Director Pediatric Epilepsy/ Professor California Northstate Medical School Sutter Health Neuroscience Institute Roseville, California
Rationale: Super refractory status epilepticus ( SRSE) is commonly associated with severe clinical sequelae. Intavenous ganaxolone (IV GNX) is an investigational drug that acts on both synaptic and extra-synaptic GABAA receptors, and therefore may have a role in treatment SRSE. We present a pediatric patient treated with IV GNX. Methods: A four-year-old (27kg) girl with Angelman and Lennox-Gastaut syndromes presented with refractory tonic (>100/day) and atypical absence seizures with an continuous video EEG showing 2.5 hz continuous slow-spike and wave activity and super refractory status epilepticus (Figure 1). Valproic serum levels were 106 ug/ml, with clobazam 1mg/kg/d. No response was seen to 1mg/kg rectal diazepam, IV lorazepam (0.5mg/kg), ethoxsuccimide 40mg/kg, perampamil (16 mg x 2 doses), or midazolam 2mg IV. Pentobarbitol anesthetic coma was titrated to 5 mg/kg/hr to maintain burst suppression on EEG. Ethoxsuccimide and perampamil were stopped, and ACTH 150mg/m2 tried for three days without improvement or ability to wean pentobarbitol. Pentobarbitol was rapidly tapered down after 4.5 days 1.5 hours before starting IV GNX obtained by emergency IND. EEG again showed status pattern as at baseline (Figure 1) before IV GNX bolus of 0.64mg/kg over 5 minutes followed by 1.12 mg/kg/hr for two hours, and then maintained at 0.46 mg/kg/hr IV infusion for 5 days followed by rapid taper and starting oral ganaxolone 300mg/kg TID (second emergent IND) . Patient was extubated after 48 hr of IV GNX. She was discharged five days later on oral GNX and baseline ASM of valproic acid and clobazam. Results: Rapid improvement on EEG within ten minutes of IV GNX (Figure 2) and EEG remained improved overall and resolution of status epilepticus was maintained over the five days until weaning IV GNX and converting to oral GNX for discharge four days later. Now four weeks after discharge the patient who was having 20 seizures per day at baseline was reported to have no clinical seizures after hospitalization of ten days for SRSE. Patient is mentally and physically returned to her functional baseline. Conclusions: Administration of IV GNX was effective in treating SRSE in this patient with Angelman Syndrome and LGS. Additional pediatric study of IV GNX for SRSE is warranted Funding: Please list any funding that was received in support of this abstract.: none
