According to estimates by the Ministry of Health, Labor and Welfare, the number of dementia patients in 2012 was 4.62 million, and the number of mild cognitive impairment patients was about 4 million. The typical symptoms of Alzheimer disease (AD) include time disorientation and delayed recall disturbance. Cerebral blood flow single photon emission computed tomography (CBF–SPECT) shows poor blood flow in the posterior cingulate gyrus and/or precuneus in AD patients. In vascular dementia, cognitive impairment is milder than in AD, and there are clinical courses such as stepwise exacerbation of symptoms, and various cerebrovascular lesions are observed on brain MRI. The patients with dementia with Lewy bodies have clinical symptoms such as visual hallucinations and Parkinsonian symptoms. CBF–SPECT and MIBG myocardial scintigraphy show the decreases of occipital lobe blood flow and cardiac uptake, respectively.

At the present, acetylcholinesterase inhibitors and the NMDA receptor antagonist memantine are currently available for the treatment of AD. Although these drugs are limited to symptomatic therapy in AD patients, recently, approaches aimed at disease–modifying therapy (DMT), especially the approaches focused on amyloid β–protein (Aβ) have been developed remarkably. Clinical trials of anti–Aβ antibodies have repeatedly reported poor results, but clinical trials of anti–Aβ antibodies that target Aβ aggregates, such as aducanumab and lecanemab, have reported significant effects on the primary endpoint in phase 3 trials. In 2021, aducanumab was approved in the United States, albeit with conditions. The approval of aducanumab in Japan was subject to continued deliberation. In 2023, lecanemab was approved in the United States, and finally in Japan. Although some issues such as amyloid–related imaging abnormalities (ARIA) should be resolved, the treatment of AD is about to take a new turn at now.

Brain tumors encompass a diverse group of intracranial neoplasms affecting not only the brain parenchyma but also the meninges and cranial nerves. This inherent heterogeneity translates into a multitude of tumor types, each with distinct treatment modalities. While advancements in molecular diagnostics have refined tumor classification, optimal treatment strategies continue to evolve.

This article delves into the complexities of central nervous system (CNS) malignancies before exploring treatment options. First, the unique immunological and anatomical properties of the CNS, often referred to as “organ specificity,” are discussed. This is followed by an examination of the significance of surgical intervention for tumors deemed unresectable with curative intent. Subsequently, the role of radiation chemotherapeutic approaches is addressed. Finally, leveraging this foundational knowledge, the article explores the recent strides made in glioma therapy guided by molecular biological markers.

By elucidating these aspects, this work aims to provide a comprehensive framework for understanding the challenges and advancements in brain tumor treatment within the burgeoning field of molecular diagnostics.

Artificial Intelligence (AI) is a computer program designed to mimic human intelligence by performing functions such as learning, reasoning, and judgment. At the core of AI is machine learning, which includes supervised learning―where models learn from labeled data―and unsupervised learning, which involves identifying patterns and classifying data without labeled examples. A key component of machine learning is neural networks, inspired by human neurons arranged in layers to form a network. Deep learning is a more advanced form of neural network, which involves networks with multiple layers that have significantly enhanced AI capabilities.

AI has found applications in a wide range of medical fields, particularly in diagnosing and treating neurological disorders, accelerating rapidly. While AI's use in neuroimaging analysis is well–established, recent advancements have expanded its applications to include automatic speech recognition and natural language processing for conducting patient interviews, as well as the digitization of neurological assessments through wearable devices and video motion analysis. These advancements have made it possible to analyze neurological signs that were previously challenging to assess with AI.

Additionally, there is growing interest in using AI to analyze multi–omics data for identifying biochemical biomarkers from biological samples, such as blood and cerebrospinal fluid. With the continued evolution of AI, more accurate and predictive diagnoses are anticipated.

We review the recent advances of rehabilitation medicine. Neuromuscular electrical stimulation, non–invasive brain stimulation, brain–machine interface, robotics, transcutaneous spinal stimulation and virtual reality were applied to the rehabilitation medicine. Most of these therapies induced use–dependent plasticity and functional recovery of motor function. There were limitations and indications to apply these newly developed rehabilitation therapies. In this article, we explain the mechanism of the functional recovery and indication of each newly developed rehabilitation therapies.

