In these days, open innovation is critical element to develop innovative treatment methods in neurological disease and globally, bio–ventures have become key players in drug discovery and development. The Japanese government is working on promoting open innovation, including infrastructure development and institutional policy formulation. The role played by academia is also important, and the Japanese Society of Neurological Therapeutics that promote drug discovery are actively involved in activities that serve as the foundation for such open innovation.

Cultural elements also have a significant impact on the promotion of open innovation. The characteristics of the Japanese people, such as their diligence, strong sense of responsibility, patience, prudence, cooperativeness and harmoniousness, consideration for others, continuous improvement orientation, and quality orientation, have led to excellent results in basic and clinical research. On the other hand, these characteristics can sometimes be incompatible with open innovation. Recognizing such challenges is also necessary to rapidly connect Japan's excellent research to clinical applications in the global ecosystem and provide better treatment methods to the patients.

Neuropalliative care and advance care planning (ACP) for Parkinson disease (PD) have not yet begun in Japan. ACP is an important part of care for people with PD. The development of ACP begins with a discussion among the patient/care partners, healthcare providers, caregivers, and other stakeholders. Medical and caregivers need to be well educated about the prognosis and other aspects of PD, and efforts should be made to ensure that those who receive ACP have an accurate understanding of the disease. By understanding care, palliative care, and ACP well enough to practice medicine, especially in the outpatient setting, PD treatment goes beyond the current drug–centered medicine and addresses a different aspect of the disease. This will bring a new perspective to medicine for the medical profession and provide a more comfortable life for PD patients, families, and care partners.

Advance care planning is one of the most valuable to total care for Parkinson disease (PD). However it is very difficult to provide appropriate opportunity for patients and their family members to think about late–stage medical treatment and end–stage care. The difficulty is due to the variety of clinical course of individuals with PD, that is PD is never single pathogenic disease, but complexed or clustered pathogenesis. Impaired cognition is another reason of difficulty. Almost 30% of PD patients are already suffered from cognitive decline, and over 80% of PD patients are suggested to have dementia according to Sydney cohort study. Initiation of ACP should be set during preserved cognition for self–determination. Device aided therapy (DAT) is admitted for motor complication of PD and has possibility to change aPD and late–stage PD life. That is the reason why DAT should be involved in ACP of PD, although it is not sure that DAT improve mortality of PD.

One of the main causes of death of PD patients is pneumonia. During treatment pneumonia, tracheostomy and mechanical ventilation are considered due to severity of pneumonia and genera condition. Sever dysphagia frequently requires nasogastric tube or gastrostomy tube feeding to maintain nutritional status. Physician should explain air way and feeding pathway management of advanced stage and that will support patients to imagine ACP.

With levodopa and many other replacement therapies, the quality of life of patients with Parkinson disease offers significant advantages over other neurodegenerative diseases. However, as the disease progresses, wearing–off and dyskinesia occur more frequently, and the patient's QOL gradually declines ; as QOL declines, it becomes difficult to ensure the patient's quality of life even with the best drug choices. Therefore, it is important to collaborate with community medical services such as home–visit medical care, home nursing care, and nursing homes. In the past, the term “collaboration” has often referred to bridging to the community and then leaving it up to the community. In this manuscript, I will report on our experience of regional collaboration at the Department of Neurology, Osaka University School of Medicine. In particular, I believe that the key point is how to ensure the quality of medical care for Parkinson disease patients in cooperation with the local community while enhancing the nursing support established by the local community. We believe that the role of core hospitals in the future will be to move away from hospital–based Parkinson disease care, which has focused on drug selection, to comprehensive PD care in the community from a broad perspective, including nursing care, rehabilitation, nutritional management, home modification, and facility enrichment.

Advance care planning (ACP) is a process of planning future medical care for the time when patients become unable to make their own decisions, and not an event. During this process, patients explore, discuss, articulate, and document their preferences. Our neurology hospital includes neurologists, nurses, and rehabilitation therapists specializing in neurological diseases, medical consultants, and registered dietitians who contribute their respective expertise to ACP. Our values are as follows: “Relationships of trust,” “Value what the patient values,” “Never give up or leave the patients alone,” and “Share the patient’s choices and thoughts with the family and care staff.” The most crucial factor of ACP is to support patients with Parkinson disease so that they can receive treatment with a peaceful mindset and live fulfilling lives in their own way because it requires long–term treatment that involves various factors such as outlook on life, family relationships, and living environment, and patients themselves have to make difficult choices. We would move forward together, intending to participate in the decision–making process, and sharing the concerns. For treating Parkinson disease, the importance of a comprehensive approach that considers not only diagnosis, treatment, and environmental preparation but also ACP, including its psychological and social significance will increase significantly.

