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The 4th MS Summer College in Kobe (5–6 August 2017) Translational research and MS / NMOSD

2018; Wiley; Volume: 9; Issue: S1 Linguagem: Inglês

10.1111/cen3.12436

1759-1961

Wakiro Sato,

Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis

Day 1: 5 August 2017. Opening Remark and Introduction 13.00–13.10 Takashi Yamamura (National Center of Neurology and Psychiatry, Tokyo, Japan) (1) Lecture 1 13.10–13.55 Chair: Takashi Yamamura (National Center of Neurology and Psychiatry, Tokyo, Japan) (L-1) Molecular pathogenesis of multiple sclerosis: From bench to clinic Frauke Zipp (Department of Neurology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany) (2) Lecture 2 13.55–14.20 Chair: Kazuya Takahashi (Iou Hospital, Ishikawa, Japan) (L-2) Mechanisms of chronic inflammation in secondary progressive multiple sclerosis Shinji Oki (National Center of Neurology and Psychiatry, Tokyo, Japan) (3) Lecture 3 14.20–14.45 Chair: Masaaki Niino (Hokkaido Medical Center, Hokkaido, Japan) (L-3) Differences between pathogenic and non-pathogenic T cells in multiple sclerosis Norio Chihara (Kobe University, Kobe, Japan) (4) Poster presentation and coffee break 14.45–15.40 Chair: Tomoko Okamoto (National Center of Neurology and Psychiatry, Tokyo, Japan) (P-1) Potential benefit of plasmapheresis for chronic pain and neurological manifestations with hypermobile Ehlers–Danlos syndrome Manabu Araki,1,2 Youwei Lin,1,2,3 Hirohiko Ono,2 Wakiro Sato1,2 and Takashi Yamamura1,2 (1Multiple Sclerosis Center, 2Department of Immunology, National Institute of Neuroscience, 3Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan) (P-2) Drug-induced progressive multifocal leukoencephalopathy in multiple sclerosis Motohiro Yukitake (Saga Central Hospital, Saga, Japan) (P-3) Our experience of using fingolimod in patients with multiple sclerosis in the regional health care supporting hospital Mizuki Kitamura, Takahiro Nakayama, Tomoki Nakamori and Ichiro Imafuku (Yokohama Rosai Hospital, Yokohama, Japan) (P-4) Efficacy of interferon-β for myelin oligodendrocyte glycoprotein antibody-positive demyelinating disorder Kimihiko Kaneko,1 Tatsuro Misu,1 Douglas Kazutoshi Sato,1,2 Ryo Ogawa,1 Tetsuya Akaishi,1,3 Yoshiki Takai,1 Syuhei Nishiyama,1 Hiroshi Kuroda,1 Toshiyuki Takahashi,1,3 Ichiro Nakashima,1,4 Kazuo Fujihara1,5,6 and Masashi Aoki1 (1Department of Neurology, Tohoku University, Sendai, Japan; 2Department of Neurology, The Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; 3Department of Neurology, NHO Yonezawa Hospital, Yonezawa 4Tohoku Medical and Pharmaceutical University Hospital, Sendai, 5Multiple Sclerosis & Neuromyelitis Optica Center, Fukushima Medical University, Fukushima, 6Department of Neurology, Southern Tohoku Research Institute for Neuroscience, Koriyama, Japan) (P-5) Barthel Index assessment of activities of daily living factors with effects on modified Rankin Scale score and Expanded Disability Status Scale in patients with progressive-type multiple sclerosis Nobuaki Uchida, Ukichiro Kawai and Makoto Matsui (Kanazawa Medical University, Ishikawa, Japan) (P-6) Overlap between limbic encephalitis and demyelinating diseases: Anti-N-methyl- D-aspartate-receptor antibody-negative case Yasuyuki Takai, Yoko Warabi, Ryohei Norioka, Maya Tojima, Jun Ikezawa, Ryoichi Okiyama and Eiji Isozaki (Department of Neurology, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan) (P-7) Neurosarcoidosis and neuromyelitis optica spectrum disorders compared using T2*-weighted imaging of the head Ryusei Nishigori, Youko Warabi and Eiji Isozaki (Tokyo Metropolitan Neurological Hospital, Tokyo, Japan) (P-8) Improvement of cognitive impairment in a multiple sclerosis patient with fingolimod treatment for 7 years Takahiro Wakasugi, Etsuji Saji, Fumihiro Yanagimura, Mariko Hokari, Kaori Yanagawa, Masatoyo Nishizawa, Osamu Onodera and Izumi Kawachi (Brain Research Institute, Niigata University, Niigata, Japan) (5) Oral presentation 15.40–16.30 Chair: Wakiro