Endoscopic Complications Are More Frequent in Levodopa-Carbidopa Intestinal Gel Treatment via JET-PEG in Parkinson's Disease Patients Compared to Nutritional PEG in Non-Parkinson's Disease Patients.

Background: To date, no studies comparing complication rates between patients with nutritional percutaneous endoscopic gastrostomy (N-PEG) and Parkinson's disease (PD) patients with percutaneous endoscopic gastro-jejunostomy (JET-PEG) for treatment administration have been published. Our study aimed to compare complication rates and the number of re-endoscopies between N-PEG and JET-PEG patients. Methods: Individuals requiring N-PEG or JET-PEG insertion between 2014 and 2021 were included in this single-center retrospective observational study. Complications were divided into time-related medical and technical complications. Reasons for post-insertion re-endoscopies and their number were also analyzed. Results: Eighty-seven subjects, 47 (54.02%) in JET-PEG group and 40 (45.98%) in the N-PEG group, were included. Early and technical complications were more frequent in JET-PEG vs. N-PEG subjects (70% vs. 10% [p < 0.001], and 54.5% vs. 5.1% [p < 0.001], respectively). The presence of psychiatric disease was associated with a higher number of early complications (p < 0.002). All three types of complications were significantly more frequent in subjects where a healthcare professional did not handle PEG (p < 0.001). Subjects with JET-PEG required a higher number of re-endoscopies compared to the N-PEG group (57.1% vs. 35%, p = 0.05). Conclusions: Complications are significantly more common in individuals with JET-PEG than those with N-PEG, which can be attributed to higher mobility in PD patients.

Heart Rate Variability in evaluation of autonomic dysfunction in idiopathic REM-sleep behaviour disorder.

INTRODUCTION: Nearly 80% of people diagnosed with idiopathic REM sleep behaviour disorder (iRBD) via video-polysomnography (v-PSG) are expected to be in the prodromal stage of an alpha-synucleinopathy. Signs of autonomic dysfunction can appear earlier than motor or cognitive alpha-synucleinopathy symptoms. Heart Rate Variability (HRV) can potentially be an objective measurement of autonomic dysfunction, and furthermore can be obtained directly from v-PSG. OBJECTIVES: The aim of this study was to evaluate dysautonomia in iRBD subjects using HRV obtained during different sleep stages and wakefulness from v-PSG. MATERIAL AND METHODS: Subjects positively screened by an RBD screening questionnaire (RBD-SQ) underwent v-PSG to diagnose RBD. HRV obtained from v-PSG recordings was correlated to dysautonomia evaluated from a Non-Motor Symptoms Scale (NMSS) questionnaire. Optimal cut-off values of HRV parameters to predict dysautonomia were calculated using receiver operating characteristics (ROC) - area under the curve (AUC) analysis. The effect of confounder variables was predicted with binomial logistic regression and multiple regression analyses. RESULTS: Out of 72 positively screened subjects, 29 subjects were diagnosed as iRBD (mean age 66 ± 7.7 years) by v-PSG. Eighty-three per cent of the iRBD subjects in our cohort were at the time of diagnosis classified as having possible or probable prodromal Parkinson's Disease (pPD) compared to zero subjects being positively screened in the control group. The iRBD-positive subjects showed significant inverse correlations of NMSS score, particularly to log low-frequency (LF) component of HRV during wakefulness: r = -0.59 (p = 0.001). Based on ROC analysis and correlation between NMSS score, log LF during wakefulness (AUC 0.74, cut-off 4.69, sensitivity 91.7%, specificity 64.7%, p = 0.028) was considered as the most accurate predictor of dysautonomia in the iRBD group. Apnoea-hypopnoea index (AHI) negatively predicted dysautonomia in the iRBD group. None of the HRV components was able to predict the presence of iRBD in the full cohort. Age, gender, and PSG variables were significant confounders of HRV prediction. CONCLUSIONS: The presented study did not confirm the possibility of using HRV from v-PSG records of patients with iRBD to predict dysautonomia expressed by questionnaire methods. This is probably due to several confounding factors capable of influencing HRV in such a cohort.

Comparison in detection of prodromal Parkinson's disease patients using original and updated MDS research criteria in two independent cohorts.

