Kyushu University [Ogata Hidenori (Assistant Professor) Kyushu University Hospital, Neurology]

Ogata Hidenori

Last modified date：2023.12.06

Assistant Professor / Neurology / Kyushu University Hospital

Papers

1.	Taiki Fukushima, Shohei Ikeda, Minoru Tomita, Yu Mori, Yuki Fukami, Haruki Koike, Masahisa Katsuno, Hidenori Ogata, Noriko Isobe, Naoki Hattori, A Case of Demyelinating Neuropathy with Markedly Elevated Serum IgG4 Levels and Anti-Contactin 1 IgG4 Antibody., Internal medicine (Tokyo, Japan), 10.2169/internalmedicine.9286-21, 2022.07, We herein report a 77-year-old man with a 4-month history of progressive gait and sensory disturbances of the extremities. A nerve conduction study indicated demyelinating polyneuropathy. Serum IgG4 levels and anti-contactin 1 IgG4 antibodies were markedly increased. The sural nerve biopsy specimen showed IgG4-positive plasma cell infiltration in the epineurium. Treatment with steroids resulted in an amelioration of functional status, improvement of nerve conduction parameters, decreased serum IgG4 levels, and negative conversion of anti-contactin1 antibody. Further studies are needed to clarify the significance of IgG4-positive plasma cell infiltration in anti-contactin 1 antibody-positive neuropathies..
2.	Xu Zhang, Jun-Ichi Kira, Hidenori Ogata, Tomohiro Imamura, Mikio Mitsuishi, Takayuki Fujii, Masaki Kobayashi, Kazuo Kitagawa, Yukihiro Namihira, Yusuke Ohya, Guzailiayi Maimaitijiang, Ryo Yamasaki, Yuko Fukata, Masaki Fukata, Noriko Isobe, Yuri Nakamura, Anti-LGI4 Antibody Is a Novel Juxtaparanodal Autoantibody for Chronic Inflammatory Demyelinating Polyneuropathy., Neurology(R) neuroimmunology & neuroinflammation, 10.1212/NXI.0000000000200081, 10, 2, 2023.03, BACKGROUND AND OBJECTIVES: The objective of this study was to discover novel nodal autoantibodies in chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: We screened for autoantibodies that bind to mouse sciatic nerves and dorsal root ganglia (DRG) using indirect immunofluorescence (IFA) assays with sera from 113 patients with CIDP seronegative for anti-neurofascin 155 and anticontactin-1 antibodies and 127 controls. Western blotting, IFA assays using HEK293T cells transfected with relevant antigen expression plasmids, and cell-based RNA interference assays were used to identify target antigens. Krox20 and Periaxin expression, both of which independently control peripheral nerve myelination, was assessed by quantitative real-time PCR after application of patient and control sera to Schwann cells. RESULTS: Sera from 4 patients with CIDP, but not control sera, selectively bound to the nodal regions of sciatic nerves and DRG satellite glia (p = 0.048). The main immunoglobulin G (IgG) subtype was IgG4. IgG from these 4 patients stained a 60-kDa band on Western blots of mouse DRG and sciatic nerve lysates. These features indicated leucine-rich repeat LGI family member 4 (LGI4) as a candidate antigen. A commercial anti-LGI4 antibody and IgG from all 4 seropositive patients with CIDP showed the same immunostaining patterns of DRG and cultured rat Schwann cells and bound to the 60-kDa protein in Western blots of LGI4 overexpression lysates. IgG from 3 seropositive patients, but none from controls, bound to cells cotransfected with plasmids containing LGI4 and a disintegrin and metalloprotease domain-containing protein 22 (ADAM22), an LGI4 receptor. In cultured rat Schwann and human melanoma cells constitutively expressing LGI4, LGI4 siRNA effectively downregulated LGI4 and reduced patients' IgG binding compared with scrambled siRNA. Application of serum from a positive patient to Schwann cells expressing ADAM22 significantly reduced the expression of Krox20, but not Periaxin. Anti-LGI4 antibody-positive patients had a relatively old age at onset (mean age 58 years), motor weakness, deep and superficial sensory impairment with Romberg sign, and extremely high levels of CSF protein. Three patients showed subacute CIDP onset resembling Guillain-Barré syndrome. DISCUSSION: IgG4 anti-LGI4 antibodies are found in some elderly patients with CIDP who present subacute sensory impairment and motor weakness and are worth measuring, particularly in patients with symptoms resembling Guillain-Barré syndrome..
3.	Takeuchi Hajime, Masaki Katsuhisa, Ogata Hidenori, Nagata Satoshi, Shimogawa Takafumi, Yamasaki Ryo, Isobe Noriko, Teaching Video NeuroImage: Reversible Parkinsonism Caused by Lumboperitoneal Shunt Overdrainage, NEUROLOGY, 10.1212/WNL.0000000000200994, 99, 11, 486-488, 2022.09.
4.	Okadome T, Takeuchi H, Yamaguchi T, Mukaino T, Ogata H, Masaki K, Shigeto H, Isobe N. , Shadowboxing-induced reflex seizures in a patient with focal epilepsy., Epilepsy & behavior reports, 10.1016/j.ebr.2022.100543, 19, 100543-100543, 2022.04.
5.	Nomura, Emi; Kawahara, Yuko; Omote, Yoshio; Tadokoro, Koh; Takemoto, Mami; Hishikawa, Nozomi; Yamashita, Toru; Ogata, Hidenori; Abe, Koji, The Oldest Japanese Case of Combined Central and Peripheral Demyelination, which Developed Nine Years After the First Instance of Optic Neuritis, INTERNAL MEDICINE, 10.2169/internalmedicine.5536-20, 60, 2, 305-308, 2021.02.
