Treatment of Neuromyelitis Optica Spectrum Disorders

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune central nervous system (CNS) inflammatory disorder that can lead to serious disability and mortality. Females are predominantly affected, including those within the reproductive age. Most patients develop relapsing attacks of optic neuritis; longitudinally extensive transverse myelitis; and encephalitis, especially brainstem encephalitis. The majority of NMOSD patients are seropositive for IgG autoantibodies against the water channel protein aquaporin-4 (AQP4-IgG), reflecting underlying aquaporin-4 autoimmunity. Histological findings of the affected CNS tissues of patients from in-vitro and in-vivo studies support that AQP4-IgG is directly pathogenic in NMOSD. It is believed that the binding of AQP4-IgG to CNS aquaporin-4 (abundantly expressed at the endfoot processes of astrocytes) triggers astrocytopathy and neuroinflammation, resulting in acute attacks. These attacks of neuroinflammation can lead to pathologies, including aquaporin-4 loss, astrocytic activation, injury and loss, glutamate excitotoxicity, microglial activation, neuroinflammation, demyelination, and neuronal injury, via both complement-dependent and complement-independent pathophysiological mechanisms. With the increased understanding of these mechanisms underlying this serious autoimmune astrocytopathy, effective treatments for both active attacks and long-term immunosuppression to prevent relapses in NMOSD are increasingly available based on the evidence from retrospective observational data and prospective clinical trials. Knowledge on the indications and potential side effects of these medications are essential for a clear evaluation of the potential benefits and risks to NMOSD patients in a personalized manner. Special issues such as pregnancy and the coexistence of other autoimmune diseases require additional concern and meticulous care. Future directions include the identification of clinically useful biomarkers for the prediction of relapse and monitoring of the therapeutic response, as well as the development of effective medications with minimal side effects, especially opportunistic infections complicated by long-term immunosuppression.

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

10.21203/rs.3.rs-27104/v1 ◽

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.

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Aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder with recurrent short partial transverse myelitis and favorable prognosis: Two new cases

Multiple Sclerosis Journal ◽

10.1177/1352458517705479 ◽

2017 ◽

Vol 23 (14) ◽

pp. 1950-1954 ◽

Cited By ~ 3

Author(s):

Jinhua Zhang ◽

Fang Liu ◽

Yiqi Wang ◽

Ying Yang ◽

Yuehong Huang ◽

...

Keyword(s):

Neuromyelitis Optica ◽

Transverse Myelitis ◽

Acute Attack ◽

Spectrum Disorder ◽

Aquaporin 4 ◽

Neuromyelitis Optica Spectrum Disorder ◽

Attack Phase ◽

Long Term Prognosis

Understanding the characteristics of neuromyelitis optica spectrum disorder (NMOSD) with recurrent short partial transverse myelitis (SPTM), which is very rare, contributes to the differential diagnosis of multiple sclerosis (MS). We present two Chinese aquaporin-4 immunoglobulin G (AQP4-IgG)-seropositive NMOSD cases who had at least twice SPTM during 4 and 6 years of follow-up, respectively. Their SPTMs have been mild and responded well to corticosteroids just like in the case of MS. The findings highlight the need of searching for serum AQP4-IgG (cell-based assay strongly recommended) in patients with recurrent SPTM and suggest that those patients may have a mild acute attack phase and favorable long-term prognosis.

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Neuromyelitis Optica

10.1093/med/9780199937837.003.0088 ◽

2017 ◽

Cited By ~ 1

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.

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Aquaporin-4-IgG Positive Neuromyelitis Optica Spectrum Disorder from Ethiopia: A Case Report

Ethiopian Journal of Health Sciences ◽

10.4314/ejhs.v30i5.25 ◽

2020 ◽

Vol 30 (5) ◽

Author(s):

Dereje Melka

Keyword(s):

