Diagnosis and classification of neuromyelitis optica (Devic's Syndrome)

doi:10.1016/j.autrev.2014.01.034

Autoimmunity Reviews

Volume 13, Issues 4–5, April–May 2014, Pages 531-533

https://doi.org/10.1016/j.autrev.2014.01.034 Get rights and content

Abstract

Neuromyelitis optica (NMO) is an autoimmune disorder, predominantly characterized by severe optic neuritis (ON) and transverse myelitis (TM). Historically considered a variant of Multiple sclerosis, the discovery that most NMO patients have autoantibodies against aquaporin-4 (AQP4) or NMO-IgG, dramatically changed our understanding of the disease. The finding of NMO-IgG revealed wider array of clinical presentations, including patients with recurrent ON of TM alone, now considered part of the NMO spectrum. Furthermore, symptoms other than optic-spinal involvement and the presence of brain lesions, do not exclude the diagnosis of NMO as traditionally accepted. We present an overview of the epidemiology, clinical manifestations and current diagnostic criteria for NMO and NMO spectrum disorders.

Introduction

Neuromyelitis optica (NMO), is an autoimmune disorder of the central nervous system (CNS), predominately affecting the spinal cord and optic nerves.

The syndrome was described first by Allbutt in 1870 [1], but Devic, who reviewed 16 cases in 1894, first coined the term “neuromyelitis optica” [2]. Based on his descriptions, NMO was then considered a severe monophasic disorder and rare variant of Multiple Sclerosis (MS), consisting of acute myelitis and optic neuritis. Subsequently, a relapsing form of NMO was recognized, with episodes of myelitis and optic neuritis occurring even years apart [3]. In light of the identification in 2004 of a serological marker for NMO — the aquaporin-4 antibody (AQP4 Ab), or NMO-IgG, great progress has been made in the understanding of pathobiology, clinical spectrum and treatment. NMO is now considered a distinct autoimmune disorder [4].

Section snippets

Epidemiology

NMO is more prevalent in women than men, with a female predominance usually higher than observed in MS. The median age of onset is also higher than MS, with a median of 35–45 years [3]. The disorder is mainly sporadic, though familial cases have been reported in 3% in some cohorts [5].

Cases of NMO have been described throughout the world, although it is found to be more prevalent in areas of non-Caucasian populations, especially in Asian countries. Population based studies reported NMO

Clinical manifestations

The hallmarks of NMO are optic neuritis, which is often bilaterally simultaneous or sequential and longitudinally extensive transverse myelitis. Symptoms include unilateral and bilateral loss of visual acuity, severe paraplegia or tetraplegia, with a well defined sensory level and sphincter dysfunction and pain and tonic spasms of the trunk and extremities [3]. Extension of the lesions to the brain stem may cause hiccups, nausea and even respiratory failure [7]. Cases of hypothalamic–pituitary

The role of NMO-IgG

Significant breakthrough in the research of NMO was made by Lennon et al. in 2004, when they described a circulating IgG auto-antibody (NMO-IgG) in patients with neuromyelitis optica, that was absent in those with multiple sclerosis. The sensitivity and specificity of the NMO-IgG in identifying NMO in their series was 73% and 91%, respectively [10].

A year later, its target was identified as the astrocyte water channel protein aquaporin 4 (AQP4) [4]. AQP4 is expressed strongly in astrocytes in

Diagnostic criteria

Due to poorer prognosis than MS and different treatment approaches, early diagnosis of NMO is essential. In 1999, Wingerchuk et al [3] proposed diagnostic criteria with three absolute requirements: optic neuritis, acute myelitis and the lack of symptoms involving other CNS regions. Diagnosis requires all absolute criterion and one major supportive criteria or two minor supportive criteria (Table 1).

However, these criteria failed to capture patients with symptoms other than optic–spinal

Conclusions

Our understanding of NMO has rapidly changed over the passing decade. From a monophasic to an MS-like disease, we've come to acknowledge a severe, relapsing antibody-mediated autoimmune disorder. Great heterogeneity still exists in this rare disease, making further debate on advancing diagnostic criteria relevant in guiding future treatment.

References (19)

V.A. Lennon et al.
A serum autoantibody marker of neuromyelitis optica: distinction form multiple sclerosis
Lancet
(2004)
M. Papadopoulos et al.
Aquaporin 4 and neuromyelitis optica
Lancet Neurol
(2012)
D.M. Wingerchuk et al.
The spectrum of neuromyelitis optica
Lancet Neurol
(2007)
T.C. Allbutt
On the ophthalmoscopic signs of spinal disease
Lancet
(1870)
E. Devic
Myelite subaigue compliquee de neurite opticqoe
Bull Med
(1894)
D.M. Wingerchuk et al.
The clinical course of neuromyelitis optica (Devic's syndrome)
Neurology
(1999)
V.A. Lennon et al.
IgG marker of optic spinal multiple sclerosis binds to the aquaporin-4 water channel
J Exp Med
(2005)
M. Matiello et al.
Familial neuromyelitis optica
Neurology
(2010)
A. Uzawa et al.
Neuromyelitis optica: concept, immunology and treatment
J clinical neurosci
(2013)

There are more references available in the full text version of this article.

