著者: Vanda A Lennon, Dean M Wingerchuk, Thomas J Kryzer, Sean J Pittock, Claudia F Lucchinetti, Kazuo Fujihara, Ichiro Nakashima, Brian G Weinshenker
雑誌名: Lancet. 2004 Dec 11-17;364(9451):2106-12. doi: 10.1016/S0140-6736(04)17551-X.
Abstract/Text
BACKGROUND: Neuromyelitis optica is an inflammatory demyelinating disease with generally poor prognosis that selectively targets optic nerves and spinal cord. It is commonly misdiagnosed as multiple sclerosis. Neither disease has a distinguishing biomarker, but optimum treatments differ. The relation of neuromyelitis optica to optic-spinal multiple sclerosis in Asia is uncertain. We assessed the capacity of a putative marker for neuromyelitis optica (NMO-IgG) to distinguish neuromyelitis optica and related disorders from multiple sclerosis.
METHODS: Indirect immunofluorescence with a composite substrate of mouse tissues identified a distinctive NMO-IgG staining pattern, which we characterised further by dual immunostaining. We tested masked serum samples from 102 North American patients with neuromyelitis optica or with syndromes that suggest high risk of the disorder, and 12 Japanese patients with optic-spinal multiple sclerosis. Control patients had multiple sclerosis, other myelopathies, optic neuropathies, and miscellaneous disorders. We also established clinical diagnoses for 14 patients incidentally shown to have NMO-IgG among 85000 tested for suspected paraneoplastic autoimmunity.
FINDINGS: NMO-IgG outlines CNS microvessels, pia, subpia, and Virchow-Robin space. It partly colocalises with laminin. Sensitivity and specificity were 73% (95% CI 60-86) and 91% (79-100) for neuromyelitis optica and 58% (30-86) and 100% (66-100) for optic-spinal multiple sclerosis. NMO-IgG was detected in half of patients with high-risk syndromes. Of 14 seropositive cases identified incidentally, 12 had neuromyelitis optica or a high-risk syndrome for the disease.
INTERPRETATION: NMO-IgG is a specific marker autoantibody of neuromyelitis optica and binds at or near the blood-brain barrier. It distinguishes neuromyelitis optica from multiple sclerosis. Asian optic-spinal multiple sclerosis seems to be the same as neuromyelitis optica.
PMID
15589308 Lancet. 2004 Dec 11-17;364(9451):2106-12. doi: 10.1016/･･･
著者: Vanda A Lennon, Thomas J Kryzer, Sean J Pittock, A S Verkman, Shannon R Hinson
雑誌名: J Exp Med. 2005 Aug 15;202(4):473-7. doi: 10.1084/jem.20050304. Epub 2005 Aug 8.
Abstract/Text
Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that selectively affects optic nerves and spinal cord. It is considered a severe variant of multiple sclerosis (MS), and frequently is misdiagnosed as MS, but prognosis and optimal treatments differ. A serum immunoglobulin G autoantibody (NMO-IgG) serves as a specific marker for NMO. Here we show that NMO-IgG binds selectively to the aquaporin-4 water channel, a component of the dystroglycan protein complex located in astrocytic foot processes at the blood-brain barrier. NMO may represent the first example of a novel class of autoimmune channelopathy.
PMID
16087714 J Exp Med. 2005 Aug 15;202(4):473-7. doi: 10.1084/jem.2･･･
著者: T Misu, K Fujihara, A Kakita, H Konno, M Nakamura, S Watanabe, T Takahashi, I Nakashima, H Takahashi, Y Itoyama
雑誌名: Brain. 2007 May;130(Pt 5):1224-34. doi: 10.1093/brain/awm047. Epub 2007 Apr 2.
