Achieved Seizure Freedom Research Articles

Intensive treatment course to identify pseudoresistant epilepsy and expedite surgery referrals - A prospective intervention study

IntroductionA significant proportion of patients do not achieve seizure freedom despite treatment attempts with two different anti-seizure medications (ASMs). A subset may not truly have drug-resistant epilepsy (“pseudoresistant”), while rapid referral of patients with genuine drug-resistant epilepsy to surgery is mandated. This study was designed to evaluate a structured and intensive treatment course with the objective of promptly identifying cases of pseudoresistance and accelerating the time to referral to epilepsy surgery. MethodsFrom May 2017 to February 2021, this prospective interventional study recruited consecutive adult patients with epilepsy treated at Odense University Hospital, Denmark, who had at least one seizure per month despite attempts with two or more ASMs. The predefined endpoint was improvement in seizure activity. Secondary endpoints were referral to epilepsy surgery, patients with pseudoresistance, and achievement of seizure freedom. ResultsOf the 41 patients enrolled, 39 completed the study. The intervention comprised a initial seizure documentation, specialist evaluation, EEG monitoring as required, and an individualized plan for intensive treatment. The plans included e.g., optimization of medical treatment, seizure classification, and improvement of medication adherence. The subsequent intensive treatment (1–4 contacts/month; 1–13 contacts in total) was led by epilepsy nurses that executed the treatment plan. The intervention significantly improved seizure control, with 41.1 % of patients achieving seizure freedom and an additional 17.8 % of patients experiencing reduced seizure frequency. One-third of the patients turned out to be “pseudoresistant” due to various reasons, including wrong classification of seizures and inadequate adherence to ASMs. Ten patients were offered a referral for epilepsy surgery at the end of the study after an average of 34.8 weeks. ConclusionThis study demonstrates the efficacy of a standardized, intensive treatment course involving epilepsy nurses in identifying and managing patients with persisting seizures despite treatment attempts with two ASMs. This approach led to favourable seizure outcomes and facilitated expedited referrals for epilepsy surgery where appropriate.

Heterozygous variants in USP25 cause genetic generalized epilepsy.

USP25 encodes ubiquitin-specific protease 25, a key member of the deubiquitinating enzyme family that is involved in neural fate determination. Although abnormal expression in Down's syndrome was reported previously, the specific role of USP25 in human diseases has not been defined. In this study, we performed trio-based whole exome sequencing in a cohort of 319 cases (families) with generalized epilepsy of unknown aetiology. Five heterozygous USP25 variants, including two de novo and three co-segregated variants, were determined in eight individuals affected by generalized seizures and/or febrile seizures from five unrelated families. The frequency of USP25 variants showed a significantly high aggregation in this cohort compared with the East Asian population and all populations in the gnomAD database. The mean age at onset of febrile and afebrile seizures were 10 months (infancy) and 11.8 years (juvenile), respectively. The patients achieved seizure freedom, except that one had occasional nocturnal seizures at the last follow-up. Two patients exhibited intellectual disability. Usp25 was expressed ubiquitously in mouse brain with two peaks, on embryonic Days 14-16 and postnatal Day 21, respectively. In human brain, likewise, USP25 is expressed in the fetus/early childhood stage and with a second peak at ∼12-20 years old, consistent with the seizure onset age in patients during infancy and in juveniles. To investigate the functional impact of USP25 deficiency in vivo, we established Usp25 knockout mice, which showed increased seizure susceptibility compared with wild-type mice in a pentylenetetrazol-induced seizure test. To explore the impact of USP25 variants, we used multiple functional detections. In HEK293 T cells, the variant associated with a severe phenotype (p.Gln889Ter) led to a significant reduction of mRNA and protein expressions but formed stable truncated dimers with an increment of deubiquitinating enzyme activities and abnormal cellular aggregations, indicating a gain-of-function effect. The p.Gln889Ter and p.Leu1045del variants increased neuronal excitability in mouse brain, with a higher firing ability in p.Gln889Ter. These functional impairments align with the severity of the observed phenotypes, suggesting a genotype-phenotype correlation. Hence, a moderate association between USP25 and epilepsy was noted, indicating that USP25 is potentially a predisposing gene for epilepsy. Our results from Usp25 null mice and the patient-derived variants indicated that USP25 would play an epileptogenic role via loss-of-function or gain-of-function effects. The truncated variant p.Gln889Ter would have a profoundly different effect on epilepsy. Together, our results underscore the significance of USP25 heterozygous variants in epilepsy, thereby highlighting the critical role of USP25 in the brain.

