記述言語：日本語   出版者・発行元：株式会社医学書院  

DOI： 10.11477/mf.1416202640

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記述言語：英語   出版者・発行元：(一社)日本神経学会  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Pediatric Neurology  

DOI： 10.1016/j.pediatrneurol.2023.12.011

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：一般社団法人 日本内科学会  

Human immunodeficiency virus (HIV)-associated neuropathy is a common complication of HIV infection and has several clinical subtypes. HIV-associated chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a demyelinating neuropathy whose clinical features are known to differ from those of CIDP in the HIV-uninfected population. We herein report a case of CIDP in an HIV-infected patient who was finally diagnosed with anti-neurofascin 155 (NF155) antibody-positive neuropathy. The clinical features, including clinical findings and therapeutic responses, were typical of paranodal antibody-mediated neuropathy. To our knowledge, this is the first case of anti-NF155 antibody-associated neuropathy in an HIV-infected patient.

DOI： 10.2169/internalmedicine.1919-23

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記述言語：英語   出版者・発行元：(一社)日本内科学会  

症例は50歳男性で、ヒト免疫不全ウイルス(HIV)に感染しており、7ヵ月前から四肢の感覚異常と筋力低下が続いていた。HIV感染は36歳時に判明し、40歳時に併用抗レトロウイルス療法を開始してHIV-RNAは検出不能レベルを維持していたが、来院の6ヵ月前に検出可能となっていた。神経学的検査の所見から進行性多発ニューロパチーが示唆された。脳脊髄液検査の所見は、タンパクの著明な上昇を除いて正常で、MRI所見からは神経根浸潤が示唆された。神経伝導検査(NCS)の所見が慢性炎症性脱髄性多発神経根障害(CIDP)の電気診断基準に合致したため、HIV関連CIDPと暫定診断した。高用量免疫グロブリン静注療法を実施後、週1回の免疫グロブリン皮下投与(SCIg)を行った。その結果、症状が軽度に緩和したが、感覚障害の進行が持続した。SCIg下での神経学的悪化中に、抗ニューロファシン155 IgG4抗体が陽性であることが判明した。ステロイド静注療法を実施後、経口プレドニゾロン投与を行った。その結果、3ヵ月で感覚障害がほぼ完全に消失し、NCSの所見が改善した。

記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Neurology and Clinical Neuroscience  

Abstract

Magnetic resonance imaging of spinal dural arteriovenous fistula (SDAVF) shows longitudinally extensive spinal cord lesions mimicking neoplastic or inflammatory myelopathy. On positron emission tomography/computed tomography (PET/CT), we report two patients who showed focal ¹⁸F‐fluorodeoxyglucose (FDG) uptake in longitudinally extensive spinal cord lesions. These lesions were indistinguishable from tumors or myelitis but were finally diagnosed as SDAVF. Although PET/CT availability may be limited, in cases of myelopathy with diagnostic challenges, it is important to recognize that focal FDG uptake can be observed in SDAVF.

DOI： 10.1111/ncn3.12794

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本神経治療学会  

DOI： 10.15082/jsnt.41.6_s202

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記述言語：日本語   出版者・発行元：日本末梢神経学会  

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記述言語：日本語   出版者・発行元：日本末梢神経学会  

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記述言語：日本語   出版者・発行元：日本末梢神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床神経生理学会  

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出版者・発行元：Neurology: Neuroimmunology and NeuroInflammation  

