A nationwide survey of opsoclonus–myoclonus syndrome in Japanese children

Hasegawa, Shunji; Matsushige, Takeshi; Kajimoto, Madoka; Inoue, Hirofumi; Momonaka, Hiroshi; Oka, Momoko; Ohga, Shouchi; Ichiyama, Takashi

doi:10.1016/j.braindev.2014.10.010

Cited by 56 publications

(58 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The age of subjects was at the time of our study, thus it may be older than the age of onset. Although a higher female sex ratio of approximately 1.2 was already evident in toddlers with OMS [2][3][4], only 10 children with OMS and NB in our study may not enough to reflect the gender difference, other literatures with a small sample size also showed much lower (2 female/3 male) [25] or higher ratios (9 female/2male, 11 female/4 male) [7,26]. Moreover, the age and gender of subjects may be affected by whether timely visiting to hospitals, misdiagnosis as other diseases before, genetic background and whether willing to enroll in the study.…”

Section: Clinical Informationmentioning

confidence: 89%

“…Some cases of pediatric OMS are paraneoplastic and are associated with NB, although varied percentages have been reported [1][2][3][4][5], the remaining cases are believed to be post-infectious or resulted from NB that has regressed prior to onset of symptoms [49]. In adults, patients with non-paraneoplastic OMS have better outcomes with fewer relapses [42], while in children, no significant difference in viral-like prodrome and neurological outcome is noted between paraneoplastic and nonparaneoplastic OMS [1,50].…”

Section: Sera and The Igg Fraction From Children With Oms And Nb Givementioning

confidence: 99%

“…Most patients suffer from persistent deficits in cognition, neurology and behavior. Some children with OMS also have neuroblastoma (NB), although varied percentages have been reported [1][2][3][4][5]. Previously, we have documented that the insulin-like growth factor 1 (IGF-1)/phosphoinositide 3-kinase cascade alleviates neuronal cytolysis induced by serum IgG from children with OMS and NB [6], others also reported that the phosphorylation of extracellular signal-regulated kinase contributes to neuronal cytolysis in pediatric OMS [7].…”

mentioning

confidence: 99%

See 2 more Smart Citations

Serum IgG-indcued microglial activation enhances neuronal cytolysis via the NO/sGC/PKG pathway in children with opsoclonus-myoclonus syndrome and neuroblastoma

Ding

Yang

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundOpsoclonus-myoclonus syndrome (OMS) is a rare neurological disease. Some children with OMS also have neuroblastoma (NB). We and others have previously documented that serum IgG from children with OMS and NB induces neuronal cytolysis via several signaling pathways. However, mechanisms underlying OMS remain unclear. Here we investigated whether nitric oxide (NO) from activated microglias and its cascade contribute to neuronal cytolysis in pediatric OMS. MethodsThe activation of cultured cerebral cortical and cerebellar microglias incubated with sera or IgG isolated from sera of children with OMS and NB was measured by the expression of the activation marker, cytokines and NO. Neuronal cytolysis was determined after exposing to IgG-treated microglia conditioned media. Using inhibitors and activators, the effects of NO synthesis and its intracellular cascade, namely soluble guanylyl cyclase (sGC) and protein kinase G (PKG), on neuronal cytolysis were evaluated. ResultsIncubation with sera or IgG from children with OMS and NB increased the activation of cerebral cortical and cerebellar microglias, but not the activation of astrocytes or the cytolysis of glial cells.Moreover, the cytolysis of neurons was elevated by conditioned media from microglias incubated with IgG from children with OMS and NB, which was relieved by the inhibitors of NO signaling. By contrast, neuronal cytolysis was exacerbated by the activators of NO signaling but not proinflammatory cytokines. Neuronal cytolysis was suppressed by pretreatment with the microglial inhibitor minocycline, a clinically tested drug. Finally, increased microglial activation did not depend on the Fab fragment of serum IgG. ConclusionsSerum IgG from children with OMS and NB potentiates microglial activation, which induces neuronal cytolysis through the NO/sGC/PKG pathway, suggesting an applicability of microglial inhibitor as a therapeutic candidate. BackgroundOpsoclonus-myoclonus syndrome (OMS) is a rare but devastating neurological disease, characterized by opsoclonus, myoclonus and ataxia. Most patients suffer from persistent deficits in cognition, neurology and behavior. Some children with OMS also have neuroblastoma (NB), although varied percentages have been reported [1][2][3][4][5]. Previously, we have documented that the insulin-like growth factor 1 (IGF-1)/phosphoinositide 3-kinase cascade alleviates neuronal cytolysis induced by serum IgG from children with OMS and NB [6], others also reported that the phosphorylation of extracellular signal-regulated kinase contributes to neuronal cytolysis in pediatric OMS [7]. Yet, the cellular and molecular mechanisms associated with neuronal cytolysis underlying pediatric OMS remain unclear. Microglias are major immune effectors in the central nervous system (CNS) and have an important physiological function in inflammation [8]. Notably, patients with pediatric OMS exhibit increased expression of a microglial marker and proinflammatory cytokines in cerebrospinal fluid (CSF) and some children with OMS are post-inf...