INTRODUCTION: MDS research criteria for prodromal Parkinson's disease (pPD) were published in 2015 and updated in 2019. We aimed to determine the difference in pPD patient detection rates in two cohorts recruited via gastrointestinal symptoms (PARCAS study) and the presence of a probable REM sleep behaviour disorder (PDBIOM study) using the original and updated criteria. METHODS: We evaluated all risk and prodromal markers, except genetic testing, plasma urate and physical inactivity, in both cohorts and DaT scan, diabetes mellitus type II and cognitive deficit in the PARCAS cohort. Thresholds of 50% probability for possible pPD and 80% for probable pPD were used. RESULTS: PPD status as identified by the original/updated criteria showed differences for probable pPD (n = 8/9; original/updated criteria) and possible pPD (n = 9/13) in the PARCAS cohort (total n = 158), as well as for probable pPD (n = 19/21) and possible pPD (n = 6/3) in the PDBIOM cohort (total n = 48). A high concordance rate was found between the two criteria sets (p < 0.001 for all groups). CONCLUSION: All probable pPD cases remained in the same category after evaluation with both criteria; three possible pPD cases based on the original criteria exceeded the threshold for probable pPD based on the updated criteria, and five possible new pPD cases were detected, with only one shift in the opposite direction. The updated MDS pPD research criteria tend to identify more patients as positive, yet their accuracy needs to be determined in prospective studies.

Scoring Algorithm-Based Genomic Testing in Dystonia: A Prospective Validation Study.

BACKGROUND: Despite the established value of genomic testing strategies, practice guidelines for their use do not exist in many indications. OBJECTIVES: We sought to validate a recently introduced scoring algorithm for dystonia, predicting the diagnostic utility of whole-exome sequencing (WES) based on individual phenotypic aspects (age-at-onset, body distribution, presenting comorbidity). METHODS: We prospectively enrolled a set of 209 dystonia-affected families and obtained summary scores (0-5 points) according to the algorithm. Singleton (N = 146), duo (N = 11), and trio (N = 52) WES data were generated to identify genetic diagnoses. RESULTS: Diagnostic yield was highest (51%) among individuals with a summary score of 5, corresponding to a manifestation of early-onset segmental or generalized dystonia with coexisting non-movement disorder-related neurological symptoms. Sensitivity and specificity at the previously suggested threshold for implementation of WES (3 points) was 96% and 52%, with area under the curve of 0.81. CONCLUSIONS: The algorithm is a useful predictive tool and could be integrated into dystonia routine diagnostic protocols. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Clinically relevant copy-number variants in exome sequencing data of patients with dystonia.

INTRODUCTION: Next-generation sequencing is now used on a routine basis for molecular testing but studies on copy-number variant (CNV) detection from next-generation sequencing data are underrepresented. Utilizing an existing whole-exome sequencing (WES) dataset, we sought to investigate the contribution of rare CNVs to the genetic causality of dystonia. METHODS: The CNV read-depth analysis tool ExomeDepth was applied to the exome sequences of 953 unrelated patients with dystonia (600 with isolated dystonia and 353 with combined dystonia; 33% with additional neurological involvement). We prioritized rare CNVs that affected known disease genes and/or were known to be associated with defined microdeletion/microduplication syndromes. Pathogenicity assessment of CNVs was based on recently published standards of the American College of Medical Genetics and Genomics and the Clinical Genome Resource. RESULTS: We identified pathogenic or likely pathogenic CNVs in 14 of 953 patients (1.5%). Of the 14 different CNVs, 12 were deletions and 2 were duplications, ranging in predicted size from 124bp to 17 Mb. Within the deletion intervals, BRPF1, CHD8, DJ1, EFTUD2, FGF14, GCH1, PANK2, SGCE, UBE3A, VPS16, WARS2, and WDR45 were determined as the most clinically relevant genes. The duplications involved chromosomal regions 6q21-q22 and 15q11-q13. CNV analysis increased the diagnostic yield in the total cohort from 18.4% to 19.8%, as compared to the assessment of single-nucleotide variants and small insertions and deletions alone. CONCLUSIONS: WES-based CNV analysis in dystonia is feasible, increases the diagnostic yield, and should be combined with the assessment of single-nucleotide variants and small insertions and deletions.