Seizure Control Research Articles

194 Responsive Neurostimulation Targeting the Centromedian Nucleus of the Thalamus Improves Seizure Control in Idiopathic Generalized Epilepsy and Select Multifocal Disease

INTRODUCTION: Although more than 30% of epilepsy patients are drug resistant, many have not traditionally been considered surgical candidates due to generalized or multifocal disease. However, responsive neurostimulation (RNS) of the centromedian nucleus (CM) of the thalamus appears promising for this patient population. We present outcomes following CM RNS for patients with idiopathic generalized epilepsy (IGE) or multifocal disease, with subgroup analyses of patients’ seizure types and targeting methodology. METHODS: 21 patients with drug resistant epilepsy underwent bilateral CM RNS implantation. Electrodes were localized and volumes of tissue activation (VTAs) were modeled in Lead-DBS. Outcome measures were extracted from electronic medical records. Clinical outcomes over time were compared between patients’ seizure types and RNS recorded long-episodes, and VTA overlap with thalamic nuclei was compared between patients with direct and indirect targeting methodologies. RESULTS: For patients with at least 1-year of follow up, average seizure reduction from pre-operative baseline was 81.3%, with 3 Engel class 1 patients, 5 Engel class 2, 8 Engel class 3, and 0 Engel class 4. Average seizure reduction was greatest for non-lesional multifocal patients. Average time to worthwhile seizure reduction was 217 days, and was shortest for myoclonic IGE patients. Long-episodes were associated with seizure reduction in IGE patients only. Direct targeting led to more anterior and medial electrodes with greater VTA overlap with CM. CONCLUSIONS: CM RNS may provide significant relief for IGE and multifocal epilepsy patients. Subsets of these patient populations may particularly benefit from CM RNS. Direct targeting may facilitate more selective stimulation of the CM. The refinement of stimulation targeting, tuning of RNS system parameters, and deliberate patient selection are ongoing areas of investigation.

183 Earlier Surgery is Associated With Improved Post-operative Language Development in Children With Tuberous Sclerosis Complex (TSC)

INTRODUCTION: Early life epilepsy in TSC has been strongly associated with lifelong intellectual disability. While improved seizure control correlates with improvements in quality of life and cognition, the importance of surgery timing in young children has not been well-studied. METHODS: Changes in patients’ preoperative (0-12 months) to postoperative (36 months) scores in neuropsychologic tests—including the Mullen Scales of Early Learning (MSEL), Vineland Adaptive Behavior Scales, Second Edition (VABS-II), and the Preschool Language Scales, 5th addition (PLS-5)—were calculated. Pearson correlation and multivariate linear regression models were used to correlate changes in test scores with age at surgery and separately with duration of epilepsy prior to surgery. Analysis was limited to those patients who demonstrated improved seizure control post-operatively (n = 18). RESULTS: Age at surgery had a statistically significant negative correlation with changes in the combined verbal sub-tests of the MSEL (R = -0.41, p = 0.04) and predicted the change in that measure outcome in a multivariate linear regression model (β: -0.09, p = 0.03). Similar trends were seen for the change in the total language score of the PLS-5 (R = -0.38, p = 0.06; β: -0.21, p = 0.07). Results were similar when the duration of epilepsy prior to surgery was assessed as the independent variable. However there were no clear trends with the VABS-II questionnaires, even in language domains. CONCLUSIONS: Our data shows that successful earlier surgery and shorter epilepsy duration prior to surgery are both associated with improved post-operative language development in a small cohort of patients with TSC. Prospective clinical trials are necessary to further elucidate this relationship.

Monopolar stereoelectroencephalography-guided radiofrequency thermocoagulation.

