Limited Ability to Adjust N2 Amplitude During Dual Task Walking in People With Drug-Resistant Juvenile Myoclonic Epilepsy

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.

Abnormal gait and motor cortical processing in drug‐resistant juvenile myoclonic epilepsy

“…In a recently published study by our group, we recorded event related potentials (ERPs) while responder JME and DR‐JME patients performed visual Go/NoGo task while walking on a treadmill. We found a reduced ability to adjust N2 potential in patients with DR‐JME, reflecting abnormal frontal inhibition mechanism that is normally active during abstaining of motor action (during the NoGo trials) (Yam et al., 2022 ). Furthermore, this attenuation in N2 potential during dual‐task walking in DR‐JME patients was maximal in the central head regions, pointing to abnormal cognitive processing in networks that involve these regions (Yam et al., 2022 ).…”

“…The Go cue consisted of white English letters appearing over a black background in the center of a computer screen, between two vertical white lines which remain on the screen throughout the whole duration of the experimental. The task included two sessions, each of 6 min that comprised 400 cues (Yam et al., 2022 ). The interstimulus interval was randomly varied between 1000 and 3000 ms with steps of 250 ms. All the correct responses and their response time were used for further analysis.…”

A systematic review and meta-analysis of factors related to first line drugs refractoriness in patients with juvenile myoclonic epilepsy (JME)

“…Mor Yam (2022) [21] Failure of adequate trials of two tolerated, appropriately chosen and used ASMs schedules Asadi-Pooya (2022) [22] Having ongoing seizures Siew-Na Lim (2023) [23] Patients who had experienced seizures in the past one year were considered to have ongoing seizures, even if the seizures occurred due to external factors such as sleep deprivation.…”

Cannabidiol‐enriched oil for adult patients with drug‐resistant epilepsy: Prospective clinical and electrophysiological study

“…We have recently demonstrated in patients with juvenile myoclonic epilepsy that drug resistance is associated with altered gait and motor-cognitive electrophysiological processing. 15,16 To this end, we aimed to examine the effects of CBDO on seizure control and on motor-cognitive functions including gait, in patients with DRE, and to reveal the electrophysiological changes in resting EEG and using event-related potentials (ERPs) during the performance of motor and cognitive tasks in patients treated with CBDO. We hypothesize that motor-cognitive functions and ERPs will differ between responders and non-responders to CBDO treatment.…”