Neuromyelitis Optica ◽

Addis Ababa ◽

Transverse Myelitis ◽

Spectrum Disorder ◽

Aquaporin 4 ◽

Inflammatory Disorder ◽

Neuromyelitis Optica Spectrum Disorder ◽

Mri Imaging ◽

Limb Weakness ◽

The Right

BACKGROUND: Neuromyelitis Optica spectrum disorder is an inflammatory disorder affecting the central nervous system), most commonly attacking the spinal cord or optic nerves. Limited cases of neuromyelitis optica have been reported in east Africa. Based on my review, if published, this would be the second published case of Neuromyelitis Optica spectrum disorder and the first published case of seropositive Neuromyelitis Optica spectrum disorder reported from Ethiopia. It signifies the need to have a high index of suspicion to promptly identify and properly treat these patients.CASE PRESENTATION: I am reporting a 32 years old female patient from Addis Ababa, Ethiopia, who presented with recurrent lower limb weakness and impairment of right eye vision of two-year duration. She was diagnosed based on Neuromyelitis Optica spectrum disorder diagnostic criteria, by having transverse myelitis, optic neuritis, confirmed by MRI imaging and high level of aquaporin-4-antibodies. Symptoms improved after providing five days of Methylprednisolone followed by low doses of corticosteroids and Azathioprine. The patient is now fully functional except for the right eye vision impairment.CONCLUSION: The patient described here signifies a classic manifestation of Neuromylitis Optica disorder with aquaporin- 4-IgG occurring in Ethiopian woman. This case highlights the existence of Devic’s disease within our setting and the need toproperly diagnose this condition even in a resource-limited setting to avert disability.

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Neuromyelitis Optica Spectrum Disorders

10.1093/med/9780199341016.003.0023 ◽

2016 ◽

Cited By ~ 3

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.

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The Spectrum of Neuromyelitis Optica (NMO) in Childhood

Journal of Child Neurology ◽

10.1177/0883073812451495 ◽

2012 ◽

Vol 27 (11) ◽

pp. 1437-1447 ◽

Cited By ~ 22

Author(s):

J.M. Tillema ◽

A. McKeon

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Neuromyelitis Optica ◽

Water Channel ◽

Transverse Myelitis ◽

Acute Disseminated Encephalomyelitis ◽

Aquaporin 4 ◽

Simultaneous Occurrence ◽

Clinical Syndromes ◽

The Central Nervous System

The evaluation of inflammatory central nervous system disorders in childhood with predominant involvement of the optic nerves and spinal cord has been greatly enhanced over the last decade with identification of a group of disorders unified by the detection of neuromyelitis optica (NMO)–IgG, an antibody targeting the central nervous system–predominant water channel aquaporin-4. Clinical syndromes are predominated by the relapsing form of NMO but also include encephalopathic variants that can mimic acute disseminated encephalomyelitis. Maintenance immunotherapy is used to prevent relapses in NMO-IgG–seropositive patients. In contrast, NMO-IgG–seronegative children with NMO more commonly have a monophasic course (simultaneous occurrence of optic neuritis and transverse myelitis) and do not require remission-maintaining immunotherapy, but close surveillance is advised. Current clinical, pathological, and pathogenetic knowledge is reviewed with a focus on clinical presentation, neuroimaging findings, serological investigations, and treatment of children with disorders within the spectrum of central nervous system aquaporin-4 autoimmunity.

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Severe aquaporin 4-IgG-positive neuromyelitis optica with disseminated herpes zoster in a pregnant woman successfully treated with intravenous immunoglobulin

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217318758119 ◽

2018 ◽

Vol 4 (1) ◽

pp. 205521731875811

Author(s):

Yuki Matsumoto ◽

Mario Tsuchiya ◽

Shakespear Norshalena ◽

Chikako Kaneko ◽

Jin Kubo ◽

...

Keyword(s):

Herpes Zoster ◽

Pregnant Woman ◽

Intravenous Immunoglobulin ◽

Neuromyelitis Optica ◽

Rescue Therapy ◽

Transverse Myelitis ◽

Aquaporin 4 ◽

High Dose ◽

Healthy Baby ◽

Severe Infections

A 26-year-old, 17-week pregnant woman developed aquaporin-4-IgG-positive severe longitudinally extensive transverse myelitis during the course of disseminated herpes zoster and became quadriparetic. She was unresponsive to high-dose intravenous methylprednisolone but became able to walk without assistance after intravenous immunoglobulin. One and a half months later, left optic neuritis developed but her vision improved with intravenous immunoglobulin. The only sequela was left T5 girdle sensation, and she delivered a healthy baby. Intravenous immunoglobulin may be a rescue therapy in aquaporin-4-IgG-positive neuromyelitis optica attacks in pregnant women, especially those with severe infections.

