RESUMO
OBJECTIVE: We explored the efficacy and safety profile of cenobamate as an adjunctive therapy in patients with refractory focal-onset epilepsy in the pediatric population. METHODS: This was a retrospective, single-center study of cenobamate used as an adjunctive medication in pediatric patients with refractory focal-onset epilepsy . We measured seizure reduction, median reduction in seizure frequency, median dose, responder rate, and treatment-emergent adverse events. RESULTS: We studied the efficacy and safety profile of cenobamate in 21 pediatric patients (mean age 15.9). Cenobamate was up titrated using the prescribed starter pack with final doses ranging from 100â¯mg to 400â¯mg daily. The mean and median dose of cenobamate was 209.8â¯mg (±98.87â¯mg) and 200â¯mg (175-275), respectively. For patients weighing less than 50â¯kg, mean and median dose was 4.0â¯mg/kg/day (3.20-4.63) and 4.32â¯mg/kg/day, respectively. Mean and median baseline seizure frequency per month in this cohort was 15.38 and 16, respectively, prior to the introduction of cenobamate. After the adjunctive use of cenobamate, mean and median seizure frequency per month reduced to 7.29 and 1, respectively; median reduction in seizure frequency was 93.7%. Seizure reduction of at least 50% (responder rate) was noted in 13 (62.5%) patients and a seizure reduction of at least 75% noted in 11 (52.4%) patients, similar to that seen in adults. Four patients (19%) achieved seizure freedom. Of the 21 pediatric patients, 9 (42.8%) patients had treatment-emergent adverse events (TEAE) with the most commonly reported symptom being ataxia (5, 23.8%) and sedation (2, 9.5%). Three (14.3%) patients discontinued early due to these side effects. No children developed drug rash with eosinophilia and systemic symptoms (DRESS). CONCLUSION: Cenobamate demonstrates similar efficacy rates and safety profile within the pediatric population when compared to the published adult data, making it an effective, safe, and tolerable adjunctive medication for children with refractory focal-onset epilepsy, even at the maximum daily dose.
Assuntos
Epilepsia Resistente a Medicamentos , Epilepsias Parciais , Epilepsia , Adolescente , Adulto , Anticonvulsivantes/uso terapêutico , Carbamatos , Criança , Clorofenóis , Epilepsia Resistente a Medicamentos/induzido quimicamente , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsias Parciais/tratamento farmacológico , Epilepsia/tratamento farmacológico , Humanos , Estudos Retrospectivos , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Tetrazóis , Resultado do TratamentoRESUMO
ABSTRACT: A 16-year-old adolescent boy with extensive travel throughout West Africa presented with a 6-year history of social withdrawal, anhedonia, and daytime sleepiness. The patient's electroencephalography was normal. Initial MRI revealed small pituitary gland and left temporal developmental venous anomaly. Subsequently obtained 18F-FDG brain PET was notable for markedly severe hypometabolism in the brainstem. Further workup revealed a normal orexin, autoimmune encephalitis panel, and negative titers for Trypanosoma brucei and cruzi in the CSF. Outpatient sleep study showed mild obstructive sleep apnea, and multiple sleep latency test revealed reduced mean sleep latency at 7 minutes with sleep-onset REM in 3/5 naps, findings consistent with narcolepsy type 2.
Assuntos
Distúrbios do Sono por Sonolência Excessiva , Narcolepsia , Adolescente , Encéfalo/diagnóstico por imagem , Fluordesoxiglucose F18 , Humanos , Masculino , Narcolepsia/diagnóstico por imagem , PolissonografiaRESUMO
PCDH19-related epilepsy is a developmental and epileptic encephalopathy typically presenting with epilepsy and varying degrees of intellectual disability. Seizures typically present in clusters of focal or generalized seizures, sometimes in the setting of fever. We present the case of a 7-month-old girl presenting with new-onset refractory status epilepticus that followed routine vaccine administration and ensuing cytokine storm. She was diagnosed with a pathogenic variant in PCDH19 The patient required 5 antiseizure medications and pentobarbital-induced burst suppression for control of seizures. She was noted to have elevated serum cytokine levels (interleukin [IL]-2, IL-4, IL-10, IL-13, IL-17, IL-1, IL-1ß, and IL-8) and CSF cytokine levels (IL-6 and IL-13). Anakinra was initiated and titrated based on serial cytokine levels, with doses ranging from 5 to 20 mg/kg/d resulting in reduction in cytokine levels and seizure reduction. By age 14 months, she was able to be maintained on 3 active antiseizure medications and ketogenic diet for seizure control.