in 5 of 6 clinically manifest PD patients, 4 of 7 pPD subjects, and 2 of 17 HCs, yielding sensitivity 83.3%, specificity 88.2%, positive predictive value (PPV) 71.43%, and negative predictive value (NPV) 93.75% for distinguishing manifest PD from HCs; and sensitivity 57.1%, specificity 88.2%, PPV 66.7%, and NPV 83.3% for distinguishing pPD subjects from HCs. Inter-rater reliability for independent section evaluations showed an agreement rate of 89.8% with good intraclass correlation coefficients (0.88; 95% confidence interval = 0.81-0.93) and weighted kappa (0.76; P < 0.001). Both HCs with positive 5G4 immunostaining reported previous frequent pesticide exposure, whereas one of them had also constipation, hyposmia, and increased MDS-UPDRS part III score; however, she did not exceed the threshold for probable prodromal PD. 5G4 immunoreactivity in colonic mucosa is able to distinguish clinically manifest and prodromal PD patients from HCs. Although these results need to be confirmed in independent and larger cohorts, our study suggests a predictive value of diagnostic colon biopsies containing mucosal tissue with nerve structures. For detailed discussion, see Supporting Materials.

The frequency and self-perceived impact on daily life of motor and non-motor symptoms in cervical dystonia

Evidence suggests that non‐motor symptoms (NMS) are the most important predictors of decreased health‐related quality of life (HR‐QoL) in patients with cervical dystonia (CD). In this study, we evaluate an NMS screening list and examine the influence of motor symptoms and NMS on HR‐QoL.