Antiseizure medications (ASMs) play a central role in seizure management, however, unpredictability in the response to treatment persists, even among patients with similar seizure manifestations and clinical backgrounds. An objective biomarker capable of reliably predicting the response to ASMs would profoundly impact epilepsy treatment. Presently, clinicians rely on a trial-and-error approach when selecting ASMs, a time-consuming process that can result in delays in receiving alternative non-pharmacological therapies such as a ketogenetic diet, epilepsy surgery, and neuromodulation therapies. Pharmacogenetic studies investigating the correlation between ASMs and genetic variants regarding their mechanistic targets offer promise in predicting the response to treatment. Sodium channel subunit genes have been extensively studied along with other ion channels and receptors as targets, however, the results have been conflicting, possibly due to methodological disparities including inconsistent definitions of drug response, variations in ASM combinations, and diversity of genetic variants/genes studied. Nonetheless, these studies underscore the potential effect of genetic variants on the mechanism of ASMs and consequently the prediction of treatment response. Recent advances in sequencing technology have led to the generation of large genetic datasets, which may be able to enhance the predictive accuracy of the response to ASMs.

Vagus nerve stimulation (VNS) has been used as an adjunctive therapeutic option for drug-resistant epilepsy for decades. Traditionally, the left vagus nerve is used for stimulation, while the right vagus nerve is rarely used. The long-term efficacy and safety of the right VNS (R-VNS) in humans are unknown. We presented three patients who were treated with R-VNS over a follow-up period of up to eight years. All three patients tolerated R-VNS well with minimal complications. R-VNS displayed reasonable effectiveness in all three patients. One patient had an excellent response and became seizure-free. The other two patients demonstrated a less favorable response to R-VNS compared to their previous left VNS therapy.

Epilepsy is a chronic neurological disorder. Drug-resistant epilepsy (DRE) accounts for about one-third of epilepsy patients worldwide. Peimine, a main active component of Fritillaria, has been reported to show anti-inflammatory effects. However, its potential therapeutic role in DRE is not yet fully understood. In this work, a DRE rat model was established by injecting 1 μg kainic acid (KA), followed by a 250 mg/kg administration of valproic acid (VPA) from day 4-31. Rats were treated with different doses of peimine (2.5 mg/kg, 5 mg/kg and 10 mg/kg) daily from day 32-62. In vitro, BV-2 microglia were exposed to different doses of peimine (7.5 μg/ml, 15 μg/ml, and 30 μg/ml) in presence of LPS. The aim of this study was to investigate the potential therapeutic effects of peimine on DRE. The results showed that peimine efficiently suppressed the KA-induced epileptic behaviors of rats in a dose-dependent manner, as recorded by electroencephalography. Furthermore, peimine ameliorated hippocampal neuron injury in DRE rats, and promoted an M1-to-M2 microglial phenotype shift in a dose-dependent manner. Mechanistically, peimine inhibited the TLR4/NF-κB/HIF-1α signaling pathway both in vivo and in vitro. Additionally, peimine suppressed the apoptosis of primary neurons induced by LPS-treated microglia. In conclusion, peimine augments the microglial polarization towards an M2 phenotype by inhibiting the TLR4/NF-κB/HIF-1α signaling pathway, thereby attenuating DRE.

BACKGROUND: Drug-resistant epilepsy is defined as failure of seizure control in spite of using 2 or 3 proper antiepileptic drugs in appropriate time. Mineral elements play important roles in neuronal function; it is believed that mineral deficiency may lead to complications through seizure management. In the present study, serum levels of zinc (Zn), copper (Cu), magnesium (Mg), calcium (Ca), and 25-hydroxy vitamin D (Vit D) in drug-resistant-epilepsy (DRE) patients were evaluated and compared with the controlled patients.
METHODS: In this cross-sectional study, epileptic patients were included and categorized into two groups of DRE and well-controlled patients. Patients\' serum samples were analysed to evaluate Zn, Cu, Mg, Ca, and Vit D levels. The primary objective was comparison of serum levels of different trace elements between the groups.
RESULTS: Sixty-four epileptic children including 33 DRE and 31 well-controlled children entered the study. The DRE children showed a significantly earlier onset of disease compared to the other group (p = 0.014). Comparing the frequency of developmental delay between the groups, the results showed this complication was significantly more frequent in the DRE group (p < 0.001). Concerning serum elements, the results showed a significantly higher concentration of Zn in the well-controlled group than the DRE group (p = 0.007). On the other hand, no significant differences were observed between the groups regarding the means of Vit D, Ca, Cu, and Mg levels (p > 0.05).
CONCLUSIONS: The results of the present study delineated that drug-resistant epilepsy patients had earlier onset of disease and were at higher risk of neurodevelopmental delay compared with well-controlled-epilepsy patients. A significant lower serum levels of Zn were also observed in drug-resistant-epilepsy patients. This finding may suggest the role of zinc supplementation in help to better control of drug-resistant seizures, as well as, the importance of serum zinc monitoring in epileptic patients.