6.	Hidenori Ogata, Xu Zhang, Saeko Inamizu, Ken-Ichiro Yamashita, Ryo Yamasaki, Takuya Matsushita, Noriko Isobe, Akio Hiwatashi, Shozo Tobimatsu, Jun-ichi Kira, Optic, trigeminal, and facial neuropathy related to anti-neurofascin 155 antibody., Annals of clinical and translational neurology, 10.1002/acn3.51220, 7, 11, 2297-2309, 2020.11.
7.	Shinobu Shimizu, Masahiro Iijima, Yuki Fukami, Natsuko Tamura, Masahiro Nakatochi, Masahiko Ando, Ryoji Nishi, Haruki Koike, Kenichi Kaida, Michiaki Koga, Takashi Kanda, Hidenori Ogata, Jun Ichi Kira, Masahiro Mori, Satoshi Kuwabara, Masahisa Katsuno, Efficacy and safety of rituximab in refractory CIDP with or without IgG4 autoantibodies (RECIPE) Protocol for a double-blind, randomized, placebo-controlled clinical trial, JMIR Research Protocols, 10.2196/17117, 9, 4, 2020.04, Background: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated peripheral neuropathy that is currently classified into several clinical subtypes, which are presumed to have different pathogenic mechanisms. Recently, studies identified a subgroup of patients with CIDP who were positive for IgG4 autoantibodies against paranodal proteins, such as neurofascin-155 and contactin-1, who respond poorly to first-line therapies for typical CIDP, including intravenous immunoglobulin therapy. Objective: This study aims to evaluate the efficacy and safety of intravenous rituximab according to IgG4 autoantibody status in patients with refractory CIDP. Methods: The Evaluation of the Efficacy and Safety of Rituximab in Refractory CIDP Patients with IgG4 Autoantibodies in the Exploratory Clinical (RECIPE) trial consists of 2 cohorts: a multicenter, placebo-controlled, randomized study cohort of 15 patients with IgG4 autoantibody-positive CIDP (rituximab:placebo = 2:1) and an open-label trial cohort of 10 patients with antibody-negative CIDP. The primary endpoint is improvement in functional outcome assessed using the adjusted Inflammatory Neuropathy Cause and Treatment Disability Scale score at 26, 38, or 52 weeks after the start of treatment with rituximab in patients with CIDP and anti-paranodal protein antibodies. Secondary outcome measures include grip strength, manual muscle testing sum scores, results of nerve conduction studies, and other functional scales. Results: We plan to enroll 25 cases for the full analysis set. Recruitment is ongoing, with 14 patients enrolled as of January 2020. Enrollment will close in September 2020, and the study is planned to end in December 2021. Conclusions: This randomized controlled trial will determine if rituximab is safe and effective in patients with anti-paranodal antibodies. An open-label study will provide additional data on the effects of rituximab in patients with antibody-negative CIDP. The results of the RECIPE trial are expected to provide evidence for the positioning of rituximab as a pathogenesis-based therapeutic for refractory CIDP..
8.	Hidenori Ogata, Anti-nodal/paranodal antibodies in human demyelinating disorders, Clinical and Experimental Neuroimmunology, 10.1111/cen3.12567, 11, S1, 41-47, 2020.03, Anti-nodal/paranodal antibodies have been reported in human demyelinating disorders. Anti-nodal protein antibodies, namely, anti-neurofascin (NF) 186 antibodies and antibodies against paranodal proteins, such as NF155, contactin 1 (CNTN1), and contactin-associated protein 1 (CASPR1), are found in subsets of chronic inflammatory demyelinating polyneuropathy (CIDP). In particular, CIDP patients with IgG4 anti-NF155 antibodies and those with IgG4 anti-CNTN1 antibodies commonly show sensory ataxia, severe demyelination on nerve conduction studies, very high cerebrospinal (CSF) protein levels and poor response to intravenous immunoglobulin. However, younger age at onset, higher frequency of tremor, and nerve root hypertrophy are characteristic of anti-NF155 antibody–positive CIDP, whereas anti-CNTN1 antibody–positive CIDP is characterized by higher age at onset, early axonal damage, subacute aggressive course, and concurrence of membranous nephropathy. Interestingly, anti-NF155 antibody–positive CIDP occasionally accompanies central nervous system lesions suggestive of demyelination. Such cases are termed combined central and peripheral demyelination. Both CIDP with anti-NF155 antibodies and CIDP with anti-CNTN1 antibodies usually demonstrate detachment of terminal loops from the axolemma at the node of Ranvier in biopsied sural nerves. IgG4 in vivo is monovalent and bispecific and lacks complement-binding capability; therefore, IgG4 autoantibodies can only interfere with protein–protein interactions. This property of IgG4 explains the sural nerve pathology but the reasons behind nerve root hypertrophy and CSF protein increase are not known. Recently, we found significant elevation of both Th1 and Th2 cytokines in CSF from anti-NF155 antibody–positive CIDP patients, indicating T-cell involvement in this condition..
9.	Hidenori Ogata, Noriko Isobe, Xu Zhang, Ryo Yamasaki, Takayuki Fujii, Akira Machida, Nobutoshi Morimoto, Kenichi Kaida, Teruaki Masuda, Yukio Ando, Motoi Kuwahara, Susumu Kusunoki, Yuri Nakamura, Takuya Matsushita, Jun ichi Kira, Unique HLA haplotype associations in IgG4 anti-neurofascin 155 antibody-positive chronic inflammatory demyelinating polyneuropathy, Journal of Neuroimmunology, 10.1016/j.jneuroim.2019.577139, 339, 2020.02, To clarify the immunogenetic background of patients with immunoglobulin G (IgG)4 anti-neurofascin 155 (NF155) antibody-positive chronic inflammatory demyelinating polyneuropathy (CIDP), we genotyped the extended human leukocyte antigen (HLA) haplotypes in 22 Japanese patients with this disorder and compared them with those of healthy Japanese controls. All IgG4 anti-NF155 antibody-positive CIDP patients exclusively carried either HLA-DRB115:01-DRB501:01-DQA101:02-DQB106:02 or -(A24:02)-B52:01-C12:02-DRB115:02-DRB501:02-DQA101:03-DQB106:01, resulting in significantly increased HLA-DRB115, -DRB115:01, -DQB106:01/06:02, -DQB106:02, and -DRB115:01-DQB1*06:02 frequencies compared with healthy Japanese controls. These findings indicate the involvement of specific HLA class II molecules in the pathomechanisms of IgG4 anti-NF155 antibody-positive CIDP..
