Associations between testing and treatment pathways in lesional temporal or extratemporal epilepsy: A census survey of NAEC center directors

Objective

The evaluation to determine candidacy and treatment for epilepsy surgery in persons with drug-resistant epilepsy (DRE) is not uniform. Many non-invasive and invasive tests are available to ascertain an appropriate treatment strategy. This study examines expert response to clinical vignettes of magnetic resonance imaging (MRI)–positive lesional focal cortical dysplasia in both temporal and extratemporal epilepsy to identify associations in evaluations and treatment choice.

Methods

We analyzed annual report data and a supplemental epilepsy practice survey reported in 2020 from 206 adult and 136 pediatric epilepsy center directors in the United States. Non-invasive and invasive testing and surgical treatment strategies were compiled for the two scenarios. We used chi-square tests to compare testing utilization between the two scenarios. Multivariable logistic regression modeling was performed to assess associations between variables.

Results

The supplemental survey response rate was 100% with 342 responses included in the analyses. Differing testing and treatment approaches were noted between the temporal and extratemporal scenarios such as chronic invasive monitoring selected in 60% of the temporal scenario versus 93% of the extratemporal scenario. Open resection was the most common treatment choice; however, overall treatment choices varied significantly (p < .001). Associations between non-invasive testing, invasive testing, and treatment choices were present in both scenarios. For example, in the temporal scenario stereo-electroencephalography (SEEG) was more commonly associated with fluorodeoxyglucose–positron emission tomography (FDG-PET) (odds ratio [OR] 1.85; 95% confidence interval [CI] 1.06–3.29; p = .033), magnetoencephalography (MEG) (OR 2.90; 95% CI 1.60–5.28; p = <.001), high density (HD) EEG (OR 2.80; 95% CI 1.27–6.24; p = .011), functional MRI (fMRI) (OR 2.17; 95% CI 1.19–4.10; p = .014), and Wada (OR 2.16; 95% CI 1.28–3.66; p = .004). In the extratemporal scenario, choosing SEEG was associated with increased odds of neuromodulation over open resection (OR 3.13; 95% CI 1.24–7.89; p = .016).

Significance

In clinical vignettes of temporal and extratemporal lesional DRE, epilepsy center directors displayed varying patterns of non-invasive testing, invasive testing, and treatment choices. Differences in practice underscore the need for comparative trials for the surgical management of DRE.     

Adjunctive brivaracetam and sustained seizure frequency reduction in very active focal epilepsy

Objective

This study aimed to explore the effectiveness of brivaracetam (BRV) according to baseline seizure frequency and past treatment history in subjects with focal epilepsy who were included in the Brivaracetam Add-On First Italian Network Study (BRIVAFIRST).

Methods

BRIVAFIRST was a 12-month retrospective, multicenter study including adults prescribed adjunctive BRV. Study outcomes included sustained seizure response (SSR), sustained seizure freedom (SSF), and the rates of treatment discontinuation and adverse events (AEs). Baseline seizure frequency was stratified as <5, 5–20, and >20 seizures per month, and the number of prior antiseizure medications (ASMs) as <5 and ≥6.

Results

A total of 994 participants were included. During the 1-year study period, SSR was reached by 45.8%, 39.3%, and 22.6% of subjects with a baseline frequency of <5, 5–20, and >20 seizures per month (p < .001); the corresponding figures for the SSF were 23.4%, 9.8%, and 2.8% (p < .001). SSR was reached by 51.2% and 26.5% participants with a history of 1–5 and ≥6 ASMs (p < .001); the corresponding rates of SSF were 24.7% and 4.5% (p < .001). Treatment discontinuation due to lack of efficacy was more common in participants with >20 seizures compared to those with <5 seizures per month (25.8% vs. 9.3%, p < .001), and in participants with history of ≥6 prior ASMs compared to those with history of 1–5 ASMs (19.6% vs. 12.2%, p = .002). There were no differences in the rates of BRV withdrawal due to AEs and the rates of AEs across the groups of participants defined according to the number of seizures at baseline and the number of prior ASMs.

