名古屋大学大学院医学系研究科 神経内科
【略歴】
2007年3月 名古屋大学医学部医学科卒業
2007年4月 愛知県厚生連豊田厚生病院（旧・加茂病院） 臨床研修医 2009年4月 同 神経内科
2014年4月 名古屋大学大学院医学系研究科 神経内科
慢性炎症性脱髄性多発根ニューロパチー（CIDP）は四肢の 運動感覚障害をきたす免疫介在性神経疾患であり、患者の ADLを高度に障害する厚労省指定難病でもある。本疾患の 詳細な病態はいまだ明らかではないが、その代表的な要因と して本疾患の臨床的多様性が挙げられる。CIDPは臨床像か ら典型的CIDPと非典型的CIDP（5つの亜型を含む）に分類さ れるが、各亜型の病態やバイオマーカーは明らかではなく、
その解明は喫緊の課題である。また治療には免疫グロブリン 大量静注療法（IVIg）、副腎皮質ステロイド、血漿浄化療法 の有効性がランダム化比較対照試験で確立しているものの、
これは主に典型的CIDPにおける知見で、非典型的CIDPは概 して治療抵抗性を示すことが指摘されている。
このようにCIDPの臨床的多様性に関する病態や各亜型にお ける患者重症度や治療反応性が不明な点が多いことを受け、
難治性疾患をはじめとする「神経免疫疾患のエビデンスによ る診断基準・重症度分類・ガイドラインの妥当性と患者QOL の検証」研究班が設置され、その一環としてCIDPの臨床的多 様性と予後を前向きに検討する全国16施設から構成される多 施設共同コホート研究（CIDP-J）が開始された。本研究では 新規に診断された未治療例と、過去に診断された治療歴のあ る既存例に大別して症例登録し、神経症候や重症度、神経伝 導検査、筋肉CT所見等の2年間にわたる継時的な蓄積と、登 録時における血清および一部の症例では髄液を集積した。
本研究は2015年10月より患者登録が開始され、2018年1月ま でに109例（新規例13例、既存例96例）が登録された。登録時 背景として、男女比1.7:1、発症時年齢45.6±17.0歳、病型内 訳は典型的CIDP 62例（67%）、遠位優位型（demyelinating acquired distal symmetric neuropathy, DADS）16例（17%）、
多巣型（multifocal acquired demyelinating sensory and motor, MADSAM）12例（13%）、純粋感覚型 2例（2%）であ り、それ以外の純粋運動型および限局型は確認できなかった。
亜型間の比較では、登録時のMRCスコア、握力、INCAT disability scaleに差異は認めず、初期治療として新規例全例 でIVIgが選択されていた。CIDPに対する多施設共同の前向 きコホート研究は本邦初の試みであり、本研究で発症早期に おける臨床的特徴と治療反応性や経過・予後との相関を解析 することで、病型別の治療体系の確立など、ガイドライン改 訂に有用な新たな知見が期待される。
24 日 シ ン ポ ジ ウ ム
シンポジウム 17
5月24日（木）15：20 ～ 17：20 第8会場 (ロイトン札幌2F エンプレス・ホール)
En
Chairs：HiroyukiMurai
DepartmentofNeurology,International UniversityofHealthandWelfare,Japan
MasakatsuMotomura
MedicalEngineeringCourse,Nagasaki InstituteofAppliedScience,Japan
≪Objective≫
The development of myasthenia gravis （MG） treatment is remarkable these days. The Japanese clinical guidelines for MG was published in 2014, setting the treatment goal as minimal manifestations with oral prednisolone of 5 mg/
day or below, and encouraged that treatment strategies should strive to attain this level as rapidly as possible.
Early fast-acting treatment is a powerful strategy for this purpose. Eculizumab is a monoclonal antibody that binds to complement protein C5 and may be beneficial to treat refractory MG. Numbers of treatment trials are in progress internationally. Here, we will discuss with an international panel the way to pursue the best treatment strategy of MG.
S-17-1 The treatment
strategies of Japanese clinical guidelines for myasthenia gravis
○ HiroyukiMurai
Department of Neurology, International University of Health and Welfare, Japan
【Curriculum Vitae】
Prof.MuraigraduatedfromKyushuUniversity,Japanin1988 andwastrainedasaneurologistthereafter.From1995to1998, hewasaffiliatedwithRoswellParkCancerInstitute,Buffalo,NY, asaNeurologyfollow.From2000,hehasservedasanassistant professoratDepartmentofNeurology,KyushuUniversity.He wasnominatedasaprofessorandchairmanofDepartmentof Neurology,SchoolofMedicine,InternationalUniversityofHealth andWelfare,anewlyestablishedmedicalschoolinNarita,in2017.