10.	Hidenori Ogata, Xu Zhang, Ryo Yamasaki, Takayuki Fujii, Akira Machida, Nobutoshi Morimoto, Kenichi Kaida, Teruaki Masuda, Yukio Ando, Motoi Kuwahara, Susumu Kusunoki, Yuri Nakamura, Takuya Matsushita, Noriko Isobe, Jun ichi Kira, Intrathecal cytokine profile in neuropathy with anti-neurofascin 155 antibody, Annals of Clinical and Translational Neurology, 10.1002/acn3.50931, 6, 11, 2304-2316, 2019.11, Objective: To characterize the CSF cytokine profile in chronic inflammatory demyelinating polyneuropathy (CIDP) patients with IgG4 anti-neurofascin 155 (NF155) antibodies (NF155⁺ CIDP) or those lacking anti-NF155 antibodies (NF155⁻ CIDP). Methods: Twenty-eight CSF cytokines/chemokines/growth factors were measured by multiplexed fluorescent immunoassay in 35 patients with NF155⁺ CIDP, 36 with NF155⁻ CIDP, and 28 with non-inflammatory neurological disease (NIND). Results: CSF CXCL8/IL-8, IL-13, TNF-α, CCL11/eotaxin, CCL2/MCP-1, and IFN-γ were significantly higher, while IL-1β, IL-1ra, and G-CSF were lower, in NF155⁺ CIDP than in NIND. Compared with NF155⁻ CIDP, CXCL8/IL-8 and IL-13 were significantly higher, and IL-1β, IL-1ra, and IL-6 were lower, in NF155⁺ CIDP. CXCL8/IL-8, IL-13, CCL11/eotaxin, CXCL10/IP-10, CCL3/MIP-1α, CCL4/MIP-1β, and TNF-α levels were positively correlated with markedly elevated CSF protein, while IL-13, CCL11/eotaxin, and IL-17 levels were positively correlated with increased CSF cell counts. IL-13, CXCL8/IL-8, CCL4/MIP-1β, CCL3/MIP-1α, and CCL5/RANTES were decreased by combined immunotherapies in nine NF155⁺ CIDP patients examined longitudinally. By contrast, NF155⁻ CIDP had significantly increased IFN-γ compared with NIND, and exhibited positive correlations of IFN-γ, CXCL10/IP-10, and CXCL8/IL-8 with CSF protein. Canonical discriminant analysis of cytokines/chemokines revealed that NF155⁺ and NF155⁻ CIDP were separable, and that IL-4, IL-10, and IL-13 were the three most significant discriminators. Interpretation: Intrathecal upregulation of type 2 helper T (Th2) cell cytokines is characteristic of IgG4 NF155⁺ CIDP, while type 1 helper T cell cytokines are increased in CIDP regardless of the presence or absence of anti-NF155 antibodies, suggesting that overproduction of Th2 cell cytokines is unique to NF155⁺ CIDP..
11.	Yuri Mizuno, Koji Shinoda, Mitsuru Watanabe, Hidenori Ogata, Noriko Isobe, Takuya Matsushita, Ryo Yamasaki, Kimihiro Tanaka, Haruki Koike, Masahisa Katsuno, Jun ichi Kira, Intractable axonal neuropathy with multifocal peripheral nerve swelling in neuromyelitis optica spectrum disorders A case report, Multiple Sclerosis and Related Disorders, 10.1016/j.msard.2019.06.033, 35, 16-18, 2019.10, We report a patient with neuromyelitis optica spectrum disorders (NMOSD) with anti-aquaporin 4 (AQP4) antibodies, who developed intractable axonal neuropathy presenting with multifocal peripheral nerve swelling by magnetic resonance (MR) neurography. A 52-year-old woman with a 12-year history of polymyositis and rheumatoid arthritis had been treated with prednisolone, tacrolimus, and abatacept (CTLA-4-Ig). She developed progressive numbness and tingling sensations in the distal parts of all limbs at the age of 50 years, followed by weakness of both upper limbs 6 months later. Neurological examination revealed severe muscle weakness and atrophy of the right upper limb with proximal dominance, diffuse moderate weakness of the left upper limb, severe sensory impairment of all modalities of four limbs in glove and stocking distribution, wide-based gait with positive Romberg's sign, and absence of all tendon reflexes. She was diagnosed with NMOSD due to positive serum anti-AQP4 antibodies and a longitudinally extensive cervical spinal cord lesion on MR images. Intravenous methylprednisolone pulse therapy, plasma exchange and intravenous immunoglobulin administration were performed, which improved the spinal cord lesion on MRI, but did not ameliorate her symptoms. Notably, she also had axonal neuropathy characterized by asymmetrical, multifocal swelling of peripheral nerves by MR neurography. Histopathological examination of the biopsied sural nerve revealed axonal degeneration and endoneurial edema but no inflammatory cell infiltration. Although she was treated with intravenous methylprednisolone, intravenous immunoglobulin, oral prednisolone, tacrolimus and tocilizumab, her symptoms gradually progressed. Neurologists should be aware of co-existing intractable axonal neuropathy in NMOSD cases presenting as immunotherapy-resistant sensorimotor disturbances..