Background and Objectives To elucidate current epidemiologic, clinical, and immunologic profiles and treatments of stiff-person syndrome (SPS) in Japan. Methods A nationwide mail survey was conducted using an established method. Data processing sheets were sent to randomly selected departments of internal medicine, neurology, pediatrics, psychiatry, and neurosurgery in hospitals and clinics throughout Japan to identify patients with SPS who were seen between January 2015 and December 2017. Results Thirty cases were identified as glutamic acid decarboxylase 65 (GAD65)-positive SPS cases on the basis of detailed clinical data of 55 cases. Four patients had α1 subunit of glycine receptor (GlyR) antibodies, and 1 patient had both GAD65 and GlyR antibodies. The total estimated number of patients with GAD65-positive SPS was 140, and the estimated prevalence was 0.11 per 100, 000 population. The median age at onset was 51 years (range, 26-83 years), and 23 (76%) were female. Of these, 70% had classic SPS, and 30% had stiff-limb syndrome. The median time from symptom onset to diagnosis was significantly longer in the high-titer GAD65 antibody group than in the low-titer group (13 months vs 2.5 months, p = 0.01). The median modified Rankin Scale (mRS) at baseline was 4, and the median mRS at the last follow-up was 2. Among the 29 GAD65-positive patients with ≥1 year follow-up, 7 received only symptomatic treatment, 9 underwent immunotherapy without long-term immunotherapy, and 13 received long-term immunotherapy such as oral prednisolone. The coexistence of type 1 diabetes mellitus and the lack of long-term immunotherapy were independent risk factors for poor outcome (mRS ≥3) in the GAD65-positive patients (odds ratio, 15.0; 95% CI 2.6-131.6; p = 0.001; odds ratio, 19.8; 95% CI 3.2-191.5; p = 0.001, respectively). Discussion This study provides the current epidemiologic and clinical status of SPS in Japan. The symptom onset to the diagnosis of SPS was longer in patients with high-titer GAD65 antibodies than in those with low-titer GAD65 antibodies. The outcome of patients with SPS was generally favorable, but more ! aggressive immunotherapies are necessary for GAD65-positive patients with SPS.

DOI： 10.1212/NXI.0000000000200165

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記述言語：日本語   出版者・発行元：(一社)日本神経免疫学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経免疫学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経免疫学会  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：株式会社医学書院  

Autoantibodies against nodal and paranodal proteins, such as neurofascin 140/186, neurofascin 155, contactin 1, and contactin-associated protein 1, have been identified in subsets of patients with chronic inflammatory demyelinating polyneuropathy. Their distinctive characteristics including poor response to immunoglobulin led to the establishment of a new disease entity called "autoimmune nodopathies." IgM monoclonal antibodies against myelin-associated glycoproteins cause intractable sensory-dominant demyelinating polyneuropathy. IgM anti-GM1 and IgG anti-LM1 antibodies are associated with multifocal motor neuropathy and chronic inflammatory demyelinating polyneuropathy, respectively. Monoclonal IgM against disialosyl ganglioside epitopes induces chronic ataxic neuropathy with ophthalmoplegia and cold agglutinin.

DOI： 10.11477/mf.1416202426

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記述言語：英語   出版者・発行元：(一社)日本内科学会  

症例は77歳男性で、4ヵ月前から進行性の下肢のしびれと歩行障害を認めていた。可溶性インターロイキン2受容体、総IgG、IgG4の血清中濃度が上昇していたが、補体を含む他の項目には明らかな異常は認められなかった。頭部および脊椎MRIと全身CTでも明らかな異常は認められなかった。神経伝導検査の所見は、脱髄性感覚運動型多発ニューロパチーに一致した。腓腹神経生検では、神経上膜にIgG4陽性形質細胞浸潤が認められた。電気生理学的検査の結果から慢性炎症性脱髄性多発神経炎と診断し、免疫グロブリン静注療法(IVIg)を開始した。2コース目のIVIgから効果を認めなかったため、ステロイド治療を行った。治療開始前の血清検査で、抗コンタクチン1抗体の陽性が判明した。治療により症状が改善すると、血清IgG4レベルが低下し、抗コンタクチン1抗体が陰性化した。

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Neurology: Neuroimmunology and NeuroInflammation  

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.

DOI： 10.1212/NXI.0000000000200081

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記述言語：日本語   出版者・発行元：(一社)日本神経免疫学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経免疫学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床神経生理学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Neurology  

A 51-year-old woman presented with apraxia of eyelid opening, followed by slowly progressive masked facies, tongue tremor, dysphagia, neck and upper extremity rigidity, and bradykinesia 6 months after lumboperitoneal shunt placement for hydrocephalus after subarachnoid hemorrhage. An MRI examination of the brain showed midbrain compression, brainstem displacement inferiorly, and cistern effacement, consistent with infratentorial hypotension. 123I-ioflupane SPECT imaging showed reduced striatal dopamine transporter binding bilaterally. All symptoms and findings ameliorated after increasing shunt pressure (Figures 1 and 2 and Video 1). UPDRS Part III score improved from 24 to 5. Intracranial hypotension with midbrain sagging can cause reversible parkinsonism1,2 when displacement shear forces impair the nigrostriatal dopamine pathway.

