scholarly journals NMO-IgG: A Specific Biomarker for Neuromyelitis Optica

2006 ◽  
Vol 22 (4) ◽  
pp. 197-206 ◽  
Author(s):  
Brian G. Weinshenker ◽  
Dean M. Wingerchuk ◽  
Sean J. Pittock ◽  
Claudia F. Lucchinetti ◽  
Vanda A. Lennon

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that principally targets the optic nerves and spinal cord and often leads to severe disability and occasionally life threatening respiratory failure. Although its clinical manifestations overlap with those of multiple sclerosis (MS), in established cases these two conditions can be distinguished on the basis of clinical, radiological, and routine spinal fluid studies. The diagnosis in early cases or limited forms of NMO is difficult. We recently discovered a unique IgG autoantibody (NMO-IgG) that is highly specific to patients with NMO and thus a valuable diagnostic aid. Its antigen, aquaporin-4 (AQP4), is the central nervous system’s predominant water channel protein. This antibody has not yet been proven to be pathogenic, but several facts suggest that it might be, including the similarity of the immunohistochemical pattern of NMO-(AQP4) IgG binding to mouse CNS tissues to the pattern of immune complex deposition in autopsied patients’ spinal cord tissue. The spectrum of diseases identified by NMO-IgG is broader than has previously been recognized clinically and includes incomplete forms of NMO, such as recurrent transverse myelitis without optic neuritis and recurrent optic neuritis without myelitis.

Author(s):  
Teri L. Schreiner ◽  
Jeffrey L. Bennett

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.


Biomedicines ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 42 ◽  
Author(s):  
Marco A. Lana-Peixoto ◽  
Natália Talim

Neuromyelitis optica spectrum disorder (NMOSD) and anti-myelin oligodendrocyte glycoprotein (anti-MOG) syndromes are immune-mediated inflammatory conditions of the central nervous system that frequently involve the optic nerves and the spinal cord. Because of their similar clinical manifestations and habitual relapsing course they are frequently confounded with multiple sclerosis (MS). Early and accurate diagnosis of these distinct conditions is relevant as they have different treatments. Some agents used for MS treatment may be deleterious to NMOSD. NMOSD is frequently associated with antibodies which target aquaporin-4 (AQP4), the most abundant water channel in the CNS, located in the astrocytic processes at the blood-brain barrier (BBB). On the other hand, anti-MOG syndromes result from damage to myelin oligodendrocyte glycoprotein (MOG), expressed on surfaces of oligodendrocytes and myelin sheaths. Acute transverse myelitis with longitudinally extensive lesion on spinal MRI is the most frequent inaugural manifestation of NMOSD, usually followed by optic neuritis. Other core clinical characteristics include area postrema syndrome, brainstem, diencephalic and cerebral symptoms that may be associated with typical MRI abnormalities. Acute disseminated encephalomyelitis and bilateral or recurrent optic neuritis are the most frequent anti-MOG syndromes in children and adults, respectively. Attacks are usually treated with steroids, and relapses prevention with immunosuppressive drugs. Promising emerging therapies for NMOSD include monoclonal antibodies and tolerization.


2020 ◽  
Author(s):  
Leung-Wah Yick ◽  
Chi-Ho Tang ◽  
Oscar Ka-Fai Ma ◽  
Jason Shing-Cheong Kwan ◽  
Koon Ho CHAN

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.


2021 ◽  
Vol 13 (4) ◽  
pp. 18-24
Author(s):  
S. V. Kotov ◽  
E. S. Novikova ◽  
A. S. Kotov

Neuromyelitis optica spectrum disorders (NMOSDs) are a group of central nervous system autoimmune diseases characterized by similar clinical manifestations, optic neuritis, and transverse myelitis being the most frequent among them. In most cases, the pathogenesis of NMOSDs is associated with autoantibodies to aquaporin-4 (AQP4-IgG). However, AQP4-IgG is not detected in at least 10-20% of patients with NMOSDs. In this subgroup and in patients with isolated transverse myelitis or optic neuritis, IgG antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) were detected. Patients seronegative for both AQP4-IgG and MOG-IgG have also been described.Objective: to evaluate rituximab (RTX) effectiveness in preventing relapses and disability in patients with NMOSDs.Patients and methods. The study included 27 patients with NMOSDs (9 men and 18 women) aged 20-51 years who received RTX in 2019-2021. The treatment protocol included intravenous infusions of 1000 mg of RTX on the 1st and 15th days, the second and subsequent courses (maintenance therapy) - intravenous infusions of 1000 mg of RTX once every six months. Treatment effectiveness was assessed by the average annualized relapse rate, the median changes of the Expanded Disability Status Scale (EDSS), and based on the magnetic resonance imaging (MRI) changes.Results and discussion. The annualized relapse rate at baseline and 18 months after the start of treatment was: all patients (n=27) — 0.6±0.3 and 0.07±0.27(p<0.0001); AQP4-IgG+ patients (n=6) — 1.1±0.9 and 0.17±0.41 (p=0.028); MOG-IgG+ patients (n=14) — 0.4±0.3 and 0.07±0.28(p=0.001); AQP4-IgG-, MOG-IgG-patients (n=7) — 0.8±0.4 and 0.0±0.0 (p=0.018). The EDSSscore at baseline and 18months after the start of treatment was: all patients — 4.5 [3.25; 6.0] and 4.0 [3.0; 5.75] (p=0.679); AQP4-IgG+ — 3.5 [2.625; 4.75] and 3.5 [2.5; 4.5] (p=0.869); MOG-IgG+ - 5.5[3.75; 6.5] and 5.5[2.75; 6.25] (p=0.465); AQP4-IgG-, MOG-IgG- - 4.0[3.75; 5.25] and 3.5[3.0; 3.5] (p=0.043). We observed two clinical relapses during the study period: one in an AQP4-IgG+ male and another one in a MOG-IgG+ woman. There was a significant decrease in the annualized relapse rate in all groups. The disability indicator did not increase during the study period, and in AQP4-IgG and MOG-IgG seronegative patients, it slightly but significantly decreased. Brain and spinal cord MRI monitoring during the treatment period revealed new active foci only in two patients with clinical relapses.Conclusion. RTX treatment in NMOSDs is reasonably efficient and safe, but with the obligatory prior patient evaluation and monitoring of treatment results.


