Background Pembrolizumab is an immune-checkpoints inhibitor that enhances the immune response against cancer cells and therefore is useful for the treatment of several carcinomas. However, pembrolizumab sometimes perturbs the immune system resulting in various autoimmune neurological complications. In this situation, autoimmune myositis due to pembrolizumab is a rare but not-negligible complication. Here, we report two cases of autoimmune myositis due to pembrolizumab, with systemic myositis involving levator palpebrae superioris, extraocular and hindneck muscles. Case presentation Case 1 was a 78-year-old man with advanced urinary cancer referred to the neurological ward presenting with bilateral ptosis, restriction of eye movements, dropped head and weakness in the lower extremities after pembrolizumab administration. His blood examination showed elevated serum levels of creatine kinase with positive anti-PM-Scl 75 and anti-signal recognition particle antibodies. Needle electromyography and MRI suggested systemic inflammatory myopathy. There were no findings to indicate myocardial involvement on electrocardiogram or echocardiogram. Administration of intravenous methylprednisolone following plasma exchange ameliorated creatine kinase levels and inhibited the progression of clinical symptoms. Case 2 was a 72-year-old female with lung cancer and multiple metastasis, including lymph nodes and brain. She presented with back pain, right-sided ptosis, weakness of her neck extensors and flexors and elevated serum creatine kinase after receiving pembrolizumab. Although myositis specific autoantibodies were negative, needle electromyography and MRI suggested systemic inflammatory myopathy and muscle biopsy indicated necrotizing myopathy. There were no signs indicating heart dysfunction and her electrocardiogram was normal. Clinical symptoms and serum creatine kinase levels were ameliorated after the administration of intravenous methylprednisolone. Conclusions Both cases showed atypical extensive inflammatory myositis including levator palpebrae superioris, extraocular and hindneck muscles, resembling myasthenia gravis (MG), but they did not have MG-related antibodies. Edrophonium test was negative and showed no daily fluctuation. Two previously reported cases also presented with systemic necrotizing systemic myositis involving extraocular and facial muscles caused by pembrolizumab. Idiopathic inflammatory myositis evolving levator palpebrae superioris and ocular muscles is quite rare; however, myositis due to immune-checkpoint inhibitors may preferentially involve these muscles. This case report will alert physicians to the possibility of systemic inflammatory myopathy evolving levator palpebrae superioris, extraocular and hindneck muscles mimicking MG due to pembrolizumab.

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.

DBS Think Tank IX was held on August 25–27, 2021 in Orlando FL with US based participants largely in person and overseas participants joining by video conferencing technology. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers and researchers (from industry and academia) can freely discuss current and emerging deep brain stimulation (DBS) technologies as well as the logistical and ethical issues facing the field. The consensus among the DBS Think Tank IX speakers was that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. After collectively sharing our experiences, it was estimated that globally more than 230,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. As such, this year’s meeting was focused on advances in the following areas: neuromodulation in Europe, Asia and Australia; cutting-edge technologies, neuroethics, interventional psychiatry, adaptive DBS, neuromodulation for pain, network neuromodulation for epilepsy and neuromodulation for traumatic brain injury.

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