Pediatric Neuromyelitis Optica Research Articles

Efficacy of Eculizumab in Acute Refractory Pediatric Neuromyelitis Optica: A Case Report (P11-14.012)

Efficacy of Eculizumab in Acute Refractory Pediatric Neuromyelitis Optica: A Case Report (P11-14.012)

Role of serostatus in pediatric neuromyelitis optica spectrum disorders: A nationwide multicentric study.

Neuromyelitis optica spectrum disorders (NMOSD) are immune-mediated inflammatory disorders of the central nervous system (CNS) mostly presenting as optic neuritis and acute myelitis. NMOSD can be associated with seropositivity for aquaporin 4 antibody (AQP4 IgG), myelin oligodendrocyte glycoprotein antibody (MOG IgG), or can be seronegative for both. In this study, we retrospectively examined our seropositive and seronegative pediatric NMOSD patients. Data were collected from all participating centres nationwide. Patients diagnosed with NMOSD were divided into three subgroups according to serology: AQP4 IgG NMOSD, MOG IgG NMOSD, and double seronegative (DN) NMOSD. Patients with at least six months of follow-up were compared statistically. The study included 45 patients, 29 female and 16 male (ratio:1.8), mean age 15.16±4.93 (range 5.5-27) years. Age at onset, clinical manifestations, and cerebrospinal fluid findings were similar between AQP4 IgG NMOSD (n=17), MOG IgG NMOSD (n=10), and DN NMOSD (n=18) groups. A polyphasic course was more frequent in the AQP4 IgG and MOG IgG NMOSD groups than DN NMOSD (p=0.007). The annualized relapse rate and rate of disability were similar between groups. Most common types of disability were related to optic pathway and spinal cord involvement. Rituximab in AQP4 IgG NMOSD, intravenous immunoglobulin in MOG IgG NMOSD, and azathioprine in DN NMOSD were usually preferred for maintenance treatment. In our series with a considerable number of double seronegatives, the three major serological groups of NMOSD were indistinguishable based on clinical and laboratory findings at initial presentation. Their outcome is similar in terms of disability, but seropositive patients should be more closely followed-up for relapses.

The Neutrophil-to-Lymphocyte Ratio and the Monocyte-to-Lymphocyte Ratio Predict Expanded Disability Status Scale Score at One Year in Pediatric Neuromyelitis Optica Spectrum Disorder but not in Multiple Sclerosis

BackgroundThe neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) are inflammatory biomarkers that may predict disease course in neuroinflammatory diseases. We examine whether NLR or MLR at the time of the first attack predicts longitudinal disease outcomes in pediatric neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). MethodsClinical data were collected retrospectively at a single institution. NLR (ratio of percent neutrophils to percent lymphocytes) and MLR (ratio of percent monocytes to percent lymphocytes) were calculated in the complete blood cell count at the time of presentation before treatments. Expanded Disability Status Scale (EDSS) score and time to next relapse were used as the outcome assessments. ResultsTwenty-eight patients with MS and eight patients with aquaporin-4-positive NMOSD were included. For NMOSD, NLR at presentation associated with EDSS at six months (P = 0.003) and one year (P = 0.032) even when adjusting for age at presentation. MLR associated with EDSS at six months (P = 0.0203) and EDSS at one year (P = 0.0079). However, NLR and MLR did not predict EDSS scores in MS. MLR and NLR did not predict time to next relapse or did not associate with magnetic resonance imaging activity in MS and NMOSD. Changes in MLR and NLR were observed with disease-modifying therapies but did not predict disease activity. ConclusionsNLR and MLR associated with six-month and one-year EDSS in children with NMOSD but not in MS. Future studies should explore whether changes in NLR and MLR could predict disease activity or treatment efficacy.

Pediatric Neuromyelitis Optica Spectrum Disorder Presenting as Intractable Vomiting

Pediatric neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease that affects the central nervous system. Common presentations include weakness and sensory changes secondary to transverse myelitis, or vision loss due to optic neuritis. Area postrema syndrome, characterized by intractable nausea, vomiting, or hiccups secondary to a demyelinating lesion in the chemoreceptor trigger zone, is part of the core diagnostic criteria for NMOSD. However, it has infrequently been described as an initial presentation of pediatric NMOSD. Here, we present the case of a 13-year-old female who presented with intractable vomiting, which was initially presumed to be secondary to gastrointestinal pathology. It was not until she developed transverse myelitis that the etiology of her intractable vomiting was identified as area postrema syndrome secondary to NMOSD. She was successfully treated with rituximab, and she remains relapse-free after the initiation of immunosuppressive therapy. This case highlights this rare presentation of NMOSD and emphasizes the need for increased awareness amongst pediatric providers in recognizing this diagnosis and preventing delays in treatment. Int J Clin Pediatr. 2022;11(2):35-38 doi: https://doi.org/10.14740/ijcp478