Abstract/Text
Neuromyelitis optica (NMO) is an inflammatory and necrotizing disease clinically characterized by selective involvement of the optic nerves and spinal cord. There has been a long controversy as to whether NMO is a variant of multiple sclerosis (MS) or a distinct disease. Recently, an NMO-specific antibody (NMO-IgG) was found in the sera from patients with NMO, and its target antigen was identified as aquaporin 4 (AQP4) water channel protein, mainly expressed in astroglial foot processes. However, the pathogenetic role of the AQP4 in NMO remains unknown. We did an immunohistopathological study on the distribution of AQP4, glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), activated complement C9neo and immunoglobulins in the spinal cord lesions and medulla oblongata of NMO (n = 12), MS (n = 6), brain and spinal infarction (n = 7) and normal control (n = 8). The most striking finding was that AQP4 immunoreactivity was lost in 60 out of a total of 67 acute and chronic NMO lesions (90%), but not in MS plaques. The extensive loss of AQP4 accompanied by decreased GFAP staining was evident, especially in the active perivascular lesions, where immunoglobulins and activated complements were deposited. Interestingly, in those NMO lesions, MBP-stained myelinated fibres were relatively preserved despite the loss of AQP4 and GFAP staining. The areas surrounding the lesions in NMO had enhanced expression of AQP4 and GFAP, which reflected reactive gliosis. In contrast, AQP4 immunoreactivity was well preserved and rather strongly stained in the demyelinating MS plaques, and infarcts were also stained for AQP4 from the very acute phase of necrosis to the chronic stage of astrogliosis. In normal controls, AQP4 was diffusely expressed in the entire tissue sections, but the staining in the spinal cord was stronger in the central grey matter than in the white matter. The present study demonstrated that the immunoreactivities of AQP4 and GFAP were consistently lost from the early stage of the lesions in NMO, notably in the perivascular regions with complement and immunoglobulin deposition. These features in NMO were distinct from those of MS and infarction as well as normal controls, and suggest that astrocytic impairment associated with the loss of AQP4 and humoral immunity may be important in the pathogenesis of NMO lesions.
PMID
17405762 Brain. 2007 May;130(Pt 5):1224-34. doi: 10.1093/brain/a･･･
著者: Dean M Wingerchuk, Vanda A Lennon, Claudia F Lucchinetti, Sean J Pittock, Brian G Weinshenker
雑誌名: Lancet Neurol. 2007 Sep;6(9):805-15. doi: 10.1016/S1474-4422(07)70216-8.
Abstract/Text
Neuromyelitis optica (also known as Devic's disease) is an idiopathic, severe, demyelinating disease of the central nervous system that preferentially affects the optic nerve and spinal cord. Neuromyelitis optica has a worldwide distribution, poor prognosis, and has long been thought of as a variant of multiple sclerosis; however, clinical, laboratory, immunological, and pathological characteristics that distinguish it from multiple sclerosis are now recognised. The presence of a highly specific serum autoantibody marker (NMO-IgG) further differentiates neuromyelitis optica from multiple sclerosis and has helped to define a neuromyelitis optica spectrum of disorders. NMO-IgG reacts with the water channel aquaporin 4. Data suggest that autoantibodies to aquaporin 4 derived from peripheral B cells cause the activation of complement, inflammatory demyelination, and necrosis that is seen in neuromyelitis optica. The knowledge gained from further assessment of the exact role of NMO-IgG in the pathogenesis of neuromyelitis optica will provide a foundation for rational therapeutic trials for this rapidly disabling disease.
PMID
17706564 Lancet Neurol. 2007 Sep;6(9):805-15. doi: 10.1016/S1474･･･
著者: Takeshi Kezuka, Yoshihiko Usui, Naoyuki Yamakawa, Yoshimichi Matsunaga, Ryusaku Matsuda, Masayuki Masuda, Hiroya Utsumi, Keiko Tanaka, Hiroshi Goto
雑誌名: J Neuroophthalmol. 2012 Jun;32(2):107-10. doi: 10.1097/WNO.0b013e31823c9b6c.
Abstract/Text
BACKGROUND: Damage to astrocytes by anti-aquaporin-4 antibody (AQP4-Ab), also known as NMO antibody, has been implicated as the cause of neuromyelitis optica. Myelin oligodendrocyte glycoprotein (MOG) is well known as the causative protein of multiple sclerosis (MS). MOG antigen is currently considered as a cause of optic neuritis (ON) associated with MS because immunization with MOG antigen derived from oligodendrocytes induces murine ON with myelitis. We investigated the relationship between NMO antibody (NMO-Ab) and anti-MOG antibody (MOG-Ab) and potential in patients with ON for recovery of vision.
