International League Against Epilepsy Class Research Articles

Assessing the Relationship between Surgical Timing and Postoperative Seizure Outcomes in Cavernoma-Related Epilepsy: A Single-Institution Retrospective Analysis of 63 Patients with a Review of the Literature.

Background: Patients with supratentorial cavernous malformations (SCMs) commonly present with seizures. First-line treatments for cavernoma-related epilepsy (CRE) include conservative management (antiepileptic drugs (AEDs)) and surgery. We compared seizure outcomes of CRE patients after early (≤6 months) vs. delayed (>6 months) surgery. Methods: We compared outcomes of CRE patients with SCMs surgically treated at our large-volume cerebrovascular center (1 January 2010-31 July 2020). Patients with 1 sporadic SCM and ≥1-year follow-up were included. Primary outcomes were International League Against Epilepsy (ILAE) class 1 seizure freedom and AED independence. Results: Of 63 CRE patients (26 women, 37 men; mean ± SD age, 36.1 ± 14.6 years), 48 (76%) vs. 15 (24%) underwent early (mean ± SD, 2.1 ± 1.7 months) vs. delayed (mean ± SD, 6.2 ± 7.1 years) surgery. Most (32 (67%)) with early surgery presented after 1 seizure; all with delayed surgery had ≥2 seizures. Seven (47%) with delayed surgery had drug-resistant epilepsy. At follow-up (mean ± SD, 5.4 ± 3.3 years), CRE patients with early surgery were more likely to have ILAE class 1 seizure freedom and AED independence than those with delayed surgery (92% (44/48) vs. 53% (8/15), p = 0.002; and 65% (31/48) vs. 33% (5/15), p = 0.03, respectively). Conclusions: Early CRE surgery demonstrated better seizure outcomes than delayed surgery. Multicenter prospective studies are needed to validate these findings.

Regulation of Keap1-Nrf2 axis in temporal lobe epilepsy-hippocampal sclerosis patients may limit the seizure outcomes.

Accumulation of reactive oxygen species (ROS) exacerbates neuronal loss during seizure-induced excitotoxicity. Keap1 (Kelch-like ECH-associated protein1)-nuclear factor erythroid 2-related factor 2 (Nrf2) axis is one of the known active antioxidant response mechanisms. Our study focused on finding the factors influencing Keap1-Nrf2 axis regulation in temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) patients. Based on post-surgical follow-up data, patient samples (n = 26) were categorized into class 1 (completely seizure-free) and class 2 (only focal-aware seizures/auras), as suggested by International League Against Epilepsy (ILAE). For molecular analyses, double immunofluorescence assay and Western blot analysis were employed. A significant decrease in expression of Nrf2 (p < 0.005), HO-1; p < 0.02) and NADPH Quinone oxidoreductase1 (NQO1; p < 0.02) was observed in ILAE class 2. Keap1 (p < 0.02) and histone methyltransferases (HMTs) like SetD7 (SET7/9; SET domain-containing 7 histone lysine methyltransferase) (p < 0.009) and enhancer of zeste homolog 2 (EZH2; p < 0.02) and methylated histones viz., H3K4me1 (p < 0.001), H3K9me3 (p < 0.001), and H3K27me3 (p < 0.001) was upregulated in ILAE class 2. Nrf2-interacting proteins viz., p21 (p < 0.001) and heat shock protein 90 (HSP90; p < 0.03) increased in class 1 compared to class 2 patients. Upregulation of HMTs and methylated histones can limit phase II antioxidant enzyme expression. Also, HSP90 and p21 that interfere with Keap1-Nrf2 interaction could contribute to a marginal increase in HO-1 and NQO1 expression despite histone methylation and Keap1. Based on our findings, we conclude that TLE-HS patients prone to seizure recurrence were found to have dysfunctional antioxidant response, in part, owing to Keap1-Nrf2 axis. The significance of Keap1-Nrf2 signaling mechanism in generation of phase II antioxidant response. Keap1-Nrf2 controls antioxidant response through regulation of phase II antioxidant enzymes like HO-1 (heme oxygenase-1), NQO1 (NADPH-Quinone Oxidoreductase1), and glutathione S-transferase (GST). Release of Nrf2 from negative regulation by Keap1 causes its translocation into nucleus, forming a complex with cAMP response-element binding protein (CBP) and small Maf proteins (sMaf). This complex subsequently binds antioxidant response element (ARE) and elicits and antioxidant response involving expression of phase II antioxidant enzymes. Reactive oxygen species (ROS) modify Cysteine 151 residue, p62 (sequsetosome-1), and interacts with Nrf2- binding site in Keap 1. p21 and HSP90 prevent Nrf2 interaction with Keap1. At transcriptional level, histone methyltransferases like EZH2 (enhancer of zeste homologue2), and SetD7 (SET7/9; SET domain-containing 7 histone lysine methyltransferase) and corresponding histone targets viz., H3K27me3, H3K9me3, and H3K4me1 influence Nrf2 and Keap1 expression respectively.

