Challenges in the treatment of convulsive status epilepticus

Convulsive status epilepticus (CSE) is a medical emergency associated with high mortality and morbidity. The most recent definition of CSE is a convulsive seizure lasting more than 5min or consecutive seizures without recovery of consciousness. In adults, for the treatment of the early stages of CSE, diazepam, lorazepam or midazolam are the most common treatments, although the choice of agent seems less important than rapid treatment. Midazolam, when administered intramuscularly (best evidence), buccally, or nasally, is effective and safe in the pre-hospital setting. The antiepileptic drugs, phenytoin, valproate, levetiracetam and, more recently lacosamide, are used in CSE that persists after first-line treatments (established CSE). Phenytoin is more difficult to administer and is less well tolerated. Evidence of the efficacy of lacosamide is scarce. Anaesthetics are the drugs of choice for the treatment of refractory CSE (not responding to second-line drugs). Midazolam seems to be the best tolerated and is the most often used drug, followed by propofol and thiopental (pentobarbital in the USA). A few studies indicate that ketamine is effective with the possible advantage that it can be co-administered with other anaesthetics, such as midazolam or propofol. CSE becomes super-refractory after more than 24h of appropriate treatments and may last weeks. Several anaesthetics have been proposed but evidence is scarce. Autoimmune refractory CSE has been recently identified, and early treatment with immuno-modulatory agents (corticosteroids and IV immunoglobulins and also second-line agents such as cyclophosphamide and rituximab followed by chronic immunosuppressive treatment) is now recommended by many experts.