Parkinson disease (PD) patients eligible for home care are categorized into the late and end–stage, experiencing motor symptoms resistant to treatment, prominent non–motor symptoms. In home care, physicians have the opportunity to visit patients at their homes, gaining insights into their daily lives and directly meeting caregivers. This enables tailored explanations considering the patient's and family's cognitive functions, values, life perspectives, and economic circumstances. However, it's important to note that PD patients receiving home care often suffer from cognitive decline and executive dysfunction, making it challenging to assess their capacity for decision–making accurately. Additionally, the private and enclosed nature of home visits raises the risk of potential legal liabilities for physicians. Thus, it is crucial not only to utilize decision support guides but also to involve multi–disciplinary in the decision–making process.

It has been reported that ACP is rarely carried out in PD, even as symptoms progress, cognitive function declines, or the disease reaches its end–stage. The lack of a direct link between PD diagnosis and mortality, coupled with the variability in disease progression, are contributing to the delayed implementation of ACP.

PD lacks a curative therapy, making it suitable for palliative care from the time of diagnosis. In contrast to conditions like cancer, transitioning to home care itself does not equate to a shift to palliative care. With the expansion of options like Device Aided Therapy (DAT), even home–based patients may aspire to DAT. But this could potentially become life–prolonging care in the end–stage. Hence, clear policies regarding the introduction and discontinuation of DAT in ACP are imperative.

Furthermore, some home–based PD patients may not want to spend their final days at home. Simultaneously, some reports suggest that ACP may facilitate the possibility of patients spending their final moments at home, emphasizing the importance of proactive ACP discussions.

We examined the actual situation of Advance Care Planning (ACP) for patients with neurological diseases from the viewpoint of general home care physicians and their requests to neurologists.

The transition from treatment under a specialist to a home care physician is considered to be a time for patients to feel the progression of their disease. Since it is a good chance for them to think about the future, we felt that it would be good to share information on ACP that has been performed up to that point. We also feel that cooperation with specialists is necessary even after the transition to home care. We hope that a system utilizing ITC will be widely established so that patients can monitor their condition without having to go to the hospital.

外来通院する片頭痛患者で抗calcitonin gene–related peptide（CGRP）抗体薬が適応であった96例を対象に実臨床における症状の評価方法と転帰を検証した．同薬を投与した71例（galcanezumab 38例，fremanezumab 33例）では3種類の指標（migraine disability assessment scale（MIDAS），headache impact test（HIT–6），visual analog scale（VAS））を用いて，投与開始後1，2，3ヵ月後にその予防効果を検証した．また同薬導入を拒否した25名の片頭痛患者に拒否理由についてアンケートを実施し，抗CGRP抗体薬の導入促進についての課題を考察した．抗CGRP抗体薬の効果については反復性片頭痛患者（epsodic migraine：EM），慢性片頭痛患者（chronic migraine：CM）ともに毎月の片頭痛日数（monthly migraine days：MMD）は有意に減少し，日常生活支障度も有意に改善していることからgalcanezumab，fremanezumabは片頭痛予防薬として有効性が高い薬剤と評価できた．また，最初の1ヵ月におけるいずれかの抗CGRP抗体製剤を投与したCM患者群，galcanezumabを投与したCM患者群の50%レスポンダー率（50%RR）はEM患者群よりも有意に低く，いずれかの抗CGRP抗体製剤を投与したCM患者群，galcanezumabを投与したCM患者は治療早期に反応しにくいことが示唆された．本検討は3種類の評価方法で日常生活支障度評価を行った初めての検討であるが，治療効果を捉える感度は，3ヵ月指標のMIDASより1ヵ月指標となるHIT–6やVASの方が優れていた．一方，抗CGRP抗体薬を拒否した患者では，負担と受診頻度が増える事が拒否の大きな理由であり，費用を抑える事，受診頻度が増えない工夫をする事が，高い予防効果を有する抗CGRP抗体薬の導入促進につながると思われた．

Parkinson病（Parkinson Disease：PD）の症状には運動症状と非運動症状があるが，wearing–off（WO）の有無は主に運動症状の変動で判断されている．本研究はWOを伴う非運動症状の発現状況や時期等を明らかにするために「全国パーキンソン病友の会」（Japan Parkinson's disease association：JPDA）会員を対象にアンケート調査を行った．結果，1,301名の回答を得た．levodopa製剤を服用している患者676名のうち，WOを伴う非運動症状が認められた患者は324名（47.9%）であった．また，WOと診断されている患者568名のうち，WO診断以前から非運動症状が出現していた患者は327名（57.6%）であった．この327名のうち，levodopa製剤で症状が改善すると回答した患者は133名（40.7%）であった．本研究から，早期治療期において，運動症状だけでなく非運動症状についてもWOの兆候に十分に注意すべきであると示唆された．

