The long-term outcomes in drug-resistant epilepsy patients who underwent subtotal hemispherotomy: A single-center retrospective cohort study.

OBJECTIVE: To evaluate the long-term outcomes of subtotal hemispherotomy (SH) in treating drug-resistant epilepsy caused by unilateral hemispheric lesions and try to give the prognostic factors for these outcomes. METHODS: We retrospectively reviewed the clinical data of 19 patients who underwent SH in Sanbo Brain Hospital, Capital Medical University, Beijing, China, from May 2008 to April 2021. All clinical data and factors related to surgical and functional outcomes, including motor, neuropsychiatric, and language function, were collected and analyzed. RESULTS: The surgical outcomes showed 13 (68 %) patients were seizure-free at the last follow-up (2-14 years, mean: 5.6±2.9). No changes were found in motor outcomes in 12 (63 %) patients; seven (37 %) patients had new permanent motor deficits (NPMD). Improvement in the full-scale intelligence quotient (FIQ) (p = 0.009) was observed. Univariate analysis found that patients who did not achieve seizure freedom had a significantly older age at surgery (p = 0.017) and acute post-operative seizures (APOS) (p = 0.046). Kaplan-Meier analysis also identified significant differences in seizure outcomes between the children and adult subgroups (p = 0.0017). Multivariate Cox analysis showed that older age at surgery (HR=1.055, p = 0.034) was associated with shorter time-to-seizure-recurrence. Resection of the central operculum and insula (OR= 80.433, p =0.031) and higher monthly seizure frequency (OR= 1.073, p = 0.040) were also poor prognostic factors for motor function outcomes. CONCLUSION: SH is an effective treatment procedure in treating patients with drug-resistant epilepsy caused by hemispheric lesions with satisfied seizure outcomes, limited impairment of motor function, and preserving neuropsychiatric outcomes.

Management of autoimmune temporal lobe epilepsy with GAD65 antibody: four case reports.

AIM OF STUDY: Glutamate decarboxylase (GAD) enzyme can be a target intracellular antigen in autoimmune focal epilepsy. GAD65 antibody is in found patients diagnosed with drug-refractory temporal lobe epilepsy (TLE). We explore the clinical features of the disease and therapeutic options. MATERIAL AND METHODS: We present the cases of four TLE patients, two of them with type 1 diabetes. All of them were drug-resistant and therefore underwent presurgical evaluation, which revealed GAD65 antibody positivity. We discuss the four GAD65 antibody positive temporal lobe epilepsy patients' electroclinical data, the treatments, and their effectiveness. RESULTS: One of them became seizure-free after right anterior temporal lobe resection, two of them did not show significant improvement with immunmodulatory agents, and the fourth patient with the shortest duration of disease had significant improvement in seizure status and normalisation of cognitive status with IVIg therapy. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our cases show that the earlier a GAD65 antibody is detected, the greater the chance of achieving seizure freedom or improvements in both seizure and cognitive status with immunomodulatory agents. However, in some cases, surgery may also bring seizure freedom, but with a risk of cognitive deterioration.

Surgical outcomes of patients with genetically refractory epilepsy: A systematic review and meta-analysis.

