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Background: Treatment algorithms for neuromyelitis optica spectrum disorder (NMOSD) vary, and sparse data exist regarding the impact of initial treatments on disease course. We aimed to determine whether administration of rituximab during first hospitalization reduces 1-year readmission rates. Methods: We conducted a retrospective cohort study of subjects with NMOSD using the Pediatric Health Information System database from 2005 to 2015. Subjects were ages 1 to 21 years who received glucocorticoids and an ICD-9-CM code indicating neuromyelitis optica (NMO) during first hospitalization. All subjects had at least 12 months of continuous enrollment. The primary exposure was ≥1 rituximab dose during first hospitalization. We tested for the association of rituximab use with all-cause re-hospitalization, the primary outcome, using survival analysis. Re-hospitalization was considered if a hospital admission occurred > 30 days after initial discharge with exclusion of admissions with re-dosing of rituximab and data were censored at 12 months. Secondary outcomes included time to and median duration of re- hospitalization using 25th percentiles of survival time and the Wilcoxon-rank sum test, respectively. Results: Of 180 subjects who met inclusion criteria, 71.7% were female and the median age was 13 years (IQR: 10, 15). Fifty-two subjects (28.9%) received rituximab during first hospitalization, and there was an increasing trend in rituximab useovertime(p < 0.01). Overall, 36.7% of children were readmitted and time to readmission was a median of 365 days (IQR: 138, 365). Rituximab exposure was not associated with re-hospitalization (adjusted HR: 0.71: 95% CI: 0.38, 1.34) nor a reduced time to re-hospitalization. Median duration of re-hospitalization was 2 days shorter in the rituximab exposed group (p = 0.02). Receipt of physical therapy, a surrogate marker for neurologic impairment, during first hospitalization was associated with re-admission within 12 months (adjusted HR: 4.81; 95% CI: 1.14, 20.29). Conclusions: Among children with NMOSD, first-line administration of rituximab was not associated with risk of or time to re-hospitalization. Rituximab use was found to be associated with a shorter duration of re-hospitalization. Need for physical therapy during first hospitalization was independently associated with an increased risk of re-admission. Keywords: Autoimmune, Demyelinating, Neuromyelitis optica, Rituximab * Correspondence: email@example.com Division of Rheumatology, Center for Pediatric Clinical Effectiveness, Children’s Hospital of Philadelphia, Philadelphia, PA, USA Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Gmuca et al. Multiple Sclerosis and Demyelinating Disorders (2018) 3:3 Page 2 of 7 Background were less likely to be incident cases. The primary expos- Neuromyelitis optica spectrum disorder (NMOSD) is a ure was defined as billing for ≥1 dose of rituximab rare, immune-mediated inflammatory disorder of the during the initial hospitalization. The primary outcome central nervous system. This chronic astrocytopathy was all-cause re-hospitalization (binary), a surrogate preferentially targets the optic nerves and spinal cord, marker for disease and treatment related morbidity. Re-- resulting in severe and potentially devastating sequelae such hospitalization was considered if a hospital admission as paralysis and blindness. Despite the life-threatening con- occurred > 30 days after initial discharge with exclusion sequences of uncontrolled disease activity, there are no vali- of re-hospitalizations with re-dosing of rituximab and dated treatment strategies for NMOSD [1–3]. data were censored at 12 months. Secondary outcomes NMOSD is rare among children and adolescents, with included time to first re-hospitalization and duration of pediatric onset NMOSD accounting for approximately re-hospitalization. 