12.	Xu Zhang, Takayuki Fujii, Hidenori Ogata, Ryo Yamasaki, Katsuhisa Masaki, Yiwen Cui, Takuya Matsushita, Noriko Isobe, Jun-Ichi Kira, Cerebrospinal fluid cytokine/chemokine/growth factor profiles in idiopathic hypertrophic pachymeningitis, Journal of Neuroimmunology, 10.1016/j.jneuroim.2019.01.010, 330, 38-43, 2019.05, Hypertrophic pachymeningitis (HP) is a rare neurologic disease causing inflammatory fibrous thickening of the brain and spinal dura mater. We investigated the cerebrospinal fluid cytokine profile of HP by measuring 28 cytokines/chemokines/growth factors with a multiplexed fluorescent immunoassay in 8 patients with HP (6 idiopathic, 1 IgG4-related, 1 anti-neutrophil cytoplasmic antibody-related), and 11 with other non-inflammatory neurologic diseases (OND). Interleukin (IL)-4, IL-5, IL-9, IL-10, TNF-α, and CXCL8/IL-8 levels were significantly higher in idiopathic HP (IHP) than OND. Cluster analyses disclosed two major clusters: one mainly consisted of IHP and the other of OND, suggesting a unique cytokine profile in IHP..
13.	Yiwen Cui, Katsuhisa Masaki, Xu Zhang, Ryo Yamasaki, Takayuki Fujii, Hidenori Ogata, Shotaro Hayashida, Hiroo Yamaguchi, Fuminori Hyodo, Hinako Eto, Sachiko Koyama, Kyoko Iinuma, Tomomi Yonekawa, Takuya Matsushita, Mari Yoshida, Kazunori Yamada, Mitsuhiro Kawano, Marie Malissen, Bernard Malissen, Jun-Ichi Kira, A novel model for treatment of hypertrophic pachymeningitis, Annals of Clinical and Translational Neurology, 10.1002/acn3.715, 6, 3, 431-444, 2019.03, Objective: Immunoglobulin (Ig)G4-related disease is a major cause of hypertrophic pachymeningitis (HP), presenting as a progressive thickening of the dura mater. HP lacks an animal model to determine its underlying mechanisms. We developed a suitable animal model for the treatment of HP. Methods: We longitudinally evaluated dura in mice with a mutation (Y136F) in the linker for activation of T cells (LAT), which induced type 2 T helper (Th2) cell proliferation and IgG1 (IgG4 human equivalent) overexpression. Mice were therapeutically administered daily oral irbesartan from 3 to 6 weeks of age. Human IgG4-related, anti-neutrophil cytoplasmic antibody-related, and idiopathic HP dura were also immunohistochemically examined. Results: LATY136F mice showing dural gadolinium enhancement on magnetic resonance imaging had massive infiltration of B220 ⁺ B cells, IgG1 ⁺ cells, CD138 ⁺ plasma cells, CD3 ⁺ T cells, F4/80 ⁺ macrophages, and polymorphonuclear leukocytes in the dura at 3 weeks of age, followed by marked fibrotic thickening. In dural lesions, transforming growth factor (TGF)-β1 was produced preferentially in B cells and macrophages while TGF-β receptor I (TGF-βRI) was markedly upregulated on fibroblasts. Quantitative western blotting revealed significant upregulation of TGF-β1, TGF-βRI, and phosphorylated SMAD2/SMAD3 in dura of LATY136F mice aged 13 weeks. A similar upregulation of TGF-βRI, SMAD2/SMAD3, and phosphorylated SMAD2/SMAD3 was present in autopsied dura of all three types of human HP. Irbesartan abolished dural inflammatory cell infiltration and fibrotic thickening in all treated LATY136F mice with reduced TGF-β1 and nonphosphorylated and phosphorylated SMAD2/SMAD3. Interpretation: TGF-β1/SMAD2/SMAD3 pathway is critical in HP and is a potential novel therapeutic target..
14.	Hiwatashi Akio, Osamu Togao, Koji Yamashita, kazufumi kikuchi, Daichi Momosaka, Hiroshi Nakatake, Ryo Yamasaki, Hidenori Ogata, Masami Yoneyama, Jun-Ichi Kira, Hiroshi Honda, Simultaneous MR neurography and apparent T2 mapping in brachial plexus Evaluation of patients with chronic inflammatory demyelinating polyradiculoneuropathy, Magnetic Resonance Imaging, 10.1016/j.mri.2018.09.025, 55, 112-117, 2019.01, Purpose: MR neurography is known to be useful to evaluate nerve pathology. The purpose of this study was to evaluate the usefulness of simultaneous apparent T2 mapping and neurography with nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation enhancement imaging (SHINKEI) to distinguish patients with chronic inflammatory demyelinating polyneuropathy (CIDP) from healthy subjects. Materials and methods: This retrospective study included 13 patients with CIDP and five healthy subjects from 2015 to 2017. The T2 relaxation time and the size of the cervical ganglia and roots of the brachial plexus were measured. Statistical analyses were performed with the Mann-Whitney U test and receiver operating characteristics (ROC) analysis. Results: The T2 relaxation times of the ganglia and roots were longer in patients with CIDP (119.31 ± 35.53 msec and 111.15 ± 33.82 msec) than in healthy subjects (101.42 ± 26.42 msec and 85.29 ± 13.22 msec, P = 0.0007 and P
15.	Yu Hashimoto, Hidenori Ogata, Ryo Yamasaki, Takakazu Sasaguri, Senri Ko, kenichiro yamashita, Zhang Xu, Takuya Matsushita, Takahisa Tateishi, Shin'Ichi Akiyama, Shoichi Maruyama, Akifumi Yamamoto, Jun-Ichi Kira, Chronic inflammatory demyelinating polyneuropathy with concurrent membranous nephropathy An anti-paranode and podocyte protein antibody study and literature survey, Frontiers in Neurology, 10.3389/fneur.2018.00997, 9, NOV, 2018.11, Background: Several case reports have described the concurrence of chronic inflammatory demyelinating polyneuropathy (CIDP) and membranous nephropathy (MN). The presence of autoantibodies against podocyte antigens phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain containing 7A (THSD7A) in MN suggests an autoimmune mechanism. Some CIDP patients also harbor autoantibodies against