Proceedings of the 2022 "Lifestyle Intervention for Epilepsy (LIFE)" symposium hosted by Cleveland Clinic.

Lifestyle interventions are strategies used to self-manage medical conditions, such as epilepsy, and often complement traditional pharmacologic and surgical therapies. The need for integrating evidence-based lifestyle interventions into mainstream medicine for the treatment of epilepsy is evident given that despite the availability of a multitude of treatments with medications and surgical techniques, a significant proportion of patients have refractory seizures, and even those who are seizure-free report significant adverse effects with current treatments. Although the evidence base for complementary medicine is less robust than it is for traditional forms of medicine, the evidence to date suggests that several forms of complementary medicine including yoga, mindfulness meditation, cognitive behavioral therapy, diet and nutrition, exercise and memory rehabilitation, and music therapy may have important roles as adjuncts in the treatment armamentarium for epilepsy. These topics were discussed by a diverse group of medical providers and scientists at the "Lifestyle Intervention for Epilepsy (LIFE)" symposium hosted by Cleveland Clinic. PLAIN LANGUAGE SUMMARY: There are many people with epilepsy who continue to have seizures even though they are being treated with medication or brain surgery. Even after seizures stop, some may experience medication side effects. There is research to suggest that certain lifestyle changes, such as yoga, mindfulness, exercise, music therapy, and adjustments to diet, could help people with epilepsy, when used along with routine treatment. Experts discussed the latest research at the "Lifestyle Intervention for Epilepsy (LIFE)" symposium hosted by Cleveland Clinic.

Unusual Involvement of Basal Ganglia and Dentate Nucleus in Children with Acute Encephalopathy with COVID-19.

Children account for 1% to 5% of diagnosed COVID-19 infection with relatively mild presentation compared to adults. The frequency of neurological involvement in acute COVID-19 infection in children is unclear. COVID-19 is also considered to be a neurotropic virus, but so far, in the pediatric age group, very few cases with involvement of basal ganglia and no case of dentate nucleus involvement have been reported in the literature. The present paper reports two cases of acute encephalopathy with COVID-19, the first case with basal ganglia involvement and the second with dentate nucleus involvement. Both cases required aggressive management and had complete neurological recovery on follow-up. Hence, these cases are reported to make everyone aware of the neurological presentation with atypical neuroimaging finding of acute COVID-19 infection in the pediatric age group; timely management improves the outcome.

Adjunctive Brivaracetam in Indian Patients with Uncontrolled Focal Epilepsy: Results from a Pooled Analysis of Two Double-Blind, Randomized, Placebo-Controlled Trials.

BACKGROUND: Nearly one-third of patients don't achieve seizure control with existing antiepileptic drugs. Brivaracetam (BRV) is a new member of the racetam class of drug, designed to selectively target SV2A, with binding affinity 15- to 30-fold greater than that of levetiracetam. OBJECTIVE: This pooled analysis reports efficacy and tolerability data of adjunct BRV (50, 100, and 200 mg/day) compared with placebo in Indian patients with uncontrolled focal epilepsy. METHODS: Data of 104 patients (aged 16-80 years) from 2 studies (N01252 and N01358) were pooled for this analysis. The studies comprised an 8-week prospective baseline period, and a 12-week treatment period. The study endpoints included median percent reduction from baseline in focal seizure frequency/28-days, ≥50% responder rate, and seizure freedom (all seizure types). The safety analysis included treatment-emergent adverse events (TEAEs). RESULTS: The efficacy population comprised 101 patients. In the Indian sub-group population, median percent reduction from baseline in focal seizure frequency/28-days was greater in the BRV dose groups: 39.7% (p = 0.00868), 46.8% (p = 0.00180) and 48.2% (p = 0.05224), for BRV 50, 100, 200 mg/day, respectively, compared with 20.6% for placebo. Responder rates (≥50%) were 38.1%, 45.7%, and 45.5% for BRV 50, 100, and 200 mg/day, respectively, compared with 11.7% for placebo. Complete seizure freedom was reported by 4.8% (1/21) and 2.9% (1/35) of patients on BRV50 and 100 mg/day, respectively, and none out of the 11 and 34 patients on BRV200 mg/day and placebo, respectively. In the safety population (n = 104), most commonly reported TEAEs (reported by ≥5% of patients taking brivaracetam) were headache and cough; most TEAEs were mild or moderate in intensity. CONCLUSION: This pooled analysis has provided evidence that adjunct brivaracetam, was effective and well-tolerated in Indian patients with uncontrolled focal epilepsy.