DOI： 10.1212/WNL.0000000000200994

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：一般社団法人 日本内科学会  

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.

DOI： 10.2169/internalmedicine.9286-21

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Epilepsy and Behavior Reports  

Exercise-induced reflex seizures are a rare form of reflex seizures that are exclusively induced by a specific type of exercise. Many patients with exercise-induced reflex seizures exhibit drug-resistance, and are therefore advised to avoid the triggering exercise. Here, we describe a focal epilepsy patient with shadowboxing-induced reflex seizures. His semiology included focal aware seizures with speech and behavioral arrest that evolved to head version to the right, preceded by cephalic aura. We identified a specific motion that induced these seizures during shadowboxing using video-electroencephalographic recording, and the patient was able to continue boxing by avoiding this motion. We speculate that a broad brain network may be the pathological substrate of his exercise-induced reflex seizures. Identification of the specific motion that induces exercise-induced reflex seizures is useful for not only understanding the underlying pathophysiology, but also for minimizing the therapeutic restriction of the exercise.

DOI： 10.1016/j.ebr.2022.100543

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記述言語：日本語   出版者・発行元：日本神経治療学会  

DOI： 10.15082/jsnt.39.6_s166

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2169/internalmedicine.5536-20

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/acn3.51220

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.5692/clinicalneurol.60.cn-001403

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.5692/clinicalneurol.cn-001413

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

DOI： 10.2196/17117

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

DOI： 10.1111/cen3.12567

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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-DRB1*15:01-DRB5*01:01-DQA1*01:02-DQB1*06:02 or -(A*24:02)-B*52:01-C*12:02-DRB1*15:02-DRB5*01:02-DQA1*01:03-DQB1*06:01, resulting in significantly increased HLA-DRB1*15, -DRB1*15:01, -DQB1*06:01/06:02, -DQB1*06:02, and -DRB1*15:01-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.

DOI： 10.1016/j.jneuroim.2019.577139

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

DOI： 10.1002/acn3.50931

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

DOI： 10.1016/j.msard.2019.06.033

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

DOI： 10.1016/j.jneuroim.2019.01.010

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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
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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.

DOI： 10.1002/acn3.715

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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 < 0.0001, respectively). The sizes of the ganglia and the roots were larger in patients with CIDP (6.25 ± 1.56 mm and 4.37 ± 1.71 mm) than in healthy subjects (5.59 ± 1.08 mm and 3.50 ± 0.62 mm, P = 0.0114 and P = 0.0014, respectively). ROC analysis revealed that T2 relaxation time of the roots was best at distinguishing CIDP patients from healthy subjects (the area under the curve = 0.748). Conclusion: Patients with CIDP could be distinguished from healthy subjects using simultaneous apparent T2 mapping and neurography with SHINKEI.

DOI： 10.1016/j.mri.2018.09.025

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

DOI： 10.3389/fneur.2018.00997

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

DOI： 10.1002/mus.25757

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

DOI： 10.1016/j.jns.2017.11.035

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

DOI： 10.2169/internalmedicine.0455-17

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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 < 0.0001, respectively). The sizes of the nerves were larger in the CIDP patients (6.19 ± 2.28 mm) compared to the controls (4.54 ± 0.86 mm, p < 0.0001). However, there was no significant difference between the sizes of the ganglia in the CIDP patients and the controls. The receiver operating characteristics analysis revealed that the T
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.