Dopamine and Glutamate Crosstalk Worsen the Seizure Outcome in TLE-HS Patients.

Temporal lobe epilepsy (TLE), accompanied by hippocampal sclerosis (HS), is the most common form of drug-resistant epilepsy (DRE). Nearly 20% of the patients showed seizure recurrence even after surgery, and the reasons are yet to be understood. Dysregulation of neurotransmitters is evident during seizures, which can induce excitotoxicity. The present study focused on understanding the molecular changes associated with Dopamine (DA) and glutamate signaling and their possible impact on the persistence of excitotoxicity and seizure recurrence in patients with drug-resistant TLE-HS who underwent surgery. According to the International League against Epilepsy (ILAE) suggested classification for seizure outcomes, the patients (n = 26) were classified as class 1 (no seizures) and class 2 (persistent seizures) using the latest post-surgery follow-up data to understand the prevalent molecular changes in seizure-free and seizure-recurrence patient groups. Our study uses thioflavin T assay, western blot analysis, immunofluorescence assays, and fluorescence resonance energy transfer (FRET) assays. We have observed a substantial increase in the DA and glutamate receptors that promote excitotoxicity. Patients who had seizure recurrence showed a significant increase in (pNR2B, p < 0.009; and pGluR1, p < 0.01), protein phosphatase1γ (PP1γ; p < 0.009), protein kinase A (PKAc; p < 0.001) and dopamine-cAMP regulated phospho protein32 (pDARPP32T34; p < 0.009) which are critical for long-term potentiation (LTP), excitotoxicity compared to seizure-free patients and controls. A significant increase in D1R downstream kinases like PKA (p < 0.001), pCAMKII (p < 0.009), and Fyn (p < 0.001) was observed in patient samples compared to controls. Anti-epileptic DA receptor D2R was found to be decreased in ILAE class 2 (p < 0.02) compared to class 1. Since upregulation of DA and glutamate signaling supports LTP and excitotoxicity, we believe it could impact seizure recurrence. Further studies about the impact of DA and glutamate signaling on the distribution of PP1γ at postsynaptic density and synaptic strength could help us understand the seizure microenvironment in patients. Dopamine, Glutamate signal crosstalk. Diagram representing the PP1γ regulation by NMDAR negative feedback inhibition signaling (green circle-left) and D1R signal (red circle-middle) domination over PP1γ though increased PKA, pDARPP32T34, and supports pGluR1, pNR2B in seizure recurrent patients. D1R-D2R hetero dimer activation (red circle-right) increases cellular Ca2+ and pCAMKIIα activation. All these events lead to calcium overload in HS patients and excitotoxicity, particularly in patients experiencing recurrent seizures.

Temporal lobe epilepsy surgery: Piriform cortex resection impacts seizure control in the long-term.

ObjectiveRecently, we showed that resection of at least 27% of the temporal part of piriform cortex (PiC) strongly correlated with seizure freedom 1 year following selective amygdalo‐hippocampectomy (tsSAHE) in patients with mesial temporal lobe epilepsy (mTLE). However, the impact of PiC resection on long‐term seizure outcome following tsSAHE is currently unknown. The aim of this study was to evaluate the impact of PiC resection on long‐term seizure outcome in patients with mTLE treated with tsSAHE.MethodsBetween 2012 and 2017, 64 patients were included in the retrospective analysis. Long‐term follow‐up (FU) was defined as at least 2 years postoperatively. Seizure outcome was assessed according to the International League against Epilepsy (ILAE). The resected proportions of hippocampus, amygdala, and PiC were volumetrically assessed.ResultsThe mean FU duration was 3.75 ± 1.61 years. Patients with ILAE class 1 revealed a significantly larger median proportion of resected PiC compared to patients with ILAE class 2–6 [46% (IQR 31–57) vs. 16% (IQR 6–38), p = 0.001]. Resected proportions of hippocampus and amygdala did not significantly differ for these groups. Among those patients with at least 27% resected proportion of PiC, there were significantly more patients with seizure freedom compared to the patients with <27% resected proportion of PiC (83% vs. 39%, p = 0.0007).ConclusionsOur results show a strong impact of the extent of PiC resection on long‐term seizure outcome following tsSAHE in mTLE. The authors suggest the PiC to constitute a key target volume in tsSAHE to achieve seizure freedom in the long term.

