Acquired Demyelinating and Other Autoimmune Disorders of the Central Nervous System in Children

Abstract

Over the past 5 years, our knowledge has been significantly enhanced in the field of immune-mediated inflammatory disorders of central nervous system in children. These exciting developments along with identification of novel autoimmune markers have provided new diagnostic approaches and, more important, have led to appropriate immunotherapy to halt disease progression and prevent relapses. Recognition of immune-mediated disorders of the central nervous system is important because these disorders are highly responsive to immunotherapy. We child neurologists have been introduced to several novel agents of immunotherapy (both immunomodulatory and immunosuppresive) for the management of immunemediated inflammation. Pediatric multiple sclerosis and other immune-mediated demyelinating disorders of the central nervous system in children are increasingly recognized in recent years in the United States and worldwide. An estimated 3% to 10% of all patients with multiple sclerosis have onset before the age of 18 years. Pediatric multiple sclerosis is rare, but it has a profound impact on the health of young children and adolescents. As a result of developing this disorder at an early age, individuals reaching any given level of impairment will be younger than individuals with adult-onset disease. The autoimmune inflammatory demyelinating disorders of the central nervous system represent a broad spectrum of conditions that vary in their clinical course, regional distribution within the central nervous system, and prognosis. Many features overlap among these various disorders: multiple sclerosis, acute disseminated encephalomyelitis, and neuromyelitis optica (Devic’s disease), as well as optic neuritis, acute transverse myelitis, and other clinically isolated syndromes. At this time only neuromyelitis optica has a specific diagnostic marker, resulting in diagnoses being made by clinical and paraclinical tools. The spectrum of childhood acquired demyelinating syndromes has been extensively described and diagnostic criteria have been proposed by the International Pediatric Multiple Sclerosis Study Group (IPMSSG) in 2007. These consensus definitions provided diagnostic criteria for pediatric multiple sclerosis, acute disseminated encephalomyelitis, neuromyelitis optica, and clinically isolated syndromes of childhood. The consensus definitions by the IPMSSG help to minimize the risk of inconsistency in diagnosis, identify the patients with high risk of multiple sclerosis, and provide a platform for future research and clinical trials. Since the dissemination of these diagnostic criteria in 2007, knowledge in the field has expanded significantly, and excellent review articles published in the past 5 years provide guidance for the diagnosis and care of these children. Several pediatric cohort studies using the consensus definitions have provided data on the long-term outcomes of children presenting with the first demyelinating event. Furthermore, the International Study Group has expanded as an organization with increasing numbers of members worldwide. Through the efforts of IPMSSG, systematic multicenter therapeutic trials in children with acquired demyelinating disorders are now under way for the first time. In the light of these developments and the expanding knowledge in the field of childhood acquired demyelinating disorders, this special issue of the Journal of Child Neurology is devoted to pediatric autoimmune inflammatory disorders of central nervous system, including both demyelinating and nondemyelinating conditions. I would like to express my sincere appreciation to the authors who participated in this issue and provided the most updated and comprehensive reviews on their topics. The first 6 articles cover the acquired demyelinating syndromes in children. In the first article, Bigi and Banwell provide an overview of the childhood multiple sclerosis including clinically isolated syndromes, neurocognitive prognosis of childhood multiple sclerosis, environmental risk factors, and differential diagnosis. The management of childhood multiple sclerosis is reviewed separately in the article written by Yeh