Significance

The baseline seizure frequency and the number of previous ASMs were predictors of sustained seizure frequency reduction with adjunctive BRV in subjects with focal epilepsy.     

Levetiracetam as a first-line antiseizure medication in WHO grade 2 glioma: Time to seizure freedom and rates of treatment failure

Objective

The high seizure burden seen in World Health Association (WHO) grade 2 gliomas is well documented. This study aims to identify factors that influence the probability of seizure freedom (12 months of seizure remission) and treatment failure (antiseizure medication [ASM] cessation or introduction of an alternative) in patients with WHO grade 2 glioma.

Methods

This is a retrospective observational analysis of patients from a regional UK neurosurgical center with histologically proven (n = 146) WHO grade 2 glioma and brain tumor related epilepsy. Statistical analyses using both Kaplan-Meier and Cox proportional hazards models were undertaken, with a particular focus on treatment outcomes when the commonly prescribed ASM levetiracetam (n = 101) is used as first line.

Results

Treatment with levetiracetam as a first-line ASM resulted in a significant increase in the probability of seizure freedom (p < .05) at 2 years compared with treatment with an alternative ASM. Individuals presenting with focal seizures without bilateral tonic-clonic progression were between 39% and 42% significantly less likely to reach seizure freedom within 10 years (p < .05) and 132% more likely to fail treatment by 5 years (p < .01) when compared to individuals who had seizures with progression to bilateral tonic-clonic activity. ASM choice did not significantly affect treatment failure rates.

Significance

More than two-thirds of patients with WHO grade 2 glioma related epilepsy treated with levetiracetam first line achieve seizure freedom within 2 years and it is a reasonable first-choice agent. Experiencing mainly focal seizures without progression infers a significant long-term reduction in the chance of seizure freedom. Further studies are needed to inform ASM selection.     

Supratentorial arachnoid cysts and seizures/epilepsy: A population study in community dwellers aged ≥20 years

Literature on the association between arachnoid cysts and seizures/epilepsy is inconsistent, and most series have been flawed due to recruitment bias. In this study, we aimed to assess the prevalence of supratentorial arachnoid cysts (SACs) in Atahualpa residents aged ≥20 years, and to estimate whether these lesions were associated with seizures/epilepsy. A total of 1157 individuals were included. Computed tomography revealed SACs in 25 individuals (2.2%). Most had middle cranial fossa SACs (n = 19). Recurrent nonprovoked seizures were diagnosed in 28 individuals and a single seizure in 4. Only 1 of 25 (4%) individuals with SACs had seizures/epilepsy as opposed to 31 of 1132 (2.7%) who did not have SACs (P = 0.508). A logistic regression model showed no association between SACs and seizures/epilepsy, after taking into account the effect of relevant confounders (odds ratio [OR] 1.71; 95% confidence interval [95% CI] 0.22‐13.3; P = 0.607). This study provides evidence of lack of association between SACs and seizures/epilepsy.     

Quality-of-life metrics with vagus nerve stimulation for epilepsy from provider survey data