Sato (National Center of Neurology and Psychiatry, Tokyo, Japan) (O-1) Case of multiple sclerosis with objective clinical evidence, but without abnormalities on conventional brain and spinal cord magnetic resonance imaging Daiki Takewaki,1,2 Youwei Lin,1,2 Wakiro Sato,1 Hirohiko Ono,1 Manabu Araki,1,2 Tomoko Okamoto,2 Yuji Takahashi2 and Takashi Yamamura1 (1Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, 2Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan) (O-2) Astroglial and oligodendroglial connexins differentially modulate acute and chronic experimental autoimmune encephalomyelitis Ryo Yamasaki, Hayato Une, Yinan Zhao, Mei Fang, Guangrui Li, Kyoko Iinuma, Katsuhisa Masaki, Koji Shinoda, Hiroo Yamaguchi and Jun-ichi Kira (Kyushu University, Fukuoka, Japan) (O-3) Derangement of γδ T-cell repertoire is associated with disease severity of multiple sclerosis Koji Shinoda,1 Guzailiayi Guzailiayi Maimaitijiang,1 Yuri Nakamura,1 Katsuhisa Masaki,1 Takuya Matsushita,1 Ryo Yamasaki,1 Yasunobu Yoshikai2 and Jun-ichi Kira1 (1Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 2Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan) (O-4) Endothelial cell activation induced by immuogloblin G from patients with Neuromyelitis optica and Multiple sclerosis on the Blood-Brain Barrier Fumitaka Shimizu, Yasuteru Sano, Yukio Takeshita, Yuka Hamamoto, Toshihiko Maeda, Susumu Fujikawa and Takashi Kanda (Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan) (6) Lecture 4 16.30–17.15 Chair: Seiji Kikuchi (Hokkaido Medical Center, Hokkaido, Japan) (L-4) Gastrointestinal influences on multiple sclerosis: Translational approaches and beyond Cris Constantinescu (Nottingham University Hospitals, Nottingham, UK) (7) Group Discussion (Case Study) 17.30–18.30 Moderator: Kazumasa Yokoyama (Juntendo University, Tokyo, Japan) Case 1: Demyelinating lesion Miwako Kawamura (Koshigaya City Hospital, Saitama Japan) Case 2: Myelitis and neuritis Hikaru Kamo (Juntendo University, Tokyo, Japan) (8) Meeting Dinner 18.30–20.15 Day 2: 6 August 2017 (9) Lecture 5 09.00–09.50 Chair: Masahiro Mori (Chiba University, Chiba, Japan) (L-5) Clinical and magnetic resonance imaging clues and pitfalls in the diagnosis and differential diagnosis of multiple sclerosis Aksel Siva (Istanbul University, Istanbul, Turkey) (10) Lecture 6 09.50–10.30 Chair: Takashi Kanda (Yamaguchi University, Yamaguchi, Japan) (L-6) Magnetic resonance imaging monitoring in multiple sclerosis treatment: Including early diagnosis of progressive multifocal leukoencephalopathy Yukio Miki (Osaka City University, Osaka, Japan) (11) Debate Training 10.40–11.40 Chair: Kazumasa Yokoyama (Juntendo University, Tokyo, Japan) How to manage an infectious risk of second-line disease-modifying therapy? Player: Hirofumi Ochi (Ehime University, Matsuyama, Japan), Shuhei Nishiyama (Tohoku University, Sendai, Japan), Yusei Miyazaki (Hokkaido Medical Center, Hokkaido, Japan) and Jin Nakahara (Keio University, Tokyo, Japan) (12) Lecture 7 11.40–12.20 Chair: Makoto Matsui (Kanazawa Medical University, Ishikawa, Japan) (L-7) Myelin oligodendrocyte glycoprotein immunoglobulin G-associated neurological disease Kazuo Fujihara (Fukushima Medical University, Fukushima, Japan) (13) Closing remarks 12.20–12.25 Masahiro Mori (Chiba University, Chiba, Japan) The 4th Annual Meeting of the Multiple Sclerosis (MS) Summer College was held at the Kobe Portopia Hotel in Kobe, Japan, on 5 and 6 August 2017. In the midst of the Japanese summer, escaping from a big typhoon coming over from the west, we enjoyed sunny, humid and hot days. More than 120 participants from all over Japan participated in the meeting, as did three special guest speakers from Germany, England and Turkey. Most sessions were carried out in English. Herein, I describe the topics covered over these 2 days. On Saturday afternoon, Professor Takashi Yamamura from the National Center of Neurology and Psychiatry – the president of this college – presented the opening remarks, introducing the main theme