OBJECTIVE: To summarize the surgical outcomes of genetically refractory epilepsy and identify prognostic factors for these outcomes. METHODS: A literature search of the PubMed, Web of Science, and Embase databases for relevant studies, published between January 1, 2002 and December 31, 2023, was performed using specific search terms. All studies addressing surgical outcomes and follow-up of genetically refractory epilepsy were included. All statistical analyses were performed using STATA software (StataCorp LLC, College Station, TX, USA). This review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, 2020 (i.e., "PRISMA") reporting guidelines. RESULTS: Of the 3833 studies retrieved, 55 fulfilled the inclusion criteria. Eight studies were eligible for meta-analysis at the study level. Pooled outcomes revealed that 74 % of patients who underwent resective surgery (95 % confidence interval [CI] 0.55-0.89; z = 9.47, p < 0.05) achieved Engel I status at the last follow-up. In the study level analysis, pooled outcomes revealed that 9 % of patients who underwent vagus nerve stimulation achieved seizure-free status (95 % CI 0.00-0.31; z = 1.74, p < 0.05), and 61 % (95 % CI 0.55-0.89; z = 11.96, p < 0.05) achieved a 50 % reduction in seizure frequency at the last follow-up. Fifty-three studies comprising 249 patients were included in an individual-level analysis. Among patients who underwent lesion resection or lobectomy/multilobar resection, 65 % (100/153) achieved Engel I status at the last follow-up. Univariate analysis indicated that female sex, somatic mutations, and presenting with focal seizure symptoms were associated with better prognosis (p < 0.05). Additionally, 75 % (21/28) of patients who underwent hemispherectomy/hemispherotomy achieved Engel I status at the last follow-up. In the individual-level analysis, among patients treated with vagus nerve stimulation, 21 % (10/47) were seizure-free and 64 % (30/47) experienced >50 % reduction in seizure frequency compared with baseline. CONCLUSION: Meticulous presurgical evaluation and selection of appropriate surgical procedures can, to a certain extent, effectively control seizures. Therefore, various surgical procedures should be considered when treating patients with genetically refractory epilepsy.

From Alpha-Thalassemia Trait to NPRL3-Related Epilepsy: A Genomic Diagnostic Odyssey.

Introduction: The NPRL3 gene is a critical component of the GATOR1 complex, which negatively regulates the mTORC1 pathway, essential for neurogenesis and brain development. Located on chromosome 16p13.3, NPRL3 is situated near the α-globin gene cluster. Haploinsufficiency of NPRL3, either by deletion or a pathogenic variant, is associated with a variable phenotype of focal epilepsy, with or without malformations of cortical development, with known decreased penetrance. Case Description: This work details the diagnostic odyssey of a neurotypical 10-year-old boy who presented at age 2 with unusual nocturnal episodes and a history of microcytic anemia, as well as a review of the existing literature on NPRL3-related epilepsy, with an emphasis on individuals with deletions who also present with α-thalassemia trait. The proband's episodes were mistaken for gastroesophageal reflux disease for several years. He had molecular testing for his α-thalassemia trait and was noted to carry a deletion encompassing the regulatory region of the α-thalassemia gene cluster. Following the onset of overt focal motor seizures, genetic testing revealed a heterozygous loss of NPRL3, within a 106 kb microdeletion on chromosome 16p13.3, inherited from his mother. This deletion encompassed the entire NPRL3 gene, which overlaps the regulatory region of the α-globin gene cluster, giving him the dual diagnosis of NPRL3-related epilepsy and α-thalassemia trait. Brain imaging postprocessing showed left hippocampal sclerosis and mid-posterior para-hippocampal focal cortical dysplasia, leading to the consideration of epilepsy surgery. Conclusions: This case underscores the necessity of early and comprehensive genetic assessments in children with epilepsy accompanied by systemic features, even in the absence of a family history of epilepsy or a developmental delay. Recognizing phenotypic overlaps is crucial to avoid diagnostic delays. Our findings also highlight the impact of disruptions in regulatory regions in genetic disorders: any individual with full gene deletion of NPRL3 would have, at a minimum, α-thalassemia trait, due to the presence of the major regulatory element of α-globin genes overlapping the gene's introns.

Association of earlier surgery with improved postoperative language development in children with tuberous sclerosis complex.

