Decrease In Seizure Frequency Research Articles

Additional Results from Two Randomized, Placebo-Controlled Trials of Stiripentol in Dravet Syndrome Highlight a Rapid Antiseizure Efficacy with Longer Seizure-Free Periods.

The efficacy of stiripentol in Dravet syndrome children was evidenced in two randomized, double-blind, placebo-controlled, phase 3 studies, namely STICLO France (October 1996-August 1998) and STICLO Italy (April 1999-October 2000), but data were not fully exploited at the time. This post-hoc analysis used additional information, notably collected during the open-label extension (OLE) month, or reported by caregivers in individual diaries, to evaluate new outcomes. Overall, 64 patients were included (31 in the placebo group, 33 in the stiripentol group) of whom 34 (53.1%) were female. Patients' mean and median (25%; 75%) age were 9.2years (range 3.0-20.7years) and 8.7years (6.0; 12.1) respectively. At the end of the double-blind treatment period, 72% of the patients in the stiripentol group had a≥50% decrease in generalized tonic-clonic seizure (GTCS) frequency, versus 7% in the placebo group (P<0.001), 56% had a profound (≥75%) decrease versus 3% in the placebo group (P<0.001), and 38% were free of GTCS, but none in the placebo group (P<0.001). The onset of stiripentol efficacy was rapid, significant from the fourth day of treatment onwards. The median longest period of consecutive days with no GTCS was 32days in the stiripentol group compared to 8.5days in the placebo group (P<0.001). Further to the switch to the third month OLE, an 80.2% decrease in seizure frequency from baseline was observed in patients previously receiving placebo, while no change in efficacy was observed in those already on stiripentol. Adverse events were more frequent in the stiripentol group, with significantly more episodes of somnolence, anorexia, and weight decrease than in the placebo group. Altogether these new analyses of the STICLO data reinforce the evidence for a remarkable efficacy of stiripentol in Dravet syndrome, with a demonstrated rapid onset of action and sustained response, as also evidenced in further post-randomized trials.

Drug resistant epilepsies: A multicentre case series of steroid therapy

PurposeOur study aimed to evaluate the effectiveness of corticosteroids on seizure control in drug-resistant epilepsies (DREs). Our primary goal was to assess the response to steroids for various underlying etiologies, interictal electroencephalographic (EEG) patterns and electroclinical seizure descriptions. Our second goal was to compare steroid responsiveness to different treatment protocols. MethodsThis is a retrospective multicentre cohort study conducted according to the STROBE guidelines (Strengthening the Reporting of Observational Studies in Epidemiology). The following data were collected for each patient: epilepsy etiology, interictal EEG pattern, seizure types and type of steroid treatment protocol administered. ResultsThirty patients with DRE were included in the study. After 6 months of therapy, 62.7 % of patients experienced reduced seizure frequency by 50 %, and 6.6 % of patients experienced complete seizure cessation. Findings associated with favourable response to steroids included structural/lesional etiology of epilepsy, immune/infectious etiology and focal interictal abnormalities on EEG. Comparing four different steroid treatment protocols, the most effective for seizure control was treatment with methylprednisolone at the dose of 30 mg/kg/day administered for 3 days, leading to greater than 50 % seizure reduction at 6 months in 85.7 % of patients. Treatment with dexamethasone 6 mg/day for 5 days decreased seizure frequency in 71.4 % of patients. Hydrocortisone 10 mg/kg administered for 3 months showed a good response to treatment in 71 %. ConclusionsIn our study, two-thirds of patients with DRE experienced a significant seizure reduction following treatment with steroids. We suggest considering steroids as a potential therapeutic option in children with epilepsy not responding to conventional antiseizure medicines (ASM).

