Pediatric Acquired Demyelinating Disorders

Abstract

PURPOSE OF REVIEW: This article reviews the clinical presentation, diagnostic evaluation, treatment, and prognosis of the most common monophasic and relapsing acquired demyelinating disorders presenting in childhood.RECENT FINDINGS: Our understanding of neuroimmune disorders of the central nervous system is rapidly expanding. Several clinical and paraclinical factors help to inform the diagnosis and ultimately the suspicion for a monophasic versus relapsing course, including the age of the patient (prepubertal versus postpubertal), presence or absence of clinical encephalopathy, identification of serum autoantibodies (eg, myelin oligodendrocyte glycoprotein [MOG] and aquaporin-4), presence of intrathecally unique oligoclonal bands, and location/extent of radiologic abnormalities. Collaborative international research efforts have facilitated understanding of the safety and efficacy of currently available immunotherapies in children with acquired demyelinating disorders, particularly multiple sclerosis.SUMMARY: Although many of the demyelinating disorders presented in this article can affect children and adults across the age spectrum, the clinical and radiologic phenotypes, treatment considerations, and long-term prognoses are often distinct in children.

Acquired Demyelinating Syndromes of the Central Nervous System in Children: The Importance of Regular Follow-up in the First Year After Onset

“…In our sample, during the follow-up period, 33% of patients had a change in the initial diagnosis and evolved toward multiple sclerosis, concordantly with the literature: it is reported that 15% to 46% of children presenting with acquired demyelinating syndromes will be diagnosed with multiple sclerosis after 5 years' follow-up. 1,2 In line with current scientific knowledge, patients initially diagnosed with clinical isolated syndrome had a higher rate of diagnosis evolution toward multiple sclerosis at T12 than patients diagnosed with acute disseminated encephalomyelitis. Moreover, being females, with higher age at onset, with demyelination in more than 1 central nervous system area and with oligoclonal bands in cerebrospinal fluid were predicting factors of evolution toward multiple sclerosis.…”

“…Moreover, being females, with higher age at onset, with demyelination in more than 1 central nervous system area and with oligoclonal bands in cerebrospinal fluid were predicting factors of evolution toward multiple sclerosis. 1,9 It is described that less than 10% of children with acute disseminated encephalomyelitis will experience a second demyelinating attack more than 3 months after the sentinel attack, and the majority of patients who relapse exhibit evidence of MOG antibodies. 21 Pediatric multiple sclerosis typically has a higher relapse rate in the early years after diagnosis compared with adult cohorts, and there is a shorter interval between the incident attack and a second demyelinating event.…”

“…Pediatric acquired demyelinating syndromes (ADS) are a group of immune-mediated inflammatory events of the central nervous system, with mono-or poly-focal neurologic manifestations, that can have a monophasic or multiphasic course, in the second case representing the sentinel attack of a chronic demyelinating disorder such as multiple sclerosis. 1 Between 15% and 46% of children presenting with acquired demyelinating syndromes will be diagnosed with multiple sclerosis after 5 years' follow-up. 2 The incidence of acquired demyelinating syndromes is between 0.5 and 1.66 per 100 000 childrenm, 2,3 and they are classified into different subtypes based on lesion location and disease time course.…”

“…The most common differential diagnoses are the antibody-mediated disorders (MOG and AQP4 antibodies), acute infections of the central nervous system (such as Epstein-Barr virus, mycoplasma, enteroviruses), inherited leukodystrophies (including Alexander disease, mitochondrial cytopathies, metachromatic leukodystrophy), inflammatory vasculopathies (including systemic lupus erythematosus, primary central nervous system vasculitis, neurosarcoidosis), and idiopathic transverse myelitis and optic neuritis. 1,3 Onset of multiple sclerosis occurs before age 18 years in up to 10% of cases and below the age of 10 years in less than 1%. 4,5 The pooled global incidence of pediatric multiple sclerosis is 0.87 per 100 000 individuals per year.…”

“…This clinical vigilance is important to ensure that patients with a monophasic disorder are not inappropriately placed on chronic immunotherapy and that those who exhibit a propensity for ongoing central nervous system demyelination are classified accurately and treated early. 1,3 In this context, objective of the study was delineating a diagnostic-prognostic protocol to follow patients over time (clinical and radiologic reassessment after 3, 6, and 12 months from the first demyelinating attack) in order to identify as soon as possible evolution toward multiple sclerosis and start precocious disease-modifying treatment. In addition, we tried to assess the presence of potential predictors for developing a relapse in our cohort.…”