OBJECTIVE: The authors evaluated the impact of the timing of epilepsy surgery on postoperative neurocognitive outcomes in a cohort of children followed in the multiinstitutional Tuberous Sclerosis Complex (TSC) Autism Center of Excellence Research Network (TACERN) study. METHODS: Twenty-seven of 159 patients in the TACERN cohort had drug-refractory epilepsy and underwent surgery. Ages at surgery ranged from 15.86 to 154.14 weeks (median 91.93 weeks). Changes in patients' first preoperative (10-58 weeks) to last postoperative (155-188 weeks) scores on three neuropsychological tests-the Mullen Scales of Early Learning (MSEL), the Vineland Adaptive Behavior Scales, 2nd edition (VABS-2), and the Preschool Language Scales, 5th edition (PLS-5)-were calculated. Pearson correlation and multivariate linear regression models were used to correlate test outcomes separately with age at surgery and duration of epilepsy prior to surgery. Analyses were separately conducted for patients whose seizure burdens decreased postoperatively (n = 21) and those whose seizure burdens did not (n = 6). Regression analysis was specifically focused on the 21 patients who achieved successful seizure control. RESULTS: Age at surgery was significantly negatively correlated with the change in the combined verbal subtests of the MSEL (R = -0.45, p = 0.039) and predicted this score in a multivariate linear regression model (ß = -0.09, p = 0.035). Similar trends were seen in the total language score of the PLS-5 (R = -0.4, p = 0.089; ß = -0.12, p = 0.014) and in analyses examining the duration of epilepsy prior to surgery as the independent variable of interest. Associations between age at surgery and duration of epilepsy prior to surgery with changes in the verbal subscores of VABS-2 were more variable (R = -0.15, p = 0.52; ß = -0.05, p = 0.482). CONCLUSIONS: Earlier surgery and shorter epilepsy duration prior to surgery were associated with greater improvement in postoperative language in patients with TSC. Prospective or comparative effectiveness clinical trials are needed to further elucidate surgical timing impacts on neurocognitive outcomes.

Comparison of various doses of oral cannabidiol for treating refractory epilepsy indications: a network meta-analysis.

Aim: To evaluate the comparative efficacy and safety of various doses of oral cannabidiol (CBD) in treating refractory epilepsy indications, thus providing more informative evidence for clinical decision-making. Methods: A literature search of PubMed, Embase, the Cochrane library, and Web of Science (WoS) was performed to retrieve relevant randomized controlled trials (RCTs) that compared different doses of oral CBD with placebo or each other in refractory epilepsy indications. The search was limited from the inception of each database to January 3, 2023. Relative risk [RR] with a 95% confidence interval [CI] was used to express results. STATA/SE 14 was employed for network meta-analysis. Results: Six RCTs involving 972 patients were included in the final data analysis. Network meta-analysis showed that, CBD10 (10 mg/kg/day) (RR: 1.77, 95%CI: 1.28 to 2.44), CBD20 (20 mg/kg/day) (RR: 1.91, 95%CI: 1.49 to 2.46), CBD25 (25 mg/kg/day) (RR: 1.61, 95%CI: 0.96 to 2.70), and CBD50 (50 mg/kg/day) (RR: 1.78, 95%CI: 1.07 to 2.94) were associated with higher antiseizure efficacy although the pooled result for CBD25 was only close to significant. In addition, in terms of the risk of treatment-emergent adverse events (TEAEs), the difference between different doses is not significant. However, CBD20 ranked first in terms of antiseizure efficacy, followed by CBD50, CBD10, and CBD25. For TEAEs, CBD25 ranked first, followed by CBD10, CBD50, CBD5, and CBD20. Conclusion: For refractory indications, CBD20 may be optimal option for antiseizure efficacy; however, CBD25 may be best for TEAEs. Therefore, an appropriate dose of oral CBD should be selected based on the actual situation. Due to the limitations of eligible studies and the limited sample size, more studies are needed in the future to validate our findings.

Drug-Resistant Epilepsy: Experience From a Tertiary Care Center in Saudi Arabia.

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.

Bromide: the good, the bad, and the ugly of the oldest antiseizure medication.

Bromide is the first effective antiseizure medication used in human medicine since the XIX century. Initially met with skepticism, bromide quickly gained enthusiasm within the medical field until being largely replaced by newer antiseizure medications with significantly fewer adverse effects in people. In veterinary medicine, bromide continues to be used in the management of epileptic patients for over 30 years, yet adverse effects can impact owners and patients alike. We sought to provide the general practitioner and veterinary neurologist with insightful information on both the positive and negative attributes of bromide, explore factors that may influence its desirability as an antiseizure medication in specific veterinary cases and elucidate its current role in modern epilepsy treatment for veterinary patients. It's also our endeavor to discuss the current use as an alternative or add-on with other known antiseizure medications and potential future studies that might enhance our understanding and use of this medication.

