MULTIPLE SCLEROSIS IN CHILDREN AND ADOLESCENTS

Abstract

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system resulting in inflammation, demyelination, and neurodegeneration. Pediatric MS was defined by the IPMSSG to include "children" (under the age of 10) And "adolescents" (aged 10 and above but prior to the 18th birthday). The worldwide prevalence and incidence of pediatric MS are unknown and the proportion of pediatric MS patients in the total MS population is unclear. There is available data from individual countries or MS centers. Demographic characteristics of pediatric MS show some differences to that known in adults and varies with age. More pathological studies are needed as there are few pathological studies in pediatric MS. Data available shows some pathological differences between pediatric and adult MS. Pathology of pediatric MS shows “Plaques”, axonal damage in NAWM, cortical lesions, meningeal and CSF pathology. Pathogenesis of the lesions of MS is heterogeneous. It is generally held that there is a breach in the integrity of the blood-brain barrier in a person who is genetically predisposed to the disease. It involves multiple immune cells, cytokines and antibodies. T cells play a key role in the pathophysiology of MS as activated T cells cross the blood-brain barrier and incite an inflammatory reaction within the CNS. B cells differentiate into plasma cells and produce autoantibodies. Autoantibodies include two crucial types, anti-MOG and anti-MBP antibodies. Still additional investigations are needed to further understand the pathogenesis of pediatric MS. The etiology of MS is complex, it is assumed that both a complex genetic background and environmental factors and their interactions contribute to disease manifestation. Genetic etiology is shown through twins concordance rate, incidence in relatives and HLA. Environmental etiology include viral infectious agents such as EBV and HSV, sun exposure and vitamin D levels, place of residence, smoking (even negative smoking) and obesity. Pediatric MS my present with encephalopathy which may occur with a first episode of MS, seizures, motor and sensory disturbances that often co-exist, transverse myelitis, brainstem involvement, cerebellar symptoms and optic neuritis. Compared to adults with MS, children and adolescents with MS tend to have polyfocal symptoms, more frequent brainstem dysfunction and optic neuritis occurrence, more frequent relapses, a clinical course that is almost universally relapsing-remitting. Younger children with MS differ clinically from adolescents with MS in clinical features, disease course, CSF profiles and MRI findings. Conventional and non-conventional MRI techniques are used in diagnosis, prognosis and monitoring of treatment efficacy of pediatric MS. Some differences are found in MRI features and involved anatomical regions between pediatric and adult MS patients. These particularities and differences raise questions about the ability to use the same diagnostic criteria in the children and adults with MS, especially in prepubertal patients in whom the clinical, biological, and radiological presentation seem to be distinct. Pediatric MS diagnosis is challenging especially those who have not yet reached puberty, because of the atypical clinical, biologic, and MRI presentations and the broader spectrum of potential differential diagnoses specific to that age range. Many efforts were done to have MRI diagnostic and predictive criteria for pediatric MS diagnosis. The 2010 Revised McDonald criteria are good in older children but less predictive in younger children. More recently the IPMSSG gave yield to proposed criteria for the diagnosis of pediatric MS and stated that sensitive and specific MRI criteria for the youngest patients with MS still need to be developed. Prognosis of pediatric MS and clinical outcomes include irreversible disability, fatigue, cognitive impairment and associated academic consequences, and psychiatric problems. The initial presentation and symptoms of MS in children are highly variable, and thus, differential diagnoses include a wider range of diseases in comparison with adult-onset MS. They include other demyelinating disorders, systemic inflammatory disorders, infections, neoplasms, leukodystrophies, mitochondrial disorders, vascular disorders.