A woman with acute myelopathy in pregnancy: case outcome

Reuß, Reinhard; Rommer, Paulus S.; Brück, Wolfgang; Paul, Friedemann; Bolz, Michael; Jarius, Sven; Boettcher, Tobias; Großmann, Annette; Bock, Alexander; Zipp, Frauke; Benecke, R.; Zettl, Uwe K.

doi:10.1136/bmj.b4026

Cited by 29 publications

(20 citation statements)

References 4 publications

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“…90 In addition, one case of AQP4-IgG attacking the placenta causing spontaneous abortion in humans has been reported. 93 Several case studies have reported normal pregnancies in women receiving treatment for NMO. 87,94,95 Overall, it is unclear whether the effects of maternal NMO on the fetoplacental unit in humans are sufficient to justify treatment in the presence of AQP4-IgG, but without active maternal disease.…”

Section: Current Therapiesmentioning

confidence: 99%

Treatment of neuromyelitis optica: state-of-the-art and emerging therapies

2014

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Neuromyelitis optica (NMO) is an autoimmune disease of the CNS that is characterized by inflammatory demyelinating lesions in the spinal cord and optic nerve, potentially leading to paralysis and blindness. NMO can usually be distinguished from multiple sclerosis (MS) on the basis of seropositivity for IgG antibodies against the astrocytic water channel aquaporin-4 (AQP4). Differentiation from MS is crucial, because some MS treatments can exacerbate NMO. NMO pathogenesis involves AQP4-IgG antibody binding to astrocytic AQP4, which causes complement-dependent cytotoxicity and secondary inflammation with granulocyte and macrophage infiltration, blood–brain barrier disruption and oligodendrocyte injury. Current NMO treatments include general immunosuppressive agents, B-cell depletion, and plasma exchange. Therapeutic strategies targeting complement proteins, the IL-6 receptor, neutrophils, eosinophils and CD19—all initially developed for other indications—are under clinical evaluation for repurposing for NMO. Therapies in the preclinical phase include AQP4-blocking antibodies and AQP4-IgG enzymatic inactivation. Additional, albeit currently theoretical, treatment options include reduction of AQP4 expression, disruption of AQP4 orthogonal arrays, enhancement of complement inhibitor expression, restoration of the blood–brain barrier, and induction of immune tolerance. Despite the many therapeutic options in NMO, no controlled clinical trials in patients with this condition have been conducted to date.

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Section: Current Therapiesmentioning

confidence: 99%

Treatment of neuromyelitis optica: state-of-the-art and emerging therapies

2014

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“…9 A recent mouse passive transfer study showed that intraperitoneal injection of both AQP4-IgG and human complement resulted in placental inflammation with increased fetal death, 10 reproducing key histologic features seen in NMO lesions of the CNS, as well as in placental lesions in a case report of a miscarriage at 20 weeks in a patient with NMO. 8 This adds to the growing clinical 8,21,22 and experimental 10,23 evidence of AQP4-IgG-mediated organ involvement beyond the CNS.…”

mentioning

confidence: 99%

“…[5][6][7] Recently, experimental and clinical reports have demonstrated the presence of AQP4 in human and animal placenta, and have linked AQP4-mediated placental inflammation to fetal death. [8][9][10] It is clear that the annualized relapse rate (ARR) of NMOSD is significantly increased in the 0-to 3-month postpartum period, 11-13 but there is a lack of information on the influence of NMOSD on the course of pregnancy.We investigated the effect of NMOSD on miscarriage and preeclampsia rates using multivariate logistic regression analysis in a retrospective international cohort of 60 women with AQP4-positive NMOSD. …”

