Seizure Freedom Research Articles

Clinical efficacy and safety of perampanel monotherapy as primary anti-seizure medication in the treatment of pediatric epilepsy: A single-center, prospective, observational study.

To assess the efficacy and safety of perampanel (PER) as primary monotherapy in patients aged 4-18 years old with epilepsy. A single-center, prospective, observational study was conducted from October 2021 to October 2023, to evaluate PER monotherapy's efficacy and safety as initial therapy for pediatric epilepsy. Changes in seizure frequency, safety, and retention rate were observed at 3, 6, 9, and 12 months after initiating PER primary monotherapy. A total of 124 children aged 4-15 years (mean age = 8.25 ± 2.50 years) were included in the Analysis Sets. The retention rates at 3, 6, 9, and 12 months were 88.71% (110/124), 84.68% (105/124), 78.26% (90/115), and 71.58% (68/95), respectively. Seizure freedom rates at 3, 6, 9, and 12 months were 85.45%, 79.09%, 76.24%, and 75.31%, respectively. The responder rates (≥50% but <100%) at the same endpoints were 9.09%, 14.55%, 12.87%, and 7.41%, respectively. Seizure freedom rate of PER was independent of age at PER initiation, seizure onset age, gender, baseline frequency, seizure types, and family history of epilepsy (p > 0.05) but associated with duration of treatment (p = 0.001) and maintenance dose (p = 0.022). Additionally, 124 patients were included in the safety analysis set. The overall adverse event rate was 38.71% (48/124), with irritability (19 cases, 15.32%) and dizziness (18 cases, 14.52%) being the most common adverse effects. One patient discontinued PER monotherapy within 1 month due to unbearable itching of the skin. PER monotherapy as the primary anti-seizure medication (ASM) for pediatric epilepsy demonstrates high efficacy and safety in real-world clinical treatment. Patients who respond well to this drug and adhere to long-term treatment can achieve favorable seizure control. Furthermore, patients achieving seizure freedom with a relatively lower dose can opt for the same dose as the maintenance dose. This study provided the efficacy and safety of PER monotherapy as the primary ASM for Chinese pediatric epilepsy. In total, 124 patients took part. The seizure freedom rates were over 70% at different observation points (OPs), along with a retention rate of 71.58% at the 12-month OP. Most of adverse effects observed were mild to moderate.

Machine learning algorithm for predicting seizure control after temporal lobe resection using peri-ictal electroencephalography

Brain resection is curative for a subset of patients with drug resistant epilepsy but up to half will fail to achieve sustained seizure freedom in the long term. There is a critical need for accurate prediction tools to identify patients likely to have recurrent postoperative seizures. Results from preclinical models and intracranial EEG in humans suggest that the window of time immediately before and after a seizure (“peri-ictal”) represents a unique brain state with implications for clinical outcome prediction. Using a dataset of 294 patients who underwent temporal lobe resection for seizures, we show that machine learning classifiers can make accurate predictions of postoperative seizure outcome using 5 min of peri-ictal scalp EEG data that is part of universal presurgical evaluation (AUC 0.98, out-of-group testing accuracy > 90%). This is the first approach to seizure outcome prediction that employs a routine non-invasive preoperative study (scalp EEG) with accuracy range likely to translate into a clinical tool. Decision curve analysis (DCA) shows that compared to the prevalent clinical-variable based nomogram, use of the EEG-augmented approach could decrease the rate of unsuccessful brain resections by 20%.

Selective Amygdalohippocampectomy versus Anterior Temporal Lobectomy in Mesial Temporal Lobe Epilepsy: A Meta-Analysis of Seizure Control and Cognitive Outcomes

Background: Mesial temporal lobe epilepsy (MTLE) is a common form of drug-resistant epilepsy often necessitating surgical intervention. The choice between selective amygdalohippocampectomy (SelAH) and anterior temporal lobectomy (ATL) remains a subject of debate, with each procedure offering potential advantages and disadvantages in terms of seizure control and cognitive outcomes. Methods: A comprehensive literature search was conducted across PubMed, Scopus, and Springer databases to identify studies published between 2013 and September 2024 that compared SELAH and ATL in patients with MTLE. The primary outcomes of interest were seizure freedom rates and changes in cognitive function, particularly IQ scores. A meta-analysis was performed using a random-effects model to pool the results of included studies. Results: The meta-analysis encompassed 5 studies involving 218 patients with MTLE (105 underwent SelAH, 113 underwent ATL). The pooled results demonstrated a statistically significant reduction in the odds of achieving seizure freedom following ATL compared to SelAH (odds ratio [OR] 0.38, 95% confidence interval [CI] 0.24-0.81, p = 0.008). Regarding cognitive outcomes, no significant difference was observed in Performance IQ (PIQ) between the two groups. However, a trend towards improved Verbal IQ (VIQ) was noted in the SelAH group, although this did not reach statistical significance. Conclusion: The findings suggest that SelAH may offer superior seizure control compared to ATL in patients with MTLE. While both procedures appear to have comparable effects on PIQ, SelAH may be associated with a trend towards better preservation or even improvement in VIQ. The choice between SelAH and ATL should be individualized based on patient-specific factors, including preoperative cognitive profile and the relative importance of seizure control versus cognitive preservation.

