Neuromyelitis optica should be classified as an astrocytopathic disease rather than a demyelinating disease

Fujihara, Kazuo; Misu, Tatsuro; Nakashima, Ichiro; Takahashi, Toshiyuki; Bradl, Monika; Lassmann, Hans; Takano, Ryosuke; Nishiyama, Shuhei; Tokura, Y.; Suzuki, Chihiro; Sato, Douglas Kazutoshi; Kuroda, Hiroshi; Nakamura, Masashi; Fujimori, Juichi; Narikawa, Koichi; Satō, Shigeru; Itoyama, Yasuto; Akiyama, Masashi

doi:10.1111/j.1759-1961.2012.00030.x

Cited by 82 publications

(98 citation statements)

References 106 publications

(229 reference statements)

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“…The median number of ON attacks was 2, range (2)(3)(4)(5). These patients had: a severe onset ON [median VFSS 5, range (4-5)], a moderate outcome from the first Optic Atrophy Type 1 (OPA1) mutation were performed in two patients and were negative.…”

Section: Relapsing Isolated On (Rion)mentioning

confidence: 97%

“…The discovery, in 2005, of aquaporin4 antibodies (AQP4-Ab) [2] has led to identify this disease as an astrocytopathy [3] and has broadened the phenotype of the disease. The term NMO spectrum disorders (NMOSD) [4] incorporates limited forms of disease, such as monophasic or recurrent longitudinally extensive transverse myelitis (LETM), brain/brainstem disease and bilateral or recurrent or isolated ON [5,6] as well as extra optico-spinal manifestations [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

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Isolated new onset ‘atypical’ optic neuritis in the NMO clinic: serum antibodies, prognoses and diagnoses at follow-up

et al. 2015

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Severe, recurrent or bilateral optic neuritis (ON) often falls within the neuromyelitis optica spectrum disorders (NMOSD), but the diagnosis can be particularly challenging and has important treatment implications. We report the features, course and outcomes of patients presenting with atypical ON when isolated at onset. We retrospectively analyzed 69 sequential patients referred to a single UK NMO center with isolated ON at onset. Aquaporin-4 antibody (AQP4-Ab) assessment was performed in all patients and IgG1 myelin-oligodenrocyte glycoprotein (MOG-Ab) in AQP4-Ab(neg) patients. 37 AQP4-Ab positive (AQP4-Ab(pos)) and 32 AQP4-Ab negative (AQP4-Ab(neg)) patients (8 with MOG-Ab) were identified. The AQP4-Ab(neg) group included heterogeneous diagnoses: multiple sclerosis (MS), NMO, relapsing isolated ON (RION), monophasic isolated ON and relapsing acute disseminated encephalomyelitis (ADEM)-like syndromes. Compared to AQP4-Ab(neg) patients, AQP4-Ab(pos) patients had a worse residual visual outcome from first attack (median VFSS 4 vs. 0, p = 0.010) and at last assessment (median VFSS 5 versus 2, p = 0.005). However, AQP4-Ab(neg) patients with RION also had poor visual outcome. Up to 35% of AQP4-Ab(neg) patients developed a LETM and two developed low positivity for AQP4-Ab over time. Eight AQP4-Ab(neg) patients (25%) were MOG-Ab positive, covering a range of phenotypes excluding MS; the first ON attack was often bilateral and most had relapsing disease with a poor final visual outcome [VFSS 4, range (0-6)]. In conlcusion, AQP4-Ab positivity is confirmed as a predictor of poor visual outcome but AQP4-Ab(neg) RION also had a poor visual outcome. Of those without AQP4-Ab, 25% had MOG-Ab and another 25% developed MS; thus, MOG-Ab is associated with AQP4-Ab(neg) non-MS ON.

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Section: Relapsing Isolated On (Rion)mentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Isolated new onset ‘atypical’ optic neuritis in the NMO clinic: serum antibodies, prognoses and diagnoses at follow-up

et al. 2015

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“…Co-injection of immunoglobulin G from NMO patients with human complement into mouse brain produced lesions with characteristic histological features of human NMO lesions [68]. Some authors have proposed that NMO should be classified as an astrocytopathic disease rather than a demyelinating disease because the astrocytic damage in NMO is much more severe than myelin and neuron damage [21].…”

Section: Immunopathological Mechanisms Of Nmomentioning

confidence: 99%

“…This condition is characterized by anti-AQP4 seropositivity status in addition to limited forms of NMO, including idiopathic single or recurrent events of longitudinally extensive myelitis, ON simultaneous bilateral or recurrent; Asian optic-spinal MS; ON or longitudinally extensive myelitis associated with systemic autoimmune disease; ON or myelitis associated with brain lesions typical of NMO (brainstem, hypothalamic, periventricular and corpus callosal) [21].…”

