The patient is a 12-year-old right-handed female with history of epilepsy of unknown cause (possible encephalitis), with onset at age 5 years. Seizures manifested with exclusively left-hemispheric onset focal seizures, with and without impairment of awareness, and with and without focal to bilateral tonic-clonic seizures. From age 5 to 12 years, long spans of seizure freedom accompanied the use of lacosamide (LAC), levetiracetam (LEV), and clobazam (CLB), though breakthrough seizures occurred approximately annually. At age 12, the patient suffered a precipitous and unexplained escalation of seizures, with evolution to SRSE. After numerous treatment failures (see Fig. 1), seizures were nearly controlled with intravenous midazolam (MDZ) or pentobarbital (PTB), though multiple attempts to wean either agent led to resurgence of seizures. With seizures localized to both the left central and frontopolar regions on EEG - despite normal neuroimaging - the clinical team prepared for extraoperative electrocorticography with the expectation that the identified epileptogenic zone would likely encompass dominant motor cortex (hand). Anticipated resection of eloquent cortex was deemed reasonable, relative to the risks of SRSE and prolonged intensive care unit hospitalization.
After more than three months of SRSE, as a last medication trial prior to surgery, the patient began treatment with CBD in the midst of frequent clinical seizures (5-20/day) and while still receiving MDZ (0.3 mg/kg/h), CLB (1 mg/kg/day), phenobarbital (PB, 0.8 mg/kg/day), LAC (10 mg/kg/day), and perampanel (PER, 0.2 mg/kg/day). CBD was administered orally with an initial dosage of 5 mg/kg/day, divided BID, with titration by 5 mg/kg/day every 3 days to a peak dose of 20 mg/kg/day. Clinical seizure-freedom was achieved on day 12 of CBD, but subclinical seizures persisted. The patient was discharged on day 21 of CBD, and complete seizure freedom was demonstrated with 24-hour video-EEG on day 64 of CBD. The patient remains seizure-free at most recent follow-up, despite the sequential discontinuation of PB, MDZ, PER, and dose-reduction of LAC. At present, the patient is maintained on CBD (20 mg/kg/day), CLB (0.8 mg/kg/day), and zonisamide (ZNS) (0.6 mg/kg/day, tapering).
CBD was generally well-tolerated with the patient having resumed all activities of daily living, though she reported substantial fatigue and gained 15 kg (25% body mass) in the first year of CBD exposure. In addition she developed new-onset non-epileptic seizures (NES), which were initially mistaken for epileptic seizures and which prompted a course of corticosteroids, titration of CBD to the original weight-based dosage of 20 mg/kg/day, and initiation of ZNS.
Of note, compared to pre-CBD baseline, serum levels of CLB and N-desmethylclobazam (NDCLB) rose substantially (Fig. 2) during both titration and maintenance of CBD treatment, and despite aforementioned reductions in the weight-based dosage of CBD and CLB. In addition, the relatively dramatic rise in CLB and NDCLB levels over the first 60 days of CBD therapy also accompanied discontinuation of PB and MDZ and dose-reduction of PER.