paranodal proteins such as neurofascin 155 (NF155) and contactin-1 (CNTN1). We investigated the relationship between CIDP and MN by assaying autoantibodies against paranodal and podocyte antigens in a CIDP patient with MN, and by a literature survey on the clinical features of CIDP with MN. Methods: Anti-CNTN1 and NF155 antibodies were measured by flow cytometry using HEK293 cell lines stably expressing human CNTN1 or NF155. Binding capacity of antibodies was validated by immunostaining mouse teased sciatic nerve fibers. Anti-PLA2R antibodies were measured by enzyme-linked sorbent assay and anti-THSD7A antibodies by indirect immunofluorescence assay. Clinical features between 14 CIDP with MN cases including two with anti-CNTN1 antibodies and 20 anti-CNTN1 antibody-positive CIDP cases were compared. Results: A patient whose ages was in the late 70 s complained of progressive weakness and superficial and deep sensory impairment in four extremities over 6 months. Nerve conduction studies showed prominent demyelination patterns. The patient presented with nephrotic syndrome. Renal biopsy disclosed basement membrane thickening with local subepithelial projections and glomerular deposits of IgG4, compatible with MN. Autoantibody assays revealed the presence of IgG4 and IgG1 anti-CNTN1 antibodies, but an absence of anti-NF155, anti-PLA2R, and anti-THSD7A antibodies. The patient's serum stained paranodes of teased sciatic nerves. CIDP with MN and anti-CNTN1 antibody-positive CIDP commonly showed male preponderance, relatively higher age of onset, acute to subacute onset in 35-50% of cases, distal dominant sensorimotor neuropathy, proprioceptive impairment leading to sensory ataxia, and very high cerebrospinal fluid protein levels. However, 11 of 13 CIDP patients with MN had a favorable response to mono- or combined immunotherapies whereas anti-CNTN1 antibody-positive CIDP was frequently refractory to corticosteroids and intravenous immunoglobulin administration. Conclusion: CIDP with MN and anti-CNTN1 antibody-positive CIDP show considerable overlap but are not identical. CIDP with MN is probably heterogeneous and some cases harbor anti-CNTN1 antibodies..
16.	Motoi Kuwahara, Hidekazu Suzuki, Nobuyuki Oka, Hidenori Ogata, Satoshi Yanagimoto, Shuji Sadakane, Yuta Fukumoto, Masaki Yamana, Yoshiko Yuhara, Keisuke Yoshikawa, Miyuki Morikawa, Shigeru Kawai, Masahiro Okazaki, Toru Tsujimoto, Jun-Ichi Kira, Susumu Kusunoki, ELectron microscopic abnormality and therapeutic efficacy in chronic inflammatory demyelinating polyneuropathy with anti-neurofascin155 immunoglobulin G4 antibody, Muscle and Nerve, 10.1002/mus.25757, 57, 3, 498-502, 2018.03, Introduction: Neurofascin155 (NF155) is a target antigen for autoantibodies in a subset of chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: We report the cases of 4 patients with anti-NF155 immunoglobulin G4 (IgG4) antibody-positive CIDP who underwent sural nerve biopsies. Results: All patients were relatively young at onset. Three patients experienced tremors, and 2 patients had severe ataxia. Although the response to intravenous immunoglobulin was poor in all patients, plasma exchange and corticosteroids were at least partially effective. Immunoadsorption plasmapheresis was performed in 1 patient but was ineffective. Electron microscopic examination of sural nerve biopsies revealed loss of paranodal transverse bands in all patients. Discussion: Anti-NF155 IgG4 antibody-positive CIDP shows distinctive clinicopathological features, indicating that the IgG4 antibody is directly associated with the pathogenic mechanisms of anti-NF155 IgG4 antibody-positive CIDP. Muscle Nerve 57: 498–502, 2018..
17.	Atsushi Fujita, Hidenori Ogata, Ryo Yamasaki, Takuya Matsushita, Jun-Ichi Kira, Parallel fluctuation of anti-neurofascin 155 antibody levels with clinico-electrophysiological findings in patients with chronic inflammatory demyelinating polyradiculoneuropathy, Journal of the Neurological Sciences, 10.1016/j.jns.2017.11.035, 384, 107-112, 2018.01, Background The long-term clinical course and closely related biomarkers in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with anti-neurofascin 155 (NF155) antibodies remain to be elucidated. Methods We retrospectively studied the longitudinal clinical courses of three Japanese male anti-NF155 antibody-positive CIDP patients. Anti-NF155 antibody levels were measured by flow cytometry using HEK293 cell lines stably expressing human NF155. Results All three patients presented with chronic progressive sensorimotor disturbance, with ages at onset of 16, 26, and 34 years old, and they were followed for 58, 31, and 38 months, respectively, from the onset. All patients had postural tremor and generalized decreased deep tendon reflexes. Peak cerebrospinal fluid protein levels were > 400 mg/dl, and nerve conduction studies (NCS) showed severe demyelination patterns. Combined immunotherapies including intravenous immunoglobulin, plasma exchange, corticosteroids, and other immunosuppressants ameliorated clinical severity and NCS abnormalities, with improvements of > 10 kg in grip strength and at least 20% in F-wave latencies. However, their symptoms exacerbated after the immunotherapies were tapered. Anti-NF155 antibody levels varied in parallel with the clinical and electrophysiological changes, or preceded them. Conclusion The patients’ clinical courses suggest that anti-NF155 antibody levels and NCS findings could be disease activity markers in anti-NF155 antibody-positive CIDP..
