Epilepsy is a neurological condition characterized by recurrent, unprovoked seizures, resulting from abnormal electrical activity in the brain. While many individuals with epilepsy can manage their condition effectively with medication, a significant portion continues to experience seizures. This persistent seizure activity, despite therapeutic efforts, defines a challenging aspect of epilepsy known as drug-resistant epilepsy.
Understanding Drug-Resistant Epilepsy
Drug-resistant epilepsy (DRE) is defined as the failure of adequate trials of two appropriately chosen and tolerated anti-seizure medications, used alone or in combination, to achieve sustained seizure freedom. It is also known as refractory, intractable, or pharmacoresistant epilepsy. The continued presence of seizures significantly impacts an individual’s quality of life. Individuals with DRE often face increased risks of injuries, psychosocial challenges, and cognitive impairment, along with an elevated risk of Sudden Unexpected Death in Epilepsy (SUDEP). Managing DRE extends beyond seizure control to addressing these broader effects on daily living.
Prevalence and Scope
Drug-resistant epilepsy affects a considerable proportion of the epilepsy population. Approximately one-third (30-40%) of all people with epilepsy experience seizures that do not respond well to anti-seizure medications. This percentage has remained largely consistent despite new medications. Given that epilepsy affects about 1% of the global population, an estimated 80 million people worldwide live with the condition, meaning approximately 24 million individuals globally may experience drug-resistant epilepsy. In the United States alone, over 1 million people continue to have seizures despite medication, highlighting the significant scope of this challenge and the ongoing need for advanced treatment and research.
Factors Contributing to Resistance
Several biological and physiological factors contribute to drug resistance. The underlying cause of epilepsy plays a role, with conditions like focal cortical dysplasia, hippocampal sclerosis, or specific genetic mutations such as SCN1A associated with a higher likelihood of resistance. The duration of epilepsy, seizure frequency, and early onset can also increase risk. One prominent mechanism involves the overexpression of drug transporters, particularly P-glycoprotein (Pgp), at the blood-brain barrier. These transporters actively pump anti-seizure medications out of the brain, reducing their concentration at target sites where they need to act. This efflux mechanism can render medications less effective, contributing to the persistence of seizures.
Identifying Drug Resistance
Healthcare professionals determine drug resistance based on specific diagnostic criteria established by organizations like the International League Against Epilepsy (ILAE). For a trial to be considered adequate, the medication must have been appropriately chosen for the individual’s seizure type, well-tolerated, and administered at a sufficient dose for a suitable duration. Once two appropriate medications have failed to control seizures, the probability of achieving seizure freedom with additional drug trials drops significantly, often to 5% or less. This low probability is a key indicator for identifying drug resistance. Accurate diagnosis is important for guiding further management strategies and exploring alternative therapeutic avenues.