3–5% of all cases . However, early recognition and Demographics were summarized by standard descrip- initiation of treatment is critical for preventing disease tive statistics including frequencies and percentages for relapses in children with NMOSD. Therapeutic manage- categorical variables (e.g. sex, race) and by range, me- ment of pediatric NMOSD is largely based on Class IV dian, and interquartile range (IQR) for continuous or evidence, extrapolated from studies of adults [5–10]. count variables. Characteristics between the rituximab Immunotherapeutic agents targeting T and B cell func- exposed and unexposed groups were compared by Wil- tions and reducing pro-inflammatory molecules from coxon rank sum test for medians, and chi-squared test the peripheral blood circulation have been shown to at- or Fisher’s exact test for proportions as appropriate. tenuate disease progression in NMOSD . Rituximab is Time to hospitalization was calculated in days from the a chimeric, murine/human monoclonal antibody directed initial hospitalization until the first readmission and sur- against the CD20 antigen that results in depletion of B vival analysis was used to calculate 25th percentiles of cells. Although small, open label  and retrospective time to re-hospitalization based on rituximab exposure. studies  have reported benefits of rituximab in Kaplan-Meier survival curves of re-hospitalization were NMOSD, the effectiveness and safety of rituximab for generated for the rituximab exposed and unexposed NMOSD remains unclear [3, 13]. We sought to determine groups and compared using the log-rank test. The pro- the impact of rituximab on all-cause re-hospitalization for portional hazards assumption for the primary exposure children and young adults with NMOSD. We hypothe- was met (Shoenfeld residuals p = 0.58). The univariate sized that subjects who received rituximab during their Cox proportional hazard regression model was used to first hospitalization were less likely to be re-admitted evaluate the marginal effect of each covariate on the out- within 12 months. come, including demographics, glucocorticoid type, level of care, physical therapy, plasma exchange (PLEX) and Methods duration of initial hospital stay. Covariates with a p-value We conducted a retrospective cohort study of subjects less than 0.2 were considered in forward selection using with NMOSD in the Pediatric Health Information the likelihood ratio test to build a multivariable cox System (PHIS) from January 2005 until December 2015. regression model with certain variables of interest PHIS is an administrative database of 46 children’s hos- forced into the model. The proportional hazards as- pitals across the United States and represents 85% of all sumption was met using Schoenfeld residuals with pediatric hospitalizations at freestanding tertiary care global test p = 0.31. According to Cox-Snell residuals, pediatric facilities. All subjects with at least 12 months thefinal modelfit thedata well. We did not assess of continuous enrollment and ≤ 21 years of age at competing risks because the data source did not in- the time of initial documentation of an ICD-9-CM code clude mortality data. The trend in the proportion of for NMO (341.0) were included. The index date was the children with NMOSD who received first-line rituxi- date of the first admission with an ICD-9-CM code for mab therapy per calendar year was tested by ‘nptrend’ NMO. We excluded patients less than 1 year of age at command implemented in Stata. All tests considered the time of diagnosis (because NMOSD is unlikely to were two-sided and a significance level of 0.05 was present within the first year of life) ; or who had an applied. Data analyses were performed using STATA ICD-9-CM code for multiple sclerosis (MS), as this is a 14 (STATA Corp, College Station TX). distinct disease from NMOSD. We also excluded sub- jects who did not receive glucocorticoids, which are fre- Results quently administered intravenously for optic neuritis or Of the 351 eligible subjects with at least one code for spinal cord deficits in NMOSD. Subjects with an ICD-9- NMO, 180 subjects met study inclusion and exclusion CM code for NMOSD but without glucocorticoid expos- criteria (Fig. 1). Table 1 shows patient characteristics. ure likely did not have active neurologic disease and The majority of subjects were female (71.7%) and a little Gmuca et al. Multiple Sclerosis and Demyelinating Disorders (2018) 3:3 Page 3 of 7 Fig. 1 Flow diagram outlining inclusion/exclusion criteria less than half were Caucasian (40.0%). Median age at greater than in the unexposed group (70.2% vs. 42. time of first hospitalization was 13 years (IQR: 10.0, 15. 0%). Overall, 36.7% of subjects were re-hospitalized at 0) and median duration of initial hospitalization was least once within the first year after diagnosis (Table 1). 