Hippocampal dentate granule cells in temporal lobe epilepsy: A morphometry and transcriptomic study.

The dentate gyrus (DG) plays a critical role in hippocampal circuitry, providing a "gate-like" function to the downstream cornu ammonis (CA) sectors. Despite this critical role, pathologies in DG are less commonly described than those in the CA sectors in the diagnosis of mesial temporal lobe epilepsy (mTLE). To elucidate the role of the DG in mTLE, we analysed hippocampal sclerosis (HS), no-HS, non-TLE epilepsy control, and non-epilepsy control cohorts using morphometry and gene expression profiling techniques. Morphometry techniques analysed DG cell spacing, nucleus size, and nucleus circularity. Our data show distinct DG morphometry and RNA expression profiles between HS and No-HS. Dentate granule cells are more dispersed in patients with HS, and the DG shows an elevated expression of the complement system, apoptosis, and extracellular matrix remodelling-related RNA. We also observe an overall decrease in neurogenesis-related RNA in HS DG. Interestingly, regardless of the pathological diagnosis, the DG morphometry correlates with post-operative outcomes. Increased cell spacing is observed in the DG of mTLE cases that achieve seizure freedom post-operatively. This study reveals the possible prognostic value of DG morphometry, as well as supporting the notion that HS and no-HS TLE may be distinct disease entities with differing contributing mechanisms.

MRI-quality and morphometric MRI analysis to identify focal cortical dysplasia: An exploratory study

BackgroundIn the pre-surgical evaluation of people with focal epilepsy and a normal MRI, Morphometric Analysis Program v2018 (MAP18) aids in detecting visually inconspicuous focal cortical dysplasia (FCD). We investigated the impact of MRI scans with reduced signal-to-noise ratio (SNR) and spatial resolution (SR) on FCD detection by MAP18, aiming to improve the chances of achieving seizure freedom through epilepsy surgery. MethodsThirty MRI scans with the identified lesion using MAP18 radiologically confirmed as FCD by a neuroradiologist, were retrospective analysed. SNR and SR were artificially reduced in ten steps, and their impact on MAP18 outcomes was assessed using multilevel analysis. ResultsThere was a significant effect after reducing SR and SNR for z-score and volume of the FCD cluster, the total number of detected clusters, and volume of these clusters. After SNR reduction, there was also a significant effect for z-score of the total number of detected clusters. FCD became undetectable by MAP18 after six steps of SR reduction (voxel size 2.8 × 2.8 × 2.8 mm³) and after two steps of SNR reduction. ConclusionsThis exploratory study suggests that reduced SR and SNR negatively affect FCD detection with MRI post-processing (MAP18). The MAP18 evaluator should screen MRI quality before post-processing, particularly for scans with significant visual noise or voxel sizes of 2.8 × 2.8 × 2.8 mm³ and upwards, as repeating a low-quality MRI scan is less burdensome than the adverse effects of continued seizures due to failure to detect FCD.

Brain Stiffness Correlates With Pathological Tissue in Patients With Drug-Resistant Epilepsy Due to Rasmussen Encephalitis and Focal Cortical Dysplasia.