Cited by (44)

IRAK1 polymorphisms are associated with susceptibility to neuromyelitis optica spectrum disorder
2020, Multiple Sclerosis and Related Disorders
Citation Excerpt :
Most of the autoimmune diseases are more common in women, probably because of hormonal and genetic factors. Similar to other autoimmune diseases, NMOSD is predominantly observed in females, with 5–9 times higher incidence in females than in males (Drori and Chapman, 2014; Flanagan et al., 2016; Houzen et al., 2017). The interleukin-1 receptor-associated kinase (IRAK1) gene is located on the X chromosome and encodes a serine/threonine protein kinase, which plays a pivotal role in the Toll/IL-1 receptor (TIR) signalling pathway via the upregulation of transcription factor NF-κB and induction of inflammation (Rao et al., 2005).
X chromosome-linked interleukin-1 receptor-associated kinase (IRAK1) polymorphisms have been demonstrated to be associated with the risks of several autoimmune diseases, such as systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, and autoimmune thyroid diseases. However, no studies have investigated the association of IRAK1 polymorphisms with neuromyelitis optica spectrum disorder (NMOSD). This case-control study was performed to determine the correlation between IRAK1 polymorphisms and the risk of NMOSD.
Two single nucleotide polymorphisms (SNPs) rs1059703G>A and rs3027898C>A of IRAK1 were selected and genotyped using SNPscan in a Chinese cohort, including 332 patients with NMOSD and 520 healthy controls. Chi-square tests and logistic regression analyses were used to determine the associations between IRAK1 polymorphisms and the risk of NMOSD.
Patients with NMOSD showed a lower frequency of the minor allele A of rs1059703 than did controls (Odds ratio [OR] = 0.68; 95% confidence intervals [CI], 0.52–0.88; P^corr = 0.007). Compared with wild genotype GG of rs1059703, homozygous mutation AA and heterozygous mutation GA were significantly associated with the decreased risk of NMOSD after adjusting for sex and age (adjusted OR = 0.64; 95%CI, 0.49–0.84; P^corr = 0.002). Similar associations were also observed for IRAK1 rs3027898C>A. Stratification analysis according to sex revealed that the significantly different allele distributions of the two SNPs were mainly found in females. However, IRAK1 polymorphisms were not correlated with aquaporin-4-IgG, onset symptoms, or age at onset.
This study is first to demonstrate that X-chromosome-linked IRAK1 polymorphisms are associated with the risk of NMOSD and provide novel insights into the underlying mechanisms of this disease. Further studies are needed to elucidate the function of IRAK1 variants in the pathogenesis of NMOSD and the underlying molecular mechanisms.
Visual impairment in neuromyelitis optica spectrum disorders (NMOSD)
2019, Journal of Chemical Neuroanatomy
Citation Excerpt :
After treatment with steroids, immunosuppressants, or monoclonal antibodies, symptoms of paralysis in NMO patients can be relieved to an extent. However, the rehabilitation of visual impairment is particularly poor even after treatment in NMO patients, and they tend to develop severe bilateral visual impairment in the long-term, which is different from that of MS (Drori and Chapman, 2014). AQP4-IgG seropositive patients exhibited significantly more severe visual loss than did seronegative patients (Kim and Kim, 2018).
Neuromyelitis optica (NMO) and NMO spectrum disorders (NMOSD) have garnered attention due to their high pathogenicity, high risk of relapse, and poor prognosis as an inflammatory central nervous system (CNS) syndrome. There is a consensus that the anti-aquaporin-4 antibody (AQP4-IgG) is the main pathogen detectable in majority of NMOSD patients, including traditional NMO and AQP4-IgG-positive optic neuritis. In serum-negative NMOSD patients, myelin oligodendrocyte glycoprotein (MOG) antibodies are considered pathogenic factors. At present, patients with NMO optic neuritis (NMO-ON) hardly benefit from common therapies. A limitation of studies on NMO-ON is the inadequacy of animal models. This review article focuses on the characteristics of visual impairments in NMOSD and the application of experimental rodent models which are required for elucidating the pathology and potential treatments for NMO visual impairment.
Diagnosis and management of neuromyelitis optica spectrum disorders - An update
2018, Autoimmunity Reviews
Citation Excerpt :
These typical and common clinical features are observed in most NMO patients, and great efforts have been made to identify diagnostic criteria that can allow a prompt and timely diagnosis of all cases, including those with partial or uncommon manifestations. These criteria are based on medical history, clinical manifestations, laboratory tests and MRI features, and have significantly evolved over the years in parallel to the increased understanding of NMO pathogenic mechanisms [34]. The basis for a consensus over NMO diagnostic criteria was set back in 1999 and revised in 2006, and the first actual international consensus was reached in 2015 when the current criteria were enunciated [1,2,33].
