Pediatric Neuromyelitis Optica Spectrum Disorders

Gombolay, Grace; Chitnis, Tanuja

doi:10.1007/s11940-018-0502-9

Cited by 34 publications

(17 citation statements)

References 91 publications

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“…Our ESPED inquiry also revealed that in five patients (4/5 were excluded from this study) no antibody testing was done at all. As antibody status could have had important diagnostic and therapeutic implications considering the disabling potential of relapses in AQP4-ab positive NMOSD, we strongly encourage pediatric neurologists to screen for MOG-and AQP4-abs in pediatric patients with ADS (32,48). Furthermore, this lack of information should lead to the creation of better guidelines, facilitating diagnosis and therapy of pediatric ADS patients, which should be disseminated among physicians caring for children in particular with NMOSD.…”

Section: Discussionmentioning

confidence: 99%

“…The reported prevalence of MOG-abs in AQP4-ab negative pediatric patients shows a wide range between different working groups, possibly due to different inclusion criteria and unreported MOGab status. Consequently, in some studies the majority of NMOSD patients show MOG-abs while others report similar frequencies of AQP4-abs in pediatric as in adult patients (23,(29)(30)(31)(32).…”

Section: Introductionmentioning

confidence: 95%

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Epidemiology of Pediatric NMOSD in Germany and Austria

et al. 2020

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Background: Neuromyelitis optica spectrum disorders (NMOSD) are severe inflammatory demyelinating disorders of the central nervous system mainly characterized by recurrent episodes of uni-or bilateral optic neuritis (ON), transverse myelitis (TM) and brainstem syndromes (BS). The majority of adult patients has serum antibodies directed against the water channel protein aquaporin 4 (AQP4-abs). In pediatric patients, AQP4-abs are less, while antibodies against myelin oligodendrocyte glycoprotein (MOG-abs) are more frequently detectable than in adults. Some children with NMOSD have neither AQP4-nor MOG-ab (double-seronegative). Objective: Evaluation of epidemiological data regarding incidence and prevalence of pediatric NMOSD in Germany and Austria. Methods: We recruited pediatric NMOSD patients between 1 March 2017 and 28 February 2019 with five different tools: (1) ESPED (Surveillance Unit for Rare Pediatric Disorders in Germany), (2) ESNEK (Surveillance for Rare Neurological Disorders during Childhood), (3) pediatric neurology working group within the Austrian Society of Pediatrics and Adolescent Medicine, (4) BIOMARKER Study and (5) NEMOS (Neuromyelitis optica Study Group). We requested data regarding clinical symptoms, antibody status, therapy regimen and response via a standardized questionnaire. Results: During the 2-year recruitment period, 46 (both incidental and prevalent) patients with a suspected diagnosis of NMOSD were brought to our attention. Twenty-two of these patients did not fulfill the inclusion criteria. Of the remaining 24 children, 22 had a median age at onset of 11 (range 3-17) years and 16/22 were female (72.7%) (no data in two patients). Sixteen of 24 patients were AQP4-ab positive (67%), 4/24 MOG-ab positive (16.7%), three children were double-seronegative and in one patient no antibody testing was done. We calculated an incidence rate of 0.022 per 100,000 person-years for Germany, while there was no incidental case in Austria during the recruitment period. The prevalence rate was 0.147 and 0.267 per 100,000 persons in Germany and Austria, respectively. Lechner et al. Epidemiology of Pediatric NMOSD Conclusion: Pediatric NMOSD, with and without associated antibodies, are very rare even considering the different limitations of our study. An unexpected finding was that a considerable proportion of patients was tested neither for AQP4-nor MOGabs during diagnostic work-up, which should prompt to establish and disseminate appropriate guidelines.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Epidemiology of Pediatric NMOSD in Germany and Austria

et al. 2020

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“…In this respect, the correlation between anti-NMDAR antibodies and clinical course is unclear, 64 while there is some correlation of CXCL13 and disease severity and relapse 65e67 that may be useful in guiding treatment. Data on doses in our literature review was limited; commonly used doses of steroid sparers in paediatric neurology are 600 mg/m 2 twice a day (maximum 1000 mg twice a day) for mycophenolate mofetil, 2e3 mg/kg/ day for azathioprine, 68 and 10 mg/m 2 /week for oral methotrexate. 30…”