Stereoelectroencephalography (SEEG)-guided radiofrequency thermocoagulation (RFTC) has the advantage of producing a lesion in the epileptogenic zone (EZ) at the end of SEEG. The majority of published SEEG-guided RFTCs have been bipolar and usually performed between contiguous contacts of the same electrode. In the present study, the authors evaluate the safety, efficacy, and benefits of monopolar RFTC at the end of SEEG. This study included a series of 31 consecutive patients who had undergone RFTC at the end of SEEG for drug-resistant focal epilepsy in the period of January 2013-December 2019. Post-RFTC seizure control was assessed after 2 months and at the last follow-up visit. Twenty-one patients underwent resective epilepsy surgery after the SEEG-guided RFTC, and the postoperative seizure outcome among these patients was compared with the post-RFTC seizure outcome. Four hundred forty-six monopolar RFTCs were done in the 31 patients. Monopolar RFTCs were performed in all cortical areas, including the insular cortex in 11 patients (56 insular RFTCs). There were 31 noncontiguous lesions (7.0%) because of vascular constraints. The volume of one monopolar RFTC, as measured on T2-weighted MRI immediately after the procedure, was between 44 and 56 mm3 (mean 50 mm3). The 2-month post-RFTC seizure outcomes were as follows: seizure freedom in 13 patients (41.9%), ≥ 50% reduced seizure frequency in 11 (35.5%), and no significant change in 7 (22.6%). Seizure outcome at the last follow-up visit (mean 18 months, range 2-54 months) showed seizure freedom in 2 patients (6.5%) and ≥ 50% reduced seizure frequency in 20 patients (64.5%). Seizure freedom after monopolar RFTC was not significantly associated with the number or location of coagulated contacts. Seizure response after monopolar RFTC had a high positive predictive value (93.8%) but a low negative predictive value (40%) for seizure outcome after subsequent resective surgery. In this series, the only complication (3.2%) was a limited intraventricular hematoma following RFTC performed in the hippocampal head, with spontaneous resolution and no sequelae. The use of monopolar SEEG-guided RFTC provides more freedom in terms of choosing the SEEG contacts for thermocoagulation and a larger thermolesion volume. Monopolar thermocoagulation seems particularly beneficial in cases with an insular EZ, in which vascular constraints could be partially avoided by making noncontiguous lesions within the EZ.

Factors Affecting the Activation and Appearances of Epileptiform Abnormalities in Routine Electroencephalography by Different Provocation Methods

Objective: The objective of this study was to observe the effects of various clinical factors on the activation and appearance of epileptiform abnormalities (EAs) in routine electroencephalography (rEEG) by different provocation methods. Methods: This observational study involved a review of 136 patients presented for EEG recording due to various indications and their EEG showing EAs during various provocation methods. Results: Generalized spike-wave discharges (GSWDs) were the most frequent activated epileptiform pattern observed in, 81 (59.1%) recordings. This pattern was seen mainly in females 49 (P = 0.00), in patients with generalized seizures 48 (P = 0.00), in prolonged EEG records 3 (P = 0.03), and in both genetic 35 (P = 0.00) and lesional epilepsies 21 (P = 0.00). Focal sharp waves with bilateral synchrony (FSWSBS) were the most activated ictal pattern (P = 0.00). Ictal EAs after hyperventilation (HV) (P = 0.03) and intermittent photic stimulation (IPS) (P = 0.01) were mainly observed in patients with uncontrolled seizures (P = 0.00), and immune-mediated epilepsy (P = 0.02). Females sex (odds ratio [OR]: 1.33, confidence interval [CI]: 0.6–2.6; P = 0.25), bilateral tonic–clonic seizures (OR: 1.17, CI: 0.5–2.4; P = 0.31) and lesional epilepsies (OR: 1.45, CI: 0.7–2.9; P = 0.20) had risk of activation of EAs by provocation methods; however this risk was not statistically significant. While sleep deprivation (SD) (OR: 6.33, CI: 2.2–18.2; P = 0.00), nonrapid eye movement sleep (NREM) (OR: 2.41, CI: 1.0–5.4; P = 0.00), and prolong EEG recording (OR: 1.91, CI: 0.9–3.9; P = 0.04) were leading to a statistically significant risk of activation and appearances of EAs due to provocation. Conclusion: Different provocation methods can activate and augment the variety of EEG patterns of diverse clinical significance. Detection of activated ictal EAs is dependent on various patient factors, including seizure control, and the provocation method applied. Further larger prospective cohort studies with adequate sample sizes are warranted.

Development of a dispersive micro solid phase extraction-HPLC method for the simultaneous quantification of antiepileptic drugs in various matrices

