Factors associated with pharmacoresistance in patients with epilepsy: analysis of clinical predictors

Abstract

Background: Pharmacoresistance in epilepsy remains a major challenge in neurological practice, despite the expansion of available therapeutic options. It is estimated that approximately one-third of patients with epilepsy have inadequate seizure control, with variation according to epileptic syndrome, etiology, age at onset, and the presence of associated neurological deficits. Recent studies indicate a higher prevalence in clinical cohorts, as well as frequent associations with neurological deficits, electroencephalographic abnormalities, and focal or symptomatic epilepsy. Objective: To analyze the main factors associated with pharmacoresistance in patients with epilepsy, with emphasis on clinical, structural, and electroencephalographic markers. Methods: This was an observational, retrospective, and analytical study conducted with patients with epilepsy followed at a specialized center. Clinical variables were analyzed, including age at seizure onset, type of epilepsy, seizure frequency, electroencephalographic findings, neuroimaging abnormalities, and number of drugs used. Pharmacoresistance was defined as the persistence of seizures despite the appropriate use of at least two suitable therapeutic regimens. Results: Studies consistently show that pharmacoresistance is related to greater clinical severity from the onset of the disease. The most recurrent factors include high seizure burden before treatment, focal epilepsy, structural etiology, neuroimaging abnormalities, abnormal electroencephalogram, multiple seizure types, and the presence of neurological deficits. In adults, the type of epilepsy/seizure, structural etiology, abnormal magnetic resonance imaging, and history of febrile seizures were also associated with a higher risk of pharmacoresistance. In children, predictors vary according to the epileptic syndrome, but may be anticipated by accessible clinical variables throughout the course of the disease. In a prospective cohort of newly diagnosed focal epilepsy, treatment resistance occurred in 22.8% of participants; very frequent seizures before treatment and psychiatric comorbidities significantly increased this risk. In addition, the literature shows that the probability of achieving seizure freedom decreases as the number of previously failed therapeutic regimens increases Conclusion: Pharmacoresistance in epilepsy appears to result from the interaction of factors related to etiology, initial severity, electroclinical pattern, and pretreatment seizure burden. The findings reinforce that patients with focal/structural epilepsy, abnormal complementary tests, higher seizure frequency, and neuropsychiatric comorbidities should be recognized early as a higherrisk group. After failure of two adequate treatments, diagnostic reassessment and early referral to a specialized center are recommended, including consideration of epilepsy surgery and other targeted approaches.