Multisystem involvement in neuromyelitis optica

We describe a case of pediatric neuromyelitis optica (NMO) with muscle and lung involvement in addition to central nervous system disease. Our patient initially presented with features of area postrema syndrome, then subsequently with optic neuritis. The patient also had recurrent hyperCKemia that responded to corticosteroids. Finally, axillary and hilar adenopathy with pulmonary consolidation were noted as well and responded to immunomodulation. Our case highlights multisystem involvement in NMO including non-infectious pulmonary findings which have not been described in the pediatric population previously.

Clinico-epidemiological profile and outcome of pediatric neuromyelitis optica spectrum disorder at an eastern Indian tertiary care center

Abstract Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing inflammatory central nervous system disorder. Patients either have antibodies to aquaporin 4 (AQ4)/myelin oligodendrocyte glycoprotein (MOG) or are double seronegatives (DSN). Aim: We aimed at comparing the clinico-epidemiological features and outcome of the subgroups of NMOSD. Design: Prospective longitudinal observational study. Materials and Methods: NMOSD was diagnosed by using the 2006 Wingerchuk criteria. Patients diagnosed between September 2016 and August 2018 were prospectively followed upto July 2020. Acute episodes were treated with steroids, and immunomodulators were started in patients with aquaporin 4 IgG (anti-AQ4+) and in relapsing cases of anti-MOG+ and DSN groups. Disability was assessed by using the Expanded Disability Status Scale (EDSS). Comparisons were made between patients who were anti-AQ4 and anti-MOG positive and those with DSN. Statistical analysis was done by SPSS 20.0 software. Results: Among 13 patients, the female:male ratio was 1.16:1, and the mean age of disease onset was 9.65 ± 3.25 years. Overall, 15.38% patients were anti-AQ4+, 30.67% were anti-MOG+, 53.86% were DSN, 69.2% had relapsing disease, and 30.8% had monophasic disease (P = 0.11). The mean to relapse was 13.16±3.5 months; 61.5% patients had long segment myelitis and 53.86% had optic neuritis on their first presentation (P = 0.99). Cerebral syndrome occurred among one patient with anti-MOG+ and in three patients with DSN. The EDSS scores were significantly lower among patients who were anti-MOG+. Conclusion: The female:male ratio was more equitable and the age of disease onset was lower in our cohort compared with western data. There was no significant difference in the clinico-demographic characteristics among the three groups; however, outcome was better in the anti-MOG+ group. Rituximab was effective for recurrent relapses.

Pediatric Neuromyelitis Optica Spectrum Disorders: Three Case Reports and Review of Literature

Pediatric Neuromyelitis Optica Spectrum Disorders: Three Case Reports and Review of Literature

Epidemiology of pediatric multiple sclerosis, neuromyelitis optica, and optic neuritis in Taiwan.

The epidemiology of pediatric acquired demyelinating disorders remains to be clarified in many parts of Asia. We carry out this study to depict the epidemiology of pediatric multiple sclerosis (MS), neuromyelitis optica (NMO), and optic neuritis (ON) in Taiwan. We conducted a retrospective nationwide population-based study using data from Taiwan's National Health Insurance Research Database. Prevalent cases of pediatric MS and NMO during 2001-2015, and incident cases of pediatric MS, NMO, and ON during 2003-2015 were identified. The demographic features and comorbidities were investigated. We identified 403 MS, 42 NMO, and 1496 ON incident cases under the age of 20 during 2003-2015. The majority of pediatric MS (86.1%) and NMO (90.5%) patients were 10years old or above. The incidence of MS and ON was relatively steady, while that of NMO increased prominently later during the study period. The average incidence of pediatric MS and NMO during 2011-2015 was 0.52 and 0.11 per 100,000 person-years, respectively. The female preponderance was evident for pediatric MS and NMO, and less so for pediatric ON. The most common autoimmune comorbidities for pediatric MS were thyrotoxicosis (1.0%) and systemic lupus erythematosus (0.7%). The epidemiology of pediatric MS was largely stationary in Taiwan during 2001-2015, while the prevalence of pediatric NMO rose steeply during this period, probably reflecting better recognition of this clinical entity. Autoimmune comorbidities were uncommon for pediatric MS and NMO in Taiwan.