Due to the widespread utilization of antiepileptic drugs for seizure control and patient well-being, it is crucial to determine their presence in biological and water samples. This is essential for optimizing therapy, comprehending drug behavior, identifying drug interactions, monitoring environmental contamination, and safeguarding public health and ecology. Hence, a novel method that combines dispersive micro solid phase extraction with HPLC-DAD was developed to simultaneously determine the presence of Lacosamide, Levetiracetam, and Phenytoin. To achieve this, a new sorbent was synthesized using the hydrothermal and sol–gel methods, which consisted of bimetallic MIL-100 (Fe, Ni) on MIL-100 (Mn), SiO2, and Fe3O4 nanoparticles. We compared the extraction capabilities of several sorbents in order to select the most effective one. The optimal ratio of components for the chosen sorbent was determined through the simplex lattice design to enhance its efficiency. The optimized values for SiO2, Fe3O4, and MIL-100 (Fe, Ni) on MIL-100 (Mn) were found to be 0.1, 0.34, and 0.56, respectively. The parameters that affected the dispersive micro solid phase extraction method were optimized using both experimental design and one factor at a time. Under the optimal conditions, the linear range for the detection of Lacosamide, Levetiracetam, and Phenytoin was determined to be 0.1–363.0, 0.3–372.0, and 0.4–435.0 ng mL−1, respectively, with low LODs below 0.13 ng mL−1. Additionally, a preconcentration factor of 492.6, 487.1, and 469.5 was achieved for measuring Lacosamide, Levetiracetam, and Phenytoin, respectively. The intra-day and inter-day relative standard deviations (RSDs) ranged from 3.8 % to 4.6 % and 4.2 % to 5.2 %, respectively. The recoveries and RSDs for analyzing real water, human urine, and serum samples were found to be between 89.6–97.0 % and 4.53–6.44 %, respectively.

Epilepsy secondary to brain injury by electrocution: A case report

Introduction: According to the Yearbook of Accidents of Electrical Origin for the year 2022, 853 accidents due to electric shock were reported in Brazil, of which 592 died, a reduction of 12.2% in mortality compared to the previous year. Three conditions elucidate trauma switches caused by the passage of electric current, the regulatory alterations by the passage of electric current, the conversion of electrical energy into thermal, known as the Joule effect, and muscle damage by the electrical stimulus of exacerbated contractions. Case Report: A 51-year-old male patient was followed up on an outpatient basis due to a nervous breakdown caused by accident with a high-voltage electrical discharge 15 years ago. After the event, he evolved with conduction aphasia, homonymous hemianopia on the right, hypoesthesia on the right side of the body, dysmetria on the right upper limb, and epileptic seizures of focal onset, evolving into tonic-clonic seizures. For seizure control, carbamazepine 200 mg 3 times a day was administered, with complete seizure control since then. Conclusion: Therefore, it is important to emphasize that the damage caused by electrocution to the central nervous system (CNS) is varied. Still, due to the patient’s clinical presentation, his neuroimaging findings, and his history, this is epilepsy secondary to electrocution. Encephalomalacia demonstrates a large scar in the brain tissue, and its control of seizure episodes with the adopted pharmacotherapy also corroborates.

Frailty as a comprehensive health measure beyond seizure control in patients with epilepsy: A cross-sectional study.

Due to the high clinical heterogeneity of epilepsy, there is a critical need for novel metrics aimed at capturing its biological and phenotypic complexity. Frailty is increasingly recognized in various medical disciplines as a useful construct to understand differences in susceptibility to adverse outcomes. Here, we develop a frailty index (FI) for patients with epilepsy (PwE) and explore its association with demographic and clinical features. In this cross-sectional study, we consecutively enrolled 153 PwE from an outpatient epilepsy clinic. Participants were assessed for various health deficits to calculate the FI. Associations between FI and demographic/clinical features, antiseizure medications (ASMs), and patient-reported outcomes were analyzed using general linear models and Spearman correlation. The median age at the time of study visit was 47 years (interquartile range = 33-60), and 89 (58.2%) patients were females. Multiple linear regression revealed that the developed 33-item FI showed an independent association with age, female sex, higher body mass index, family history of epilepsy, intellectual disability, and the number of ASMs used. A robust analysis of covariance showed higher FI levels in patients using cytochrome P450 3A4-inducer ASMs. We found a moderate positive correlation between FI and psychological distress, lower quality of life, and physical frailty, measured by the Hospital Anxiety and Depression Scale, Quality of Life in Epilepsy Inventory-10, and handgrip strength, respectively. Finally, a weak association was observed between higher FI scores and an increased number of epileptic falls. This study highlights the significance of frailty as a comprehensive health measure in epilepsy. It suggests that frailty in this specific population is not only a manifestation of aging but is inherently linked to epilepsy and treatment-related factors. Future research is warranted to validate and refine the FI in diverse epilepsy populations and investigate its impact on specific adverse outcomes in longitudinal studies.

