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Review Multiple Sclerosis Management of Children with Multiple Sclerosis Anusha K Yeshokumar and Brenda Banwell Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, US T he care of children and adolescents with multiple sclerosis (MS) requires appreciation of the impact of the disease on the developing brain and, in particular, the risk for cognitive impairment and academic challenges. Relapse rates in the first three years from onset are high, with an average of 1.5 relapses per year, and often require hospitalization for acute corticosteroid therapy. Disease modulatory therapies are typically prescribed, although formal clinical trials in the pediatric MS population are only just now being realized. In this review, we discuss strategies to optimize therapy for an individual child or teenager, including utilization of a multidisciplinary approach to care. Keywords Pediatric multiple sclerosis, immunomodulation, safety, efficacy, relapse, treatment Disclosure: Anusha K Yeshokumar has no relevant conflicts of interest to declare. Brenda Banwell has received remuneration for work as a central MRI reviewer for Novartis. No funding was received in the publication of this article. Compliance with Ethics: This study involves a review of the literature and did not involve any studies with human or animal subjects performed by any of the authors. Authorship: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit. Received: December 19, 2016 Accepted: February 7, 2017 Citation: US Neurology, 2017;13(1):42–6 Corresponding Author: Anusha K Yeshokumar, Division of Child Neurology, Children's Hospital of Philadelphia, Colket Translational Research Building, 10th Floor, 35th Street and Civic Center Boulevard, Philadelphia, PA 19104-4399, US. E: yeshokumaa@email.chop.edu Multiple sclerosis (MS) onset during childhood or adolescence follows a relapsing-remitting pattern, with a high early relapse frequency, and is associated with a risk for cognitive impairment and future physical disability. Acute management of relapses, modulation of chronic disease course, cognitive evaluations and strategies for academic modifications, and multidisciplinary team approaches to the management of fatigue, bladder issues, and coping and emotional health are also key components of care. While the vast majority of MS patients experience onset in adulthood, up to 10% of patients experience symptom onset prior to 18 years of age. 1,2 Relapses in pediatric MS patients, including the sentinel first “attack,” are characterized by optic neuritis, transverse myelitis, brainstem syndromes, or rarely, an acute disseminated encephalomyelitis- (ADEM) like (encephalopathy and polyfocal deficits) syndrome. By definition, an individual attack is defined by a new neurological deficit persisting more than 24 hours, and not better explained by another etiology, and occurring more than 30 days from the last recorded attack. 3 MS diagnosis is confirmed by recurrent attacks and supported by magnetic resonance imaging (MRI) evidence for new lesions involving different regions of the central nervous system (CNS). The 2010 McDonald MS diagnostic criteria also allow for diagnosis to be made at the time of the first acute demyelinating attack if MRI demonstrates clinically silent lesions in two of the four regions typical for MS, at least one of which enhances with gadolinium. 4 Application of the 2010 McDonald MS diagnostic criteria at the time of a first attack in a pediatric cohort requires consideration of the patient’s age. When applied to patients over the age of 11, the criteria very accurately identify children who later experience further MS attacks. Children who do not demonstrate the MRI features described in the 2010 McDonald criteria did not experience further disease and were not diagnosed with MS. 5 In younger children, however, lesions are typically larger with less well-defined margins and may completely resolve. 6,7 The positive predictive value of the 2010 McDonald criteria at the time of a first attack is only 55%, and thus caution must be used in applying the criteria in this age group, often requiring evidence of new disease over time on serial clinical and MRI examinations before confirming MS. 8 Of note, a normal brain MRI at the time of a first demyelinating attack (in presentations of optic neuritis or transverse myelitis) strongly suggests a monophasic illness, with less than 3% of such children being diagnosed with MS over time. 9 Over 90% of patients will experience near complete neurological recovery from relapses early in the disease. 10 However, secondary disease progression, in which accrual of neurological disability occurs independent of relapses, may occur over time. While pediatric MS patients may take longer to develop secondary disease progression, they do so at a younger age than patients with onset in adulthood. 11 Fundamental to the diagnosis of MS is the exclusion of other diagnoses. Progressive symptoms from onset would not be typical of the relapsing-remitting course seen in over 97% of pediatric MS patients and should lead to consideration of leukodystrophies, mitochondrial disease, compressive 42 TOUCH ME D ICA L ME D IA