Figure 2. Synaptic dysfunction and hyperexcitability as a result of seizures, inflammation, and antibody-mediated encephalitis.

Diagram showing multiple inflammatory/innate immunity mechanisms triggered by seizures and epileptogenesis, along with inflammation-related transcriptional and nontranscriptional pathways that lead to synaptic dysfunction, changes in plasticity, and hyperexcitability (corresponding with blue and red arrows). In contrast to these mechanisms, the antibody-mediated encephalitides such as those associated with NMDAR, AMPAR, LGI1, or GABAbR autoantibodies (see others in Tables 3 and 4), represent a direct antibody-mediated alteration of the corresponding targets also leading to synaptic dysfunction, impairment of synaptic plasticity, and hyperexcitability (purple arrow). The degree of involvement of inflammatory/innate immunity molecules and pathways of inflammation in antibody-mediated encephalitis is currently unknown.