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[Multiple sclerosis with early onset: pathogenesis, clinical characteristics, possibilities in the treatment of its
Insights
Early onset multiple sclerosis (MS) in children presents unique patterns. Younger onset (under 10) shows slower relapses but faster disability progression, linked to specific HLA-DRB1 genes.
Area of Science:
- Neurology
- Immunogenetics
Background:
- Early onset multiple sclerosis (MS) exhibits distinct clinical and pathological features compared to adult-onset MS.
- Understanding these peculiarities is crucial for accurate diagnosis and effective management in pediatric populations.
Purpose of the Study:
- To investigate the clinical, immunogenetic, and neurophysiological characteristics of multiple sclerosis with onset before 15 years of age.
- To explore associations between clinical presentation, disease progression, MRI findings, and specific genetic markers in pediatric MS.
Main Methods:
- Clinical data collection and analysis from 56 patients with definite MS onset under 15.
- Neuroimaging using MRI to assess T2-lesion load and distribution.
- HLA-DRB1 genomic typing and transmission/disequilibrium test (TDT) analysis.
Main Results:
- Patients with onset under 10 years experienced rarer relapses but more rapid disability progression than those aged 11-15.
- MRI T2 lesion load correlated with age of onset, disease duration, and relapse frequency.
- A significantly higher frequency of the HLA-DRB1*15 allele was observed in children with MS compared to controls, with TDT analysis strongly supporting its linkage to susceptibility.
Conclusions:
- Age at onset significantly influences the clinical course and disability progression in early-onset MS.
- The HLA-DRB1*15 allele is strongly associated with susceptibility to sporadic MS in children with disease onset before 15 years.
- Further research into early-onset MS pathogenesis and treatment strategies, including beta-interferon-1a, is warranted.
Abstract:
Early onset multiple sclerosis (MS) has some peculiarities in the disease course. 56 patients with definite MS with the onset at the age under 15 years were included in this clinical, immunogenetical and neurophisiological study. The analyses of the relations between different clinical characteristics of MS in children has shown, that patients with onset under 10 years, had rare relapses, but more progressive development of disability in contrast to the patients with MS onset at the age of 11-15 years. Duration of the first remission was associated with the time to sustained disability in children with MS. The number and volume of MRI T2-positive lesions in the white matter of the brain was associated with the age of onset, duration of the disease and with the number of relapses. In several cases the phenomena of clinical-MRI dissociation was observed. Generic HLA-DRB1 genomic typing was performed in all the patients. High frequency of DR2(15) genotype in MS-affected children in comparison with the group of healthy controls was more expressed as compared with MS-affected adults. The comparison of frequencies of DRB1 alleles in transmitted, i.e. appeared in the affected child haplotypes and in non-transmitted haplotypes confirmed results of the case-control study showing the very significant association of MS with DR2 alleles and extremely significant--with its DR15 subtype in children. The data of transmission/disequilibrium test (TDT) analysis provide strong evidence for linkage of DR15 alleles and susceptibility to sporadic MS in patients with disease onset before 15 years. The positive experience of management (beta-interferon-1a) was shown in MS-affected children in three cases.