Adjunctive pregabalin vs gabapentin for focal seizures: Interpretation of comparative outcomes.

OBJECTIVE: To evaluate the comparative safety and adjunctive efficacy of pregabalin and gabapentin in reducing seizure frequency in patients with partial-onset seizures based on prestudy modeling showing superior efficacy for pregabalin. METHODS: The design of this comparative efficacy and safety study of pregabalin and gabapentin as adjunctive treatment in adults with refractory partial-onset seizures was randomized, flexible dose, double blind, and parallel group. The study included a 6-week baseline and a 21-week treatment phase. The primary endpoint was the percentage change from baseline in 28-day seizure rate to the treatment phase. RESULTS: A total of 484 patients were randomized to pregabalin (n = 242) or gabapentin (n = 242). Of these, 359 patients (187 pregabalin, 172 gabapentin) completed the treatment phase. The observed median and mean in percentage change from baseline was -58.65 and -47.7 (SD 48.3) for pregabalin and -57.43 and -45.28 (SD 60.6) for gabapentin. For the primary endpoint, there was no significant difference between treatments. The Hodges-Lehman estimated median difference was 0.0 (95% confidence interval -6.0 to 7.0). Safety profiles were comparable and consistent with prior trials. CONCLUSIONS: The absence of the anticipated efficacy difference based on modeling of prior, nearly identical trials and the larger-than-expected response rates of the 2 antiepileptic drugs were unexpected. These findings raise questions that are potentially important to consider in future comparative efficacy trials. CLINICALTRIALSGOV IDENTIFIER: NCT00537940. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with partial seizures enrolled in this study, pregabalin is not superior to gabapentin in reducing seizure frequency. Because of the atypical response rates, the results of this study are poorly generalizable to other epilepsy populations.

The relationship between sleep and epilepsy.

The occurrence of seizures in the sleep state is observed in nearly one third of patients. This is caused by an intimate relationship between the physiological state of sleep and the pathological process underlying epileptic seizures. Both sleep and sleep deprivation influence the frequency of epileptiform discharges on electroencephalograms as well as the occurrence of clinical seizures, typically during nonrapid eye movement sleep. The relationship of epileptiform activity to nonrapid eye movement sleep is vividly shown in the syndrome of continuous spikes in slow-wave sleep and the Landau-Kleffner syndrome. Seizure semiology can also be influenced by sleep and sleep deprivation. Sleep disorders may influence seizure control, and effective treatment of sleep disorders can improve seizure control. Seizures, antiepileptic drugs, ketogenic diet, and vagus nerve stimulation all influence sleep quality, daytime alertness, and neurocognitive function.

Acceptance and Commitment Therapy and yoga for drug-refractory epilepsy: a randomized controlled trial.

OBJECTIVE: There is a need for controlled outcome studies on behavioral treatment of epilepsy. The purpose of this study was to evaluate Acceptance and Commitment Therapy (ACT) and yoga in the treatment of epilepsy. METHODS: The design consisted of a randomized controlled trial with repeated measures (N=18). All participants had an EEG-verified epilepsy diagnosis with drug-refractory seizures. Participants were randomized into one of two groups: ACT or yoga. Therapeutic effects were measured using seizure index (frequency x duration) and quality of life (Satisfaction with Life Scale, WHOQOL-BREF). The treatment protocols consisted of 12 hours of professional therapy distributed in two individual sessions, two group sessions during a 5-week period, and booster sessions at 6 and 12 months posttreatment. Seizure index was continuously assessed during the 3-month baseline and 12-month follow-up. Quality of life was measured after treatment and at the 6-month and 1-year follow-ups. RESULTS: The results indicate that both ACT and yoga significantly reduce seizure index and increase quality of life over time. ACT reduced seizure index significantly more as compared with yoga. Participants in both the ACT and yoga groups improved their quality of life significantly as measured by one of two quality-of-life instruments. The ACT group increased their quality of life significantly as compared with the yoga group as measured by the WHOQOL-BREF, and the yoga group increased their quality of life significantly as compared with the ACT group as measured by the SWLS. CONCLUSIONS: The results of this study suggest that complementary treatments, such as ACT and yoga, decrease seizure index and increase quality of life.