METHODS: Thirty-three eyes of 23 patients with ON were studied. At presentation, serum NMO-Ab was measured by immunofluorescence using HEK 293 cells transfected with AQP4-GFP, and anti-MOG1-125 antibody was measured by enzyme-linked immunosorbent assay. MOG-Ab seropositivity was defined by comparing with MOG-Ab level obtained from 8 healthy normal subjects.
RESULTS: Eleven (47%) of 23 ON patients were NMO-Ab seropositive, while 8 (34%) of the 23 patients were MOG-Ab seropositive. Six (26%) of 23 patients were seropositive for both NMO-Ab and MOG-Ab. Ten (43%) of 23 patients were seronegative for both antibodies. Three (50%) of 6 eyes of patients seropositive for both antibodies did not respond to corticosteroid pulse therapy and plasmapheresis, and visual acuity remained unchanged. In the NMO-Ab/MOG-Ab group, visual acuity improved significantly (P < 0.0001). In the other 3 groups (NMO-Ab/MOG-Ab, NMO-Ab/MOG-Ab, and NMO-Ab/MOG-Ab), visual acuity did not change significantly (P = 0.53, 0.42, and 0.45, respectively).
CONCLUSION: NMO-Ab and MOG-Ab could be potential biomarkers to determine visual prognosis in patients with ON.
PMID
22157536 J Neuroophthalmol. 2012 Jun;32(2):107-10. doi: 10.1097/･･･
著者: Douglas Kazutoshi Sato, Dagoberto Callegaro, Marco Aurelio Lana-Peixoto, Patrick J Waters, Frederico M de Haidar Jorge, Toshiyuki Takahashi, Ichiro Nakashima, Samira Luisa Apostolos-Pereira, Natalia Talim, Renata Faria Simm, Angelina Maria Martins Lino, Tatsuro Misu, Maria Isabel Leite, Masashi Aoki, Kazuo Fujihara
雑誌名: Neurology. 2014 Feb 11;82(6):474-81. doi: 10.1212/WNL.0000000000000101. Epub 2014 Jan 10.
Abstract/Text
OBJECTIVE: To evaluate clinical features among patients with neuromyelitis optica spectrum disorders (NMOSD) who have myelin oligodendrocyte glycoprotein (MOG) antibodies, aquaporin-4 (AQP4) antibodies, or seronegativity for both antibodies.
METHODS: Sera from patients diagnosed with NMOSD in 1 of 3 centers (2 sites in Brazil and 1 site in Japan) were tested for MOG and AQP4 antibodies using cell-based assays with live transfected cells.
RESULTS: Among the 215 patients with NMOSD, 7.4% (16/215) were positive for MOG antibodies and 64.7% (139/215) were positive for AQP4 antibodies. No patients were positive for both antibodies. Patients with MOG antibodies represented 21.1% (16/76) of the patients negative for AQP4 antibodies. Compared with patients with AQP4 antibodies or patients who were seronegative, patients with MOG antibodies were more frequently male, had a more restricted phenotype (optic nerve more than spinal cord), more frequently had bilateral simultaneous optic neuritis, more often had a single attack, had spinal cord lesions distributed in the lower portion of the spinal cord, and usually demonstrated better functional recovery after an attack.
CONCLUSIONS: Patients with NMOSD with MOG antibodies have distinct clinical features, fewer attacks, and better recovery than patients with AQP4 antibodies or patients seronegative for both antibodies.
PMID
24415568 Neurology. 2014 Feb 11;82(6):474-81. doi: 10.1212/WNL.0･･･
著者: Ryusaku Matsuda, Takeshi Kezuka, Akihiko Umazume, Yoko Okunuki, Hiroshi Goto, Keiko Tanaka
雑誌名: Neuroophthalmology. 2015 Oct;39(5):213-219. doi: 10.3109/01658107.2015.1072726. Epub 2015 Aug 25.