Telemedicine and Epilepsy. Experience of the Central Hospital "Dr. Ignacio Morones Prieto" During and Post-pandemic COVID-19

Background: Telemedicine is a real-time interactive communication that enables providers to join with patients and consultants across challenging geographic distances in a cost-effective, accessible manner. Telemedicine is helpful in the treatment of epilepsy and other neurological disorders. This work aims to share the use of telemedicine in the management of patients with epilepsy belonging to suburban communities during the COVID-19 pandemic and its post-pandemic follow-up. Material and Methods: A retrospective, descriptive, and analytical study was conducted. The Telemedicine database in our hospital underwent a retrospective analysis. The inclusion criteria encompassed patients who had an initial consultation during the confinement period (2020-2021) and had at least one videoconference in the post-confinement period (2022-2023). Various parameters, including the number of consultations received, city of origin, treatment, etiology, type of epilepsy, comorbidities, and treatment outcomes, were gathered to facilitate a comparison between the two periods. Statistical analyses were performed using IBM SPSS Statistics V.25 for Mac. Results: Ninety-eight patients with an initial consultation between 2020 and 221 were identified, discarding 41 due to loss of follow-up during post-confinement, resulting in N=57 cases for analysis. Conclusions: During the COVID-19 confinement period in our hospital, Telemedicine emerged as the sole feasible option for providing care to patients in remote communities. It demonstrated remarkable success in monitoring the short and midterm progression of epileptic patients. The decrease in seizure frequency was sustained during the midterm.

Sleep quality and depression in mothers of children with epilepsy and its relation to their children’s sleep

ObjectiveThis study aimed to evaluate the relationship between sleep disturbances in children with epilepsy (CWE) and maternal sleep quality and depression severity. MethodsA Cross-sectional study was conducted in pediatric sleep disturbances using questionnaires on mother-reported sleep of CWE [Children's Sleep Habits Questionnaire (CSHQ)], maternal sleep quality [Pittsburgh Sleep Quality Index (PSQI)], and maternal depression status [Self-Rating Depression Scale (SDS)]. 114 dyads consisting of CWE and their mothers were included in this study. ResultsOver three-quarters (78.9 %) of mothers reported poor sleep quality (total PSQI score ≥ 5), and nearly a third (29.8 %) met clinical criteria for moderate or severe depression levels. The mothers' total PSQI scores were between 5.93 ± 2.44 (range: 2–16 points). The most affected PSQI subcomponents were sleep latency (AUC = 0.826p < 0.001) and daytime dysfunction (AUC = 0.800p < 0.001). The majority of children (88.6 %) were stated by their mothers to have sleep-related problems. The total CSHQ scores of the children were between 49.06 ± 9.20 (range: 33–86 points). The most affected CSHQ subcomponents were detected sleep anxiety (AUC = 0.856, p < 0.001), bedtime resistance (AUC = 0.818, p < 0.001) and daytime sleepiness (AUC = 0.807, p < 0.001). There was a statistically significant positive correlation between maternal sleep quality and depression severity (rho = 0.842; p < 0.001). A statistically significant positive moderate correlation was detected between sleep problems in CWE and maternal sleep quality and depression severity (rho = 0.406; p < 0.001, rho = 0.399; p < 0.001, respectively). As a result of multiple stepwise logistic regression analysis, the presence of seizures during sleep and generalized epileptiform discharges on electroencephalography were associated risk factors with poor maternal sleep quality (OR:6.6, p = 0.014; OR:11.5, p = 0.018, respectively). A borderline insignificant relationship was observed between a less than 50 % decrease in seizure frequency and the poor maternal sleep quality (OR:20.59p = 0.059). Seizures during sleep was associated risk factor with children's sleep disturbances (OR:7.2, p = 0.02). ConclusionsSleep problems in CWE may lead to negative consequences such as sleep quality and/or depression in mothers. Interventions planned to correct sleep disturbances in mothers suggest that children's sleep problems should be optimally managed.

Use of ketogenic dietary therapy for drug-resistant epilepsy in early infancy.

