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.

Real–world clinical outcomes were examined in 96 patients with migraine who were eligible for treatment with anti–calcitonin gene–related peptide (CGRP) antibodies. In 71 patients who received this treatment, three assessment tools (Migraine Disability Assessment Scale (MIDAS), Headache Impact Test (HIT–6), and Visual Analog Scale (VAS)) were used to evaluate the efficacy of the drugs. The 25 patients who declined to take anti–CGRP antibody drugs were asked about the reasons for their refusal and issues about use of these drugs. Patients with episodic migraine (EM) or chronic migraine (CM) had significantly decreased monthly migraine days (MMD) and improved daily disability after treatment with Galcanezumab or Fremanezumab. The two drugs were rated as very effective migraine prophylactics. The 50% responder rate (50%RR) for patients with CM who received Galcanezumab in the first month was significantly lower than that for patients with EM, Galcanezumab was less responsive to treatment for patients with CM. This is also the first study to evaluate the degree of daily life disability using three assessment tools concurrently. The results showed that HIT–6 and VAS, which are one–month indicators, were more sensitive than MIDAS, which is a three–month indicator. The main concerns among patients for introduction of anti–CGRP antibody drugs were the high cost and the increased frequency of hospital visits. Therefore, reduction of costs and fewer visits are needed to promote use of anti–CGRP antibody drugs with high efficacy.

Parkinson's disease involves both motor and non–motor symptoms. Physicians typically identify wearing off (WO) states based on motor symptoms. We conducted a questionnaire survey of members of the Japan Parkinson's Disease Association to investigate the occurrence and timing of non–motor symptoms associated with WO. Responses were received from 1,301 patients. Of the 676 patients who reported that they subjectively perceive motor or non–motor symptoms, 324 (47.9%) only had non–motor symptoms. Of the 568 patients with a physician–confirmed case of WO, 327 (57.6%) had developed non–motor symptoms before the confirmation of WO. Of these 327 patients, 133 (40.7%) reported that their symptoms improved with levodopa treatment. These findings suggest that in the early stages of treatment, patients should be carefully monitored for signs of WO, based on assessment of not only motor symptoms but also non–motor symptoms.

Spasticity is one of the most frequently observed symptoms in patients with cerebral palsy. Since it leads to impairments in the ability to walk and in the activities of daily living, interventions such as botulinum therapy, selective dorsal rhizotomy, and soft tissue dissection are considered available treatment options. However, non–invasive and effective treatments are required owing to the side effects of the former treatments, including pain and invasiveness. In our study, we encountered three patients with spasticity due to cerebral palsy (an 11–year–old boy, a 26–year–old man, and a 12–year–old boy) who were successfully treated with mediVR KAGURA–guided brain reprogramming therapy (virtual reality [VR] rehabilitation). All patients showed reduced spasticity and improved activities of daily living, such as walking. Since VR rehabilitation does not require hospitalization, pain, or other invasive interventions, our findings suggested that it might be effective in treating spasticity in school–aged or working–aged patients with cerebral palsy. Moreover, its ease of implementation at home or at a local facility might be an additional strength. Therefore, further studies with larger sample sizes are required.

A four–year–old boy with oculobulbar symptoms visited our hospital and was diagnosed with anti–MuSK positive antibodies. He had been prednisolone (PSL) dependent (0.5–2mg/kg/day) with tacrolimus and been worsened gradually. When he was referred to the adult neurological department at the age of 19, with a prescription of PSL of 40 mg/48 hours, he presented with chronic muscle power deterioration and atrophy even without fatigue. Symptoms were significant in the trunk and limbs with his drophead and type 2 respiratory failure with the forced vital capacity (FCV) of 0.68 L. He was not able to stay in the chair to study or to sleep in a spine position. He also showed the complications of steroids : the moon face, glaucoma, hypertension, and hyperglycemia. At age of 19, the fast–acting treatment (FT) with plasma exchanges and repeated intravenous immune globulin (IVIg) improved his symptoms in activities of daily living with the FVC of 1.7 L. Repeated IVIg in one to two months and Efgartigimod infusions showed the therapeutic effects as maintenance and allowed the decrease of oral PSL to 15 mg/day. Although there is little evidence regarding the treatment of juvenile myasthenia gravis and the transitional medicine to adults, FT can possibly play a role in various stages, including transitions of MG treatment.

The encephalitic form of myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) is a poorly understood disease. We report 3 cases of the encephalitic form of MOGAD. All of the patients presented with headache and 2 patients had fever. All of the patients developed optic neuritis (ON) during the course of the disease. The patients had abnormal cerebral blood flow or cerebral perfusion in one side of the brain. The patients were all treated with methylprednisolone, and one patient was treated with plasma exchange and intravenous immunoglobulin. The encephalitic form of MOGAD should be suspected in patients who have encephalitis with ON, headache, or abnormal cerebral blood flow on one side of the brain.

A 70–year–old man went to bed with a brazier in December X 2021. The next day, he felt ill and missed two days of work. However, the patient recovered thereafter. Twenty days after illness. He developed cognitive dysfunction. The patient visited the previous hospital, wherein a head magnetic resonance imaging scan showed leukoencephalopathy. He was suspected of delayed neurologic sequelae of carbon monoxide intoxication. He was referred to our hospital on day X+35 for hyperbaric oxygen therapy (HBOT). The patient underwent HBOT on the same day of admission. Although there was little improvement after 10 sessions, rapid improvement was observed after 30 sessions. Therefore, the patient was discharged after completing 43 sessions. After discharge, 1–month and 5–month follow–up revealed sustained improvement. HBOT has been reported to be effective in the treatment of carbon monoxide poisoning. However, there is no established theory or guidelines for the duration of treatment with HBOT. We suggest that long–term HBOT might have contributed to the improvement in symptoms in this case.

In 2010, a 48–year–old woman underwent extended thymectomy and radiation therapy for treatment of thymoma. In 2011, she came to our department because of ptosis and muscle weakness in her upper limbs and was diagnosed with generalized myasthenia gravis (MG) on the basis of an anti–acetylcholine receptor antibody level of 85 nmol/L. She underwent corticosteroid pulse therapy and plasma exchange, and her MG symptoms gradually improved. Subsequently, she was in remission for over 10 years under treatment with small amounts of dexamethasone and tacrolimus. In October 2021, she received combination anti–programmed cell death protein–1/CTLA–4 antibody therapy after surgical treatment for stage IV transverse colon cancer at our Department of Surgery. Then, she presented with generalized muscle weakness with elevated serum creatinine kinase, ptosis, and worsening of swallowing function and was diagnosed with myositis and MG crisis as an immune–related adverse event (irAE). The dexamethasone dosage was increased, and intravenous immunoglobulin was administered ; however, respiratory failure progressed, and she was placed on an artificial ventilator. On day 12 after the start of symptoms, hematemesis occurred, and upper endoscopy led to a diagnosis of gastroenteritis as an irAE. Thereafter, liver enzymes rapidly increased, and because no other diseases were involved, a diagnosis of hepatitis by an irAE was made. Plasma exchange therapy was performed, but the patient did not respond to treatment, and oral mycophenolate mofetil for hepatitis was not effective. She subsequently developed pneumonia due to cytomegalovirus and died on day 94 after the start of symptoms. This case highlights that physicians must be aware that patients with MG may experience a variety of irAEs when treated with immune–checkpoint inhibitors, even when they are in remission.