Showing papers on "Epilepsy surgery published in 2019"

Analysis of Morbidity and Outcomes Associated With Use of Subdural Grids vs Stereoelectroencephalography in Patients With Intractable Epilepsy.

Abstract: Importance A major change has occurred in the evaluation of epilepsy with the availability of robotic stereoelectroencephalography (SEEG) for seizure localization. However, the comparative morbidity and outcomes of this minimally invasive procedure relative to traditional subdural electrode (SDE) implantation are unknown. Objective To perform a comparative analysis of the relative efficacy, procedural morbidity, and epilepsy outcomes consequent to SEEG and SDE in similar patient populations and performed by a single surgeon at 1 center. Design, Setting and Participants Overall, 239 patients with medically intractable epilepsy underwent 260 consecutive intracranial electroencephalographic procedures to localize their epilepsy. Procedures were performed from November 1, 2004, through June 30, 2017, and data were analyzed in June 2017 and August 2018. Interventions Implantation of SDE using standard techniques vs SEEG using a stereotactic robot, followed by resection or laser ablation of the seizure focus. Main Outcomes and Measures Length of surgical procedure, surgical complications, opiate use, and seizure outcomes using the Engel Epilepsy Surgery Outcome Scale. Results Of the 260 cases included in the study (54.6% female; mean [SD] age at evaluation, 30.3 [13.1] years), the SEEG (n = 121) and SDE (n = 139) groups were similar in age (mean [SD], 30.1 [12.2] vs 30.6 [13.8] years), sex (47.1% vs 43.9% male), numbers of failed anticonvulsants (mean [SD], 5.7 [2.5] vs 5.6 [2.5]), and duration of epilepsy (mean [SD], 16.4 [12.0] vs17.2 [12.1] years). A much greater proportion of SDE vs SEEG cases were lesional (99 [71.2%] vs 53 [43.8%];P Conclusions and Relevance This direct comparison of large matched cohorts undergoing SEEG and SDE implantation reveals distinctly better procedural morbidity favoring SEEG. These modalities intrinsically evaluate somewhat different populations, with SEEG being more versatile and applicable to a range of scenarios, including nonlesional and bilateral cases, than SDE. The significantly favorable adverse effect profile of SEEG should factor into decision making when patients with pharmacoresistant epilepsy are considered for intracranial evaluations.

Stereoelectroencephalography: retrospective analysis of 742 procedures in a single centre.

Abstract: This retrospective description of a surgical series is aimed at reporting on indications, methodology, results on seizures, outcome predictors and complications from a 20-year stereoelectroencephalography (SEEG) activity performed at a single epilepsy surgery centre. Prospectively collected data from a consecutive series of 742 SEEG procedures carried out on 713 patients were reviewed and described. Long-term seizure outcome of SEEG-guided resections was defined as a binomial variable: absence (ILAE classes 1-2) or recurrence (ILAE classes 3-6) of disabling seizures. Predictors of seizure outcome were analysed by preliminary uni/bivariate analyses followed by multivariate logistic regression. Furthermore, results on seizures of these subjects were compared with those obtained in 1128 patients operated on after only non-invasive evaluation. Survival analyses were also carried out, limited to patients with a minimum follow-up of 10 years. Resective surgery has been indicated for 570 patients (79.9%). Two-hundred and seventy-nine of 470 patients operated on (59.4%) were free of disabling seizures at least 2 years after resective surgery. Negative magnetic resonance and post-surgical lesion remnant were significant risk factors for seizure recurrence, while type II focal cortical dysplasia, balloon cells, glioneuronal tumours, hippocampal sclerosis, older age at epilepsy onset and periventricular nodular heterotopy were significantly associated with seizure freedom. Twenty-five of 153 patients who underwent radio-frequency thermal coagulation (16.3%) were optimal responders. Thirteen of 742 (1.8%) procedures were complicated by unexpected events, including three (0.4%) major complications and one fatality (0.1%). In conclusion, SEEG is a safe and efficient methodology for invasive definition of the epileptogenic zone in the most challenging patients. Despite the progressive increase of MRI-negative cases, the proportion of seizure-free patients did not decrease throughout the years.