Complete resection of epileptogenic zone is the single most important determinant of favorable seizure outcomes in resective surgery. However, identifying and resecting this zone is challenging in patients harboring diffuse; MRI-occult malformations of cortical development, such as focal cortical dysplasia; or acquired pathology, such as Rasmussen encephalitis. Intraoperative adjuncts that can aid in identifying the lesion and/or epileptogenic zone can optimize the extent of resection and seizure outcome. We sought to study a novel intraoperative tool, brain tonometer, to measure brain stiffness and correlate with histopathological and radiological findings. Brain stiffness was measured at various presumed normal and abnormal areas of the cortex during surgery in 2 patients with drug-resistant epilepsy. These results were correlated with preoperative and intraoperative neuroimaging and histopathology. We found brain stiffness correlated well with the degree of inflammation and cortical disorganization. Brain tonometry may help to intraoperatively identify inflammatory brain tissue along with structural and histopathological abnormalities. In select cases, this could potentially allow more tailored resections of the underlying lesion, to ensure complete removal of the epileptogenic lesion and improve the probability of achieving seizure freedom, while sparing normal brain leading to better functional outcomes.

MEG in MRI-Negative Patients with Focal Epilepsy.

To review the evidence on the clinical value of magnetic source imaging (MSI) in patients with refractory focal epilepsy without evidence for an epileptogenic lesion on magnetic resonance imaging ("MRI-negative" or "non-lesional MRI"). We conducted a systematic literature search on PUBMED, which was extended by researchrabbit.ai using predefined criteria to identify studies that applied MSI in MRI-negative patients with epilepsy. We extracted data on patient characteristics, MSI methods, localization results, surgical outcomes, and correlation with other modalities. We included 23 studies with a total of 512 non-lesional epilepsy patients who underwent MSI. Most studies used equivalent current dipole (ECD) models to estimate the sources of interictal epileptic discharges (IEDs). MEG detected IEDs in 32-100% of patients. MSI results were concordant with other modalities, such as EEG, PET, and SPECT, in 3892% of cases. If MSI concordant surgery was performed, 52-89% of patients achieved seizure freedom. MSI contributed to the decision-making process in 28-75% of cases and altered the surgical plan in 5-33% of cases. MSI is a valuable diagnostic tool for MRI-negative patients with epilepsy, as it can detect and localize IEDs with high accuracy and sensitivity, and provides useful information for surgical planning and predicts outcomes. MSI can also complement and refine the results of other modalities, such as EEG and PET, and optimize the use of invasive recordings. MSI should be considered as part of the presurgical evaluation, especially in patients with non-lesional refractory epilepsy.

Hippocampal sclerosis in women with temporal lobe epilepsy: seizure and pregnancy outcomes

BackgroundTemporal lobe epilepsy with hippocampal sclerosis (TLE-HS) is typically resistant to pharmacological interventions; however, achieving seizure freedom is possible through surgery. Our objective was to focus on the pregnancy and seizure outcomes during pregnancy of women with TLE-HS, and aim to identify predictors of seizure control.MethodsThe West China Registry of Pregnancy of Women with Epilepsy (WCPR_EPi) was a monocentric prospective cohort study of women with epilepsy (WWE). We screened women with TLE-HS in this database. Their clinical profile, anti-seizure medication (ASM) use, and pregnancy outcomes were extracted from the records of the registry (2010–2023).ResultsOut of 2320 WWE followed up, 47 pregnancies in women with TLE-HS were identified and analyzed. Seizure exacerbation occurred in 40.4% of pregnancies, and seizure freedom was present in 34.0% of these during pregnancy. Factors associated with seizure exacerbation during pregnancy was ASM non-adherence (odds ratio [OR] =7.00, 95% confidence interval [CI] 1.43–34.07, P=0.016). The surgery group showed a significantly higher seizure freedom rate (OR = 6.87, 95% CI 1.02–46.23, P=0.016) and lower rate of induced labor (0.0% vs 26.5%, P=0.047) compared to the medically-treated group alone. Caesarean section was chosen in 77.1% of cases due to seizure concerns, with comparable in epilepsy-related (n=20) and obstetric causes (n=24). No major congenital malformations were reported.ConclusionsSurgical treatment before pregnancy appears to offer a higher chance of seizure freedom compared to medication alone. Most of women with TLE-HS can deliver healthy offspring regardless of suboptimal seizure control and unwarranted concerns.