Hehasdevotedhiscareertostudyingmyastheniagravis（MG）.
Hisdoctoralthesiswasaboutimmunohistologicalstudyofthymus inMG.HeperformednationwideepidemiologicalsurveyofMGin Japanin2006.HeisanexecutivememberofJapanMGRegistry StudyGroup.HealsoservedasamemberofJapaneseCommittee ontheClinicalGuidelinesforMG.Internationally,heservedas amemberofMGFATaskForceonInternationalMGTreatment Guidelines.
The clinical guidelines for myasthenia gravis （MG） in Japan prioritize maintaining patients' health-related quality of life. The initial treatment goal is defined as a post-intervention status of minimal manifestations or better, with an oral prednisolone dose of 5 mg/day or lower.
Every effort should be made to attain this level as rapidly as possible. To achieve this goal, the guidelines recommend to minimize the oral prednisolone dose, to start calcineurin inhibitors early in the course of treatment, to make good use of intravenous methylprednisolone infusion sometimes combined with plasma exchange/plasmapheresis or intravenous immunoglobulin, and to treat patients effectively with an early fast-acting treatment strategy.
Thymectomy is considered an option for treating non-thymomatous early-onset myasthenia gravis in patients with positive anti-acetylcholine receptor antibodies and thymic hyperplasia in the early stages of the disease.
24 シ ン ポ ジ ウ ム 日 シンポジウム 16
5月24日（木）15：20 ～ 17：20 第7会場 (ロイトン札幌1F キャッスル)
Jp
S-16-4 CIDP-Jの現況
○池田 昇平
名古屋大学大学院医学系研究科 神経内科
【略歴】
2007年3月 名古屋大学医学部医学科卒業
2007年4月 愛知県厚生連豊田厚生病院（旧・加茂病院） 臨床研修医 2009年4月 同 神経内科
2014年4月 名古屋大学大学院医学系研究科 神経内科
慢性炎症性脱髄性多発根ニューロパチー（CIDP）は四肢の 運動感覚障害をきたす免疫介在性神経疾患であり、患者の ADLを高度に障害する厚労省指定難病でもある。本疾患の 詳細な病態はいまだ明らかではないが、その代表的な要因と して本疾患の臨床的多様性が挙げられる。CIDPは臨床像か ら典型的CIDPと非典型的CIDP（5つの亜型を含む）に分類さ れるが、各亜型の病態やバイオマーカーは明らかではなく、
その解明は喫緊の課題である。また治療には免疫グロブリン 大量静注療法（IVIg）、副腎皮質ステロイド、血漿浄化療法 の有効性がランダム化比較対照試験で確立しているものの、
これは主に典型的CIDPにおける知見で、非典型的CIDPは概 して治療抵抗性を示すことが指摘されている。
このようにCIDPの臨床的多様性に関する病態や各亜型にお ける患者重症度や治療反応性が不明な点が多いことを受け、
難治性疾患をはじめとする「神経免疫疾患のエビデンスによ る診断基準・重症度分類・ガイドラインの妥当性と患者QOL の検証」研究班が設置され、その一環としてCIDPの臨床的多 様性と予後を前向きに検討する全国16施設から構成される多 施設共同コホート研究（CIDP-J）が開始された。本研究では 新規に診断された未治療例と、過去に診断された治療歴のあ る既存例に大別して症例登録し、神経症候や重症度、神経伝 導検査、筋肉CT所見等の2年間にわたる継時的な蓄積と、登 録時における血清および一部の症例では髄液を集積した。
本研究は2015年10月より患者登録が開始され、2018年1月ま でに109例（新規例13例、既存例96例）が登録された。登録時 背景として、男女比1.7:1、発症時年齢45.6±17.0歳、病型内 訳は典型的CIDP 62例（67%）、遠位優位型（demyelinating acquired distal symmetric neuropathy, DADS）16例（17%）、
多巣型（multifocal acquired demyelinating sensory and motor, MADSAM）12例（13%）、純粋感覚型 2例（2%）であ り、それ以外の純粋運動型および限局型は確認できなかった。
亜型間の比較では、登録時のMRCスコア、握力、INCAT disability scaleに差異は認めず、初期治療として新規例全例 でIVIgが選択されていた。CIDPに対する多施設共同の前向 きコホート研究は本邦初の試みであり、本研究で発症早期に おける臨床的特徴と治療反応性や経過・予後との相関を解析 することで、病型別の治療体系の確立など、ガイドライン改 訂に有用な新たな知見が期待される。
24 日 シ ン ポ ジ ウ ム
シンポジウム 17
5月24日（木）15：20 ～ 17：20 第8会場 (ロイトン札幌2F エンプレス・ホール)
En
S-17-2 An approach to optimal treatments for patients with myasthenia gravis
○ TedM.Burns
University of Virginia, USA
【Curriculum Vitae】
Ted M. Burns, MD, is the Harrison Distinguished Professor at the University of Virginia. He is the Neuromuscular Division Chief and Director of the Electromyography Laboratory. Dr. Burns won the Myasthenia Gravis Foundation of Amercia's （MGFA） national
“Doctor of the Year” award in 2010. He was also the Chair of the MGFA's Medical and Scientific Advisory Board from 2013-2015.