Changing concepts in presurgical assessment for epilepsy surgery

Abstract: Candidates for epilepsy surgery must undergo presurgical evaluation to establish whether and how surgical treatment can stop seizures without causing neurological deficits. Various techniques, including MRI, PET, single-photon emission CT, video-EEG, magnetoencephalography and invasive EEG, aim to identify the diseased brain tissue and the involved network. Recent technical and methodological developments, encompassing both advances in existing techniques and new combinations of technologies, are enhancing the ability to define the optimal resection strategy. Multimodal interpretation and predictive computer models are expected to aid surgical planning and patient counselling, and multimodal intraoperative guidance is likely to increase surgical precision. In this Review, we discuss how the knowledge derived from these new approaches is challenging our way of thinking about surgery to stop focal seizures. In particular, we highlight the importance of looking beyond the EEG seizure onset zone and considering focal epilepsy as a brain network disease in which long-range connections need to be taken into account. We also explore how new diagnostic techniques are revealing essential information in the brain that was previously hidden from view.

Epilepsy in Asia: Disease burden, management barriers, and challenges.

Abstract: This article reviews the burden of epilepsy in Asia, the challenges faced by people with epilepsy, and the management of epilepsy. Comparison is made with other parts of the world. For this narrative review, data were collected using specified search criteria. Articles investigating the epidemiology of epilepsy, diagnosis, comorbidities and associated mortality, stigmatization, and treatment were included. Epilepsy is a global health care issue affecting up to 70 million people worldwide. Nearly 80% of people with epilepsy live in low- and middle-income countries with limited resources. People with epilepsy are prone to physical and psychological comorbidities, including anxiety and depression, which can negatively impact their quality of life. Furthermore, people with epilepsy are at higher risk of premature death than people without epilepsy. Discrimination or stigmatization of people with epilepsy is common in Asia and can affect their education, work, and marriage opportunities. Access to epilepsy treatment varies throughout Asia. Although highly advanced treatment is available in some countries, up to 90% of people with epilepsy are not adequately treated or are not treated with conventional antiepileptic therapy in resource-limited countries. People in remote areas often do not receive any epilepsy care. First-generation antiepileptic drugs (AEDs) are available, but usually only in urban areas, and second-generation AEDs are not available in all countries. Newer AEDs tend to have more favorable safety profiles than first-generation AEDs and provide options to tailor therapy for individual patients, especially those with comorbidities. Active epilepsy surgery centers are present in some countries, although epilepsy surgery is often underutilized given the number of patients who could benefit. Further epidemiologic research is needed to provide accurate epilepsy data across the Asian region. Coordinated action is warranted to improve access to treatment and care.

Virtual resection predicts surgical outcome for drug-resistant epilepsy.

Abstract: Patients with drug-resistant epilepsy often require surgery to become seizure-free. While laser ablation and implantable stimulation devices have lowered the morbidity of these procedures, seizure-free rates have not dramatically improved, particularly for patients without focal lesions. This is in part because it is often unclear where to intervene in these cases. To address this clinical need, several research groups have published methods to map epileptic networks but applying them to improve patient care remains a challenge. In this study we advance clinical translation of these methods by: (i) presenting and sharing a robust pipeline to rigorously quantify the boundaries of the resection zone and determining which intracranial EEG electrodes lie within it; (ii) validating a brain network model on a retrospective cohort of 28 patients with drug-resistant epilepsy implanted with intracranial electrodes prior to surgical resection; and (iii) sharing all neuroimaging, annotated electrophysiology, and clinical metadata to facilitate future collaboration. Our network methods accurately forecast whether patients are likely to benefit from surgical intervention based on synchronizability of intracranial EEG (area under the receiver operating characteristic curve of 0.89) and provide novel information that traditional electrographic features do not. We further report that removing synchronizing brain regions is associated with improved clinical outcome, and postulate that sparing desynchronizing regions may further be beneficial. Our findings suggest that data-driven network-based methods can identify patients likely to benefit from resective or ablative therapy, and perhaps prevent invasive interventions in those unlikely to do so.