In response to the evolving landscape of healthcare, particularly in digital transformation (DX), artificial intelligence (AI), and information and communication technology (ICT), the Japanese Headache Society's Clinical Improvement Committee proposed the “Digital Headache Bank” in December 2023. This initiative, aimed at aligning Japan with international healthcare innovation, emphasizes the active submission of proposals to the Ministry of Health, Labour and Welfare following approvals from central bodies like the Central Social Insurance Medical Council and the Japan Medical Association.

The objectives of the initiative encompass addressing unmet needs of headache patients, mitigating stigma, raising awareness, and fostering a paradigm shift in headache care. To achieve these goals, a “Metaverse Headache Platform” was officially approved during the Japan Headache Society's board meeting on February 21, 2024.

The Metaverse platform, set to launch on February 22, 2024, will serve as a virtual space facilitating interaction among headache patients, medical professionals, and researchers. Users, represented by anonymous avatars, can engage in continuous learning, share experiences, and seek advice, overcoming time and space constraints. The platform will also disseminate complex information on the latest headache treatments, contributing to a deeper understanding and alleviating anxiety among participants.

Activities planned for the platform include periodic seminars, patient meetings, and headache consultations. While initially free of charge, the long–term vision includes considerations for sustaining and expanding the initiative, potentially involving user fees, sponsorship, research grants, or crowdfunding.

The proposed “Digital Headache Bank” represents a strategic step for the Japanese Headache Society, positioning Japan as the one of the global leader in healthcare DX and AI. By leveraging innovative approaches such as Metaverse technology, the society aims to not only address the immediate needs of headache patients but also foster a dynamic and sustainable platform for advancing headache care and research.

Nagasaki Prefecture has four remote island medical districts (Iki, Tsushima, Kamigoto, and Goto) located around 100 to 200 km from the center of Nagasaki City. Nagasaki City and Omura City on the mainland are among the areas with the enormous excess of physicians in Japan, while the remote islands are in the exact opposite situation and can be considered a microcosm of the uneven distribution of doctors in Japan. Until now, the remote island emergency imaging and diagnosis support system has run effectively, leading to the establishment of a D–to–D type of telemedicine. In 2021, specialized medical teleconsultation of D to D to P/ D to P with D telemedicine by Nagasaki University Hospital was adopted by the Ministry of Internal Affairs and Communications for the “Development demonstration for the realization of problem-solving local 5G”. Based on the results, in 2023, the project was implemented in actual clinical practice to support attending physicians on remote islands by utilizing next–generation telecommunications technology by specialists in gastroenterology, neurology, and dermatology, where high–resolution, real–time images are considered particularly effective. In addition to the benefits of specialized medical care, such as early diagnosis and intervention for remote island patients, reduction of off–island consultations, and reform in how specialists work, human resource development for physicians and medical staff is highly anticipated.

Patients with rare diseases should have access to high–level medical care regardless of their location within the country. However, due to the scarcity of specialists in rare diseases, these patients often face significant challenges in accessing specialist medical care, requiring them to travel extensively to visit hospitals. In recent years, advancements in information and communication technology (ICT) have found applications across various sectors, including healthcare. Telemedicine, which has been included as a service under health insurance following the medical fee revision in Japan since April 2018, is a prime example of this integration. A survey among patients with HTLV–1–associated myelopathy (HAM) indicates a strong demand for online medical services, with patients and caregivers expressing high satisfaction due to the reduced burden that online medical care provides. To further promote telemedicine, it is essential to consider the relaxation of regulatory requirements, tailoring them to real–world needs and experiences.

In the past decade, there has been a growing recognition of specific nutritional pathophysiology in neurodegenerative diseases. Nutritional intervention has been discussed as a form of disease–modifying therapy. Most neurodegenerating diseases, such as amyotrophic lateral sclerosis and Parkinson disease, are progressive, depriving patients of the joy of eating during the course of the diseases. Patients may also experience weight loss and malnutrition both in the early and advanced stages of the disease. Accumulating evidence suggests that weight loss or malnutrition may exacerbate disease severity and negatively impact survival prognosis in some of neurodegenerative diseases.

A high–fat, high–calorie diet has been reported to be effective in improving survival in amyotrophic lateral sclerosis. However, effective nutritional therapies have not yet been established for most neurodegenerative diseases, and indications for gastrostomy have not been clearly defined for each neurodegenerative disease. Compared to pharmacological therapy, nutritional therapy excels in terms of safety and cost–effectiveness. As an inexpensive and side–effect–free form of disease–modifying treatment, nutritional therapy is expected to show increasing promise to the future.