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.

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.

Seizure burden and healthcare resource utilization among people living with drug-resistant focal epilepsy in the United States

Objective This study investigated clinical characteristics, burden of uncontrolled seizures, and seizure-related healthcare resource utilization (HRU) among individuals living with drug-resistant focal epilepsy (FE) in the United States (US). Methods Medical charts of adults with drug-resistant FE who initiated third-line (3 L) anti-seizure medication were extracted from clinical practices in the US (1/1/2013–1/31/2020). The index date, defined as the date of 3 L initiation, was used to indicate the emergence of drug resistance. Individuals on cenobamate were followed for any length of time from the index date. Demographic and clinical characteristics were analyzed descriptively. Primary clinical outcomes included seizure burden (i.e. change in seizure frequency and time to the first and second seizure events) and epilepsy-related HRU. Results Overall, 189 neurologists/epileptologists contributed 345 charts of individuals living with drug-resistant FE (66% male; average age 24 years at diagnosis and 32 years at index date). 66% had ≥1 neurologic/neuropsychiatric comorbidity at baseline. Average monthly seizure rate decreased from 6.1 at baseline to 3.8 at follow-up; however, nearly half of individuals experienced worse/no change or only some improvement (<50% reduction) in seizure frequency. Most individuals (91%) had ≥1 epilepsy-related outpatient visit during follow-up. Unplanned HRU included emergency department visits (43%) and hospitalizations (24%), primarily due to breakthrough seizure events. Conclusion Despite the availability of many anti-seizure medications in the US, people living with drug-resistant FE continue to experience multiple seizures per month and incur substantial healthcare resources. Novel pharmacotherapies may help individuals living with drug-resistant epilepsy achieve seizure freedom.

Therapeutic approaches targeting seizure networks.

Epilepsy is one of the most common neurological disorders, affecting over 65 million people worldwide. Despite medical management with anti-seizure medications (ASMs), many patients fail to achieve seizure freedom, with over one-third of patients having drug-resistant epilepsy (DRE). Even with surgical management through resective surgery and/or neuromodulatory interventions, over 50 of patients continue to experience refractory seizures within a year of surgery. Over the past 2decades, studies have increasingly suggested that treatment failure is likely driven by untreated components of a pathological seizure network, a shift in the classical understanding of epilepsy as a focal disorder. However, this shift in thinking has yet to translate to improved treatments and seizure outcomes in patients. Here, we present a narrative review discussing the process of surgical epilepsy management. We explore current surgical interventions and hypothesized mechanisms behind treatment failure, highlighting evidence of pathologic seizure networks. Finally, we conclude by discussing how the network theory may inform surgical management, guiding the identification and targeting of more appropriate surgical regions. Ultimately, we believe that adapting current surgical practices and neuromodulatory interventions towards targeting seizure networks offers new therapeutic strategies that may improve seizure outcomes in patients suffering from DRE.

Maintenance of response to ketogenic diet therapy for drug-resistant epilepsy post diet discontinuation: A multi-centre case note review