Piriform Cortex Ablation Volume Is Associated With Seizure Outcome in Mesial Temporal Lobe Epilepsy

Growing evidence suggests that piriform cortex resection during anterior temporal lobectomy is important for achieving good seizure outcome in mesial temporal lobe epilepsy (mTLE). However, the relationship between seizure outcome and piriform cortex ablation during MR-guided laser interstitial thermal therapy (MRgLITT) remains unclear. To determine whether ablation of piriform cortex was associated with seizure outcome in patients with mTLE undergoing MRgLITT. We performed preablation and postablation volumetric analyses of hippocampus, amygdala, piriform cortex, and ablation volumes in patients with mTLE who underwent MRgLITT at our institution from 2014 to 2019. Thirty nine patients with mTLE were analyzed. In univariate logistic regression, percent piriform cortex ablation was associated with International League Against Epilepsy (ILAE) class 1 at 6 months (odds ratio [OR] 1.051, 95% CI [1.001-1.117], P = .045), whereas ablation volume, percent amygdala ablation, and percent hippocampus ablation were not ( P > .05). At 1 year, ablation volume was associated with ILAE class 1 (OR 1.608, 95% CI [1.071-2.571], P = .021) while percent piriform cortex ablation became a trend (OR 1.050, 95% CI [0.994-1.109], P = .054), and both percent hippocampus ablation and percent amygdala ablation were not significantly associated with ILAE class 1 ( P > .05). In multivariable logistic regression, only percent piriform cortex ablation was a significant predictor of seizure freedom at 6 months (OR 1.085, 95% CI [1.012-1.193], P = .019) and at 1 year (OR 1.074, 95% CI [1.003-1.178], P = .041). Piriform cortex ablation volume is associated with seizure outcome in patients with mTLE undergoing MRgLITT. The piriform cortex should be considered a high yield ablation target to achieve good seizure outcome.

Predictors of postoperative long-term seizure outcome in pediatric patients with focal cortical dysplasia type II at a German tertiary epilepsy center.

Focal cortical dysplasia (FCD) is a common cause of early-onset intractable epilepsy, and resection is a highly sufficient treatment option. In this study, the authors aimed to provide a retrospective analysis of pre- and postoperative factors and their impact on postoperative long-term seizure outcome. The postoperative seizure outcomes of 50 patients with a mean age of 8 ± 4.49 years and histologically proven FCD type II were retrospectively analyzed. Furthermore, pre- and postoperative predictors of long-term seizure freedom were assessed. The seizure outcome was evaluated based on the International League Against Epilepsy (ILAE) classification. Complete resection of FCD according to MRI criteria was achieved in 74% (n = 37) of patients. ILAE class 1 at the last follow-up was achieved in 76% (n = 38) of patients. A reduction of antiepileptic drugs (AEDs) to monotherapy or complete withdrawal was achieved in 60% (n = 30) of patients. Twelve patients (24%) had a late seizure recurrence, 50% (n = 6) of which occurred after reduction of AEDs. A lower number of AEDs prior to surgery significantly predicted a favorable seizure outcome (p = 0.013, HR 7.63). Furthermore, younger age at the time of surgery, shorter duration of epilepsy prior to surgery, and complete resection were positive predictors for long-term seizure freedom. The duration of epilepsy, completeness of resection, number of AEDs prior to surgery, and younger age at the time of surgery served as predictors of postoperative long-term seizure outcome, and, as such, may improve clinical practice when selecting and counseling appropriate candidates for resective epilepsy surgery. The study results also underscored that epilepsy surgery should be considered early in the disease course of pediatric patients with FCD type II.