of the meeting: “Translational research and MS/NMOSD (Fig. 1).” He provided a historical perspective, noting that while basic and clinical medicine had been united in the past, as each domain developed and became more specialized, they began to diverge. The gap between the two domains has widened, and there remains a difficult, but critical, need for translational research.1 Professor Yamamura suggested that now is a good time to reunite basic and clinical medicine research, so that the two streams could again work together to solve the many perplexing issues of neuroimmunology. Three special lectures were then delivered. The first was presented by Professor Frauke Zipp of the Department of Neurology at the University Medical Center of the Johannes Gutenberg University in Germany. One of her current research interests is the cross-talk between the immune and nervous systems in neurology. Introducing a wide range of research tools of her own, including genetically engineered mice, 7-Tesla magnetic resonance imaging (MRI) and live imaging of the brain during inflammation, she illustrated new approaches by which we could further elucidate the mechanisms involved in the pathogenesis of MS. The second lecture was presented by Dr Shinji Oki of the National Center of Neurology and Psychiatry. He introduced his research on a newly developed mouse model mimicking the secondary progressive MS phenotype.2 Previous work identified the NR4A2 gene as the most upregulated gene in relapsing–remitting MS T cells. While experimental autoimmune encephalomyelitis (EAE) induced in mice lacking the NR4A2 gene in helper T cells resulted in milder disease, the mice unexpectedly developed a late and chronic form of EAE in which atypical helper T cells expressing eomesodermin with cytotoxic properties were involved. Intriguingly, eomesodermin+ helper T cells were also significantly increased in the peripheral blood of secondary progressive MS patients. Dr Oki's research has resulted in a potentially informative model for use in translational research. The third lecture was presented by Dr Norio Chihara of Kobe University, and focused on the factors controlling the disease course of MS. Exhausted T cells evidently arise in chronic disease settings and show deficits in effector functions, as well as expressing high levels of co-inhibitory receptors, such as PD-1, Tim-2, Lag-3 and TIGIT. He applied a state-of-the-art methodology using single-cell RNA sequencing and “cytometry by time of flight” (dubbed “CyTOF”) to reveal how various co-inhibitory and co-stimulatory receptors are co-expressed. His findings provide a platform for the identification of novel molecules and pathways that lead to exhausted T cell states in various disease settings including cancer, infection and MS. The next session consisted of poster presentations. First, each presenter provided a short oral description of their studies. Free discussions followed, with each researcher in attendance in front of their posters. Nine posters were presented in total, and their themes were diverse, including Ehlers–Danlos syndrome, progressive multifocal leukoencephalopathy, anti-myelin oligodendrocyte glycoprotein antibody-related disorder and interferon-beta therapy, and MRI findings associated with neurosarcoidosis, among others. Next came four oral presentations. Dr Daiki Takewaki from the National Center of Neurology and Psychiatry described an intriguing case that met the 2010 McDonald criteria for diagnosis of MS through objective clinical evidence, but lacked demonstrable brain or spinal cord MRI abnormalities. He presented a case series suggesting that they are clinically (by treatment effect), immunologically (by peripheral blood analyses) and radiologically (by imaging analyses) justified as immune-mediated encephalomyelitis, which should be considered distinct from somatoform disorders. Dr Ryo Yamasaki from Kyushu University then presented a talk on connexins (Cxs). Cxs form gap junction channels; astroglial Cx43 and oligodendroglial