Magnetoencephalography for epileptic focus localization in a series of 1000 cases.

Abstract: The aim of epilepsy surgery in patients with focal, pharmacoresistant epilepsies is to remove the complete epileptogenic zone to achieve long-term seizure freedom. In addition to a spectrum of diagnostic methods, magnetoencephalography focus localization is used for planning of epilepsy surgery. We present results from a retrospective observational cohort study of 1000 patients, evaluated using magnetoencephalography at the University Hospital Erlangen over the time span of 28 years. One thousand consecutive cases were included in the study, evaluated at the University Hospital Erlangen between 1990 and 2018. All patients underwent magnetoencephalography as part of clinical workup for epilepsy surgery. Of these, 405 underwent epilepsy surgery after magnetoencephalography, with postsurgical follow-ups of up to 20 years. Sensitivity for interictal epileptic activity was evaluated, in addition to concordance of localization with the consensus of presurgical workup on a lobar level. We evaluate magnetoencephalography characteristics of patients who underwent epilepsy surgery versus patients who did not proceed to surgery. In operated patients, resection of magnetoencephalography localizations were related to postsurgical seizure outcomes, including long-term results after several years. In comparison, association of lesionectomy with seizure outcomes was analysed. Measures of diagnostic accuracy were calculated for magnetoencephalography resection and lesionectomy. Sensitivity for interictal epileptic activity was 72% with significant differences between temporal and extra-temporal lobe epilepsy. Magnetoencephalography was concordant with the presurgical consensus in 51% and showed additional or more focal involvement in an additional 32%. Patients who proceeded to surgery showed a significantly higher percentage of monofocal magnetoencephalography results. Complete magnetoencephalography resection was associated with significantly higher chances to achieve seizure freedom in the short and long-term. Diagnostic accuracy was significant in temporal and extra-temporal lobe cases, but was significantly higher in extra-temporal lobe epilepsy (diagnostic odds ratios of 4.4 and 41.6). Odds ratios were also higher in non-lesional versus lesional cases (42.0 versus 6.2). The results show that magnetoencephalography provides non-redundant information, which significantly contributes to patient selection, focus localization and ultimately long-term seizure freedom after epilepsy surgery. Specifically in extra-temporal lobe epilepsy and non-lesional cases, magnetoencephalography provides excellent accuracy.

Interictal and ictal source localization for epilepsy surgery using high-density EEG with MEG: a prospective long-term study.