Lesionectomy for cerebral sparganosis and concomitant epilepsy: A case series of 15 patients

ObjectiveTo report the clinical characteristics and surgical outcomes of patients with cerebral sparganosis and concomitant epilepsy. MethodsWe retrospectively collected the clinical data of all patients with cerebral sparganosis and concomitant epilepsy who underwent lesionectomy as treatment at Xiangya Hospital, Central South University between January 2015 and August 2019. Seizure outcomes were evaluated according to the International League Against Epilepsy (ILAE) classification. ILAE classes 1 and 2 were defined as favorable seizure outcomes, whereas ILAE classes 3–6 were defined as unfavorable seizure outcomes. ResultsFifteen patients with cerebral sparganosis and concomitant epilepsy who underwent lesionectomy as treatment met the inclusion criteria. Live worms were surgical removed in 80 % of patients. With a mean follow-up of 2.4 ± 1.1 years, 66.7 % of patients demonstrated favorable seizure outcomes, with improvement of symptoms other than seizures. Longer seizure duration associated with unfavorable seizure outcomes. ConclusionsLesionectomy is an effective treatment for patients with cerebral sparganosis and concomitant epilepsy. Early surgical treatment may offer more benefits to such patients.

Seizure outcome in temporal glioblastoma surgery: lobectomy as a supratotal resection regime outclasses conventional gross-total resection

IntroductionThe postoperative seizure freedom represents an important secondary outcome measure in glioblastoma surgery. Recently, supra-total glioblastoma resection in terms of anterior temporal lobectomy (ATL) has gained growing attention with regard to superior long-term disease control for temporal-located glioblastoma compared to conventional gross-total resections (GTR). However, the impact of ATL on seizure outcome in these patients is unknown. We therefore analyzed ATL and GTR as differing extents of resection in regard of postoperative seizure control in patients with temporal glioblastoma and preoperative symptomatic seizures.MethodsBetween 2012 and 2018, 33 patients with preoperative seizures underwent GTR or ATL for temporal glioblastoma at the authors’ institution. Seizure outcome was assessed postoperatively and 6 months after tumor resection according to the International League Against Epilepsy (ILAE) classification and stratified into favorable (ILAE class 1) versus unfavorable (ILAE class 2–6).ResultsOverall, 23 out of 33 patients (70%) with preoperative seizures achieved favorable seizure outcome following resection of temporal located glioblastoma. For the ATL group, postoperative seizure freedom was present in 13 out of 13 patients (100%). In comparison, respective rates for the GTR group were 10 out of 20 patients (50%) (p = 0.002; OR 27; 95% CI 1.4–515.9).ConclusionsATL in terms of a supra-total resection strategy was associated with superior favorable seizure outcome following temporal glioblastoma resection compared to GTR. Regarding above mentioned survival benefit following ATL compared to GTR, ATL as an aggressive supra-total resection regime might constitute the surgical modality of choice for temporal-located glioblastoma.

Resection of piriform cortex predicts seizure freedom in temporal lobe epilepsy.

ObjectiveTranssylvian selective amygdalo‐hippocampectomy (tsSAHE) represents a generally recognized surgical procedure for drug‐resistant mesial temporal lobe epilepsy (mTLE). Although postoperative seizure freedom can be achieved in about 70% of tsSAHE, there is a considerable amount of patients with persisting postoperative seizures. This might partly be explained by differing extents of resection of various tsSAHE target volumes. In this study we analyzed the resected proportions of hippocampus, amygdala as well as piriform cortex in regard of postoperative seizure outcome.MethodsBetween 2012 and 2017, 82 of 103 patients with mTLE who underwent tsSAHE at the authors’ institution were included in the analysis. Resected proportions of hippocampus, amygdala and temporal piriform cortex as target structures of tsSAHE were volumetrically assessed and stratified according to favorable (International League Against Epilepsy (ILAE) class 1) and unfavorable (ILAE class 2–6) seizure outcome.ResultsPatients with favorable seizure outcome revealed a significantly larger proportion of resected temporal piriform cortex volumes compared to patients with unfavorable seizure outcome (median resected proportional volumes were 51% (IQR 42–61) versus (vs.) 13 (IQR 11–18), P = 0.0001). Resected proportions of hippocampus and amygdala did not significantly differ for these groups (hippocampus: 81% (IQR 73–88) vs. 80% (IQR 74–92) (P = 0.7); amygdala: 100% (IQR 100–100) vs. 100% (IQR 100–100) (P = 0.7)).InterpretationThese results strongly suggest temporal piriform cortex to constitute a key target resection volume to achieve seizure freedom following tsSAHE.