A novel AAV9-dual microRNA-vector targeting GRIK2 in the hippocampus as a treatment for mesial temporal lobe epilepsy

Mesial temporal lobe epilepsy (mTLE) is the most prevalent type of epilepsy in adults. First and subsequent generations of anti-epileptic therapy regimens fail to decrease seizures in a large number of patients suffering from mTLE, leaving surgical ablation of part of the hippocampus as the only therapeutic option to potentially reach seizure freedom. GluK2 has recently been identified as a promising target for the treatment of mTLE using gene therapy. Here, we engineered an adeno-associated virus serotype 9 vector expressing a cluster of two synthetic microRNAs (miRNAs), expressed from the human synapsin promoter, that target GRIK2 mRNA. Intra-hippocampal delivery of this vector in a mouse model of mTLE significantly reduced GRIK2 expression and daily seizure frequency. This treatment also improved the animals' health, reduced their anxiety, and restored working memory. Focal administration of the vector to the hippocampus of cynomolgus monkeys in GLP toxicology studies led to the selective transduction of hippocampal neurons with little exposure elsewhere in the brain and no transduction outside the central nervous system. Expression of miRNAs in hippocampal neurons resulted in substantially decreased GRIK2 mRNA expression. These data suggest that the intra-hippocampal delivery of a GMP-grade AAV9 coding for a synthetic miRNAs targeting GRIK2 is a promising treatment strategy for mTLE.

Pediatric peri-insular hemispherotomy and functional hemispherectomy for severe medically refractory epilepsy: comparison of two techniques

PurposeSince it was first described in the 1970s, functional hemispherotomy has been an essential tool in treating disabling, medically refractory epilepsy resulting from diffuse unilateral hemispheric disease. We report our experience with 23 patients who underwent hemispherotomy, both using the functional hemispherotomy (FH) as well as a modified peri-insular hemispherotomy (PIH) technique. We present the surgical technique for the latter, review outcomes following disconnection surgery and discuss the differences between the techniques when it comes to complications and postoperative results. MethodsA retrospective study of 23 patients with refractory seizures who underwent cerebral hemispherectomy. A thorough analysis of the clinical, imaging, surgical features and postoperative results was performed. We also present the surgical technique for a modified PIH technique. ResultsBetween 2000 and 2020, 23 pediatric patients with refractory seizures underwent hemispherotomy (12 FHs, 11 modified PIHs). 91.3% of patients were seizure free at 6 months, 87% at 1 year, and 78.3% at last follow-up. None of the 23 patients presented Engel IV outcome. FH was found to have statistically longer surgical duration (5 ± 1.5 vs. 3.83 ± 0.5 h; p = <0.001). Neurocognition was improved in two thirds of the patients (66.9%). Our study also shows improvement of motor activity in the majority of the patients, regardless of the pathology and surgical technique. In the present report we modified the Cook et al. technique by implementing an amygdalohippocampectomy with resection of the tail of the hippocampus posteriorly and medially, to achieve temporo-occipital disconnection, instead of a complete temporal lobectomy. ConclusionWhen patients are wisely selected, the hemispherectomy procedure should be considered as a most attractive and curative treatment for children with refractory seizures, not only giving the patient a high chance of seizure freedom but also providing an improvement in motor and cognitive skills. In our particular case and based on the present study, the modified PIH proves to be a highly effective technique. It not only has a shorter surgical time but also a very low complication rate.

One-year seizure freedom and quality of life in patients with drug-resistant epilepsy receiving adjunctive vagus nerve stimulation in Japan.

