Use of cannabidiol in child with refractory seizures: sustained clinical improvements

Case presentation: A 7 month-old was admitted for presenting a clinical condition suggestive of an Inborn Error of metabolism, as she showed development delay, early onset refractory seizures and generalized dystonia associated with infectious events. After 3 years, she remained unresponsive to treatment, presenting over 15 tonic-clonic events per day, and complementary exams were nonspecific, as EEG showed left temporo-occipital intermittent slow activity and MRI revealed hypersignal on T2, with diffusion restriction in the medial longitudinal fascicles. Also, genetic testing was inconclusive, though it indicated mitochondriopathy. Due to this suspicion, Valproate was suspended and Cannabidiol (400 mg/day) was recommended for seizure control, along with Phenobarbital (5 mg/kg/day), Oxcarbazepine (35 mg/kg/day), Clobazam (1 mg/kg/day) and co-factors (L-carnitine, thiamine and riboflavin). Since this therapy was established, she presented full control of the seizures and increased her development process. Therefore, it is understood that the relevance of the case is closely linked to the need for an adequate and appropriate prescription.

Discussion: Even though refractory epilepsy is a recurrent and morbidity associated condition, its management is not fully mastered. In this context, cannabidiol (CDB) treatment has gained prominence, as it has been shown that it might reduce seizure frequency and have an adequate safety profile in these patients. Although its mechanism is not completely known, it is known that CBD is a potent inhibitor of the CYP3A and CYP2C enzymes, which are responsible for metabolism of clobazam and other antiseizure medications, suggesting that metabolite levels of this drugs can rise with concomitant use of CBD. These findings corroborate with the benefit obtained after the concomitant treatment of CBD and Phenobarbital, Oxcarbazepine, Clobazam in this case report.

Final comments: Worldwide medicinal use of CBD is rapidly escalating, despite limited evidence of its efficacy from preclinical and clinical studies. Yet, recent clinical trials of cannabidiol in refractory epilepsy support its clinical efficacy for reduction of seizure frequency. So, though we reinforce that patients receiving cannabinoids should be monitored, we showed here that CBD treatment can have an acceptable safety profile and lead to sustained clinical improvements. Considering this, the absence of this treatment can determine not only a great negative impact on the development, but also the death of the child.

 

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Artikel online veröffentlicht:
18. September 2023