Nutritional intervention is increasingly recognized as a potential disease–modifying therapy in amyotrophic lateral sclerosis (ALS), particularly for patients with rapid disease progression. This highlights the importance of identifying high–risk patients early. Hypermetabolism in ALS patients is typically associated with a poorer prognosis. However, contrasting findings from ALS model mice, where increased β–oxidation resulted in higher resting energy expenditure and extended survival. Considering the ‘Fuel switch’ phenomenon, where starvation leads to a primary focus on fat metabolism, the impact of hypermetabolism on survival may differ based on metabolic pathways.

In our study, we explored the relationship between hypermetabolism and survival in ALS patients, taking into account their nutritional status. Our findings reveal that hypermetabolism's effect on survival varies with nutritional status : it is generally linked to shorter survival in well–nourished patients but correlates with longer survival in malnourished ones. These results, highlighting the potential protective role of fat metabolism, led us to investigate the relationship between cholesterol levels and ALS prognosis. Contrary to previous studies that linked low low–density lipoprotein cholesterol (LDL) levels with reduced survival and considered high–density lipoprotein cholesterol (HDL) levels non–influential, our study indicates that high HDL levels in both sexes and low LDL levels in women might be associated with poorer prognosis.

Moreover, we assessed the impact of oral calorie intake on ALS prognosis. While the Shimizu formula for total energy expenditure (TEE) is a recognized standard, our findings suggest that actual oral intake relative to ideal body weight (IBW) is a more critical indicator of nutritional status and survival than the gap between TEE and actual intake. Based on this result, percutaneous endoscopic gastrostomy may need to be considered for patients whose oral intake does not meet TEE and is below 25 kcal/kgIBW.

Our study emphasizes the intricate relationship between metabolism, nutritional status, and ALS progression, offering valuable insights for patient management and treatment strategies.

Japan’s aging population presents significant challenges in managing Parkinson’s disease (PD), a condition whose prevalence rises with age. Approximately 1 in 100 people over 65 are affected by PD, and addressing its progression, treatment optimization, and caregiving burden requires a comprehensive approach. PD symptoms vary across disease stages: early on, clinical manifestations are mild and often respond to levodopa treatment, but in the advanced stages, motor complications such as wearing–off, dyskinesia may occur, and freezing of gait, falls, and dysphagia, which do not respond well to dopamine therapy, may become problematic. Unfortunately, current treatments struggle to adapt to these changing disease stages. Weight loss, a common non–motor symptom in PD, has gained attention due to the concept of frailty. Healthcare professionals need guidelines to manage weight loss in patients with PD effectively in their daily practice.

The causes of nutritional disorders in neurological diseases include dysphagia, cognitive dysfunction, and an increase in the energy requirement. Body weight, reflecting nutritional status, controlled by brain–mediated organ interactions. Leptin suppresses appetite and increases energy expenditure through the sympathetic nervous system from the hypothalamus. Ghrelin secreted by stomach shows appetite stimulation and energy storage effects through the hypothalamus.

In multiple system atrophy (MSA), patients needing tube feeding or tracheostomy showed a remarkable BMI decline, yet in the advanced stable stage with gastrostomy and tracheostomy, BMI increased despite low–calorie intake. We found that this advanced stage showed subcutaneous fat accumulation and increased leptin levels correlated to the autonomic symptom onset duration. It suggested that fat accumulation occurred due to leptin resistance caused by autonomic nervous system disorders. Sato et al. noted low albumin levels despite maintained body weight in the advanced MSA, indicating malnutrition.

In amyotrophic lateral sclerosis (ALS), weight loss is a poor prognostic factor, and high–calorie nutritional therapy may improve prognosis. We have shown that low ghrelin levels in male ALS patients are a poor prognostic factor, which may also be the case in MSA. Metabolic regulation via ghrelin suggests the potential for improving prognosis of some neurological diseases. We also found that serum albumin, BMI reduction rate, and prognostic nutritional index (PNI) are prognosis factors in the early stage of MSA to have diagnosis.

Appropriate nutritional intervention may improve the prognosis and quality of life in neurological diseases, underscoring the need for more evidence in MSA.