Amount of seizure-free days is a critical determinant of quality of life (QoL) in patients with drug-resistant epilepsy (DRE). The fractions of patients experiencing prolonged periods of seizure freedom with adjunctive vagus nerve stimulation (VNS) have yet to be assessed on a large scale. Retrospective analysis of patients in the Japanese VNS prospective observational registry who experienced at least 1 year of seizure freedom from all seizures, focal seizures, or tonic-clonic seizures (TCS), as well as patient-reported change in QoL in these groups. The study included 362 patients with DRE, 147 were female (40.6%), and the median age at VNS implant was 23.0 years (range: 1.0-73.0). A total of 225 patients reported focal seizures and 184 patients reported TCS. After 36 months of adjunctive VNS, the cumulative proportion of patients experiencing at least 1 year of complete seizure freedom was 11% (38/356) with an average duration of seizure freedom of 19.4 months. In patients with focal seizures, 25% (n = 57/225) experienced at least 1 year of freedom from focal seizures with an average duration of 24.8 months. Higher cumulative rates of freedom from TCS were observed: 55% (n = 101/184) experienced at least 1 year without TCS with an average duration of TCS-free periods of 28.9 months. 82.1% of patients with 12-month complete seizure freedom reported markedly improved or improved QoL compared with 51.9% of patients who were not seizure-free. QoL changes in patients with 12-month seizure freedom from TCS and focal seizures were similar: 61.8% and 63% of respective patients reported either markedly improved or improved QoL at 36 months. Complete seizure freedom is rare in patients treated with VNS; however, this analysis found approximately half of patients who experienced TCS prior to VNS experienced prolonged periods of freedom from TCS with adjunctive VNS. We studied patients in Japan with epilepsy that is difficult to treat. To understand if adding vagus nerve stimulation (VNS) helps such patients, we looked at which patients stopped having all seizures or stopped having a specific seizure type (such as tonic-clonic seizures or focal seizures), and how long these periods lasted. With VNS treatment, about 2 out of 4 patients with tonic-clonic seizures and 1 out of 4 patients with focal seizures had more time without these seizure types. Without seizures, patients felt better about their daily lives. Even patients who still had seizures felt better about their daily lives after 3 years of VNS treatment. The clinical trial registry number is UMIN000014728.

Epilepsy in Patients With Primary CNS Lymphoma: Prevalence, Risk Factors, and Prognostic Significance.

Epilepsy is a common comorbidity of brain tumors; however, little is known about the prevalence, onset time, semiology, and risk factors of seizures in primary CNS lymphoma (PCNSL). Our objectives were to determine the prevalence of epilepsy in PCNSL, to identify factors associated with epilepsy, and to investigate the prognostic significance of seizures in PCNSL. We performed an observational, retrospective single-center study at a tertiary neuro-oncology center (2011-2023) including immunocompetent patients with PCNSL and no history of seizures. We collected clinical, imaging, and treatment data; seizure status over the course of PCNSL; and oncological and seizure outcome. The primary outcome was to determine the prevalence of epilepsy. Furthermore, we aimed to identify clinical, radiologic, and treatment-related factors associated with epilepsy. Univariate analyses were conducted using the χ2 test for categorical variables and unpaired t test for continuous variables. Predictors identified in the unadjusted analysis were included in backward stepwise logistic regression models. We included 330 patients, 157 (47.6%) were male, median age at diagnosis was 68 years, and the median Karnofsky Performance Status score was 60. Eighty-three (25.2%) patients had at least 1 seizure from initial diagnosis to the last follow-up, 40 (12.1%) as the onset symptom, 16 (4.8%) during first line of treatment, 27 (8.2%) at tumor progression and 6 (1.8%) while in remission. Focal aware seizures were the most frequent seizure type, occurring in 43 (51.8%) patients. Seizure freedom under antiseizure medication was observed in 97.6% patients. Cortical contact (odds ratio [OR] 8.6, 95% CI 4.2-15.5, p < 0.001) and a higher proliferation index (OR 5.7, 95% CI 1.3-26.2, p = 0.02) were identified as independent risk factors of epilepsy. Patients with PCNSL and epilepsy had a significantly shorter progression-free survival (median progression-free survival 9.6 vs 14.1 months, adjusted hazard ratio 1.4, 95% CI 1.0-1.9, p = 0.03), but not a significantly shorter overall survival (17 vs 44.1 months, log-rank test, p = 0.09). Epilepsy affects a quarter of patients with PCNSL, with half experiencing it at the time of initial presentation and potentially serving as a marker of disease progression. Further research is necessary to assess the broader applicability of these findings because they are subject to the constraints of a retrospective design and tertiary center setting.