Validation of claims-based diagnoses of adult and pediatric neuromyelitis optica spectrum disorder and variations in diagnostic evaluation and treatment initiation

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is a rare demyelinating disease in need of more studies to determine effective treatment regimens. The rarity of the disorder, however, makes large randomized-controlled trials challenging. Validation of the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code for NMO could facilitate the use of large healthcare claims data for future research. We aimed 1) to determine the positive predictive value (PPV) of the ICD-9-CM code for NMO as well as evaluate case-finding algorithms for the identification of patients with NMO/NMOSD and 2) to compare the evaluation of and treatment for pediatric versus adult patients. MethodsThis was a multicenter retrospective cohort study of patients with ≥ 1 ICD-9 code for NMO seen at 3 pediatric and 2 adult United States medical centers from 2001–2016. Using a standardized data entry form, pediatric and adult neurologists and rheumatologists reviewed patients’ medical records to determine whether patients fulfilled the 2006 criteria for NMO and/or the 2015 criteria for NMOSD in order to determine the positive predictive value (PPV) for the ICD-9-CM code. Demographic and clinical information was abstracted from patient medical records to ascertain variables then evaluated in case-based finding algorithms for further identification of patients with true NMO/NMOSD. We also evaluated differences in clinical characteristics between pediatric and adult patients using chi-squared or Fisher's exact tests, as appropriate, to assess for treatment variation. ResultsA single code for NMO had a PPV of 47% across all sites, with significant site variation (0–77%). The best case-finding algorithm included at least 5 codes as well as a documented hospitalization (PPV = =90% for children and PPV = 92% for adults). Children were more likely to be evaluated by a rheumatologist or ophthalmologist, undergo magnetic resonance imaging of the orbits, and receive immunosuppressive and biologic agents than their adult counterparts. Rituximab was administered similarly among the two groups. ConclusionThe ICD-9 code for neuromyelitis optica (NMO) is inaccurate for identification of NMO/NMOSD. Using case-finding algorithms increases the PPV. The initial diagnostic evaluation and treatment of NMOSD differs significantly between children and adults.

Incidence of pediatric neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease in Denmark 2008‒2018: A nationwide, population-based cohort study

BackgroundThe incidence of pediatric neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease have not been reported previously. Our aim was to estimate the incidence of pediatric NMOSD and the occurrence of anti-MOG antibody-associated disease in Denmark during 2008–18, and to evaluate the diagnostic usefulness of antibodies against MOG and aquaporin-4 (AQP4) in children <18 years. MethodsWe undertook a nationwide, population-based, multicenter cohort study using data from the Danish National Patient Register, the Danish Multiple Sclerosis Registry, and laboratories providing anti-AQP4 and anti-MOG antibody analyses. Diagnoses were confirmed by review of the medical records, including blinded MRI review in most children with acute disseminated encephalomyelitis (ADEM). ResultsIn children with acquired demyelinating syndromes, anti-AQP4 antibodies were detected in 4% and anti-MOG antibodies in 18%, including in the two children with ADEM who relapsed. We identified four children with NMOSD, equivalent to an incidence of 0.031/100,000 (95% confidence interval = 0.011‒0.082). In anti-MOG antibody-positive children, 32% relapsed during follow-up. ConclusionsPediatric NMOSD and MOG antibody-associated disease are rare, but one-third of anti-MOG-positive children relapsed. In pediatric ADEM, only anti-MOG antibody-positive children relapsed, but the overall risk of relapse after pediatric ADEM was low.

So Dramatic They Could Never Be Overlooked: History of Pediatric Neuromyelitis Optica

So Dramatic They Could Never Be Overlooked: History of Pediatric Neuromyelitis Optica

Hematopoietic Stem Cell Transplantation for CNS Autoimmune Disorders for Adults and Children: Long-Term Outcomes - Experience of the Russian Federation