Genotype-phenotype correlations in Polish patients with SCN8A-related epilepsy: A multicentre observational study.

BACKGROUND: Voltage-gated sodium channels are involved in the initial depolarisation of neurones. As such, they play important roles in neurotransmission. Variants in the genes encoding these channels may lead to altered functionality and neurodevelopmental disorders. Pathogenic variants of SCN8A, which encodes the voltage-gated Na+ channel Nav1.6, have been associated with various encephalopathies characterised by developmental delay and epileptic seizures. Herein, we discuss the genotype-phenotype associations in a group of 17 novel Polish patients with SCN8A mutations, further expanding the molecular and phenotypic spectrum of SCN8A-related diseases. METHODS: The participants were recruited from five clinical centres in Poland. Pathogenic and likely pathogenic SCN8A variants were identified using a next-generation sequencing (NGS) panel and exome sequencing, respectively. Magnetic resonance imaging (MRI) and electroencephalography (EEG) recordings were performed to obtain relevant clinical data on brain malformations and epileptic seizures. RESULTS: Three phenotypes were observed in the study group: developmental and epileptic encephalopathy, early onset epileptic encephalopathy, and neurodevelopmental disorders without epilepsy. Patients in the first two phenotypic subgroups presented with epileptic seizures within the first few months of life. Their semiology evolved with age, comprising mostly tonic, clonic, and tonic-clonic seizures, with eyelid myoclonia, myoclonic seizures, and epileptic spasms. The most prevalent neurological feature was developmental delay. Alterations in muscle tone were more frequent than in previous reports. CONCLUSIONS: Seventeen patients with 11 novel mutations in SCN8A had alterations in muscular tone accompanied by typical features of SCN8A-related encephalopathies (i.e., developmental delay and a wide range of seizures).

Preliminary study on the mechanism of SAHA in the treatment of refractory epilepsy induced by GABRG2(F343L) mutation.

Mutations in the γ-amino butyric acid type A (GABAA) receptor γ2 subunit gene, GABRG2, have been associated with refractory epilepsy. Increasing evidence indicates that suberoylanilide hydroxamic acid (SAHA), a broad-spectrum histone acetyltransferases (HDACs) inhibitor, can inhibit seizure onset. However, the mechanisms involved remains unknown. The present study aimed to explore the anti-epileptic effect and underlying mechanisms of SAHA in the treatment of refractory epilepsy induced by GABRG2 mutation. In the zebrafish line expressing human mutant GABRG2(F343L), Tg(hGABRG2F343L), SAHA was found to reduce seizure onset, swimming activity, and neuronal activity. In both Tg(hGABRG2F343L) zebrafish and HEK293T cells transfected with GABAA receptor subunits, SAHA could improve the pan-acetylation level and reduce the expression of HDAC1/10. The decreased expressions of GABAA receptor subunits could be rescued by SAHA treatment both in vivo and in vitro, which might be the result of increased gene transcription and protein trafficking. The up-regulated acetylation of histone H3 and H4 as well as Bip expression might be involved in the process. Taken together, our data proved that both histone and non-histone acetylation might contribute to the anti-epileptic effect of SAHA in refractory epilepsy caused by GABRG2(F343L) mutation, demonstrating SAHA as a promising therapeutic agent for refractory epilepsy.

Beyond the Norm: A Report of a Rare Case of Sodium Channel 8 Alpha (SCN8A) Gene-Related Epilepsy Unveiled in a Nine-Year-Old Child.