Section: Classificationmentioning

confidence: 99%

Epidemiological, clinical, and immunological characteristics of neuromyelitis optica: A review

Pereira

Reiche

Kallaur

et al. 2015

Journal of the Neurological Sciences

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The aim of this study was to review the epidemiological and clinical characteristics of neuromyelitis optica (NMO) and the immunopathological mechanisms involved in the neuronal damage. NMO is an inflammatory demyelinating autoimmune disease of the central nervous system that most commonly affects the optic nerves and spinal cord. NMO is thought to be more prevalent among non-Caucasians and where multiple sclerosis (MS) prevalence is low. NMO follows a relapsing course in more than 80-90% of cases, which is more commonly in women. It is a complex disease with an interaction between host genetic and environmental factors and the main immunological feature is the presence of anti-aquaporin 4 (AQP4) antibodies in a subset of patients. NMO is frequently associated with multiple other autoantibodies and there is a strong association between NMO with other systemic autoimmune diseases. AQP4-IgG can cause antibody-dependent cellular cytotoxicity (ADCC) when effector cells are present and complement-dependent cytotoxicity (CDC) when complement is present. Acute therapies, including corticosteroids and plasma exchange, are designed to minimize injury and accelerate recovery. Several aspects of NMO pathogenesis remain unclear. More advances in the understanding of NMO disease mechanisms are needed in order to identify more specific biomarkers to NMO diagnosis.

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“…In experimental studies, purified immunoglobulin G (IgG) from AQP4 antibody seronegative patients did not reproduce NMO-like pathology with astrocytic destruction as seen with the infusion of same material from AQP4 antibody seropositive patients 17 . Therefore, it is unclear Douglas Kazutoshi Sato et al Seronegative NMO spectrum if AQP4 antibody seronegative NMO patients have the same autoimmune astrocytopathic disease as seropositive patients 51,53 .…”

Section: The Differences Between Aqp4 Antibody Positive and Negative mentioning

confidence: 99%

Seronegative Neuromyelitis Optica Spectrum - The challenges on disease definition and pathogenesis

Sato

Callegaro

Lana-Peixoto

et al. 2014

Arq. Neuro-Psiquiatr.

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Neuromyelitis optica spectrum disorders (NMOSD) are characterized by severe optic neuritis and/or longitudinally extensive transverse myelitis, and some brain lesions are also unique to NMOSD. Serum autoantibodies against aquaporin-4 (AQP4) are detected in most cases of NMOSD. However, some patients with NMOSD remain seronegative despite repetitive testing during attacks with highly sensitive cellbased assays. The differential diagnosis of NMOSD is not restricted to multiple sclerosis and it includes many diseases that can produce longitudinally extensive myelitis and/or optic neuritis. We review the clinical features, imaging, and laboratory findings that can be helpful on the diagnostic work-up, discuss the differences between AQP4 antibody positive and negative patients with NMOSD, including features of NMOSD with antibodies against myelin oligodendrocyte glycoprotein.Keywords: neuromyelitis optica, aquaporin-4, myelin oligodendrocyte glycoprotein, antibody, myelitis, optic neuritis, differential diagnosis. RESUMOO espectro da neuromielite óptica (NMOSD) é caracterizado por ataques graves de neurite óptica e mielite. Anticorpos séricos contra a aquaporina-4 (AQP4) são usualmente presentes nestes pacientes. Entretanto, alguns pacientes com NMOSD são seronegativos mesmo com testes repetidos em amostras obtidas durante ataques usando métodos altamente sensíveis baseados em células. O diagnóstico diferencial não é restrito à esclerose múltipla e inclui muitas doenças que podem produzir mielite longitudinalmente extensa e/ou neurite óptica. São abordadas as características clínicas, de imagem e de laboratório que podem ser úteis no diagnóstico, as diferenças entre os pacientes positivos para o anticorpo anti-AQP4 e os negativos, incluindo as características dos pacientes com NMOSD que possuem anticorpos contra a glicoproteína associada ao oligodendrócito.Palavras-chave: neuromielite óptica, aquaporina-4, glicoproteína associada ao olidendrócito, mielite, neurite óptica, diagnóstico diferencial.

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Neuromyelitis optica should be classified as an astrocytopathic disease rather than a demyelinating disease

Cited by 82 publications

References 106 publications

Isolated new onset ‘atypical’ optic neuritis in the NMO clinic: serum antibodies, prognoses and diagnoses at follow-up

Isolated new onset ‘atypical’ optic neuritis in the NMO clinic: serum antibodies, prognoses and diagnoses at follow-up

Epidemiological, clinical, and immunological characteristics of neuromyelitis optica: A review

Seronegative Neuromyelitis Optica Spectrum - The challenges on disease definition and pathogenesis

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