PurposeThere is limited research on the proportion of individuals with epilepsy who maintain response to ketogenic diet therapy (KDT) after discontinuing treatment. We aimed to determine the proportion of individuals who did / did not maintain response post KDT and explore factors that may influence the likelihood of maintaining response. MethodsRetrospective data were collected from 97 individuals from 9 KDT centres. Individuals had achieved ≥50 % seizure reduction on KDT for at least 12 months, with seizure frequency data available at 3 months+ post diet. Outcome 1 was: recurrence of seizures or increase in seizure frequency post diet; outcome 2: recurrence of seizures, increase in seizure frequency or an additional anti-seizure treatment started post diet. Results61/97 (62.9 %) individuals maintained response at latest follow-up (mean 2.5[2.0] years since stopping KDT). Approximately one third maintained response without further anti-seizure treatments. One quarter of individuals had an increase in frequency or recurrence of seizures within 6 months (95 %CI 4, 12) for outcome 1 and within 3 months (3, 6) for outcome 2.Individuals who did not achieve seizure freedom on diet were significantly more likely to have an increase in seizures or to require additional anti-seizure treatments post diet compared to those who were seizure-free on diet (hazard ratio 4.02, 95 %CI (1.46, 11.16) p < 0.01). ConclusionOur findings should help guide clinical teams with the information they provide patients and their families regarding likelihood of long-term seizure response to KDT. Realistic costings for KDT services may need to be considered.

Cenobamate add-on therapy for drug-resistant focal epilepsy.

Although most people with epilepsy achieve complete seizure cessation, approximately one-third of those with the condition continue experiencing seizures despite the use of antiseizure medications (ASMs) given as monotherapy or polytherapy. In this review, we summarised the evidence from randomised controlled trials (RCTs) about cenobamate as an add-on treatment for focal epilepsy uncontrolled by one or more concomitant ASMs. To assess the efficacy and tolerability of add-on oral cenobamate for the treatment of drug-resistant focal-onset seizures, defined as seizures persisting despite treatment with one or more ASMs. We searched the Cochrane Register of Studies (CRS Web) and MEDLINE Ovid (September 2022). In addition, we contacted the manufacturer of cenobamate and experts in the field to enquire after any ongoing or unpublished studies. RCTs comparing add-on cenobamate to placebo or another ASM in people with focal epilepsy uncontrolled by one or more concomitant ASMs. Two review authors independently selected trials for inclusion, extracted data, performed risk of bias assessment, and assessed the certainty of the evidence using the GRADE approach. Our primary outcomes were at least a 50% reduction in total seizure frequency, seizure freedom, and the occurrence of adverse events. We used an intention-to-treat approach for our primary analyses. For each outcome we estimated summary risk ratios (RRs) with their 95% confidence intervals (CIs). We summarised the estimates of effects and certainty of the evidence for each outcome in a summary of findings table. We included two studies (659 adult participants, 442 allocated to cenobamate and 217 to placebo). The overall RR for at least a 50% reduction in seizure frequency for add-on cenobamate at any dose compared to placebo was 2.17 (52% versus 24%, 95% CI 1.66 to 2.84; 2 studies, 605 participants; moderate-certainty evidence). The RR for seizure freedom for add-on cenobamate at any dose compared to placebo was 4.45 (16% versus 5%, 95% CI 2.25 to 8.78; 2 studies, 605 participants; moderate-certainty evidence). The RR for the occurrence of adverse events for add-on cenobamate at any dose compared to placebo was 1.14 (77% versus 67%, 95% CI 1.02 to 1.27; 2 studies, 659 participants; moderate-certainty evidence). We judged the two included RCTs as at low or unclear risk of bias. Both studies were sponsored by the drug company that produces cenobamate. Add-on cenobamate is probably better than placebo in reducing the frequency of seizures by at least 50% and in achieving seizure freedom in adults with focal epilepsy uncontrolled by one or more concomitant ASMs (moderate level of certainty). Its use is probably associated with an increased risk of adverse events (moderate level of certainty). Further prospective, controlled trials are required to evaluate the efficacy and tolerability of add-on cenobamate compared to other ASMs. The efficacy and tolerability of cenobamate as adjunctive treatment for focal epilepsy in children should be further investigated. Finally, the long-term efficacy and tolerability of add-on cenobamate treatment in people with other epilepsy types (e.g. generalised epilepsy) or specific epilepsy syndromes, as well as its use as monotherapy, require additional study.