6 days (IQR: 3.0, 12.0). Only 3 subjects had a concomi- Kaplan-Meier estimates comparing the probability of re- tant systemic rheumatologic condition. A total of 16 hospitalization for children with NMOSD treated with ri- subjects (8.9%) received oral glucocorticoids only; 76 tuximab versus those treated with alternative therapies (42.2%) received methylprednisolone only; and 88 (48. showed no statistically significant difference between 9%) received a combination of oral and intravenous groups (log-rank test p = 0.76) (Fig. 3). Median duration of glucocorticoids. Table 2 lists the proportion of subjects re-hospitalization was 2 days (IQR: 1.0, 4.0) in subjects ad- who received each of the glucocorticoid sparing therap- ministered first-line rituximab compared to 4 days (IQR: ies administered during initial hospitalization. The most 2.0, 6.0) in those subjects who did not receive rituximab common were plasma exchange (PLEX) (31.1%), rituxi- (p = 0.02). 25% of rituximab exposed subjects were re-hos- mab (28.9%), and intravenous immunoglobulin (IVIg) pitalized within 137 days (95% CI: 65, 295) and 25% of ri- (18.3%); 61 subjects (33.9%) did not receive any gluco- tuximab unexposed were re-hospitalized within 134 days corticoid sparing therapies. Of those subjects who (95% CI: 92, 192), indicating a similar time to re- received rituximab (n = 52), 20 subjects (38.5%) also re- hospitalization irrespective of rituximab exposure. ceived plasma exchange and 23 subjects (44.2%) received In univariate Cox regression modeling, the relative haz- rituximab without any other non-glucocorticoid im- ard of all-cause re-hospitalization in the first 12 months munosuppressive therapy. was 1.08 (95% CI: 0.64, 1.83) for those treated with Fifty-two subjects (28.9%) received rituximab during rituximab compared to those not treated with rituxi- their first hospitalization with an increasing trend mab (p = 0.77). In the final multivariate model over time (p < 0.01) (Fig. 2). Comparing subjects in (Table 3), the hazard ratio (HR) of re-hospitalization the rituximab exposed to unexposed, the proportion within 12 months was 0.71 (95% CI: 0.38, 1.34) for of non-Caucasian subjects in the rituximab group was those children who received rituximab compared to those Gmuca et al. Multiple Sclerosis and Demyelinating Disorders (2018) 3:3 Page 4 of 7 Table 1 Patient characteristics Total (n = 180) Rituximab exposed Rituximab unexposed (n = 52) (n = 128) Demographics Female, n (%) 129 (71.7) 43 (82.7) 86 (67.2) Age, median (IQR) 13.0 (10.0, 15.0) 13.0 (10.0, 16.0) 12.5 (9.0, 15.0) Caucasian , n (%) 72 (48.9) 14 (29.8) 58 (58.0) Region, n (%) Northeast 29 (16.1) 9 (17.3) 20 (15.6) Midwest 29 (16.1) 8 (15.4) 21 (16.4) South 98 (54.4) 30 (57.7) 68 (53.1) West 24 (13.3) 5 (9.6) 19 (14.8) Systemic lupus erythematosus, n (%) 2 (1.1) 2 (3.9) 0 (0.0) Sjögren syndrome, n (%) 1 (0.6) 1 (1.9) 0 (0.0) ICU status, n (%) 31 (17.2) 11 (21.2) 20 (15.6) Length of stay (days), median (IQR) 6 (3.0, 12.0) 7.0 (3.0, 17.0) 6.0 (3.0, 11.0) Primary outcome Re-hospitalization in 12 months, n (%) 66 (36.7) 20 (38.5) 46 (35.9) Secondary outcomes Length of re-hospitalization (days), median (IQR) 3.0 (1.0, 5.0) 2.0 (1.0, 4.0) 4.0 (2.0, 6.0) Time to re-hospitalization (days), median (IQR) 365 (138, 365) 365 (138, 365) 365 (137, 365) ICU intensive care unit, IQR interquartile range Race was missing for 33 subjects. Rituximab exposure was defined as having received at least one dose of rituximab during initial hospitalization witha documented ICD-9-CM code for neuromyelitis optica (341.0) who did not (p = 0.29). Receipt of physical therapy was all-cause re-hospitalization or time to all-cause re- independently associated with an increased risk of re- hospitalization. Although first-line rituximab use was as- hospitalization within the first 12 months (HR: 4.82; 95% CI: sociated with a shorter duration of re-hospitalization, 1.14, 20.29). the clinical significance of this is unclear. Receipt of physical therapy was independently associated with an Discussion increased risk of re-hospitalization. Using a database of 46 freestanding children’s hospitals, This study, to our knowledge, comprises the largest we assessed the impact of first-line rituximab use on cohort of pediatric subjects with NMOSD administered children and adolescents with NMOSD. We did not ob- rituximab first-line. Previous work has largely focused serve an association between rituximab use and risk of on the use of rituximab as maintenance therapy in the treatment of NMOSD, with a limited number of studies examining the efficacy of first-line rituximab use [1, 5, Table 2 Proportion of