Abstract: Drug-resistant focal epilepsy is a major clinical problem and surgery is under-used. Better non-invasive techniques for epileptogenic zone localization are needed when MRI shows no lesion or an extensive lesion. The problem is interictal and ictal localization before propagation from the epileptogenic zone. High-density EEG (HDEEG) and magnetoencephalography (MEG) offer millisecond-order temporal resolution to address this but co-acquisition is challenging, ictal MEG studies are rare, long-term prospective studies are lacking, and fundamental questions remain. Should HDEEG-MEG discharges be assessed independently [electroencephalographic source localization (ESL), magnetoencephalographic source localization (MSL)] or combined (EMSL) for source localization? Which phase of the discharge best characterizes the epileptogenic zone (defined by intracranial EEG and surgical resection relative to outcome)? Does this differ for interictal and ictal discharges? Does MEG detect mesial temporal lobe discharges? Thirteen patients (10 non-lesional, three extensive-lesional) underwent synchronized HDEEG-MEG (72-94 channel EEG, 306-sensor MEG). Source localization (standardized low-resolution tomographic analysis with MRI patient-individualized boundary-element method) was applied to averaged interictal epileptiform discharges (IED) and ictal discharges at three phases: 'early-phase' (first latency 90% explained variance), 'mid-phase' (first of 50% rising-phase, 50% mean global field power), 'late-phase' (negative peak). 'Earliest-solution' was the first of the three early-phase solutions (ESL, MSL, EMSL). Prospective follow-up was 3-21 (median 12) months before surgery, 14-39 (median 21) months after surgery. IEDs (n = 1474) were recorded, seen in: HDEEG only, 626 (42%); MEG only, 232 (16%); and both 616 (42%). Thirty-three seizures were captured, seen in: HDEEG only, seven (21%); MEG only, one (3%); and both 25 (76%). Intracranial EEG was done in nine patients. Engel scores were I (9/13, 69%), II (2/13,15%), and III (2/13). MEG detected baso-mesial temporal lobe epileptogenic zone sources. Epileptogenic zone OR [odds ratio(s)] were significantly higher for earliest-solution versus early-phase IED-surgical resection and earliest-solution versus all mid-phase and late-phase solutions. ESL outperformed EMSL for ictal-surgical resection [OR 3.54, 95% confidence interval (CI) 1.09-11.55, P = 0.036]. MSL outperformed EMSL for IED-intracranial EEG (OR 4.67, 95% CI 1.19-18.34, P = 0.027). ESL outperformed MSL for ictal-surgical resection (OR 3.73, 95% CI 1.16-12.03, P = 0.028) but was outperformed by MSL for IED-intracranial EEG (OR 0.18, 95% CI 0.05-0.73, P = 0.017). Thus, (i) HDEEG and MEG source solutions more accurately localize the epileptogenic zone at the earliest resolvable phase of interictal and ictal discharges, not mid-phase (as is common practice) or late peak-phase (when signal-to-noise ratios are maximal); (ii) from empirical observation of the differential timing of HDEEG and MEG discharges and based on the superiority of ESL plus MSL over either modality alone and over EMSL, concurrent HDEEG-MEG signals should be assessed independently, not combined; (iii) baso-mesial temporal lobe sources are detectable by MEG; and (iv) MEG is not 'more accurate' than HDEEG-emphasis is best placed on the earliest signal (whether HDEEG or MEG) amenable to source localization. Our findings challenge current practice and our reliance on invasive monitoring in these patients. 10.1093/brain/awz015_video1 awz015media1 6018582479001.

Epilepsy duration and seizure outcome in epilepsy surgery: A systematic review and meta-analysis

Abstract: Objective To conduct a systematic review and meta-analysis on the effect of earlier or later resective epilepsy surgery on seizure outcome. Methods We searched the electronic databases PubMed, EMBASE, and Cochrane Library for studies investigating the association of epilepsy duration and seizure freedom after resective surgery. Two reviewers independently screened citations for eligibility and assessed relevant studies for risk of bias. We combined data in meta-analyses using a random effects model. We assessed the certainty of evidence according to Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results Twenty-five studies were included, 12 of which had data suitable for meta-analyses. Comparing seizure outcome if epilepsy surgery was performed before vs after 2, 5, 10, and 20 years of epilepsy duration, and comparing epilepsy duration 10 years, we found significant effects favoring shorter duration with risk differences ranging from 0.15 to 0.21 and risk ratios ranging from 1.20 to 1.33 ( p Conclusion People with shorter epilepsy duration are more likely to be seizure-free at follow-up. Furthermore, there is a positive association between shorter duration and seizure freedom also for very long epilepsy durations. Patients who might benefit from epilepsy surgery should therefore be referred for presurgical assessments without further delay, regardless of epilepsy duration. The low certainty of evidence acknowledges concerns regarding study heterogeneity and possible residual confounding.

Epilepsy Gene Therapy Using an Engineered Potassium Channel.