Rationale. More than 70 000 of patients registered with multiple sclerosis (MS) registered in Russia annually. Some of adults and children with CNS autoimmune disorder (AD) require hematopoietic stem cell transplantation (HSCT). We analyzed long-term outcomes and late effects in adults and children with MS and neuromyelitis optica (NMO) after HSCT treated in three Russian centers.Patients and Methods. Sixteen children were treated in the Russian Children's Research Hospital in collaboration with Dmitry Rogachev Center: MS - 13, NMO - 3. MS: female (F) - 9, male (M)- 4; NMO: all females. MS median age - 16,8±1,6 y.o., median Expanded Disability Status Scale (EDSS) 6,16±0,2. NMO pts median age - 12,7±1,4 y.o. All patients had severe refractory disease. MS children received Cyclophosphomide and horse ATG, NMO - Treosulfan, Fludarabine, Rituximab and horse ATG. Nighty nine MS adults received HSCT in National Pirogov Medical Surgical Center with reduced-intensity BEAM-like conditioning regimen in mean age-35 y.o.; M:F=39:60; median EDSS = 3.5; disease status - 43 relapsing/remitting MS, 56 progressive MS. Thirty-two MS adult patients were transplanted in Raisa Gorbacheva Research Institute during 2 periods of time: 25 patients in 2000 - 2010 (mean age - 34,4 y.o., M:F=12:13, mean EDSS=4,3) with conditioning regimen BEAM and horse ATG and in 2018 (mean age - 36 y.o., M:F=3:4, mean EDSS=4.5) with conditioning regimen based on Cyclophosphomide and horse ATG.Results. Rapid improvement of EDSS registered in children - EDSS decreasing on 3,1±0,3 during first 60 days. Median follow-up - 52,1 ± 2,3 months (12-86 months). Two MS patients relapsed (clinical and MRI). Almost all NMO patients stopped the progression and improved neurologically (clinical and MRI) except 1 pt - died due to refractory ADV-infection. Median follow-up - 24,2±4,5 months (1- 62 months). MS patients late effects cardio-vascular - 5 pts, endocrine - 3 pts (all females). NMO patients late effects: cardio-vascular - 2 pts., late immune reconstitution - 1 pt. In Pirogov Medical Surgical Center group at 6 months post-transplant, neurological improvement or stabilization was observed in all the patients except one. Cumulative incidence of disease progression was 16.7 % at 8 years after HSCT. Sixty-four patients who did not progress during the first 3 years post-transplant and were monitored for more than 3 years were included in long-term outcome analysis. At the median long-term follow-up of 62 months, 47 % of patients improved by at least 0.5 points on the EDSS as compared to baseline and exhibited improvement during the entire period of follow-up; 45 % of patients were stable. In Raisa Gorbacheva Research Institute 50% of patients (group transplanted in 2000 - 2010) relapsed, group transplanted in 2018 - 4 patients were improved on therapy and 3 - stabilized.Conclusions. HSCT is used both for children and adults in Russia. It is successful approach for refractory MS and pediatric NMO treatment. In-time HSCT can significantly improve the outcome. Late effects can be found in these patients, so it's important to find it and give adequate rehabilitation. Thus, the risk/benefit ratio of HSCT in our population of these patients are very favorable. DisclosuresNo relevant conflicts of interest to declare.

MRI findings in pediatric neuromyelitis optica spectrum disorder with MOG antibody: Four cases and review of the literature

BackgroundMyelin oligodendrocyte glycoprotein antibodies (MOG Abs) are frequently detected in pediatric acquired demyelinating syndrome (ADS), and MOG-Ab-positive ADS differs from multiple sclerosis (MS) and aquaporin-4 (AQP4)-Ab-positive neuromyelitis optica spectrum disorder (NMOSD) in terms of age distribution, therapeutic response, and prognosis. MethodsBased on medical records, we retrospectively evaluated patients with MOG-Ab-positive NMOSD treated in the acute phase who were followed up in the chronic phase at our hospital from January 2011 to December 2017. ResultsThe patients comprised two boys and two girls aged 3–12 (median, 8) years. Peak MOG-Ab titers were 1:2048 to 1:32768 (median, 1:10240), and the relapse rate ranged from 0 to 1.25 times/year (median, 0.59 times/year); no sequelae were observed in any cases. Lesions other than those of optic neuritis were distributed at the cortex in one patient, subcortical white matter in four, deep white matter in three, and brainstem in one, all of which were disseminated lesions. No lesions were found in the corpus callosum, periventricular white matter, diencephalon, and regions adjacent to the third and fourth ventricles. The lesions tended to be asymptomatic, and two patients aged >5 years had well-demarcated lesions. ConclusionAll the patients showed disseminated lesions in the subcortical region to deep white matter, which were different from those found in MS and AQP4-Ab-positive NMOSD and were consistent with the characteristics of brain lesions in MOG-Ab-positive ADS, including other disease types.

