title: Immunopathophysiology of pediatric CNS inflammatory demyelinating diseases.
abstract: Elucidating pathophysiologic mechanisms underlying the spectrum of pediatric-onset CNS demyelinating diseases, particularly those that may distinguish multiple sclerosis (MS) from other entities, promises to both improve diagnostics and guide more-informed therapeutic decisions. Observations that pediatric- and adult-onset MS share the same genetic and environmental risk factors support the view that these conditions represent essentially the same illness manifesting at different ages. Nonetheless, special consideration must be given when CNS inflammation manifests in early life, at a time when multiple organs (including immune and nervous systems) are actively maturing. CSF analysis in pediatric-onset MS points to chronic CNS inflammation, supported by observations from limited pathologic material available for study. Emerging results implicate abnormalities in both effector and regulatory T cell subsets, and potentially immune senescence, in children with MS. Although CNS-directed antibodies (including antibodies recognizing myelin antigens; Kir4.1) can be documented in pediatric-onset MS, their pathophysiologic significance (as in adults) remains unclear. This is in contrast to the presence of serum and/or CSF antibodies recognizing aquaporin-4, which, when measured using validated cell-based assays, supports the diagnosis of a neuromyelitis optica spectrum disorder, distinct from MS. Presence of anti-myelin oligodendrocyte glycoprotein antibodies documented with similar cell-based assays may also be associated with pathophysiologically distinct disease phenotypes in children. The substantial impact of pediatric-onset MS on normal brain development and function underscores the importance of elucidating both the immunobiology and neurobiology of disease. Ongoing efforts are aimed at developing and validating biological measures that define pathophysiologically distinct monophasic and chronic forms of pediatric CNS demyelination.
authors: From the Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; Department of Neurology (R.Q.H.), MS Centre ErasMS, Neurology, Erasmus MC, Rotterdam, the Netherlands; Neuroimmunology Group (R.C.D.), Institute for Neuroscience and Muscle Research, the Children's Hospital at Westmead, University of Sydney, Australia; Department of Pediatric Neurology (K.R.), Witten/Herdecke University, Children's Hospital Datteln, Datteln, Germany; Department of Neuropathology (W.B.), University Medical Center Göttingen, Georg-August-University, Göttingen, Germany; and Partners Pediatric MS Center (T.C.), Massachusetts General Hospital, Harvard Medical School, Boston, MA. amit.bar-or@mcgill.ca.
authors: Amit
authors: A
authors: Bar-Or
authors: From the Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; Department of Neurology (R.Q.H.), MS Centre ErasMS, Neurology, Erasmus MC, Rotterdam, the Netherlands; Neuroimmunology Group (R.C.D.), Institute for Neuroscience and Muscle Research, the Children's Hospital at Westmead, University of Sydney, Australia; Department of Pediatric Neurology (K.R.), Witten/Herdecke University, Children's Hospital Datteln, Datteln, Germany; Department of Neuropathology (W.B.), University Medical Center Göttingen, Georg-August-University, Göttingen, Germany; and Partners Pediatric MS Center (T.C.), Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors: Rogier Q
authors: RQ
authors: Hintzen
authors: From the Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; Department of Neurology (R.Q.H.), MS Centre ErasMS, Neurology, Erasmus MC, Rotterdam, the Netherlands; Neuroimmunology Group (R.C.D.), Institute for Neuroscience and Muscle Research, the Children's Hospital at Westmead, University of Sydney, Australia; Department of Pediatric Neurology (K.R.), Witten/Herdecke University, Children's Hospital Datteln, Datteln, Germany; Department of Neuropathology (W.B.), University Medical Center Göttingen, Georg-August-University, Göttingen, Germany; and Partners Pediatric MS Center (T.C.), Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors: Russell C
authors: RC
authors: Dale
authors: From the Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; Department of Neurology (R.Q.H.), MS Centre ErasMS, Neurology, Erasmus MC, Rotterdam, the Netherlands; Neuroimmunology Group (R.C.D.), Institute for Neuroscience and Muscle Research, the Children's Hospital at Westmead, University of Sydney, Australia; Department of Pediatric Neurology (K.R.), Witten/Herdecke University, Children's Hospital Datteln, Datteln, Germany; Department of Neuropathology (W.B.), University Medical Center Göttingen, Georg-August-University, Göttingen, Germany; and Partners Pediatric MS Center (T.C.), Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors: Kevin
authors: K
authors: Rostasy
authors: From the Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; Department of Neurology (R.Q.H.), MS Centre ErasMS, Neurology, Erasmus MC, Rotterdam, the Netherlands; Neuroimmunology Group (R.C.D.), Institute for Neuroscience and Muscle Research, the Children's Hospital at Westmead, University of Sydney, Australia; Department of Pediatric Neurology (K.R.), Witten/Herdecke University, Children's Hospital Datteln, Datteln, Germany; Department of Neuropathology (W.B.), University Medical Center Göttingen, Georg-August-University, Göttingen, Germany; and Partners Pediatric MS Center (T.C.), Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors: Wolfgang
authors: W
authors: Brück
authors: From the Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; Department of Neurology (R.Q.H.), MS Centre ErasMS, Neurology, Erasmus MC, Rotterdam, the Netherlands; Neuroimmunology Group (R.C.D.), Institute for Neuroscience and Muscle Research, the Children's Hospital at Westmead, University of Sydney, Australia; Department of Pediatric Neurology (K.R.), Witten/Herdecke University, Children's Hospital Datteln, Datteln, Germany; Department of Neuropathology (W.B.), University Medical Center Göttingen, Georg-August-University, Göttingen, Germany; and Partners Pediatric MS Center (T.C.), Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors: Tanuja
authors: T
authors: Chitnis
mesh_terms: D017668:Age of Onset; D020278:Demyelinating Autoimmune Diseases, CNS / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D043025:Oligoclonal Bands / Q000134:cerebrospinal fluid; D010372:Pediatrics; D050378:T-Lymphocytes, Regulatory / Q000473:pathology
chemical_list: D043025:Oligoclonal Bands