People with intractable diseases often experience various symptoms and fluctuating physical conditions, making it difficult to balance treatment with work and studies. Creating an environment that allows continued treatment while supporting social participation and age-appropriate growth and development remains essential. Using consultation services and support personnel, as well as improving health literacy, further helps individuals manage their treatment and daily life effectively.
In recent years, with the advancement of genetic medicine for intractable diseases, opportunities for genetic testing and diagnosis have increased. Because genetic information is shared among blood relatives, cases in which a patient's diagnosis leads to the diagnosis of other relatives are increasing. It is important to establish support systems that enable patients with hereditary intractable diseases and their families to understand and adapt to their conditions and genetic risks, as well as consultation systems tailored to life events. Healthcare professionals who are close to patients and their families should collaborate in their care and refer them for genetic counseling as needed.
Respiratory impairment in neuromuscular diseases is primarily characterized by restrictive ventilatory dysfunction caused by progressive respiratory muscle weakness, which significantly affects survival and quality of life. This article outlines the clinical significance of respiratory rehabilitation in neuromuscular diseases from a pathophysiological perspective, focusing on two core interventions: Lung Volume Recruitment Therapy (LVRT), aimed at preserving lung and chest wall compliance, and Mechanical Insufflation-Exsufflation (MI-E), designed to support airway clearance by augmenting cough efficacy.
Many monogenic disorders do not yet have sufficiently established curative treatments, requiring affected individuals and their families to engage in ongoing decision-making regarding pregnancy and long-term life planning. In reproductive and perinatal medicine, preimplantation genetic testing for monogenic disorders (PGT-M) and prenatal genetic testing represent important options; however, advances in therapeutic interventions and the identification of novel genetic variants have made assessments of disease severity increasingly challenging. In Japan, the Japan Society of Obstetrics and Gynecology has conducted case-by-case reviews of PGT-M applications, yet the appropriateness of the current framework continues to be discussed. Establishing a continuous genetic care system supported by multidisciplinary collaboration is therefore essential.
In neurological care, ethical issues often arise because of cognitive decline and prognostic uncertainty. These conflicts typically stem from competing values among the four principles of biomedical ethics. To address these issues, practicing shared decision-making (SDM)-which respects the patient's subjective quality of life (QOL) and personal values-is essential. Clinicians must recognize the ambiguity of "life-sustaining treatment" in this context and avoid hasty conclusions. Instead, they should strive to achieve the best possible consensus through continuous dialogue.
The establishment of the transitional care support centers for patients with childhood-onset chronic conditions has steadily progressed. Committees on transitional care from pediatric to adult healthcare were established by the Japanese Society of Neurology in 2020 and by the Japanese Society of Medical Networking for Intractable Diseases in 2022, and these committees have worked in close collaboration. The framework for transition support to adulthood is defined by the Intractable Disease Control Act and the Child Welfare Act, while specific operational details are provided in guidelines and handbooks, together with multiple consultation and support systems. To ensure an appropriate transition that respects patients' wishes, it is essential for all stakeholders to share information and collaborate in providing support.
Disasters can strike anywhere in Japan at any time. For patients who rely on life-sustaining equipment such as ventilators, disruption of essential services, including electricity, directly threatens their lives. Many patients with neurological disorders require specialized evacuation support during disasters, making preparedness during peacetime critical. It is desirable for relevant stakeholders to collaborate in developing individualized evacuation plans that address the securing of evacuation support personnel, evacuation methods, and post-evacuation living arrangements. The Japanese Society of Neurology has developed a disaster response manual, utilizes a disaster support network bulletin board, and has appointed network leaders and liaisons for intractable neurological diseases.
The management of neurological intractable diseases is constrained by structural barriers, including the uneven distribution of specialists and the chronic, progressive course of these conditions, which limits timely access to appropriate care. In the context of an aging society and emerging infectious diseases, telemedicine and telehealth have gained prominence as strategies to improve access to specialized services. Advances in digital and information-communication technologies further strengthen these approaches by enabling remote monitoring and data-driven evaluation. In addition, integration with artificial intelligence may transform disease management by supporting continuous, proactive, and personalized care.