Muscular dystrophy (MD) is a genetic disease characterized by progressive muscle weakness. Regardless of the disease type of MD, chronically progressive muscle atrophy and motor function decline are important factors related to nutritional and metabolic disorders. Loss of skeletal muscle mass and decreased physical activity affect total energy expenditure. Therefore, in MD, it is necessary to estimate energy requirements by taking into account the intensity of daily life activities according to the stage of disease progression. Furthermore, since a decrease in skeletal muscle mass causes an increase in insulin resistance and the destroyed muscle tissue is replaced with adipose tissue, measures against glycolipid metabolic disorders must also be taken into consideration. Furthermore, in MD, problems related to development and growth, problems related to heart/respiratory dysfunction, and swallowing dysfunction are deeply related to nutritional/metabolic disorders. Among MDs, myotonic dystrophy (DM1) is known to exhibit a specific disorder of glycolipid metabolism, resulting from a combination of factors, primarily insulin resistance based on abnormal splicing of the insulin receptor. Hyperinsulinemia is observed in 70% of patients, although it is estimated that the incidence of diabetes mellitus with DM1 in Japan is about 20% based on the Neuromuscular Patient Registry (Remudy) data survey. Studies using continues glucose monitoring have pointed out that there are many cases in which hypoglycemia occurs on a daily basis even without any subjective symptoms. Additionally, lipid abnormalities and liver dysfunction are often complicated in DM1. Glycolipid metabolic disorders and liver dysfunction are closely related, so sufficient caution should be taken. Metabolic disorders are complications that could be treated with current knowledge and technology. Nutritional therapy is one of the important modifying treatments in MD.

The Nakajima study is a population–based longitudinal cohort study that investigates cognitive decline in older adults. The study was conducted in Nakajima, in Nanao City of Ishikawa Prefecture, Japan. The proportion of the elderly in Nakajima was higher to that of the whole of Japan and would be almost identical with that of the whole of Japan in the future of 30 years later. The total population of the town has been stable for longtime. In this cohort study, we showed that tooth loss–related dietary patterns were associated with a high prevalence of cognitive decline. We also showed that vitamins C and E reduce the risk of cognitive decline in women with ApoE ε4 and men without ApoE ε4, respectively. In addition, green tea consumption was significantly associated with reduced risk of cognitive decline.

Dementia, Parkinson disease, and stroke are typical common diseases in the field of neurology. All of them rank high among the underlying causes requiring caregiving, and considering the increasingly aging population in Japan, it is anticipated that some form of new initiative will become essential. The development of treatments relies heavily on research into early diagnosis and prevention of onset, making prospective studies targeting healthy elderly populations one of the key approaches for achieving this goal.

Since 2016, we have been participating in the “Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD),” aiming to achieve a healthy and long–lived society. In Yahaba, Iwate, we initiated the prospective cohort study, “Yahaba Active Aging and Healthy Brain Study (YAHABA Study)” focusing on not only dementia but also Parkinson disease and stroke as major research targets. The first comprehensive survey was conducted by 2017. At the start of the study, there were 2,591 elderly residents aged 65 and above living in Yahaba, and we could recruit 951 participants, including 536 women and 415 men. We have completed the second comprehensive survey by 2022 and have initiated visit and follow–up surveys. Some evidences have already been established and the summaries are reported in this paper. We believe that the mission of the YAHABA Study is to disseminate evidence useful in the real world from Yahaba, Iwate.

We will introduce the differences between PDD and DLB from a neuropsychological perspective. We also will introduce diagnostic criteria for PDD and PD–MCI (PD with mild cognitive impairment), as well as an attempt to detect the onset of dementia at an early stage by examination of dysarthria and olfactory dysfunction. DLB had impairment in memory, attention/executive function, and visual–spatial cognition. Compared to AD, visual–spatial cognition, attention, and working memory deficits are more severe than verbal memory. Comparing cognitive function between DLB and PDD, executive function is more impaired in PDD than in DLB. Among the PD–MCI group, those with impairments in multiple cognitive domains had a high rate of conversion to PDD. DLB has more diverse and severe neuropsychiatric symptoms than PDD. Lewy bodies and neurofibrillary tangles in the limbic system and cerebral cortex are associated with the onset of visual hallucinations, visual misperceptions, and delusions of misidentification. The onset of dysarthria in PD may be one of the symptoms suggesting cognitive decline. It is known that cross–modality integration related to the olfactory and vision in PD is impaired before a cognitive decline occurs and may be related to dopaminergic dysfunction.

