Letter: Forecasting Seizure Freedom After Epilepsy Surgery Assessing Concordance Between Noninvasive and StereoEEG Findings

OBJECTIVERecent trials for temporal lobe epilepsy (TLE) highlight the challenges of investigating surgical outcomes using randomized controlled trials (RCTs). Although several reviews have examined seizure-freedom outcomes from existing data, there is a need for an overall seizure-freedom rate estimated from level I data as investigators consider other methods besides RCTs to study outcomes related to new surgical interventions.METHODSThe authors performed a systematic review and meta-analysis of the 3 RCTs of TLE in adults and report an overall surgical seizure-freedom rate (Engel class I) composed of level I data. An overall seizure-freedom rate was also collected from level II data (prospective cohort studies) for validation. Eligible studies were identified by filtering a published Cochrane meta-analysis of epilepsy surgery for RCTs and prospective studies, and supplemented by searching indexed terms in MEDLINE (January 1, 2012–April 1, 2018). Retrospective studies were excluded to minimize heterogeneity in patient selection and reporting bias. Data extraction was independently reverified and pooled using a fixed-effects model. The primary outcome was overall seizure freedom following surgery. The historical benchmark was applied in a noninferiority study design to compare its power to a single-study cohort.RESULTSThe overall rate of seizure freedom from level I data was 72.4% (55/76 patients, 3 RCTs), which was nearly identical to the overall seizure-freedom rate of 71.7% (1325/1849 patients, 18 studies) from prospective cohorts (z = 0.134, p = 0.89; z-test). Seizure-freedom rates from level I and II studies were consistent over the years of publication (R2< 0.01, p = 0.73). Surgery resulted in markedly improved seizure-free outcomes compared to medical management (RR 10.82, 95% CI 3.93–29.84, p < 0.01; 2 RCTs). Noninferiority study designs in which the historical benchmark was used had significantly higher power at all difference margins compared to using a single cohort alone (p < 0.001, Bonferroni’s multiple comparison test).CONCLUSIONSThe overall rate of seizure freedom for temporal lobe surgery is approximately 70% for medically refractory epilepsy. The small sample size of the RCT cohort underscores the need to move beyond standard RCTs for epilepsy surgery. This historical seizure-freedom rate may serve as a useful benchmark to guide future study designs for new surgical treatments for refractory TLE.

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The Role of KRAS Mutations in Cortical Malformation and Epilepsy Surgery: A Novel Report of Nevus Sebaceous Syndrome and Review of the Literature

Brain Sciences ◽

10.3390/brainsci11060793 ◽

2021 ◽

Vol 11 (6) ◽

pp. 793

Author(s):

Chiara Pepi ◽

Luca de Palma ◽

Marina Trivisano ◽

Nicola Pietrafusa ◽

Francesca Romana Lepri ◽

...

Keyword(s):

Epilepsy Surgery ◽

Focal Cortical Dysplasia ◽

Hippocampal Sclerosis ◽

Brain Mri ◽

Seizure Freedom ◽

Histopathological Diagnosis ◽

Cortical Malformation ◽

Cognitive Improvement ◽

Cortical Malformations ◽

Nevus Sebaceous

The rare nevus sebaceous (NS) syndrome (NSS) includes cortical malformations and drug-resistant epilepsy. Somatic RAS-pathway genetic variants are pathogenetic in NS, but not yet described within the brain of patients with NSS. We report on a 5-year-old boy with mild psychomotor delay. A brown-yellow linear skin lesion suggestive of NS in the left temporo-occipital area was evident at birth. Epileptic spasms presented at aged six months. EEG showed continuous left temporo-occipital epileptiform abnormalities. Brain MRI revealed a similarly located diffuse cortical malformation with temporal pole volume reduction and a small hippocampus. We performed a left temporo-occipital resection with histopathological diagnosis of focal cortical dysplasia type Ia in the occipital region and hippocampal sclerosis type 1. Three years after surgery, he is seizure-and drug-free (Engel class Ia) and showed cognitive improvement. Genetic examination of brain and skin specimens revealed the c.35G > T (p.Gly12Val) KRAS somatic missense mutation. Literature review suggests epilepsy surgery in patients with NSS is highly efficacious, with 73% probability of seizure freedom. The few histological analyses reported evidenced disorganized cortex, occasionally with cytomegalic neurons. This is the first reported association of a KRAS genetic variant with cortical malformations associated with epilepsy, and suggests a possible genetic substrate for hippocampal sclerosis.