Sodium channel 8 alpha (SCN8A) mutations encompass a spectrum of epilepsy phenotypes with diverse clinical manifestations, posing diagnostic challenges. We present a case of a nine-year-old male with SCN8A gene-associated developmental and epileptic encephalopathies (DEEs), characterized by generalized tonic-clonic seizures (GTCS) since infancy. Despite treatment with multiple antiepileptic drugs (AEDs), including phenytoin, valproate, levetiracetam, carbamazepine, and clobazam, seizure control remained elusive, prompting genetic testing. Whole exome sequencing confirmed a heterozygous mutation (p.Phe210Ser) in SCN8A exon 6, indicative of DEE-13. Functional studies revealed a gain-of-function mechanism in SCN8A variants, resulting in heightened ion channel activity and altered voltage dependence of activation. Despite treatment adjustments, the patient's seizures persisted until topiramate was introduced, offering partial relief. SCN8A, encoding Nav1.6 sodium channels, modulates neuronal excitability, with mutations leading to increased persistent currents and hyperexcitability. Early seizure onset and developmental delays are hallmarks of SCN8A-related DEE. This case highlights the significance of genetic testing in refractory epilepsy management, guiding personalized treatment strategies. Sodium channel blockers like phenytoin and carbamazepine are often first-line therapies, while topiramate presents as a potential adjunctive option in SCN8A-related DEE. Overall, this case underscores the diagnostic and therapeutic complexities of managing SCN8A-related epileptic encephalopathy, emphasizing the importance of long-term monitoring and personalized treatment approaches for optimizing outcomes in refractory epilepsy.

Cortico-cortical evoked potential and language mapping: A meta-analysis.

PURPOSE: The purpose of this meta-analysis was to determine the best available evidence for the use of cortico-cortical evoked potential (CCEP) for language mapping. METHODS: PubMed/Medline/Google Scholar/Cochrane and Scopus electronic databases were searched for articles using CCEP for language mapping. CCEP data was obtained including the area of the cortex generating CCEP, resection data, and post-resection language outcomes. Inclusion criteria were clinical articles reporting the use of CCEP in language regions of the brain, reporting language outcomes and whether there was final resection of the cortex, studies with more than five patients, and studies in either English or Spanish. Review articles, systematic reviews, meta-analyses, or case series with less than five patients were excluded. RESULTS: Seven studies with a total of 59 patients were included in this meta-analysis. The presence of CCEPs from stimulation of Broca's area or posterior perisylvian region in the resection predicts language deficits after surgery. The diagnostic odds ratio shows values greater than 0 perioperatively (0.69-5.82) and after six months (1.38-11), supporting a high likelihood of a language deficit if the presence of CCEPs from stimulation of Broca's area or posterior perisylvian region are included in the resection and vice versa. The True Positive rate varied between 0.38 and 0.87. This effect decreases after six months to 0.61 (0.30-0.86). However, the True Negative rate increased from 0.53 (0.32-0.79) to 0.71 (0.55-0.88). CONCLUSION: This meta-analysis supports the utility of CCEP to predict the probability of having long-term language deficits after surgery. .

Optimizing automated detection of high frequency oscillations using visual markings does not improve SOZ localization.

OBJECTIVE: High frequency oscillations (HFOs) are a biomarker of the seizure onset zone (SOZ) and can be visually or automatically detected. In theory, one can optimize an automated algorithm's parameters to maximize SOZ localization accuracy; however, there is no consensus on whether or how this should be done. Therefore, we optimized an automated detector using visually identified HFOs and evaluated the impact on SOZ localization accuracy. METHODS: We detected HFOs in intracranial EEG from 20 patients with refractory epilepsy from two centers using (1) unoptimized automated detection, (2) visual identification, and (3) automated detection optimized to match visually detected HFOs. RESULTS: SOZ localization accuracy based on HFO rate was not significantly different between the three methods. Across patients, visually optimized detector settings varied, and no single set of settings produced universally accurate SOZ localization. Exploratory analysis suggests that, for many patients, detection settings exist that would improve SOZ localization. CONCLUSIONS: SOZ localization accuracy was similar for all three methods, was not improved by visually optimizing detector settings, and may benefit from patient-specific parameter optimization. SIGNIFICANCE: Visual HFO marking is laborious, and optimizing automated detection using visual markings does not improve localization accuracy. New patient-specific detector optimization methods are needed.

Efficacy and tolerability of classical and polyunsaturated fatty acids ketogenic diet in controlling paediatric refractory epilepsy - A randomized study.

