Although the mechanisms of refractory epilepsy (RE) are multifactorial and involve environmental, genetic, and disease and treatment related factors, another factor to consider in this complex system is neuroinflammation. Recently, neuroinflammation and blood-brain-barrier (BBB) dysfunction has been proposed as a possible mechanism. The inflammatory process has been shown to trigger hyperexcitability due to different cellular and molecular events. However, information regarding inflammation and DRE is limited. In recent decades, autoantibodies have emerged as underlying causes of unexplained epilepsy, and a link between autoimmunity and epilepsy has been suggested. In addition to the increased susceptibility to seizures caused by inflammation, a direct epileptogenic role of many specific autoantibodies against a large diversity of neuronal and glial proteins has been recognized, making diagnosis more difficult. The International League Against Epilepsy (ILAE) introduced the concept of "epilepsy of immunologic etiology" (AEAE) to refer to patients whose epilepsy "is the direct result of an immunologic disorder, in which seizures are a central symptom. The pathophysiology of AEAE is clearly distinct from that of autoimmune encephalitis epileptic seizures (AIE).
On the other hand, histopathological studies have shown that intracellular antibody conditions are caused by a cytotoxic T-cell attack against neurons in a complex immunological network, leading to structural brain damage. All these highlight the need for further research on the role of inflammation and the immune response in the central nervous system, particularly in RE, to understand the mechanisms in this clinical entity and to identify new immunomodulatory treatments, particularly for those cases in which surgery is not a therapeutic alternative. This review summarizes the current knowledge on the role of specific neuronal antibodies in epilepsy-related syndromes, the incidence in our population and the main clinical presentations that will help the clinician to improve diagnosis and treatment.