Seizure freedom on subtherapeutic levels of valproic acid

A BSTRACT Valproic acid (VPA) is a well-established antiseizure medication typically prescribed to maintain serum levels between 50 and 100 μg/mL. This case report presents a 25-year-old male with idiopathic generalized epilepsy who achieved long-term seizure freedom while on significantly subtherapeutic VPA levels. The patient initially maintained seizure control on a 750 mg once-daily regimen, with a measured VPA level of 35 μg/mL and a normal sleep-deprived EEG. Following a reduction to 500 mg daily due to medication-related tremors, seizure control persisted and a repeat EEG remained normal. However, after a further reduction to 250 mg daily, a subsequent EEG revealed new-onset generalized epileptiform discharges. Despite reverting promptly to the prior 500 mg dose, the patient experienced a seizure 3 days later. He remained seizure-free for 1 year following this episode while continuing on the 500 mg dose. This case highlights two important clinical observations: First, seizure freedom can be sustained at subtherapeutic serum VPA levels in certain patients; second, EEG abnormalities may serve as an early biomarker of increased seizure risk following dose adjustments. To our knowledge, such a pattern has not been previously documented. This case emphasizes the utility of EEG in guiding treatment decisions and monitoring subclinical changes in patients with idiopathic generalized epilepsy.