ObjectiveDrug-resistant epilepsy is a devastating disorder associated with diminished quality of life (QOL). Surgical resection leads to seizure freedom and improved QOL in many epilepsy patients, but not all individuals are candidates for resection. In these cases, neuromodulation-based therapies such as vagus nerve stimulation (VNS) are often used, but most VNS studies focus exclusively on reduction of seizure frequency. QOL changes and predictors with VNS remain poorly understood.MethodUsing the VNS Therapy Patient Outcome Registry, we examined 7 metrics related to QOL after VNS for epilepsy in over 5000 patients (including over 3000 with ≥ 12 months follow-up), as subjectively assessed by treating physicians. Trends and predictors of QOL changes were examined and related to post-operative seizure outcome and likelihood of VNS generator replacement.ResultsAfter VNS therapy, physicians reported patient improvement in alertness (58–63%, range over follow-up period), post-ictal state (55–62%), cluster seizures (48–56%), mood change (43–49%), verbal communication (38–45%), school/professional achievements (29–39%), and memory (29–38%). Predictors of net QOL improvement included shorter time to implant (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.1–1.6), generalized seizure type (OR, 1.2; 95% CI, 1.0–1.4), female gender (OR, 1.2; 95% CI, 1.0–1.4), and Caucasian ethnicity (OR, 1.3; 95% CI, 1.0–1.5). No significant trends were observed over time. Patients with net QOL improvement were more likely to have favorable seizure outcomes (chi square [χ²] = 148.1, p < 0.001) and more likely to undergo VNS generator replacement (χ² = 68.9, p < 0.001) than those with worsened/unchanged QOL.SignificanceVNS for drug-resistant epilepsy is associated with improvement on various QOL metrics subjectively rated by physicians. QOL improvement is associated with favorable seizure outcome and a higher likelihood of generator replacement, suggesting satisfaction with therapy. It is important to consider QOL metrics in neuromodulation for epilepsy, given the deleterious effects of seizures on patient QOL.     

Predictors of seizure outcome after temporal lobectomy for intractable epilepsy

OBJECTIVES: To assess predictors of outcome of temporal lobectomy for intractable epilepsy. MATERIAL AND METHODS: In 63 adult patients operated with anterior temporal lobectomy during 198892, we used logistic regression analysis to assess predictors of being seizure-free (Engel's class I) 2 years after surgery. As potential predictors, we included the following variables: gender, age at operation, age at onset of seizures, epilepsy duration, etiology, generalized vs not generalized seizures, seizure frequency, intelligence quotient, ictal electroencephalography, magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), side of resection, and extent of the resection. RESULTS: About 44% of the surgery patients were seizure-free (Engel's class I) 2 years after surgery. In multivariate analysis (n = 55), MRI pathology defined as atrophy in the temporal lobe, angioma, tumor or mesial temporal sclerosis (odds ratio, OR 7.4, 95%CI: 1.7-32.9) and extent of the hippocampal resection (increase of 1 cm) (OR 2.2, 95%CI: 1.1-4.6) predicted being seizure-free. CONCLUSION: Focal pathology in preoperative MRI and the extent of the hippocampal resection were the only significant predictors of being seizure-free after 2 years.     

Pediatric epilepsy surgery from 2000 to 2018: Changes in referral and surgical volumes,patient characteristics,genetic testing,and postsurgical outcomes

Objective

Neurosurgery is a safe and effective form of treatment for select children with drug-resistant epilepsy. Still, there is concern that it remains underutilized, and that seizure freedom rates have not improved over time. We investigated referral and surgical practices, patient characteristics, and postoperative outcomes over the past two decades.

Methods

We performed a retrospective cohort study of children referred for epilepsy surgery at a tertiary center between 2000 and 2018. We extracted information from medical records and analyzed temporal trends using regression analyses.

Results

A total of 1443 children were evaluated for surgery. Of these, 859 (402 females) underwent surgical resection or disconnection at a median age of 8.5 years (interquartile range [IQR] = 4.6–13.4). Excluding palliative procedures, 67% of patients were seizure-free and 15% were on no antiseizure medication (ASM) at 1-year follow-up. There was an annual increase in the number of referrals (7%, 95% confidence interval [CI] = 5.3–8.6; p < .001) and surgeries (4% [95% CI = 2.9–5.6], p < .001) over time. Duration of epilepsy and total number of different ASMs trialed from epilepsy onset to surgery were, however, unchanged, and continued to exceed guidelines. Seizure freedom rates were also unchanged overall but showed improvement (odds ratio [OR] 1.09, 95% CI = 1.01–1.18; p = .027) after adjustment for an observed increase in complex cases. Children who underwent surgery more recently were more likely to be off ASMs postoperatively (OR 1.04, 95% CI = 1.01–1.08; p = .013). There was a 17% annual increase (95% CI = 8.4–28.4, p < .001) in children identified to have a genetic cause of epilepsy, which was associated with poor outcome.