痙縮は脳性麻痺患者で最も頻繁に認められる症候の1つである．歩行機能や日常生活動作能力の低下に繋がるため，ボツリヌス療法や選択的脊髄後根切断術，軟部組織解離術等の介入手段が存在するが，副作用による影響や治療による疼痛，侵襲性などが存在するため非侵襲的かつ効果的な治療が望まれている．今回我々は，脳性麻痺による痙縮を有する3例（11歳の男児，26歳の成人期男性，12歳男児）にmediVRカグラ^®ガイド下脳再プログラミング療法を行い，痙縮の改善や各種日常生活動作能力の改善が得られた症例を経験した．VRリハには入院や痛みを伴う侵襲的な介入を必要としないため，学齢期や就労期の脳性麻痺患者の痙縮治療に対する有用性が示唆されたと考えた．また，自宅や施設での実施容易性も強みであると考えた．今後症例数を集積したさらなる検討が望まれる．

症例は20歳男性．4歳時に眼筋障害で発症し，胸腺腫非合併，抗アセチルコリンレセプター（acetylcholine receptor antibody：AChR）抗体陰性，抗筋特異的チロシンキナーゼ（muscle–specific tyrosine kinase：MuSK）抗体が陽性であった．Tacrolimsを併用するもprednisolone依存下に緩徐に増悪し，19歳時移行医療が適応された際，prednisolone 40 mg/48時間毎の内服で，眼筋・咽頭筋・呼吸筋・四肢筋力の慢性的な低下と筋萎縮がみられ，%forced vital capacity（FVC）17.3%の呼吸障害のほか，首下がりが顕著で在宅療養をしていた．血漿交換やintravenous immunoglobulin therapy（IVIg）を使用し，数ヶ月で首下がりの改善と%FVCが39.8%と改善した．IVIgとefgartigimodによる維持的な治療，および内服のcyclosporinへの変更を行い，約1年でprednisolone 15 mg/日まで漸減できた．小児発症で難治長期経過例でも速効性治療を取り入れることで，症状の改善効果や維持効果が認められる．

ミエリンオリゴデンドロサイト糖蛋白抗体関連疾患（myelin oligodendrocyte glycoprotein antibody associated disease：MOGAD）は多彩な臨床病型を呈するが，なかでも自己免疫性脳炎を表現型とする，脳炎型MOGADについては未だ知見が少ない．今回，我々は脳炎型MOGAD 3例を経験した．全例で頭痛，視神経炎を認め，2例で37.5°C以上の発熱を認めた．全例で脳血流や脳灌流に左右差を認めた．全例に対してmethylprednisolone療法を行い，1例は血漿交換と免疫グロブリン大量静注療法を併用し，全例で症状が改善した．視神経炎を合併もしくは既往に持つ脳炎や，頭痛を伴う脳炎，脳血流の左右差を認める脳炎では脳炎型MOGADを鑑別に挙げるべきである．

症例は70歳男性．2021年12月X日に火鉢をつけたまま就寝し，翌日から気分不良が出現し2日間仕事を休んだが以降は普段通りに回復した．X+20日頃より遂行機能障害が出現し，前医にて頭部MRI検査で白質脳症を認め，間歇型一酸化炭素(CO)中毒を疑われ，高気圧酸素治療（Hyperbaric oxygen therapy：HBOT）目的にX+35日目に当科を紹介受診した．同日からHBOTを開始し，10回終了後では症状の改善は乏しかったが，30回終了頃より認知機能検査の急激な改善を認め，合計43回で治療終了し退院した．退院1ヵ月後，5ヵ月後で認知機能を評価したが改善を維持できていた．

CO中毒の治療にHBOTが有効とされているが定説は得られておらず，また治療期間も定まっていない．本症例は計43回に及ぶ長期間のHBOTが症状改善に寄与したと考え，文献的考察を加えて報告する．

患者は48歳，女性．既往歴，胸腺腫．2002年に眼瞼下垂と上肢の筋力低下が出現し当科受診した．抗アセチルコリン受容体抗体（抗ACh–R抗体）陽性，エドロホニウム試験陽性であり重症筋無力症（myasthenia graves：MG）の診断で，副腎皮質ステロイドパルス療法，血漿交換を施行した．その後は少量の免疫抑制剤の内服で寛解状態を維持していた．2021年10月，横行結腸癌stage Ⅳbと診断され，外科的治療後に免疫チェックポイント阻害薬（immune–checkpoint inhibitors：ICIs）の2剤併用療法を受けた．その後，血清CK値上昇，全身の筋力低下，眼瞼下垂，嚥下機能悪化を認め，免疫関連副作用（immune–related adverse events：irAE）による筋炎とMGのクリーゼ合併と診断され，その後，呼吸障害が出現し，人工呼吸器管理となった．Dexamethasoneの増量，免疫グロブリン大量療法，血漿交換を行うも効果はなかった．その後，irAE腸炎・肝炎の合併を来し，第94病日に永眠した．MG治療中の患者では寛解期であってもICIsを使用する場合は多彩なirAEを合併する可能性があり，注意が必要と思われた．