Abstract: Refractory focal epilepsy is a devastating disease for which there is frequently no effective treatment. Gene therapy represents a promising alternative, but treating epilepsy in this way involves irreversible changes to brain tissue, so vector design must be carefully optimized to guarantee safety without compromising efficacy. We set out to develop an epilepsy gene therapy vector optimized for clinical translation. The gene encoding the voltage-gated potassium channel Kv1.1, KCNA1, was codon optimized for human expression and mutated to accelerate the recovery of the channels from inactivation. For improved safety, this engineered potassium channel (EKC) gene was packaged into a nonintegrating lentiviral vector under the control of a cell type-specific CAMK2A promoter. In a blinded, randomized, placebo-controlled preclinical trial, the EKC lentivector robustly reduced seizure frequency in a male rat model of focal neocortical epilepsy characterized by discrete spontaneous seizures. When packaged into an adeno-associated viral vector (AAV2/9), the EKC gene was also effective at suppressing seizures in a male rat model of temporal lobe epilepsy. This demonstration of efficacy in a clinically relevant setting, combined with the improved safety conferred by cell type-specific expression and integration-deficient delivery, identify EKC gene therapy as being ready for clinical translation in the treatment of refractory focal epilepsy. SIGNIFICANCE STATEMENT Pharmacoresistant epilepsy affects up to 0.3% of the population. Although epilepsy surgery can be effective, it is limited by risks to normal brain function. We have developed a gene therapy that builds on a mechanistic understanding of altered neuronal and circuit excitability in cortical epilepsy. The potassium channel gene KCNA1 was mutated to bypass post-transcriptional editing and was packaged in a nonintegrating lentivector to reduce the risk of insertional mutagenesis. A randomized, blinded preclinical study demonstrated therapeutic effectiveness in a rodent model of focal neocortical epilepsy. Adeno-associated viral delivery of the channel to both hippocampi was also effective in a model of temporal lobe epilepsy. These results support clinical translation to address a major unmet need.

Deep brain stimulation of the anterior nucleus of the thalamus for drug-resistant epilepsy.

Abstract: Despite the use of first-choice anti-epileptic drugs and satisfactory seizure outcome rates after resective epilepsy surgery, a considerable percentage of patients do not become seizure free. ANT-DBS may provide for an alternative treatment option in these patients. This literature review discusses the rationale, mechanism of action, clinical efficacy, safety, and tolerability of ANT-DBS in drug-resistant epilepsy patients. A review using systematic methods of the available literature was performed using relevant databases including Medline, Embase, and the Cochrane Library pertaining to the different aspects ANT-DBS. ANT-DBS for drug-resistant epilepsy is a safe, effective and well-tolerated therapy, where a special emphasis must be given to monitoring and neuropsychological assessment of both depression and memory function. Three patterns of seizure control by ANT-DBS are recognized, of which a delayed stimulation effect may account for an improved long-term response rate. ANT-DBS remotely modulates neuronal network excitability through overriding pathological electrical activity, decrease neuronal cell loss, through immune response inhibition or modulation of neuronal energy metabolism. ANT-DBS is an efficacious treatment modality, even when curative procedures or lesser invasive neuromodulative techniques failed. When compared to VNS, ANT-DBS shows slightly superior treatment response, which urges for direct comparative trials. Based on the available evidence ANT-DBS and VNS therapies are currently both superior compared to non-invasive neuromodulation techniques such as t-VNS and rTMS. Additional in-vivo research is necessary in order to gain more insight into the mechanism of action of ANT-DBS in localization-related epilepsy which will allow for treatment optimization. Randomized clinical studies in search of the optimal target in well-defined epilepsy patient populations, will ultimately allow for optimal patient stratification when applying DBS for drug-resistant patients with epilepsy.

Association of Cortical Stimulation-Induced Seizure With Surgical Outcome in Patients With Focal Drug-Resistant Epilepsy.