Significance

Children with drug-resistant epilepsy continue to be put forward for surgery late, despite national and international guidelines urging prompt referral. Seizure freedom rates have improved over the past decades, but only after adjustment for a concurrent increase in complex cases. Finally, genetic testing in epilepsy surgery patients has expanded considerably over time and shows promise in identifying patients in whom surgery is less likely to be successful.     

Surgical hematoma evacuation of cortical intracerebral hemorrhage ≥10 ml reduces risk of subsequent epilepsy by more than 70%: A retrospective monocenter study

Aim

The aim of this study was to re-evaluate risk factors for post-ICH epilepsy (PICHE) and examine the impact of surgical hematoma evacuation on epilepsy development after ICH.

Background and purpose

Epilepsy is a common complication after intracerebral hemorrhage (ICH). Information on risk factors is still scarce and the role of ICH evacuation remains uncertain.

Methods

We retrospectively included patients with spontaneous ICH treated in our hospital in 2006–2019. Patients' medical records were analyzed. In addition, mailed questionnaires and telephone interviews were used to complete the dataset. Uni- and multivariable hazard ratios (HRs) were applied to investigate risk factors for PICHE and the impact of surgical ICH evacuation.

Results

Among 587 ICH patients available for analyses, 139 (23.7%) developed PICHE (mean follow-up 1795 ± 1378 days). The median time of epilepsy onset was 7 months after ICH (range 1–132 months). Risk factors associated with PICHE were cortical hemorrhage (multivariable HR 1.65 [95% CI 1.14–2.37]; p = 0.008), ICH volume > 10 ml (multivariable HR 1.91 [95% CI 1.33–2.73]; p < 0.001) and acute symptomatic seizures (multivariable HR 1.81 [95% CI 1.20–2.75]; p = 0.005). Patients with cortical ICH > 10 ml who underwent surgical hematoma evacuation were less likely to develop epilepsy than those with conservative treatment alone (multivariable HR 0.26 [95% CI 0.08–0.84]; p = 0.025).

Conclusions

Post-ICH epilepsy is frequent and predicted by large cortical ICH and acute symptomatic seizures. Hematoma evacuation reduced the risk of PICHE by more than 70% in patients with large cortical ICH. This finding could be considered in the clinical decision making on the acute treatment of ICH.     

以癫癎为首发症状的低级别星形细胞瘤病人术后癫癎预后分析

目的探讨影响以癫癎为首发症状的低级别星形细胞瘤癫癎预后的因素。方法回顾性分析以癫癎为首发症状的低级别星形细胞瘤病例,经手术切除肿瘤1年后的癫癎症状改善情况,本组研究数据应用SPSS17．0统计软件进行卡方检验和多因素Logistic回归分析。结果术后癫癎预后为改良Engel I级102例（67．5％）,Ⅱ级以上49例（32．5％）。卡方检验显示：术前病人有语言障碍（P=0．038）、术前肿瘤累及岛叶（P=0．010）、肿瘤未全切除（P=0．001）对术后癫癎预后差异有统计学意义。多因素Logistic回归分析：术前病人有语言障碍（P=0．022）、术前肿瘤累及岛叶（P=0．007）及肿瘤未全切除（P=0．002）均为影响术后癫癎发作的独立危险因素。结论术前病人有语言障碍、术前肿瘤累及岛叶及肿瘤未全切除是影响以癫癎为首发症状的低级别星形细胞瘤病人术后癫癎预后的独立危险因素。     

Short-term outcomes and predictors of post-surgical seizures in patients with supratentorial low-grade gliomas