Neuromyelitis optica (NMO) and Neuromyelitis optica spectrum disorders (NMOSD) are a group of autoimmune conditions characterized by inflammatory involvement of the optic nerve, spinal cord and central nervous system. Novel evidence showed a key role of autoantibodies against aquaporin-4 immunoglobulin G (AQP4 IgG) in the pathogenesis of NMOSD and, recently, new classification and diagnostic criteria have been adopted to facilitate an earlier identification and improve the management of these conditions. Diagnosis of NMOSD is currently based on clinical, neuroimaging and laboratory features. Standard treatment is based on the use of steroids and immunosuppressive drugs and aims to control the severity of acute attacks and to prevent relapses of the disease. This review gives an update of latest knowledge of NMOSD and NMO, emphasizing the novel diagnostic criteria and both current and future therapeutic approaches.
Neuromyelitis Optica
2017, Rheumatic Disease Clinics of North America
Citation Excerpt :
Following the discovery of AQP4-IgG, there has been increased awareness of additional potential clinical manifestations, including brainstem and cerebral syndromes, leading to revised diagnostic criteria published by the International Panel for NMO Diagnosis (IPND) in 2015 (see “diagnostic criteria” section later in this article).21 Attacks are characterized by neurologic deficits that develop over days with variable resolution during subsequent months, leading to progressive disability.20,22 Most patients (80%–90%) suffer from recurrent disease, and relapses often occur early at unpredictable intervals.
Epidemiology of neuromyelitis optica in Costa Rica: A multicenter analysis
2018, Neurologia Argentina
La neuromielitis óptica es una enfermedad desmielinizante que afecta principalmente el nervio óptico y la médula espinal; se caracteriza por brotes recurrentes y discapacidad severa. En la actualidad no existen estudios epidemiológicos publicados en Costa Rica acerca de esta enfermedad.
Describir la epidemiología de la neuromielitis óptica en la Caja Costarricense de Seguro Social.
Se revisaron los expedientes de pacientes con neuromielitis óptica que cumplieran los criterios publicados en 2006 durante el periodo de agosto de 2011 a diciembre de 2015 en los hospitales de la Caja Costarricense de Seguro Social que cuentan con neurólogo de adultos.
El número total de pacientes con diagnóstico de neuromielitis óptica fueron 40, con una incidencia acumulada por año de la enfermedad de 0,13 a 0,44 por 100.000 habitantes. El 62% de los pacientes fueron mujeres, con un ratio mujeres/hombres de 1,6:1. El número de pacientes seropositivos para acuaporina-4 (AQP-4) fueron 15; sin embargo, 17 pacientes no contaban con la realización de la prueba. La mayoría de los pacientes presentaba una neuromielitis óptica de tipo recurrente (97,5%) y algunos asociaban otras enfermedades concomitantes, tales como Sjögren, porfiria aguda intermitente, hipotiroidismo, púrpura trombocitopénica trombótica, lupus eritematoso sistémico y síndrome antifosfolípido.
La incidencia de neuromielitis óptica en Costa Rica fue mayor de lo esperado, caracterizada por ser más frecuente en mujeres, de tipo recurrente y con una mediana de edad de 35,5 años.
Neuromyelitis optica is a demyelinating disease that affects mainly optic nerve and spinal cord, presenting recurrent relapses and important disability. There are none studies published from Costa Rica.
Describe the epidemiology of neuromyelitis optica in the Caja Costarricense de Seguro Social.
Review of medical records from patients that fulfilled 2006 neuromyelitis optica criteria, from August 2011 until December 2015 in the hospitals of the Caja Costarricense de Seguro Social.
The total of patients with diagnosis of neuromyelitis optica were 40, with an accumulated incidence from 0.13 to 0.44 per 100,000 per year. 62% of the patients were women, with a ratio of 1.6:1. The total of patients with a positive antibody against AQP-4 were 15, however 17 patients did not have the test done. Most of the patients had recurrent type (97.5%) and some were associated with other diseases, such as Sjogren, porphyria, hypothyroidism, thrombotic thrombocytopenic purpura, systemic lupus erythematous and antiphospholipid syndrome.
Prevalence of neuromyelitis optica was greater than expected, being much more frequent in women, of recurrent type and with an average age of 35.5 years.
Therapeutic plasma exchange for optic neuritis attacks in patients with neuromyelitis optica spectrum disorders
2022, Therapeutic Apheresis and Dialysis

View all citing articles on Scopus

View full text

ReviewDiagnosis and classification of neuromyelitis optica (Devic's Syndrome)

Abstract

Introduction

Section snippets

Epidemiology

Clinical manifestations

The role of NMO-IgG

Diagnostic criteria

Conclusions

Lancet

Lancet Neurol

Lancet Neurol

On the ophthalmoscopic signs of spinal disease

Lancet

Myelite subaigue compliquee de neurite opticqoe

Bull Med

The clinical course of neuromyelitis optica (Devic's syndrome)

Neurology

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

J Exp Med

Familial neuromyelitis optica

Neurology

Neuromyelitis optica: concept, immunology and treatment

J clinical neurosci

Review
Diagnosis and classification of neuromyelitis optica (Devic's Syndrome)