Pediatric Epilepsy Genetic Testing Results and Long-term Seizure Freedom.

Objective: To determine whether there is a correlation of genetic diagnosis/result with long-term seizure freedom in pediatric epilepsy patients. Methods: This was a prospective and retrospective cohort study of children with epilepsy referred for genetic testing at a single center. The primary outcomes were presence and type of genetic diagnosis (pathogenic, benign, or variant of uncertain significance) and patient epilepsy status (seizure free, treatment failure, uncertain). Epilepsy gene panels were the primary method of genetic testing. Results: The prospective cohort had 22 patients followed for >11 years and for whom genetic testing was then performed; the retrospective cohort had 78 patients with previous genetic testing followed for >8 years. In the prospective cohort, one patient each of the seizure free or treatment failure groups had a pathogenic genetic variant; mean Combined Annotation Dependent Depletion (CADD) scores 22 and 24, respectively (P = .62). In the retrospective cohort, there was no difference in the number of variants (P = .97), the variant interpretations (P = .29 ClinVar, P = .39 lab interpretation) or mean CADD scores (P = .29) between the seizure-free, treatment failure, and uncertain epilepsy patients. Whole exome and genome sequencing identified pathogenic variants in 70% of patients with treatment failure but were not performed in seizure-free patients. Significance: Our findings show no correlation of the presence or type of epilepsy gene panel result with long-term seizure freedom in pediatric patients. The yield and specificity of pathogenic variants may be higher using whole exome and whole genome sequencing in patients with treatment-resistant epilepsy. Whole exome and whole genome sequencing, or more targeted understanding of specific variants, may be needed to improve the utility of pediatric epilepsy genetic testing.

Bilateral Todd's paralysis in a patient with left fronto-opercular epilepsy.

Postictal paresis ("Todd's paralysis") is commonly observed as a unilateral, transient motor weakness, lasting minutes to hours, after focal or focal to bilateral tonic-clonic seizures, contralateral to the epileptogenic zone. Bilateral postictal paresis is exceedingly rare and could be misinterpreted, especially if the preceding convulsive phase was not witnessed. An 18-year-old right-handed male patient with refractory focal epilepsy with seizure onset at age 3 years, was admitted for presurgical video-EEG monitoring. His seizures were predominantly nocturnal, consisting of a laryngeal somatosensory aura, occasionally evolving to bilateral tonic or tonic-clonic seizures with occasional asymmetrical limb extension during the tonic phase (right arm extension). Postictally, consciousness recovery was fast, if ever lost. At that stage, we documented severe dysarthria and bilateral symmetrical arm paresis lasting several minutes. The ictal pattern and interictal epileptiform activity were projected on the fronto-central midline. Brain MRI was highly suggestive of a bottom-of-sulcus dysplasia with underlying transmantle sign on the left premotor, fronto-opercular region and an FDG-PET-CT showed a concordant left fronto-operculo-insular hypometabolism. A complete lesionectomy was performed, with the additional guidance of intraoperative electrocorticography, resulting in sustained seizure freedom. Anatomo-pathology confirmed a type 2b focal cortical dysplasia. We speculate that, in our patient, a left fronto-opercular ictal onset with an early spread to both primary motor cortices and relative sparing of consciousness networks allowed the emergence of a clinically detectable postictal bilateral paresis.

Mammalian Target of Rapamycin Inhibitor Levels Decrease Under Cenobamate Treatment

BackgroundEverolimus therapy has been approved in Tuberous Sclerosis Complex (TSC), for drug-resistant epilepsy as adjunctive therapy. A novel anti-seizure medication is cenobamate, which was approved for adults as adjunctive treatment for focal-onset seizures in drug-resistant epilepsy and is now commonly used in patients with TSC. Drug-drug interactions between cenobamate and mammalian target of rapamycin (mTORi) have not been prospectively evaluated, even though these agents are frequently administered together. MethodsWe performed a retrospective analysis of patients with TSC and compared mTORi drug levels before and after treatment initiation with cenobamate. ResultsWe evaluated 20 patients with clinically diagnosed TSC (male: 55%, female: 45%) with a median current age at last visit of 17.0 years (range: 4-41 years, interquartile range [IQR]: 12.5 years). All patients received mTORi treatment of either everolimus (N = 12, 60%) or sirolimus (N = 8, 40%). Cenobamate treatment led to seizure freedom in 2 patients (10%), reduction of seizures in 9 patients (45%) and no change in seizure frequency in 9 patients (45%). Median maximal cenobamate dose was 200 mg (range: 100-500 mg, IQR: 262.5 mg), for example, 3.2 mg/kg/day (range: 0.8-9.5 mg/kg/day, IQR: 3.2 mg/kg/day). Median everolimus levels decreased significantly after cenobamate initiation from 5.1 ng/ml (range: 1.9-11.6 ng/ml, IQR: 3.8 ng/ml) to 3.4 ng/ml (range: 1-7.9 ng/ml, IQR: 1.7 ng/ml, P = 0.01221). The median sirolimus level did not decrease significantly (P = 0.3828). ConclusionEverolimus levels decreased following cenobamate initiation. This is likely due to CYP3A4 induction of cenobamate. We recommend monitoring of serum plasma levels of mTORi co-administered with cenobamate and adjustment of mTORi doses accordingly.