OBJECTIVES: To measure and compare the efficacy and tolerability of a classical ketogenic diet (CKD) and a polyunsaturated fatty acids ketogenic diet (PUFAKD) in managing childhood refractory epilepsy. Efficacy was assessed by measuring the change in seizure frequency at 3, 6, 9, and 12 months within and between groups. The percentage reduction in seizures at <50 %, 50-90 %, >90 %, and 100 % was also measured. Tolerability was assessed and compared by recording adverse events - vomiting, nausea, lethargy, and constipation. METHODS: 52 children, aged 2-10 years, were randomized, 25 in the CKD group and 27 in the PUFAKD group. Fat: carbohydrate + protein ratio of 2.2:1-4:1 was maintained in both diets; the PUFAKD group only used unsaturated fats with an omega 3: omega 6 ratio of 1:2.8. Ketone levels were measured using keto-dipsticks, with 4+ and 4++ (80-160 mg/dL) being the most optimal values. RESULTS: A significant decrease (p=0.001) in seizures was observed (n=52), with no significant difference (p=0.537) between the two groups. The mean seizure reduction was 71.1 %, with no significant difference (p=0.488) in both groups. The mean compliance rate was 78.3 % (n=52). A statistically significant linear trend existed between a higher compliance rate and a greater reduction in seizures (p = 0.042, Z=4.039) among all children (n=52). Nausea (p=0.033) and vomiting (p=0.014) occurred more in PUFAKD than in CKD. CONCLUSION: No significant difference was seen in seizure reduction between the two groups. Compliance correlates with a greater seizure reduction. Despite similar seizure reduction rates, the novel PUFAKD exhibited poorer compliance and more pronounced adverse effects compared to CKD. CKD remained a superior choice over the novel PUFAKD in the management of paediatric refractory epilepsy. More controlled trials with varying PUFA compositions are recommended for long-term evaluations.

Continuous epileptiform discharges are associated with worse neurodevelopmental findings in a congenital Zika syndrome prospective cohort.

PURPOSE: This study aimed to identify continuous epileptiform discharges (CEDs) on electroencephalograms (EEG) and to determine their clinical significance in children with congenital Zika syndrome (CZS). METHODS: This prospective cohort study included 75 children diagnosed with CZS born from March 2015 and followed up until September 2018 (age up to 36 months). EEG was performed to detect CEDs up to 24 months old. Data on obstetric, demographic, and clinical signs; cranial computed tomography (CT); ophthalmology examination; anti-seizure medication; growth; and motor development were collected. Fisher's exact test was used to verify the associations between categorical variables, and the T- test was used to compare the mean z-scores of anthropometric measurements between the groups with and without CED. RESULTS: CEDs were identified in 41 (54.67 %) children. The mean age of CEDs identification was 12.24 ± 6.86 months. Bilateral CEDs were shown in 62.89 % of EEGs. CEDs were associated with severe congenital microcephaly, defined by z-score >3 standard deviation of head circumference (HC) below the mean for sex and age (p = 0.025), and worse outcomes, including first seizure before 6 months (p = 0.004), drug-resistant epilepsy (p < 0.001), chorioretinal scarring or mottling (p = 0.002), and severe CT findings (p = 0.002). The CED group had lower mean z-scores of HC up to 24 months of age. CONCLUSION: This is the first description of the prevalence and significance of CEDs that also remains during wakefulness in patients with CZS. New investigations may suggest that it is more appropriate to classify the EEG not as a CED, but as a periodic pattern. Anyway, CEDs may be a marker of neurological severity in children with CSZ.

Use of cannabidiol in the treatment of drug-refractory epilepsy in children and young adults: A systematic review.