Clinical features of unilateral multilobar and hemispheric polymicrogyria (PMG)-related epilepsy and seizure outcome with different treatment options.

To provide evidence for choosing surgical or nonsurgical treatment for epilepsy in patients with unilateral multilobar and hemispheric polymicrogyria (PMG). We searched published studies until September 2022 related to unilateral multilobar and hemispheric PMG and included patients who were followed up at the Pediatric Epilepsy Centre of Peking University First Hospital in the past 10 years. We summarized the clinical characteristics and compared the long-term outcomes after surgical or nonsurgical (anti-seizure medications, ASMs) treatment. A total of 70 patients (49 surgical, 21 non-surgical) with unilateral multilobar and hemispheric PMG were included. The median age at epilepsy onset was 2.5 years (1.0-4.1). The most common seizure types were focal and atypical absence seizures. In the whole cohort, 87.3% had hemiparesis and 67.1% had electrical status epilepticus during slow sleep (ESES). There were significant differences in age at epilepsy onset, extent of lesion, and EEG interictal discharges between the two groups. At the last follow-up (median 14.1 years), the rates of seizure-freedom (81.6% vs. 57.1%, p = 0.032) and ASM discontinuation (44.4% vs. 6.3%, p = 0.006) were higher in the surgical group than in the nonsurgical group. Patients in the surgical group had a higher rate of seizure-freedom with complete resection/disconnection than with subtotal resection (87.5% vs. 55.6%, p = 0.078), but with no statistically significant difference. In the nonsurgical group, more extensive lesions were associated with worse seizure outcomes. Cognition improved postoperatively in 90% of surgical patients. In patients with unilateral multilobar and hemispheric PMG, the age of seizure onset, the extent of the lesion and EEG features can help determine whether surgery should be performed early. Additionally, surgery could be more favorable for achieving seizure freedom and cognitive improvement sooner. We aim to summarize clinical characteristics and compare the long-term outcomes after surgical and nonsurgical (ASM) treatment to provide a basis for treatment decisions for patients with unilateral multilobar and hemispheric polymicrogyria (PMG)-related epilepsy. We found that patients with unilateral hemispheric and multilobar PMG had significantly higher rates of seizure freedom and ASM discontinuation with surgical treatment than with nonsurgical treatment. In the surgical group, seizure outcomes were better in patients treated with complete resection/disconnection than in those treated with subtotal resection, but the difference was not statistically significant.

Trends, outcomes, and complications of surgery for lesional epilepsy in infants and toddlers: A multicenter study.

To assess seizure and developmental outcomes, their predictors, and complications in 160 children who, between 1998 and 2022, underwent surgery for lesional epilepsy with curative intent before the age of 3 years. To compare trends in epilepsy surgery in this age group before and after the year 2014. Retrospective multicenter study. Descriptive and univariate analyses, and multivariable models for all outcomes. These 160 patients (76 F; 47.5%) underwent 169 surgeries (age at surgery 20.4 ± 9.4 months). At the last follow-up (77 ± 57.4 months), 121 patients (75.6%) were in Engel class I, 106 (66.2%) of whom were in Engel class Ia. Antiseizure medications were stopped in 84 patients (52.5%). Complications requiring reoperations were observed in 16 patients (10%; 9.5% of surgeries) and unexpected permanent deficits in 12 (7.5%; 7.1% of surgeries). Postoperative cognitive functions remained unchanged in 56 patients (44.4%), improved in 51 (40.5%), and worsened in 19 (15.1%). Multivariable analyses showed that the probability of achieving Engel class Ia was lower when the duration of epilepsy was longer, patients underwent preoperative video-EEG, and unexpected postoperative permanent deficits occurred. Cognitive improvement after surgery was associated with lower preoperative seizure frequency, better preoperative developmental level, and a longer postoperative follow-up. FCDII and tumors were the histopathologies carrying a higher probability of achieving seizure freedom, while polymicrogyria was associated with a lower probability of cognitive improvement. The number of patients operated on after 2014 was higher than before (61.3% vs. 38.7%), with stable outcomes. Epilepsy surgery is effective and safe in infants and toddlers, although the complication rate is higher than seen in older patients. Shorter duration of epilepsy, lower seizure frequency, no need for video-EEG, tumors, and some malformations of cortical development are robust predictors of seizure and cognitive outcome that may be exploited to increase earlier referral. This study analyzed the results of epilepsy surgery in 160 children who had been operated on before the age of 3 years at four Italian centers between 1998 and 2022. At the last follow-up (77 ± 57.4 months), 121 patients (75.6%) were free from disabling seizures, of which 106 (66.2%) were completely seizure-free since surgery. Major surgical complications occurred in 28 patients (17.5%), which is higher than observed with epilepsy surgery in general, but similar to hemispheric/multilobar surgery. Postoperative cognitive function remained unchanged in 56 patients (44.4%), improved in 51 (40.5%), and worsened in 19 (15.1%). Epilepsy surgery is effective and safe in infants and toddlers.

