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 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.

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.

Atypical myelitis in patients with multiple sclerosis: Characterization and comparison with typical multiple sclerosis and neuromyelitis optica spectrum disorders

2020 ◽  
pp. 135245852090699
Author(s):  
K Bigaut ◽  
C Lambert ◽  
L Kremer ◽  
C Lebrun ◽  
M Cohen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neuromyelitis Optica ◽  
Transverse Myelitis ◽  
First Episode ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Disability Status ◽  
Plane Transverse ◽  
Spectrum Disorders ◽  
Extensive Transverse Myelitis

Background: Atypical myelitis in multiple sclerosis (MS) is characterized by extensive myelitis in the longitudinal (longitudinally extensive transverse myelitis) or axial plane (transverse myelitis). Objective: To characterize a cohort of MS patients with atypical myelitis. Methods: Atypical myelitis was extracted from the French and Luxembourg MS databases and compared to two cohorts of MS patients with typical myelitis and neuromyelitis optica spectrum disorders (NMOSDs) patients with myelitis. Results: We enrolled 28 MS patients with atypical myelitis, 68 MS patients with typical myelitis and 119 NMOSD patients with a first episode of myelitis. MS patients with atypical myelitis were characterized by a mean age of 34.0 (±10.7) years and 64.3% were women. In 82.1% of the patients, atypical myelitis was the first episode of MS. Mean Expanded Disability Status Scale (EDSS) scores at nadir and 3–6 months after onset were 4.1 ± 2.1 and 3.3 ± 2, respectively. Differences between groups revealed a predominance of cervicothoracic myelitis and a higher level of disability in NMOSD patients. Disability in MS patients with atypical myelitis was more severe than in the MS patients with typical myelitis; 28% had already converted to progressive MS within our mean follow-up of 39.6 (±30.4) months. Conclusion: Atypical myelitis may be the first presentation of MS and is associated with poorer prognosis.

scholarly journals Short segment myelitis as the initial and only manifestation of aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorders

2020 ◽  
Vol 13 ◽  
pp. 175628641989859
Author(s):  
Wei Fang* ◽  
Yang Zheng* ◽  
Fan Yang ◽  
Meng-Ting Cai ◽  
Chun-Hong Shen ◽  
...  
Keyword(s):  
Neuromyelitis Optica ◽  
Immunoglobulin G ◽  
Correct Diagnosis ◽  
Transverse Myelitis ◽  
Aquaporin 4 ◽  
Chinese Patients ◽  
Careful Study ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Short Segment ◽  
Spectrum Disorders

Background: Short segment myelitis (SSM, < 3 vertebral segments) is an under-recognized initial manifestation of neuromyelitis optica spectrum disorders (NMOSD). Though infrequent, failure to recognize SSM in patients with NMOSD would lead to incorrect diagnosis and treatment. Therefore, delineation of features of NMOSD-associated SSM is of paramount importance. Objective: Our study aimed to determine the demographic, clinical and radiological features of NMOSD-associated SSM, and compare those with NMOSD-associated longitudinally extensive transverse myelitis (LETM) and multiple sclerosis (MS)-associated SSM, respectively. Methods: Chinese patients presenting initially only with acute myelitis and diagnosed with NMOSD ( n = 46) and MS ( n = 11) were included. Clinical, serological, imaging and disability data were collected. Mann–Whitney U test or two-tailed Fisher’s exact tests were used to analyse the data. Results: Of the 46 enrolled NMOSD patients, 34 (74%) collectively had 38 LETM lesions, while 12 (26%) had 14 SSM lesions. When compared with LETM, NMOSD presenting with SSM were more likely to have a delayed diagnosis and a lower level of disability at nadir during the first attack. T1-weighted imaging hypointensity was more prominent in NMOSD-associated LETM lesions than NMOSD-associated SSM lesions. When compared with MS-associated SSM, NMOSD-associated SSM lesions were more likely to be centrally located, grey matter involving and transversally extensive on axial imaging and spanned no less than 2 vertebral segments on sagittal imaging. Conclusion: These findings suggest that SSM does not preclude the possibility of a NMOSD diagnosis. Testing for serum aquaporin-4 immunoglobulin G (AQP4-IgG) and careful study of lesions on spinal cord magnetic resonance imaging could aid in an earlier and correct diagnosis.

scholarly journals The Frequency of Anti-Aquaporin-4 Ig G Antibody in Neuromyelitis Optica and Its Spectrum Disorders at a Single Tertiary Referral Center in Malaysia