Epilepsy surgery for tuberous sclerosis complex in children: literature review and clinical case

Tuberous sclerosis complex (TSC) is a multisystem, autosomal-dominant, neurocutaneous syndrome that is characterized by the presence of hamartomas involving multiple organs, including the brain. Epilepsy is the most common neurological manifestation and the main cause of disability in children. Drug-resistant epilepsy is seen in 62.5 % of cases. The challenge of surgical treatment in these patients is the multifocal nature of epilepsy. Nonetheless, there is available data to suggest that surgical intervention is most likely to achieve long-term seizure freedom.The aim of the work – to analyze current data and aspects of surgical treatment of epilepsy associated with tuberous sclerosis in children.A literature search for was done on PubMed, Google Scholar, and eLIBRARY. RU for the period from 2000 to 2022. Search phrases included: TSC-associated epilepsy in children, epilepsy surgery in children with TSC, epilepsy surgery for TSC. The tubers are not the only source of epileptic activity; the perituberal brain tissue is also a proven focus. Currently, there is a tendency towards early pre-surgical evaluation and surgical treatment, which is recommended after the failure of two antiepileptic drugs. Considering the multiple brain lesions and multifocal epilepsy, the use of invasive electroencephalography is invaluable in the preoperative assessment of these patients. The effectiveness of resection surgery is 65–75 %. Over time, the proportion of patients in complete remission from seizures decreases. Lobectomy and tuberectomy plus procedures are favorable prognostic factors. Surgical treatmentsignificantly increasesthe chances of seizure freedom. Eliminating seizures in children has been shown to improve cognitive development.There is no algorithm for pre-surgical patient evaluation or selection criteria for surgical treatment. Some methods of presurgical evaluation are not included in the compulsory health insurance system, making early diagnosis and treatment very difficult. This leads to an increase in the number of patients with disabilities and a poor quality of life.

Candesartan restores blood-brain barrier dysfunction, mitigates aberrant gene expression, and extends lifespan in a knockin mouse model of epileptogenesis.

Blockade of Angiotensin type 1 receptor (AT1R) has potential therapeutic utility in the treatment of numerous detrimental consequences of epileptogenesis, including oxidative stress, neuroinflammation, and blood-brain barrier (BBB) dysfunction. We have recently shown that many of these pathological processes play a critical role in seizure onset and propagation in the Scn8a-N1768D mouse model. Here we investigate the efficacy and potential mechanism(s) of action of candesartan (CND), an FDA-approved angiotensin receptor blocker (ARB) indicated for hypertension, in improving outcomes in this model of pediatric epilepsy. We compared length of lifespan, seizure frequency, and BBB permeability in juvenile (D/D) and adult (D/+) mice treated with CND at times after seizure onset. We performed RNAseq on hippocampal tissue to quantify differences in genome-wide patterns of transcript abundance and inferred beneficial and detrimental effects of canonical pathways identified by enrichment methods in untreated and treated mice. Our results demonstrate that treatment with CND gives rise to increased survival, longer periods of seizure freedom, and diminished BBB permeability. CND treatment also partially reversed or 'normalized' disease-induced genome-wide gene expression profiles associated with inhibition of NF-κB, TNFα, IL-6, and TGF-β signaling in juvenile and adult mice. Pathway analyses reveal that efficacy of CND is due to its known dual mechanism of action as both an AT1R antagonist and a PPARγ agonist. The robust effectiveness of CND across ages, sexes and mouse strains is a positive indication for its translation to humans and its suitability of use for clinical trials in children with SCN8A epilepsy.

