Status epilepticus: Updates on mechanisms and treatments

Status epilepticus (SE) consists of prolonged, self-sustaining seizures and is a common neurological emergency that causes respiratory compromise and neuronal injury. Without prompt treatment, the seizures can become resistant to benzodiazepines, leading to the progressive evolution of established, refractory, and super-refractory SE. Studies in experimental animals have found impaired GABAergic inhibition and potentiated glutamatergic neurotransmission in SE animals. These alterations increase the number of active neurons and expand the seizure network. Here, we first discuss the changes in GABA-A, NMDA, and AMPA receptor-mediated synaptic transmission during SE and elaborate on emerging studies showing the neuronal consumption of alternate energy sources to cope with increased energy demand. Then, we discuss the clinical studies that have tested the efficacy of various benzodiazepines and other anticonvulsant agents in treating SE in prehospital and in-hospital settings. Finally, we briefly summarize the ongoing clinical studies and the potential for other anticonvulsant agents to be tested for treating SE. PLAIN LANGUAGE SUMMARY: Most seizures are self-limiting, but some seizures change the brain such that a constant state of seizures, SE, is generated. These prolonged seizures can cause neuronal injury and increase the risk of death. We discuss the molecular mechanisms that sustain these seizures and the accompanying neuronal and network plasticity. We also review the current SE treatment and future directions.