There is growing evidence that ketogenic dietary therapy (KDT) can be safely and efficiently used in young children, but little evidence exists on its use in newborns. Developmental and epileptic encephalopathies starting in the neonatal period or early infancy usually present a poor prognosis. The aim of this study was to evaluate effectiveness, safety, and survival of infants younger than 3 months of age with drug-resistant epilepsy in whom KDT was used. A retrospective study was conducted to evaluate neonates and infants younger than 3 months who started KDT for drug-resistant developmental and epileptic encephalopathies at three referral centers. Data were collected on demographic features, time of epilepsy onset, epilepsy syndrome, seizure type, seizure frequency at diet onset, etiology, details regarding diet initiation, type of ketogenic formula, breastfeeding, route of administration, blood ketones, growth, length of NICU stay, and survival. Nineteen infants younger than 12 weeks of life who received KDT with a minimum follow-up of 1 month were included; 13 had early-infantile developmental and epileptic encephalopathy, four epilepsy of infancy with migrating focal seizures, and two focal epilepsy. A >50% response was observed in 73.7% at 1 month on the diet; 37% achieved a > 75% seizure reduction, and 10.5% became seizure free. At 3 months, a >50% decrease in seizure frequency was observed in 72.2%; 15.8% had a >75% reduction; 21% became seizure free. Overall survival was 76% at 1 year on diet. Incidence of acute and late adverse effects was low and most adverse effects were asymptomatic and manageable. Our experience suggests that KDT is safe and effective in newborns and very young infants; however, further studies on the management of the diet in this vulnerable age group are necessary.

Repurposing dimethyl fumarate as an antiepileptogenic and disease-modifying treatment for drug-resistant epilepsy

BackgroundEpilepsy affects over 65 million people worldwide and significantly burdens patients, caregivers, and society. Drug-resistant epilepsy occurs in approximately 30% of patients and growing evidence indicates that oxidative stress contributes to the development of such epilepsies. Activation of the Nrf2 pathway, which is involved in cellular defense, offers a potential strategy for reducing oxidative stress and epilepsy treatment. Dimethyl fumarate (DMF), an Nrf2 activator, exhibits antioxidant and anti-inflammatory effects and is used to treat multiple sclerosis.MethodsThe expression of Nrf2 and its related genes in vehicle or DMF treated rats were determined via RT-PCR and Western blot analysis. Neuronal cell death was evaluated by immunohistochemical staining. The effects of DMF in preventing the onset of epilepsy and modifying the disease were investigated in the kainic acid-induced status epilepticus model of temporal lobe epilepsy in rats.The open field, elevated plus maze and T-Maze spontaneous alteration tests were used for behavioral assessments.ResultsWe demonstrate that administration of DMF following status epilepticus increased Nrf2 activity, attenuated status epilepticus-induced neuronal cell death, and decreased seizure frequency and the total number of seizures compared to vehicle-treated animals. Moreover, DMF treatment reversed epilepsy-induced behavioral deficits in the treated rats.Moreover, DMF treatment even when initiated well after the diagnosis of epilepsy, reduced symptomatic seizures long after the drug was eliminated from the body.ConclusionsTaken together, these findings suggest that DMF, through the activation of Nrf2, has the potential to serve as a therapeutic target for preventing epileptogenesis and modifying epilepsy.

Long-term outcome of epileptic dogs treated with implantable vagus nerve stimulators.

The long-term effect of implantable vagus nerve stimulators (VNS) on seizures has not been evaluated in epileptic dogs. Report seizure frequency in medication-resistant epileptic dogs before and after VNS implantation. Twelve client-owned dogs with idiopathic epilepsy and >1 seizure day per 3 weeks despite 3 months of appropriate use of 2 antiseizure medications and seizure diaries maintained 6 months before and >12 months after VNS implantation. Uncontrolled, open-label, before and after study. Mean monthly seizures and inter-seizure periods obtained from contemporaneous seizure diaries in the 6 months before implantation were compared with 0 to 6 months, 7 to 12 months, and subsequent 12-month periods after implantation. The number of dogs with >50% decrease in seizure frequency, >3 times increase in inter-ictal period interval, and seizure freedom for >3 months at the time of death or last follow-up were recorded. Five of 12 dogs were euthanized <12 months after implantation. All 7 remaining dogs showed >50% decrease in seizure frequency until last follow-up, starting at a median of 37 to 48 months after implantation (range, 0-6 to 61-72 months) and a >3-fold increase in mean inter-seizure interval starting a median of 25 to 36 months after implantation (range, 0-6 months to 49-60 months), 3/7 dogs were seizure-free at death or last follow-up. Monthly seizure frequencies decreased and inter-seizure intervals increased in all dogs 2 to 3 years after VNS implantation, but a high proportion were euthanized before this time point. Prospective clinical trials are required to establish causality and the magnitude of this association.