Endoscopic endonasal resection of olfactory tract hamartoma for pediatric epilepsy.

Non-hypothalamic glioneural hamartomas are rare entities known to cause medically refractory epilepsy. Olfactory bulb hamartomas, in particular, are exceptionally rare. We describe a case of an olfactory bulb hamartoma that was surgically resected at our institution. We also performed a literature review of all glioneural hamartomas and discuss the clinical presentation, diagnosis, and management of these lesions. Herein, we present the unusual case of a typically developing 17-year-old boy with a near life-long history of drug-resistant epilepsy, found to have a 0.8 × 1.0cm right olfactory bulb hamartoma. Endoscopic endonasal trans-cribriform resection of the lesion led to seizure freedom in the 6-month follow-up period (Engel class 1 outcome). Comprehensive literature review revealed only one other sporadic case, which was also successfully treated with total surgical resection. Our case of an olfactory bulb hamartoma adds to the limited literature currently available, illustrating key clinical characteristics of these exceedingly rare lesions and outlining an effective, minimally invasive, and low-morbidity treatment strategy.

Cenobamate as an Early Adjunctive Treatment in Drug-Resistant Focal-Onset Seizures: An Observational Cohort Study.

Cenobamate (CNB) is a new antiseizure medication (ASM) to treat drug-resistant, focal-onset seizures. Data on its use in early therapy lines are not yet available, and clinicians frequently consider CNB to be a later ASM drug choice. We investigated the efficacy and safety of CNB as an early adjunctive treatment in drug-resistant, focal-onset seizures. The study population were patients with drug-resistant, focal-onset seizures who were initiated with CNB after they did not respond to two or three lifetime ASMs, including all prior and concomitant ASMs. These patients were matched (1:2) by sex, age, and seizure frequency to controls who were initiated with any ASM other than CNB. All participants participated in the Mainz Epilepsy Registry. We evaluated the retention rate after 12 months of CNB and after each new adjunctive ASM in the control group. In addition, seizure freedom and the response rate (reduction of seizure frequency by ≥ 50% from baseline) after 12 months were estimated. We included 231 patients aged 44.4 ± 15.8 years. Of these, 33.3% (n = 77) were on CNB, 19.0% (n = 44) on valproate (VPA), 17.3% (n = 40) on lacosamide (LCS), 16.4% (n = 38) on levetiracetam (LEV), and 13.9% (n = 32) on topiramate (TPM). The highest retention rate after 12 months since the beginning of the early adjunctive therapy was observed on CNB (92.0%), compared with LCS (80.0%), LEV (73.3%), VPA (68.2%), or TPM (62.5%) (p < 0.05). Seizure freedom and response rate were also the best on CNB (19.5% and 71.4%, respectively) compared with other ASMs (8.3% and 52.5%, respectively; p < 0.05). No significant differences in adverse events between CNB and other ASMs were observed. Our study provides evidence that CNB is an effective ASM with a good safety profile in the early therapy lines of drug-resistant, focal-onset seizures. This data should support medical decision making in the management of patients with refractory epilepsy. NCT05267405.

The effectiveness and safety of bevacizumab in improving the efficacy of antiseizure medication in treating refractory epilepsy induced by stereotactic radiosurgery in meningiomas

Background: Refractory epilepsy (RE) increases rapidly after stereotactic radiosurgery (SRS), but the reports on RE treatment are rare, with various methods and efficacy. In recent years, bevacizumab (BEV) has been widely used as it is effective in eliminating intracranial oedema and reducing radioactive damage. The aim of this study was to evaluate the application of additional BEV to RE after SRS in the real world. Methods: Seizure freedom and seizure response were defined as 100% and &gt; 50% reduction in seizure frequency at baseline and 6-, 9- and 12-month follow-ups. The sustained seizure-free (SSF), sustained seizure response (SSR) was used to assess the effectiveness of BEV. The number of anti-seizure medications (ASM), seizure severity (NH3), and epilepsy quality of life rating scale (QOLIE-31) scores were compared before and 12 months after treatment. Results: Forty-one patients were included from January 2020 to December 2022. During the 1-year follow-up, 5 patients (12.2%) achieved SSF lasting 12 months, and 4.9% and 7.3% enjoyed SSF more than 6 months and 9 months, respectively. Twelve patients (29.3%) achieved SSR lasting for 12 months, and 19.5% and 24.4% of the study cohort achieved SSR more than 6 months and 9 months, respectively. Patients’ ASM, NH3, and QOLIE-31 scores significantly improved 12 months after treatment, and the adverse reactions were controllable. Conclusion: This study is the first to explore and report the additional use of BEV in the treatment of RE after SRS in meningiomas. BEV was effective and safe in the treatment of SRS-induced RE.