subjects administered non-glucocorticoid 16]. Zephir et al. reported a retrospective analysis of 32 treatment regimens during first hospitalization (n = 180) adults with NMOSD who received first-line rituximab Treatment n, (%) and found that at the end of the follow-up period (mean Plasma exchange (PLEX) 56 (31.1) 28.7 months), 84.3% were relapse free . Olivieri et al. Rituximab 52 (28.9) described the case of a 9-year-old girl who received rituxi- Intravenous immunoglobulin (IVIg) 33 (18.3) mab along with administration of methylprednisolone and Mycophenolate mofetil 23 (12.8) plasma exchange and had a slow but full neurologic recov- Azathioprine 15 (8.3) ery . Longoni et al. performed a retrospective cohort study of 5 pediatric subjects (all aquaporin-4 antibody Cyclophosphamide 10 (5.6 positive) with NMOSD treated with first-line rituximab; Methotrexate 1 (0.6) 60% (3/5) had a relapse of their disease within 12 months Legend. Subjects were able to contribute to more than one treatment of initial rituximab therapy but relapses were reportedly regimen therefore total does not equal 100% PLEX + rituximab (n = 20) less severe than prior to treatment and all patients demon- Rituximab only, without any of the above listed non-glucocorticoid strated neurologic improvements by the end of the follow- agent (n = 23) IVIg + rituximab (n =8) up period . Gmuca et al. Multiple Sclerosis and Demyelinating Disorders (2018) 3:3 Page 5 of 7 flares was less. Therefore, in light of the potential for sig- nificant morbidity and mortality in children with newly diagnosed NMOSD, first-line rituximab should be care- fully considered. Receipt of physical therapy during initial hospitalization was found to be an independent predictor of re- hospitalization within 12 months. Likely, those children necessitating physical therapy during their initial hospital encounter, had a more severe presen- tation of their NMOSD. Children with physical ther- apy services likely incurred significant morbidity such as paralysis and for this reason alone would be more likely to have subsequent complications leading to re-admissions. Unfortunately, such insults cannot be reversed even with first-line rituximab use. With respect to demographics, we found that non- Caucasian subjects were more likely to receive rituximab during their first hospitalization. Previous research has Fig. 2 Proportion of subjects with NMOSD administered first-line ri- tuximab per year (n = 180) shown that certain races, specifically Afro-Caribbeans, have greater relapse rates . This may drive providers to treat non-Caucasian patients more aggressively and Our findings did not show a statistically significant re- favor first-line rituximab in this patient population. duction in risk of all-cause re-hospitalization with first- This study has limitations. First, there is a possibility line rituximab use. However, it is possible that our study of misclassification bias because the NMO ICD-9-CM was underpowered or did not fully account for residual code has not been validated. However, given the specifi- confounding by indication, resulting in negative findings. city of language for this code and the rarity of this We did find that the duration of re-hospitalization, how- disease, we believe it would be unlikely for practitioners ever, was statistically significantly shorter among those to incorrectly assign patients an ICD-9-CM code for subjects who received rituximab therapy upfront. This NMO. We also attempted to increase the specificity of suggests, similar to the findings of Longoni et al., that the code by requiring receipt of glucocorticoids and even for rituximab exposed children who experienced excluding subjects with codes for MS. We may, how- disease flares within 12 months, the severity of their ever, have failed to capture all patients with NMOSD. Fig. 3 Kaplan-Meier estimates of re-hospitalization by rituximab exposure Gmuca et al. Multiple Sclerosis and Demyelinating Disorders (2018) 3:3 Page 6 of 7 Table 3 Multivariate Cox proportional hazards for re- Conclusions hospitalization within 12 months Among children with NMOSD, first-line rituximab ther- Covariate Adjusted HR 95% CI P-value apy was not associated with a decreased risk of or time to all-cause re-hospitalization within 12 months. However, Rituximab exposure 0.71 0.38, 1.34 0.29 first-line rituximab use was associated with a decreased Male gender 0.68 0.35, 1.32 1.32 duration of re-hospitalization, suggesting its