DOI： 10.1259/bjr.20180501

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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 < 0.0001, respectively). The CNRs of the ganglions and roots were larger in patients with CIDP (40.79 ± 43.19 and 37.16 ± 48.31) than in non-CIDP patients (25.90 ± 10.41 and 18.37 ± 32.83, P < 0.0001, respectively). The CRs of the ganglions and roots were larger in patients with CIDP (0.74 ± 0.13 and 0.66 ± 0.17) than in non-CIDP patients (0.72 ± 0.12 and 0.50 ± 0.17, P = 0.004 and P < 0.0001, respectively). The sizes of the ganglions and the roots were larger in patients with CIDP (6.62 ± 1.81 mm and 5.76 ± 3.24 mm) than in non-CIDP patients (5.23 ± 1.17 mm and 4.24 ± 1.11 mm, P < 0.0001, respectively). ROC analysis showed the best diagnostic performance with the CNR of the roots. Conclusion Patients with CIDP could be distinguished from controls on 3D SHINKEI.

DOI： 10.1016/j.ejrad.2017.05.031

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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<0.05). Conclusions Paranodal dissection without classical macrophage-mediated demyelination is the characteristic feature of patients with CIDP with autoantibodies to paranodal axo-glial junctional molecules.

DOI： 10.1136/jnnp-2016-314895

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00330-016-4406-3

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

DOI： 10.5692/clinicalneurol.cn-000964

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jneuroim.2016.10.013

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1136/jnnp-2014-309831

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

DOI： 10.1002/acn3.248

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

DOI： 10.1212/WNL.0b013e3182a1aa9c

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

DOI： 10.5692/clinicalneurol.51.595

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

DOI： 10.1016/j.neuron.2005.01.004

開催年月日： 2022年10月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：長崎   国名：日本国  

開催年月日： 2022年9月

記述言語：日本語  

開催地：東京   国名：日本国  

開催年月日： 2022年9月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：東京   国名：日本国  

開催年月日： 2022年9月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：東京   国名：日本国  

開催年月日： 2022年5月

記述言語：日本語  

開催地：東京   国名：日本国  

開催年月日： 2022年5月

記述言語：英語   会議種別：口頭発表（一般）  

開催地：東京   国名：日本国  

開催年月日： 2022年5月

記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：東京   国名：日本国  

開催年月日： 2022年5月

記述言語：英語   会議種別：口頭発表（一般）  

開催地：Miami   国名：アメリカ合衆国  

開催年月日： 2021年12月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：福岡(Web開催)   国名：日本国  

開催年月日： 2021年10月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：福岡(Web開催)   国名：日本国  

開催年月日： 2021年10月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：福岡(Web開催)   国名：日本国  

開催年月日： 2021年9月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：和歌山   国名：日本国  

開催年月日： 2021年5月

記述言語：英語   会議種別：口頭発表（一般）  

開催地：京都   国名：日本国  

開催年月日： 2021年5月

記述言語：英語   会議種別：口頭発表（一般）  

開催地：京都   国名：日本国  

開催年月日： 2020年10月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：金沢(Web開催)   国名：日本国  

開催年月日： 2020年10月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：金沢(Web開催)   国名：日本国  

開催年月日： 2020年8月 - 2020年9月

記述言語：英語   会議種別：口頭発表（一般）  

開催地：岡山   国名：日本国  

開催年月日： 2020年8月 - 2020年9月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：岡山   国名：日本国  

開催年月日： 2019年11月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：福岡   国名：日本国  

開催年月日： 2019年9月 - 2020年9月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：千葉   国名：日本国  

