Researchers at University College, Queen Square, London, UK have evaluated the world literature on the treatment of super-refractory status epilepticus (SRSE) and proposed a protocol and flowchart for management. SRSE is defined as status epilepticus that continues or recurs 24 hours or more after the onset of anesthetic therapy or after reduction or withdrawal of anesthesia. Stages of treatment are as follows: Stage 1. Early status; first 30 min; treat with iv lorazepam, iv or rectal diazepam; Stage 2. Established status; 30-120 min; treat with iv antiepileptic drugs, phenytoin, phenobarbital or valproate; Stage 3. Refractory status; >120 min; treat with general anesthesia (eg. propofol, midazolam, or thiopental/pentobarbital); Stage SRSE; after 24 hours in status. Treatments used and recommended for SRSE include the following in this order: anesthetic agents and antiepileptic drugs, identify and treat the cause, magnesium infusion, iv pyridoxine, consider steroids and immunotherapy, consider resective neurosurgery in lesional SE, consider multiple subpial transection, hypothermia, ketogenic diet, transcranial magnetic stimulation, vagal nerve stimulation, consider deep brain stimulation, electroconvulsive therapy, drainage of cerebrospinal fluid, and older drug therapies. Treatment of the underlying cause is stressed. Premature withdrawal of therapy is discouraged, since recovery can occur after even weeks of status epilepticus. A multinational database of outcomes of individual therapies is urgently needed. 
COMMENT. The authors offer an interesting review of the mechanism of super-refractory SE. A reduction in GABAergic activity is proposed as a reason for status epilepticus to develop and also for an increasing ineffectiveness of GABAergic drugs (such as benzodiazepines or barbiturates) in controlling status. Other reported proposed causes for SRSE include mitochondrial insufficiency, changes in extracellular ionic environment, inflammatory disease, opening of the blood brain barrier, and possible changes in gene expression. Emergency therapy directed at the cause is crucial in terminating the seizure. (Neligan and Shorvon, 2011).