Electroclinical characteristics and therapies of tonic spasms

BackgroudEpileptic spasms followed by a tonic component have been frequently observed in patients with late-onset spasms (LOS). However, there is a lack of comprehensive analysis and summary of clinical data related to tonic spasms (TS), including seizures, video-electroencephalogram (V-EEG), synchronous electromyography (EMG) and follow-up data.MethodsTo investigate the characteristics of TS, we prospectively collected the clinical data, including 24-h V-EEG and synchronous EMG data of 32 enrolled patients who suffered from epileptic spasms followed by a TS onset at least once during the 24-h V-EEG in the epilepsy center of Xijing Hospital between June 2015 and July 2020. The patients were prescribed anti-seizure medications (ASMs) and followed up for 2–7 years.ResultsThe average age of epilepsy onset was 48.06 ± 16.07 months (range: 25 to 88 months). Among the enrolled patients, 22 patients presented with mild intellectual deficits. During the 24-h video-EEG monitoring, an average of 6.94 TS events (range: 3 to 21) were recorded, and these TS seizures often occurred in clusters. In addition to TS, 26 patients experienced generalized tonic-clonic seizures (GTCS), atypical absence seizures, myoclonic seizure, and epileptic spasms. None of the 32 patients with TS displayed hypsarrhythmia during the 24-h video-EEG recording. A total of 28 patients showed normal EEG backgrounds. Interictal epileptic discharges, including slow waves (SW), spike/sharp slow waves (SSW), and spikes, often displayed multifocally. Notably, two patients achieved seizure freedom for more than 2 years through monotherapy with oxcarbazepine (OXC), which was associated with normalization of the EEG.ConclusionsIt is difficult to classify the patients with TS as any existing epileptic syndromes, which were distinct from West syndrome or Lennox-Gastaut syndrome. TS might be an underreported seizure type and further studies are needed to gain a more comprehensive understanding of the electro-clinical features and appropriate choice of ASMs for treating tonic spasms.

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

ObjectiveTo 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. MethodsWe 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. ResultsThe 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. ConclusionSH 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.

Minimally Invasive Epilepsy Surgery.

Surgery remains a critical and often necessary intervention for a subset of patients with epilepsy. The overarching objective of surgical treatment has consistently been to enhance the quality of life for these individuals, either by achieving seizure freedom or by eliminating debilitating seizure types. This review specifically examines minimally invasive surgical approaches for epilepsy. Contemporary advancements have introduced a range of treatments that offer increased safety and efficacy compared to traditional open resective epilepsy surgeries. This manuscript provides a comprehensive review of these techniques and technologies.

Factors influencing disparities in epilepsy surgery: analysis of the National Inpatient Sample and Kids' Inpatient Database.