開催年月日： 2019年9月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：千葉   国名：日本国  

開催年月日： 2019年8月

記述言語：日本語   会議種別：口頭発表（一般）  

国名：日本国  

開催年月日： 2019年8月

記述言語：日本語   会議種別：口頭発表（一般）  

国名：日本国  

開催年月日： 2019年5月

記述言語：日本語   会議種別：口頭発表（一般）  

国名：日本国  

開催年月日： 2019年5月

記述言語：英語  

開催地：大阪   国名：日本国  

開催年月日： 2019年5月

記述言語：日本語  

国名：日本国  

開催年月日： 2018年11月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：東京   国名：日本国  

開催年月日： 2018年11月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：東京   国名：日本国  

開催年月日： 2018年10月

記述言語：英語   会議種別：口頭発表（一般）  

開催地：Atlanta   国名：アメリカ合衆国  

開催年月日： 2018年9月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：郡山   国名：日本国  

開催年月日： 2018年9月

記述言語：日本語   会議種別：口頭発表（招待・特別）  

開催地：下関   国名：日本国  

開催年月日： 2018年9月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：下関   国名：日本国  

開催年月日： 2018年5月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：札幌   国名：日本国  

開催年月日： 2018年5月 - 2015年5月

記述言語：英語   会議種別：口頭発表（一般）  

開催地：札幌   国名：日本国  

開催年月日： 2017年10月

記述言語：日本語   会議種別：口頭発表（一般）  

国名：日本国  

開催年月日： 2017年9月

記述言語：英語   会議種別：口頭発表（一般）  

開催地：Kyoto   国名：日本国  

開催年月日： 2017年8月

記述言語：日本語   会議種別：口頭発表（招待・特別）  

開催地：愛知   国名：日本国  

開催年月日： 2017年8月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：愛知   国名：日本国  

開催年月日： 2017年7月

記述言語：英語   会議種別：口頭発表（一般）  

開催地：Barcelona   国名：スペイン  

開催年月日： 2017年6月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：大阪国際会議場   国名：日本国  

開催年月日： 2017年6月

記述言語：英語   会議種別：口頭発表（一般）  

開催地：Glasgow University   国名：グレートブリテン・北アイルランド連合王国(英国)  

開催年月日： 2017年6月

記述言語：英語   会議種別：口頭発表（一般）  

開催地：神戸国際会議場   国名：日本国  

開催年月日： 2016年8月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：大阪国際会議場   国名：日本国  

開催年月日： 2016年4月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：東京国際フォーラム   国名：日本国  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語  

記述言語：日本語  

記述言語：英語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語  

記述言語：日本語  

記述言語：日本語   出版者・発行元：(一社)日本神経学会  

慢性炎症性脱髄性多発根ニューロパチー(chronic inflammatory demyelinating polyradiculoneuropathy,以下CIDPと略記)は,複数の病態により引き起こされる症候群と認識されている.2010年代に入り,一部のCIDP症例でランビエ絞輪部および傍絞輪部に局在する膜蛋白に対する自己抗体が陽性になること明らかとなった.同様の結果が各地で再現され,2021年に改訂された国際CIDP診療ガイドラインでは,自己免疫性ノドパチー(autoimmune nodopathies)という新たな疾患概念が提唱されるに至った.本稿ではneurofascin 155抗体,contactin 1抗体を中心に自己免疫性ノドパチーにおける自己抗体の意義について考察する.(著者抄録)

記述言語：日本語   出版者・発行元：(有)科学評論社  

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

DOI： 10.11477/mf.1416202426

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

DOI： 10.15082/jsnt.40.4_479

記述言語：日本語   出版者・発行元：(株)医学書院  

＜文献概要＞過去10年でランヴィエ絞輪部,傍絞輪部に局在する膜蛋白に対する自己抗体の存在が明らかとなり,自己免疫性ノドパチーの概念が提唱された。免疫グロブリンM(immunoglobulin M:IgM)単クローン血症に伴うミエリン関連糖蛋白質抗体は難治性脱髄性ニューロパチーを引き起こす。ジシアロシル基を有するガングリオシドに対するIgM自己抗体,IgM GM1抗体,IgG LM1抗体も各種慢性自己免疫性脱髄性ニューロパチーの診断・治療方針決定に役立つ。

記述言語：日本語   出版者・発行元：(一社)日本神経治療学会  

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：日本語   出版者・発行元：(株)日本臨床社  

記述言語：日本語   出版者・発行元：(株)日本臨床社  

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：英語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

