Astrocytic damage is far more severe than demyelination in NMO

Takano, Ryosuke; Misu, Tatsuro; Takahashi, Toshiyuki; Sato, Shinya; Fujihara, Kazuo; Itoyama, Yasuto

doi:10.1212/wnl.0b013e3181e2414b

Cited by 226 publications

(182 citation statements)

References 36 publications

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“…31 In neuromyelitis optica, astrocytes die before demyelination occurs, and cerebral spinal fluid or serum levels of S100B correlate with the clinical manifestations of the disease. 32 We explored the possibility that astrocyte death in ODS induces S100B release by evaluating serum S100B levels after hyponatremia correction. We observed that there was a significant increase in serum S100B at 12 hours postcorrection that continued until 3 days postcorrection (P Ͻ 0.001 compared with S100B levels before the correction; Figure 6A).…”

Section: Early Downregulation Of Astrocyte-oligodendrocyte Gap Junctimentioning

confidence: 99%

Astrocytes Are an Early Target in Osmotic Demyelination Syndrome

Kengne

Nicaise²,

Soupart³

et al. 2011

Journal of the American Society of Nephrology

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Abrupt osmotic changes during rapid correction of chronic hyponatremia result in demyelinative brain lesions, but the sequence of events linking rapid osmotic changes to myelin loss is not yet understood. Here, in a rat model of osmotic demyelination syndrome, we found that massive astrocyte death occurred after rapid correction of hyponatremia, delineating the regions of future myelin loss. Astrocyte death caused a disruption of the astrocyte-oligodendrocyte network, rapidly upregulated inflammatory cytokines genes, and increased serum S100B, which predicted clinical manifestations and outcome of osmotic demyelination. These results support a model for the pathophysiology of osmotic brain injury in which rapid correction of hyponatremia triggers apoptosis in astrocytes followed by a loss of trophic communication between astrocytes and oligodendrocytes, secondary inflammation, microglial activation, and finally demyelination.

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Section: Early Downregulation Of Astrocyte-oligodendrocyte Gap Junctimentioning

confidence: 99%

Astrocytes Are an Early Target in Osmotic Demyelination Syndrome

Kengne

Nicaise²,

Soupart³

et al. 2011

Journal of the American Society of Nephrology

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“…27 Neuropathologic and CSF analyses in NMO demonstrated massive destruction of astrocytes in acute NMO lesions, but there were no such changes in MS. 28,29 More recent experimental studies clearly showed that AQP4 antibody derived from patients with NMO, predominantly of the IgG1 subclass, ac- tivated the complement pathway efficiently and caused astrocytic necrosis in cell culture and NMOlike lesions in animals with experimental autoimmune encephalomyelitis. 30 Purified IgG from AQP4 antibody-negative patients did not induce those morphologic changes.…”

Section: Clinical Features Of Aqp4 Antibody-negative Cmsmentioning

confidence: 99%

AQP4 antibody–positive Thai cases

Siritho¹,

Nakashima²,

Takahashi³

et al. 2011

Neurology

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Objective: To evaluate the prevalence of aquaporin-4 (AQP4) antibody in Thai patients with idiopathic inflammatory demyelinating CNS diseases (IIDCDs) and to analyze the significance of the autoantibody to distinguish neuromyelitis optica (NMO) and other NMO spectrum disorders (ONMOSDs) from other IIDCDs, especially multiple sclerosis (MS). Methods:We retrospectively evaluated 135 consecutive patients with IIDCDs seen at the MS clinic at Siriraj Hospital, Bangkok, Thailand, and classified them into NMO, ONMOSDs, optic-spinal MS (OSMS), classic MS (CMS), and clinically isolated syndrome (CIS) groups in this order with accepted diagnostic criteria. The patients' coded sera were tested separately for AQP4 antibody. Then the relations between the clinical diagnosis and the AQP4 antibody serologic status were analyzed. Results:Among the 135 patients, 53 (39.3%) were AQP4 antibody-positive. Although the AQP4 antibody-positive group had features of NMO, such as female predominance, long cord lesions (Ͼ3 vertebral bodies), and CSF pleocytosis, only 18 patients (33% of 54) fully met Wingerchuk 2006 criteria except for AQP4 antibody-seropositive status. We also detected some AQP4 antibody-positive patients in the OSMS (4 of 7), CMS (11 of 46), and CIS (1 of 16) groups. These patients had been misdiagnosed with MS because they often had brain lesions and never underwent spinal cord MRI examination or lacked long cord lesions.Conclusions: AQP4 antibody was highly prevalent (almost 40%) in Thai patients with IIDCDs.Moreover, only one-third of AQP4 antibody-positive patients fully met Wingerchuk 2006 criteria, and many were misdiagnosed with MS. A sensitive AQP4 antibody assay is required in this region because the therapy for NMO is different from that for MS. Neurology ® 2011;77:827-834 GLOSSARY ANA ϭ antinuclear antibody; AQP4 ϭ aquaporin-4; CIS ϭ clinically isolated syndrome; CMS ϭ classic multiple sclerosis; IIDCD ϭ idiopathic inflammatory demyelinating CNS disease; IgG ϭ immunoglobulin G; MS ϭ multiple sclerosis; NMO ϭ neuromyelitis optica; NMOSD ϭ neuromyelitis optica spectrum disorder; OB ϭ oligoclonal immunoglobulin G band; ONMOSD ϭ other neuromyelitis optica spectrum disorder; OSMS ϭ optic-spinal multiple sclerosis; VB ϭ vertebral body.Neuromyelitis optica (NMO) is an idiopathic inflammatory demyelinating CNS disease (IIDCD) that typically develops into severe optic neuritis and longitudinally extensive transverse myelitis.1-3 The relation between NMO and multiple sclerosis (MS) has been controversial, but since the discovery of aquaporin-4 (AQP4), an NMO-specific autoantibody, 4,5 clinical and laboratory features that distinguish NMO from MS have become clear. 4 -6 In addition, treatment strategies for the 2 diseases are different. 7,8 AQP4 antibody studies showed that besides definite NMO defined by Wingerchuk 2006 criteria, 9 there are other AQP4 antibodypositive patients with NMO spectrum disorders (NMOSDs). -13The ratios of NMO to MS are much higher in Asian countries than in Western countries.14,15...