Abstract 6304: Seizure self-report and monitoring: Agreement between patient and clinician report and implications for care in patients with IDH-mutant and IDH-wild type gliomas

Abstract Primary brain tumor (PBT) patients commonly experience seizures, which can be measured and monitored by a variety of tools. Here, we explore the concordance between 2 tools and their use in reporting seizures over time among PBT patients enrolled in a natural history study (NCT02851706, PI: T. Armstrong). Patients complete the M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT), which measures symptom severity (including seizure) within the last 24 hours from 0-10; and, as part of the same visit, pairs of clinicians and patients complete the Seizure Control Composite Index (RANO-SCCI), which includes the questions ‘Have you ever had a seizure’ (RANO-SCCIQ1) and ‘Have you had a seizure since your last clinic visit’ (RANO-SCCIQ2). Responses to each measure are reported in aggregate and by IDH status. Participants included 89 patients with gliomas who were primarily white (84%) males (62%) with a median age of 48 years (range: 27-78) and KPS ≥ 90 (85%). Based on patient reports, 65% endorsed ever having a seizure (RANO-SCCIQ1), 17% had a recent seizure (RANO-SCCIQ2), and 12% had a seizure within the last 24 hours (MDASI-BT). For the RANO-SCCIQ1 data, patients and clinicians generally agreed except for 6 pairs (7%) where clinicians indicated a seizure but patients did not. Of the 59 who reported recent seizures (RANO-SCCIQ2), two pairs (3%) disagreed, with patients indicating a recent seizure but clinicians not endorsing a seizure had occurred. Good overall agreement (86%) was observed between the RANO-SCCIQ2 and MDASI-BT for both clinician and patient responses, with 3 and 2 paired disagreements respectively, in which seizures were indicated in the last 24 hours but not recorded as a recent seizure on the (RANO-SCCIQ2). Comparing clinician report of seizures in those with IDH-mutated (n=39) to IDH-wildtype (n=15) tumors, 85% (33/39) versus 47% (7/15) reported ever having a seizure and 7 of 33 (21%) with IDH-mutant and 1 of 7 (14%) with IDH-wild type (IDH-WT) tumors respectively reported a seizure since the last visit. Disparities in recognition of seizures between patient and clinician highlights a need for patient education to increase awareness of events and recognition of ongoing risk. Although those with IDH-mutated tumors are at higher risk of having seizures, nearly half of those with IDH-WT reported ever having seizures, underscoring the need for all patients to be educated on recognizing and assessing seizure symptoms. Citation Format: Hope Miller, Ewa Grajkowska, Alvina Acquaye-Mallory, Anna Choi, Jennifer Reyes, Mark R. Gilbert, Edward K. Avila, Terri S. Armstrong, Elizabeth Vera. Seizure self-report and monitoring: Agreement between patient and clinician report and implications for care in patients with IDH-mutant and IDH-wild type gliomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6304.

Effectiveness of a Self-efficacy Enhanced Program Using Cartoon Animation for Self-care Behaviors Among Schoolchildren with Epilepsy: A Quasi-experimental Study

Epilepsy is one of the most common chronic neurological diseases in children and may cause repeated seizures and complications. Thus, self-care behavior is vital for effective seizure control. This quasi-experimental study examined the effectiveness of the Self-efficacy Enhanced Program Using Cartoon Animation for self-care behaviors among school children with epilepsy. The study was conducted at a pediatric neurological clinic in the outpatient department of a tertiary hospital in Bangkok, Thailand. There were 42 children with epilepsy, aged 10 to 12 years, who participated in the study: 21 in the experiment group and 21 in the control group. The experimental group received the program, which used two cartoon animation videos to enhance self-care behaviors for eight weeks, while the control group received regular care only. The data were collected using demographic and self-care behavior questionnaires and were analyzed using chi-square and t-tests.The results demonstrated that after program completion, the mean scores of total self-care behavior and subscale on medication taking, avoiding triggers seizures, and self-care of abnormal symptoms and seeking information in the experimental group were significantly higher than before receiving it and higher than those in the control group significantly. Nurses should use this program to increase self-care behaviors among children with epilepsy. However, testing the program in other settings with long-term follow-up is needed before it can be used widely.

Gluten sensitivity based on HLA genotyping in patients with epilepsy in a tertiary hospital in Malaysia

