This editorial describes new MDS criteria for multiple system atrophy (MSA). The criteria aim to improve the accuracy of the diagnosis of MSA and to increase diagnostic accuracy in the early stages of the disease leading to increased patient enrollment in clinical trials. The criteria provide detailed definitions of diagnostic findings in a lexicon, which should be reviewed during the interview and diagnosis. The criteria define four levels of diagnostic certainty. The newly created “possible prodromal MSA” is a research category with low specificity, but it is expected to be used to establish future diagnostic biomarkers to catch patients in the earliest stages of the disease.

Remudy (REgistry of MUscular DYstrophy) is a patient registry started in 2009 in collaboration with TREAT–NMD, an international clinical research network, to promote clinical development of hereditary neuromuscular diseases. In close collaboration with the Japan Muscular Dystrophy Association, a patient organization, the registry office was established at the National Center of Neurology and Psychiatry, and the registry started with dystrophinopathies, and is now operating registries for GNE myopathy, myotonic dystrophy, Facioscapulohumeral muscular dystrophy, and congenital muscular disorders. It has conducted various epidemiological studies, contributed to clinical trial feasibility studies and patient recruitment, and disseminated information to patients. In recent years, the use of real–world data in therapeutic development has been attracting attention, and among these, the utilization of the registry under the pharmaceutical system is being promoted under the Clinical Innovation Network. It is hoped that the registry will be widely utilized in areas ranging from therapeutic development to safety monitoring activities.

The patient registry of amyotrophic lateral sclerosis (ALS) can play many roles in providing appropriate care to patients and promoting therapeutic development for ALS. In Japan, a multicenter registration and follow–up system called Japanese Consortium for Amyotrophic Lateral Sclerosis research (JaCALS) was built in 2006. Genomic DNA samples and B–cell lines of ALS patients were stored and linked to the clinical information. JaCALS showed natural histories and genetic backgrounds of Japanese ALS patients and clinical and genetic factors associated with progression and prognosis of ALS. Technology has been developed to create iPS cells from B–cell lines and perform phenotypic analysis, indicating that the combination of clinical and genomic information with iPS cells may play an important role in pathophysiological analysis and therapeutic drug screening. Efforts are also being made to create real–world evidence by utilizing large–scale longitudinal clinical information. The role of the patient registry in therapeutic development and validation is expected to increase in the future.

Clinical research based on patient registries has recently been a global trend. J–CAT (Japan Consortium of Ataxias) is the only registry in Japan characterized by Web–based patient–driven registration with informed consent. Detailed clinical information and clinical resources including genomic DNA, plasma and B–lymphoblast cell line have been accumulated in J–CAT. Mutational screening for major disease types has been conducted in all the registrants. On September 2022, 2365 registrants, 1949 genomic DNA, 515 plasma samples, and 334 B–lymphoblast cell lines have been obtained. Ongoing projects based on J–CAT include elucidation of molecular epidemiology, establishment of disease–specific prospective natural history, delineation of idiopathic cerebellar ataxia (IDCA) and support for differential diagnosis of autoimmune cerebellar ataxia. J–CAT plays an indispensable role in clinical researhes for the development of cures for ataxias.

Multiple system atrophy (MSA) is a neurodegenerative disease characterized by autonomic failure with various combination of cerebellar ataxia, Parkinsonism and pyramidal signs with the average age at onset in late 50s. The prevalence of MSA in Japan has been estimated to be 12,000. The detailed natural history and molecular basis of MSA, however, still remain to be elucidated. To facilitate the research on MSA, we established the MSA registry in 2016. In this registry, detailed clinical information including Unified Multiple System Atrophy Rating Scale parts 1 and 2 has been collected in a prospective manner. The bioresource including genomic DNA, plasma and lymphoblastoid cell lines has been collected, and deposited to the Rare Disease Bank at The National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN). To date, 530 patients with MSA have been registered in this registry. The detailed natural history of MSA established based on the MSA registry is expected to contribute to design future clinical trials.