Recent advances in molecular genetics and cellular modeling have begun to transform the landscape of neurodegenerative diseases, long regarded as "incurable and poorly understood." The identification of causative genes and disease-associated proteins, together with analytical technologies such as induced pluripotent stem (iPS) cell-based platforms, has deepened our understanding of disease mechanisms and clarified therapeutic targets. In parallel, emerging targeted therapies-including nucleic acid-based treatments and therapeutic antibodies-have demonstrated levels of clinical benefit previously considered unrealistic, such as slowing disease progression or reducing relapse rates. These developments signal the arrival of a new era in the treatment of intractable neurological disorders. At the same time, these advances raise a wide range of issues, including challenges related to the implementation and long-term sustainability of such treatments, national-level debate regarding drug pricing and healthcare expenditure, and ethical concerns associated with the broader use of genetic testing. This article summarizes these recent therapeutic developments and the accompanying social and ethical issues that warrant careful attention in this evolving era.
Amyotrophic lateral sclerosis (ALS) care in Japan should be re-evaluated not simply as a matter of clinical choice but as a function of the public support system structure. In Japan, care is distinguished by a publicly funded model that supports home-based living and social participation following tracheostomy invasive ventilation. In contrast, Europe reflects a model centered on non-invasive ventilation and palliative care, and the United States reflects a system in which precision therapies are approved earlier but access remains highly unequal. Further, Canada reflects a model integrating multidisciplinary ALS clinics with Medical Assistance in Dying within a shared policy framework. These differences extend beyond treatment preferences and instead reflect broader social, institutional, and ethical configurations that shape the future of individuals with ALS. As access to emerging disease-modifying therapies increasingly depends on genetic testing, the central challenge in ALS care is shifting from end-of-life decision-making to the equitable distribution of precision medicine. Comparative reappraisal of national care models is therefore critical for understanding ALS not only as a neurological disease but also as a condition shaped by welfare systems, care infrastructure, and policy design.
Coordinators for intractable diseases are deployed in 44 prefectures across Japan as part of the National Intractable Disease Countermeasures program, totaling 65 coordinators (as of May 2025). They handle a wide range of consultations, including coordination with medical institutions and responses to inquiries regarding medical care. Although the presence of these coordinators is highly valued in intractable disease medical settings, their activities vary considerably depending on the needs of each prefecture. Establishing a system to educate and support these coordinators, along with ensuring the quality of their training, remains a key challenge for the future.
Neurological intractable diseases are progressive, and as the disease advances, symptoms can include not only motor impairments but also autonomic nervous system disorders and higher brain dysfunction, with a wide range of pathologies. Patients face a variety of difficulties in daily life, and various issues were identified even in a survey targeting home care support service provider that create care plans on-site. The role of rehabilitation is to provide a stable home life and to maintain ADL (activities of daily living) and QOL (quality of life), which are crucial points. In home settings, there are issues such as staff lacking knowledge of rehabilitation for intractable diseases, not knowing which rehabilitation content is more appropriate, a shortage of human resources for rehabilitation, and insufficient teamwork. Consideration is being given to creating rehabilitation pamphlets to assist in rehabilitation guidance. Additionally, there have been reports on the development of rehabilitation using new devices [external stimulation, VR (virtual reality), tDCS (transcranial direct current stimulation)], indicating progress in clinical research.
Communication support for patients with neurological disorders extends beyond high-technology communication aids. It also includes non-aided and low-technology methods and requires flexible selection and the combined use of these methods depending on the situation. Gaining experience with various communication strategies in a stepwise manner from an early stage enables the smoother introduction of advanced communication devices when necessary. Effective support must be tailored to the disease stage, as communication abilities and needs change over time. In this context, collaboration among multiple professionals is essential. Such interprofessional collaboration enables appropriate assessment, timely intervention, and continuity of care across disease stages. A team-based, continuous support system benefits patients, and caregivers and professionals involved in their care. By sharing knowledge, skills, and responsibilities within a support team, the burden on individual supporters can be reduced, and the quality and consistency of communication support can be enhanced. Looking to the future, further development of emerging technologies such as eye-gaze input systems, personalized speech synthesis, and brain-machine interfaces is highly anticipated. However, careful consideration of their characteristics, limitations, and potential risks is necessary to ensure their safe and effective use in clinical practice.
Research using brain tissue obtained through autopsies is essential for the development of treatments for several neurological disorders and for elucidating their pathophysiologies. However, owing to a decline in the number of autopsies, opportunities to examine central nervous system tissues are diminishing. It is therefore necessary to collaborate with brain banks and establish a system to ensure the proper storage, research utilization, and diagnostic analysis of nervous system tissues obtained through autopsies.