18.	Hiwatashi Akio, Osamu Togao, Koji Yamashita, kazufumi kikuchi, Daichi Momosaka, Hiroshi Nakatake, Ryo Yamasaki, Hidenori Ogata, Masami Yoneyama, Jun-Ichi Kira, Hiroshi Honda, Lumbar plexus in patients with chronic inflammatory demyelinating polyradiculoneuropathy Evaluation with simultaneous T ₂ mapping and neurography method with SHINKEI, British Journal of Radiology, 10.1259/bjr.20180501, 91, 1092, 2018.01, Objective: To evaluate the usefulness of simultaneous T ₂ mapping and neurography with nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation enhancement imaging (SHINKEI) in the lumbar plexus to distinguish patients with chronic inflammatory demyelinating polyneuropathy (CIDP) from healthy controls. Methods: Our institutional review boards approved this retrospective study, and written informed consent was waived. 10 patients with CIDP from 2015 to 2017 were studied along with 5 healthy controls on a 3 T scanner. The T ₂ relaxation time and the size of the dorsal root ganglia and nerves of the lumbar plexus at L3-S1 were measured. Statistical analyses were performed with the Mann-Whitney U test and a receiver operating characteristics analysis. Results: The T ₂ relaxation times of the dorsal root ganglia and the nerves of the lumbar plexus were longer in the CIDP patients (133.34 ± 41.36 and 130.40 ± 47.78 ms) compared to the healthy controls (114.69 ± 24.90 and 83.72 ± 17.51 ms, p = 0.0265 andp ₂ relaxation time of the nerves was best at distinguishing the CIDP patients from the controls (Az = 0.848). Conclusion: Patients with CIDP could be distinguished from healthy controls using simultaneous T ₂ mapping and neurography with SHINKEI in the lumbar plexus. Advances in knowledge: Patients with CIDP could be distinguished from healthy controls using simultaneous T ₂ mapping and neurography with SHINKEI in the lumbar plexus..
19.	Haruki Koike, Ryoji Nishi, Shohei Ikeda, Yuichi Kawagashira, Masahiro Iijima, Naoki Atsuta, Tomohiko Nakamura, Masaaki Hirayama, Hidenori Ogata, Ryo Yamasaki, Jun-Ichi Kira, Masahisa Katsuno, Gen Sobue, Restoration of a conduction block after the long-term treatment of CIDP with anti-neurofascin 155 antibodies Follow-up of a case over 23 years, Internal Medicine, 10.2169/internalmedicine.0455-17, 57, 14, 2061-2066, 2018.01, We herein report a woman with chronic inflammatory demyelinating polyneuropathy (CIDP) in whom positivity for anti-neurofascin 155 antibodies was revealed 23 years after the onset of neuropathy. The patient initially reported numbness in the face at 50 years of age and subsequently manifested features compatible to typical CIDP. Steroid administration initiated at 54 years of age ameliorated her neuropathic symptoms. Although the nerve conduction indices at 59 years of age deteriorated, those at 68, 72, and 73 years of age showed a gradual recovery. The deterioration and subsequent restoration of compound muscle action potential amplitudes was the most dramatic, suggesting that a conduction block can be reversed earlier than other electrophysiological indices..
20.	Hiwatashi Akio, Osamu Togao, Koji Yamashita, kazufumi kikuchi, Ryotato Kamei, Daichi Momosaka, Hidenori Ogata, Ryo Yamasaki, Masami Yoneyama, Jun-Ichi Kira, Hiroshi Honda, Lumbar plexus in patients with chronic inflammatory demyelinating polyneuropathy Evaluation with 3D nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation enhancement imaging (3D SHINKEI), European Journal of Radiology, 10.1016/j.ejrad.2017.05.031, 93, 95-99, 2017.08, Purpose To evaluate whether 3D SHINKEI in the lumbar plexus could identify patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Materials and methods Twenty-one patients with CIDP and 15 non-CIDP patients were studied in this retrospective study. The SNR, contrast-to-noise ratio (CNR), contrast ratio (CR) and the size of the lumbar ganglions and roots were measured. Statistical analyses were performed with Mann-Whitney U test and receiver operating characteristics (ROC) analysis. Results The SNRs of the ganglions and roots were larger in patients with CIDP (8.30 ± 4.87 and 8.24 ± 4.92) than in non-CIDP patients (4.95 ± 2.05 and 5.08 ± 1.97, P
21.	Haruki Koike, Masato Kadoya, Ken Ichi Kaida, Shohei Ikeda, Yuichi Kawagashira, Masahiro Iijima, Daisuke Kato, Hidenori Ogata, Ryo Yamasaki, Noriyuki Matsukawa, Jun-Ichi Kira, Masahisa Katsuno, Gen Sobue, Paranodal dissection in chronic inflammatory demyelinating polyneuropathy with anti-neurofascin-155 and anti-contactin-1 antibodies, Journal of Neurology, Neurosurgery and Psychiatry, 10.1136/jnnp-2016-314895, 88, 6, 465-473, 2017.06, Objective To investigate the morphological features of chronic inflammatory demyelinating polyneuropathy (CIDP) with autoantibodies directed against paranodal junctional molecules, particularly focusing on the fine structures of the paranodes. Methods We assessed sural nerve biopsy specimens obtained from 9 patients with CIDP with anti-neurofascin-155 antibodies and 1 patient with anti-contactin-1 antibodies. 13 patients with CIDP without these antibodies were also examined to compare pathological findings. Results Characteristic light and electron microscopy findings in transverse sections from patients with anti-neurofascin-155 and anti-contactin-1 antibodies indicated a slight reduction in myelinated fibre density, with scattered myelin ovoids, and the absence of macrophage-mediated demyelination or onion bulbs. Teased-fibre preparations revealed that segmental demyelination tended to be found in patients with relatively higher frequencies of axonal degeneration and was tandemly found at consecutive nodes of Ranvier in a single fibre. Assessment of longitudinal sections by electron microscopy revealed that detachment of terminal myelin loops from the axolemma was frequently found at the paranode in patients with anti-neurofascin-155 and anti-contactin-1 antibody-positive CIDP compared with patients with antibody-negative CIDP. Patients with anti-neurofascin-155 antibodies showed a positive correlation between the frequencies of axo-glial detachment at the paranode and axonal degeneration, as assessed by teased-fibre preparations (p
22.	Akio Hiwatashi, Osamu Togao, Koji Yamashita, Kazufumi Kikuchi, Hidenori Ogata, Ryo Yamasaki, Masami Yoneyama, Jun-ichi Kira, Hiroshi Honda, Evaluation of chronic inflammatory demyelinating polyneuropathy: 3D nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation enhancement imaging (3D SHINKEI), EUROPEAN RADIOLOGY, 10.1007/s00330-016-4406-3, 27, 2, 447-453, 2017.02.
