scholarly journals Devic’s neuromyelitis optica: a critical review

2008 ◽  
Vol 66 (1) ◽  
pp. 120-138 ◽  
Author(s):  
Marco Aurélio Lana-Peixoto
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Neuromyelitis Optica ◽  
Brain Mri ◽  
Water Channel ◽  
Demyelinating Diseases ◽  
Aquaporin 4 ◽  
Igg Antibody ◽  
Vascular Walls ◽  
Devic’S Neuromyelitis Optica

Devic's neuromyelitis optica (NMO) is an idiopathic inflammatory demyelinating and necrotizing disease characterized by predominant involvement of the optic nerves and spinal cord. In Asian countries relapsing NMO has been known as opticospinal multiple sclerosis. It has long been debated if NMO is a variant of multiple sclerosis (MS) or a distinct disease. Recent studies have shown that NMO has more frequently a relapsing course, and results from attack to aquaporin-4 which is the dominant water channel in the central nervous system, located in foot processes of the astrocytes. Distinctive pathological features of NMO include perivascular deposition of IgG and complement in the perivascular space, granulocyte and eosinophil infiltrates and hyalinization of the vascular walls. These features distinguish NMO from other demyelinating diseases such as MS and acute demyelinating encephalomyelopathy. An IgG-antibody that binds to aquaporin-4, named NMO-IgG has high sensitivity and specificity. Magnetic resonance imaging (MRI) studies have revealed that more frequently there is a long spinal cord lesion that extends through three or more vertebral segments in length. Brain MRI lesions atypical for MS are found in the majority of cases. Treatment in the acute phase includes intravenous steroids and plasma exchange therapy. Immunosupressive agents are recommended for prophylaxis of relapses.

scholarly journals IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel

2005 ◽  
Vol 202 (4) ◽  
pp. 473-477 ◽  
Author(s):  
Vanda A. Lennon ◽  
Thomas J. Kryzer ◽  
Sean J. Pittock ◽  
A.S. Verkman ◽  
Shannon R. Hinson
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Blood Brain Barrier ◽  
Neuromyelitis Optica ◽  
Immunoglobulin G ◽  
Protein Complex ◽  
Demyelinating Disease ◽  
Water Channel ◽  
Aquaporin 4 ◽  
Specific Marker

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.

Neuromyelitis Optica

2017 ◽  
Author(s):  
Teri L. Schreiner ◽  
Jeffrey L. Bennett
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Optic Neuritis ◽  
Neuromyelitis Optica ◽  
Water Channel ◽  
Transverse Myelitis ◽  
Inflammatory Disorder ◽  
The Central Nervous System

Neuromyelitis optica (NMO), or Devic’s disease is an inflammatory disorder of the central nervous system that preferentially affects the optic nerves and spinal cord. Initially considered a variant of multiple sclerosis (MS), NMO is now clearly recognized to have distinct clinical, radiographic, and pathologic characteristics. Historically, the diagnosis of NMO required bilateral optic neuritis and transverse myelitis; however, the identification of a specific biomarker, NMO-IgG, an autoantibody against the aquaporin-4 (AQP4) water channel, has broadened NMO spectrum disease to include patients with diverse clinical and radiographic presentations. This chapter addresses the diagnosis, pathophysiology, and management of the disease.

scholarly journals Memantine ameliorates motor impairments and pathologies in a mouse model of neuromyelitis optica spectrum disorders.

2020 ◽  
Author(s):  
Leung-Wah Yick ◽  
Chi-Ho Tang ◽  
Oscar Ka-Fai Ma ◽  
Jason Shing-Cheong Kwan ◽  
Koon Ho CHAN
Keyword(s):  
Spinal Cord ◽  
Neuromyelitis Optica ◽  
Neurotrophic Factor ◽  
Water Channel ◽  
Transverse Myelitis ◽  
Aquaporin 4 ◽  
Glutamate Excitotoxicity ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Motor Impairments ◽  
Spectrum Disorders