Characterization of the Epileptogenic Phenotype and Response to Antiseizure Medications in Lissencephaly Patients.

Patients with lissencephaly typically present with severe psychomotor retardation and drug-resistant seizures. The aim of this study was to characterize the epileptic phenotype in a genotypically and radiologically well-defined patient cohort and to evaluate the response to antiseizure medication (ASM). Therefore, we retrospectively evaluated 47 patients of five genetic forms (LIS1/PAFAH1B1, DCX, DYNC1H1, TUBA1A, TUBG1) using family questionnaires, standardized neuropediatric assessments, and patients' medical reports. All but two patients were diagnosed with epilepsy. Median age at seizure onset was 6 months (range: 2.1-42.0), starting with epileptic spasms in 70%. Standard treatment protocols with hormonal therapy (ACTH or corticosteroids) and/or vigabatrin were the most effective approach for epileptic spasms, leading to seizure control in 47%. Seizures later in the disease course were most effectively treated with valproic acid and lamotrigine, followed by vigabatrin and phenobarbital, resulting in seizure freedom in 20%. Regarding psychomotor development, lissencephaly patients presenting without epileptic spasms were significantly more likely to reach various developmental milestones compared to patients with spasms. Classic lissencephaly is highly associated with drug-resistant epilepsy starting with epileptic spasms in most patients. The standard treatment protocols for infantile epileptic spasms syndrome lead to freedom from seizures in around half of the patients. Due to the association of epileptic spasms with an unfavorable course of psychomotor development, early and reliable diagnosis and treatment of spasms should be pursued. For epilepsies occurring later in childhood, ASM with valproic acid and lamotrigine, followed by vigabatrin and phenobarbital, appears to be most effective.

Optimizing ketogenic diet therapy for childhood epilepsy: Identifying key factors for seizure control and psychomotor enhancement.

To identify key factors influencing the therapeutic efficacy of the ketogenic diet (KD) for children with drug-resistant epilepsy and elucidate their interconnected relationships to optimize clinical practice. Participants were selected from children receiving KD treatment at West Second University Hospital of Sichuan University from September 2015 to October 2023. Clinical factors pre-KD and post-KD (at the third month) were analyzed systematically using an analytical framework. Descriptive analyses, univariate analyses, and multivariate regression analyses were performed for the entire cohort and subgroups of genetic and non-genetic (i.e., structural and unknown) etiologies. Thereby, the most significant predictors were identified for each relevant dependent variable. Path analysis diagrams were used for visual representation. Of 156 patients, genetic etiology was prevalent (38.5%). In the genetic subgroup, channelopathies predicted lower baseline seizure frequency and increased chance of seizure freedom with KD. Frequent seizures and complex history of anti-seizure medications (ASMs) predicted severe baseline psychomotor abnormalities. Younger age at KD initiation benefited psychomotor improvement. In the non-genetic subgroup, lower baseline seizure frequency increased the likelihood of seizure freedom post-KD. Concurrent use of multiple ASMs helped achieve ≥50% seizure reduction. Boys were more likely to experience psychomotor improvement. A significant correlation was found between ≥50% seizure reduction and psychomotor improvement in both subgroups. Delayed KD initiation (longer epilepsy duration at KD start) was related to a greater number of ASMs used, infrequent seizures, and older age at epilepsy onset. In addition, patients with channelopathies had delayed initiation of KD. Children with genetic epilepsy display more pronounced characteristics of epileptic encephalopathy. Early KD intervention is crucial for channelopathies, notably SCN1A variants. For other drug-resistant epilepsy cases, KD alongside diverse ASMs may improve seizure control and developmental outcomes. However, the patient population benefiting most from early KD tends to start the treatment later, urging a re-evaluation of KD decision-making paradigms.

Interictal blood-brain barrier dysfunction in piriform cortex of people with epilepsy.