To explore the predictive factors and short-term outcomes of post-surgical seizures in patients with supratentorial low-grade gliomas (LGGs). A consecutive series of 70 supratentorial LGG patients with seizures were reviewed to determine the predictors and short-term outcomes of seizures. Univariate analyses and multivariate logistic regression analyses were performed to determine the predictive factors associated with postoperative seizure outcomes. We identified the preoperative seizure frequency threshold by plotting a receiver operating characteristic curve. A Kaplan-Meier curve was constructed to illustrate the seizure-free survival rate of our cohort over time. 54 patients who remained seizure -free post-surgery were classified into the Engel class I, and the other 16 patients whose seizures relapsed were classified into Engel classes II–IV. Univariate and multivariate logistic regression analyses showed that the preoperative seizure frequency (X² = 16.069, P = 0.001), extent of resection (x² = 5.031, P = 0.025), IDH1 mutation (x² = 4.435, P = 0.035) and adjuvant chemotherapy of temozolomide (X² = 4.081, P = 0.043) were related to the postoperative short-term seizure outcome. The ROC curve indicated that the area under the curve for the preoperative seizure frequency test was 0.805 (95% confidence interval 0.690–0.920, p < 0.05), which corresponded to an optimal threshold of 2 preoperative seizures. The IDH1^WT status and adjuvant chemotherapy with temozolomide were related to a better post-operative seizure outcome. Within the first year after the surgical resection, seizures reoccurred among 16 patients (22.9%) with a mean time of 10.8 months. The preoperative seizure frequency, extent of resection, IDH1 status, and adjuvant chemotherapy with temozolomide were predictive factors of short-term postoperative seizure outcomes for supratentorial LGGs. To obtain a favorable seizure outcome, early intervention and removal are warranted. IDH1 mutation is the predictive biomarker of postoperative seizure outcomes. The adjuvant chemotherapy with temozolomide appears to be associated with better seizure outcomes, and it may be useful in helping to control the postoperative seizures.     

Cross-national disparities contribute to heterogeneity in patient outcomes following invasive monitoring: A hierarchical mixed-effects analysis

There is substantial variability in outcomes following invasive monitoring and surgical treatment of drug-resistant epilepsy (DRE). Patients with DRE are uniquely vulnerable to cross-national health care disparities, as their epilepsy is difficult to treat and requires extensive resources. In a large cross-national database of patients undergoing invasive monitoring for epilepsy surgery, we sought to evaluate the association between social, economic, and educational indicators of the country of treatment and patient outcomes following invasive monitoring. We performed a mixed-effects analysis of an individual patient database of 595 subjects enrolled in 33 studies encompassing 25 neurosurgical centers in 10 countries of invasive monitoring for epilepsy from 1996 to 2019. Upon preliminary univariate analysis, significant nation-level predictors of seizure outcome following either stereoelectroencephalography or subdural electrodes were hospital beds per 100,000 population, physician density, gross domestic product (GDP) growth, male and female educational attainment, and unemployment rate. On multivariate mixed-effects logistic regression, physician density (β = −0.5112, P<.00697) and GDP growth (β = 0.53822, P<.00404) were the only nation-level covariates of significance associated with seizure outcome. A higher physician density was associated with lesser seizure freedom rates, whereas higher GDP growth was associated with greater seizure freedom rates. Although patient-specific variables were the primary determinant of seizure outcomes, cross-national disparities also contribute to heterogeneities. Our findings highlight the importance of a systems-level dialogue to improve surgical outcomes for DRE patients.     

Betweenness centrality of intracranial electroencephalography networks and surgical epilepsy outcome

Objective

We sought to determine whether the presence or surgical removal of certain nodes in a connectivity network constructed from intracranial electroencephalography recordings determines postoperative seizure freedom in surgical epilepsy patients.

Correlation between scalp high-frequency oscillations and prognosis in patients with benign epilepsy of childhood with centrotemporal spikes

Aims

The study aimed to explore whether high-frequency oscillations (HFOs) can predict seizure risk and atypical manifestations of benign epilepsy of childhood with centrotemporal spikes (BECTS).

Methods

We recruited 60 patients and divided them into three groups: (1) seizure-free BECTS, (2) active typical BECTS, and (3) active atypical forms of BECTS. Electroencephalogram was used to record the number, location, average amplitude, and duration of spikes, and spike ripples were analyzed using time-frequency technology. Multivariable logistic regression analysis was used to investigate independent predictive factors for prognosis.

