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Neuronal antibody prevalence in children with seizures under 3 years: A prospective national cohort
Joseph D Symonds1, Teresa C Moloney1, Bethan Lang1
1From the Paediatric Neurosciences Research Group (J.D.S., M.E.O., S.M., A.B., L.D., M.W., S.M.Z.), Royal Hospital for Children; College of Medical, Veterinary & Life Sciences (J.D.S., A.B., L.D., S.M.Z.), University of Glasgow; Nuffield Department of Clinical Neurosciences (T.C.M., B.L., A.V., S.T.), John Radcliffe Hospital, Oxford; Department of Paediatric Neurosciences (A.M., J.S.), Royal Hospital for Sick Children, Edinburgh; Paediatric Neurology (A.J., M.K., P.B., E.P.), Tayside Children's Hospital, Dundee; Neuroradiology (K.F.), Queen Elizabeth University Hospitals, Glasgow; Department of Paediatrics (I.A.-A., R.G.), Forth Valley Royal Hospital, Larbert; Department of Paediatrics (J.A., M.C.), University Hospital Wishaw; Department of Paediatrics (J.C.), Victoria Hospital, Kirkcaldy; Department of Paediatrics (C.F., C.A.M.), University Hospital Crosshouse, Kilmarnock; Department of Paediatrics (J. MacDonnell), Borders General Hospital, Melrose; Department of Paediatrics (J. McKnight), Dumfries and Galloway Royal Infirmary; Department of Paediatrics (L.N.), Royal Alexandra Hospital, Paisley; Paediatric Neurology (E.S.), Royal Aberdeen Children's Hospital; and Department of Paediatrics (A.W.), Raigmore Hospital, Inverness, UK.
Insights
Neuronal antibodies are found in 6.0% of young children with seizures. However, these antibodies are rarely linked to autoimmune encephalitis in this age group, suggesting limited clinical significance for routine testing.
Area of Science:
- Pediatric Neurology
- Neuroimmunology
- Epileptology
Background:
- Autoimmune encephalitis is a rare condition in early childhood.
- Identifying the prevalence of anti-neuronal antibodies in young children with seizures is crucial for understanding potential autoimmune contributions to epilepsy.
Purpose of the Study:
- To determine the prevalence of anti-neuronal antibodies in a national cohort of children under three years old presenting with new-onset seizures.
- To assess the clinical significance of these antibodies in the absence of clear autoimmune encephalitis symptoms.
Main Methods:
- A prospective, population-based national cohort study was conducted over three years.
- Serum samples from 298 children with new-onset seizures were tested for seven specific neuronal antibodies using live cell-based assays.
- Clinical data and EEG records were reviewed to exclude other causes of seizures and identify potential autoimmune encephalitis cases.
Main Results:
- Anti-neuronal antibodies were detected in 18 out of 298 children (6.0%).
- The most common antibodies found were against GABA receptor B (2.7%) and contactin-associated protein 2 (1.3%).
- None of the antibody-positive children presented with the typical clinical picture of autoimmune encephalitis, and seizure characteristics did not correlate with antibody presence.
Conclusions:
- While neuronal antibodies are present in a small percentage of young children with seizures, autoimmune encephalitis remains very rare in this demographic.
- Routine antibody testing is not recommended for early childhood-onset epilepsy without additional features suggestive of encephalitis.
- Antibody testing should be reserved for children with specific clinical indicators of autoimmune encephalitis.
Objective:
To report the prevalence of anti-neuronal antibodies in a prospective 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 third birthday over a 3-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 7 neuronal antibodies using live cell-based assays. Clinical data were collected with structured proformas at recruitment and 24 months after presentation. In addition, patients with seizures and clinically suspected autoimmune encephalitis were independently identified by a review of the case records of all children <3 years of age in Scotland who had undergone EEG.
Results:
Two hundred ninety-eight patients were identified and recruited and underwent autoantibody testing. Antibody positivity was identified in 18 of 298 (6.0%). The antibodies identified were GABA receptor B (n = 8, 2.7%), contactin-associated protein 2 (n = 4, 1.3%), glycine receptor (n = 3, 1.0%), leucine-rich glioma inactivated 1 (n = 2, 0.7%), NMDA receptor (n = 1, 0.3%), and GABA receptor A (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 at <3 years of age. Antibody testing should not be a routine clinical test in early childhood-onset epilepsy because, 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.
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