Neuromyelitis optica (NMO) is an inflammatory CNS syndrome distinct from multiple sclerosis (MS) that is associated with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). Prior NMO diagnostic criteria required optic nerve and spinal cord involvement but more restricted or more extensive CNS involvement may occur. The International Panel for NMO Diagnosis (IPND) was convened to develop revised diagnostic criteria using systematic literature reviews and electronic surveys to facilitate consensus. The new nomenclature defines the unifying term NMO spectrum disorders (NMOSD), which is stratified further by serologic testing (NMOSD with or without AQP4-IgG). The core clinical characteristics required for patients with NMOSD with AQP4-IgG include clinical syndromes or MRI findings related to optic nerve, spinal cord, area postrema, other brainstem, diencephalic, or cerebral presentations. More stringent clinical criteria, with additional neuroimaging findings, are required for diagnosis of NMOSD without AQP4-IgG or when serologic testing is unavailable. The IPND also proposed validation strategies and achieved consensus on pediatric NMOSD diagnosis and the concepts of monophasic NMOSD and opticospinal MS.

These definitions are proposed for clinical and research purposes. Their utility will depend on the outcomes of their application in prospective research.

Childhood acute disseminated encephalomyelitis is a benign condition, affecting boys more frequently. No association was found between MRI groups and disability. Disability was related to optic nerve involvement at presentation. Even in relapsing cases, the distinction between acute disseminated encephalomyelitis and MS was possible on the basis of long-term clinical and neuroimaging follow-up and the absence of oligoclonal bands in CSF.

CNS inflammatory demyelinating disorders presenting in children and adolescents can be defined and distinguished. However, prospective research is necessary to determine the validity and utility of the proposed diagnostic categories.

Acute disseminated encephalomyelitis (ADEM) is an immune-mediated inflammatory disorder of the CNS characterized by a widespread demyelination that predominantly involves the white matter of the brain and spinal cord. The condition is usually precipitated by a viral infection or vaccination. The presenting features include an acute encephalopathy with multifocal neurologic signs and deficits. Children are preferentially affected. In the absence of specific biologic markers, the diagnosis of ADEM is still based on the clinical and radiologic features. Although ADEM usually has a monophasic course, recurrent or multiphasic forms have been reported, raising diagnostic difficulties in distinguishing these cases from multiple sclerosis (MS). The International Pediatric MS Study Group proposes uniform definitions for ADEM and its variants. We discuss some of the difficulties in the interpretation of available literature due to the different terms and definitions used. In addition, this review summarizes current knowledge of the main aspects of ADEM, including its clinical and radiologic diagnostic features, epidemiology, pathogenesis, and outcome. An overview of ADEM treatment in children is provided. Finally, the controversies surrounding pediatric MS and ADEM are addressed.

Since its initial reports in the 19th century, neuromyelitis optica (NMO) had been thought to involve only the optic nerves and spinal cord. However, the discovery of highly specific antiaquaporin-4 antibody diagnostic biomarker for NMO enabled recognition of more diverse clinical spectrum of manifestations. Brain MRI abnormalities in patients seropositive for anti-aquaporin-4 antibody are common and some may be relatively unique by virtue of localization and configuration. Some seropositive patients present with brain involvement during their first attack and/or continue to relapse in the same location without optic nerve and spinal cord involvement. Thus, characteristics of brain abnormalities in such patients have become of increased interest. In this regard, MRI has an increasingly important role in the differential diagnosis of NMO and its spectrum disorder (NMOSD), particularly from multiple sclerosis. Differentiating these conditions is of prime importance because early initiation of effective immunosuppressive therapy is the key to preventing attack-related disability in NMOSD, whereas some disease-modifying drugs for multiple sclerosis may exacerbate the disease. Therefore, identifying the MRI features suggestive of NMOSD has diagnostic and prognostic implications. We herein review the brain, optic nerve, and spinal cord MRI findings of NMOSD. Neuromyelitis optica (NMO) is an inflammatory disease of the CNS that is characterized by severe attacks of optic neuritis (ON) and longitudinally extensive transverse myelitis (LETM). 1The past decade has witnessed dramatic advances in our understanding of NMO. Such advances were initiated by the discovery of the disease-specific autoantibody, NMO-immunoglobulin G (NMO-IgG), and subsequent identification of the main target autoantigen, aquaporin-4 (AQP4), which has distinguished NMO as a distinct disease from multiple sclerosis (MS). 2Current diagnostic criteria, however, still require both ON and myelitis for an NMO diagnosis.3 Nevertheless, the identification of anti-AQP4 antibodies beyond the current diagnostic criteria of NMO indicates a broader clinical phenotype of this disorder, so-called "NMO spectrum disorder" (NMOSD). 4,5 The NMOSD encompasses anti-AQP4 antibody seropositive patients with limited or inaugural forms of NMO and with specific brain abnormalities. It also includes anti-AQP4 antibody seropositive patients with other autoimmune disorders such as systemic

The role of autoantibodies in the pathogenesis of multiple sclerosis (MS) and other demyelinating diseases is controversial, in part because widely used western blotting and ELISA methods either do not permit the detection of conformation-sensitive antibodies or do not distinguish them from conformation-independent antibodies. We developed a sensitive assay based on self-assembling radiolabeled tetramers that allows discrimination of antibodies against folded or denatured myelin oligodendrocyte glycoprotein (MOG) by selective unfolding of the antigen domain. The tetramer radioimmunoassay (RIA) was more sensitive for MOG autoantibody detection than other methodologies, including monomer-based RIA, ELISA or fluorescent-activated cell sorting (FACS). Autoantibodies from individuals with acute disseminated encephalomyelitis (ADEM) selectively bound the folded MOG tetramer, whereas sera from mice with experimental autoimmune encephalomyelitis induced with MOG peptide immunoprecipitated only the unfolded tetramer. MOG-specific autoantibodies were identified in a subset of ADEM but only rarely in adult-onset MS cases, indicating that MOG is a more prominent target antigen in ADEM than MS.The role of autoantibodies in the pathogenesis of human demyelinating diseases of the central nervous system (CNS) is an important, unresolved issue. In animal models, autoantibodies that recognize epitopes on the surface of myelin or myelin-producing oligodendrocytes can enhance demyelination 1,2 . A monoclonal antibody (8-18C5) against myelin oligodendrocyte glycoprotein (MOG) induces severe demyelination in mice and rats with mild experimental autoimmune encephalomyelitis (EAE) but does not induce disease in healthy animals because the antibody cannot gain access to the CNS parenchyma 1,2 . MOG is a minor component of myelin but is localized on the outer surface of the multilamellar myelin structure and is thus accessible to antibodies, whereas more abundant antigens such as myelin basic protein are inaccessible in intact myelin 1 . In the marmoset primate model of EAE, immunization with MOG induces a chronic demyelinating disease with pathological features reminiscent of MS (ref. 3). In mouse models, however, severe demyelination is observed in the absence of antibodies and B cells 4 , indicating that autoantibodies are not required for demyelination in all species.These elegant studies in animal models have shown the demyelinating potential of autoantibodies to myelin surface proteins, but their role in the pathogenesis of human inflammatory demyelinating diseases such as MS and acute disseminated encephalomyelitis (ADEM) is far less certain. MOG has been extensively studied as a potential target antigen for autoantibodies in MS (refs. 5-8) Unlike MS, ADEM typically has a rapidly progressive clinical presentation that includes encephalopathy 11 . The disease course is usually self limiting, although in a minority of cases relapses may occur. The pathogenic relationship between MS and ADEM is unclear, and it remains to be d...

No abstract