Major Category: Research and Disease Areas
Subcategory: Loss of Tolerance
By Pavanish Kumar (Team Lead),
Amanda Lim,
Bhairav Paleja,
Camillus Chua,
Sharifah Nur Hazirah
Epilepsy affects more than 50 million people worldwide and onset typically occurs in childhood. Epileptic seizures are initiated unprovoked in affected patients, arising from uncontrolled electrical activity in the brain. Conventional anticonvulsants that largely target ion channels only improve seizure control and cannot directly prevent epileptogenesis. Refractory epilepsy, or Drug-refractory epilepsy (RE) is defined as a failure of 2 appropriate and adequate anti-epileptic drugs to control seizures. Drug-refractory epilepsy (RE) occurs in 30% of epilepsy cases. RE is associated with notable cognitive, behavioural and socio-economic difficulties. Autoimmune encephalopathy (AIE) is an increasingly recognized cause of encephalopathy in children. AIE is often triggered by infections, and patients develop seizures as part of their clinical presentation. Some AIE disorders are associated with pathogenic neuronal auto-antibodies. Patients who recover from AIE often remain affected by epilepsy, which in many cases is refractory. Although AIE responds well to immunotherapy and children with epileptic encephalopathies and refractory seizures are treated with steroids, there is little evidence for the efficacy of corticosteroids in RE as a whole. The mechanism of action for corticosteroids in AIE is unclear; the therapeutic effects are postulated to be due to direct neuronal effects, metabolic changes and immune-modulation or suppression. Here we are working to unravel the specific immune mechanism that contributes to refractory epilepsy pathogenesis. Deep understanding of the immunome in patients from refractory epilepsy will lead to development of better diagnostic, prognostic and therapeutic tools.