Can Parkinson disease with dementia and Lewy body dementia be considered on the same spectrum? From a neuropathological perspective, the common denominator of both diseases is Lewy pathology. When focusing on Lewy pathology, Parkinson disease, PDD, and DLB can be considered to be on the same spectrum, and are sometimes collectively referred to as Lewy body disease. The most common of these pathologies are amyloid pathology and tau pathology, and the degree of complications also influences clinical symptoms. Recent research results have also pointed out the possibility that PD and DLB may have different fiber structures based on ultrastructural studies. More detailed studies are expected in the future.

Parkinson disease (PD) is a neurodegenerative disorder characterized by tremor, rigidity, and bradykinesia due to the degeneration of dopaminergic neurons in the substantia nigra. PD also includes numerous non–motor symptoms and can progress to dementia, known as Parkinson disease with dementia (PDD). Dementia with Lewy bodies (DLB) is another neurodegenerative disorder, diagnosed by fluctuating cognition, visual hallucinations, REM sleep behavior disorder, and parkinsonism. The clinical and pathological overlap between PDD and DLB, especially the presence of Lewy bodies, has led to discussions on whether they lie on the same disease spectrum. Key genes implicated in PDD include SNCA, GBA1, and APOE. These genes are also involved in DLB, but recent genetic studies have highlighted additional genes linked to Alzheimer disease pathology and glucocerebrosidase function in DLB. Further genetic research helps elucidate the commonalities and differences between PDD and DLB, advancing our understanding and guiding the identification of therapeutic targets of these disorders.

Lewy body diseases (LBD) are defined as the accumulation of Lewy bodies composed of an aggregation of α–synuclein (αSyn). It was reported that not only the sole aggregation of αSyn but also the co–aggregation of amyloid–β (Aβ) and tau in LBD. Fluid biomarkers of pathogenic protein such as αSyn, Aβ and tau have been developed. We recently showed that plasma Aβ42/40 ratio was significantly decreased in patients with Aβ+LBD compared with those with Aβ–LBD.

Dementia with Lewy bodies (DLB) and Parkinson disease with dementia (PDD) have been recognized as being on the same spectrum because DLB and PDD exhibit Alzheimer disease pathology characterized by various degrees of amyloid–beta and tau in a background of Lewy bodies containing alpha–synuclein. Although these disorders are similar in neuroimaging, patients with DLB tend to show more amyloid–beta deposition, tau deposition, decreased glucose metabolism in the anterior cingulate gyrus, and thalamic atrophy than those with PDD. Furthermore, asymmetric reduction of dopamine transporter in the striatum may be stronger in patients with PDD than those with DLB, and DAT reduction is essential for diagnosis of PD, while some patients with DLB do not show DAT reduction. In terms of amyloid–beta and tau deposition, both diseases are considered to be on the same spectrum, but DLB clearly differs from PDD in that it lacks DAT reduction in some cases. There are few reports of reduced glucose metabolism extending to the frontal lobe, of thalamic atrophy and patients with normal striatal DAT uptake in DLB, and additional studies are warranted.

Multiple sclerosis (MS) often develops in the 20s and 30s, and has a major impact on later life for patients. Patients often suffered from relapses, and activities of daily living (ADL) of patients often declines as symptoms progress gradually from the early stage of the disease. In Japan, eight types of disease modifying drugs (DMDs) for MS have been marketed since 2000. The efficacy, side effects, and route of administration of each drug differ, and the appropriate DMD should be selected at the appropriate time, taking into consideration the patient's disease activity and poor prognostic factors, as well as recent life events and the patient's needs. The Guidelines for Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders have been revised as a benchmark for this purpose. This article discusses the treatment algorithm for MS, referring to the guidelines.

Currently, the treatment of multiple sclerosis (MS) is divided into acute phase and relapse/progression prevention treatment.

Conventional escalation therapy for relapse prevention in relapsing–remitting MS (RRMS) in Japan has been the use of injectable interferon beta 1a, 1b and glatiramer acetate as first–line treatment, oral dimethyl fumarate (speaker's personal opinion), then second–line fingolimod hydrochloride and finally natalizumab and ofatumumab as third–line agents have been used. However, overseas data have shown that early diagnosis and treatment can improve ADL and QOL in MS patients over the long term, and early high–efficacy therapy (HET), in which third–line drugs are used from early diagnosis, is becoming the global trend in relapsing–remitting therapy. In this context, the drug lag for newly approved MS drugs in Japan has been shortened through global clinical trials, and siponimod for secondary progressive MS (SPMS) and ofatumumab for SPMS with active disease have become the drugs of choice.