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The influence of lesion volume, perilesion resection volume, and completeness of resection on seizure outcome after resective epilepsy surgery for cortical dysplasia in children

Journal of Neurosurgery Pediatrics ◽

10.3171/2014.10.peds14282 ◽

2015 ◽

Vol 15 (6) ◽

pp. 644-650 ◽

Cited By ~ 30

Author(s):

Chima O. Oluigbo ◽

Jichuan Wang ◽

Matthew T. Whitehead ◽

Suresh Magge ◽

John S. Myseros ◽

...

Keyword(s):

Epilepsy Surgery ◽

Seizure Control ◽

Brain Mri ◽

Age At Onset ◽

Cortical Dysplasia ◽

Complete Resection ◽

Seizure Outcome ◽

Seizure Freedom ◽

Lesion Volume ◽

Resection Volume

OBJECT Focal cortical dysplasia (FCD) is one of the most common causes of intractable epilepsy leading to surgery in children. The predictors of seizure freedom after surgical management for FCD are still unclear. The objective of this study was to perform a volumetric analysis of factors shown on the preresection and postresection brain MRI scans of patients who had undergone resective epilepsy surgery for cortical dysplasia and to determine the influence of these factors on seizure outcome. METHODS The authors reviewed the medical records and brain images of 43 consecutive patients with focal MRI-documented abnormalities and a pathological diagnosis of FCD who had undergone surgical treatment for refractory epilepsy. Preoperative lesion volume and postoperative resection volume were calculated by manual segmentation using OsiriX PRO software. RESULTS Forty-three patients underwent first-time surgery for resection of an FCD. The age range of these patients at the time of surgery ranged from 2 months to 21.8 years (mean age 7.3 years). The median duration of follow-up was 20 months. The mean age at onset was 31.6 months (range 1 day to 168 months). Complete resection of the area of an FCD, as adjudged from the postoperative brain MR images, was significantly associated with seizure control (p = 0.0005). The odds of having good seizure control among those who underwent complete resection were about 6 times higher than those among the patients who did not undergo complete resection. Seizure control was not significantly associated with lesion volume (p = 0.46) or perilesion resection volume (p = 0.86). CONCLUSIONS The completeness of FCD resection in children is a significant predictor of seizure freedom. Neither lesion volume nor the further resection of perilesional tissue is predictive of seizure freedom.

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Forecasting Seizure Freedom After Epilepsy Surgery Assessing Concordance Between Noninvasive and StereoEEG Findings

Neurosurgery ◽

10.1093/neuros/nyaa322_s065 ◽

2021 ◽

Vol 89 (Supplement_2) ◽

pp. S65-S65

Author(s):

Reinaldo Uribe San Martin ◽

Roberta Di Giacomo ◽

Roberto Mai ◽

Francesca Gozzo ◽

Veronica Pelliccia ◽

...

Keyword(s):

Epilepsy Surgery ◽

Seizure Freedom

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European trends in epilepsy surgery

Neurology ◽

10.1212/wnl.0000000000005776 ◽

2018 ◽

Vol 91 (2) ◽

pp. e96-e106 ◽

Cited By ~ 37

Author(s):

Maxime O. Baud ◽

Thomas Perneger ◽

Attila Rácz ◽

Max C. Pensel ◽

Christian Elger ◽

...

Keyword(s):

Epilepsy Surgery ◽

Disease Duration ◽

Focal Epilepsy ◽

Seizure Freedom ◽

Early Referral ◽

Temporal Epilepsy ◽

Included Patient ◽

Class 1 ◽

Postsurgical Outcomes ◽

Over Time

ObjectiveResective surgery is effective in treating drug-resistant focal epilepsy, but it remains unclear whether improved diagnostics influence postsurgical outcomes. Here, we compared practice and outcomes over 2 periods 15 years apart.MethodsSixteen European centers retrospectively identified 2 cohorts of children and adults who underwent epilepsy surgery in the period of 1997 to 1998 (n = 562) or 2012 to 2013 (n = 736). Data collected included patient (sex, age) and disease (duration, localization and diagnosis) characteristics, type of surgery, histopathology, Engel postsurgical outcome, and complications, as well as imaging and electrophysiologic tests performed for each case. Postsurgical outcome predictors were included in a multivariate logistic regression to assess the strength of date of surgery as an independent predictor.ResultsOver time, the number of operated cases per center increased from a median of 31 to 50 per 2-year period (p = 0.02). Mean disease duration at surgery decreased by 5.2 years (p < 0.001). Overall seizure freedom (Engel class 1) increased from 66.7% to 70.9% (adjusted p = 0.04), despite an increase in complex surgeries (extratemporal and/or MRI negative). Surgeries performed during the later period were 1.34 times (adjusted odds ratio; 95% confidence interval 1.02–1.77) more likely to yield a favorable outcome (Engel class I) than earlier surgeries, and improvement was more marked in extratemporal and MRI-negative temporal epilepsy. The rate of persistent neurologic complications remained stable (4.6%–5.3%, p = 0.7).ConclusionImprovements in European epilepsy surgery over time are modest but significant, including higher surgical volume, shorter disease duration, and improved postsurgical seizure outcomes. Early referral for evaluation is required to continue on this encouraging trend.