Results

The number of sleep spike ripples, rather than spikes, was an independent risk factor for the active period of the disease (odds ratio [OR] = 4.714, p = 0.003) and atypical forms of BECTS (OR = 1.455, p = 0.049); the optimal thresholds for the spike ripple rate were >0 (area under the curve [AUC] = 0.885, sensitivity = 96.15%, specificity = 73.33%) and >0.6/min (AUC = 0.936, sensitivity = 84.21%, specificity = 96.15%), respectively. Furthermore, in typical BECTS, the spike ripple rate showed significant negative correlations with time since the last seizure (ρ = −0.409, p = 0.009) and age (ρ = −0.379, p = 0.016), while the spike rate did not.

Conclusion

Spike ripple was a marker for distinguishing typical and atypical forms of BECTS and reflected the risk of seizure recurrence better than the spike alone. The present findings might assist clinicians in BECTS treatment.     

A predictive risk model for medical intractability in epilepsy

ObjectiveThis study aimed to investigate early predictors (6 months after diagnosis) of medical intractability in epilepsy.MethodsAll children < 12 years of age having two or more unprovoked seizures 24 h apart at Xinhua Hospital between 1992 and 2006 were included. Medical intractability was defined as failure, due to lack of seizure control, of more than 2 antiepileptic drugs at maximum tolerated doses, with an average of more than 1 seizure per month for 24 months and no more than 3 consecutive months of seizure freedom during this interval. Univariate and multivariate logistic regression models were performed to determine the risk factors for developing medical intractability. Receiver operating characteristic curve was applied to fit the best compounded predictive model.ResultsA total of 649 patients were identified, out of which 119 (18%) met the study definition of intractable epilepsy at 2 years after diagnosis, and the rate of intractable epilepsy in patients with idiopathic syndromes was 12%. Multivariate logistic regression analysis revealed that neurodevelopmental delay, symptomatic etiology, partial seizures, and more than 10 seizures before diagnosis were significant and independent risk factors for intractable epilepsy. The best model to predict medical intractability in epilepsy comprised neurological physical abnormality, age at onset of epilepsy under 1 year, more than 10 seizures before diagnosis, and partial epilepsy, and the area under receiver operating characteristic curve was 0.7797. This model also fitted best in patients with idiopathic syndromes.ConclusionA predictive model of medically intractable epilepsy composed of only four characteristics is established. This model is comparatively accurate and simple to apply clinically.     

Sudden unexpected death in epilepsy during cenobamate clinical development

Objective

We assessed mortality, sudden unexpected death in epilepsy (SUDEP), and standardized mortality ratio (SMR) among adults treated with cenobamate during the cenobamate clinical development program.

Methods

We retrospectively analyzed deaths among all adults with uncontrolled focal (focal to bilateral tonic–clonic [FBTC], focal impaired awareness, focal aware) or primary generalized tonic–clonic (PGTC) seizures who received ≥1 dose of adjunctive cenobamate in completed and ongoing phase 2 and 3 clinical studies. In patients with focal seizures from completed studies, median baseline seizure frequencies ranged from 2.8 to 11 seizures per 28 days and median epilepsy duration ranged from 20 to 24 years. Total person-years included all days that a patient received cenobamate during completed studies or up to June 1, 2022, for ongoing studies. All deaths were evaluated by two epileptologists. All-cause mortality and SUDEP rates were expressed per 1000 person-years.

Results

A total of 2132 patients (n = 2018 focal epilepsy; n = 114 idiopathic generalized epilepsy) were exposed to cenobamate for 5693 person-years. Approximately 60% of patients with focal seizures and all patients in the PGTC study had tonic–clonic seizures. A total of 23 deaths occurred (all in patients with focal epilepsy), for an all-cause mortality rate of 4.0 per 1000 person-years. Five cases of definite or probable SUDEP were identified, for a rate of .88 per 1000 person-years. Of the 23 overall deaths, 22 patients (96%) had FBTC seizures, and all 5 of the SUDEP patients had a history of FBTC seizures. The duration of exposure to cenobamate for patients with SUDEP ranged from 130 to 620 days. The SMR among cenobamate-treated patients in completed studies (5515 person-years of follow-up) was 1.32 (95% confidence interval [CI] .84–2.0), which was not significantly different from the general population.