He has received “Best Doctor” recognition for many years. He was also the national Chair of the American Academy of Neurology's Neuromuscular Section in 2013. He has over 100 publications.
His academic interests include quality of life for patients with neuromuscular disorders and the development and validation of user-friendly outcome measures for neuromuscular disorders, especially myasthenia gravis and chronic polyneuropathy. Another interest of his is podcasting for the education of physicians, patients and families. He is creator and editor of the Neurology journal's weekly podcast and the American Association of Neuromuscular and Electrodiagnostic Medicine's （AANEM） podcast. The Neurology Podcast enjoys over 50,000 downloads per week, with over 16 million total downloads since 2007. He is also the creator of the MGFA's podcast series designed to educate patients and families about practical aspects of MG.
The first steps in deciding best treatment options in myasthenia gravis （MG） include sufficient clinical characterization of the individual's MG. Characterization should be based on severity, distribution of weakness, serology, past history with MG, including previous treatments and treatment responses, thymus status, co-morbidities and age. For example, ocular MG should be distinguished from generalized MG and AChR+ MG should be considered different than MuSK MG. Conventional MG treatments should beindividualized based on these and other clinical characteristics. Newer promising therapies for AChR MG include complement inhibitors
（eg Eculizumab） and possibly Rituximab. For MuSK MG, early Rituximab treatment appears to be desirable.
Recently Japanese and international guidelines should be referenced and followed. This is also an exciting time for other innovative and promising interventions, but cost of these potential future treatments may present challenges.
S-17-3 Complement Inhibition in the Treatment of Myasthenia Gravis
○ JamesF.HowardJr
The University of North Carolina at Chapel Hill, USA
【Curriculum Vitae】
Dr. Howard received his MD degree from the University of Vermont School of Medicine. He completed his residency in Neurology and fellowship training in Neuromuscular Disorders-EMG at the University of Virginia. He joined the Department of Neurology at The University of North Carolina at Chapel Hill in 1979 and became Chief of the Neuromuscular Disorders Section in 1996. He is the Director of the MDA Clinic and Medical Director of the EMG Section of the Clinical Neurophysiology Laboratory.
He is a fellow in the American Academy of Neurology and the American Association of Neuromuscular and Electrodiagnostic Medicine. He is member of the American Neurological Association.
Dr. Howard serves as a member of the National Medical/Scientific Advisory Board of the Myasthenia Gravis Foundation of America and was a prior member of the Medical Advisory Committee of the Muscular Dystrophy Association. Dr. Howard has served previously as a member of the Board of Directors for the American Association of Neuromuscular & Electrodiagnostic Medicine, the American Board of Electrodiagnostic Medicine and as a member of the Executive Committee for the Muscle Study Group and as Chair of the National Medical/Scientific Advisory Board of the Myasthenia Gravis Foundation of America.
Neuromuscular transmission in Myasthenia Gravis （MG）
is impaired by multiple mechanisms including functional blockade of the acetylcholine receptor （AChR）, antigenic modulation of AChR and by complement activation at the neuromuscular junction. Current therapies focus on broad immune suppression each with variable eff ect, signifi cant side eff ects and patient intolerance. Targeting the terminal complement component （membrane attack complex, MAC） is a newly recognized approach to treat MG.