AbstractIntroductionGluten sensitivity (GS) is present in approximately 1% of the Malaysian population (Yap et al., PLoS One, 10, 2015, e0121908). GS is associated with several neurological conditions including epilepsy. Individuals with GS often exhibit a genetic predisposition associated with human leukocyte antigens (HLA) (Cecilio & Bonatto, Arq Bras Cir Dig, 28, 2015, 183). The purpose of this study was to investigate the prevalence of GS based on HLA genotyping in patients with epilepsy (PWE).MethodIn total, 50 PWE and 50 controls were recruited. DNA was extracted from the venous blood samples and genotyped for HLA‐DQ2.2, DQ2.5, DQ7 and DQ 8. In this study, GS was diagnosed if any subject showed positive for one or more of the HLA‐DQ alleles. The type of epilepsy and number of antiseizure medication (ASM) used were recorded.ResultsOnly 2 alleles (HLA‐DQ 2.2 & HLA‐DQ8) were detected among 46 out of 100 subjects. 18 PWE and 19 controls were positive for HLA‐DQ8 (p = 0.836). 9 of the PWE, but no controls were positive for HLA‐DQ 2.2 (p = 0.003). 8 of these 9 PWE who were positive for HLA‐DQ 2.2 were also positive for HLA‐DQ8 (double positive), and these patients required multiple ASM for seizure control (p = 0.006).ConclusionHLA‐DQ2.2 was seen highly prevalent in PWE. The double positives required more than one ASM for seizure control postulating malabsorption of ASM in these individuals. These findings suggest that HLA‐DQ genotyping may be a valuable additional test in PWE especially in those needing more than one ASM. Prescribing gluten‐free diet (GFD) to PWE with GS may potentially be an additional measure to achieve seizure control.

Effective Factors in Cognitive Functions of Patients with Temporal Lobe Epilepsy

Background: Temporal lobe epilepsy (TLE) is the most common form of partial epilepsy and increases the risk of cognitive impairment, negatively impacting the quality of life of affected individuals. Objectives: This study aimed to investigate cognitive function in patients with low socioeconomic status affected by TLE and identify factors influencing such function. Methods: This case-control study, conducted between July 2021 and August 2022, compared the cognitive function of 40 patients affected by TLE to 92 healthy controls. The Montreal cognitive assessment (MoCA) was used for neurocognitive evaluation. Data analysis was performed using SPSS 25.0 for Windows. Results: The mean age of the patient group was 33.35 years, compared to 35.37 years in the control group. Moreover, 70% of patients affected by TLE displayed cognitive impairment and demonstrated lower performance in cognitive functions than the control group (P < 0.05). Significant correlations were identified between overall MoCA scores and several factors, including seizure frequency, educational level, polytherapy, disease duration, and self-esteem scores (P < 0.05). Multivariate analysis revealed that seizure control and higher educational level were statistically significant predictors of overall MoCA scores in patients affected by TLE. Conclusions: In low-income patients affected by TLE, seizure control and a higher educational level emerged as predictors of cognitive performance. These findings underscore the importance of identifying and managing comorbidities and the need for tailored cognitive rehabilitation programs for this population.

Efficacy and Safety of adjunctive Perampanel in a prospective, real-world, Phase IV study in Indian patients aged ≥12 years for Treatment of focal-onset Epilepsy: Study 508.

ESPRITE (Study 508; NCT03836924) evaluated the real-world safety, tolerability, and efficacy of adjunctive perampanel in patients aged ≥12 years with focal-onset seizures (FOS), with or without focal to bilateral tonic-clonic seizures (FBTCS), in India. ESPRITE was a prospective, multicenter, single-arm, observational, Phase IV study with a 6-month Treatment Period. Patients were aged ≥12 years and had been prescribed perampanel for adjunctive treatment of FOS, with or without FBTCS. Assessments included incidence of treatment-emergent adverse events (TEAEs; primary endpoint), median percent reduction in seizure frequency per 28 days from baseline, 50% responder rates, and seizure-freedom rates. Overall, 200 patients were enrolled (199 patients in the Safety Analysis Set and 174 patients who completed all visits in the main efficacy analyses). TEAEs (all mild or moderate in severity) were reported in 18.1% (n = 36/199) of patients (the most common were dizziness [3.0%] and irritability [2.0%]). TEAEs leading to discontinuation of perampanel were reported in 2.0% of patients; no deaths or serious TEAEs occurred. At 6 months, median percent reduction in seizure frequency was 100.0%, 50% responder rate was 83.3%, and seizure-freedom rate was 49.4%. Adjunctive perampanel (at a mean daily dose of 4 mg/day) was shown to be well tolerated and effective in patients aged ≥12 years with FOS, with or without FBTCS, from India. Many patients do not receive adequate treatment for epilepsy and need effective seizure control medications. In this 6-month clinical study, 199 patients from India, aged 12 years or older, added perampanel to the anti-seizure medications they were already taking. At 6 months, 49% of patients experienced no seizures since starting perampanel and seizure frequency was reduced by half in 83% of patients. Side effects occurred in 18% of patients (most commonly dizziness and irritability) and caused 2% to stop perampanel; no deaths were reported. Perampanel was an effective and generally safe added medication for patients with epilepsy from India.