Section: Modes Of Use Of Steroid Sparing Agentsmentioning

confidence: 99%

“…In general, some adverse reactions are common to mycophenolate mofetil, azathioprine and methotrexate, and include gastrointestinal symptoms (abdominal pain, diarrhoea, vomiting), myelosuppression with increased risk of infections, and hepatotoxicity with elevation of liver enzymes. 68,74,75 Steroid sparing agents should be used very cautiously in women of childbearing age. 74,75 Mycophenolate mofetil and azathioprine carry an increased risk of malignancies, particularly lymphoproliferative disorders and nonmelanoma skin cancers for azathioprine.…”

Section: Safetymentioning

confidence: 99%

Mycophenolate mofetil, azathioprine and methotrexate usage in paediatric anti-NMDAR encephalitis: A systematic literature review

Nosadini

Mohammad

Toldo

et al. 2019

European Journal of Paediatric Neurology

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Background: Available data on mycophenolate mofetil (MMF), azathioprine (AZA) and methotrexate (MTX) for paediatric-onset anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) is limited. Methods: Systematic literature review on patients treated with MMF/AZA/MTX for paediatric-onset anti-NMDARE, with focus on modes of use, efficacy and safety. Results: 87 patients were included (age at onset median 11 years, range 0.8e18 years; 69% females). 46% had a relapsing course. 52% received MMF, 27% AZA, 15% MTX, and 6% a combination of MMF/AZA/MTX (7 patients received intrathecal MTX). Before MMF/AZA/ MTX, 100% patients received steroids, 83% intravenous immunoglobulin and 45% plasma exchange, and 50% received second-line treatments (rituximab/cyclophosphamide). MMF/ AZA/MTX were administered >6 months from onset in 51%, and only after relapse in 40%. Worst mRS before MMF/AZA/MTX was median 4.5 (range 3e5). At last follow-up (median 2 years, range 0.2e8.6), median mRS was 1 (range 0e6). Median annualised relapse rate was 0.4 (range 0e6.7) pre-MMF/AZA/MTX (excluding first events), and 0 on MMF/AZA/ MTX (mean 0.03, range 0e0.8). 7% patients relapsed on MMF/AZA/MTX. These relapsing patients had low rate of second-line treatments before MMF/AZA/MTX (25%), long median time between onset and MMF/AZA/MTX usage (18 months), and frequently they were started on MMF/AZA/MTX only after relapse (75%). Relapse rate was lower among patients who received first immune therapy 30 days (25%) than later (64%), who received second-line treatments at first event (14%) rather than

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“…The 20 MOG-AAD patients had the following diagnoses at the time of sample collection according to International Pediatric MS Study Group diagnostic criteria: 7 with MS, 7 with ADEM-ON, 1 with multiphasic ADEM, 1 with ADEM-TM, 1 with CIS, 1 with a demyelinating neurological disorder and 2 with NMO-SD 48 . Patients were diagnosed with NMO-SD if presenting with ON, TM and at least two of these 3 criteria: MRI evidence of a continuous spinal cord lesion, brain MRI that was non-diagnostic of MS, and NMO IgG seroposivity 48,49 . Out of the 20 MOG-AAD patients, 15 patients had longitudinal samples, including treated/untreated and relapse/non-relapse samples.…”

Section: Methodsmentioning

confidence: 99%

Identification of TNFAIP3 as relapse biomarker and potential therapeutic target for MOG antibody associated diseases

Saxena

Lokhande

Gombolay

et al. 2020

Sci Rep

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MOG-antibody associated disease (MOG-AAD) is a recently recognized demyelinating disorder predominantly affecting children but also occurs in adults, with a relapsing course in approximately 50% of patients. We evaluated peripheral blood mononuclear cells from MOG-AAD patients by flow cytometry and found a strong antigen specific central memory cell (CMC) response with increased Th1 and Th17 cells at the time of a relapse. Transcriptomic analysis of CMCs by three independent sequencing platforms revealed TNFAIP3 as a relapse biomarker, whose expression was down regulated at a relapse compared to remission in MOG-AAD patients. Serum in an additional cohort of patients showed decreased TNFAIP3 levels at relapse compared to remission state in MOG-AAD patients. Our studies suggest that alterations in TNFAIP3 levels are associated with relapses in MOG-AAD patients, which may have clinical utility as a disease course biomarker and therapeutic target.

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Pediatric Neuromyelitis Optica Spectrum Disorders

Cited by 34 publications

References 91 publications

Epidemiology of Pediatric NMOSD in Germany and Austria

Epidemiology of Pediatric NMOSD in Germany and Austria

Mycophenolate mofetil, azathioprine and methotrexate usage in paediatric anti-NMDAR encephalitis: A systematic literature review

Identification of TNFAIP3 as relapse biomarker and potential therapeutic target for MOG antibody associated diseases

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