Refractory generalized myasthenia gravis is a chronic, debilitating, rare disorder of severe muscle weakness resulting from autoantibody-mediated destruction of the neuromuscular junction in 10% to 15% of patients with MG. Eculizumab, a humanized monoclonal antibody to the 5th complement protein （C5） is shown to be eff ective in the management of previously treated but refractory patients with generalized, AChR antibody positive MG. Patients are induced with 900-mg intravenously weekly for one month followed by 1200-mg thereafter at two week intervals.
Onset of eff ect is rapid, most improving within 12 weeks with a durable response over several years. Improvement is seen in all domains （ocular, bulbar, respiratory and limb） as measured by the Quantified Myasthenia Gravis
（QMG） Score, the MG Activities of Daily Living Score
（MG-ADL）, the MG Composite （MGC） Score and the MG Quality of Life （MG-QoL15） instrument. Adverse events are mild to moderate in degree. It is necessary that all patients be immunized against Neisseria meningitidis.
24 日 シ ン ポ ジ ウ ム
シンポジウム 17
5月24日（木）15：20 ～ 17：20 第8会場 (ロイトン札幌2F エンプレス・ホール)
En
S-17-4 How to achieve early treatment target in generalized myasthenia gravis
○ KimiakiUtsugisawa
Department of Neurology, Hanamaki General Hospital, Japan
【Curriculum Vitae】
Kimiaki Utsugisawa is Director of Neurology at Hanamaki General Hospital. He graduated from Hirosaki University School of Medicine and received his MD in 1988. He passed the qualifying examination to become a Certified Medical Specialist of Neurology in 1992, then acquired his PhD in Medical Science （Iwate Medical University）
in 1995. His major research interests lie in neuroimmunological diseases, particularly issues in the management of myasthenia gravis to improve patients' health-related quality of life.
He presently serves as: Certified Medical Specialist of Neurology of The Japanese Society of Neurology; Board Certified Member of The Japanese Society of Neuroimmunology; Board Certified Member of the Japanese Society of Neurological Therapeutics; Vice Chair of the Committee for Clinical Practice Guidelines for Myasthenia Gravis in Japan; Chair of the Japan MG registry study group; and a Medical/Scientific Advisory Board member of the Myasthenia Gravis Foundation of America.
Long-term full remission without immune treatment is rare among patients with myasthenia gravis （MG）.Many patients remain burdened by insufficient improvement and the long-term side effects of oral steroids. More effort is required to reduce the severity of the illness and oral steroid doses.The health-related quality of life （QOL） of patients with minimal manifestations （MM） or better status who are treated with ≤ 5 mg prednisolone/day
（MM-or-better-5 mg） is almost identical to that of patients who achieve complete stable remission. Thus, the early achievement of MM-or-better-5 mg is now proposed as a practical target for MG treatment in Japan to enable patients to have a normal QOL. However, the percentage of patients who can achieve MM-or-better-5 mg is not high, and higher doses of oral steroids and longer treatment duration do not correlate with achieving this target, indicating that the treatment strategy should be changed to further increase success.
Aggressive early fast-acting treatment strategies （EFT）
for MG include non-oral immunotherapies such as plasmapheresis, intravenous immunoglobulin, and high-dose intravenous methylprednisolone, often in combination with early use of calcineurin inhibitors. Such fast-acting immunotherapies can be repeated as needed during the early and maintenance stages of treatment, and thus EFT can lead to earlier improvement with lower doses of oral steroids. These probably result in the early and frequent achievement of MM-or-better-5 mg, which can last for some time. We investigated whether or not EFT could promote the early achievement of MM-or-better-5 mg for >6 months and which of low-, intermediate-, or high-dose oral steroid regimens would be the optimal choice of therapy for generalized MG.
24 シ ン ポ ジ ウ ム 日 シンポジウム 17
5月24日（木）15：20 ～ 17：20 第8会場 (ロイトン札幌2F エンプレス・ホール)
En
S-17-2 An approach to optimal treatments for patients with myasthenia gravis
○ TedM.Burns
University of Virginia, USA
【Curriculum Vitae】
Ted M. Burns, MD, is the Harrison Distinguished Professor at the University of Virginia. He is the Neuromuscular Division Chief and Director of the Electromyography Laboratory. Dr. Burns won the Myasthenia Gravis Foundation of Amercia's （MGFA） national
“Doctor of the Year” award in 2010. He was also the Chair of the MGFA's Medical and Scientific Advisory Board from 2013-2015.
