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

OBJECTIVE: Cannabidiol-enriched oil (CBDO) is being used increasingly to improve seizure control in adult patients with drug-resistant epilepsy (DRE), despite the lack of large-scale studies supporting its efficacy in this patient population. We aimed to assess the effects of add-on CBDO on seizure frequency as well as on gait, cognitive, affective, and sleep-quality metrics, and to explore the electrophysiological changes in responder and non-responder DRE patients treated with add-on CBDO. METHODS: We prospectively recruited adult DRE patients who were treated with add-on CBDO. Patients were evaluated prior to treatment and following 4 weeks of a maintenance daily dose of ≈260 mg CBD and ≈12 mg Δ9-tetrahydrocannabinol (THC). The outcome measures included seizure response to CBDO (defined as ≥50% decrease in seizures compared to pre-CBDO baseline), gait testing, Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HADS), and sleep-quality questionnaire assessments. Patients underwent electroencephalography (EEG) recording during rest as well as event-related potentials (ERPs) during visual Go/NoGo task while sitting and while walking. RESULTS: Nineteen patients were recruited, of which 16 finished pre- and post-CBDO assessments. Seven patients (43.75%) were responders demonstrating an average reduction of 82.4% in seizures, and nine patients (56.25%) were non-responders with an average seizure increase of 30.1%. No differences in demographics and clinical parameters were found between responders and non-responders at baseline. However, responders demonstrated better performance in the dual-task walking post-treatment (p = .015), and correlation between increase in MoCA and seizure reduction (r = .810, p = .027). Post-CBDO P300 amplitude was lower during No/Go-sitting in non-responders (p = .028) and during No/Go-walking in responders (p = .068). SIGNIFICANCE: CBDO treatment can reduce seizures in a subset of patients with DRE, but could aggravate seizure control in a minority of patients; yet we found no specific baseline clinical or electrophysiological characteristics that are associated with response to CBDO. However, changes in ERPs in response to treatment could be a promising direction to better identify patients who could benefit from CBDO treatment.

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

BACKGROUND: Juvenile myoclonic epilepsy (JME) is characterized by generalized seizures. Nearly 30% of JME patients are drug-resistant (DR-JME), indicating a widespread cortical dysfunction. Walking is an important function that necessitates orchestrated coordination of frontocentral cortical regions. However, gait alterations in JME have been scarcely investigated. Our aim was to assess changes in gait and motor-evoked responses in DR-JME patients. METHODS: Twenty-nine subjects (11 JME drug-responder, 8 DR-JME, and 10 healthy controls) underwent a gait analyses during usual walking and dual-task walking. Later, subjects underwent 64-channel EEG recordings while performing a simple motor task. We calculated the motor-evoked current source densities (CSD) at a priori chosen cortical regions. Gait and CSD measures were compared between groups and tasks using mixed model analysis. RESULTS: DR-JME patients demonstrated an altered gait pattern that included slower gait speed (p = .018), reduced cadence (p = .003), and smaller arm-swing amplitude (p = .011). The DR-JME group showed higher motor-evoked CSD in the postcentral gyri compared to responders (p = .049) and both JME groups showed higher CSD in the superior frontal gyri compared to healthy controls (p < .011). Moreover, higher CSD in the superior frontal gyri correlated with worse performance in dual-task walking (r > |-0.494|, p < .008). CONCLUSIONS: These alterations in gait and motor-evoked responses in DRE-JME patients reflect a more severe dysfunction of motor-cognitive neural processing in frontocentral regions, leading to poorer gait performance. Further studies are needed to investigate the predictive value of altered gait and cortical motor processing as biomarkers for poor response to treatment in JME and other epilepsy syndromes.

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

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.

Social recognition in laboratory mice requires integration of behaviorally-induced somatosensory, auditory and olfactory cues.

In humans, discrimination between individuals, also termed social recognition, can rely on a single sensory modality, such as vision. By analogy, social recognition in rodents is thought to be based upon olfaction. Here, we hypothesized that social recognition in rodents relies upon integration of olfactory, auditory and somatosensory cues, hence requiring active behavior of social stimuli. Using distinct social recognition tests, we demonstrated that adult male mice do not exhibit recognition of familiar stimuli or learn the identity of novel stimuli that are inactive due to anesthesia. We further revealed that impairing the olfactory, somatosensory or auditory systems prevents behavioral recognition of familiar stimuli. Finally, we found that familiar and novel stimuli generate distinct movement patterns during social discrimination and that subjects react differentially to the movement of these stimuli. Thus, unlike what occurs in humans, social recognition in mice relies on integration of information from several sensory modalities.