Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinson\u27s disease study

\ua9 The Author(s) 2024. Estimates of the spectrum and frequency of pathogenic variants in Parkinson’s disease (PD) in different populations are currently limited and biased. Furthermore, although therapeutic modification of several genetic targets has reached the clinical trial stage, a major obstacle in conducting these trials is that PD patients are largely unaware of their genetic status and, therefore, cannot be recruited. Expanding the number of investigated PD-related genes and including genes related to disorders with overlapping clinical features in large, well-phenotyped PD patient groups is a prerequisite for capturing the full variant spectrum underlying PD and for stratifying and prioritizing patients for gene-targeted clinical trials. The Rostock Parkinson’s disease (ROPAD) study is an observational clinical study aiming to determine the frequency and spectrum of genetic variants contributing to PD in a large international cohort. We investigated variants in 50 genes with either an established relevance for PD or possible phenotypic overlap in a group of 12 580 PD patients from 16 countries [62.3% male; 92.0% White; 27.0% positive family history (FH+), median age at onset (AAO) 59 years] using a next-generation sequencing panel. Altogether, in 1864 (14.8%) ROPAD participants (58.1% male; 91.0% White, 35.5% FH+, median AAO 55 years), a PD-relevant genetic test (PDGT) was positive based on GBA1 risk variants (10.4%) or pathogenic/likely pathogenic variants in LRRK2 (2.9%), PRKN (0.9%), SNCA (0.2%) or PINK1 (0.1%) or a combination of two genetic findings in two genes (∼0.2%). Of note, the adjusted positive PDGT fraction, i.e. the fraction of positive PDGTs per country weighted by the fraction of the population of the world that they represent, was 14.5%. Positive PDGTs were identified in 19.9% of patients with an AAO ≤ 50 years, in 19.5% of patients with FH+ and in 26.9% with an AAO ≤ 50 years and FH+. In comparison to the idiopathic PD group (6846 patients with benign variants), the positive PDGT group had a significantly lower AAO (4 years, P = 9 7 10−34). The probability of a positive PDGT decreased by 3% with every additional AAO year (P = 1 7 10−35). Female patients were 22% more likely to have a positive PDGT (P = 3 7 10−4), and for individuals with FH+ this likelihood was 55% higher (P = 1 7 10−14). About 0.8% of the ROPAD participants had positive genetic testing findings in parkinsonism-, dystonia/dyskinesia- or dementia-related genes. In the emerging era of gene-targeted PD clinical trials, our finding that ∼15% of patients harbour potentially actionable genetic variants offers an important prospect to affected individuals and their families and underlines the need for genetic testing in PD patients. Thus, the insights from the ROPAD study allow for data-driven, differential genetic counselling across the spectrum of different AAOs and family histories and promote a possible policy change in the application of genetic testing as a routine part of patient evaluation and care in PD

Public understanding on geoconservation strategies at the Passagem das Pedras Geosite, Paraíba (Brazil): contribution to the Rio do Peixe Geopark Proposal

The Rio do Peixe basin, which is developed during the Lower Cretaceous, consists of the Sousa, Uiraúna-Brejo das Freiras, Pombal and Vertentes sub-basins. They have abundant ichnofauna represented by dinosaur tracks of theropods, sauropods and ornithopods, these being the main objects of geological heritage in the region. The majority of palaeontological sites are found in the Sousa basin and the most important geosite in terms of distribution of fossil footprints is Passagem das Pedras (Municipality of Sousa—Sousa basin). In 1992, this area was classified as the BValley of the Dinosaurs Natural Monument^ and initially had high-quality infrastructure and trained tour guides; however, following a period of neglect, the local infrastructure became precarious. In 2014, revitalization of the museum, kiosks and walkways in Valley was performed; however, there are inefficient measures to protect the dinosaur footprints from human and natural threats. Thus, 500 interviews with the urban and rural population of Sousa in addition to traders and teachers were done, seeking public understanding of geoconservation strategies at the Passagem das Pedras geosite. Critical analysis of the results was performed as a contribution to the proposal for the Rio do Peixe Geopark. The perception is that the geoconservation strategies are not effective in protecting the Passagem das Pedras geosite or in raising the Sousa population’s awareness as to the importance of geological heritage. The other palaeontological sites of the Sousa basin are also quite vulnerable and with deteriorating geological elements. Therefore, the region currently has low potential to become a geopark.This study was supported by CNPq, CAPES and FAPER

EuroInf 2: Subthalamic stimulation, apomorphine, and levodopa infusion in Parkinson's disease

Objective: Real‐life observational report of clinical efficacy of bilateral subthalamic stimulation (STN‐DBS), apomorphine (APO), and intrajejunal levodopa infusion (IJLI) on quality of life, motor, and nonmotor symptoms (NMS) in Parkinson's disease (PD). / Methods: In this prospective, multicenter, international, real‐life cohort observation study of 173 PD patients undergoing STN‐DBS (n = 101), IJLI (n = 33), or APO (n = 39) were followed‐up using PDQuestionnaire‐8, NMSScale (NMSS), Unified PD Rating Scale (UPDRS)‐III, UPDRS‐IV, and levodopa equivalent daily dose (LEDD) before and 6 months after intervention. Outcome changes were analyzed with Wilcoxon signed‐rank or paired t test when parametric tests were applicable. Multiple comparisons were corrected (multiple treatments/scales). Effect strengths were quantified with relative changes, effect size, and number needed to treat. Analyses were computed before and after propensity score matching, balancing demographic and clinical characteristics. / Results: In all groups, PDQuestionnaire‐8, UPDRS‐IV, and NMSS total scores improved significantly at follow‐up. Levodopa equivalent daily dose was significantly reduced after STN‐DBS. Explorative NMSS domain analyses resulted in distinct profiles: STN‐DBS improved urinary/sexual functions, mood/cognition, sleep/fatigue, and the miscellaneous domain. IJLI improved the 3 latter domains and gastrointestinal symptoms. APO improved mood/cognition, perceptual problems/hallucinations, attention/memory, and the miscellaneous domain. Overall, STN‐DBS and IJLI seemed favorable for NMSS total score, and APO favorable for neuropsychological/neuropsychiatric NMS and PDQuestionnaire‐8 outcome. / Conclusions: This is the first comparison of quality of life, nonmotor. and motor outcomes in PD patients undergoing STN‐DBS, IJLI, and APO in a real‐life cohort. Distinct effect profiles were identified for each treatment option. Our results highlight the importance of holistic nonmotor and motor symptoms assessments to personalize treatment choices. © 2019 International Parkinson and Movement Disorder Societ