Analysis of clinical characteristics and histopathological transcription in 40 patients afflicted by epilepsy stemming from focal cortical dysplasia.

This study aims to comprehensively analyze the clinical characteristics and identify the differentially expressed genes associated with drug-resistant epilepsy (DRE) in patients with focal cortical dysplasia (FCD). A retrospective investigation was conducted from July 2019 to June 2022, involving 40 pediatric cases of DRE linked to FCD. Subsequent follow-ups were done to assess post-surgical outcomes. Transcriptomic sequencing and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to examine differential gene expression between the FCD and control groups. Among the 40 patients included in the study, focal to bilateral tonic-clonic seizures (13/40, 32.50%) and epileptic spasms (9/40, 22.50%) were the predominant seizure types. Magnetic resonance imaging (MRI) showed frequent involvement of the frontal (22/40, 55%) and temporal lobes (12/40, 30%). In cases with negative MRI results (13/13, 100%), positron emission tomography/computed tomography (PET-CT) scans revealed hypometabolic lesions. Fused MRI/PET-CT images demonstrated lesion reduction in 40.74% (11/27) of cases compared with PET-CT alone, while 59.26% (16/27) yielded results consistent with PET-CT findings. FCD type II was identified in 26 cases, and FCD type I in 13 cases. At the last follow-up, 38 patients were prescribed an average of 1.27 ± 1.05 anti-seizure medications (ASMs), with two patients discontinuing treatment. After a postoperative follow-up period of 23.50 months, 75% (30/40) of patients achieved Engel class I outcome. Transcriptomic sequencing and qRT-PCR analysis identified several genes primarily associated with cilia, including CFAP47, CFAP126, JHY, RSPH4A, and SPAG1. This study highlights focal to bilateral tonic-clonic seizures as the most common seizure type in patients with DRE due to FCD. Surgical intervention primarily targeted lesions in the frontal and temporal lobes. Patients with FCD-related DRE showed a promising prognosis for seizure control post-surgery. The identified genes, including CFAP47, CFAP126, JHY, RSPH4A, and SPAG1, could serve as potential biomarkers for FCD. This study aimed to comprehensively evaluate the clinical data of individuals affected by focal cortical dysplasia and analyze transcriptomic data from brain tissues. We found that focal to bilateral tonic-clonic seizures were the most prevalent seizure type in patients with drug-resistant epilepsy. In cases treated surgically, the frontal and temporal lobes were the primary sites of the lesions. Moreover, patients with focal cortical dysplasia-induced drug-resistant epilepsy exhibited a favorable prognosis for seizure control after surgery. CFAP47, CFAP126, JHY, RSPH4A, and SPAG1 have emerged as potential pathogenic genes for the development of focal cortical dysplasia.

Caffeine Decreases Topiramate Levels in Zebrafish Larvae in a Pentylenetetrazol-Induced Seizure Model.

Epilepsy ranks as the second-most prevalent neurological disease, and is characterized by seizures resulting in neurobiological and behavioral impairment. Naturally occurring in coffee beans or tea leaves, the alkaloid caffeine (CAF) is the most prevalent global stimulant. Caffeine has been observed to influence epileptic seizures and the efficacy of antiepileptic medications, with a notable impact on topiramate (TPM). This study aimed to explore the influence of CAF on TPM's anticonvulsant effects in zebrafish larvae within a PTZ-induced seizure model, concurrently determining TPM concentrations through a sophisticated analytical approach based on ultrahigh-performance liquid chromatography and subsequent mass spectrometric detection. Zebrafish larvae four days post-fertilization were incubated for 18 h with varying doses of TPM or combinations of CAF + TPM, and locomotor activity was then assessed. Seizures were induced by introducing a PTZ solution to achieve a final concentration of 20 mM. Utilizing liquid chromatography-mass spectrometry (LC-MS/MS), TPM levels in the larvae were quantified. CAF co-administration (especially in higher doses) with TPM caused a decrease in the average locomotor activity in the larvae compared to TPM alone. Moreover, CAF decreased TPM levels in the larvae at all investigated doses. In conclusion, these findings offer a novel perspective on the interplay between CAF and TPM, shedding light on previously unexplored facets. The potential impact of CAF consumption in assisting with epileptic seizure control, unless proven otherwise, suggests a noteworthy consideration for future research and clinical practices.

May anti-seizure medications alter brain structure in temporal lobe epilepsy? A prospective study.