Human T–cell leukemia virus type 1 (HTLV–1)–associated myelopathy (HAM) is a severe refractory disease, with only few effective treatments, characterized by progressive paraparesis due to chronic inflammation of the spinal cord. Due to its low prevalence in other developed countries outside Japan, only limited data on biomarkers or treatment strategies for HAM are available. As a result, there is no internationally recognized treatment for HAM and the quality of clinical care is low. In rare diseases such as HAM, large scale studies to collect continuous clinical data have been difficult. Since a patient registry could be useful to prospectively collect information from many patients. We established the nationwide registration system “HAM–net” in 2012. The HAM–net has been an effective tool for promoting epidemiological studies.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small vessel disease characterized by recurrent stroke and progressive cognitive impairment, which is caused by the NOTCH3 mutation. Although CADASIL was previously considered a rare disease, recent genomic studies have recognized pathogenic NOTCH3 mutations in approximately 1% of the general population in East Asia. The clinical course is not uniform in CADASIL patients. The genotype–phenotype correlations remain elusive.

We are currently conducting an AMCAD trial to evaluate the safety and efficacy of adrenomedullin, a vasoactive peptide with strong angiogenic, anti–inflammatory, and oligodendrogenetic effects, in CADASIL patients. However, since CADASIL appears to be underdiagnosed, it would be difficult to conduct a larger confirmatory trial in Japan ; international collaborative research is important to promote drug development for CADASIL. We therefore plan to establish an East Asian CADASIL registry in collaboration with Taiwan and South Korea. Researchers in each country will enter clinical data of CADASIL patients, which will be stored in an electronic data capture system. MRI data will be evaluated by an independent review board. More than 1000 CADASIL patients will be enrolled in the registry.

Intractable/Rare Diseases Act (effective in 2015) covers more than 20 syndromes/diseases in which epileptic seizure is a main symptom or one of the main symptoms. To unveil the present situations of intractable/rare epilepsy syndromes/diseases, the “Rare Epilepsy Syndrome Registry (RES–R)” was initiated in 2014 in Japan. RES–R covers a wide variety of items about epilepsy, from seizure type to psychosocial status. With the collaboration of physicians engaged in epilepsy practice from all over Japan, RES–R accumulates and in part follows epilepsy cases to gain epidemiological evidence on intractable/rare epilepsy syndromes/diseases. There are 3454 cases registered as of Nov 2021. Interim analysis showed that 63% of patients with epilepsy other than idiopathic or self–limited syndrome suffered from monthly seizures, 71% comorbidities, and 87% fulfilled the severity criteria of the Act. However, the number of cases registered might represent only about 4% of the cases of rare epilepsy syndrome/disease in Japan estimated from the literature. A follow–up study of 27 new–onset West syndrome patients revealed improved seizure status after 2 years in 66.7%, but worsened intellectual developmental status in 55.6%, with overall improvement in 51.9%. We also conducted a prospective cohort study in which 60 patients with focal cortical dysplasia type II registered in RES–R were included as an external control of investigator–initiated sirolimus trial. In parallel with RES–R, we started a Cause of Death in Epilepsy registry since 2018, where sudden unexpected death consists of one fourth of the causes of death in epilepsy so far. Epilepsy syndrome registry should help facilitate proper application of the Intractable/Rare Diseases Act as well as collaborative clinical studies on epilepsy.

Patient registry is useful and essential for understanding of disease pathology and natural history in real world. Lysosomal Storage Diseases are ultra–rear diseases and most of them are progressive course. Recently many therapeutic interventions are developed and the prognosis is getting better. However it gets more important to elucidate the pathophysiology of the disease using patient registry to find the best way of treatment for each of the patient. Now it is a big issue how to create the patient registry which is effective for establishing natural history. I describe the situation and the hurdle for the establishing the patient registry in this section.

