Abstracts

Rationale: Cannabidiol (CBD) is a promising investigational therapy for several forms of treatment resistant epilepsy, most notably the syndromes of Dravet, Lennox-Gastaut, and West (infantile spasms). We present the case of a child with super-refractory status epilepticus (SRSE) treated with pure cannabidiol.  Methods: Clinical data were abstracted from the medical record. The use of CBD (Epidiolex®, GW Pharmaceuticals, UK) was accomplished via the Emergency Investigational New Drug (EIND) program.  Results: The patient is a 12-year-old right-handed girl with history of focal epilepsy with onset at age 5 years in the setting of presumed encephalitis. Seizures were of exclusively left-hemispheric onset and clinically manifested with right hand shaking, without aura, and with variable evolution including frequent secondary generalization. Serial MRI exams and extensive testing for infectious and autoimmune encephalitides were unrevealing. Over 7 years, long spans of seizure freedom accompanied the use of lacosamide (LAC), levetiracetam (LEV), and clobazam (CLB), though breakthrough clusters of seizures occurred approximately annually. At age 12 years, the patient suffered a precipitous and unexplained escalation of seizures with evolution to SRSE. After numerous treatment failures of standard AED therapy and investigational progesterone and immunological therapies (Table 1), seizures were nearly controlled with intravenous midazolam (MDZ) or pentobarbital, independently, though multiple consecutive attempts to wean either agent led to resurgence of seizures. After obtaining an EIND, the patient was started on a trial of CBD on hospital day 97, in the midst of frequent clinical seizures (5-20/day) and while still receiving MDZ (0.3 mg/kg/hr), CLB (1 mg/kg/d), phenobarbital (PHB, 0.8 mg/kg/d), LAC (10 mg/kg/d), and perampanel (PER, 0.2 mg/kg/d). Initial CBD dosage was 5 mg/kg/d, p.o., divided BID, with titration by 5 mg/kg/d every 3 days to a peak dose of 20 mg/kg/d. Clinical seizure-freedom was achieved on day 10 of CBD (20 mg/kg/d), which preceded electrographic seizure freedom.  Overnight video-EEG (vEEG) (day 16 of CBD) revealed >100 brief subclinical seizures and repeat overnight vEEG (day 64 of CBD) revealed complete seizure-freedom. At most recent follow-up (day 106 of CBD), seizure-freedom has been maintained despite discontinuation of PHB (day 6) and MDZ (day 17), and ongoing taper of PER. The patient has returned to school and resumed all activities of daily living. Of note, CBD exposure accompanied a substantial rise in serum levels of CLB (29→608 ng/mL) and N-desmethylclobazam (NDCLB, 769→10068 ng/mL). The patient reports fatigue, but no other side effects.  Conclusions: To our knowledge, this is the first report of successful treatment of a non Febrile Infection-Related Epilepsy Syndrome (FIRES) case of SRSE which is likely from use of CBD. We must consider other potential—albeit less likely—mediators of response including a late effect of allopregnanolone, elevated CLB/NDCLB levels, or spontaneous resolution of SRSE. Further study is clearly warranted. Funding: None