[Initiatives for supporting the health care transition in various regions: activities of transitional care support centers].

The Japanese Society of Neurology's Special Committee on Measures for Transition from Pediatric to Adult Health Care held a workshop to discuss the activities of the transitional care support centers (TCSCs). The following points were addressed: (1) from Kanagawa Prefecture, the activities of the TCSC, which is set up alongside the Intractable Disease Consultation Support Center and the Intractable Disease Information Coordination Center, separated from medical institutions, and the efforts addressing cases of difficult transitions and consultations where patients cannot transition from specific pediatric chronic diseases to designated intractable diseases; (2) from Nagano Prefecture, the supporting the health care transition undertaken by the neurologist as intractable disease medical coordinator, and (3) the efforts of the transitional health care support coordinator at the TCSC established at the university hospital in collaboration with the Nagano Children's Hospital and the government. For the creation of a seamless support system, we hope that the pioneering activities reported at this time will spread nationwide.

[Issues of transition support to adulthood and the practices of pediatric-adult healthcare transition in neurological diseases].

A workshop of the Special Committee on Measures for Transition from Pediatric to Adult Health Care, the Japanese Society of Neurology was held to discuss various issues and practices involved in healthcare transition. The following points were addressed: (1) the history of, and issues involved in, promoting support for patients requiring medical care, (2) cooperation between pediatric medical centers and university hospitals, (3) collaboration between pediatrics and neurology in medical and rehabilitation facilities, and (4) a questionnaire survey of members of the Japanese Society of Neurology. The reasons for extreme difficulties in pediatric-adult healthcare transition for patients with neurological diseases, especially those who require continuous intensive medical care over a long period of time, include the difference in the operating systems of pediatric and adult departments, in addition to the difference in the diseases treated during childhood and adulthood.

A disease-specific iPS cell resource for studying rare and intractable diseases.

Background: Disease-specific induced pluripotent stem cells (iPSCs) are useful tools for pathological analysis and diagnosis of rare diseases. Given the limited available resources, banking such disease-derived iPSCs and promoting their widespread use would be a promising approach for untangling the mysteries of rare diseases. Herein, we comprehensively established iPSCs from patients with designated intractable diseases in Japan and evaluated their properties to enrich rare disease iPSC resources.

[Current practices of transition from pediatric to adult health care for patients with neurological disease: promote the cooperation between child and adult neurologists].

The Special Committee for Measures Against Transition from Pediatric to Adult Health Care of the Japanese Society of Neurology, which consists of child and adult neurologists, started to tackle the issues of pediatric to adult health care transition for patients with neurological disease in July 2020. The Committee held a workshop with a theme of "cooperation between child and adult neurologists," which is a critical issue in the pediatric to adult health care transition. To solve the many problems in the pediatric to adult health care transition, it is crucial that child and adult neurologists and primary care physicians cooperate on the following issues: preparing child neurologists for the transition, encouraging adult neurologists to study child neurology, promoting the formation of multidisciplinary teams, improving the medical system and medical fees, appealing to governmental agencies for issues of community health care and welfare services.

[Muscular Dystrophy: A Banana? At This Time of the Night?].

In Japan, specialized wards for muscular dystrophy have been established in national hospitals since 1964, and opportunities for medical care, rehabilitation training, and education have been provided. Since the 90s, advances in ventilatory therapy and heart failure pharmacotherapy have resulted in increased life expectancy in patients with muscular dystrophy. The social infrastructure has also improved, but it still took long to develop support systems for the social lives of individuals with disabilities.

Rapid and comprehensive diagnostic method for repeat expansion diseases using nanopore sequencing.

We developed a diagnostic method for repeat expansion diseases using a long-read sequencer to improve currently available, low throughput diagnostic methods. We employed the real-time target enrichment system of the nanopore GridION sequencer using the adaptive sampling option, in which software-based target assignment is available without prior sample enrichment, and built an analysis pipeline that prioritized the disease-causing loci. Twenty-two patients with various neurological and neuromuscular diseases, including 12 with genetically diagnosed repeat expansion diseases and 10 manifesting cerebellar ataxia, but without genetic diagnosis, were analyzed.

RNA-seq analysis, targeted long-read sequencing and in silico prediction to unravel pathogenic intronic events and complicated splicing abnormalities in dystrophinopathy.

Dystrophinopathy is caused by alterations in DMD. Approximately 1% of patients remain genetically undiagnosed, because intronic variations are not detected by standard methods. Here, we combined laboratory and in silico analyses to identify disease-causing genomic variants in genetically undiagnosed patients and determine the regulatory mechanisms underlying abnormal DMD transcript generation.

Relationship Between Pneumonia and Dysphagia in Patients With Multiple System Atrophy.

Introduction: Dysphagia is one of the most clinically significant disabilities in patients with multiple system atrophy (MSA), because it can cause aspiration pneumonia, which is potentially fatal. In this study, the Neuromuscular disease Swallowing Status Scale (NdSSS), which was developed to evaluate dysphagia in patients with neuromuscular diseases, was used to evaluate patients with MSA. In addition, correlation between a history of pneumonia and swallowing function was evaluated.

Tranilast for advanced heart failure in patients with muscular dystrophy: a single-arm, open-label, multicenter study.