目的：好酸球性多発血管炎性肉芽腫症（eosinophilic granulomatosis with polyangiitis：EGPA）に伴う末梢神経障害の急性期治療による，筋力および電気生理学的パラメータの長期の変化について検討する．

方法：1999年4月から2019年3月までの期間にEGPAによる末梢神経障害を発症した24例に対し後方視的検討を行った．Prednisolone単剤にて治療した群と免疫抑制薬を併用した強化治療群とにおいて，初診時と治療1年後の筋力および電気生理学的指標の変化量を比較検討した．

結果：経時的には両群において脛骨神経複合筋活動電位と前脛骨筋・腓腹筋の筋力で有意な改善がみられたが，腓腹神経感覚神経活動電位（sensory nerve action potentials：SNAP）では振幅低下がみられた．両群間に有意な改善の差はみとめられなかった．

結論：EGPAの末梢神経障害における治療効果について報告した．腓腹神経SNAPは筋力の回復に反して経時的に低下がみられ，治療後も遺残する感覚症状を反映している可能性がある．

［目的］視神経脊髄炎スペクトラム障害（neuromyelitis optica spectrum disorder：NMOSD）の急性期における血液浄化療法（plasma pheresis：PP）の現状と有効性を明らかにする．

［方法］2008年から2020年までに当院に入院した抗アクアポリン4（AQP4）抗体陽性NMOSD 7例について後方視的な臨床的検討を行った．

［結果］Expanded Disability Status Scale（EDSS）−2.0と最も改善効果を認めた1例はEDSS 8.5と重症ではあったが，比較的若年（52歳）で，発症5日以内にPPが導入されていた．EDSS−1.0の改善を示した2例は発症からPP導入まで平均20日を経過していたが，これらは比較的若年（平均48歳）であり，軽症例（平均EDSS 2.5）であった．一方，EDSS＜1.0の改善しか認めなかった4例は高齢（平均75.3歳）かつ重症例（平均EDSS 9.0）で発症からPP導入まで平均24日が経過していた．

［結論］PPは重症であっても超早期の導入が有効であり，若年，軽症例では亜急性期でも一定の改善効果を示すと考えられた．

筋萎縮性側索硬化症（amyotrophic lateral sclerosis：ALS）患者の体位調整は，患者が言語的コミュニケーション障害による意思伝達が困難である中で微細な体位調整条件の希望があり，介護者は患者の希望に沿うために，時間を費やす上に困難性を感じる．しかし，我々が日々体位調整を実践する中で，体位調整条件には大まかな共通性があると感じた．そこで体位調整条件の共通性と根拠を明らかにすることで，患者にとっての心地良い体位調整ができ，安楽に繋がるのではと考え研究に取り組んだ．対象は全介助による体位変換が必要なALS患者29名で，頭側挙上と側臥位の角度・上下肢の保持方法・枕・掛物の好みとその根拠を調査した．調査の結果，頭側・上下肢の挙上，低めの側臥位角度，枕・掛物の選択に体位調整条件の共通性を認めた．共通する体位調整条件の多くは，ALSの特徴である感覚機能が保たれるがゆえに自覚する苦痛症状の緩和対策と考えられた．共通する体位調整条件の活用により，安楽な体位調整が可能と考える．

入院中の神経難病患者に対して，作業療法の一環としてテレプレゼンスロボットの一つであるOriHime^®を使用することで認められた生活の質（quality of life：QOL）の変化について報告する．対象は長期療養入院中の進行性筋ジストロフィー患者1名と筋萎縮性側索硬化症患者3名である．患者はベッド上から自宅等に設置したテレプレゼンスロボットを遠隔操作することで疑似的に外出を体験して，家族などとコミュニケーションをとった．ロボット使用前後にQOL評価のためSchedule for the Evaluation of Individual Quality of Life – Direct Weighting（以下SEIQoL–DW）を施行した．ロボット使用後には全ての患者でQOLの指標であるSEIQoL indexが上昇し，自身の生活に重要と考えられる領域（キュー）に“家族”を全員が挙げるようになったほか，“家族”のキューの重要度や満足度が上昇していた．コミュニケーションや移動に制限がある神経難病入院患者において，テレプレゼンスロボットを用いた支援は，患者と家族との繋がりの確認や強化に役立ち，その結果，QOLの向上をもたらすことができると考えられた．