On the other hand, the mechanism of action of each drug for RRMS and SPMS is different, and the use of each drug should be determined by considering age, gender and number of risks. The number of patients with MS in Japan is about 1/10 of those in Europe and the USA, and it is not a common disease. Even neurologists with less than 10 outpatient cases of MS and little experience in treating patients with MS are often hesitant to make decisions on initial diagnosis, selection of acute phase, post–treatment and relapse prevention, decision–making on progressive transition, drug selection and modification including vaccination and pregnancy, and informed consent to the patient.

The 2023 MS/NMOSD guideline therefore presents a drug selection algorithm for relapse/progression prophylaxis treatment, unlike the previous edition. Patient with MS was quite theoretically armed with information from the internet, in some cases due to information overload in many young patients with MS. In order to respond to the questions posed by such patients in the outpatient setting, it is necessary to collect the correct information to be able to respond to them. In this article, we use the experience and knowledge we have gained from web lectures, You tube videos and booklets produced in collaboration with the Neuroimmunology Outpatient Department of a university hospital and patient groups such as the MS cabin, and from correspondence with MS experts at home and abroad, to provide information on information gathering before treatment initiation, what to remember during treatment, complications and side–effects, and what to expect during treatment. The lecture will also cover complications and side effects, precautions during pregnancy and breast–feeding, and the fact that inertia is not just about changing drugs, but also about when to discontinue drugs in the elderly.

Multiple sclerosis (MS) is a chronic inflammatory disease in the central nervous system, which usually begins with relapsing–remitting course followed by insidious disability worsening. There is currently no cure for MS, but given the increasing numbers of available disease–modifying drugs with differences in risks and benefits, shared decision making (SDM) in the treatment of MS seems to be essential to offer the optimum outcome and improve the quality of life in patients with MS. The aim of this symposium is to review the concept of SDM and discuss main challenges in clinical care of MS patients.

Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system characterized by dissemination in space (DIS) and time (DIT). No diagnostic criteria exist at this time to differentiate MS from the other conditions. Currently accepted McDonald criteria were developed to diagnose subjects with clinically isolated syndrome (CIS). To date, typical presentations of MS including MRI findings have been well studied but have applied McDonald criteria only for CIS subjects. The use of typical presentations for diagnosis has not reached consensus for subjects who have experienced more than two episodes due to different lesions. Instead, “no better explanation” has been offered, yet the interpretation of “no better explanation” changes over time and can be different for different investigators. As a result, some investigators offer a diagnosis of atypical MS whereas others conclude that it is an MS mimic. We previously reported distinction between typical and atypical MS with regards to cytokine profiles of cerebrospinal fluids and response to MS–Disease modifying drugs and corticosteroids/immunosuppressants. Therapeutic strategies of atypical MS are proposed in this review paper.

In recent years, the development of disease–modifying drugs (DMD) has significantly expanded the treatment options for multiple sclerosis (MS), demonstrating the potential to suppress relapses and disability progression when initiating effective DMD early. However, evidence guiding the selection of DMD is still insufficient. Choosing the right DMD involves considering factors such as relapse frequency, severity, recovery extent, disability level, MRI lesion characteristics, DMD efficacy, safety, administration route, and patient preferences. Regular assessment of disease activity is crucial post–DMD initiation, aiming for “no evidence of disease activity” (NEDA) and prompt adjustment to more effective DMD if necessary. Clinical cases are presented to illustrate the decision–making process for DMD selection based on individual patient characteristics.

In the clinical setting, guidelines suggest considering interferonβ, glatiramer acetate, or dimethyl fumarate for patients with low relapse frequency, low MRI activity, and low disability. However, due to suboptimal efficacy and side effects, newer options like natalizumab and ofatumumab are often preferred. Escalation therapy, starting with lower efficacy DMD like dimethyl fumarate and escalating to higher efficacy therapies if needed, is emphasized for patients without poor prognostic factors. Early intensive therapy is recommended for patients with poor prognostic factors, starting with high–efficacy DMD like natalizumab or ofatumumab.