Despite the proven efficacy of surgical intervention for achieving seizure freedom and improved quality of life for many epilepsy patients, this treatment remains underutilized. In this study, the authors assessed sociodemographic trends in epilepsy surgery in the National Inpatient Sample (NIS) and the Kids' Inpatient Database (KID) and sought to determine whether disparities in surgical intervention for epilepsy may be attributed to insurance and comorbidity status. This cross-sectional study utilized data from the NIS database and KID from the Healthcare Cost and Utilization Project between the years 2012 and 2018. Outcomes of interest were rates of neurosurgical intervention, including resection, neuromodulation, or laser ablation. The authors utilized logit regression models to test the association between rates of neurosurgical intervention and the variables of interest and calculated the adjusted mean proportion of patients who received surgery using marginal effects. Of 336,015 admissions with intractable epilepsy in the NIS, 6.1% were patients who underwent neurosurgical treatment. Of 39,655 admissions from KID, 5.0% received surgical treatment. Private insurance was associated with a greater odds of surgical intervention compared with Medicaid (NIS: OR 1.63, KID: OR 1.62; p < 0.001). Patients assigned White race had an increased odds ratio of undergoing surgery when compared with those assigned Black race, adjusted for comorbidity burden (NIS: OR 1.59, p < 0.001; KID: OR 1.44, p = 0.027). Patients with an Elixhauser Comorbidity Index score of 0 or 1 were associated with a lower likelihood of surgery when compared to their higher scoring counterparts who had 4 or more comorbidities (NIS: OR 0.74, KID: OR 0.62; both p < 0.001). This study demonstrates that marginalized patients and those with Medicaid had decreased odds of neurosurgical intervention for epilepsy. Results of this research support the need for increased attention toward epilepsy patients from marginalized groups. Further investigation into the root cause of socioeconomic inequities in epilepsy surgery is necessary.

Simulated resections and RNS placement can optimize post-operative seizure outcomes when guided by fast ripple networks.

In medication-resistant epilepsy, the goal of epilepsy surgery is to make a patient seizure free with a resection/ablation that is as small as possible to minimize morbidity. The standard of care in planning the margins of epilepsy surgery involves electroclinical delineation of the seizure onset zone (SOZ) and incorporation of neuroimaging findings from MRI, PET, SPECT, and MEG modalities. Resecting cortical tissue generating high-frequency oscillations (HFOs) has been investigated as a more efficacious alternative to targeting the SOZ. In this study, we used a support vector machine (SVM), with four distinct fast ripple (FR: 350-600 Hz on oscillations, 200-600 Hz on spikes) metrics as factors. These metrics included the FR resection ratio (RR), a spatial FR network measure, and two temporal FR network measures. The SVM was trained by the value of these four factors with respect to the actual resection boundaries and actual seizure free labels of 18 patients with medically refractory focal epilepsy. Leave one out cross-validation of the trained SVM in this training set had an accuracy of 0.78. We next used a simulated iterative virtual resection targeting the FR sites that were highest rate and showed most temporal autonomy. The trained SVM utilized the four virtual FR metrics to predict virtual seizure freedom. In all but one of the nine patients seizure free after surgery, we found that the virtual resections sufficient for virtual seizure freedom were larger in volume (p<0.05). In nine patients who were not seizure free, a larger virtual resection made five virtually seizure free. We also examined 10 medically refractory focal epilepsy patients implanted with the responsive neurostimulator system (RNS) and virtually targeted the RNS stimulation contacts proximal to sites generating FR at highest rates to determine if the simulated value of the stimulated SOZ and stimulated FR metrics would trend toward those patients with a better seizure outcome. Our results suggest: 1) FR measures can accurately predict whether a resection, defined by the standard of care, will result in seizure freedom; 2) utilizing FR alone for planning an efficacious surgery can be associated with larger resections; 3) when FR metrics predict the standard of care resection will fail, amending the boundaries of the planned resection with certain FR generating sites may improve outcome; and 4) more work is required to determine if targeting RNS stimulation contact proximal to FR generating sites will improve seizure outcome.