Highly purified cannabidiol in the treatment of drug-resistant epilepsies: A real-life impact on seizure frequency, quality of life, behavior, and sleep patterns from a single Italian center

Seizure frequency in treatment-resistant epilepsies seems to be decreased by cannabidiol (CBD), but contrasting data are available on its effect on sleep, behavior, and quality of life (QoL), and no data is reported on its effect on parental stress in patients with epilepsy (PWE). Thus, we conducted a retrospective study on a cohort of children and adults with drug-resistant epilepsy (DRE) who had been treated with highly purified, pharmaceutical-grade CBD to evaluate its effects on seizure frequency, QoL, behavior, parental stress, and sleep. Eighteen patients (12 adults and 6 children) were included in the cohort and followed for a median of 9 months. At the last follow-up (Tn), nine patients (50%) were considered CBD responders with at least a 50% decrease in seizure frequency. No serious adverse effects were found. No statistically significant differences were found concerning sleep, including daytime sleepiness, and no statistically significant effect was found on parental stress at Tn. An improvement was found for social interaction in quality of life (p < 0.05) for all patients. Our results demonstrate that CBD is a safe and effective antiseizure medication (ASM). CBD doesn’t seem to affect sleep measures in adults and children or worsen daytime sleepiness. However, CBD improves specific QoL measures, which could indicate a possible use of CBD for other childhood disabilities. No impact of CBD was seen on parental stress, which could possibly be due to the limited follow-up or could mean that parental stress is not dependent on seizure frequency.

Effect of a ketogenic diet on decrease of seizures in refractory epilepsy among children (infancy to 14 years old) in Saudi Arabia: a cross-sectional study.

Refractory (intractable/pharmaco-resistant) epilepsy in children is considered if disabling seizures continue despite appropriate trials of two anti-seizure drugs, either alone or in combination. Ketogenic diets are used as a treatment option in many countries for children with refractory seizures; however, few patients have tried it in Saudi Arabia. Therefore, we examined the relationship between the exposure to a ketogenic diet and its effect in decreasing seizure frequency in infants and children up to 14 years who had refractory epilepsy and assessed factors that could improve the outcome of seizures. This cross-sectional study was conducted at King Fahad Medical City, Riyadh, Saudi Arabia. Data were collected by reviewing medical records of eligible children (infants and children up to 14 years old) with refractory epilepsy who were on ketogenic diets. Socioeconomic data of the parents (guardians) were collected via phone interviews after verbal consent from the parents (guardians). We recruited 95 children (aged 10 months to 14 years) with refractory epilepsy and on Ketogenic diets. Up to 44% of patients on 3:1 and 4.5:1 ratio ketogenic diets had decreased seizure frequency while patients on 1:1 and 2:1 ratio ketogenic diets showed no decrease in seizures. Patients with generalized epilepsy who were on ketogenic diets had the most improvement in seizure outcomes (56.1%) and patients on ketogenic diets who were ambulatory indoors and outdoors (66.7%) showed a high level of improvement in seizure outcomes compared to patients with who were non-ambulatory (21.9%). Lower improvements in seizure frequency in epileptic patients on ketogenic diets were associated with low education levels of parents (33.3% high school vs. 50% undergraduate school), low incomes [<11,400±7,560.864 Saudi riyal (SR)], and diagnosis of seizures in patients >8 years old. Ketogenic diets are a promising approach for treatment of refractory epilepsy among children. The improvement in seizure outcomes was associated with higher ratios of ketogenic diets (3:1 and 4.5:1), and higher physical activity. Sociodemographic factors, including parents' (guardians') education levels and income influenced the improvement of seizures.

Temporo-Parietal Extraventricular Approach for Deep Brain Stimulation Targeting the Anterior Nucleus of the Thalamus: Institutional Experience.