show abstract

Section: Clinical Informationmentioning

confidence: 89%

Section: Sera and The Igg Fraction From Children With Oms And Nb Givementioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Serum IgG-indcued microglial activation enhances neuronal cytolysis via the NO/sGC/PKG pathway in children with opsoclonus-myoclonus syndrome and neuroblastoma

Ding

Yang

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…in approximately 40% of cases. 46,47 Other cases of OMAS occur as an infectious process or, more commonly, a para- or postinfectious process. In some patients, there is evidence of tumor and infection.…”

Section: Neuroimmunology Of Omasmentioning

confidence: 99%

The “neuro” of neuroblastoma: Neuroblastoma as a neurodevelopmental disorder

Ratner

Brodeur

Dale

et al. 2016

Annals of Neurology

View full text Add to dashboard Cite

Neuroblastoma is a childhood cancer derived from cells of neural crest origin. The hallmarks of its enigmatic character include its propensity for spontaneous regression under some circumstances and its association with paraneoplastic opsoclonus, myoclonus, and ataxia. The neurodevelopmental underpinnings of its origins may provide important clues for development of novel therapeutic and preventive agents for this frequently fatal malignancy and for the associated paraneoplastic syndromes.

show abstract

“…neurology and behavior. Some children with OMS also have neuroblastoma (NB), although varied percentages have been reported [1][2][3][4][5]. Previously, we have documented that the insulin-like growth factor 1 (IGF-1)/phosphoinositide 3-kinase (PI3K) cascade is compensatively activated to alleviate neuronal cytolysis induced by serum IgG from children with OMS and NB [6], and others reported that the phosphorylation of extracellular signal-regulated kinase contributes to neuronal cytolysis in pediatric OMS [7].…”

mentioning

confidence: 99%

Serum IgG-induced microglial activation enhances neuronal cytolysis via the NO/sGC/PKG pathway in children with opsoclonus-myoclonus syndrome and neuroblastoma

Ding

Yang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disease. Some children with OMS also have neuroblastoma (NB). We and others have previously documented that serum IgG from children with OMS and NB induces neuronal cytolysis and activates several signaling pathways. However, the mechanisms underlying OMS remain unclear. Here we investigated whether nitric oxide (NO) from activated microglias and its cascade contribute to neuronal cytolysis in pediatric OMS.Methods: The activation of cultured cerebral cortical and cerebellar microglias incubated with sera or IgG isolated from sera of children with OMS and NB was measured by the expression of the activation marker, cytokines and NO. Neuronal cytolysis was determined after exposing to IgG-treated microglia conditioned media. Using inhibitors and activators, the effects of NO synthesis and its intracellular cascade, namely soluble guanylyl cyclase (sGC) and protein kinase G (PKG), on neuronal cytolysis were evaluated.Results: Incubation with sera or IgG from children with OMS and NB increased the activation of cerebral cortical and cerebellar microglias, but not the activation of astrocytes or the cytolysis of glial cells. Moreover, the cytolysis of neurons was elevated by conditioned media from microglias incubated with IgG from children with OMS and NB. Furthermore, the expression of NO, sGC and PKG was increased. Neuronal cytolysis was relieved by the inhibitors of NO signaling, while neuronal cytolysis was exacerbated by the activators of NO signaling but not proinflammatory cytokines. The cytolysis of neurons was suppressed by pretreatment with the microglial inhibitor minocycline, a clinically tested drug. Finally, increased microglial activation did not depend on the Fab fragment of serum IgG.Conclusions: Serum IgG from children with OMS and NB potentiates microglial activation, which induces neuronal cytolysis through the NO/sGC/PKG pathway, suggesting an applicability of microglial inhibitor as a therapeutic candidate.

show abstract

A nationwide survey of opsoclonus–myoclonus syndrome in Japanese children

Cited by 56 publications

References 20 publications

Serum IgG-indcued microglial activation enhances neuronal cytolysis via the NO/sGC/PKG pathway in children with opsoclonus-myoclonus syndrome and neuroblastoma

Serum IgG-indcued microglial activation enhances neuronal cytolysis via the NO/sGC/PKG pathway in children with opsoclonus-myoclonus syndrome and neuroblastoma

The “neuro” of neuroblastoma: Neuroblastoma as a neurodevelopmental disorder

Serum IgG-induced microglial activation enhances neuronal cytolysis via the NO/sGC/PKG pathway in children with opsoclonus-myoclonus syndrome and neuroblastoma

Contact Info

Product

Resources

About