Abstract
Juvenile myoclonic epilepsy (JME) is one of the most common epileptic syndromes; it is estimated to affect 1 in 1,000 people worldwide. Most people with JME respond well to medication, but up to 30% of them are drug-resistant. To date, there are no biomarkers for drug resistance in JME, and the poor response to medications is identified in retrospect. People with JME have frontal dysfunction manifested as impaired attention and difficulties in inhibiting habitual responses and these dysfunctions are more pronounced in drug-resistant individuals. Frontal networks play an important role in walking and therefore, gait can be used to overload the neural system and expose subtle changes between people with drug-responsive and drug-resistant JME. Electroencephalogram (EEG) is a promising tool to explore neural changes during real-time functions that combine a cognitive task while walking (dual tasking, DT). This exploratory study aimed to examine the alteration in electrical brain activity during DT in people with drug-responsive and drug-resistant JME. A total of 32 subjects (14 males and 18 females) participated: 11 drug-responsive (ages: 31.50 ± 1.50) and 8 drug-resistant (27.27 ± 2.30) people with JME, and 13 healthy controls (29.46 ± 0.69). The participants underwent EEG examination during the performance of the visual Go/NoGo (vGNG) task while sitting and while walking on a treadmill. We measured latencies and amplitudes of N2 and P3 event-related potentials, and the cognitive performance was assessed by accuracy rate and response time of Go/NoGo events. The results demonstrated that healthy controls had earlier N2 and P3 latencies than both JME groups (N2: p = 0.034 and P3: p = 0.011), however, a limited ability to adjust the N2 amplitude during walking was noticeable in the drug-resistant compared to drug-responsive. The two JME groups had lower success rates (drug-responsive p < 0.001, drug-resistant p = 0.004) than healthy controls, but the drug-resistant showed longer reaction times compared to both healthy controls (p = 0.033) and drug-responsive (p = 0.013). This study provides the first evidence that people with drug-resistant JME have changes in brain activity during highly demanding tasks that combine cognitive and motor functions compared to people with drug-responsive JME. Further research is needed to determine whether these alterations can be used as biomarkers to drug response in JME.
Highlights
Epilepsy is amongst the most common chronic neurological disorders affecting more than 70 million people worldwide [1]
Comparison of color trail test (CTT) scores between each patient group and healthy controls revealed that there was no difference between healthy controls and drug-responsive CTT scores (t = −1.279, p = 0.218, d = 0.556) but that healthy controls had higher scores than people with drug-resistant Juvenile myoclonic epilepsy (JME) (W = 10, p = 0.006, Rank96 Biserial correlation = 0.750)
People with drug-resistant JME were prescribed a higher number of current medications (t = −2.367, p = 0.030, d = −1.100)
Summary
Epilepsy is amongst the most common chronic neurological disorders affecting more than 70 million people worldwide [1]. Juvenile myoclonic epilepsy (JME) is a generalized epilepsy syndrome, accounting for up to 10% of all epilepsies [2]. It is characterized by several generalized seizure types and diffuse epileptiform activity that is maximal over frontocentral regions [3]. People with JME usually respond well to antiseizure medications (ASMs), yet about 15–30% of them will continue to experience seizures despite appropriate ASMs and suffer from drug-resistant epilepsy (DRE) [4,5,6]. Despite several attempts to find a marker for DRE [10,11,12], there are no biomarkers for drug resistance in people with JME, and the poor response to medications is identified retrospectively
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