The anterior nucleus of the thalamus (ANT) is a common target for deep brain stimulation (DBS) for drug-resistant epilepsy (DRE). However, the surgical approach to the ANT remains challenging because of its unique anatomy. This study aims to summarize our experience with the posterior temporo-parietal extraventricular (TPEV) approach targeting the ANT for DBS in DRE. We performed a retrospective analysis of patients with DRE who underwent ANT-DBS using the TPEV approach between January 2011 and February 2021. Subjects with at least 6-month follow-up were eligible. The final lead position and number of active contacts targeting the anteroventral nucleus (AV) of the ANT were assessed using Lead-DBS. Mean seizure frequency reduction percentage and responder rate (≥50% decrease in seizure frequency) were determined. Thirty-one patients (mean age: 32.9 years; 52% female patients) were included. The mean follow-up period was 27.6 months ± 13.9 (29, 16-36). The mean seizure frequency reduction percentage was 65% ± 26 (75, 50-82). Twenty-six of 31 participants (83%) were responders, P < .001. Two subjects (6%) were seizure-free for at least 6 months at the last evaluation. Antiepileptic drugs dose and/or number decreased in 17/31 subjects (55%). The success rate for placing at least 1 contact at AV was 87% (27/31 patients) bilaterally. The number of active contacts at the AV was significantly greater in the responder group, 3.1 ± 1.3 (3, 2-4) vs 1.8 ± 1.1 (2, 1-2.5); P = .041 with a positive correlation between the number of active contacts and seizure reduction percentage; r = 0.445, R 2 = 0.198, P = .012. The TPEV trajectory is a safe and effective approach to target the ANT for DBS. Future studies are needed to compare the clinical outcomes and target accuracy with the standard approaches.

Sex steroid hormones and epilepsy: Effects of hormonal replacement therapy on seizure frequency of postmenopausal women with epilepsy-A systematic review.

Hormonal replacement therapy (HRT) is used for symptomatic treatment of menopause. Some evidence suggests a proconvulsant effect of estrogen and an anticonvulsant role of progesterone. Thus, the use of exogenous sex steroid hormones might influence the course of epilepsy in peri- and postmenopausal women with epilepsy (WWE). We conducted a systematic review on the impact of HRT on the frequency of seizures of WWE. PubMed and Scopus were searched for articles published from inception until August 2022. Abstracts from the past 5 years from the European Academy of Neurology and European Epilepsy Congresses were also reviewed. Article reference lists were screened, and relevant articles were retrieved for consultation. Interventional and observational studies on WWE and animal models of estrogen deficiency were included. Critical appraisal was performed using the revised Cochrane risk-of-bias tool for randomized trials and ROBINS-E tool. Of 497 articles screened, 13 studies were included, including three human studies. One cross-sectional study showed a decrease in seizure frequency in WWE using combined HRT, a case-control study showed an increase in comparison with controls, and a randomized clinical trial found a dose-dependent increase in seizure frequency in women with focal epilepsy taking combined HRT. Ten studies addressing the impact of HRT in rat models were also included, which showed conflicting results. There is scarce evidence of the impact of HRT in WWE. Further studies should evaluate the harmful potential, and prospective registries are needed for monitoring this population.

Efficacy of brivacetam as an anti-epileptic in patients with epilepsy, with special reference to previous exposure to levetiractam

Brivaracetam (BRV) is a new antiepileptic drug (AED) approved for adjunctive treatment of focal (partial-onset) seizures in adults. It is a selective, high-affinity ligand for synaptic vesicle 2A (SV2A) with much higher affinity than Levetiracetam (LEV). It has a high lipid solubility and rapid brain penetration, and has been shown to have potent broad-spectrum antiepileptic activity in animal models. The aim of the study was to evaluate the efficacy and tolerability of BRV in everyday clinical practice. This observational study included 35 participants, suffering from different types of epilepsy. Patients were observed over a period of 1 year and data was collected using an interview design model. After the initial interview, a final interview took place after 1 year. Various parameters studied included demographic parameters, seizure frequency and duration, any side effects such as behavioral issues. This study included total 35 patients. The mean age of the participants was 33 years (range 3 – 90 years). Approximately 63% patients demonstrated a decrease in seizure frequency after switching to Brivacetam. Out of these patients, 76% patients were those patients, who were earlier treated with Levetiracetam, and it was discontinued either due to inadequate control of seizures or prominent side-effects. Brivaracetam also improved emotional balance in the treated patients (treatment naïve or Levetiracteam associated behavioral issues).Brivaracetam seems to be an effective and safe antiepileptic drug in the routine clinical setting.