Abstract Background: Neuromyelitis optica spectrum disorders (NMOSD) are central nervous system (CNS) autoimmune inflammatory demyelinating diseases characterized by recurrent episodes of acute optic neuritis and transverse myelitis. Aquaporin-4 immunoglobulin G (AQP4-IgG) autoantibodies, which target the water channel aquaporin-4 (AQP4) on astrocytic membrane, are pathogenic in NMOSD. Glutamate excitotoxicity, which is triggered by internalization of AQP4-glutamate transporter complex after AQP4-IgG binding to astrocytes, is involved in early NMOSD pathophysiologies. We studied the effects of memantine, a N-methyl-D-aspartate (NMDA) receptor antagonist, on motor impairments and spinal cord pathologies in mice which received human AQP4-IgG. Methods: Purified IgG from AQP4-IgG-seropositive NMOSD patients were passively transferred to adult C57BL/6 mice with disrupted blood-brain barrier. Memantine was administered by oral gavage. Motor impairments of the mice were assessed by beam walking test. Spinal cords of the mice were assessed by immunofluorescence and ELISA. Results: Oral administration of memantine ameliorated the motor impairments induced by AQP4-IgG, no matter the treatment was initiated before (preventive) or after (therapeutic) disease flare. Memantine profoundly reduced AQP4 and astrocyte loss, and attenuated demyelination and axonal loss in the spinal cord of mice which had received AQP4-IgG. The protective effects of memantine were associated with inhibition of apoptosis and suppression of neuroinflammation, with decrease in microglia activation and neutrophil infiltration and reduction of increase in levels of proinflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF- α). In addition, memantine elevated growth factors including brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF) in the spinal cord. Conclusions: Our findings support that glutamate excitotoxicity and neuroinflammation plays important roles in complement-independent pathophysiology during early development of NMOSD lesions, and highlight the potential of oral memantine as a therapeutic agent in NMOSD acute attacks.

Is Devic's neuromyelitis optica a separate disease? A comparative study with multiple sclerosis

2003 ◽  
Vol 9 (5) ◽  
pp. 521-525 ◽  
Author(s):  
J de Seze ◽  
C Lebrun ◽  
T Stojkovic ◽  
D Ferriby ◽  
M Chatel ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Optic Neuritis ◽  
Neuromyelitis Optica ◽  
Brain Mri ◽  
Oligoclonal Bands ◽  
Time And Space ◽  
Laboratory Findings ◽  
Therapeutic Trials ◽  
The Difference ◽  
Devic’S Neuromyelitis Optica

Devic's neuromyelitis optica (NMO) associates optic neuritis and myelopathy without other neurological signs. Many patients with NMO may be diagnosed as having multiple sclerosis (MS). However, there have been no previous studies comparing these two patho logies and it is still unclear if NMO is a separate entity or a subtype of MS. In the present study, we compared a series of NMO patients with a series of MS patients for whom optic neuritis or myelopathy was the presenting symptom, in order to determine the place of NMO in the spectrum of MS. We retrospectively studied 30 patients diagnosed with NMO and we compared these patients with 50 consecutive MS cases revealed by optic neuritis or acute myelopathy. MS patients were only included if a relapse occurred demonstrating time and space dissemination. We compared the two groups in terms of clinical presentatio n, laboratory findings (MRI and C SF) and clinical outcome. NMO patients were older and more frequently women than MS patients but the difference was not significant. C SF and MRI data were clearly different: oligoclonal bands (O C B) were found in 23% of NMO cases and 88% of MS (P B/0.001), abnormal brain MRI data were observed in 10% of NMO cases and 66% of MS (P B/0.001) and a large spinal cord lesion was observed in 67% of NMO cases and 7.4% of MS cases (P B/0.001). C linical outcome was evaluated as more severe in the NMO group (P B/0.001). O n the basis of clinical data, all NMO patients but three had dissemination in time and space. When we included MRI parameters, only two of the NMO patients met criteria for MS and one of the MS patients met criteria for NMO. O ur study demonstrates that NMO and MS should be considered as two different entities. The respective criteria for NMO and MS were able to distinguish these two patho logies but only when MRI data were applied. This finding could have implications for future therapeutic trials.

scholarly journals NMO in pediatric patients: brain involvement and clinical expression