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Outcomes of cingulate epilepsy surgery: insights from an institutional and patient-level systematic review and meta-analysis

Journal of Neurosurgery ◽

10.3171/2021.8.jns211558 ◽

2021 ◽

pp. 1-10

Author(s):

Panagiotis Kerezoudis ◽

Rohin Singh ◽

Gregory A. Worrell ◽

Jamie J. Van Gompel

Keyword(s):

Epilepsy Surgery ◽

Literature Search ◽

Anterior Cingulate ◽

Postoperative Outcomes ◽

Cochrane Library ◽

Rank Test ◽

Seizure Freedom ◽

Low Grade ◽

Cingulate Gyrus

OBJECTIVE Due to their deep and medial location, range of seizure semiologies, and poor localization on ictal electroencephalography (EEG), cingulate gyrus seizures can be difficult to diagnose and treat. The aim of this study was to review the available evidence on postoperative outcomes after cingulate epilepsy surgery. METHODS A comprehensive literature search of the PubMed/MEDLINE, Ovid Embase, Ovid Scopus, and Cochrane Library databases was conducted to identify studies that investigated postoperative outcomes of patients with cingulate epilepsy. Seizure freedom at the last follow-up (at least 12 months) was the primary endpoint. The literature search was supplemented by the authors’ institutional series (4 patients). RESULTS Twenty-one studies were identified, yielding a total of 105 patients (68 with lesional epilepsy [65%]). Median age at surgery was 23 years, and 56% of patients were male. Median epilepsy duration was 7.5 years. Invasive EEG recording was performed on 69% of patients (53% of patients with lesional epilepsy and 97% of those with nonlesional epilepsy, p < 0.001). The most commonly resected region was the anterior cingulate (55%), followed by the posterior (17%) and middle (14%) cingulate. Lesionectomy alone was performed in 9% of patients. Additional extracingulate treatment was performed in 54% of patients (53% of patients with lesional epilepsy vs 57% of those with nonlesional epilepsy, p = 0.87). The most common pathology was cortical dysplasia (54%), followed by low-grade neoplasm (29%) and gliosis (8%). Seizure freedom was noted in 72% of patients (median follow-up 24 months). A neurological deficit was noted in 27% of patients (24% had temporary deficit), with the most common deficit being motor weakness (13%) followed by supplementary motor area syndrome (9.5%). Univariate survival analysis revealed significantly greater probability of seizure freedom in patients with lesional epilepsy (p = 0.015, log-rank test). CONCLUSIONS Surgical treatment of drug-resistant focal epilepsy originating from the cingulate gyrus is safe, leads to low rates of permanent adverse effects, and leads to high rates of long-term seizure freedom in carefully selected patients. These data may serve as a benchmark for surgical counseling of patients with cingulate epilepsy.

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Epilepsziasebészeti beavatkozások eredményei a Pécsi Epilepszia Centrumban 2005 és 2016 között

Orvosi Hetilap ◽

10.1556/650.2019.31321 ◽

2019 ◽

Vol 160 (7) ◽

pp. 270-278 ◽

Cited By ~ 1

Author(s):

Katalin Nóra Lőrincz ◽

Beáta Bóné ◽

Márton Tóth ◽

Réka Horváth ◽

Norbert Kovács ◽

...

Keyword(s):