Significance

These data suggest that effective long-term medical treatment with cenobamate may reduce excess mortality associated with epilepsy.     

Adjunctive cenobamate in highly active and ultra-refractory focal epilepsy: A “real-world” retrospective study

Objective

Recent clinical trials have shown that cenobamate substantially improves seizure control in focal-onset drug-resistant epilepsy (DRE). However, little is known about cenobamate's performance in highly active ( ≥ 20 seizures/month) and ultra-refractory focal epilepsy ( ≥ 6 failed epilepsy treatments, including antiseizure medications [ASMs], epilepsy surgery, and vagus nerve stimulation). Here, we studied cenobamate's efficacy and tolerability in a “real-world” severe DRE cohort.

Methods

We conducted a single-center retrospective analysis of consecutive adults treated with cenobamate between October 2020 and September 2022. All patients received cenobamate through an Early Access Program. Cenobamate retention, seizure outcomes, treatment-emergent adverse events, and adjustments to concomitant ASMs were analyzed.

Results

Fifty-seven patients received cenobamate for at least 3 months (median duration, 11 months). The median cenobamate dose was 250 mg/day (range 75–350 mg). Baseline demographics were consistent with highly active (median seizure frequency, 60/month) and ultra-refractory epilepsy (median previously failed ASMs, nine). Most (87.8%) had prior epilepsy surgery and/or vagus nerve stimulation. Six patients stopped cenobamate due to lack of efficacy and/or adverse events. One patient died from factors unrelated to cenobamate. Among patients who continued cenobamate, three achieved seizure freedom (5.3% of cohort), 24 had a 75%–99% reduction in seizures (42.1% of cohort), and 16 had a 50%–74% reduction (28.1% of cohort). Cenobamate led to abolition of focal to bilateral tonic–clonic seizures in 55.6% (20/36) of patients. Among treatment responders, 67.4% (29/43) were treated with cenobamate doses of ≥ 250 mg/day. Three-fourths of patients reported at least one side-effect, most commonly fatigue and somnolence. Adverse events most commonly emerged at cenobamate doses of ≥ 250 mg/day. Side-effects were partially manageable by reducing the overall ASM burden, most often clobazam, eslicarbazepine, and perampanel.

Significance

Patients with highly active and ultra-refractory focal epilepsy experienced meaningful seizure outcomes on cenobamate. Emergence of adverse events at doses above 250 mg/day may limit the potential for further improvements in seizure control at higher cenobamate doses.     

Temporal lobe gangliogliomas associated with chronic epilepsy: Long-term surgical outcomes

Objective

To review the clinical features and surgical outcome in patients with temporal lobe gangliogliomas associated with intractable chronic epilepsy.

Methods

The Rush University Surgical Epilepsy Database was queried to identify patients with chronic intractable epilepsy who underwent resection of temporal lobe gangliogliomas at Rush University Medical Center. Medical records were reviewed for age of seizure onset, delay to referral for surgery, seizure frequency and characteristics, pre-operative MRI results, extent of resection, pathological diagnosis, complications, length of follow-up, and seizure improvement.

Results

Fifteen patients were identified. Average duration between seizure onset and surgery was 14.3 years. Complex partial seizures were the most common presenting symptom. Detailed operative data was available for 11 patients – of these, 90.9% underwent complete resection of the amygdala and either partial or complete resection of the hippocampus, in addition to lesionectomy. Average follow-up was 10.4 years (range 1.6–27.5 years), with 14 patients improving to Engel's class I and one patient to Engel's class III. There were no recurrences, and permanent complications were noted in one patient.