Efficacy, safety, and tolerability of soticlestat as adjunctive therapy for the treatment of seizures in patients with Dup15q syndrome or CDKL5 deficiency disorder in an open-label signal-finding phase II study (ARCADE)

ObjectiveChromosome 15q duplication (Dup15q) syndrome and cyclin‑dependent kinase-like 5 deficiency disorder (CDD) are rare neurodevelopmental disorders associated with epileptic encephalopathies, with a lack of specifically approved treatment options. ARCADE assessed the efficacy and safety of adjunctive soticlestat (TAK-935) for the treatment of seizures in patients with Dup15q syndrome or CDD (NCT03694275). MethodsARCADE was a phase II, open-label, pilot study of soticlestat (≤300 mg/day twice daily, weight-adjusted) in pediatric and adult patients 2–55 years of age with Dup15q syndrome or CDD who experienced ≥3 motor seizures per month in the 3 months before screening and at baseline. The 20-week treatment period consisted of a dose-optimization period and a 12-week maintenance period. Efficacy endpoints included the change from baseline in motor seizure frequency during the maintenance period and the proportion of treatment responders. Safety endpoints included the incidence of treatment-emergent adverse effects (TEAEs). ResultsThe modified-intent-to-treat population included 20 participants who received ≥1 dose of soticlestat and had ≥1 efficacy assessment (Dup15q syndrome, n = 8; CDD, n = 12). Soticlestat administration during the maintenance period was associated with a median change from baseline in motor seizure frequency of +11.7% in the Dup15q syndrome group and −23.6% in the CDD group. Reductions in all seizure frequency of −23.4% and −30.5% were also observed during the maintenance period in the Dup15q syndrome group and the CDD group, respectively. Most TEAEs were of mild or moderate severity. Serious TEAEs were reported by three patients (15.0%); none were considered drug related. The most common TEAEs were constipation, rash, and seizure. No deaths were reported. ConclusionsAdjunctive soticlestat treatment was associated with a decrease in motor seizure frequency from baseline in patients with CDD and a decrease in all seizure frequency in both patient groups. Soticlestat treatment was associated with an increase in motor seizure frequency in patients with Dup15q syndrome.

Anticholinergics: A potential option for preventing posttraumatic epilepsy.

Interest in the use of anticholinergics to prevent the development of epilepsy after traumatic brain injury (TBI) has grown since recent basic studies have shown their effectiveness in modifying the epileptogenic process. These studies demonstrated that treatment with anticholinergics, in the acute phase after brain injury, decreases seizure frequency, and severity, and the number of spontaneous recurrent seizures (SRS). Therefore, anticholinergics may reduce the risk of developing posttraumatic epilepsy (PTE). In this brief review, we summarize the role of the cholinergic system in epilepsy and the key findings from using anticholinergic drugs to prevent PTE in animal models and new clinical trial protocols. Furthermore, we discuss why treatment with anticholinergics is more likely to prevent PTE than treatment for other epilepsies.

Effects of high-dose docosahexaenoic acid supplementation as an add-on therapy for canine idiopathic epilepsy: A pilot study.

The anti-epileptic effects of docosahexaenoic acid (DHA) in dogs and humans remain controversial. The dosage and efficacy of DHA were various in the previous reports. The effects of high-dose DHA supplementation as add-on therapy for idiopathic epilepsy in dogs were evaluated. An open-label clinical trial was designed in this pilot study. Six dogs (median age: 6 years) with idiopathic epilepsy were included. All the patients were diagnosed with idiopathic epilepsy using magnetic MRI and cerebrospinal fluid examination (median: 2.0 years before the trial). They had 5-45 seizures and/or auras (median: 9.0) in the month before starting DHA supplementation. DHA was adjunctively administered at doses of 69-166 mg/kg/day without changing other prescriptions. Four of the six patients completed the 6-month observation period. All the patients showed a decrease in seizure frequency of 50% or more within 2-3 months after the start of the administration, and three patients decreased to a frequency of 0-1 per month after 5-6 months. No clear adverse events were observed in the general condition or blood test results in any patients. Although the sample size was small and the study was not a randomized controlled trial, the data suggest that add-on supplementation of DHA could be useful in reducing the frequency of seizures in canine idiopathic epilepsy.