possible role Caucasian 0.90 0.50, 1.61 0.72 in mitigating the severity of subsequent disease relapses. Region (reference: Midwest) Further research is warranted to determine the long-term Northeast 0.74 0.28, 1.91 0.53 effects of first-line rituximab on morbidity and mortality, South 0.70 0.33, 1.47 0.35 which will help guide the optimal treatment regimen for NMOSD taking into consideration disease progression, West 1.09 0.40, 2.95 0.87 adverse events, and re-admissions. Length of Initial Stay (days) 0.98 0.94, 1.03 0.41 ICU status 1.41 0.61, 3.25 0.43 Abbreviations Receipt of PT 4.81 1.14, 20.29 0.03 HR: Hazard ratio; ICU: Intensive care unit; IVIg: Intravenous immunoglobulin; MS: Multiple sclerosis; NMO: Neuromyelitis optica; NMOSD: Neuromyelitis Receipt of PLEX 1.01 0.49, 2.08 0.98 optica spectrum disorder; PHIS: Pediatric health information system; Glucocorticoid (reference: oral only) PLEX: Plasma exchange; SLE: Systemic lupus erythematosus Intravenous only 0.88 0.28, 2.72 0.82 Acknowledgements Oral + intravenous 1.72 0.57, 5.18 0.33 The authors thank Emily R. Schriver for her assistance with data Physical therapy (PT) exposure defined as at least one procedure code for PT management. during initial hospitalization. Oral glucocorticoids defined as at least one billing code for dexamethasone, hydrocortisone, prednisone or prednisolone CI confidence interval, ICU intensive care unit, PLEX plasma exchange Funding Dr. Gmuca is supported by the National Institute of Health Rheumatology Research Training Grant T32-AR007442-29. Dr. Waldman has received funding from the National Institute of Neurologic Disorders and Stroke Grant K23- NS069806. This study was funded by the Children’s Hospital of Philadelphia Additionally, the relatively recent discovery of the anti- Center for Pediatric Clinical Effectiveness (CPCE) Pilot Grant Program. myelin oligodendrocyte glycoprotein (MOG) antibodies [18–20] could lead to misclassification bias in our study. Availability of data and materials During the study interval, testing for MOG would not have The datasets used and/or analyzed during the current study are available been available to providers and would not affect treatment from the corresponding author on reasonable request. decision making; however, subjects with NMOSD who are seropositive for anti-MOG, have more favorable outcomes Authors’ contributions and tend to be glucocorticoid responsive . Therefore, SG, PW, AW, JG are responsible for the conception and design of the work. SG is responsible for data collection, data analysis and drafting of the dependent on the number of subjects with anti-MOG posi- manuscript. SG, PW, AW, JG contributed to the data interpretation. All the tivity in this study, this could bias our primary outcome to- authors are responsible for critical revision of the article and gave final wards the null and, in part, explain our study’s negative approval of the version to be published. findings. Second, we likely did not identify all outcomes of interest by using retrospective data; however, by only in- Ethics approval and consent to participate This study was determined by The Children’s Hospital of Philadelphia cluding patients with 12 months of available follow-up time institutional review board to not meet the requirements of human subjects in thedatabaseweaimed to minimize anyoutcomebias. research and therefore consent was not required. Third, by using claims data we were limited in our ability to assess clinical severity or aquaporin-4 antibody status in Competing interests this cohort of patients with NMOSD. Of note, laboratory The authors declare that they have no competing interests. detection of aquaporin-4 antibodies is a send-out test for most institutions with a turn-around-time of 5–8days; thus Publisher’sNote most providers make treatment decisions for a patient’sini- Springer Nature remains neutral with regard to jurisdictional claims in tial attack prior to receiving the test results. Fourth, there published maps and institutional affiliations. may have been residual confounding by indication. How- Author details ever, we attempted to address confounding by indication by Division of Rheumatology, Center for Pediatric Clinical Effectiveness, adjusting for receipt of PLEX, receipt of PT, duration of ini- 2 Children’s Hospital of Philadelphia, Philadelphia, PA, USA. Department of tial hospitalization, and ICU status in our final multivariate Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Division