Predictive value of electrically induced seizures for postsurgical seizure outcome

ObjectiveTo determine whether semiological similarity of electrically induced seizures (EIS) and spontaneously occurring habitual seizures (SHS) is associated with postsurgical seizure outcome in patients undergoing invasive video-EEG monitoring (VEM) before resective epilepsy surgery. MethodsData of patients undergoing invasive VEM were retrospectively reviewed and included if at least one EIS and SHS during VEM occurred and the brain region in which EIS were elicited was resected. Seizure outcome was evaluated at three follow-up (FU) visits after surgery (1, 2 years and last available FU) according to the classification by Engel and the International League Against Epilepsy (ILAE). The level of semiological similarity of EIS and SHS was rated blinded to the surgical outcome. Statistics were done using Fisher’s exact test and a mixed linear-logistic regression model. Results65 patients were included. Postsurgical seizure freedom was achieved in 51% (ILAE class 1) and 58% (Engel class I) at last FU (median 36 months). Patients with identical EIS and SHS displayed significantly better postsurgical seizure outcomes (ILAE class 1 at last FU: 76% vs. 31%, p < 0.001; Engel class I: 83% vs. 39%, p < 0.001). ConclusionEIS are useful to confirm the location of the epileptogenic zone. A high level of similarity between EIS and SHS is associated with a favorable postsurgical seizure outcome. SignificanceEIS may be used as an additional predictor of postsurgical outcome when counselling patients to proceed to resective epilepsy surgery.

Stereotactic radiofrequency thermocoagulation and resective surgery for patients with hypothalamic hamartoma.

In this study, the authors compared the efficacy and safety of stereotactic radiofrequency thermocoagulation (SRT) and resective surgery (RS) for patients with hypothalamic hamartoma (HH). The authors included all patients with HHs who were treated by SRT or hamartoma resection. Seizure outcomes were assessed by blinded observers according to the International League Against Epilepsy (ILAE) classification. Favorable seizure outcomes were defined as ILAE classes 1 and 2, and unfavorable seizure outcomes were defined as ILAE classes 3-6. Twenty-nine patients who underwent SRT or RS met the inclusion criteria; 3 were excluded because they had completed less than 12 months of follow-up. Most of the patients (20 of 26; 76.9%) had small HHs (i.e., maximum HH diameter less than 20 mm). The patients' follow-up time ranged from 12 to 66 months (median 60 months). At the last follow-up, favorable outcomes were observed in 9 patients (69.2%) who had undergone SRT and 10 patients (76.9%) who had undergone HH resection. No significant difference was found in seizure outcomes between SRT and RS recipients. Patients with giant HHs were more likely than patients with smaller tumors to undergo multiple resections (p = 0.043, univariate logistic regression; significant). However, no significant difference was found between SRT and RS recipients in terms of the number of procedures per patient. SRT recipients had fewer and less-severe adverse events than RS recipients. For patients with small HHs, SRT provides similar seizure outcomes to RS with a less invasive procedure. Patients who underwent SRT experienced fewer and lighter adverse effects than patients who had RS. Patients with giant HHs were more likely to undergo multiple HH resections.

Efficacy and Safety of Epilepsy Surgery for Older Adult Patients with Refractory Epilepsy.

PurposeThe population of elderly patients with epilepsy has been growing rapidly and the chances of referring older patients with refractory epilepsy for surgical options could be increasing. In general, epilepsy surgery at higher ages has been less likely to be performed, because little is known regarding the risks and benefits in elderly patients. We, therefore, investigated surgical outcomes and comorbidities in a population ≥50 years old who underwent epilepsy surgery.MethodsPatients ≥50 years old who underwent epilepsy surgery were identified from the database of our epilepsy center for the period from 2009 to 2017. Surgical complications and seizure outcome were reviewed, and seizure outcomes were evaluated using the International League Against Epilepsy (ILAE) surgery outcome scale.ResultsThe mean age of 32 patients at the time of surgery was 56.1±5.1 years. The mean duration of epilepsy was 23.4±18.5 years and mean follow-up was 2.7±2.0 years. As of the most recent visit, 56.3% of patients remained completely seizure-free (ILAE Class I). The surgery-related complication rate was 11.5%, comprising permanent deficits in 3.8% and transient deficits in 7.7%.ConclusionThese results suggest that epilepsy surgery may represent a valuable approach in selected adult patients.

Resective surgery for drug-resistant posttraumatic epilepsy: predictors of seizure outcome.

