Neuronal antibody prevalence in children with seizures under 3 years

Abstract

Objective:To report the prevalence of anti-neuronal antibodies in a prospectively whole nation cohort of children presenting with seizures before their third birthday.Methods:This was a prospective population-based national cohort study involving all children presenting with new onset epilepsy or complex febrile seizures before their 3rd birthday over a three-year period. Patients with previously identified structural, metabolic or infectious cause for seizures were excluded. Serum samples were obtained at first presentation and tested for seven neuronal antibodies using live cell-based assays. Clinical data were collected using structured proformas at recruitment, and 24 months after presentation. In addition, patients with seizures and clinically suspected autoimmune encephalitis were independently identified by reviewing the case records of all children < 3 years in Scotland who had undergone electroencephalography (EEG).Results:298 patients were identified, recruited and underwent autoantibody testing. Antibody positivity was identified in 18/298 (6.0%). The antibodies identified were: GABABR (n = 8, 2.7%), CASPR2 (n = 4, 1.3%), GlyR (n = 3, 1.0%), LGI1 (n = 2, 0.7%), NMDAR (n = 1, 0.3%), and GABAAR (n = 1, 0.3%). None of these patients had a clinical picture of autoimmune encephalitis. Seizure classification and clinical phenotype did not correlate with antibody positivity.Conclusions:Autoimmune encephalitis is very rare in early childhood. However serum neuronal antibodies are identified in 6.4% of children presenting with seizures < 3 years. Antibody testing should not be a routine clinical test in early childhood-onset epilepsy as in the absence of other features of autoimmune encephalitis antibody-positivity is of doubtful clinical significance. Antibody testing should be reserved for patients with additional features of encephalitis.

Association between autoimmune encephalitis and epilepsy: Systematic review and meta-analysis

“…Forest plot of the incidence or prevalence of seizures in AE patients (A); forest plot of the incidence or prevalence of AE in epilepsy patients (B); forest plot of the incidence or prevalence of antibody positivity in patients with epilepsy (C); forest plot of the incidence or prevalence of anti-NMDAR in epilepsy patients (D); forest plot of the incidence or prevalence of anti-LGI1 in epilepsy patients (E); forest plot of the incidence or prevalence of anti-CASPR2 in epilepsy patients (F). [46][47][48][49][50]54]. The pooled-period prevalence of anti-LGI1 in epilepsy in these studies was 1% (95% CI: 0.00-0.02, p = 0.040, Z = 3.20, I 2 = 54.4%) (Fig.…”

“…Therefore, we calculated the incidence/prevalence of NMDAR, IGL1, and CAPSR2 in epilepsy, which are the common antibodies associated with AE. Eleven studies examined NMDAR antibodies [41,42,45,46,50,53,54,[56][57][58]60]. After excluding one study that focused only on anti-NMDAR encephalitis [53], we found that the pooled-period prevalence of anti-NMDAR in epilepsy was 1% (95% CI: 0.01-0.02, p < 0.0001, Z = 4.74, I 2 = 88.8%) (Fig.…”

“…2E). Six studies detected CASPR2 antibodies [46][47][48][49]54,60], and the pooled-period prevalence of anti-CASPR2 in epilepsy was 2% (95% CI: 0.01-0.02, p = 0.755, Z = 4.10, I 2 = 0.0%) (Fig. 2F).…”

“…AE was reported as one of the etiologies of epilepsy in six studies [41][42][43][44][45][46]. Two studies were conducted on adults and pediatrics, three studies on adults, and one study on pediatric patients only.…”

“…Nineteen studies reported the incidence or prevalence of antibody positivity in patients with epilepsy [47][48][49][50][51][52][53][54][55][56][57][58][59][60]. Five of the studies included an epilepsy group with AE, since they also tested for autoantibodies [41][42][43][44][45][46]. Both adult and pediatric populations were included in six studies, only adults in five studies, and only pediatrics in another three studies.…”