of Neurology, logistic regression model. We did not find that these indica- Children’s Hospital of Philadelphia, Philadelphia, PA, USA. Division of tors of disease severity were independently associated with Infectious Diseases, Center for Pediatric Clinical Effectiveness, Children’s re-hospitalization. Hospital of Philadelphia, Philadelphia, PA, USA. Gmuca et al. Multiple Sclerosis and Demyelinating Disorders (2018) 3:3 Page 7 of 7 Received: 8 January 2018 Accepted: 9 April 2018 References 1. Zephir H, Bernard-Valnet R, Lebrun C, Outteryck O, Audoin B, Bourre B, Pittion S, Wiertlewski S, Ouallet JC, Neau JP, et al. Rituximab as first-line therapy in neuromyelitis optica: efficiency and tolerability. J Neurol. 2015; 262:2329–35. 2. Kimbrough DJ, Fujihara K, Jacob A, Lana-Peixoto MA, Leite MI, Levy M, Marignier R, Nakashima I, Palace J, de Seze J, et al. Treatment of neuromyelitis optica: review and recommendations. Mult Scler Relat Disord. 2012;1:180–7. 3. Kim SH, Kim HJ. Rituximab in Neuromyelitis Optica Spectrum disorders: why not as first-line therapy. JAMA Neurol. 2017;74:482. 4. Tenembaum S, Chitnis T, Nakashima I, Collongues N, McKeon A, Levy M, Rostasy K. Neuromyelitis optica spectrum disorders in children and adolescents. Neurology. 2016;87:S59–66. 5. Longoni G, Banwell B, Filippi M, Yeh EA. Rituximab as a first-line preventive treatment in pediatric NMOSDs: preliminary results in 5 children. Neurol Neuroimmunol Neuroinflamm. 2014;1:e46. 6. Torres J, Pruitt A, Balcer L, Galetta S, Markowitz C, Dahodwala N. Analysis of the treatment of neuromyelitis optica. J Neurol Sci. 2015;351:31–5. 7. Evangelopoulos ME, Andreadou E, Koutsis G, Koutoulidis V, Anagnostouli M, Katsika P, Evangelopoulos DS, Evdokimidis I, Kilidireas C. Treatment of neuromyelitis optica and neuromyelitis optica spectrum disorders with rituximab using a maintenance treatment regimen and close CD19 B cell monitoring. A six-year follow-up. J Neurol Sci. 2017;372:92–6. 8. Radaelli M, Moiola L, Sangalli F, Esposito F, Barcella V, Ferre L, Rodegher M, Colombo B, Fazio R, Martinelli V, Comi G. Neuromyelitis optica spectrum disorders: long-term safety and efficacy of rituximab in Caucasian patients. Mult Scler. 2016;22:511–9. 9. Kim SH, Huh SY, Lee SJ, Joung A, Kim HJ. A 5-year follow-up of rituximab treatment in patients with neuromyelitis optica spectrum disorder. JAMA Neurol. 2013;70:1110–7. 10. Kim SH, Jeong IH, Hyun JW, Joung A, Jo HJ, Hwang SH, Yun S, Joo J, Kim HJ. Treatment outcomes with rituximab in 100 patients with neuromyelitis optica: influence of FCGR3A polymorphisms on the therapeutic response to rituximab. JAMA Neurol. 2015;72:989–95. 11. Bienia B, Balabanov R. Immunotherapy of neuromyelitis optica. Autoimmune Dis. 2013;2013:741490. 12. Cree BA, Lamb S, Morgan K, Chen A, Waubant E, Genain C. An open label study of the effects of rituximab in neuromyelitis optica. Neurology. 2005;64:1270–2. 13. Damato V, Evoli A, Iorio R. Efficacy and safety of rituximab therapy in neuromyelitis optica spectrum disorders: a systematic review and meta- analysis. JAMA Neurol. 2016;73:1342–8. 14. Hardin AP, Hackell JM. Age limit of pediatrics. Pediatrics. 2017;140:e20172151. 15. Derle E, Gunes HN, Konuskan B, Tuncer-Kurne A. Neuromyelitis optica in children: a review of the literature. Turk J Pediatr. 2014;56:573–80. 16. Olivieri G, Nociti V, Iorio R, Stefanini MC, Losavio FA, Mirabella M, Mariotti P. Rituximab as a first-line treatment in pediatric neuromyelitis optica spectrum disorder. Neurol Sci. 2015;36:2301–2. 17. Tackley G, O’Brien F, Rocha J, Woodhall M, Waters P, Chandratre S, Halfpenny C, Hemingway C, Wassmer E, Wasiewski W, et al. Neuromyelitis optica relapses: race and rate, immunosuppression and impairment. Mult Scler Relat Disord. 2016;7:21–5. 18. Chalmoukou K, Alexopoulos H, Akrivou S, Stathopoulos P, Reindl M, Dalakas MC. Anti-MOG antibodies are frequently associated with steroid-sensitive recurrent optic neuritis. Neurol Neuroimmunol Neuroinflamm. 2015;2:e131. 19. Kitley J, Woodhall M, Waters P, Leite MI, Devenney E, Craig J, Palace J, Vincent A. Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype. Neurology. 2012;79:1273–7. 20. Waters P, Woodhall M, O’Connor KC, Reindl M, Lang B, Sato DK, Jurynczyk M, Tackley G, Rocha J, Takahashi T, et al. MOG cell-based assay detects non-MS patients with inflammatory neurologic disease. Neurol Neuroimmunol Neuroinflamm. 2015;2:e89.
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