Treatment of Super-Refractory Status Epilepticus in FIRES

“Effectiveness of Electroconvulsive Therapy for Refractory Status Epilepticus in Febrile Infection–Related Epilepsy Syndrome”

“Febrile Infection–Related Epilepsy Syndrome: Clinical Review and Hypotheses of Epileptogenesis”

The treatment of status epilepticus (SE) consists of administration of benzodiazepines (early SE), followed by phenobarbital, phenytoin, or valproate (established SE). If therapy with at least two adequately dosed anticonvulsants remains unsuccessful and SE continues or reappears, refractory SE is present. At that point, general anesthesia is introduced to establish a burst suppression pattern electroencephalogram (EEG). If all these measures remain ineffective, a “super-refractory status epilepticus” (SRSE) is reached. Treatment of SRSE is difficult, and controlled trials are mostly lacking. If several courses of anesthesia and standard AED treatment are of no avail, remaining options become scarce, and they may include desperate measures such as magnesium infusion, ketogenic diet, hypothermia, emergency neurosurgery, or even electroconvulsive therapy to name only some.[1]

In this issue van Baalen and coworkers review FIRES (febrile infection-related epilepsy syndrome), an obscure epileptic encephalopathy, most likely immune mediated, that usually presents with SRSE as initial manifestation.[2] The authors have a long-standing interest in this disorder and have contributed significantly to the literature on this syndrome. FIRES is one of the most malignant, sporadic epileptic encephalopathies of childhood. A significant number of children with FIRES have died during intensive care therapy, whereas others have remained on intensive care for almost 1 year. Even if SE or SRSE is more or less readily controlled, basically all patients will immediately suffer from severe intellectual impairment and chronic epilepsy. The sudden onset of this irreversible “gray matter failure” resembles the most striking and most unparalleled feature of FIRES. There are only very few cases of children surviving FIRES without severe sequelae reported. Controlled trials are hardly possible in a disease with a prevalence of 1/100,000. However, there are some indications that SE therapy in FIRES might differ from that in other etiologies. The authors point out that “emergency introduction” of ketogenic diet, and possibly also high-dose phenobarbital and benzodiazepines, might offer the best success chances.[3] Van Baalen et al discuss possible immune-mediated mechanisms in FIRES that are educative also for the nonimmunologist reader.[2] I am, however, a little reluctant with their suggestion to rename FIRES to “fulminant immune response epilepsy syndrome.” A new name won't help the lack of new data.

Also in this issue, Veiga and coworkers report a well-documented FIRES case with SRSE and successful electroconvulsive therapy after 8 weeks of futile treatment on an intensive care unit.[4] After what may be called standard treatment of SE and SRSE, the authors felt forced to introduce ketogenic diet, immunoglobulins, lidocaine, plasmapheresis, and therapeutic hypothermia, albeit without success. Finally they turned to electroconvulsive therapy. Altogether 14 sessions were performed. Only five resulted in a generalized tonic-clonic seizure that is considered a prerequisite of effectiveness. In contrast to most previously reported cases in children, Veiga et al give a detailed report on the technical settings and doses they used.[4] In face of the fact that FIRES is a potentially fatal disease, this case report may be of interest for future cases.

In their review on therapy options in SRSE, Ferlisi and Shovron also mention “cerebrospinal fluid drainage” as a possible, however remote, option in refractory cases that was in use already in the 1940s.[1] The last positive report on this method comes from Köhrmann et al.[5] The authors theorize that the effect may be based on the removal of inflammatory or toxic substances in the cerebrospinal fluid (CSF). It may be speculated that in a possibly immune-mediated debilitating encephalopathy such as FIRES, this might be a possible option if all other strategies have failed.

This article is an editorial comment on “Febrile infection–related epilepsy syndrome: clinical review and hypothesis of epileptogenesis” by van Baalen et al (Neuropediatrics 2017;48(1):5–18) and on “Effectiveness of electroconvulsive therapy for refractory status epilepticus in febrile infection-related epilepsy syndrome” by Veiga et al (Neuropediatrics 2017;48(1):45–48).

• References

• 1 Ferlisi M, Shorvon S. The outcome of therapies in refractory and super-refractory convulsive status epilepticus and recommendations for therapy. Brain 2012; 135 (Pt 8) 2314-2328
• 2 Van Baalen A, Vezzani A, Häusler M, Kluger G. Febrile infection–related epilepsy syndrome: clinical review and hypothesis of epileptogenesis. Neuropediatrics 2017; 48 (1) 5-18
• 3 Kramer U, Chi CS, Lin KL , et al. Febrile infection-related epilepsy syndrome (FIRES): pathogenesis, treatment, and outcome: a multicenter study on 77 children. Epilepsia 2011; 52 (11) 1956-1965
• 4 Veiga AM, Moreno DC, Gomez Menéndez AI , et al. Effectiveness of electroconvulsive therapy for refractory status epilepticus in febrile infection-related epilepsy syndrome. Neuropediatrics 2016; 48 (1) 45-48
• 5 Köhrmann M, Huttner HB, Gotthardt D, Nagel S, Berger C, Schwab S. CSF-air-exchange for pharmacorefractory status epilepticus. J Neurol 2006; 253 (8) 1100-1101