Objectives: Epilepsy poses a significant challenge in pediatric and adolescent populations, impacting not only seizures but also psychological and cognitive comorbidities, leading to higher mortality rates than the general population. Drug-refractory epilepsy, resistant to conventional treatments, affects a range of 7-20% of pediatric patients. The search for alternative therapies has led to exploring the therapeutic potential of Cannabis sativa L. compounds, particularly cannabidiol (CBD). Examine the use of CBD for treating drug-refractory epilepsy in children and young adults, summarizing existing evidence on its efficacy. Materials and Methods: A systematic review, following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, assessed studies from 2018 to 2023, focusing on CBD's efficacy and safety for treatment-resistant epilepsy in pediatric and juvenile populations. The search spanned seven databases, and the studies underwent rigorous screening and data extraction. Results: Out of 6351 identified articles, eight were selected for review. The included studies reported positive outcomes, with CBD leading to a reduction in seizure frequency ranging from 50% to complete seizure freedom. Adverse effects were mostly mild and reversible, including drowsiness, diarrhea, and loss of appetite. Conclusion: The CBD emerges as a promising tool for refractory epilepsy in pediatric patients, showing efficacy in reducing seizure frequency and improving overall quality of life. Despite mild and reversible adverse effects, CBD's benefits outweigh the risks. However, more research on long-term effects is needed to fully understand its implications.

Perampanel as monotherapy or first adjunctive therapy in pediatric and adult patients with epilepsy: the first United States-based phase IV open-label ELEVATE study.

ELEVATE (Study 410; NCT03288129) is the first prospective, multicenter, open-label, Phase IV study of perampanel as monotherapy or first adjunctive therapy in patients aged ≥ 4 years with focal-onset seizures or generalized tonic-clonic seizures in the United States. The study included Screening, Titration (≤ 13 weeks), Maintenance (39 weeks), and Follow-up (4 weeks) Periods. During Titration, perampanel was initiated at 2 mg/day and up-titrated to 4 mg/day at Week 3. Depending on response and tolerability, optional up-titrations to a maximum of 12 mg/day occurred. The primary endpoint was retention rate; additional endpoints included seizure-freedom rate, 50% responder rate, and incidence of treatment-emergent adverse events (TEAEs). At baseline, 10 (18.5%) patients were assigned to the monotherapy group and 44 (81.5%) patients to the first adjunctive therapy group. However, due to the addition of an anti-seizure medication along with perampanel on the first day of treatment, one patient was excluded from the monotherapy subgroup analyses. The mean perampanel exposure duration was 39.8 weeks and 32 (59.3%) patients completed the study. Retention rate at 12 months (or study completion) was 63.0% (monotherapy, 77.8%; first adjunctive therapy, 59.1%). Seizure-freedom rate during the Maintenance Period was 32.7% (monotherapy, 44.4%; first adjunctive therapy, 29.5%) and the 50% responder rate was 78.7% (monotherapy, 85.7%; first adjunctive therapy, 76.9%). TEAEs and serious TEAEs were reported by 88.9% (n = 48/54) and 7.4% (n = 4/54) of patients, respectively. Overall, the efficacy and safety of perampanel as monotherapy or first adjunctive therapy support the use of perampanel as early-line treatment for epilepsy.

Multimodal Approach for the Treatment of Complex Hypothalamic Hamartomas.

Hypothalamic hamartomas (HHs) are rare congenital lesions formed by heterotopic neuronal and glial cells attached to the mammillary bodies, tuber cinereum, and hypothalamus.They often present with an intractable epilepsy typically characterized by gelastic seizures but commonly associated with other types of refractory seizures. The clinical course is progressive in most of the cases, starting with gelastic seizures in infancy and deteriorating into complex seizure disorders that result in catastrophic epilepsy associated with cognitive decline and behavioral disturbances.Hamartomas are known to be intrinsically epileptogenic and the site of origin for the gelastic seizures. As antiepileptic drugs are typically ineffective in controlling HH-related epilepsy, different surgical options have been proposed as a treatment to achieve seizure control. Resection or complete disconnection of the hamartoma from the mammillothalamic tract has proved to achieve a long-lasting control of the epileptic syndrome.Usually, symptoms and their severity are typically related to the size, localization, and type of attachment. Precocious puberty appears mostly in the pedunculated type, while epileptic syndrome and behavioral decline are frequently related to the sessile type. For this reason, different classifications of HHs have been developed based on their size, extension, and type of attachment to the hypothalamus.The bigger and more complex hypothalamic hamartomas typically present with severe refractory epilepsy, behavioral disturbances, and progressive cognitive decline posing a formidable challenge for the control of these symptoms.We present here our experience with the multimodal treatment for complex hypothalamic hamartomas. After an in-depth review of the literature, we systematize our approach for the different types of hypothalamic hamartomas.