The object of this study was to evaluate surgical outcomes and prognosis factors in patients with drug-resistant posttraumatic epilepsy (PTE) who had undergone resective surgery. The authors retrospectively reviewed the records of all patients with drug-resistant PTE who had undergone resective surgery at Sanbo Brain Hospital, Capital Medical University, in the period from January 2008 to December 2016. All patients had a follow-up period of at least 2 years. Seizure outcomes were evaluated according to the International League Against Epilepsy (ILAE) classification. Patients in ILAE classes 1 and 2 during the last 2 years of follow-up were classified as having a favorable outcome; patients in all other classes were considered to have an unfavorable outcome. Univariate analysis and a multivariate logistic regression model in a backward fashion were used to identify the potential predictors of seizure outcomes. Among 90 patients with a follow-up of 2-10 years (mean ± standard deviation, 5.79 ± 2.84 years), 70% (63 patients) were seizure free, of whom 68.9% (62 patients) had an ILAE class 1 outcome and 1.1% (1 patient) had an ILAE class 2 outcome. Permanent neurological deficits were observed in 10 patients (11.1%). Univariate and multivariate analyses revealed that only the duration of seizures ≤ 8 years was an independent predictor of a favorable seizure outcome (OR 0.34, 95% CI 0.13-0.92). Resective surgery is an effective treatment for patients with drug-resistant PTE with an acceptable incidence of complications. The information on prognosis factors suggests that early surgery may offer more benefits to patients with drug-resistant PTE.

Navigation-assisted trans-inferotemporal cortex selective amygdalohippocampectomy for mesial temporal lobe epilepsy; preserving the temporal stem

Objective: Selective amygdalohippocampectomy (SAH) can be used to obtain satisfactory seizure control in patients with mesial temporal lobe epilepsy (MTLE). Several SAH procedures have been reported to achieve satisfactory outcomes for seizure control, but none yield fully satisfactory outcomes for memory function. We hypothesized that preserving the temporal stem might play an important role. To preserve the temporal stem, we developed a minimally invasive surgical procedure, ‘neuronavigation-assisted trans-inferotemporal cortex SAH’ (TITC-SAH).Methods: TITC-SAH was performed in 23 patients with MTLE (MTLE on the language-non-dominant hemisphere, n = 11). The inferior horn of the lateral ventricle was approached via the inferior or middle temporal gyrus along the inferior temporal sulcus under neuronavigation guidance. The hippocampus was dissected in a subpial manner and resected en bloc together with the parahippocampal gyrus. Seizure control at one year and memory function at 6 months postoperatively were evaluated.Results: One year after TITC-SAH, 20 of the 23 patients were seizure-free (ILAE class 1), 2 were class 2, and 1 was class 3. Verbal memory improved significantly in 13 patients with a diagnosis of hippocampal sclerosis, for whom WMS-R scores were available both pre- and post-operatively. Improvements were seen regardless of whether the SAH was on the language-dominant or non-dominant hemisphere. No major complication was observed.Conclusion: Navigation-assisted TITC-SAH performed for MTLE offers a simple, minimally invasive procedure that appears to yield excellent outcomes in terms of seizure control and preservation of memory function, because this procedure does not damage the temporal stem. TITC-SAH should be one of the feasible surgical procedures for MTLE.Abbreviations: SAH: Amygdalohippocampectomy; MTLE: Mesial temporal lobe epilepsy (MTLE); TITC-SAH: Ttrans-inferotemporal cortex SAH; ILAE: International League Against Epilepsy (ILAE); MRI: Magnetic resonance imaging; EEG: Electroencephalography (EEG); FDG-PET: 8F-fluorodeoxyglucose (FDG)-positron emission tomography; ECoG: Electrocorticography; MEG: Magnetoencephalography; IMZ-SPECT: N-isopropyl-p(123I)-iodoamphetamine single photon emission computed tomography; WMS-R: Wechsler Memory Scale-Revised.

Cost-effectiveness analysis of epilepsy surgery in a controlled cohort of adult patients with intractable partial epilepsy: A 5-year follow-up study.

Despite its well-known effectiveness, the cost-effectiveness of epilepsy surgery has never been demonstrated in France. We compared cost-effectiveness between resective surgery and medical therapy in a controlled cohort of adult patients with partial intractable epilepsy. A prospective cohort of adult patients with surgically remediable and medically intractable partial epilepsy was followed over 5 years in the 15 French centers. Effectiveness was defined as 1 year without a seizure, based on the International League Against Epilepsy (ILAE) classification. Clinical outcomes and direct costs were compared between surgical and medical groups. Long-term direct costs and effectiveness were extrapolated over the patients' lifetimes with a Monte-Carlo simulation using a Markov model, and an incremental cost-effectiveness ratio (ICER) was computed. Indirect costs were also evaluated. Among the 289 enrolled surgery candidates, 207 were operable-119 in the surgical group and 88 in the medical group-65 were not operable and not analyzed here, 7 were finally not eligible, and 10 were not followed. The proportion of patients completely seizure-free during the last 12 months (ILAE class 1) was 69.0% in the operated group and 12.3% in the medical group during the second year (p < 0.001), and it was respectively 76.8% and 21% during the fifth year (p < 0.001). Direct costs became significantly lower in the surgical group the third year after surgery, as a result of less antiepileptic drug use. The value of the discounted ICER was 10,406 (95% confidence interval [CI] 10,182-10,634) at 2 years and 2,630 (CI 95% 2,549-2,713) at 5 years. Surgery became cost-effective between 9 and 10 years after surgery, and even earlier if indirect costs were taken into account as well. Our study suggests that in addition to being safe and effective, resective surgery of epilepsy is cost-effective in the medium term. It should therefore be considered earlier in the development of epilepsy.

