Role of Immunity in Pediatric Drug Resistant Epilepsy: Clinical, Neurophysiological, Neuroimaging and Immunological Study

Introduction: Autoimmune epilepsy was an under-recognized condition, and its true incidence was unknown in pediatrics. Serum antibodies suggesting a potential autoimmune etiology were detected in 34.8% of patients presented by epilepsy of unknown etiology. Diagnosis of autoimmune epilepsy would be of great value in the search for potential preventive treatments for disabling seizures and cognitive impairment.

Autoimmune epilepsy was characterized by a depressed or altered level of consciousness, lasting more than 24 h, lethargy, or change in personality or behavior and at least one of the following features: neuropsychiatric symptoms, seizures, movement disorder, or cognitive dysfunction. Patients were excluded if an alternative diagnosis was made. The presence of neuronal antibodies and MRI changes supported the diagnosis. This study aimed to assess the possible role of immunity in the pathogenesis of pediatric drug resistant epilepsy through clinical electroencephalographic, neuroimaging and neuro-immunological testing.

Subjects and Methods: This study was conducted on twenty-four drug resistant epileptic children with suspected autoimmune etiology over the period from 2016-2018. The control group comprised twenty four children with idiopathic controlled epilepsy matched to the drug-resistant epilepsy sample for age and gender. Both groups were subjected to clinical examination, neuronal antibodies in serum and CSF, Mini-Mental State Examination (MMSE), Chalfont seizure severity scale (CSSS), EEG, and brain MRI studies.

Results: There was a large percentage of autoimmune epilepsy in pediatric cryptogenic drug-resistant epilepsy. 55% of DRE cases presented with mild pleocytosis and elevated CSF proteins. Serum and CSF neuronal antibodies were positive in about 66.63% and 65% of cases respectively. Serum neuronal antibodies to GAD were positive in 8.33%, NMDA Abs were positive in 33.3%, and VGKC Abs were in 25.0% of cases. In the CSF, GAD antibodies were positive in 10%, NMDA antibodies in 40%, and VGKC antibodies in 20% of cases. Seizures reduction was achieved with immunotherapy, also was prevalent in seropositive cases.

Conclusion: Pediatric patients presented by drug-resistant epilepsy should receive immunotherapy for a definite diagnosis. MRI changes in the form of temporal hyperintensity, claustrum, cortical hyperintensities were a common finding in pediatric patients presented by drug-resistant epilepsy. CSF changes in the form of elevated proteins and /or mild pleocytosis signified inflammatory changes in the CNS and blood brain barrier (BBB) disruption. Steroid responsiveness played a major role in the diagnosis of autoimmune epilepsy, especially seronegative cases.