Design and validation of a diagnostic suspicion checklist to differentiate epileptic from psychogenic nonepileptic seizures (PNES-DSC).

OBJECTIVE: Psychogenic non-epileptic seizures (PNES) are complex clinical manifestations and misdiagnosis as status epilepticus remains high, entailing deleterious consequences for patients. Video-electroencephalography (vEEG) remains the gold-standard method for diagnosing PNES. However, time and economic constraints limit access to vEEG, and clinicians lack fast and reliable screening tools to assist in the differential diagnosis with epileptic seizures (ES). This study aimed to design and validate the PNES-DSC, a clinically based PNES diagnostic suspicion checklist with adequate sensitivity (Se) and specificity (Sp) to discriminate PNES from ES. METHODS: A cross-sectional study with 125 patients (n = 104 drug-resistant epilepsy; n = 21 PNES) admitted for a vEEG protocolised study of seizures. A preliminary PNES-DSC (16-item) was designed and used by expert raters blinded to the definitive diagnosis to evaluate the seizure video recordings for each patient. Cohen's kappa coefficient, leave-one-out cross-validation (LOOCV) and balance accuracy (BAC) comprised the main validation analysis. RESULTS: The final PNES-DSC is a 6-item checklist that requires only two to be present to confirm the suspicion of PNES. The LOOCV showed 71.4% BAC (Se = 45.2%; Sp = 97.6%) when the expert rater watched one seizure video recording and 83.4% BAC (Se = 69.6%; Sp = 97.2%) when the expert rater watched two seizure video recordings. CONCLUSION: The PNES-DSC is a straightforward checklist with adequate psychometric properties. With an integrative approach and appropriate patient history, the PNES-DSC can assist clinicians in expediting the final diagnosis of PNES when vEEG is limited. The PNES-DSC can also be used in the absence of patients, allowing clinicians to assess seizure recordings from smartphones.

The impact of social determinants of health on utilization of pediatric epilepsy surgery: a systematic review.

OBJECTIVE: A minority of pediatric patients who may benefit from epilepsy surgery receive it. The reasons for this utilization gap are complex and not completely understood. Patient and caregiver social determinants of health (SDOH) may impact which patients undergo surgery and when. The authors conducted a systematic review examining SDOH and surgical intervention in children with drug-resistant epilepsy (DRE). They aimed to understand which factors influenced time to surgical program referral or receipt of epilepsy surgery among children with DRE, as well as identify areas to characterize the SDOH impacting epilepsy surgery in children and guide efforts aimed to promote health equity in epilepsy. METHODS: A systematic review was conducted using the PubMed, Embase, and Scopus databases in January 2022. Studies were analyzed by title and abstract, then full text, to identify all studies examining the impact of SDOH on utilization of epilepsy surgery. Studies meeting inclusion criteria were analyzed for SDOH examined, outcomes, and key findings. Quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: Of 4545 resultant articles, 18 were included. Studies examined social, cultural, and environmental factors that contributed to SDOH impacting epilepsy surgery. Patients who underwent surgical evaluation were found to be most commonly White and privately insured and have college-educated caregivers. Five studies found differences in time to referral/surgery or rates of surgery by racial group, with most finding an increased time to referral/surgery or lower rates of surgery for those who were Hispanic and/or non-White. Four studies found that private insurance was associated with higher surgical utilization. Three studies found higher household income was related to surgical utilization. No studies examined biological, psychological, or behavioral factors that contributed to SDOH impacting epilepsy surgery. CONCLUSIONS: The authors conducted a systematic review exploring the impact of SDOH in DRE surgery utilization. They found that race, ethnicity, insurance type, caregiver educational attainment, and household income demonstrate relationships with pediatric epilepsy surgery. Further study is necessary to understand how these factors, and others not identified in this study, contribute to the low rates of utilization of epilepsy surgery and potential target areas for interventions aiming to increase equity in access to epilepsy surgery in children.