2011 ◽  
Vol 69 (1) ◽  
pp. 34-38 ◽  
Author(s):  
Joaquín A. Peña ◽  
María Elena Ravelo ◽  
Eduardo Mora-La Cruz ◽  
Cecilia Montiel-Nava
Keyword(s):  
Multiple Sclerosis ◽  
Optic Neuritis ◽  
Neuromyelitis Optica ◽  
Optic Neuropathy ◽  
Pediatric Patients ◽  
Brain Mri ◽  
Water Channel ◽  
Suggested Method ◽  
Clinical Expression ◽  
Brain Involvement

OBJECTIVE: To analyze the clinical, neuroimaging characteristics and positivity of the acquaporin water channel (NMO-IgG) in pediatric patients with neuromyelitis optica (NMO). This disorder could have a variable clinical expression. To address such variability, the term NMO spectrum has been suggested. METHOD: We evaluated six pediatric patients, with a median age of 11 years at the time of the study, with the diagnosis of NMO by the Wingerchuck criteria. RESULTS: All the cases exhibited bilateral optic neuritis (ON). Four patients had abnormalities on brain MRI from the onset,although only three of them developed symptoms correlated to those lesions during the course of their disorder. NMO-IgG was positive in 80%. CONCLUSION: Optic neuropathy is the most impaired feature in NMO patients. Brain MRI lesions are not compatible with multiple sclerosis and positivity of the NMO-IgG are also present in NMO pediatric patients, confirming the heterogeneity in the expression of this disorder.

Central vein sign and other radiographic features distinguishing myelin oligodendrocyte glycoprotein antibody disease from multiple sclerosis and aquaporin-4 antibody-positive neuromyelitis optica

2021 ◽  
pp. 135245852110070
Author(s):  
John R Ciotti ◽  
Noah S Eby ◽  
Matthew R Brier ◽  
Gregory F Wu ◽  
Salim Chahin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Optic Nerve ◽  
Neuromyelitis Optica ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Aquaporin 4 ◽  
Central Vein ◽  
Nerve Involvement ◽  
Fluid Attenuated Inversion Recovery ◽  
Optic Nerve Involvement

Background: Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) can radiographically mimic multiple sclerosis (MS) and aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD). Central vein sign (CVS) prevalence has not yet been well-established in MOGAD. Objective: Characterize the magnetic resonance imaging (MRI) appearance and CVS prevalence of MOGAD patients in comparison to matched cohorts of MS and AQP4+ NMOSD. Methods: Clinical MRIs from 26 MOGAD patients were compared to matched cohorts of MS and AQP4+ NMOSD. Brain MRIs were assessed for involvement within predefined regions of interest. CVS was assessed by overlaying fluid-attenuated inversion recovery (FLAIR) and susceptibility-weighted sequences. Topographic analyses were performed on spinal cord and orbital MRIs when available. Results: MOGAD patients had fewer brain lesions and average CVS+ rate of 12.1%, compared to 44.4% in MS patients ( p = 0.0008). MOGAD spinal cord and optic nerve involvement was lengthier than MS (5.8 vs 1.0 vertebral segments, p = 0.020; 3.0 vs 0.5 cm, p < 0.0001). MOGAD patients tended to have bilateral/anterior optic nerve pathology with perineural contrast enhancement, contrasting with posterior optic nerve involvement in NMOSD. Conclusion: CVS+ rate and longer segments of involvement in the spinal cord and optic nerve can differentiate MOGAD from MS, but do not discriminate as well between MOGAD and AQP4+ NMOSD.

Reappraisal of brain MRI features in patients with multiple sclerosis and neuromyelitis optica according to anti-aquaporin-4 antibody status

2010 ◽  
Vol 291 (1-2) ◽  
pp. 37-43 ◽  
Author(s):  
Takuya Matsushita ◽  
Noriko Isobe ◽  
Hua Piao ◽  
Takeshi Matsuoka ◽  
Takaaki Ishizu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neuromyelitis Optica ◽  
Brain Mri ◽  
Aquaporin 4 ◽  
Mri Features ◽  
Aquaporin 4 Antibody

scholarly journals Cytoprotective IgG antibodies in sera from a subset of patients with AQP4-IgG seropositive neuromyelitis optica spectrum disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lukmanee Tradtrantip ◽  
Michael R. Yeaman ◽  
A. S. Verkman
Keyword(s):  
Neuromyelitis Optica ◽  
Protective Factor ◽  
Water Channel ◽  
Spectrum Disorder ◽  
Aquaporin 4 ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Igg Antibody ◽  
Igg Binding ◽  
Complement Dependent Cytotoxicity ◽  
Wide Range

AbstractNeuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system. Most NMOSD patients are seropositive for immunoglobulin G (IgG) autoantibodies against astrocyte water channel aquaporin-4 (AQP4), called AQP4-IgG. AQP4-IgG binding to aquaporin-4 causes complement-dependent cytotoxicity (CDC), leading to inflammation and demyelination. Here, CDC was measured in AQP4-expressing cells exposed to human complement and heat-inactivated sera from 108 AQP4-IgG seropositive NMOSD subjects and 25 non-NMOSD controls. AQP4-IgG positive sera produced a wide range of CDC, with 50% maximum cytotoxicity produced by as low as 0.2% serum concentration. Unexpectedly, 58 samples produced no cytotoxicity, and of those, four sera were cytoprotective against cytotoxic AQP4-IgG. Cytoprotection was found against different cytotoxic monoclonal AQP4-IgGs and NMOSD patient sera, and in primary astrocyte cultures. Mechanistic studies revealed that the protective factor is an IgG antibody that did not inhibit complement directly, but interfered with binding of cytotoxic AQP4-IgG to AQP4 and consequent C1q binding and complement activation. Further studies suggested that non-pathogenic AQP4-IgG, perhaps with altered glycosylation, may contribute to reduced or ineffectual binding of cytotoxic AQP4-IgG, as well as reduced cell-surface AQP4. The presence of natural cytoprotective antibodies in AQP4-IgG seropositive sera reveals an added level of complexity in NMOSD disease pathogenesis, and suggests the potential therapeutic utility of ‘convalescent’ serum or engineered protective antibody to interfere with pathogenic antibody in AQP4-IgG seropositive NMOSD.

Neuromyelitis Optica Spectrum Disorders

2016 ◽  
Author(s):  
Dean M. Wingerchuk
Keyword(s):  
Multiple Sclerosis ◽  
Neuromyelitis Optica ◽  
Water Channel ◽  
Transverse Myelitis ◽  
Central Nervous System Disease ◽  
Aquaporin 4 ◽  
Pathogenic Potential ◽  
System Disease ◽  
Secondary Demyelination ◽  
Spectrum Disorders

Neuromyelitis optica (NMO) is an inflammatory demyelinating central nervous system disease. It has been classically defined as a monophasic, isolated co-occurrence of optic neuritis and transverse myelitis with uncertain relationship to multiple sclerosis. In the past decade, however, NMO has emerged as a distinct disorder associated with serum antibodies that target the astrocyte water channel aquaporin-4, distinguishing it from multiple sclerosis. The specificity of aquaporin-4 antibodies has led to appreciation of a wider spectrum of clinical and neuroimaging features, termed NMO spectrum disorders (NMOSD), than was encompassed by the classic NMO definition. Moreover, immunopathological studies have demonstrated that aquaporin-4 antibodies have pathogenic potential and that the disorder is a primary astrocytopathy with secondary demyelination. This chapter discusses the clinical definition and diagnosis of NMOSD and approaches to management, many informed by rapid advances in the understanding of NMO pathobiology.

scholarly journals No association of AQP4 polymorphisms with neuromyelitis optica and multiple sclerosis

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Ting-Ting Yang ◽  
Yang He ◽  
Ya-Juan Xiang ◽  
Dong-Hui Ao ◽  
Yang-Yang Wang ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Environmental Factors ◽  
Neuromyelitis Optica ◽  
Water Channel ◽  
Aquaporin 4 ◽  
The Central Nervous System ◽  
Genetic And Environmental Factors ◽  
Demyelinating Disorders

AbstractMultiple sclerosis (MS) and neuromyelitis optica (NMO) are inflammatory demyelinating disorders of the central nervous system (CNS). Various genetic and environmental factors have been identified to contribute to etiology of MS and NMO. Aquaporin 4 (AQP4), is the most abundant water channel in CNS.

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