He has received “Best Doctor” recognition for many years. He was also the national Chair of the American Academy of Neurology's Neuromuscular Section in 2013. He has over 100 publications.
His academic interests include quality of life for patients with neuromuscular disorders and the development and validation of user-friendly outcome measures for neuromuscular disorders, especially myasthenia gravis and chronic polyneuropathy. Another interest of his is podcasting for the education of physicians, patients and families. He is creator and editor of the Neurology journal's weekly podcast and the American Association of Neuromuscular and Electrodiagnostic Medicine's （AANEM） podcast. The Neurology Podcast enjoys over 50,000 downloads per week, with over 16 million total downloads since 2007. He is also the creator of the MGFA's podcast series designed to educate patients and families about practical aspects of MG.
The first steps in deciding best treatment options in myasthenia gravis （MG） include sufficient clinical characterization of the individual's MG. Characterization should be based on severity, distribution of weakness, serology, past history with MG, including previous treatments and treatment responses, thymus status, co-morbidities and age. For example, ocular MG should be distinguished from generalized MG and AChR+ MG should be considered different than MuSK MG. Conventional MG treatments should beindividualized based on these and other clinical characteristics. Newer promising therapies for AChR MG include complement inhibitors
（eg Eculizumab） and possibly Rituximab. For MuSK MG, early Rituximab treatment appears to be desirable.
Recently Japanese and international guidelines should be referenced and followed. This is also an exciting time for other innovative and promising interventions, but cost of these potential future treatments may present challenges.
S-17-3 Complement Inhibition in the Treatment of Myasthenia Gravis
○ JamesF.HowardJr
The University of North Carolina at Chapel Hill, USA
【Curriculum Vitae】
Dr. Howard received his MD degree from the University of Vermont School of Medicine. He completed his residency in Neurology and fellowship training in Neuromuscular Disorders-EMG at the University of Virginia. He joined the Department of Neurology at The University of North Carolina at Chapel Hill in 1979 and became Chief of the Neuromuscular Disorders Section in 1996. He is the Director of the MDA Clinic and Medical Director of the EMG Section of the Clinical Neurophysiology Laboratory.
He is a fellow in the American Academy of Neurology and the American Association of Neuromuscular and Electrodiagnostic Medicine. He is member of the American Neurological Association.
Dr. Howard serves as a member of the National Medical/Scientific Advisory Board of the Myasthenia Gravis Foundation of America and was a prior member of the Medical Advisory Committee of the Muscular Dystrophy Association. Dr. Howard has served previously as a member of the Board of Directors for the American Association of Neuromuscular & Electrodiagnostic Medicine, the American Board of Electrodiagnostic Medicine and as a member of the Executive Committee for the Muscle Study Group and as Chair of the National Medical/Scientific Advisory Board of the Myasthenia Gravis Foundation of America.
Neuromuscular transmission in Myasthenia Gravis （MG）
is impaired by multiple mechanisms including functional blockade of the acetylcholine receptor （AChR）, antigenic modulation of AChR and by complement activation at the neuromuscular junction. Current therapies focus on broad immune suppression each with variable eff ect, signifi cant side eff ects and patient intolerance. Targeting the terminal complement component （membrane attack complex, MAC） is a newly recognized approach to treat MG.
Refractory generalized myasthenia gravis is a chronic, debilitating, rare disorder of severe muscle weakness resulting from autoantibody-mediated destruction of the neuromuscular junction in 10% to 15% of patients with MG. Eculizumab, a humanized monoclonal antibody to the 5th complement protein （C5） is shown to be eff ective in the management of previously treated but refractory patients with generalized, AChR antibody positive MG. Patients are induced with 900-mg intravenously weekly for one month followed by 1200-mg thereafter at two week intervals.
Onset of eff ect is rapid, most improving within 12 weeks with a durable response over several years. Improvement is seen in all domains （ocular, bulbar, respiratory and limb） as measured by the Quantified Myasthenia Gravis
（QMG） Score, the MG Activities of Daily Living Score
（MG-ADL）, the MG Composite （MGC） Score and the MG Quality of Life （MG-QoL15） instrument. Adverse events are mild to moderate in degree. It is necessary that all patients be immunized against Neisseria meningitidis.