In the past, children with viral encephalitis were common in clinics.[4, 9] The clinical presentations were mainly classified into types, including mental symptoms, epileptic seizures, motor disorders, language disorders, sleep disorders, autonomic nervous dysfunction and ventilation disorders. The duration of the disease could be several months or more, which was costly, and the lesions often involved the limbic system, mainly the cingulate gyrus, hippocampus and frontal lobe.[11, 12] Previously, it was diagnosed as sporadic encephalitis. However, in recent years, studies have found that the disease is closely associated with a variety of autoantibodies, which has been regarded as a common autoimmune disease. The involved part of the brain parenchyma went beyond the limbic system and was later called AE. It involved many parts of the central nervous system.
Compared with adult patients with AE, there were significant differences in clinical presentation, antibody levels, treatment and prognosis of children with AE. The children with AE showed different types of clinical presentation, as mentioned above. Infection and fever were mainly prodromal symptoms. EEG monitoring is necessary for children with AE. In this study, more than 80% of the EEG was abnormal. These showed unilateral or bilateral epileptic activity focus and focal/extensive slow waves. Cerebrospinal fluid examination showed that about 60% of children with AE had a mild increase of lymphocytes, but the total number of lymphocytes was usually in the range of 100 /ul and no more than 150 mg/dl. The protein content may increase slightly, but the sugar content still maintains a normal level. For patients with or without inflammatory changes in cerebrospinal fluid (CSF), 70%~80% showed high signal intensity, asymmetry and unilateral abnormal lesions on flair or T2 images, and other parts could be involved. AE refers to a disease in which the immune system of the body responds to the antigens and antibodies produced by central nervous system antigens, resulting in central nervous system damage. With the increasing understanding of AE, related reports are present from time to time. For children with suspected AE, serum and cerebrospinal fluid antibody tests, brain MRI and EEG examinations, and systemic tumour screening should be carried out as soon as possible. Suitable treatment should be carried out immediately to obtain a good prognosis. After hospitalisation, 75.64%(59/78)child patients basically recovered and were normally discharged according to the recent (one-year) follow-up according to the mRS score. This was consistent with 80% of the expert consensus.
The pathogenesis of AE has not been clear. Previous studies have shown that AE is associated with virus infection, tumour or autoimmunity.[15, 16] Since the concept of ‘borderline encephalitis’ was put forward in 1968, researchers from home or abroad have found related autoantibodies, such as Huanti body and anti-glutamate dehydrogenase antibody. In addition, some studies pointed out that the occurrence of AE was also associated with antithyroid antibodies. It is suggested that the pathogenesis of AE is closely related to autoimmune dysfunction. Therefore, this study reviewed the clinical database of 78 children with AE, according to the recent follow-up mRS score (prognosis), to explore the relationship between humoral immune function, cellular immune function and the short-term prognosis of children with AE.
Humoral immunity is a specific immunity, mainly caused by the production of corresponding antibodies by B-lymphocyte under the stimulation of antigens. When an antigen enters the body, B-lymphocyte will be sensitised under its stimulation, accelerating the value-added and differentiation, and producing corresponding antibodies, referred to as immunoglobulin. According to the composition and structure, immunoglobulins can be divided into five categories: IgA, IgM, IgG, IgD and IgE. Among them, IgA, IgM and IgG levels can be used as important indicators to evaluate humoral immune function.[18, 19] T-lymphocytes mainly mediate cellular immunity and, at the same time, can regulate humoral immunity. There are many CD molecules on the surface of T-cells, such as CD3, CD4, and CD8, which are widely involved in the whole process of T-cell recognition, activation and proliferation, apoptosis, and elimination of allogeneic antigen. The surface antigen of T-lymphocytes can be divided into a CD4 subgroup and a CD8 subgroup. CD4 cells and CD8 cells coordinate and restrict each other under normal physiological conditions, and the ratio of CD4/CD8 is in dynamic equilibrium. When the dynamic balance is broken, the ratio of CD4/CD8 is decreased, which indicates that the immune regulatory network is out of balance and the immune function is decreased. In the low immune state, the decrease of CD4 content and CD4/CD8 ratio can further stimulate B-lymphocytes to secrete antibodies, form immune complexes, and activate complements, which may cause a variety of diseases.
In this study, humoral immunity and cellular immune levels of the two groups of children with AE found that the two groups had great differences in remission immune function. Abnormal immune status in poor AE (57.89%) was significantly higher than in good AE (20.34%), and the two groups were significantly different. The IgA, IgG, IgM, CD4, and CD4/CD8 levels in children with good prognosis were significantly better than in children with poor prognosis. It was suggested that overall hyperthyroidism of humoral immunity in AE in children with poor prognosis was more obvious than in children with a good prognosis. There was a significant negative correlation between mRS score and CD4/CD8 at admission, which suggested that there was a close relationship between immune function and prognosis. In addition, this study analysed the factors affecting the prognosis of children with AE and found that young age, disturbance of consciousness, limb movement disorder and abnormal immune function in remission stage were the risk factors for poor prognosis of children with AE.[22–24] Other risk factors were consistent with previous studies except for the younger age. However, there is no statistical data on the population and age of children with high incidence. In this study, young age was the risk factor for the conclusion. The reasons may be as follows: (1) AE accounted for about 10%~20% of all encephalitis, and this study had a small sample size, resulting in inconsistent conclusions; (2) compared with older children, the immune function of young children is weaker, and the immune network is more likely to be unbalanced, which leads to poor prognosis. Because of the small sample size, the varied response to therapy in our study could be explained with different autoimmune encephalitis antibodies, making it difficult to draw conclusions from each group.