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Objective: Short‐term outcomes of deep brain stimulation of the anterior nucleus of the thalamus (ANT‐DBS) were reported for people with drug‐resistant focal epilepsy (PwE). Because long‐term data are still scarce, the Medtronic Registry for Epilepsy (MORE) evaluated clinical routine application of ANT‐DBS. Methods: In this multicenter registry, PwE with ANT‐DBS were followed up for safety, efficacy, and battery longevity. Follow‐up ended after 5 years or upon study closure. Clinical characteristics and stimulation settings were compared between PwE with no benefit, improvers, and responders, that is, PwE with average monthly seizure frequency reduction rates of ≥50%. Results: Of 170 eligible PwE, 104, 62, and 49 completed the 3‐, 4‐, and 5‐year follow‐up, respectively. Most discontinuations (68%) were due to planned study closure as follow‐up beyond 2 years was optional. The 5‐year follow‐up cohort had a median seizure frequency reduction from 16 per month at baseline to 7.9 per month at 5‐year follow‐up (p <.001), with most‐pronounced effects on focal‐to‐bilateral tonic–clonic seizures (n = 15, 77% reduction, p =.008). At last follow‐up (median 3.5 years), 41% (69/170) of PwE were responders. Unifocal epilepsy (p =.035) and a negative history of epilepsy surgery (p =.002) were associated with larger average monthly seizure frequency reductions. Stimulation settings did not differ between response groups. In 179 implanted PwE, DBS‐related adverse events (AEs, n = 225) and serious AEs (n = 75) included deterioration in epilepsy or seizure frequency/severity/type (33; 14 serious), memory/cognitive impairment (29; 3 serious), and depression (13; 4 serious). Five deaths occurred (none were ANT‐DBS related). Most AEs (76.3%) manifested within the first 2 years after implantation. Activa PC depletion (n = 37) occurred on average after 45 months. Significance: MORE provides further evidence for the long‐term application of ANT‐DBS in clinical routine practice. Although clinical benefits increased over time, side effects occurred mainly during the first 2 years. Identified outcome modifiers can help inform PwE selection and management. [ABSTRACT FROM AUTHOR]

Introduction: Circadian rhythms (CRs) orchestrate intrinsic 24-hour oscillations which synchronize an organism's physiology and behaviour with respect to daily cycles. CR disruptions have been linked to Parkinson's Disease (PD), the second most prevalent neurodegenerative disorder globally, and are associated to several PD-symptoms such as sleep disturbances. Studying molecular changes of CR offers a potential avenue for unravelling novel insights into the PD progression, symptoms, and can be further used for optimization of treatment strategies. Yet, a comprehensive characterization of the alterations at the molecular expression level for core-clock and clock-controlled genes in PD is still missing. Methods and analysis: The proposed study protocol will be used to characterize expression profiles of circadian genes obtained from saliva samples in PD patients and controls. For this purpose, 20 healthy controls and 70 PD patients will be recruited. Data from clinical assessment, questionnaires, actigraphy tracking and polysomnography will be collected and clinical evaluations will be repeated as a follow-up in one-year time. We plan to carry out sub-group analyses considering several clinical factors (e.g., biological sex, treatment dosages, or fluctuation of symptoms), and to correlate reflected changes in CR of measured genes with distinct PD phenotypes (diffuse malignant and mild/motor-predominant). Additionally, using NanoStringⓇ multiplex technology on a subset of samples, we aim to further explore potential CR alterations in hundreds of genes involved in neuropathology pathways. Discussion: CLOCK4PD is a mono-centric, non-interventional observational study aiming at the molecular characterization of CR alterations in PD. We further plan to determine physiological modifications in sleep and activity patterns, and clinical factors correlating with the observed CR changes. Our study may provide valuable insights into the intricate interplay between CR and PD with a potential to be used as a predictor of circadian alterations reflecting distinct disease phenotypes, symptoms, and progression outcomes. [ABSTRACT FROM AUTHOR]