Background: The transient receptor potential cation channel subfamily V member 2 (TRPV2) is a stretch-sensitive calcium channel. TRPV2 overexpression in the sarcolemma of skeletal and cardiac myocytes causes calcium influx into the cytoplasm, which triggers myocyte degeneration. In animal models of cardiomyopathy and muscular dystrophy (MD), TRPV2 inhibition was effective against heart failure and motor function.

Repeat conformation heterogeneity in cerebellar ataxia, neuropathy, vestibular areflexia syndrome.

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, slow-progressing multisystem neurodegenerative disorder. Biallelic AAGGG repeat expansion in RFC1 has been identified as causative of this disease, and repeat conformation heterogeneity (ACAGG repeat) was also recently implied. To molecularly characterize this disease in Japanese patients with adult-onset ataxia, we accumulated and screened 212 candidate families by an integrated approach consisting of flanking PCR, repeat-primed PCR, Southern blotting and long-read sequencing using Sequel II, GridION or PromethION.

Effects of mouthpiece shape and expiratory threshold loading on contraction of the lateral abdominal muscles: A cross-sectional study.

Background: Expiratory tasks may facilitate transversus abdominis (TrA) activity for spinal stabilization. The purpose of this study was to verify whether a combination of pursed-lip breathing (PLB) and use of an expiratory threshold loading (ETL) device to increase expiratory resistance would promote TrA contraction comparable to that for a stabilization exercise.

Methods: Twenty healthy men performed expiratory tasks or an abdominal drawing-in maneuver (ADIM).

Efficacy of steroid therapy for Fukuyama congenital muscular dystrophy.

Although there is only symptomatic treatment for Fukuyama congenital muscular dystrophy (FCMD), several reports have suggested that steroid therapy could be effective for FCMD; however, no independent intervention studies have been conducted. This study aimed to evaluate the efficacy of steroid therapy for restoring motor functions in FCMD patients. This study involved 3-to-10-year-old FCMD patients who exhibited a decline in motor functions, requested steroid therapy.

Study Protocol for a Multicenter, Open-Label, Single-Arm Study of Tranilast for Cardiomyopathy of Muscular Dystrophy.

Duchenne (DMD) and other forms of muscular dystrophy (MD) are collectively rare and affect approx imately 20 per 100,000 people. The on-going development of exon skipping and other novel therapies for DMD is expected to lead to improvements in motor function prognosis. However, improvements in motor dysfunction with these novel therapies are associated with the risk of increase in cardiac burden.

Clinical efficacy of haematopoietic stem cell transplantation for adult adrenoleukodystrophy.

Accumulated experience supports the efficacy of allogenic haematopoietic stem cell transplantation in arresting the progression of childhood-onset cerebral form of adrenoleukodystrophy in early stages. For adulthood-onset cerebral form of adrenoleukodystrophy, however, there have been only a few reports on haematopoietic stem cell transplantation and the clinical efficacy and safety of that for adulthood-onset cerebral form of adrenoleukodystrophy remain to be established. To evaluate the clinical efficacy and safety of haematopoietic stem cell transplantation, we conducted haematopoietic stem cell transplantation on 12 patients with adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy in a single-institution-based prospective study.

Strategies for learning glossopharyngeal breathing in boys with Duchenne muscular dystrophy: A feasibility case series.

Objective: To propose alternative learning strategies for glossopharyngeal breathing in patients with Duchenne muscular dystrophy (DMD) and healthy men.

Design: A feasibility study with small case series.

Subjects: Five boys with DMD and 7 male physical therapists as healthy controls who had not learned glossopharyngeal breathing.

Cardiac Conduction Disorders as Markers of Cardiac Events in Myotonic Dystrophy Type 1.

Background Myotonic dystrophy type 1 involves cardiac conduction disorders. Cardiac conduction disease can cause fatal arrhythmias or sudden death in patients with myotonic dystrophy type 1. Methods and Results This study enrolled 506 patients with myotonic dystrophy type 1 (aged ≥15 years; >50 cytosine-thymine-guanine repeats) and was treated in 9 Japanese hospitals for neuromuscular diseases from January 2006 to August 2016.

Assessment of dysarthria with Frenchay dysarthria assessment (FDA-2) in patients with Duchenne muscular dystrophy.

Purpose: The purpose of this study was to test the psychometric properties of the Japanese version of Frenchay Dysarthria Assessment (FDA-2) and to use this tool to describe the features of speech in patients with Duchenne muscular dystrophy (DMD).

Materials And Methods: The Japanese version of FDA-2 was culturally adapted, and reliability and validity were examined in 22 and 50 patients, respectively. The Japanese version of FDA-2 was administered to 51 patients with DMD.

[Pitfalls in Diagnostic Evaluation of Muscle Diseases].

Diagnostic procedures for muscle diseases provide confirmation of the presence of muscle disorder, and their etiological assessments and precise classification, including the molecular analysis. It is important to understand the correlation between structural changes observed in muscle pathology and functional changes with electrophysiological tests to avoid pitfalls in the diagnostic evaluation of muscle diseases. Here, I present two cases with difficulties in differentiating between inflammatory and hereditary muscle diseases, and discuss pitfalls in the diagnostic process.