Drug-Resistant Epilepsy: Potential Causes and Treatments Rose Ludecke
Abstract: One in three people with Epilepsy are nonresponsive to drugs attempting to suppress their epileptic episodes. This is known as Refractory Epilepsy and is defined as when a patient is unresponsive to two sufficient trials of anti-seizure medications (ASMs).1 A variety of treatments are possible, and further research looks more closely into potential mechanisms that may cause this condition. Introduction to Epilepsy Epilepsy is a condition that affects the Central Nervous System. Specifically, it is a neurological disorder in which the brain acts abnormally causing uncontrollable seizures, behaviors, sensations, and sometimes loss of awareness.2 The types of seizures or symptoms present among patients can vary in severity. Some will stare blankly, while others will twitch or seize uncontrollably.2 The brain operates through bursts of electricity between different neurons that work collectively to control thoughts, emotions, and movements. During an epileptic episode, something is disrupting this communication between the neurons, which can potentially cause a seizure to occur. There are two main categories for types of seizures: focal onset seizures and generalized onset. Focal onset seizures originally start in one specific area of the brain, and then spread across the brain. Patients with focal onset seizures usually have had some sort of trauma to a specific part of the brain that is now the origin of focal onset seizures, like a stroke or meningitis.3 Further, some patients can feel focal seizures start to occur before the 16
symptoms become more intense. In generalized onset seizures, the activity occurs on both sides of the brain as opposed to originating in one specific part of the brain, and then spreading across the brain (Figure 1).
Figure 1: Generalized vs. Focal Seizures 4
Generalized onset seizures can be genetic, and usually start during childhood because of the brain’s inability to regulate the electricity between the neurons. Most patients who have epilepsy are able to be treated through medication. However, around 1/3 of the population with Epilepsy cannot be treated with medication, and instead have a form of Epilepsy known as Refractory Epilepsy. Drug-Resistant Epilepsy Drug-resistant Epilepsy is clinically defined as when a patient has been unable to stay seizure-free after two sufficient trials of antiseizure medications.1 This condition affects about 1/3 of all patients with epilepsy. The reasons for drug-resistance to Epilepsy vary and have different contributing factors from patient-to-patient due to different circumstances, and theoretically the action site of the medication being used.4 Potential Causes to Drug-Resistant Epilepsy There is no consensus on the cause or causes of drug-resistant epilepsy. Simpler ideas put forth by doctors and scientists identify factors such as age, where older patients reported better results to the medication, and were more likely to be seizure-free.4
