Parkinson’s disease (PD) is a common neurodegenerative disorder, with a continuously increasing prevalence. With improved clinical and therapeutic management of PD, more patients reach later stages of the disease, meaning they may face new clinical problems that were not commonly approached. This gave way to the description of a new PD stage, late-stage PD (LSPD), which is clinically discernible from the advanced-stage one. Therefore, LSPD patients have new and different needs, regarding pharmacological and non pharmacological interventions, including palliative care and multidisciplinary teams. LSPD patients constitute an‘orphan population’, who traditionally was excluded from previous studies, due to its high disability. With this manuscript, we intend to review specific management challenges of LSPD patients, covering this new concept and its clinical features, how to assess these patients, therapeutic recommendations, as well as discussing ongoing research and future perspectives.

Mobile health (mHealth) has emerged as a potential solution to providing valuable ecological information about the severity and burden of Parkinson’s disease (PD) symptoms in real-life conditions. Objective: The objective of our study was to explore the feasibility and usability of an mHealth system for continuous and objective real-life measures of patients’ health and functional mobility, in unsupervised settings. Methods: Patients with a clinical diagnosis of PD, who were able to walk unassisted, and had an Android smartphone were included. Patients were asked to answer a daily survey, to perform three weekly active tests, and to perform a monthly in-person clinical assessment. Feasibility and usability were explored as primary and secondary outcomes. An exploratory analysis was performed to investigate the correlation between data from the mKinetikos app and clinical assessments. Results: Seventeen participants (85%) completed the study. Sixteen participants (94.1%) showed a medium-to-high level of compliance with the mKinetikos system. A 6-point drop in the total score of the Post-Study System Usability Questionnaire was observed. Conclusions: Our results support the feasibility of the mKinetikos system for continuous and objective real-life measures of a patient’s health and functional mobility. The observed correlations of mKinetikos metrics with clinical data seem to suggest that this mHealth solution is a promising tool to support clinical decisions.

Myocyte enhancer factor 2C (MEF2C) is increasingly expressed in mice along with breast cancer brain metastases (BCBM) development. We aim to ascertain MEF2C expression in human BCBM, establish the relationship with disease severity, disclose the involvement of vascular endothelial growth factor receptor-2 (VEGFR-2) and β-catenin, also known as KDR and CTNNB1, respectively, and investigate if matched primary tumors express the protein. We studied resected BCBM for the expression of MEF2C, VEGFR-2, and ß-catenin, as well as proliferation (Ki-67) and epithelial (pan Cytokeratin) markers, and related experimental and clinical data. MEF2C expression was further assessed in matched primary tumors and non-BCBM samples used as controls. MEF2C expression was observed in BCBM, but not in controls, and was categorized into three phenotypes (P): P1, with extranuclear location; P2, with extranuclear and nuclear staining, and P3, with nuclear location. Nuclear translocation increased with metastases extension and Ki-67-positive cells number. P1 was associated with higher VEFGR-2 plasma membrane immunoreactivity, whereas P2 and P3 were accompanied by protein dislocation. P1 was accompanied by β-catenin membrane expression, while P2 and P3 exhibited β-catenin nuclear translocation. Primary BC samples expressed MEF2C in mammary ducts and scattered cells in the parenchyma. MEF2C emerges as a player in BCBM associated with disease severity and VEGFR-2 and β-catenin signaling.

Dravet syndrome (DS) is associated with severely refractory seizures. Recent studies suggest possible antiepileptic effects of serotonergic drugs. We report the case of a 25-year-old woman with DS-related epilepsy (SCN1A mutation), with daily seizures since childhood, associated with developmental delay. Several antiepileptic drug regimens were tested, without clear benefit. Over the years, she maintained a pattern of diurnal and nocturnal seizures, with a nocturnal predominance averaging two tonic–clonic seizures per night, with periods of seizure clusters. On routine electroencephalography (EEG), frequent, subtle myoclonic seizures during sleep were detected. A seizure-free period or significant reduction in seizure frequency was never attained. Trazodone was started due to insomnia. This led to a remarkable as well as long-standing clinical and neurophysiological improvement: less than one reported tonic–clonic seizure per month during the next 18 months, reduction in interictal epileptiform activity (170/h vs. 30/h of sleep), myoclonic seizures (90/h vs. 0.7/h of sleep), and tonic–clonic seizures (2/night to 0) on video-EEG. Serotonergic pathway modulation effects on DS-related epilepsy were observed in animal studies, in addition to small case series using lorcaserin and fenfluramine. To the best of our knowledge, no clinical data exist showing that trazodone may be an efficacious agent in patients with DS. Despite limitation of an isolated case with possible chance factors, our data, given the striking effect, provide this clinical evidence for the first time, and may have important clinical implications in patients with DS, reinforcing the need for further research on this subject.