**6. Diagnostic criteria**

cell proliferation to myelin peptides in children with MS and also found an increased proportion of dividing CD4+ T cell to myelin peptides with a memory phenotype which

Humoral immunity has also been implicated in MS pathogenesis. B lymphocytes, plasma cells, immunoglobulins, and complement deposition have been shown in MS lesions. Anti-myelin oligodendrocyte glycoprotein antibodies (anti-MOG) have been reported in pediatric cases with inflammatory demyelinating diseases, predominantly in children with ADEM-like first episodes and in pediatric MS patients younger than 10 years of age at disease onset. Anti-MOG antibodies have also been observed in pediatric patients with recurrent optic neuritis and seronegative NMO [10, 17]. The presence of anti-MOG antibodies has been reported in a subgroup of adults with seronegative NMO but only rarely in adults with MS [18]. Moreover, antibody-independent functions of B lymphocytes such as cytokine production play a role in

Neurodegeneration and axonal damage are other processes in the pathogenesis of MS. Mechanisms of axonal damage in multiple sclerosis include a specific immunologic attack on axons; the presence of soluble mediators such as proteases, cytokines, and free radicals released during the inflammatory process and lack of neurotrophic factors provided to the

The cellular content of MS lesions includes primarily T lymphocytes (CD4+ and CD8+) and macrophages. Lucchinetti et al. have described four distinct pathological patterns of demye‐ lination in autopsy and biopsy samples from adult MS patients. Patterns I and II showed T cell/macrophage inflammation and there was also T cell plus antibody-mediated autoim‐ mune damage in pattern II. Patterns III and IV were suggestive of a primary oligodendro‐ cyte dystrophy. Oligodendrocyte apoptosis or death and lesser macrophage-T cell inflammation were observed in patterns III and IV [20]. In another study, Trapp et al. demonstrated axonal damage in normal appearing white matter [21]. Additionally, subpial cortical, intracortical, and leukocortical lesions were found in adult-onset multiple sclerosis patients' biopsy specimens. Immune cells were also identified within the pia-arachnoid in adult-onset multiple sclerosis and ectopic B-cell follicles with germinal centers were detect‐ ed in the meninges of patients with secondary progressive multiple sclerosis. All these pathological findings were identified in adult patients [10, 22, 23]. Neuropathological studies are limited in pediatric multiple sclerosis [10]. Tumefactive demyelinating lesions have been investigated in pediatric patients with MS [24]. The pathological characteristics of tumefac‐ tive demyelinating lesions include relative axonal preservation, perivascular and parenchy‐

axon by oligodendrocytes as a result of chronic demyelination [10, 19].

mal lymphocyte and macrophage inflammation [25].

produced interleukin 17 [10].

172 Trending Topics in Multiple Sclerosis

MS immunopathogenesis.

**5. Pathology**

In 2007, the International Pediatric Multiple Sclerosis Study Group (IPMSSG) proposed a consensus on definitions for pediatric acquired demyelinating disorders of the central nervous system and pediatric MS. Pediatric MS referred to "children" (under the age of 10) and "adolescents" (aged 10 and above but younger than 18) in this definition. In 2012, the study group revised the criteria in consideration of studies that had applied 2007 pediatric MS criteria and the 2010 revised McDonald's criteria for adults [26–28].

According to the 2012 revised criteria, pediatric MS can be satisfied by any of the following:

