MOG-ON and AQP4-ON are more commonly bilateral and longitudinally extensive. MOG-ON tends to involve the anterior optic pathway, whereas AQP4-ON the posterior optic pathway.

This study provides Class IV evidence that in pediatric autoimmune and inflammatory CNS disorders, rituximab improves neurologic outcomes with a 7.6% risk of adverse infections.

Acute disseminated encephalomyelitis (ADEM) is an immune-mediated demyelinating CNS disorder with predilection to early childhood. ADEM is generally considered a monophasic disease. However, recurrent ADEM has been described and defined as multiphasic disseminated encephalomyelitis. ADEM often occurs postinfectiously, although a causal relationship has never been established. ADEM and multiple sclerosis are currently viewed as distinct entities, generally distinguishable even at disease onset. However, pathologic studies have demonstrated transitional cases of yet unclear significance. ADEM is clinically defined by acute polyfocal neurologic deficits including encephalopathy. MRI typically demonstrates reversible, ill-defined white matter lesions of the brain and often also the spinal cord, along with frequent involvement of thalami and basal ganglia. CSF analysis may reveal a mild pleocytosis and elevated protein, but is generally negative for intrathecal oligoclonal immunoglobulin G synthesis. In the absence of a specific diagnostic test, ADEM is considered a diagnosis of exclusion, and ADEM mimics, especially those requiring a different treatment approach, have to be carefully ruled out. The role of biomarkers, including autoantibodies like antimyelin oligodendrocyte glycoprotein, in the pathogenesis and diagnosis of ADEM is currently under debate. Based on the presumed autoimmune etiology of ADEM, the current treatment approach consists of early immunotherapy. Outcome of ADEM in pediatric patients is generally favorable, but cognitive deficits have been reported even in the absence of other neurologic sequelae. This review summarizes the current knowledge on epidemiology, pathology, clinical presentation, neuroimaging features, CSF findings, differential diagnosis, therapy, and outcome, with a focus on recent advances and controversies. Neurology ® 2016;87 (Suppl 2):S38-S45 GLOSSARY ADEM 5 acute disseminated encephalomyelitis; ADEM-ON 5 acute disseminated encephalomyelitis followed by optic neuritis; AHL 5 acute hemorrhagic leukoencephalopathy; IgG 5 immunoglobulin G; IPMSSG 5 International Pediatric Multiple Sclerosis Study Group; MDEM 5 multiphasic disseminated encephalomyelitis; MOG 5 myelin oligodendrocyte glycoprotein; MS 5 multiple sclerosis; NMOSD 5 neuromyelitis optica spectrum disorders; OCB 5 oligoclonal band.Acute disseminated encephalomyelitis (ADEM) is an immune-mediated demyelinating CNS disorder, characterized clinically by new-onset polyfocal neurologic symptoms including encephalopathy, coupled with neuroimaging evidence of multifocal demyelination. ADEM is classically considered a monophasic illness, with highest incidence in early childhood. The first descriptions of an ADEM-like disorder with recognition of a temporal relationship to infections (especially smallpox and measles) date back to the 18th century.1 Over a century later, an association of ADEM with vaccines, notably rabies, was reported. Mortality rates were high (up to 30% for ADEM following measles infection), and neur...

Acute disseminated encephalomyelitis is an immune-mediated inflammatory and demyelinating disorder of the central nervous system, commonly preceded by an infection. It principally involves the white matter tracts of the cerebral hemispheres, brainstem, optic nerves, and spinal cord. Acute disseminated encephalomyelitis mainly affects children. Clinically, patients present with multifocal neurologic abnormalities reflecting the widespread involvement in central nervous system. Cerebrospinal fluid may be normal or may show a mild pleocytosis with or without elevated protein levels. Magnetic resonance image (MRI) shows multiple demyelinating lesions. The diagnosis of acute disseminated encephalomyelitis requires both multifocal involvement and encephalopathy by consensus criteria. Acute disseminated encephalomyelitis typically has a monophasic course with a favorable prognosis. Multiphasic forms have been reported, resulting in diagnostic difficulties in distinguishing these cases from multiple sclerosis. In addition, many inflammatory disorders may have a similar presentation with frequent occurrence of encephalopathy and should be considered in the differential diagnosis of acute disseminated encephalomyelitis.

The aim of this study was to compare the characteristics of the first demyelinating event between acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS). Children with acute demyelinating disease of the central nervous system and an abnormal brain magnetic resonance image (MRI) were studied. Patients were assigned a final diagnosis after long‐term follow‐up. Comparisons were made between the MS and ADEM groups. Proposed definitions by the Pediatric MS Study Group were applied to our cohort in retrospect and are discussed. Fifty‐two children and adolescents with a documented abnormal brain MRI were identified (24 females, 28 males; mean age 10y 11mo [SD 5y 4mo] range 1y 10mo–19y 7mo). To date, 26 children have been diagnosed with MS, and 24 with ADEM. One child has relapsing neuromyelitis optica and one child has clinically isolated optic neuritis. Follow‐up duration was 6 years 8 months in monophasic patients, and 5 years 6 months in relapsing patients. None of the patients with MS had encephalopathy while encephalopathy was present in 42% of patients with ADEM. Cerebrospinal fluid oligoclonal bands, an elevated immunoglobulin and the periventricular perpendicular ovoid lesions correlated with MS outcome. Several clinical characteristics differ between ADEM and MS at first presentation; encephalopathy, when present, strongly suggests the diagnosis of ADEM.

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Background-There is lack of reported MRI studies of idiopathic acute transverse myelitis in children.

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.