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Shanthi Viswanathan ◽  
Masita Arip ◽  
Norhazlin Mustafa ◽  
Jasbir S. Dhaliwal ◽  
Norzainie Rose ◽  
...  
Keyword(s):  
High Risk ◽  
Neuromyelitis Optica ◽  
Demyelinating Disease ◽  
Transverse Myelitis ◽  
Female Gender ◽  
Aquaporin 4 ◽  
Central Gray Matter ◽  
Tertiary Referral Center ◽  
Spectrum Disorders ◽  
Ig G

Background. In the past the occurrence of neuromyelitis optica in Malaysia was thought to be uncommon and the frequency of anti-aquaporin-4 Ig G antibody was unknown.Objective. To evaluate the frequency of anti-aquaporin-4 Ig G antibody (Anti-AQP4 antibody) amongst patients with neuromyelitis optica (NMO) and its spectrum disorders (NMOSD) and the differences between the seropositive and seronegative groups.Methods. Retrospectively, 96 patients with NMO/high risk syndromes for NMOSD (HRS-NMOSD) were identified out of 266 patients with idiopathic inflammatory demyelinating disease from a single center hospital based registry. Anti-AQP4 seropositivity was found in 38/48 (79.2%) with NMO, 12/21 (57.1%) with brain involvement at high risk for NMOSD, 12/15 (80%) with transverse myelitis (i.e., 11/15 with relapsing transverse myelitis and one with monophasic transverse myelitis), and 3/7 (42.8%) with relapsing optic neuritis. Sixty-five out of 96 patients, that is, 67.7%, with NMO/HRS for NMOSD were seropositive. Seropositivity was significantly associated with female gender, a higher number of mean relapses, that is, 5.15 ± 4.42 versus 2.10 ± 1.68, longer length of spinal cord lesions, that is, 6.6 ± 4.9 versus 2.9 ± 2.5, vertebral bodies, higher EDSS, 4.5 ± 2.4 versus 2.4 ± 2.6, presence of paroxysmal tonic spasms, and blindness (unilateral/bilateral);P<0.001. Longitudinally extensive cord lesions (contiguous or linear), presence of lesions in the cervical and thoracic regions, and involvement of the central gray matter or holocord regions on axial scans, were also significantly associated with seropositivity;P<0.001.Conclusion. NMO and HRS for NMOSD are present in larger numbers than previously thought in Malaysia. More than 2/3rds are seropositive. Seropositive and seronegative NMO/NMOSD have differences that are useful in clinical practice.

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.

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 Updated diagnostic criteria for neuromyelitis optica spectrum disorder: Similar outcomes of previously separate cohorts

2018 ◽  
Vol 4 (4) ◽  
pp. 205521731881592 ◽  
Author(s):  
M McCreary ◽  
MA Mealy ◽  
DM Wingerchuk ◽  
M Levy ◽  
A DeSena ◽  
...  
Keyword(s):  
Neuromyelitis Optica ◽  
Retrospective Chart Review ◽  
Central Nervous System Disease ◽  
Spectrum Disorder ◽  
Aquaporin 4 ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Clinical Criteria ◽  
System Disease ◽  
Pre Treatment ◽  
Aquaporin 4 Antibody

Background The specificity of the aquaporin-4 antibody to predict recurrent inflammatory central nervous system disease has led to the design of the 2015 neuromyelitis optica spectrum disorder criteria which capture all aquaporin-4 antibody seropositive patients. Objective The purpose of this study was to compare treatment outcomes in aquaporin-4 antibody seropositive patients who met the previous 2006 clinical criteria for neuromyelitis optica with patients who meet the 2015 neuromyelitis optica spectrum disorder criteria. Methods The study involved a three-center retrospective chart review of clinical outcomes among aquaporin-4 patients diagnosed with neuromyelitis optica and neuromyelitis optica spectrum disorder. Results Hazard ratios of relapse during immunosuppressive therapy, relative to pre-therapy, were not significantly different for patients who met the 2006 criteria of neuromyelitis optica versus the 2015 neuromyelitis optica spectrum disorder criteria among those treated with azathioprine (  p = 0.24), mycophenolate mofetil (  p = 0.63), or rituximab (  p = 0.97). Conclusion Reductions in the hazard of relapse during treatment with immunosuppressive therapies, relative to average pre-treatment, were not different for aquaporin-4 antibody seropositive patients categorized using the 2006 criteria of neuromyelitis optica and the 2015 neuromyelitis optica spectrum disorder criteria. These therapeutic findings support the design of the 2015 neuromyelitis optica spectrum disorder criteria which capture all aquaporin-4 antibody seropositive patients.

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