Background/Objectives: To determine the impact of psychiatric disorders on epilepsy treatment outcomes and healthcare utilization in children with epilepsy (CWE) based on the presence or timing of the onset of psychiatric disorders. Methods: This retrospective controlled study enrolled children (age < 18 years) with newly diagnosed epilepsy into four groups stratified by the presence and timing of the onset of psychiatric disorders (None: no psychiatric disorders; Before: psychiatric disorders only preceding the epilepsy diagnosis; After: new psychiatric disorders diagnosed only after the epilepsy diagnosis; Mixed: different psychiatric disorders diagnosed both before and after epilepsy diagnosis) and compared the intergroup differences in epilepsy treatment outcomes and healthcare utilization. Results: Among the CWE (n = 37,678), 13,285 (35.26%) had comorbid psychiatric disorders. The After (n = 7892), Mixed (n = 3105), and Before (n = 2288) groups had significantly longer treatment periods than those in the None group (p < 0.001). Compared with the None group, the remaining groups had significantly higher frequencies of outpatient visits, emergency room visits, and admissions and higher rates of status epilepticus and drug-resistant epilepsy (p < 0.001, respectively), with higher odds ratios [95% confidence interval] for status epilepticus (2.92 [2.68-3.18]) and drug-resistant epilepsy (3.01 [2.85-3.17]) in the After group. Conclusions: Psychiatric comorbidities, diagnosed before and after epilepsy diagnosis, negatively affected the treatment outcomes. CWE without prior psychiatric disorders that were newly diagnosed during epilepsy treatment had the worst outcomes and the highest healthcare utilization rates.

OBJECTIVE: The goal of this study is to evaluate the complications and mortality associated with vagus nerve stimulation (VNS).
METHODS: We retrospectively reviewed medical records of patients who underwent VNS implantation for the treatment of drug-resistant epilepsy (DRE) between 2000 and 2023. The mean follow-up time was 10.6 years, ranging from three months to 22 years.
RESULTS:  In total, 55 adult and pediatric patients received VNS therapy with 117 procedures performed over 23 years. The most common early complications were hoarseness and cough which were reported in eight adult patients (6.8%). Four children with intellectual disability (ID) had infection (3.4%), eight patients had lead breakage (6.8%), and two had device migration (1.7%). Four of all patients (7.3%) demonstrated late complications due to chronic nerve stimulation including vocal cord dysfunction, late-onset severe AV block, and obstructive sleep apnea (OSA). Three patients (5.5%) had VNS deactivated permanently due to complications and/or lack of efficacy. Two patients died from probable sudden unexpected death in epilepsy (SUDEP) with an incidence of 3.4/1000 person-years.
CONCLUSIONS:  VNS therapy is safe over long-term follow-up but not without risks. Most post-operative complications are minor and transient for adults. Children with ID tend to have infection and device migration. Late-onset cardiac complications and OSA can develop in some patients during VNS therapy and should not be overlooked. The SUDEP rate may decrease with VNS therapy over time.

Epilepsy treatment primarily involves antiseizure medications (ASMs) to eliminate seizures and improve the quality of life, but many patients develop drug-resistant epilepsy (DRE), necessitating alternative interventions. This study aimed to evaluate the long-term efficacy and safety of vagus nerve stimulation (VNS) in managing DRE. We retrospectively analyzed data from 105 adult patients treated at Agostino Gemelli Hospital from 1994 to 2022. Among the 73 patients with follow-up data, 80.8% were responders, experiencing significant reductions in seizure frequency over an average follow-up period of 9.4 years. Although 19.2% were non-responders, many of these patients still opted for generator replacements due to improvements in quality of life, such as fewer falls and shorter post-ictal periods. The overall complication rate was 12.3%, with most complications being mild and manageable. These findings suggest that VNS offers substantial long-term benefits for patients with DRE, improving seizure control and quality of life. This study underscores the importance of VNS as a viable long-term treatment option for DRE, highlighting its potential to significantly enhance patient outcomes and quality of life.

Objectives This study aimed to describe the clinical characteristics, investigational results, and management strategies in patients with drug-resistant epilepsy (DRE). Methods This retrospective cohort study included all adult and adolescent patients (aged 14 years or older) diagnosed with DRE who visited the adult neurology clinic at King Abdulaziz Medical City, Jeddah, Saudi Arabia from January 2019 to December 2021. DRE was defined as failure to achieve seizure freedom despite undergoing adequate trials of two well-tolerated and appropriately selected antiseizure medications. Results This study included 299 patients with DRE. Most patients were in their second to fourth decade, with a mean age of 37 ± 17 years. Focal onset epilepsy was diagnosed in 52.5% of the patients, and an etiology for epilepsy was determined in 44.1% of the patients. Findings in brain magnetic resonance imaging were abnormal in 49% of the patients, whereas abnormal findings in electroencephalograms were found in 27.5%. The most common antiseizure medication was levetiracetam (67.6% of cases). Conclusion The findings of this study confirm the challenges in diagnosing and managing patients with DRE and emphasize the necessity for careful and comprehensive patient evaluation. Further research is needed to investigate the effectiveness, safety, and accessibility of diagnostic and therapeutic resources for patients with DRE.

Stereoelectroencephalography (SEEG) is the gold standard to investigate the epileptic network in cases of drug-resistant epilepsy. Robot-assisted SEEG is increasingly being used; however, its installation process in the operating room is more difficult than that of the stereotactic frame procedure. New robotic tools and 3D intraoperative imaging ease the setup while achieving the same mechanical precision and a lower complication rate. In this video, the authors illustrate the surgical technique and step-by-step workflow using a robotic arm (neuromate) guided by a frameless registration system (neurolocate), registered with an intraoperative flat-panel CT scanner (O-arm). The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID2419.

Hypothalamic hamartomas are congenital lesions of the hypothalamus, with a range of symptoms defined by lesion location. Common presenting symptoms include gelastic seizures and precocious puberty. When hamartoma-related seizures become resistant to medications, laser interstitial thermal therapy (LITT) has been shown to be an effective treatment. The authors present a case of robot-assisted LITT for a patient with an 11-year history of epilepsy due to hypothalamic hamartoma. In addition, they demonstrate the use of a stereotactic biopsy needle implemented during the procedure for possible biopsy of deep cranial lesions. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID2415.