Abstract/Text
We have studied the clinical picture of anti-aquaporin antibody (AQP4-Ab)- and anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-positive optic neuritis. However, optic neuritis associated with MOG-Abs has not been elucidated using new methods such as cell-based assay. Hence, we conducted a comprehensive investigation on its clinical profile. Serum samples from 70 patients (17 males and 53 females, mean age 43.1 years) with optic neuritis were tested for MOG-Abs by cell-based assay. In MOG-Ab seropositive patients, the disease type, recurrence status, and visual function outcome were analysed. Among 70 patients, 18 were MOG-Ab seropositive. The 18 patients comprised 2 with chronic relapsing inflammatory optic neuropathy, 2 with AQP4-Ab seropositive optic neuritis (neuromyelitis optica), 12 with idiopathic optic neuritis, and 2 with optic neuritis associated with multiple sclerosis. Excluding two cases that were also AQP4-Ab seropositive, MOG-Ab seropositive cases had relatively favourable visual acuity outcome (although not significantly different from seronegative cases) but had significant residual visual field deficit (p = 0.0015). Furthermore, the number of relapses of optic neuritis per year was significantly greater in MOG-Ab seropositive cases than in seronegative cases (0.82 vs. 0.40; p = 0.0005). MOG-Abs may contribute to the heterogeneous clinical picture of optic neuritis, and although visual acuity outcome is favourable, there is a tendency of residual visual field deficit and a possibility of repeated relapses.
PMID
27928358 Neuroophthalmology. 2015 Oct;39(5):213-219. doi: 10.310･･･
著者: D M Wingerchuk, V A Lennon, S J Pittock, C F Lucchinetti, B G Weinshenker
雑誌名: Neurology. 2006 May 23;66(10):1485-9. doi: 10.1212/01.wnl.0000216139.44259.74.
Abstract/Text
BACKGROUND: The authors previously proposed diagnostic criteria for neuromyelitis optica (NMO) that facilitate its distinction from prototypic multiple sclerosis (MS). However, some patients with otherwise typical NMO have additional symptoms not attributable to optic nerve or spinal cord inflammation or have MS-like brain MRI lesions. Furthermore, some patients are misclassified as NMO by the authors' earlier proposed criteria despite having a subsequent course indistinguishable from prototypic MS. A serum autoantibody marker, NMO-IgG, is highly specific for NMO. The authors propose revised NMO diagnostic criteria that incorporate NMO-IgG status.
METHODS: Using final clinical diagnosis (NMO or MS) as the reference standard, the authors calculated sensitivity and specificity for each criterion and various combinations using a sample of 96 patients with NMO and 33 with MS. The authors used likelihood ratios and logistic regression analysis to develop the most practical and informative diagnostic model.
RESULTS: Fourteen patients with NMO (14.6%) had extra-optic-spinal CNS symptoms. NMO-IgG seropositivity was 76% sensitive and 94% specific for NMO. The best diagnostic combination was 99% sensitive and 90% specific for NMO and consisted of at least two of three elements: longitudinally extensive cord lesion, onset brain MRI nondiagnostic for MS, or NMO-IgG seropositivity.
CONCLUSIONS: The authors propose revised diagnostic criteria for definite neuromyelitis optica (NMO) that require optic neuritis, myelitis, and at least two of three supportive criteria: MRI evidence of a contiguous spinal cord lesion 3 or more segments in length, onset brain MRI nondiagnostic for multiple sclerosis, or NMO-IgG seropositivity. CNS involvement beyond the optic nerves and spinal cord is compatible with NMO.
PMID
16717206 Neurology. 2006 May 23;66(10):1485-9. doi: 10.1212/01.w･･･
著者: Dean M Wingerchuk, Brenda Banwell, Jeffrey L Bennett, Philippe Cabre, William Carroll, Tanuja Chitnis, Jérôme de Seze, Kazuo Fujihara, Benjamin Greenberg, Anu Jacob, Sven Jarius, Marco Lana-Peixoto, Michael Levy, Jack H Simon, Silvia Tenembaum, Anthony L Traboulsee, Patrick Waters, Kay E Wellik, Brian G Weinshenker, International Panel for NMO Diagnosis
雑誌名: Neurology. 2015 Jul 14;85(2):177-89. doi: 10.1212/WNL.0000000000001729. Epub 2015 Jun 19.
