Autoimmune Diseases of the Central Nervous System in Childhood

The pathogenesis, classification, diagnosis, treatment, and prognosis of inflammatory diseases of the central nervous system (CNS) in children have evolved over the last decade owing to improved access to neuroimaging, international consensus on diagnostic criteria, and recognition of pathogenic antibodies and other biological markers. These advances have enabled earlier and more precise diagnoses.

Many of the neuroinflammatory diseases manifest with distinct features in children, relative to those observed in adults, with the clinical course and outcome shaped by the inflammatory insult to the developing brain. As an example, pediatric patients with multiple sclerosis (MS) experience more frequent clinical relapses,[1] [2] a greater burden of infratentorial lesions, and an overall higher brain lesion volume when compared to patients with adult-onset MS, matched for disease duration.[3] [4] Furthermore, it is recognized that magnetic resonance imaging (MRI) features of inflammation in the pediatric brain differ from the inflammatory disease expression in the adult CNS.

Current research focuses on immunological assays that interrogate the balance of effector and regulatory T cells and define antibody signatures present within pediatric neuroimmune as well as adult-onset disorders (with foreknowledge that pediatric patients are much less likely to have a paraneoplastic etiology).

This special issue was created to extensively encompass the spectrum of pediatric neuroinflammatory diseases. Broadly, acquired demyelinating syndromes are reviewed with specific focus on diagnostic considerations, standardized evaluations, and individualized risk assessments for recurrent or relapsing disease. Relapsing neuroimmune disorders are then discussed in detail, with a focus on MS and neuromyelitis optica spectrum disorders (NMOSDs). Current knowledge of pediatric MS risk, as defined by genetic features and environmental exposures, is covered in the next chapter. Therapy for MS and NMOSD, as well as the management of acute attacks, is then reviewed with a focus on the exciting new arena of clinical trials. Safety of current immunotherapies is also discussed, with an emphasis on the special treatment considerations in a pediatric population.

The next chapter focuses on the expanding field of antibody-mediated encephalitis found in children. With the rise in identification of these disorders, autoimmune-mediated encephalitis cases have now surpassed individual viral etiologies.[5] Following this, we provide a detailed chapter focused on systemic inflammatory conditions that can affect the CNS and mimic primary CNS inflammation.

While the clinical features and examination remain the cornerstone of diagnosis, advances in standardized neuroimaging protocols and the development of sequences that interrogate brain microstructure are now pivotal for diagnosis, prognosis, and research. A dedicated chapter in this edition discusses the role of neuroimaging in the diagnostic evaluation of children with primary and secondary inflammatory diseases of the CNS.

This special issue on Autoimmune Neurological Disorders in Childhood is timely given the rapid growth of this subspecialty. The success of this compilation is entirely attributed to the work of all contributors and international authorities who composed the manuscripts. This collaborative effort signifies the growing diversity of our field and the collective value of our varied backgrounds. Given the relative rarity and variety of the diseases discussed, national and international collaborative efforts must continue to fill the gaps in our current knowledge of underlying pathobiology, diagnostic considerations, treatment approaches, and long-term outcomes.

• References

• 1 Benson LA, Healy BC, Gorman MP. , et al. Elevated relapse rates in pediatric compared to adult MS persist for at least 6 years. Mult Scler Relat Disord 2014; 3 (02) 186-193
• 2 Gorman MP, Healy BC, Polgar-Turcsanyi M, Chitnis T. Increased relapse rate in pediatric-onset compared with adult-onset multiple sclerosis. Arch Neurol 2009; 66 (01) 54-59
• 3 Ghassemi R, Narayanan S, Banwell B, Sled JG, Shroff M, Arnold DL. ; Canadian Pediatric Demyelinating Disease Network. Quantitative determination of regional lesion volume and distribution in children and adults with relapsing-remitting multiple sclerosis. PLoS One 2014; 9 (02) e85741
• 4 Verhey LH, Signori A, Arnold DL. , et al. Clinical and MRI activity as determinants of sample size for pediatric multiple sclerosis trials. Neurology 2013; 81 (14) 1215-1221
• 5 Gable MS, Sheriff H, Dalmau J, Tilley DH, Glaser CA. The frequency of autoimmune N-methyl-D-aspartate receptor encephalitis surpasses that of individual viral etiologies in young individuals enrolled in the California Encephalitis Project. Clin Infect Dis 2012; 54 (07) 899-904