2005 ◽  
Vol 202 (4) ◽  
pp. 473-477 ◽  
Author(s):  
Vanda A. Lennon ◽  
Thomas J. Kryzer ◽  
Sean J. Pittock ◽  
A.S. Verkman ◽  
Shannon R. Hinson

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.


2011 ◽  
Vol 114 (3) ◽  
pp. 830-833 ◽  
Author(s):  
Nam-Hee Kim ◽  
Keun-Tae Cho ◽  
Hyung Suk Seo

Intracranial dural arteriovenous fistula (DAVF) is rare and potentially life-threatening disease often presenting as vascular myelopathy. The early and proper diagnosis is challenging because the clinical manifestations are related to the distribution of the draining vein, not the fistula site, and imaging findings are similar to demyelinating disease of the spinal cord. The authors present the case of a 45-year-old man who developed acute progressive quadriplegia and respiratory difficulty with an enhancing, longitudinally extensive cervical cord lesion. These symptoms were highly suspicious for transverse myelitis but were caused by an intracranial DAVF. Intracranial DAVF with venous reflux to the brainstem and spinal cord is a rare but important differential diagnosis of progressive worsening myelopathy that is treatment resistant and gives the diagnostic impression of transverse myelitis.


2014 ◽  
Vol 7 ◽  
pp. CCRep.S15177 ◽  
Author(s):  
Mohammad Adawi ◽  
Bishara Bisharat ◽  
Abdalla Bowirrat

Neuromyelitis optica (NMO) is usually a relapsing demyelinating disease of the central nervous system associated with optic neuritis, transverse myelitis involving three or more contiguous spinal cord segments, and seropositivity for NMO-IgG antibody. NMO is often mistaken for multiple sclerosis and there are relatively sporadic publications about NMO and overlapping systemic or organ-specific autoimmune diseases, such as systemic lupus erythematosus (SLE). We described a unique case of a 25-year-old Arab young woman who was diagnosed with SLE, depending on clinical, laboratory investigations and after she had fulfilled the diagnostic criteria for SLE and had presented the following findings: constitutional findings (fatigue, fever, and arthralgia); dermatologic finding (photosensitivity and butterfly rash); chronic renal failure (proteinuria up to 400 mg in 24 hours); hematologic and antinuclear antibodies (positivity for antinuclear factor (ANF), anti-double-stranded DNA antibodies, direct Coombs, ANA and anti-DNA, low C4 and C3, aCL by IgG and IgM). Recently, she presented with several episodes of transverse myelitis and optic neuritis. Clinical, radiological, and laboratory findings especially seropositivity for NMO-IgG were compatible with NMO. Accurate diagnosis is critical to facilitate initiation of immunosuppressive therapy for attack prevention. This case illustrates that NMO may be associated with SLE.


2017 ◽  
Vol 16 (03) ◽  
pp. 164-170
Author(s):  
Rachel Gottlieb-Smith ◽  
Amy Waldman

AbstractAcquired demyelinating syndromes (ADS) present with acute or subacute monofocal or polyfocal neurologic deficits localizing to the central nervous system. The clinical features of distinct ADS have been carefully characterized including optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis. These disorders may all be monophasic disorders. Alternatively, optic neuritis, partial transverse myelitis, and acute disseminated encephalomyelitis may be first presentations of a relapsing or polyphasic neuroinflammatory disorder, such as multiple sclerosis or neuromyelitis optica. The clinical features of these disorders and the differential diagnosis are discussed in this article.


2013 ◽  
Vol 71 (1-2) ◽  
pp. 35-41 ◽  
Author(s):  
Aiyu Lin ◽  
Jiting Zhu ◽  
Xiaoping Yao ◽  
Shifang Lin ◽  
Shenxing Murong ◽  
...  

2020 ◽  
pp. 10.1212/CPJ.0000000000001012
Author(s):  
Mary Clare McKenna ◽  
Nuala McNicholas ◽  
Conor Fearon ◽  
David Bradley

Background:Neuromyelitis optica (NMO) is a rare autoimmune inflammatory disorder of the central nervous system1. Pathogenic aquaporin 4 (AQP4) antibodies are present in 65-88% of cases1. The majority of cases follow a relapsing course preferentially involving the optic nerves, spinal cord, brainstem, diencephalon or cerebral regions1, 2. Within the acute diencephalic clinical presentations, symptomatic hypothalamic lesions may have a diverse range of clinical manifestations including homeostatic dysfunction of neuroendocrine systems2-4. We report a case of recurrent hypothalamic dysfunction secondary to NMO manifesting as syndrome of inappropriate secretion of antidiuretic hormone (SIADH), thermal dysregulation, dysautonomia and disorder of alertness.


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