Vagus Nerve Stimulation for Drug Resistant Epilepsy: Clinical Outcome, Adverse Events, and Potential Prognostic Factors in a Single Center Experience.

Vagus nerve stimulation (VNS) has been used for adjunctive treatment in drug resistant epilepsy (DRE) for decades. Nevertheless, information is lacking on possible potential prognostic factors. Our study presents the efficacy and safety of VNS with a focus on prognostic factors in 45 patients with DRE. We retrospectively evaluated the clinical outcome of 45 consecutive patients with DRE undergoing VNS implantation in The First Affiliated Hospital of Anhui Medical University between November 2016 and August 2021. Medical records were aggregated across all patient visits. Cox proportional hazards regression was used to estimate the prognostic factors. Significant decrease in seizure frequency was observed after intermittent stimulation of the vagus nerve. According to the modified McHugh classification, 11 patients (24.4%) were Class I, 11 patients (24.4%) were Class II, four patients (8.9%) were Class III, 10 patients (22.2%) were Class IV, and nine patients (20.0%) were Class V. Notably, 22 patients (48.9%) were responders and four patients (8.9%) were seizure-free at the final follow-up. No significant prognostic factors were found in this cohort. Furthermore, 37 patients reported improved quality of life. Of the patients, 22 (48.9%) experienced adverse events after surgery; hoarseness, discomfort at the surgical site, and coughing were the most common. The results confirmed the efficacy and safety of VNS. No prognostic factors were identified.

Centromedian thalamic deep brain stimulation for drug-resistant epilepsy: single-center experience.

Neuromodulation of the centromedian nucleus of the thalamus (CM) has unclear effectiveness in the treatment of drug-resistant epilepsy. Prior reports suggest that it may be more effective in the generalized epilepsies such as Lennox-Gastaut syndrome (LGS). The objective of this study was to determine the outcome of CM deep brain stimulation (DBS) at the authors' institution. Retrospective chart review was performed for all patients who underwent CM DBS at Emory University, which occurred between December 2018 and May 2021. CM DBS electrodes were implanted using three different surgical methods, including frame-based, robot-assisted, and direct MRI-guided. Seizure frequency, stimulation parameters, and adverse events were recorded from subsequent clinical follow-up visits. Fourteen patients underwent CM DBS: 9 had symptomatic generalized epilepsy (including 5 with LGS), 3 had primary or idiopathic generalized epilepsy, and 2 had bifrontal focal epilepsy. At last follow-up (mean [± SEM] 19 ± 5 months, range 4.1-33 months, ≥ 6 months in 11 patients), the median seizure frequency reduction was 91%. Twelve patients (86%) were considered responders (≥ 50% decrease in seizure frequency), including 10 of 12 with generalized epilepsy and both patients with bifrontal epilepsy. Surgical adverse events were rare and included 1 patient with hardware breakage, 1 with a postoperative aspiration event, and 1 with a nonclinically significant intracranial hemorrhage. CM DBS was an effective treatment for drug-resistant generalized and bifrontal epilepsies. Additional studies and analyses may investigate whether CM DBS is best suited for specific epilepsy types, and the relationship of lead location to outcome in different epilepsies.

Cannabidiol (CBD) Reduces Epileptic Seizures in the Asian Population: Cross-sectional Study for Intractable Epilepsy Patients in Japan

