Acute disseminated encephalomyelitis in children: clinical features and HLA‐DR linkage

Abstract

This study includes 90 children (41 female and 49 male) in the age range of 2-16 years with acute disseminated encephalomyelitis (ADEM). Thirty-three patients developed ADEM following rubella infection, 26 children following varicella infection, 20 suspected viral aetiology ADEM and 11 multiphasic disseminated encephalomyelitis (MDEM). All patients had neurological, routine laboratory and viral serology study with an enzyme-linked immunosorbent assay. Brain and/or spinal cord magnetic resonance imaging (MRI) were performed in 14 children. A follow-up study was in 1-5 years. Typing of DRB1 gene HLA class II was performed in 38 patients. We established that the varicella and rubella groups had preferential patterns. Rubella ADEM is characterized by acute explosive onset, seizures, coma and moderate pyramidal signs, whereas varicella infection is characterized by cerebella ataxia and mild pyramidal dysfunction. The suspected viral aetiology ADEM was characterized by polisymptomatic presentation. MDEM was characterized by older age of patients (11.6 +/- 2.8 years), more severe and prolonged local neurological symptoms, including myelitis symptoms and marked extrapyramidal signs, with distinct demyelination in MRIs. As a whole, ADEM is associated with DRB1*01 and DRB1*017(03) in the Russian population. Thus, ADEM is a separate autoimmune condition with a specific mechanism due to the type of genetic immunoregulatory base and specificity of viral trigger.

Acute disseminated encephalomyelitis: clinical features, HLA DRB1*1501, HLA DRB1*1503, HLA DQA1*0102, HLA DQB1*0602, and HLA DPA1*0301 allelic association study

“…The HLA DQB1*0602 allele confers genetic susceptibility to Brazilian MS patients from Rio de Janeiro City (RJC), independently of the genetic background [21][22][23] . The presence of a common allele conferring genetic susceptibility for both MS and ADEM in the same population was found by Idrissovaet al 20 among Russian MS and ADEM patients. In the present study, we found the HLA DQB1*0602 and HLA DRB1*1501 alleles sharing genetic susceptibility to MS and ADEM in patients from RJC.…”

“…The significantly association of ADEM patients with HLA DRB1*1501 allele can speculate about a protector role of these allele among the monophasic course and rapid improvement of those patients. Accordingly to this point of view, Idrissovaet al 20 also found association of HLA DRB1*01 allele with ADEM susceptibility in Russian patients. And like DRB1*1501, DRB1*01 has been described as an allele associated to low morbidity in MS patients.…”

“…Nevertheless, the second subsequent relapsing in both of them was not associated to encephalopathy; they presented new neurological clinical manifestations and new MRI lesions. If we apply the pediatric criteria 20 , these two adult patients move, in this moment, to the diagnosis of clinical isolated syndrome (CIS) 10 ; the reason is because they did not presented associated encephalopathy, and in this case their second demyelinating event is considered the first of a possible demyelinating condition that can, or not, be evaluated MS. These two adult patients continue evaluating with relapsing-remitting neurological symptoms after their second demyelinating event (classified as CIS) and after the third demyelinating event they should be moved to the diagnosis of MS (Figs 3 and 4) according the pediatric criteria 10 .…”

“…The pediatric RDEM is defined as a new event of ADEM, with recurrence of the same initial signs and symptoms, always associated to encephalopathy; magnetic resonance image (MRI) shows no new lesion and the original ones can have enlarged, during a interval time of three months, or more, of the remission, and at least one month after the last treatment with corticosteroids [10][11][12] . The pediatric MDEM diagnoses requires encephalopathy associated to new polysymptomatic neurological dysfunction, new MRI lesions, and an equal interval time of three months, or more, after the recovering of the first attack and at least one month after corticosteroids treatment ending 20 ; the MRI needs to show new areas of involvement and complete or partial resolution of the first ADEM event 11,12 .…”

“…ADEM followed poliomyelitis vaccine virus was reported in a Japanese child associated with the HLA-Cw3 and HLA-DR2, which are related to multiple sclerosis (MS) in Japan 8 . A linkage genetic study in children showed that ADEM was associated with HLA DRB1*01 and DRB1*017(03) in the Russian population, and these alleles are associated with MS in Russian patients 20 . In Brazil, MS has been associated with HLA DR2 in Caucasian 21 patients and with HLA DQB1*0602 independently of DRB1*1501, in African-descendent patients of Rio de Janeiro City (RJC) [21][22][23] .…”