Cx32 and Cx47 are frequently lost in acute and chronic lesions of MS and neuromyelitis optica spectrum disorders (NMOSD).3 By utilizing various strains of genetically engineered mice, he showed how astroglial and oligodendroglial Cxs differentially modulate acute and chronic EAE. Dr Koji Shinoda of Kyushu University presented his research on gamma/delta T cells in MS, suggesting that the peripheral blood gamma/delta T-cell repertoire is skewed in MS patients. He further showed that the skewness was correlated with regulatory T cells and disease severity. Finally, Dr Fumitaka Shimizu of Yamaguchi University presented his recent high-impact research showing that serum immunoglobulin G from NMOSD patients could activate blood–brain barrier endothelial cells. His research was recently published in Science Translational Medicine.4 A lecture was then presented by a guest from the UK, Professor Cris Constantinescu of Nottingham University Hospitals. He first provided a comprehensive review of the current evidence relating to how microbiota and MS are closely linked, incorporating EAE studies, epidemiological studies and studies of microbiomes from MS patients' fecal samples. Next, he introduced an investigator-initiated clinical trial of his own, in which MS patients were experimentally infected with the hookworm, Necator americanus. The trial only recently concluded, and preliminary results suggest favorable outcomes with regard to MS relapse rates and biomarker analyses. The last session of the first day was a case study session chaired by Dr Kazumasa Yokoyama of Juntendo University (Fig. 2). Two perplexing cases were presented. All the participants were divided into small groups, and instructed to freely discuss how to diagnose and treat the patients described. Both cases were difficult to diagnose as either MS or neuromyelitis optica (NMO), and in both cases treatment selection was difficult. The general consensus among participants was that differentiating between MS and NMOSD is sometimes so difficult that we need to be cautious to decide the diagnosis and treatment. On the evening of day 1, the winners of the “Best Presentations” awards were announced (Fig. 3). The three winners were Dr Takewaki, Dr Yamasaki and Dr Shimizu. Day 2 commenced with a lecture presented by Professor Aksel Siva of Istanbul University, in which he provided a comprehensive review on the differential diagnosis of MS and NMOSD, with a focus on MRI findings. He described many important studies, including a recently published report entitled “MRI criteria for the diagnosis of MS”.5 A lecture was then given by Professor Sachio Miki of Osaka City University, in which he presented various examples of brain MRI derived from patients with progressive multifocal leukoencephalopathy that developed during MS treatment. The next session was “Debate Training”, and the theme was “How to manage an infectious risk of second-line drugs, fingolimod and natalizumab”. Fingolimod is an oral disease-modifying drug used in MS patients. Although the dosage and usage of each drug are fixed by Pharmaceutical Affairs Law, as MS experts, we should endeavor to maximize the efficacy of the treatment and to minimize the associated risks. Two presenters, one “pro” and the other “con”, presented evidence supporting their positions. Each presentation was so persuasive that the final judgment by the participants was that the debate was a draw. The final lecture was presented by Professor Kazuo Fujihara of Fukushima Medical University. As one of the leaders in his field, he eloquently summarized the available information on myelin oligodendrocyte glycoprotein antibody-associated disease to date. His comprehensive talk provided not only detailed insights into the methodological issues associated with measuring these antibodies, but also practical clinical issues that included how to treat patients with the antibody. The 5th Annual MS Summer College Meeting will take place in Tokyo or Yokohama, on 5 and 6 August 2018. None declared.