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PEMILIHAN KONTRASEPSI BERDASARKAN EFEK SAMPING PADA DUA KELOMPOK USIA REPRODUKSI

Unnes Journal of Public Health ◽

10.15294/ujph.v6i3.11543 ◽

2017 ◽

Vol 6 (3) ◽

pp. 167

Author(s):

Erna Setiawati ◽

Oktia Woro Kasmini Handayani ◽

Asih Kuswardinah

Keyword(s):

Side Effects ◽

High Risk ◽

Random Sampling ◽

High Risk Pregnancy ◽

Reproductive Age ◽

Cross Sectional ◽

Whitney Test ◽

Mann Whitney Test ◽

Risk Pregnancy

ABSTRACT Kelompok usia reproduksi terbagi dalam tiga fase yaitufase menunda kehamilan (<20 tahun), fase menjarangkan kehamilan (20-30 tahun) dan fase mengakhiri kehamilan (>30 tahun). Cara yang ditempuh yaitu dengan pemakaian kontrasepsi.baik MKJPmaupunnon MKJP. Tujuan penelitian ini adalah untuk mengetahui ada atau tidak perbedaan pemilihan kontrasepsi MKJP dan non MKJP berdasarkan efek samping pada dua kelompok usia reproduksi. Penelitin ini menggunakan desain cross sectional, pengambilan data dengan kuesioner. Sampel dalam penelitian ini adalah akseptor KB baik MKJP maupun non MKJP pada bulan april sampai juni sebanyak 200 responden, dimana tekhnik pengambilan datanya dengan random sampling dan kuota sampling. Hasil penelitian kemudian diuji dengan mann-whitney test.Hasil penelitian dengan uji mann whitney test diperoleh p = 0.662 dengan kata lain p > α (0.05) yang berarti tidak ada perbedaan pemilihan MKJP dan non MKJP berdasarkan efek samping di Wilayah Kabupaten Semarang. ABSTRACT Reproductive-age category can be divided into three groups which are the group of delayed interval pregnancy (less than 20 years old), the group of intervalcontrol pregnancy (20 to 30 years old), and the group of high risk pregnancy (more than 30 years old). An alternative to avoid high risk pregnancy is by using contraception tool namely long-term contraception (MKJP) and non long-term contraception (non MKJP).The purpose of this research is to analysedwhether there are differences in choosing MKJP and non –MKJP based on side effects in the two reproductive-age groups.This research was an explanatory research with cross-sectional design. The population were all women of contraception acceptors in Semarang Regency.The samples were 200 respondents, used simple random sampling and quota sampling. This research used quisionaire instrument and analyze used mann whitney test (α=0,05). Theresult showed thatP = 0,662 meaning P > α = 0.05 which means there is no difference in choosing MKJP and non-MKJP based on side effects in the two reproduction-age groups in Semarang regency.

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Neuromyelitis optica spectrum disorder (NMOSD) presenting as acute transverse myelitis with positive aquaporin 4 antibodies

BMJ Case Reports ◽

10.1136/bcr-2020-238992 ◽

2021 ◽

Vol 14 (1) ◽

pp. e238992

Author(s):

Katherine Thornley ◽

Carlo Canepa

Keyword(s):

Spinal Cord ◽

Transverse Myelitis ◽

Aquaporin 4 ◽

Sensory Level ◽

Mri Scan ◽

Acute Transverse Myelitis ◽

Longitudinal Extensive Transverse Myelitis ◽

Oral Steroids ◽

Extensive Transverse Myelitis

An 80-year-old, previously healthy patient presents with acute transverse myelitis with sensory level at T8. The MRI scan of the spinal cord showed longitudinal extensive transverse myelitis, and she tested positive for aquaporin 4 antibodies in serum. She received treatment with intravenous and oral steroids, with no improvement and then underwent plasma exchange. She was then started on azathioprine for prevention of relapses, while continuing physiotherapy and occupational therapy. Eventually, she was transferred to a specialised spinal cord centre for long-term rehabilitation.

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