Purpose of study: Despite very strict cannabis regulations in Japan, some cannabidiol (CBD) products have been legally distributed since 2013 and taken by some epilepsy patients. However, its efficacy and safety have not been evaluated. Basic procedures: A self-administered questionnaire was sent to 38 patients with intractable epilepsy who were taking CBD. The questionnaire sought information on patient background (sex, age) and medical history (diagnosis, type of seizures), characteristics of CBD use (frequency, route of administration), and the safety of CBD use (adverse events, side effects). Patients were also asked about changes in seizure frequency, intensity, and duration; effect on sleep; effect on daytime activity/vitality; increase/decrease in antiepileptic drugs dosage; quality of life (QOL); and caregiver-assessed QOL. Findings: Responses were received from 28 of 38 patients. The median CBD intake was 12.0 mg/kg/day. Nine patients (32.1%) were suspected of having an adverse event, but all were mild and no patients discontinued CBD due to adverse events. Fifteen patients (53.6%) reported a decrease in seizure frequency, and 2 patients (7.1%) showed complete resolution of seizures. No significant correlation was found between the patient’s diagnosis and the seizure type or efficacy. Conclusions: This is the first cross-sectional study of CBD users in Japan, suggesting that CBD may be an effective option for Asian patients with refractory epilepsy, regardless of diagnosis or seizure type.

Long-term follow-up of vagus nerve stimulation in drug-resistant KCNT1-related epilepsy: a case presentation

BackgroundThe KCNT1 gene encodes a Na+-activated K+ channel. Gain-of-function mutations of KCNT1 lead to autosomal dominant sleep-related hypermotor epilepsy, early-onset epileptic encephalopathy, focal epilepsy and other epileptic encephalopathies. In this paper, we report a boy carrying a KCNT1 gene mutation, who presented with drug-resistant focal-onset seizures. He had decreased seizure frequency and improvement of background changes in electroencephalography (EEG) after vagus nerve stimulation (VNS).Case presentationThe case was a nonverbal 9-year-old male who presented with drug-resistant focal-onset seizures since age 3 and had underwent VNS therapy for 2 years. He had hypermotor symptoms, automatism and bilateral asymmetric tonic seizures with cognitive decline and aphasis from age 3. The patient had a variety of seizure types that only occurred at night. The most common seizure type was automatisms, and ictal video EEG showed high-amplitude delta waves, followed by a fast rhythmic sharp activity in the mesial frontal and bitemporal regions. The patient was diagnosed with KCNT1-related epilepsy, epileptic encephalopathy and cognitive disorder. He was refractory to multiple anti-seizure medicines (ASM) and ketogenic diet. After VNS treatment at age 7, the frequency of seizures was reduced significantly and EEG was improved in background slowing.ConclusionsChildren with KCNT1-related epilepsy usually have early onset of disease, are nonverbal, and are refractory to ASM. This boy with drug-resistant KCNT1-related epilepsy showed significantly reduced seizure frequency after VNS. This report may provide reference for management of cases of KCNT1-related epilepsy.

Responsive neurostimulation in pediatric patients with drug-resistant epilepsy.

Medically refractory epilepsy remains a therapeutic challenge when resective surgery is not a practical option and indirect neurostimulation efficacy may be limited. In these instances responsive neurostimulation (RNS) has been used in adults, with good outcomes in most patients. However, the utility of RNS in children and young adults has not been systematically explored. In this study, the authors present a single institution's experience with RNS in pediatric patients. A single-center retrospective chart review of patients who underwent RNS implantation at Phoenix Children's Hospital during the 4-year period between January 2018 and December 2021 was performed. Following evaluation for epilepsy surgery, 22 patients underwent RNS implantation using different anatomical targets depending on the predetermined epileptic focus/network. In the cohort, 59% of patients were male, the mean age at implantation was 16.4 years (range 6-22 years), and the mean follow-up time was 2.7 years (range 1.0-4.3 years). All patients had a preoperative noninvasive evaluation that included MRI, video-electroencephalography, and resting-state functional MRI. Additionally, 13 patients underwent invasive monitoring with stereo-electroencephalography to help determine RNS targets. All patients had variable positive responses with reduction of seizure frequency and/or intensity. Overall, seizure frequency reduction of > 50% was seen in the majority (86%) of patients. There were two complications: one patient experienced transitory weakness and one generator failed, requiring replacement. A patient died of sudden unexpected death in epilepsy 3 years after implantation despite being seizure free during the previous year. RNS used in children with medically refractory epilepsy improved seizure control after implantation, with decreases in seizure frequency > 50% from preoperative baseline in the majority of patients. Preliminary findings indicate that functional MRI and stereo-electroencephalography were helpful for RNS targeting and that RNS can be used safely even in young children.