23.	Mikito Shimizu, Tohru Koda, Yuji Nakatsuji, Hidenori Ogata, Jun ichi Kira, Hideki Mochizuki, A case of anti-neurofascin 155 antibody-positive combined central and peripheral demyelination successfully treated with plasma exchange, Clinical Neurology, 10.5692/clinicalneurol.cn-000964, 57, 1, 41-44, 2017.01, A 21-year-old man was admitted to our hospital in June 2015. He felt paresthesia of toes in April 2015, which had been spreading upward, and he became difficult to walk in June. Nerve conduction study showed peripheral demyelinating neuropathy that met the diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP), and the cerebrospinal fluid (CSF) examination revealed the remarkably increased protein level. In addition, magnetic resonance imaging of his brain showed a few plaques in white matter, so he was finally diagnosed with combined central and peripheral demyelination (CCPD). Moreover, anti-neurofascin155 (NF155) antibodies assayed in his serum and CSF turned out to be positive. Although he was treated with intravenous immunoglobulin and intravenous methylprednisolone, his symptoms were not ameliorated. However, plasma exchange therapy was apparently effective, and the titer of anti-NF155 antibody was reduced. Recently, the number of case reports of CIDP with CNS lesions has gradually been increasing, while the information about the diagnosis and the treatment responses are not enough. Thus, we reported our case with CCPD who was successfully treated with plasma exchange..
24.	Masato Kadoya, Kenichi Kaida, Haruki Koike, Hiroshi Takazaki, Hidenori Ogata, Kota Moriguchi, Jun Shimizu, Eiichiro Nagata, Shunya Takizawa, Atsuro Chiba, Ryo Yamasaki, Jun-ichi Kira, Gen Sobue, Katsunori Ikewaki, IgG4 anti-neurofascin 155 antibodies in chronic inflammatory demyelinating polyradiculoneuropathy: Clinical significance and diagnostic utility of a conventional assay, JOURNAL OF NEUROIMMUNOLOGY, 10.1016/j.jneuroim.2016.10.013, 301, 16-22, 2016.12.
25.	Hidenori Ogata, Dai Matsuse, Ryo Yamasaki, Nobutoshi Kawamura, Takuya Matsushita, Tomomi Yonekawa, Makoto Hirotani, Hiroyuki Murai, Jun-ichi Kira, A nationwide survey of combined central and peripheral demyelination in Japan, JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 10.1136/jnnp-2014-309831, 87, 1, 29-36, 2016.01.
26.	Hidenori Ogata, Ryo Yamasaki, Hiwatashi Akio, Nobuyuki Oka, Nobutoshi Kawamura, Dai Matsuse, Motoi Kuwahara, Hidekazu Suzuki, Susumu Kusunoki, Yuichi Fujimoto, Koji Ikezoe, Hitaru Kishida, Fumiaki Tanaka, Takuya Matsushita, Hiroyuki Murai, Jun-Ichi Kira, Characterization of IgG4 anti-neurofascin 155 antibody-positive polyneuropathy, Annals of Clinical and Translational Neurology, 10.1002/acn3.248, 2, 10, 960-971, 2015.10, Objective: To investigate anti-neurofascin 155 (NF155) antibody-positive chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: Sera from 50 consecutive CIDP patients diagnosed in our clinic, 32 patients with multiple sclerosis, 40 patients with other neuropathies including 26 with Guillain–Barré syndrome (GBS)/Fisher syndrome, and 30 healthy controls were measured for anti-NF antibodies by flow cytometry using HEK293 cell lines stably expressing human NF155 or NF186. Four additional CIDP patients with anti-NF155 antibodies referred from other clinics were enrolled for clinical characterization. Results: The positivity rate for anti-NF155 antibodies in CIDP patients was 18% (9/50), who all showed a predominance of IgG4 subclass. No other subjects were positive, except one GBS patient harboring IgG1 anti-NF155 antibodies. No anti-NF155 antibody carriers had anti-NF186 antibodies. Anti-NF155 antibody-positive CIDP patients had a significantly younger onset age, higher frequency of drop foot, gait disturbance, tremor and distal acquired demyelinating symmetric phenotype, greater cervical root diameter on magnetic resonance imaging neurography, higher cerebrospinal fluid protein levels, and longer distal and F-wave latencies than anti-NF155 antibody-negative patients. Marked symmetric hypertrophy of cervical and lumbosacral roots/plexuses was present in all anti-NF155 antibody-positive CIDP patients examined by neurography. Biopsied sural nerves from two patients with anti-NF155 antibodies demonstrated subperineurial edema and occasional paranodal demyelination, but no vasculitis, inflammatory cell infiltrates, or onion bulbs. Among anti-NF155 antibody-positive patients, treatment responders more frequently had daily oral corticosteroids and/or immunosuppressants in addition to intravenous immunoglobulins than nonresponders did. Interpretation: Anti-NF155 antibodies occur in a subset of CIDP patients with distal-dominant involvement and symmetric nerve hypertrophy..