Quality Of Life ◽

Epilepsy Surgery ◽

Employment Status ◽

Postoperative Outcome ◽

Seizure Freedom ◽

Neurologic Disease ◽

Exact Test ◽

Epileptic Patients

Abstract: Introduction: Epilepsy as a chronic, severe neurologic disease significantly influences the quality of life of the epileptic patients. In candidates well selected for surgery, the seizure freedom is realistically achievable, and the quality of life can be further improved with complex individual rehabilitation. Aim: We aimed to evaluate the postoperative outcome of patients who underwent epilepsy surgery between 2005 and 2016 at the Epilepsy Center at Pécs. Method: We evaluated seizure status at regular follow-up visits after surgery and the quality of life using questionnaires focusing on employment and social status. Results: 76% of the 72 patients who underwent surgical resection for epilepsy were free from disabling seizures , and 10% had rare disabling seizures (almost seizure-free), 7% experienced worthwhile improvement and 7% had no worthwhile improvement. Comparing the employment status of patients free from disabling seizures to patients not free from disabling seizures, we found that the employment status is significantly influenced by seizure freedom (p<0.01, Fisher’s exact test). While 67% of seizure-free patients were employed, only 19% of patients not free from disabling seizures were hired. Conclusion: Our results resemble the international tendencies and success rate, proving epilepsy surgery as an available, valid and effective treatment in well selected patients. Orv Hetil. 2019; 160(7): 270–278.

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Results of Epilepsy Surgery: Still So Much to Learn

Epilepsy Currents ◽

10.1111/j.1535-7511.2006.00105.x ◽

2006 ◽

Vol 6 (3) ◽

pp. 80-82

Author(s):

Donna C. Bergen

Keyword(s):

Temporal Lobe Epilepsy ◽

Epilepsy Surgery ◽

Disease Duration ◽

Seizure Freedom ◽

Hippocampal Atrophy ◽

Younger Age ◽

Seizure Relapse ◽

Clonic Seizures

Predicting Long-Term Seizure Outcome after Resective Epilepsy Surgery: The Multicenter Study Spencer SS, Berg AT, Vickrey BG, Sperling MR, Bazil CW, Shinnar S, Langfitt JT, Walczak TS, Pacia SV Neurology 2005;65(6):912–918 Background In a seven-center prospective observational study of resective epilepsy surgery, the authors examined probability and predictors of entering 2-year remission and the risk of subsequent relapse. Methods Patients aged 12 years and over were enrolled at time of referral for epilepsy surgery, and underwent standardized evaluation, treatment, and follow-up procedures. The authors defined seizure remission as 2 years completely seizure-free after hospital discharge with or without auras, and relapse as any seizures after 2-year remission. The authors examined type of surgery, seizure, clinical and demographic variables, and localization study results with respect to prediction of seizure remission or relapse, using χ2 and proportional hazards analysis. Results Of 396 operated patients, 339 were followed over 2 years, and 223 (66%) experienced 2-year remission, not significantly different between medial temporal (68%) and neocortical (50%) resections. In multivariable models, only absence of generalized tonic–clonic seizures and presence of hippocampal atrophy were significantly and independently associated with remission, and only in the medial temporal resection group. Fifty-five patients relapsed after 2-year remission, again not significantly different between medial temporal (25%) and neocortical (19%) resections. Only delay to remission predicted relapse, and only in medial temporal patients. Conclusion Hippocampal atrophy and a history of absence of generalized tonic clonic seizures were the sole predictors of 2-year remission, and only for medial temporal resections. Antiepileptic Drug Withdrawal after Successful Surgery for Intractable Temporal Lobe Epilepsy Kim YD, Heo K, Park SC, Huh K, Chang JW, Choi JU, Chung SS, Lee BI Epilepsia 2005;46(2):251–257 Purpose To investigate the prognosis related to antiepileptic drug (AED) discontinuation after successful surgery for intractable temporal lobe epilepsy. Methods The clinical courses after temporal lobectomies (TLs) were retrospectively analyzed in 88 consecutive patients. All the patients had TLs as the only surgical procedure, and they had been followed up for longer than 3 years. AED discontinuation was attempted if the patient had been seizure free without aura for ≥1 year during the follow-up period. Results Sixty-six (75%) patients achieved complete seizure freedom for ≥1 year; 28 patients were seizure free immediately after surgery (immediate success); and 38 patients became seizure free after some period of recurrent seizures (delayed success). AED discontinuation was attempted in 60 (91%) of 66 patients with a successful outcome. In 13 (22%) patients, seizure relapse developed during AED reduction ( n = 60), and in 7 (12%) patients after discontinuation of AEDs ( n = 38). The seizure recurrence rate was not different between the immediate- and delayed-success groups. Among 20 patients with seizure relapse related to AED tapering, 9 (45%) of them regained seizure freedom after reinstitution of AED treatment, and AEDs were eventually discontinued in 6 of them. Seizures that recurred after complete AED discontinuation had a better prognosis than did the seizures that recurred during AED reduction (seizure freedom in 86% vs 23%). At the final assessment, 54 (61%) patients had been seizure free ≥1 year; 37 without AEDs and 17 with AEDs. The successful discontinuation of AEDs was more frequent for patients with a younger age at the time of surgery and for those patients with shorter disease duration. Conclusions Our results suggest that seizure freedom without aura at ≥1 year is a reasonable indication for the attempt at AED discontinuation. The subsequent control of recurrent seizures was excellent, especially if seizures relapsed after the complete discontinuation of AEDs. Younger age at the time of surgery and a shorter disease duration seem to affect successful AED discontinuation for a long-term period.