Clinical and imaging characteristics of pediatric neuromyelitis optica spectrum disorders

Objective To analyze the clinical and imaging characteristics of pediatric neuromyelitis optica spectrum disorders(NMOSD) in children. Methods The clinical data, imaging manifestations and follow-up data of 16 NMOSD patients at Department of Pediatric Neurology, Shandong Provincial Hospital Affiliated to Shandong University between July 2013 and September 2017 were respectively analyzed. Results In 16 patients, initial presentations included optica neuritis(ON) in 5 cases, longitudinally extensive transverse myelitis(LETM) in 6 cases, and among them there were 2 cases with acute disseminated encephalomyelitis and 3 cases with both ON and LETM. Eleven cases received aquaporin-4(AQP4) antibody examination and 4 cases were found seropositive.One case out of 7 detected cases was found AQP4 antibody positive in cerebrospinal fluid.Eleven cases received optica magnetic resonance imaging (MRI), and 8 cases were found abnormal signals in optic nerve and optica chiasma.The spinal cord MRI showed 13 cases with LETM manifestations, and abnormal signals were found in vertebral segments(5-13), and among them 1 case had cervical cord, 3 cases were thoracic cord and 9 cases were both of the above.Lesions in the cervical cord in 2 cases were extended upward to the medulla.Fifteen cases received brain MRI and all of them had brain lesions, which were mainly involved in the central and subcortical white matter, thalamus, corpus callosum, brainstem, the junction of spinal cord and medulla, cerebellum, and so on.All patients received treatment for acute attacks with high-dose Methylprednisolone and/or gamma globulin and got obvious relief.Two cases with recurrent ON received treatment of Rituximab and their vision became improved.Fifteen patients were followed up, and 2 cases had limb disorders and 4 cases had visual impairment, other patients had no clinical symptoms. Conclusions Pediatric NMOSD has a diverse clinical pre-sentation at the onset disease.Those who are initial diagnosed acute myelitis, ON and acute disseminated encephalomyelitis should be considered the possibility of NMOSD.Antibody to AQP4 testing can assist the diagnosis.The typical imaging characters of NMOSD children are abnormal signals in the high expression area of AQP4.Intracranial lesions are more common in children.The acute treatment includes the high-dose Methylprednisolone and gamma globulin.Rituximab can be used for the recurrent patients. Key words: Neuromyelitis optica spectrum disorders; Aquaporin-4; Child

Pediatric-onset multiple sclerosis in Brazilian patients: Clinical features, treatment response and comparison to pediatric neuromyelitis optica spectrum disorders

BackgroundMultiple Sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are acquired demyelinating syndromes of the central nervous system more frequently in young adults and their beginning before 18 years of age is rare. They are autoimmune diseases with distinct pathophysiology, clinical presentation, treatment and prognoses. During childhood these conditions often present similar clinical features and differential diagnosis among pNMOSD, pMS and acute disseminated encephalomyelitis (ADEM) is still difficult at disease onset. The aim of this article is to describe the epidemiologic and clinical features, to evaluate the response to treatment and to compare the mains characteristics between the patients with MS and NMOSD who had the first event prior to 18 years of age followed at the Universidade Federal de São Paulo (UNIFESP). MethodsRetrospective analysis of patients with MS and NMOSD who started the disease before 18 years of age followed for at UNIFESP. All patients fulfilled the McDonald 2010 criteria for MS and the IPND 2015 criteria or 2006 diagnostic criteria for NMOSD. For treatment analysis, we select patients with a follow-up of more than 6 months. ResultsSixty-eight patients fulfilled the inclusion criteria for MS and were selected for analysis. Mean age of onset was 15 years, 73.5% were female and the mean follow-up was 6.7 years. Mean annualized relapse rate (aRR) observed was 0,82 relapse/year and mean progression index (PI) was 0.31 EDSS points/year. The multivariate analysis showed a significant association between the EDSS on first appointment and total number of relapses with neurological disabilities in long term in patients with MS. The treatment with interferon-beta (IFN-β) and glatiramer acetate (GA) was safe and patients treated with high dose IFN-β and GA had a statistically significant reduction in disability progression. Eleven patients fulfilled the inclusion criteria for NMOSD: mean age of onset was 14 years, 72.7% were female and the mean follow-up was 6.3 years. Mean aRR observed was 1.5 relapse/year and mean PI was 2.2 EDSS points/year. The treatment with azathioprine was safe and significant halts disability progression. Patients with NMOSD reached EDSS 6 prior than those with MS. ConclusionsPediatric demyelinating diseases in Brazil are similar to the diseases described abroad. In patients with pMS, the EDSS score at the first appointment and the total number of relapses were associated with poor prognosis. NMOSD is more severe than MS in pediatric patients. Treatment with DMD and azathioprine was well tolerated and effective in reducing relapse rate and disability.