Abstract: Importance Cortical stimulation is used during presurgical epilepsy evaluation for functional mapping and for defining the cortical area responsible for seizure generation. Despite wide use of cortical stimulation, the association between cortical stimulation–induced seizures and surgical outcome remains unknown. Objective To assess whether removal of the seizure-onset zone resulting from cortical stimulation is associated with a good surgical outcome. Design, Setting, and Participants This cohort study used data from 2 tertiary epilepsy centers: Montreal Neurological Institute in Montreal, Quebec, Canada, and Grenoble-Alpes University Hospital in Grenoble, France. Participants included consecutive patients (n = 103) with focal drug-resistant epilepsy who underwent stereoelectroencephalography between January 1, 2007, and January 1, 2017. Participant selection criteria were cortical stimulation during implantation, subsequent open surgical procedure with a follow-up of 1 or more years, and complete neuroimaging data sets for superimposition between intracranial electrodes and the resection. Main Outcomes and Measures Cortical stimulation–induced typical electroclinical seizures, the volume of the surgical resection, and the percentage of resected electrode contacts inducing a seizure or encompassing the cortical stimulation–informed and spontaneous seizure-onset zones were identified. These measures were correlated with good (Engel class I) and poor (Engel classes II-IV) surgical outcomes. Electroclinical characteristics associated with cortical stimulation–induced seizures were analyzed. Results In total, 103 patients were included, of whom 54 (52.4%) were female, and the mean (SD) age was 31 (11) years. Fifty-nine patients (57.3%) had cortical stimulation–induced seizures. The percentage of patients with cortical stimulation–induced electroclinical seizures was higher in the good outcome group than in the poor outcome group (31 of 44 [70.5%] vs 28 of 59 [47.5%];P = .02). The percentage of the resected contacts encompassing the cortical stimulation–informed seizure-onset zone correlated with surgical outcome (median [range] percentage in good vs poor outcome: 63.2% [0%-100%] vs 33.3% [0%-84.6%]; Spearman ρ = 0.38;P = .003). A similar result was observed for spontaneous seizures (median [range] percentage in good vs poor outcome: 57.1% [0%-100%] vs 32.7% [0%-100%]; Spearman ρ = 0.32;P = .002). Longer elapsed time since the most recent seizure was associated with a higher likelihood of inducing seizures (>24 hours: 64.7% vs Conclusions and Relevance Seizure induction by cortical stimulation appears to identify the epileptic generator as reliably as spontaneous seizures do; this finding might lead to a more time-efficient intracranial presurgical investigation of focal epilepsy as the need to record spontaneous seizures is reduced.

Association of piriform cortex resection with surgical outcomes in patients with temporal lobe epilepsy

Abstract: Importance A functional area associated with the piriform cortex, termed area tempestas, has been implicated in animal studies as having a crucial role in modulating seizures, but similar evidence is limited in humans. Objective To assess whether removal of the piriform cortex is associated with postoperative seizure freedom in patients with temporal lobe epilepsy (TLE) as a proof-of-concept for the relevance of this area in human TLE. Design, Setting, and Participants This cohort study used voxel-based morphometry and volumetry to assess differences in structural magnetic resonance imaging (MRI) scans in consecutive patients with TLE who underwent epilepsy surgery in a single center from January 1, 2005, through December 31, 2013. Participants underwent presurgical and postsurgical structural MRI and had at least 2 years of postoperative follow-up (median, 5 years; range, 2-11 years). Patients with MRI of insufficient quality were excluded. Findings were validated in 2 independent cohorts from tertiary epilepsy surgery centers. Study follow-up was completed on September 23, 2016, and data were analyzed from September 24, 2016, through April 24, 2018. Exposures Standard anterior temporal lobe resection. Main Outcomes and Measures Long-term postoperative seizure freedom. Results In total, 107 patients with unilateral TLE (left-sided in 68; 63.6% women; median age, 37 years [interquartile range {IQR}, 30-45 years]) were included in the derivation cohort. Reduced postsurgical gray matter volumes were found in the ipsilateral piriform cortex in the postoperative seizure-free group (n = 46) compared with the non-seizure-free group (n = 61). A larger proportion of the piriform cortex was resected in the seizure-free compared with the non-seizure-free groups (median, 83% [IQR, 64%-91%] vs 52% [IQR, 32%-70%]; P < .001). The results were seen in left- and right-sided TLE and after adjusting for clinical variables, presurgical gray matter alterations, presurgical hippocampal volumes, and the proportion of white matter tract disconnection. Findings were externally validated in 2 independent cohorts (31 patients; left-sided TLE in 14; 54.8% women; median age, 41 years [IQR, 31-46 years]). The resected proportion of the piriform cortex was individually associated with seizure outcome after surgery (derivation cohort area under the curve, 0.80 [P < .001]; external validation cohorts area under the curve, 0.89 [P < .001]). Removal of at least half of the piriform cortex increased the odds of becoming seizure free by a factor of 16 (95% CI, 5-47; P < .001). Other mesiotemporal structures (ie, hippocampus, amygdala, and entorhinal cortex) and the overall resection volume were not associated with outcomes. Conclusions and Relevance These results support the importance of resecting the piriform cortex in neurosurgical treatment of TLE and suggest that this area has a key role in seizure generation.