DOI： doi:10.1111/cen3.12567

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：英語  

Demyelination diseases involving the central and peripheral nervous systems are etiologically heterogeneous with both cell-mediated and humoral immunities playing pathogenic roles. Recently, autoantibodies against nodal and paranodal proteins, such as neurofascin186 (NF186), neurofascin155 (NF155), contactin-1 (CNTN1), contactin-associated protein 1 (CASPR1) and gliomedin, have been discovered in not only chronic demyelinating conditions, such as multiple sclerosis (MS) and chronic inflammatory demyelinating polyradiculoneuropathy, but also in acute demyelinating conditions, such as Guillain-Barré syndrome. Only a minority of these patients harbor anti-nodal/paranodal protein antibodies; however, these autoantibodies, especially IgG4 subclass autoantibodies to paranodal proteins, are associated with unique features and these conditions are collectively termed nodopathy or paranodopathy. Establishing a concept of IgG4-related nodopathy/paranodopathy contributes to diagnosis and treatment strategy because IgG4 autoantibody-related neurological diseases are often refractory to conventional immunotherapies. IgG4 does not fix complements, or internalize the target antigens, because IgG4 exists in a monovalent bispecific form in vivo. IgG4 autoantibodies can bock protein-protein interaction. Thus, the primary role of IgG4 anti-paranodal protein antibodies may be blockade of interactions between NF155 and CNTN1/CASPR1, leading to conduction failure, which is consistent with the sural nerve pathology presenting paranodal terminal loop detachment from axons with intact internodes in the absence of inflammation. However, it still remains to be elucidated how these autoantibodies belonging to the same IgG4 subclass can cause each IgG4 autoantibody-specific manifestation. Another important issue is to clarify the mechanism by which IgG4 antibodies to nodal/paranodal proteins emerge. IgG4 antibodies develop on chronic antigenic stimulation and can block antibodies that alleviate allergic inflammation by interfering with the binding of allergen-specific IgE to allergens. Thus, environmental antigens cross-reacting with nodal and paranodal proteins may warrant future study.

DOI： 10.1016/j.neuint.2018.12.011

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：英語  

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an intractable inflammatory disease affecting peripheral nerves. The etiology of CIDP remains to be established, but it is regarded as a mixture of heterogeneous conditions presenting a variety of clinical and electrophysiological manifestations. In recent years, autoantibodies against paranodal cell adhesion molecules, such as neurofascin 155 (NF155), contactin 1 and contactin-associated protein 1, have been detected in subsets of CIDP patients. The clinical characteristics of anti-NF155 antibody-positive CIDP have been delineated, and include a younger onset age, higher frequency of distal muscle weakness, sensory ataxia and tremor, higher cerebrospinal fluid protein levels, more conspicuous demyelination on nerve conduction studies, and nerve root hypertrophy on magnetic resonance neurography, when compared with anti-NF155 antibody-negative CIDP patients. Predominant elevation of immunoglobulin G4 subclass is also a characteristic of this disease. Sural nerve biopsy specimens of anti-NF155 antibody-positive CIDP patients show axo-glial detachment in paranodes without inflammatory cell infiltrates or onion bulb formation. While intravenous immunoglobulin is not as effective as expected against anti-NF155 antibody-positive CIDP patients, other immunotherapies, such as corticosteroids, plasmapheresis and B-cell depletion therapy, seem to be effective. Early diagnosis and treatment is important for preventing secondary axonal degeneration. The present review summarizes the emerging details of anti-NF155 antibody-related neuropathy.

DOI： 10.1111/cen3.12444

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

種別：大会・シンポジウム等 

種別：大会・シンポジウム等 

種別：大会・シンポジウム等 

種別：査読等 

外国語雑誌　査読論文数：7

日本語雑誌　査読論文数：1

種別：大会・シンポジウム等 

種別：大会・シンポジウム等 

種別：査読等 

外国語雑誌　査読論文数：6

種別：大会・シンポジウム等 

種別：査読等 

外国語雑誌　査読論文数：5

種別：大会・シンポジウム等 

種別：査読等 

外国語雑誌　査読論文数：1

日本語雑誌　査読論文数：0

国際会議録　査読論文数：0

国内会議録　査読論文数：0

種別：大会・シンポジウム等 

種別：大会・シンポジウム等 

種別：大会・シンポジウム等 

種別：大会・シンポジウム等 

種別：大会・シンポジウム等