Long-term approach to patients with postsurgical seizures.

The main purpose of the study was to analyze the long-term outcomes and therapeutic approaches for patients with seizures within the first year after surgery. The secondary aim of the study was to evaluate the relationship between 1-year outcome and long-term outcome and choice of therapy. Our study was a retrospective investigation of the long-term outcomes of 95 patients (33.5% of all surgically treated patients) with seizure recurrence in the first year after surgery. The patients had follow-up visits for >5 years. At the 5-year follow-up visit (FU5), 28 (29.5%) of the 95 patients were completely seizure-free (International League Against Epilepsy (ILAE) class 1), 17 (17.9%) had auras only (ILAE class 2), and 21 (22.1%) were unimproved (ILAE classes 5 and 6). Statistically significant factors for these long-term outcomes were the focus localization of the epilepsy, preoperative MRI findings, and postoperative follow-up results in the first year. The patients with <3 seizure days in the first postoperative year (ILAE 3) represented 53.6% of the seizure-free patients at FU5; the patients with auras in the first year constituted 64.7% of the patients with only auras at FU5; and the patients unimproved in the first year represented 76.2% of the unimproved patients at FU5. Postoperative outcome depends to a certain extent on the outcome achieved in the first postoperative year. More than one third of the patients with postoperative seizures reached a long-term seizure-free outcome, and more than half of them did not experience disabling seizures in the last outcome year. The most therapeutic options were used in patients who were minimally influenced by the operation; the majority of patients with considerable improvement because of the operation do not use any other add-on antiepileptic drugs or other kinds of therapy.

Long-term outcomes of resective epilepsy surgery after invasive presurgical evaluation in children with tuberous sclerosis complex and bilateral multiple lesions.

Tuberous sclerosis complex (TSC) with medically refractory epilepsy is characterized by multifocal brain abnormalities, traditionally indicating poor surgical candidacy. This single-center, retrospective study appraised seizurerelated, neuropsychological, and other outcomes of resective surgery in TSC patients with medically refractory epilepsy, and analyzed predictors for these outcomes. Patients with multilesional TSC who underwent epilepsy surgery between 2007 and 2012 were identified from an electronic database. All patients underwent multimodality noninvasive and subsequent invasive evaluation. Seizure outcomes were classified using the International League Against Epilepsy (ILAE) scale. The primary outcome measure was complete seizure remission (ILAE Class 1). Secondary outcome measures included 50% responder rate, change in full-scale IQ, electroencephalography improvement, and reduction in antiepileptic drug (AED) burden. A total of 37 patients with TSC underwent resective surgery during the study period. After a mean follow-up of 5.68 ± 3.67 years, 56.8% achieved complete seizure freedom (ILAE Class 1) and 86.5% had ILAE Class 4 outcomes or better. The full-scale IQ on follow-up was significantly higher in patients with ILAE Class 1 outcome (66.70 ± 12.36) compared with those with ILAE Class 2 or worse outcomes (56.00 ± 1.41, p = 0.025). In 62.5% of the patients with ILAE Class 2 or worse outcomes, the number of AEDs were found to be significantly reduced (p = 0.004). This study substantiates the evidence for efficacy of resective epilepsy surgery in patients with bilateral multilesional TSC. More than half of the patients were completely seizure free. Additionally, a high proportion achieved clinically meaningful reduction in seizure burden and the number of AEDs.