“These Cases Are So Dramatic That They Could Never Be Overlooked:” A History of Pediatric Neuromyelitis Optica (S39.005)

“These Cases Are So Dramatic That They Could Never Be Overlooked:” A History of Pediatric Neuromyelitis Optica (S39.005)

Diagnostic Challenges in Pediatric Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

AbstractThis review highlights the most common presentations of demyelination of the central nervous system (CNS, termed acquired demyelinating syndrome) in children, the difficulty in determining whether the first episode represents a monophasic/transient illness or relapsing disease, and the potential underlying etiologies that must be considered, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and disorders associated with antibodies to myelin oligodendrocyte glycoprotein (MOG) antibodies. The initial clinical and magnetic resonance imaging (MRI) features, as well as those observed over time, are highlighted, emphasizing the distinct and overlapping features of each of these disorders.

Acute Inpatient Rehabilitation Management of Spinal Cord Injury in Pediatric Neuromyelitis Optica

Acute Inpatient Rehabilitation Management of Spinal Cord Injury in Pediatric Neuromyelitis Optica

Environmental and genetic factors in pediatric inflammatory demyelinating diseases.

The onset of multiple sclerosis (MS) occurs in childhood in about 5% of all patients with MS. The disease in adults has a complex genetic and environmental inheritability. One of the main risk factors, also confirmed in pediatric MS, is HLA DRB1*1501 In addition to genetic factors, a large part of disease susceptibility in adults is conferred by environmental risk factors such as low vitamin D status, exposure to cigarette smoking, and remote Epstein-Barr virus (EBV) infection. In children, both exposure to cigarette smoking and prior EBV infection have been reported consistently as risk factors for MS. The role of vitamin D remains to be confirmed in this age category. Finally, although very likely critical in disease processes, few gene-environment interactions and epigenetic changes have been reported for adult and pediatric MS susceptibility. Of interest, some of the risk factors for MS have also been associated with disease course modification, such as low 25(OH) vitamin D serum levels in pediatric and adult MS. Age is also a clear disease modifier of clinical, CSF, and MRI phenotype in children with the disease. Finally, although much has yet to be unraveled regarding molecular processes at play in MS, there is a larger gap in our knowledge of genetic and environmental risk factors for pediatric neuromyelitis optica spectrum disorders and acute disseminated encephalomyelitis and only collaborative studies will answer those questions.

Rituximab monitoring and redosing in pediatric neuromyelitis optica spectrum disorder.

Objective:To study rituximab in pediatric neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD) and the relationship between rituximab, B cell repopulation, and relapses in order to improve rituximab monitoring and redosing.Methods:Multicenter retrospective study of 16 children with NMO/NMOSD receiving ≥2 rituximab courses. According to CD19 counts, events during rituximab were categorized as “repopulation,” “depletion,” or “depletion failure” relapses (repopulation threshold CD19 ≥10 × 106 cells/L).Results:The 16 patients (14 girls; mean age 9.6 years, range 1.8–15.3) had a mean of 6.1 events (range 1–11) during a mean follow-up of 6.1 years (range 1.6–13.6) and received a total of 76 rituximab courses (mean 4.7, range 2–9) in 42.6-year cohort treatment. Before rituximab, 62.5% had received azathioprine, mycophenolate mofetil, or cyclophosphamide. Mean time from rituximab to last documented B cell depletion and first repopulation was 4.5 and 6.8 months, respectively, with large interpatient variability. Earliest repopulations occurred with the lowest doses. Significant reduction between pre- and post-rituximab annualized relapse rate (ARR) was observed (p = 0.003). During rituximab, 6 patients were relapse-free, although 21 relapses occurred in 10 patients, including 13 “repopulation,” 3 “depletion,” and 4 “depletion failure” relapses. Of the 13 “repopulation” relapses, 4 had CD19 10–50 × 106 cells/L, 10 had inadequate monitoring (≤1 CD19 in the 4 months before relapses), and 5 had delayed redosing after repopulation detection.Conclusion:Rituximab is effective in relapse prevention, but B cell repopulation creates a risk of relapse. Redosing before B cell repopulation could reduce the relapse risk further.Classification of evidence:This study provides Class IV evidence that rituximab significantly reduces ARR in pediatric NMO/NMOSD. This study also demonstrates a relationship between B cell repopulation and relapses.