Mild mesial temporal lobe epilepsy (MTLE) patients may remain untreated for a considerable time after disease onset or achieve seizure control with a single anti-seizures medication (ASM). Thus, they represent an optimal population to investigate whether ASMs might have influence on brain structure. We consecutively enrolled 56 mild MTLE patients (22/56 untreated, 34/56 on-monotherapy) and 58 healthy controls, matched for age and gender. All subjects underwent 3T-brain MRI, using FreeSurfer for automated morphometry. Differences in gray matter were assessed using one-way Analysis of Covariance (ANCOVA), adjusting for age, disease duration and intracranial volume. No significant change was observed between treated and untreated patients. We observed a significant reduction in cortical thickness of left inferior parietal, inferior temporal, middle temporal gyri, and right inferior parietal gyrus, temporal pole in monotherapy patients compared to healthy controls, as well as an increase in left isthmus of cingulate gyrus in untreated MTLE subjects compared to controls. Surface and subcortical volumes analysis revealed no differences among groups. Our study demonstrated no substantial morphological abnormalities between untreated mild MTLE patients and those undergoing monotherapy. Although exploratory, these results may reassure about safety of commonly used drugs and their marginal role in influencing neuroimaging results. PLAIN LANGUAGE SUMMARY: This study investigated the following question: can medications against epileptic seizures have an effect on brain structure in mild mesial temporal lobe? Preliminary results from our analyses suggest not, as we did not find any difference in brain gray matter between untreated patients and those treated with a single anti-seizures medication. On the other hand, epilepsy patients presented cortical thinning compared to healthy controls in several regions of the temporal and parietal lobes, in line with previous studies investigating the disease.

Evaluation of Outcomes and Complications of Sphenoid Wing Meningiomas in Tertiary Care Hospital of KPK

Objective: The objective of this study is to evaluate the outcomes and complications associated with pterional craniotomy and extended pterional craniotomy for the resection of Sphenoid Wing Meningiomas. Material and Methods: A prospective study was conducted on 34 patients at the Neurosurgery department, Prime Teaching Hospital, Pakistan, and Ali Institute of Neurosciences. We examined 34 recently diagnosed cases of sphenoid wing meningiomas, selected through a total enumerative sampling method. Diagnosis of these meningiomas was confirmed by comprehensive neurological assessment and imaging studies. Various surgical techniques, such as Pterional and Extended Pterional approaches, were employed in the procedures. Assessment of clinical outcomes and complications was conducted during follow-up evaluations. A total of 34 patients diagnosed with sphenoid wing meningiomas were covered as the study’s target population. All patients met certain criteria to be included in the study. Results: 25 (73.6%) of the total number of patients were females and 9 (26.4%) were males. The mean age at diagnosis was 47 ± 5 years. Presenting symptoms included headache, seizures, visual loss, motor deficit, and cognitive decline. Surgical techniques used in tumor resection were pterional craniotomy and extended pterional craniotomy. Post-operative evaluation after follow-up studies showed that the symptoms reversed, including a reduction in headache, vision restoration, seizure control, and motor and cognitive function improvement. Conclusion: Pterional approach and extended Pterional approaches related to SWM removal are satisfactory rates of an acceptable and safe surgical treatment with satisfactory results concerning the total resection rate and related clinical improvement.

Isoflurane treatment for refractory and super-refractory status epilepticus in dogs.

Resistant epileptic episodes, such as refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE), are neurological emergencies that require immediate medical treatment. Although inhalational anesthetics, such as isoflurane (ISO), have been proposed as a means of seizure control in dogs, there is currently a lack of both experimental and clinical studies on this subject. This is a retrospective clinical study. Records of dogs that received ISO for the management of RSE and SRSE during their intensive care unit (ICU) hospitalization at the Companion Animal Clinic of the Aristotle University of Thessaloniki were included in the present study. The study period spanned from February 2013 to March 2023. Dogs were identified as responders (R) when RSE/SRSE ceased after ISO administration, and the dogs were successfully discharged from the ICU after ISO discontinuation. Dogs were identified as non-responders (NR) when RSE/SRSE ceased after ISO administration, but RSE/SRSE reoccurred after ISO discontinuation. Additional data about the number and time of ISO cycles, the time of ICU hospitalization, the side effects of ISO administration, and an additional administration of antiepileptic drugs (AEDs) and anesthetic drugs were also recorded. A total of 20 dogs with 26 recorded RSE/SRSE episodes and 26 anesthetic cycles with ISO were included in the present study. The clinical termination of seizure activity was achieved 100% (26/26) in all episodes. In 73.1% (19/26) of the episodes, ISO administration resulted in successful RSE/SRSE treatment. Poor outcome was recorded in 26.9% (7/26) of the episodes because RSE/SRSE reoccurred after ISO discontinuation, and the dogs were euthanatized or died due to cardiac arrest. Inspiratory ISO ranged between 0.5 and 4.0%. The median time of the anesthetic cycles with ISO was 12.67 h (4.00-62.00). The median duration of the ICU hospitalization was 48.00 h (24.00-120.00). At least one ISO-related side effect was recorded in 23 out of 26 (88.5%) episodes. To the authors' knowledge, this is the first clinical study that addresses the administration of ISO for RSE/SRSE treatment in dogs. The use of ISO may be beneficial in terminating RSE/SRSE; however, further prospective studies are necessary to confirm this observation.