Surgical management and long-term outcome of pediatric patients with different subtypes of epilepsy associated with cerebral cavernous malformations

Sufficient data on surgical treatment and seizure outcome of pediatric patients with different types of epilepsy, especially drug-resistant epilepsy and associated cerebral cavernous malformations, are scarce. The aim of this study was to carefully evaluate seizure outcome using the International League Against Epilepsy (ILAE) classification with regard to the presurgical symptom duration. Fifty-one pediatric patients younger than 19 years with cerebral cavernous malformations of all CNS localizations have been surgically treated at the authors' institution. Twenty-two patients with seizures or epilepsy who harbored cortically located supratentorial cerebral cavernous malformations underwent surgical treatment and were retrospectively analyzed. More extensive resections were used in 82% of all patients with epilepsy symptoms for longer than 2 years. Eighty-two percent of patients with symptom duration shorter than 2 years underwent circumscribed lesionectomy including the surrounding hemosiderotic rim. The overall rate of mild permanent, unanticipated postoperative deficits was 4.5%; the rate of anticipated neurological deficits was 9%. The mean follow-up was longer than 117 months in all groups. Seizure outcome was excellent in the group with symptom duration shorter than 2 years (100% ILAE Class 1). Seizure outcome was significantly worse in the group with longer symptom duration (p = 0.02). Seven patients were seizure free after surgery. Seizure outcome was stable over the years. Since seizure outcome is worse with longer seizure duration, early surgery and, if needed, interdisciplinary intervention, is recommended. Even in cases of multiple cerebral cavernous malformations and epilepsy, surgery should be considered.

Vagus nerve stimulation for medically refractory absence epilepsy

PurposeA proportion of patients with childhood and juvenile absence epilepsies (CAE, JAE) are likely to be classified as medically refractory. In view of evidence gap for the treatment of such patients, this series is reported to generate estimate for efficacy of vagus nerve stimulation (VNS) in this patient population. MethodsPatients were identified by a chart review of all VNS recipients between January 1, 2006 and December 31, 2011. The diagnosis of CAE and JAE was based on conventional criteria. Details of demography, epilepsy phenomenology, management and outcomes were extracted. The outcome measures included reduction in daily seizure frequency measured as a percentage of pre-VNS seizure frequency and classified on International League Against Epilepsy (ILAE) outcome scale. ResultsNine patients (7 CAE, 2 JAE) with a mean age of seizure onset of 5.4 years (±3.9) were identified. Mean duration of epilepsy prior to VNS implant was found to be 3.9 years (±1.4). These patients had failed a median of 5 anti-epileptic drugs before being referred for consideration of surgical treatment. After a mean follow-up of 33.9 months (±25.5, minimum 4 months), 1 patient attained complete seizure freedom (ILAE class 1), 6 had ILAE class 4 and 2 had ILAE class 5 outcomes, respectively. Mean reduction in daily seizure frequency was found to be 53.5±60.3% (1-sided p-value for paired t-test=0.04), with a 50% responder rate of 55.6%. ConclusionVNS may be considered as a therapeutic option in patients with medically refractory absence epilepsy.

Outcome of frontal lobe epilepsy surgery

There is still controversy in deciding which patients with frontal lobe epilepsy (FLE) should undergo resective surgery, even though it is a well-established therapy. The aim of this study is to define multiple outcome measures and determine whether there are certain subpopulations of preferred surgical candidates that have a more favorable seizure prognosis. Fifty-eight patients underwent resective FLE surgery with a mean follow-up period of 79.3 months (range 12-208 months). Patient demographics, clinical seizure characteristics, seizure-onset zone within the frontal lobes, and diagnostic tests were tabulated. Engel class, International League Against Epilepsy (ILAE) class, postoperative seizure patterns, time to first recurrent seizure, and seizures and employment during the last year of follow-up were used as outcome measures. Neuropsychological performance and Beck Depression Inventory (BDI) scores were used to define neuropsychological outcome and examined as predictors of seizure outcome. Thirty-three (57%) patients with resective surgery had an Engel class I outcome and 29 (50%) had an ILAE class I outcome. Mean time to first seizure after surgery was 33.3 months (range 0-208). Only 14 patients (24%) were completely seizure-free without auras (Engel IA) throughout the entire follow-up period. The most common pattern of seizure recurrence was mixed, with prolonged periods of seizure freedom intermixed with recurrences. In addition, 32% of patients made gains in employment and 52% were able to reduce use of antiepileptic drugs (AEDs), although only 9% discontinued AEDs. No significant association was found between class I or class IA outcome and the presence of a focal magnetic resonance imaging (MRI) abnormality, any specific localization of seizure focus within the frontal lobe, or neuropsychological change. Findings indicate that that long-term outcome is generally favorable in FLE resective surgery, and support the need for considering multiple outcome measures to more fully characterize clinically relevant postsurgical changes. Outcome can be favorable even in MRI-negative patients.