The piriform cortex is considered to be highly epileptogenic. Its resection during epilepsy surgery is a predictor for postoperative seizure freedom in temporal lobe epilepsy. Epilepsy is associated with a dysfunction of the blood-brain barrier. We investigated blood-brain barrier dysfunction in the piriform cortex of people with temporal lobe epilepsy using quantitative T1-relaxometry. Gadolinium-based contrast agent was administered ictally and interictally in 37 individuals before undergoing quantitative T1-relaxometry. Postictal and interictal images were co-registered, and subtraction maps were created as biomarkers for peri-ictal (∆qT1interictal-postictal) and interictal (∆qT1noncontrast-interictal) blood-brain barrier dysfunction. Values were extracted for the piriform cortex, hippocampus, amygdala, and the whole cortex. In temporal lobe epilepsy (n = 14), ∆qT1noncontrast-interictal was significantly higher in the piriform cortex than in the whole cortex (p = 0.02). In extratemporal lobe epilepsy (n = 23), ∆qT1noncontrast-interictal was higher in the hippocampus than in the whole cortex (p = 0.05). Across all individuals (n = 37), duration of epilepsy was correlated with ∆qT1noncontrast-interictal (ß = 0.001, p < 0.001) in all regions, while the association was strongest inthe piriform cortex. Impaired verbal memory was associated with ∆qT1noncontrast-interictal only in the piriform cortex (p = 0.04). ∆qT1interictal-postictal did not show differences in any region. Interictal blood-brain barrier dysfunction occurs in the piriform cortex in temporal lobe epilepsy. This dysfunction is linked to longer disease duration and worse cognitive deficits, emphasizing the central role of the piriform cortex in the epileptogenic network of temporal lobe epilepsy.

Seizure outcome in drug-resistant epilepsy in the setting of polymicrogyria

ObjectiveWe aimed to analyze seizure outcomes and define ictal onset with intracranial electroencephalography (ICEEG) in patients with polymicrogyria (PMG)-related drug-resistant epilepsy (DRE), considering surrounding cortex and extent of surgical resection. MethodsRetrospective study of PMG-diagnosed patients (2001 to June 2018) at a single epilepsy center was performed. Primary outcome was complete seizure freedom (SF), based on Engel classification with follow-up of ≥ 1 year. Univariate analyses identified predictive clinical variables, later integrated into multivariate Cox proportional hazards models. ResultsThirty-five patients with PMG-related DRE (19 adults/16 pediatric: 20 unilateral/15 bilateral) were studied. In surgical group (n = 23), 52 % achieved SF (mean follow-up:47 months), whereas none in non-resective treatment group (n = 12) attained SF (mean follow-up:39.3 months) (p = 0.002). In surgical group, there were no significant differences in SF, based on the laterality of the PMG [uni or bilateral,p = 0.35], involvement of perisylvian region(p = 0.714), and extent of the PMG resection [total vs. partial,p = 0.159]. Patients with ictal ICEEG onset in both PMG and non-PMG cortices, and those limited to non- PMG cortices had a greater chance of achieving SF compared to those limited to the PMG cortices. ConclusionResective surgery guided by ICEEG for defining the epileptogenic zone (EZ), in DRE patients with PMG, leads to favorable seizure outcomes. ICEEG-guided focal surgical resection(s) may lead to SF in patients with bilateral or extensive unilateral PMG. ICEEG aids in EZ localization within and/or outside the MRI-identified PMG. Complete removal of PMG identified on MRI does not guarantee SF. Hence, developing preimplantation hypotheses based on epileptogenic networks evaluation during presurgical assessment is crucial in this patient population.

The spectrum of indications for ultralong-term EEG monitoring

PurposeWe assessed clinical cases to investigate the spectrum of indications for ultra-longterm EEG monitoring using a subcutaneous implantable device in adult patients with focal epilepsy. MethodsElectronic charts were reviewed from patients undergoing ultra-longterm recordings at the European Epilepsy centers Barcelona, Freiburg and Vienna. Specific patient settings approached in the three centers were analyzed, and the main clinical question was extracted. Results from recordings were analyzed based on the specific results and information obtained. Results24 patients in whom ultra-longterm recordings were available were analyzed. A total of 11 main indications for subcutaneous long-term EEG recordings were identified, including the identification of active epilepsy in patients with low seizure frequency, under- and overreporting of patients, differentiation of non-epileptic from epileptic events, assessment of seizure severity, circadian and multidian rhythms of seizure occurrence, validation of treatment efficacy, improvement of patient-based reporting and medicolegal evidence for seizure freedom. This is reported with patient-specific case vignettes. ConclusionUltra-longterm monitoring using subcutaneous implantable EEG devices can provide relevant diagnostic and treatment information in a large spectrum of clinical situations. This is discussed considering the intrinsic limitations of the method related to spatial coverage, sensitivity and validity as a biomarker of ongoing seizures.