The efficacy and safety of novel antiepileptic drugs in treatment of epilepsy of patients with brain tumors.

This meta-analysis aimed to assess the effectiveness and safety of novel antiepileptic drugs (AEDs) in treating epilepsy in patients with brain tumors (BTRE). A search was conducted on PubMed, EMBASE, Web of Science, and the Cochrane Library from inception to February 2023, with English language restriction. In this meta-analysis, 18 clinical trials involving 755 BTRE patients were included to assess the efficacy and safety of novel AEDs in BTRE treatment. At the last follow-up, a ≥50% reduction in seizure frequency was experienced by 72% of patients (random-effects model, 95% CI = 0.64-0.78) using novel AEDs. At the last follow-up, seizure freedom was experienced by 34% of patients (random-effects model, 95% CI = 0.28-0.41) using novel AEDs. The pooled incidence of AEs was found to be 19% (95% CI: 13%-26%), with a withdrawal rate due to adverse effects of only 3%. Comparable efficacy and incidence of adverse effects were observed between lacosamide and perampanel. This meta-analysis suggests that novel antiepileptic drugs are deemed effective for seizure control in brain tumor patients, particularly when used as adjunctive therapy. Although lacosamide and perampanel received more focus in studies, no significant difference was observed in the efficacy and adverse reactions of these two drugs in seizure control. Further randomized controlled trials are deemed necessary to validate our findings.

Providing quality care for people with CDKL5 deficiency disorder: A European expert panel opinion on the patient journey.

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a developmental and epileptic encephalopathy caused by variants in the CDKL5 gene. The disorder is characterized by intractable early-onset seizures, severe neurodevelopmental delay, hypotonia, motor disabilities, cerebral (cortical) visual impairment and microcephaly. With no disease-modifying therapies available for CDD, treatment is symptomatic with an initial focus on seizure control. Another unmet need in the management of people with CDD is the lack of evidence to aid standardized care and guideline development. To address this gap, experts in CDD and representatives from patient advocacy groups from Denmark, Finland, France, Germany, Italy, Poland, Spain, and the United Kingdom convened to form an Expert Working Group. The aim was to provide an expert opinion consensus on how to ensure quality care in routine clinical practice within the European setting, including in settings with limited experience or resources for multidisciplinary care of CDD and other developmental and epileptic encephalopathies. By means of one-to-one interviews around the current treatment landscape in CDD, insights from the Expert Working Group were collated and developed into a Europe-specific patient journey for individuals with CDD, which was later validated by the group. Further discussions followed to gain consensus of opinions on challenges and potential solutions for achieving quality care in this setting. The panel recognized the benefit of early genetic testing, a holistic personalized approach to seizure control (taking into consideration various factors such as concomitant medications and comorbidities), and age- and comorbidity-dependent multidisciplinary care for optimizing patient outcomes and quality of life. However, their insights and experiences also highlighted much disparity in management approaches and resources across different European countries. Development of standardized European recommendations is required to align realistic diagnostic criteria, treatment goals, and management approaches that can be adapted for different settings. PLAIN LANGUAGE SUMMARY: Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a rare condition caused by a genetic mutation with a broad range of symptoms apparent from early childhood, including epileptic seizures that do not respond to medication and severe delays in development. Due to the lack of guidance on managing CDD, international experts and patient advocates discussed best practices in the care of people with CDD in Europe. The panel agreed that early testing, a personalized approach to managing seizures,and access to care from different disciplines are beneficial. Development of guidelines to ensure that care is standardized would also be valuable.

MTORC2: The "Ace in the Hole" for a Broader Control of Epileptic Seizures?

mTORC2: The "Ace in the Hole" for a Broader Control of Epileptic Seizures?