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confidence: 99%

Pregnancy outcomes in aquaporin-4–positive neuromyelitis optica spectrum disorder

et al. 2016

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Objective: To investigate the association between neuromyelitis optica spectrum disorder (NMOSD) and pregnancy outcome.Methods: An international cohort of women with aquaporin-4 antibody-positive NMOSD and $1 pregnancy was studied retrospectively. Multivariate logistic regression was used to investigate whether pregnancy after NMOSD onset was associated with an increased risk of miscarriage (cohort of 40 women) or preeclampsia (cohort of 57 women).Results: Miscarriage rate was higher in pregnancies after NMOSD onset (42.9% [95% confidence interval 17.7%-71.1%] vs 7.04% [2.33%-15.7%]). Pregnancies conceived after, or up to 3 years before, NMOSD onset had an increased odds ratio of miscarriage (7.28 [1.03-51.6] and 11.6 [1. , respectively), independent of maternal age or history of miscarriage. Pregnancies after, or up to 1 year before, NMOSD onset ending in miscarriage were associated with increased disease activity from 9 months before conception to the end of pregnancy, compared to viable pregnancies (mean annualized relapse rate 0.707 vs 0.100). The preeclampsia rate (11.5% [6.27%-18.9%]) was significantly higher than reported in population studies. The odds of preeclampsia were greater in women with multiple other autoimmune disorders or miscarriage in the most recent previous pregnancy, but NMOSD onset was not a risk factor.Conclusions: Pregnancy after NMOSD onset is an independent risk factor for miscarriage, and pregnancies conceived at times of high disease activity may be at increased risk of miscarriage. Women who develop NMOSD and have multiple other autoimmune disorders have greater odds of preeclampsia, independent of NMOSD onset timing. Neurology ® 2016;86:79-87 GLOSSARY AQP4 5 aquaporin-4; ARR 5 annualized relapse rate; CI 5 confidence interval; IgG 5 immunoglobulin G; NMO 5 neuromyelitis optica; NMOSD 5 neuromyelitis optica spectrum disorder; ON 5 optic neuritis; OR 5 odds ratio.Neuromyelitis optica spectrum disorder (NMOSD) is a severe recurrent antibody-mediated inflammatory disorder of the CNS, mainly characterized by optic neuritis (ON) and longitudinally extensive transverse myelitis, 1 but also affecting other areas in the CNS (e.g., brainstem and hypothalamus). The presence of immunoglobulin G (IgG) that binds to aquaporin-4 (AQP4), 2,3 known to be key in the pathogenic process of this disorder, distinguishes NMOSD from other CNS inflammatory disorders.1 NMOSD is up to 8 times more prevalent in women, 4 many of whom have active disease during childbearing years. [5][6][7] Recently, experimental and clinical reports have demonstrated the presence of AQP4 in human and animal placenta, and have linked AQP4-mediated placental inflammation to fetal death. [8][9][10] It is clear that the annualized relapse rate (ARR) of NMOSD is significantly increased in the 0-to 3-month postpartum period, 11-13 but there is a lack of information on the influence of NMOSD on the course of pregnancy.We investigated the effect of NMOSD on miscarriage and preeclampsia rates using multivariate logistic regre...

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“…In line with this notion, interferon-gamma (IFNc) was found to induce AQP4 expression in cultured astrocytes [11], to enhance the availability of AQP4 epitopes recognized by pathogenic AQP4 antibodies from human NMO patients in kidney cells [12], and to exacerbate AQP4-and complement-mediated tissue damage in AQP4-IgG-induced spinal cord slice cultures [13]. Similarly, animal experiments have demonstrated AQP4 upregulation around CNS blood vessels during pregnancy and post partum [14], a period associated with an elevated relapse rate in AQP4-Ab-positive NMO patients [15][16][17]. In addition, increased AQP4 expression may represent an independent risk factor not only in NMO, but in CNS inflammation in general [18]: the degree of AQP4 expression has been postulated to influence inflammation outcome directly by affecting cell swelling, water and K+ homeostasis, concentrations of excitatory neurotransmitters, and astrocyte activation and migration [19].…”

Section: Hypothesismentioning

confidence: 94%