27.	Nobutoshi Kawamura, Ryo Yamasaki, Tomomi Yonekawa, Takuya Matsushita, Susumu Kusunoki, Shigemi Nagayama, Yasuo Fukuda, Hidenori Ogata, Dai Matsuse, Hiroyuki Murai, Jun-Ichi Kira, Anti-neurofascin antibody in patients with combined central and peripheral demyelination, Neurology, 10.1212/WNL.0b013e3182a1aa9c, 81, 8, 714-722, 2013.08, Objectives: We aimed to identify the target antigens for combined central and peripheral demyelination (CCPD). Methods: We screened target antigens by immunohistochemistry and immunoblotting using peripheral nerve tissues to identify target antigens recognized by serum antibodies from selected CCPD and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) cases. We then measured the level of antibody to the relevant antigen in 7 patients with CCPD, 16 patients with CIDP, 20 patients with multiple sclerosis, 20 patients with Guillain-Barré syndrome, 21 patients with other neuropathies, and 23 healthy controls (HC) by ELISA and cell-based assays using HEK293 cells. Results: At the initial screening, sera from 2 patients with CCPD showed cross-like binding to sciatic nerve sections at fixed intervals, with nearly perfect colocalization with neurofascin immunostaining at the node and paranode. ELISA with recombinant neurofascin revealed significantly higher mean optical density values in the CCPD group than in other disease groups and HC. Anti-neurofascin antibody positivity rates were 86% in patients with CCPD, 10% in patients with multiple sclerosis, 25% in patients with CIDP, 15% in patients with Guillain-Barré syndrome, and 0% in patients with other neuropathies and HC. The cell-based assay detected serum anti-neurofascin antibody in 5 of 7 patients with CCPD; all others were negative. CSF samples examined from 2 patients with CCPD were both positive. In anti-neurofascin antibody- positive CCPD patients, including those with a limited response to corticosteroids, IV immunoglobulin or plasma exchange alleviated the symptoms. Conclusion: Anti-neurofascin antibody is frequently present in patients with CCPD. Recognition of this antibody may be important, because patients with CCPD who are antibody positive respond well to IV immunoglobulin or plasma exchange..
28.	Hidenori Ogata, Hiroshi Shigeto, Takako Torii, Nobutoshi Kawamura, Yasumasa Ohyagi, Jun-Ichi Kira, A case of Charles Bonnet syndrome following syphilitic optic neuritis, Clinical Neurology, 10.5692/clinicalneurol.51.595, 51, 8, 595-598, 2011.08, Charles Bonnet syndrome refers to visual hallucinations in patients with visual acuity loss or visual field loss without dementia. We report a case of Charles Bonnet syndrome following syphilitic optic neuritis. A 62-year-old man was admitted to our hospital suffering acute bilateral visual loss in a few months. On admission, he was almost blind and his optic discs were found to be atrophic on fundoscopy. In addition to increased cell counts and protein concentration in cerebrospinal fluid (CSF), serum and CSF rapid plasma reagin tests were positive. A diagnosis of syphilitic optic neuritis was made and he was treated with intravenous penicillin G (24 million units per day for 14 days) without any recovery. After treatment finished, he began to experience complex, vivid, elaborate and colored visual hallucinations. He recognized these visions as unreal and felt distressed by them. No cognitive impairment was observed on several neuropsychological tests. We diagnosed the patient as suffering from Charles Bonnet syndrome. Brain MRI revealed diffuse mild atrophy of the cerebral cortex and multiple T₂ high signal intensity lesions in the deep cerebral white matter. Single photon emission computed tomography revealed decreased regional cerebral blood flow in bilateral medial occipital lobes. Administration of olanzapine resulted in a partial remission of visual hallucinations. Charles Bonnet syndrome following syphilitic optic neuritis is rare. In the present case, visual loss and dysfunction of bilateral medial occipital lobes may have triggered the visual hallucinations, which were alleviated by olanzapine..
29.	Yuki Hashimotodani, Takako Ohno-Shosaku, Hiroshi Tsubokawa, Hidenori Ogata, Ken Emoto, Takashi Maejima, Kenji Araishi, Hee Sup Shin, Masanobu Kano, Phospholipase Cβ serves as a coincidence detector through its Ca ²⁺ dependency for triggering retrograde endocannabinoid signal, Neuron, 10.1016/j.neuron.2005.01.004, 45, 2, 257-268, 2005.01, Endocannabinoids mediate retrograde signal and modulate transmission efficacy at various central synapses. Although endocannabinoid release is induced by either depolarization or activation of G_q/11-coupled receptors, it is markedly enhanced by the coincidence of depolarization and receptor activation. Here we report that this coincidence is detected by phospholipase Cβ1 (PLCβ1) in hippocampal neurons. By measuring cannabinoid-sensitive synaptic currents, we found that the receptor-driven endocannabinoid release was dependent on physiological levels of intracellular Ca²⁺ concentration ([Ca²⁺]_i), and markedly enhanced by depolarization-induced [Ca²⁺]_i elevation. Furthermore, we measured PLC activity in intact neurons by using exogenous TRPC6 channel as a biosensor for the PLC product diacylglycerol and found that the receptor-driven PLC activation exhibited similar [Ca²⁺]_i dependence to that of endocannabinoid release. Neither endocannabinoid release nor PLC activation was induced by receptor activation in PLCβ1 knockout mice. We therefore conclude that PLCβ1 serves as a coincidence detector through its Ca²⁺ dependency for endocannabinoid release in hippocampal neurons..

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