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Seizure freedom off antiepileptic drugs after temporal lobe epilepsy surgery

Seizure ◽

10.1016/j.seizure.2006.10.007 ◽

2007 ◽

Vol 16 (2) ◽

pp. 95-98 ◽

Cited By ~ 26

Author(s):

Muhammad Al-Kaylani ◽

Peter Konrad ◽

Barry Lazenby ◽

Bennett Blumenkopf ◽

Bassel Abou-Khalil

Keyword(s):

Temporal Lobe Epilepsy ◽

Antiepileptic Drugs ◽

Temporal Lobe ◽

Epilepsy Surgery ◽

Seizure Freedom

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Chronic unlimited recording electrocorticography–guided resective epilepsy surgery: technology-enabled enhanced fidelity in seizure focus localization with improved surgical efficacy

Journal of Neurosurgery ◽

10.3171/2014.1.jns131592 ◽

2014 ◽

Vol 120 (6) ◽

pp. 1402-1414 ◽

Cited By ~ 27

Author(s):

Daniel J. DiLorenzo ◽

Erwin Z. Mangubat ◽

Marvin A. Rossi ◽

Richard W. Byrne

Keyword(s):

Epilepsy Surgery ◽

Primary Motor Cortex ◽

Epileptiform Activity ◽

Seizure Freedom ◽

Monitoring Technology ◽

Resective Surgery ◽

Depth Electrodes ◽

Small Series ◽

Number Of Patients ◽

Ablative Surgery

Object Epilepsy surgery is at the cusp of a transformation due to the convergence of advancements in multiple technologies. Emerging neuromodulatory therapies offer the promise of functionally correcting neural instability and obviating the need for resective or ablative surgery in select cases. Chronic implanted neurological monitoring technology, delivered as part of a neuromodulatory therapeutic device or as a stand-alone monitoring system, offers the potential to monitor patients chronically in their normal ambulatory setting with outpatient medication regimens. This overcomes significant temporal limitations, pharmacological perturbations, and infection risks inherent in the present technology comprising subacute percutaneous inpatient monitoring of presurgical candidates in an epilepsy monitoring unit. Methods As part of the pivotal study for the NeuroPace Responsive Neurostimulation (RNS) System, the authors assessed the efficacy of the RNS System to control seizures in a group of patients with medically refractory epilepsy. Prior to RNS System implantation, these patients were not candidates for further resective surgery because they had temporal lobe epilepsy with bilateral temporal sources, frontal lobe reflex epilepsy with involvement of primary motor cortex, and occipital lobe epilepsy with substantial involvement of eloquent visual cortex. Without interfering with and beyond the scope of the therapeutic aspect of the RNS System study, the authors were able to monitor seizure and epileptiform activity from chronically implanted subdural and depth electrodes in these patients, and, in doing so, they were able to more accurately localize the seizure source. In 5 of these study patients, in whom the RNS System was not effective, the notion of resective surgery was revisited and considered in light of the additional information gleaned from the chronic intracranial recordings obtained from various permutations of electrodes monitoring sources in the frontal, temporal, parietal, and occipital lobes. Results Through long-term analysis of chronic unlimited recording electrocorticography (CURE) from chronically implanted electrodes, the authors were able to further refine seizure source localization and sufficiently increase the expected likelihood of seizure control to the extent that 4 patients who had previously been considered not to be candidates for surgery did undergo resective surgery, and all have achieved seizure freedom. A fifth patient, who had a double-band heterotopia, underwent surgery but did not achieve significant seizure reduction. Conclusions Chronic unlimited recording electrocorticography–guided resective epilepsy surgery employs new monitoring technology in a novel way, which in this small series was felt to improve seizure localization and consequently the potential efficacy of resective surgery. This suggests that the CURE modality could improve outcomes in patients who undergo resective surgery, and it may expand the set of patients in whom resective surgery may be expected to be efficacious and therefore the potential number of patients who may achieve seizure freedom. The authors report 4 cases of patients in which this technique and technology had a direct role in guiding surgery that provided seizure freedom and that suggest this new approach warrants further study to characterize its value in presurgical evaluation. Clinical trial no.: NCT00572195 (ClinicalTrials.gov).

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