Abstract/Text
Neuromyelitis optica (NMO) is an inflammatory CNS syndrome distinct from multiple sclerosis (MS) that is associated with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). Prior NMO diagnostic criteria required optic nerve and spinal cord involvement but more restricted or more extensive CNS involvement may occur. The International Panel for NMO Diagnosis (IPND) was convened to develop revised diagnostic criteria using systematic literature reviews and electronic surveys to facilitate consensus. The new nomenclature defines the unifying term NMO spectrum disorders (NMOSD), which is stratified further by serologic testing (NMOSD with or without AQP4-IgG). The core clinical characteristics required for patients with NMOSD with AQP4-IgG include clinical syndromes or MRI findings related to optic nerve, spinal cord, area postrema, other brainstem, diencephalic, or cerebral presentations. More stringent clinical criteria, with additional neuroimaging findings, are required for diagnosis of NMOSD without AQP4-IgG or when serologic testing is unavailable. The IPND also proposed validation strategies and achieved consensus on pediatric NMOSD diagnosis and the concepts of monophasic NMOSD and opticospinal MS.
© 2015 American Academy of Neurology.
PMID
26092914 Neurology. 2015 Jul 14;85(2):177-89. doi: 10.1212/WNL.0･･･
著者: Hitoshi Ishikawa, Takeshi Kezuka, Keigo Shikishima, Akiko Yamagami, Miki Hiraoka, Hideki Chuman, Makoto Nakamura, Keika Hoshi, Toshiaki Goseki, Kimiyo Mashimo, Osamu Mimura, Takeshi Yoshitomi, Keiko Tanaka, Working Group on Diagnostic Criteria for Refractory Optic Neuritis Based on Neuroimmunological Perspective
雑誌名: Ophthalmology. 2019 Oct;126(10):1385-1398. doi: 10.1016/j.ophtha.2019.04.042. Epub 2019 May 6.
Abstract/Text
PURPOSE: To elucidate the clinical and epidemiologic characteristics of optic neuritis in Japan.
DESIGN: Multicenter cross-sectional, observational cohort study.
PARTICIPANTS: A total of 531 cases of unilateral or bilateral noninfectious optic neuritis identified in 33 institutions nationwide in Japan.
METHODS: Serum samples from patients with optic neuritis were tested for anti-aquaporin-4 antibodies (AQP4-Abs) and anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) using a cell-based assay and were correlated with the clinical findings.
MAIN OUTCOME MEASURES: Antibody positivity, clinical and radiologic characteristics, and visual outcome.
RESULTS: Among 531 cases of optic neuritis, 12% were AQP4-Ab positive, 10% were MOG-Ab positive, 77% were negative for both antibodies (double-negative), and 1 case was positive for both antibodies. Pretreatment visual acuity (VA) worsened to more than a median 1.0 logarithm of the minimum angle of resolution (logMAR) in all groups. After steroid pulse therapy (combined with plasmapheresis in 32% of patients in AQP4-Ab-positive group), median VA improved to 0.4 logMAR in the AQP4-Ab-positive group, 0 logMAR in the MOG-Ab-positive group, and 0.1 logMAR in the double-negative group. The AQP4-Ab-positive group showed a high proportion of females, exhibited diverse visual field abnormalities, and demonstrated concurrent spinal cord lesions on magnetic resonance imaging (MRI) in 22% of the patients. In the MOG-Ab-positive group, although posttreatment visual outcome was good, the rates of optic disc swelling and pain with eye movement were significantly higher than those in the AQP4-Ab-positive and double-negative groups. However, most cases showed isolated optic neuritis lesions on MRI. In the double-negative group, 4% of the patients had multiple sclerosis. Multivariate logistic regression analysis of all participants identified age and presence of antibodies (MOG-Ab and AQP4-Ab) as significant factors affecting visual outcome.
CONCLUSIONS: The present large-scale cohort study revealed the clinicoepidemiologic features of noninfectious optic neuritis in Japan. Anti-aquaporin-4 antibody-positive optic neuritis has poor visual outcome. In contrast, MOG-Ab positive cases manifested severe clinical findings of optic neuritis before treatment, but few showed concurrent lesions in sites other than the optic nerve and generally showed good treatment response with favorable visual outcome. These findings indicate that autoantibody measurement is useful for prompt diagnosis and proper management of optic neuritis that tends to become refractory.
Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
PMID
31196727 Ophthalmology. 2019 Oct;126(10):1385-1398. doi: 10.1016･･･