Support measures for intractable diseases in Japan began in 1972 and, since 2015, have been implemented under the Act on Medical Care for Patients with Intractable Diseases. This article provides an overview of key activities and achievements of designated research groups that contribute to intractable disease policy, focusing on (1)challenges in developing healthcare delivery systems; (2)rehabilitation for patients with intractable diseases; (3)the roles of Intractable Disease Consultation and Support Centers and public health centers at the community level; (4)intractable disease care management by certified care managers; (5)support for balancing work and medical treatment; (6)inter facility and inter-professional collaboration, including disability welfare services; (7)ensuring the quality of home-visit nursing; (8)disaster preparedness; and (9)the development of e-learning environments for training human resources engaged in intractable disease support.
Dysphagia is common in patients with neuro degenerative diseases. It is associated with aspiration pneumonia, malnutrition, and reduced quality of life. Swallowing assessment should incorporate therapeutic perspectives, including the use of compensatory strategies. In conditions such as amyotrophic lateral sclerosis, weight loss is associated with a poor prognosis, and nutritional therapy may function as a disease-modifying intervention. Clinical ethical issues may arise, including decisions regarding gastrostomy or care for patients with impaired decision-making capacity. A multidisciplinary team approach is essential for managing dysphagia and nutritional problems in these patients.
Yamagata University Hospital, which serves as a core hospital for intractable disease treatment collaboration, has established a "collaboration center for intractable disease treatment." Within the center, physicians from all medical departments at Yamagata University Hospital, including adult medicine and pediatrics, participate in building a collaborative system for intractable disease treatment, including multidisciplinary collaboration between hospitals and clinics. The collaboration center for intractable disease treatment has created a website and holds annual lectures for medical professionals to disseminate information regarding intractable disease treatment, including multidisciplinary collaboration between hospitals and clinics. The center plays a central role in the intractable disease treatment liaison council of Yamagata Prefecture in addressing multiple issues related to interprofessional collaboration.
Human herpesvirus 6B (HHV-6B) is a β-herpesvirus that establishes latency following primary infection during early childhood. In immunocompromised individuals, particularly those who have undergone allogeneic hematopoietic stem cell transplantation, HHV-6B reactivation occurs in 30-80% of cases, with notably high rates observed after cord blood or HLA-mismatched transplants. HHV-6B encephalitis poses a serious and often life-threatening neurological complication for these transplant recipients. The mortality rate associated with this condition remains approximately 30-50%, and many survivors endure long-term neurocognitive sequelae. Clinical manifestations include altered consciousness, memory impairment, and seizures, which are often preceded by hyponatremia resulting from the syndrome of inappropriate antidiuretic hormone secretion. A definitive diagnosis requires the detection of HHV-6B DNA in cerebrospinal fluid by polymerase chain reaction, the exclusion of inherited chromosomally integrated HHV-6, and the ruling out of other potential etiologies. Due to the rapid progression and poor prognosis associated with delayed treatment, empirical antiviral therapy should be initiated promptly whenever HHV-6B encephalitis is suspected. In Japan, foscarnet is recommended as the first-line treatment due to its superior clinical outcomes and antiviral potency, whereas ganciclovir serves as a second-line alternative. Recent advancements in early diagnosis and timely treatment have contributed to improved survival outcomes.
Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy (HAM) is a neuroimmunological disorder in which the infiltration of HTLV-1-infected T cells into the spinal cord triggers chronic inflammation and neurological damage. HAM predominantly affects the mid-to-lower thoracic cords. Improving long-term outcomes requires accurate assessment of disease activity and timely initiation of therapy. Activity stratification based on cerebrospinal fluid biomarkers is clinically useful.
Acute subdural empyema is a severe intracranial infection characterized by purulent accumulation between the dura mater and the arachnoid. It commonly affects children and young adults, typically as a complication of sinusitis, otitis media, or bacterial meningitis. In adults, however, head trauma and postoperative c infections are more common causes. Clinical symptoms include fever, headache, seizures, focal neurological deficits, and altered consciousness, with rapid neurological deterioration due to increased intracranial pressure. Diagnosis relies heavily on magnetic resonance imaging, with diffusion-weighted imaging detecting characteristic high-intensity signals. Although computed tomography may aid in initial evaluation, it is less sensitive for accurate diagnosis. Laboratory findings typically show elevated inflammatory markers, while bacterial cultures are often negative. Treatment involves prompt administration of antibiotics such as third-generation cephalosporins, vancomycin, and metronidazole, followed by adjustment based on culture results. Surgical intervention, via burr hole drainage or craniotomy, is often required for pus evacuation and decompression. Treatment of the primary infection source, such as sinus surgery, may also be necessary. Prognosis depends on the patient's condition at presentation and the speed of intervention. Although outcomes have improved with modern therapies, mortality remains substantial in severe cases, and long-term neurological sequelae are common.
