We describe the case of a 51-year-old man with Parkinson's disease (PD) presenting with motor fluctuations, who received bilateral subthalamic deep brain stimulation (DBS) with an adaptive DBS (aDBS) device, Percept™ PC (Medtronic, Inc. , Minneapolis, MN). This device can deliver electrical stimulations based on fluctuations of neural oscillations of the local field potential (LFP) at the target structure. We observed that the LFP fluctuations were less evident inside the hospital than outside, while the stimulation successfully adapted to beta oscillation fluctuations during the aDBS phase without any stimulation-induced side effects. Thus, this new device facilitates condition-dependent stimulation; this new stimulation method is feasible and provides new insights into the pathophysiological mechanisms of PD.

Edited by Lukas HuberKeywords: Retromer VPS35 VPS29 VPS26 Ubiquitin Proteasome Cation independent mannose-6-phosphate receptor SNXs a b s t r a c tRetromer is a complex of proteins that functions in the endosome-to-Golgi retrieval cargo transport pathway. VPS35 works as the central subunit of retromer to recognize the cargos and binds with VPS29 and VPS26 via distinct domains. We show that deficiency of VPS35 or VPS29 accompanies degradation of other subunits, whereas VPS26 deficiency had no effect on VPS29 and VPS35 levels. Although VPS35 forms VPS26-VPS35 and VPS29-VPS35 sub-complexes with similar efficiency in vitro, VPS26-VPS35 was more easily degradable by the ubiquitin-proteasome-system than VPS29-VPS35. These results indicate that VPS29 and VPS35 form a biologically stable sub-complex in vivo.

IntroductionChronic constipation worsens the quality of life (QOL) of patients with Parkinson’s disease (PD). Elobixibat, an ileal bile acid transporter inhibitor, is a useful laxative, but its effect on chronic constipation in patients with PD remains unclear. Therefore, we designed a placebo-controlled, randomised, double-blind study to investigate the efficacy and safety of elobixibat in patients with PD with chronic constipation.Methods and analysisThe study will consist of 2-week observation and 4-week treatment periods. Patients with clinically established PD will record the status of spontaneous bowel movements and use of rescue medications/concomitant medications in a Bowel Movement Diary from the start of the observation period at visit 1 (week −2). At visit 2 (week 0), patients will be assessed for final registration based on the diary records and physical examinations, and allocated to either the elobixibat or placebo group. Daily intake of the investigational drug will be recorded in the diary. Patients will undergo laboratory tests and answer constipation-related, PD-related and QOL-related questionnaires at visits 2 and 4 (week 4). Subjective symptoms and objective findings will be collected at visits 2, 3 (week 2) and 4. Since patients’ motor function might be improved by treatment of constipation, the use of dopamine preparations will also be monitored. Bowel movement data and other parameters will be compared between groups.Safety information will be collected as adverse events, specifically focusing on those occurring in association with study conduct.Ethics and disseminationThis study will be conducted in accordance with the Helsinki Declaration, the Clinical Trials Act of the Japan Ministry of Health, Labour and Welfare, and related laws and regulations. The study was approved by the Juntendo University Certified Review Board. The results will be disseminated through an online study registry (Japan Registry of Clinical Trials), presented at scientific conferences, and published in medical journals.Trial registration numberJPRN-jRCTs031200172; Pre-results.

We herein report the rare case of a 56-year-old man who suffered from heat stroke. Although he was in a coma with convulsions on arrival and developed multiorgan failure, he recovered after two weeks of successful treatments. Hyperintense signals on the right temporoparietooccipital cortex, which disappeared within one week, were demonstrated on diffusion-weighted magnetic resonance images. A diagnosis of transient cortical injury caused by heat stroke was suggested. Although the cerebellum is most susceptible to lesion formation, the mechanisms underlying heat stroke are multifactorial and may result in a variety of brain lesions.

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