Conclusions

Long-term follow-up of patients with temporal lobe gangliogliomas associated with chronic intractable epilepsy demonstrates excellent results in seizure improvement with surgery and increasingly low incidence of complications with improvements in microsurgical techniques.     

MEG abnormalities and mechanisms of surgical failure in neocortical epilepsy

Objective

Epilepsy surgery fails to achieve seizure freedom in 30%–40% of cases. It is not fully understood why some surgeries are unsuccessful. By comparing interictal magnetoencephalography (MEG) band power from patient data to normative maps, which describe healthy spatial and population variability, we identify patient-specific abnormalities relating to surgical failure. We propose three mechanisms contributing to poor surgical outcome: (1) not resecting the epileptogenic abnormalities (mislocalization), (2) failing to remove all epileptogenic abnormalities (partial resection), and (3) insufficiently impacting the overall cortical abnormality. Herein we develop markers of these mechanisms, validating them against patient outcomes.

Methods

Resting-state MEG recordings were acquired for 70 healthy controls and 32 patients with refractory neocortical epilepsy. Relative band-power spatial maps were computed using source-localized recordings. Patient and region-specific band-power abnormalities were estimated as the maximum absolute z-score across five frequency bands using healthy data as a baseline. Resected regions were identified using postoperative magnetic resonance imaging (MRI). We hypothesized that our mechanistically interpretable markers would discriminate patients with and without postoperative seizure freedom.

Results

Our markers discriminated surgical outcome groups (abnormalities not targeted: area under the curve [AUC] = 0.80, p = .003; partial resection of epileptogenic zone: AUC = 0.68, p = .053; and insufficient cortical abnormality impact: AUC = 0.64, p = .096). Furthermore, 95% of those patients who were not seizure-free had markers of surgical failure for at least one of the three proposed mechanisms. In contrast, of those patients without markers for any mechanism, 80% were ultimately seizure-free.

Significance

The mapping of abnormalities across the brain is important for a wide range of neurological conditions. Here we have demonstrated that interictal MEG band-power mapping has merit for the localization of pathology and improving our mechanistic understanding of epilepsy. Our markers for mechanisms of surgical failure could be used in the future to construct predictive models of surgical outcome, aiding clinical teams during patient pre-surgical evaluations.     

Persons with onchocerciasis‐associated epilepsy and nodding seizures have a more severe form of epilepsy with more cognitive impairment and higher levels of Onchocerca volvulus infection

Aims. Following previous reports of very high epilepsy prevalence in the onchocerciasis‐endemic villages in Maridi County, South Sudan, a study was conducted to investigate the association between the level of Onchocerca volvulus infection, epilepsy, and related outcomes. Methods. In December 2018, persons with epilepsy (PWE) were recruited from villages where an epilepsy prevalence of 4.4% (range: 3.5–11.9%) was documented. We enrolled 318 participants from whom two skin snips were taken for microscopic detection of O. volvulus microfilariae (mf). Seizure history was obtained for all PWE and their degree of disability assessed using the modified Rankin scale. Results. Almost all (84.9%) PWE had detectable mf in their skin snips. Onchocerciasis‐infected PWE experienced nodding seizures more often than uninfected PWE (p=0.034). Moreover, persons with nodding seizures had more frequent seizures (p<0.001) and higher disability scores (p<0.001), and were more often cognitively impaired and younger at the time of their first epileptic seizure (nine years vs 12 years, p<0.001) compared to PWE without nodding seizures. Based on multivariate models, nodding seizures were associated with higher mf densities (aOR: 1.022; 95% CI: 1.005–1.041). Epilepsy onset at a younger age was associated with a worse outcome. Higher frequency of seizures, longer duration of epilepsy and younger age were associated with increased disability. Regular antiepileptic drug use was associated with better cognitive and disability outcomes. Conclusion. PWE with nodding seizures have a more severe form of onchocerciasis‐associated epilepsy, with earlier seizure onset and higher levels of O. volvulus infection. Younger PWE were prone to worse epilepsy outcomes, which would be prevented with regular antiepileptic treatment.