The decision to discontinue DMD in elderly patients remains under debate, with caution and careful observation required. The fundamental approach to MS treatment involves early intensive therapy, particularly with natalizumab or ofatumumab. The choice between them depends on factors like JC virus antibody status and age. Individualized assessment and continuous reevaluation of disease activity are essential for making informed decisions in MS management.

Recent advances in neurology have been remarkable, and it has become possible to control diseases and symptoms that can be cured. On the other hand, there are still a wide variety of problems faced by intractable neurological diseases, and among them, there are also various problems related to palliative care. Amyotrophic lateral sclerosis (ALS) is an incurable disease that causes motor neuron damage, and as it progresses, breathing problems occur. Respiratory support therapies include noninvasive ventilation (NIV) and tracheostomy invasive ventilation (TIV). Past reports suggest that NIV therapy not only improves various symptoms caused by respiratory disorders, but also improves and maintains the quality of life during the non–TIV period, improves the quality of sleep, and suppresses the decline in respiratory function. On the other hand, in advanced stages, it is difficult to deal with upper airway obstruction due to saliva aspiration, tongue base subsidence, etc., and respiratory symptoms may not be alleviated with NIV alone. In addition to respiratory physical therapy, NIV therapy has been used to alleviate respiratory symptoms, prolong survival time, and improve quality of life (QOL). Further research is needed to assess the extent to which this contributes to QOL. In this symposium, we will outline the process of examining how NIV therapy contributes to QOL in ALS patients from the perspective of palliative care, as well as the concerns that patients have difficulty expressing in words.

Multiple sclerosis (MS) presents with a variety of neurological symptoms in varying degrees and combinations, resulting in a wide range of physical pain, psychological pain, social pain, and spiritual pain. Patients with MS experience a great decrease in Quality of Life (QOL) due not only to the loss of ADLs caused by motor impairments but also invisible distress such as numbness, pain, and fatigue and emotional distress from not having their symptoms understood. The unpredictability of the disease course of MS also causes patients to have anxiety and fear of relapse or progression, even when symptoms are stable. Social pain caused by MS includes a high unemployment rate, economic burden of treatment, and impacts on life plans such as marriage and child–bearing. Since MS is more prevalent in the younger generation, patients are likely to have unstable economic backgrounds, which may lead to social and psychological pain. The long lasting physical, psychological, and social pain impact the well–being and mindfulness of patients and can easily lead to strong spiritual pain.

This guideline focuses on the physical, psychological, social, and spiritual pain that MS patients experience and investigate the need for palliative care not only for patients in the advanced stage with severe physical symptoms but also for patients in the early stages of the disease. Specifically, we conducted a systematic review (SR) of the clinical question (CQ) “Is continuous outpatient nursing care for MS patients effective from the perspective of their daily lives?”. A total of 1306 articles related to the CQ were obtained by a literature search on PubMed. Screening of the titles and abstracts was conducted by two neurologists, and 72 articles were extracted from 1306 articles. These articles covering a wide range of issues including counseling, rehabilitation, dysuria care, spasticity care, and caregiver/family burden reduction/psychological support indicated that palliative care for MS requires multidisciplinary intervention. To establish recommendations regarding the CQ, full text screening of the 72 articles is currently underway. On the other hand, only a few large–scale prospective studies in which the usefulness of continuous outpatient nursing care was examined were found, indicating the difficulty of building evidence in palliative care. We hope this guideline will draw attention to palliative care for patients with MS and that there will be a further accumulation of useful information in the future.

In the palliative care guideline for neurological diseases “muscular dystrophy,” we have set the following six Q&As. “Does palliative care for muscular dystrophy differ depending on the disease type?”, “When should palliative care be started for muscular dystrophy?”, “What kind of painful symptoms occur in muscular dystrophy?”, “How should we perform advanced care planning for muscular dystrophy?”, “How can we support the families and caregivers of patients with muscular dystrophy?” and “Under what conditions should opioids be used in patients with muscular dystrophy?” This report provides an overview of the underlying muscular dystrophy symptoms and their palliative care. The main symptom of muscular dystrophy is motor dysfunction due to skeletal muscle damage, but accompanying this, various functional disorders and complications occur. Muscular dystrophy includes a variety of disease types and conditions, making it difficult to provide a uniform treatment. It is essential to fully understand the disease, including its prognosis and natural history, and palliative care based on individuality is necessary. In ACP for muscular dystrophy, it is important to have repeated discussions with the patients, families, and medical/care team, and multidisciplinary collaboration is necessary. The main painful symptoms of muscular dystrophy include pain and dyspnea, and painful symptoms that warrant the use of opioids can occur in muscular dystrophy. The guideline is expected to contribute to future medical treatment of muscular dystrophy.