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“…However, unique clinical and laboratory features found in NMO patients like poor functional recovery and rare chronic progression, relatively common involvement of optic chiasm, spinal cord lesions longitudinally extending over three or more vertebral segments, absence of oligoclonal immunoglobulin G (IgG) bands, and prominent elevation of glial fibrillary acidic protein (GFAP) levels in the cerebrospinal fluids differentiate NMO patients from other demyelinating diseases. Additionally, pathological findings in NMO patients like perivascular deposition of immunoglobulins and complement, severe astrocytic damage (demonstrated by loss of AQP-4 and GFAP stainings) and a relative preservation of myelin strongly suggest that NMO is a clinical entity distinct from MS 5,6 .…”

Section: Introductionmentioning

confidence: 99%

Atypical presentations of neuromyelitis optica

Sato

Fujihara

2011

Arq. Neuro-Psiquiatr.

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Neuromyelitis optica (NMO) is an inflammatory disease of central nervous system classically characterized by acute, severe episodes of optic neuritis and longitudinally extensive transverse myelitis, usually with a relapsing course. The identification of an autoantibody exclusively detected in NMO patients against aquaporin-4 (AQP-4) has allowed identification of cases beyond the classical phenotype. Brain lesions, once thought as infrequent, can be observed in NMO patients, but lesions have different characteristics from the ones seen in multiple sclerosis. Additionally, some AQP-4 antibody positive patients may present with a variety of symptoms not being restricted to optic neuritis and acute myelitis during the first attack or in a relapse. Examples are not limited to, but may include patients only with brain and/or brainstem lesions, narcolepsy with hypothalamic lesions or patients with intractable hiccups, nausea and vomiting. The prompt identification of NMO patients with atypical presentations may benefit these patients with institution of early treatment to reduce disability and prevent further attacks. Key words: neuromyelitis optica, aquaporin 4, myelitis, optic neuritis, diagnosis, differential, nausea, vomiting, hiccup, brain diseases.Apresentações atípicas da neuromielite óptica RESUMO Neuromielite óptica (NMO) é uma doença inflamatória do sistema nervoso central caracterizada classicamente por neurite óptica grave e mielite transversa longitudinalmente extensa, com um curso usualmente recorrente. A identificação do anticorpo detectado exclusivamente nos pacientes com NMO contra a aquaporina-4 (AQP-4) permitiu a identificação de casos além do fenótipo clássico. Lesões cerebrais, que antes eram descritas como infrequentes, podem ser observadas em pacientes com NMO, mas as lesões possuem características diferentes das lesões observadas na esclerose múltipla. Além disso, alguns pacientes positivos para o anticorpo contra a AQP-4 podem apresentar uma variedade de sintomas não restritos à neurite óptica e mielite aguda, seja durante o primeiro ataque seja em uma recorrência. Exemplos não estão limitados aos descritos a seguir, mas incluem pacientes com lesões cerebrais e/ou tronco cerebral, narcolepsia com lesões hipotalâmicas ou pacientes com quadros intratáveis de soluços, náusea e vômitos. A identificação rápida dos pacientes com NMO com apresentações atípicas pode beneficiar estes pacientes com a instituição precoce do tratamento a fim de reduzir a incapacidade e prevenir ataques subsequentes. Palavras-Chave: neuromielite óptica, aquaporina 4, mielite, neurite óptica, diagnóstico diferencial, náusea, vômito, soluço, encefalopatias.

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Astrocytic damage is far more severe than demyelination in NMO

Abstract: Astrocytic damage reflected by elevated CSF glial fibrillary acidic protein is a clinically relevant, primary pathologic process in neuromyelitis optica, and is far more severe than demyelination.

Cited by 226 publications

References 36 publications

Astrocytes Are an Early Target in Osmotic Demyelination Syndrome

Astrocytes Are an Early Target in Osmotic Demyelination Syndrome

AQP4 antibody–positive Thai cases

Atypical presentations of neuromyelitis optica

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