Diversification of therapeutic modalities has led to groundbreaking drug development, enabling effective treatment strategies for diseases that were previously challenging to address. During the era when small–molecule drugs were predominant, self–sufficiency among large pharmaceutical companies was central to innovation. However, in the era of diversified modalities, open innovation led by academia and academic startups has become indispensable. This marks a significant transformation in the drug discovery process, highlighting the essential role of open innovation activation in the emergence of revolutionary new drugs. The global distribution of pharmaceutical startups is overwhelmingly concentrated in the United States, with the United Kingdom and France following as remaining hotspots. Interestingly, the headquarters of eight out of the top 10 leading pharmaceutical companies, excluding the two based in Switzerland, coincide with these hotspots. On the other hand, turning attention to Japan, a country advocating for a science and technology–driven nation, there are limited success stories in drug discovery through open innovation, suggesting the existence of specific bottlenecks.

In recent, a variety of issues have piled up, including worsening global environmental problems and the arrival of declining birthrate and aging population. In order to resolve these issues there are great expectations placed on Academia such as universities and national centers to help Japan demonstrate leadership to the international community. For Academia to solve these social issues and bring new value to future society from the perspective of science and technology, co–creation with society and industry, or open innovation, is essential. There is also a need to develop the way of industry–academia collaboration.

In this regard, in Japan, the Ministry of Education, Culture, Sports, Science and Technology launched an “Open Innovation Organization development project” in 2018, 12 universities selected and worked to develop a system to promote “full-fledged industry-academia collaboration”. In this project, each universities acquired human resources from industry and experts to strengthen the university's organization and system. And they are creating joint research that is deeply involved in corporate business strategies and also doing project management.

Furthermore, there are special characteristics in medical industry–academia collaboration. Japanese Medical researchers are not only researchers, but also have diverse positions such as doctors, pharmaceutical review experts, entrepreneurs and etc. This unique position of medical researchers has high expectations from companies and others. In other words, their knowledge and experience are expected to be of great help in a variety of situations in the research, development, and commercialization processes of drug discovery, medical devices and healthcare business. On the other hand, in medical industry–academia collaboration, especially in clinical research and clinical trials, compliance with related laws, contract management, and conflicts of interest management are necessary to maintain safety, reliability, and fairness.

This article introduces the system development and measures for promoting open innovation activities at TokyoMedical&DentalUniversity (TMDU). TMDU had participated in “Open Innovation Organization development project” mentioned above and has worked to develop a system with the unique characteristics of medical academia. Using TMDU's nucleic acid medicine project as an sample, introduce issues surrounding open innovation in the medical field and ways to promote it.

Academia research plays a major role in drug development, and is expected to be the driving force behind the creation of innovative drugs. However, in the framework of open innovation, it is not enough for academia to simply present their research results at academic conferences or in papers ; they need to promote development research to a certain extent in order to pass their assets on to companies. As a result, academia is now required to develop strategies for two issues that have not been given much attention in the past : securing high–quality patents and promoting research and development. Regarding patents, in the conventional flow of small molecule drug development, it was the role of pharmaceutical companies to create ones. That is, even if a new therapeutic target is discovered in academia and target validation is performed, a lead compound is selected and optimized by companies to produce the final product. In other words, the chemical structure of the final product cannot be imagined based on the initial research results, and there is little point in obtaining a patent at the academic stage. However, with the rise of new medical modalities such as antibody and nucleic acid drugs, this basic framework is changing dramatically. In other words, it has become possible and even necessary for academia to secure patents related to conceptual or final product structures from their research results. With the advent of various platform technologies, academia's involvement in conventional medicine is also expanding. Under these circumstances, academia is required to have the ability to fully incorporate the scientific potential for practical application of their research results into patent specifications. Since this process requires deep expertise in both medicine and intellectual property, it is important that medical researchers at least acquire a minimum level of intellectual property literacy. At the same time, in house intellectual property experts who accompany the researchers are needed.