Method of invasive monitoring in epilepsy surgery and seizure freedom and morbidity: A systematic review.

Abstract: Objective Invasive monitoring is sometimes necessary to guide resective surgery in epilepsy patients, but the ideal method is unknown. In this systematic review, we assess the association of postresection seizure freedom and adverse events in stereoelectroencephalography (SEEG) and subdural electrodes (SDE). Methods We searched three electronic databases (MEDLINE, Embase, and CENTRAL [Cochrane Central Register of Controlled Trials]) from their inception to January 2018 with the keywords "electroencephalography," "intracranial grid," and "epilepsy." Studies that presented primary quantitative patient data for postresection seizure freedom with at least 1 year of follow-up or complication rates of SEEG- or SDE-monitored patients were included. Two trained investigators independently collected data from eligible studies. Weighted mean differences (WMDs) with 95% confidence interval (CIs) were used as a measure of the association of SEEG or SDE with seizure freedom and with adverse event outcomes. Results Of 11 462 screened records, 48 studies met inclusion criteria. These studies reported on 1973 SEEG patients and 2036 SDE patients. Our systematic review revealed SEEG was associated with 61.0% and SDE was associated with 56.4% seizure freedom after resection (WMD = +5.8%, 95% CI = 4.7-6.9%, P = .001). Furthermore, SEEG was associated with 4.8% and SDE was associated with 15.5% morbidity (WMD = -10.6%, 95% CI = -11.6 to -9.6%, P = .001). SEEG was associated with 0.2% mortality and SDE was associated with 0.4% mortality (WMD = -0.2%, 95% CI = -0.3 to -0.1%, P = .001). Significance In this systematic review of SEEG and SDE invasive monitoring techniques, SEEG was associated with fewer surgical resections yet better seizure freedom outcomes in those undergoing resections. SEEG was also associated with lower mortality and morbidity than SDE. Clinical studies directly comparing these modalities are necessary to understand the relative rates of seizure freedom, morbidity, and mortality associated with these techniques.

Epilepsy Surgery in the First 3 Years of Life: Predictors of Seizure Freedom and Cognitive Development.

Abstract: Background Although the majority of children undergoing epilepsy surgery are younger than 3 yr at epilepsy manifestation, only few actually receive surgical treatment in early childhood. Past studies have, however, suggested that earlier intervention may correlate with superior developmental outcomes. Objective To identify predictors for long-term seizure freedom and cognitive development following epilepsy surgery in the first 3 yr of life and determine the appropriate timing for surgical treatment in this age group. Methods We retrospectively analyzed the data of 48 consecutive children aged 1.1 ± 0.7 yr at surgery. Results Final surgeries comprised 52% hemispherotomies, 13% multilobar, and 35% intralobar resections. Etiology included cortical malformations in 71%, peri- or postnatal ischemic lesions in 13%, and benign tumor or tuberous sclerosis in 8% each. At last follow-up (median 4.3, range 1-14.3 yr), 60% of children remained seizure-free: 38% had discontinued antiepileptic drugs. Intralobar lesionectomy resulted more often in seizure control than multilobar or hemispheric surgery. Postsurgical seizure freedom was determined by the completeness of resection. Early postsurgical seizures were key markers of seizure recurrence. Presurgical adaptive and cognitive developmental status was impaired in 89% children. Longer epilepsy duration and larger lesion extent were detrimental to presurgical development, which, in turn, determined the postsurgical developmental outcome. Conclusion Our study demonstrates that epilepsy surgery in very young children is safe as well as efficient regarding long-term seizure freedom and antiepileptic drug cessation in selected candidates. Longer epilepsy duration is the only modifiable predictor of impaired adaptive and cognitive development, thus supporting early surgical intervention.

Responsive neurostimulation targeting the anterior nucleus of the thalamus in 3 patients with treatment-resistant multifocal epilepsy.

Abstract: Electrical stimulation in the anterior nucleus of the thalamus (ANT) has previously been found to be efficacious for reducing seizure frequency in patients with epilepsy. Bilateral deep brain stimulation (DBS) of the ANT is an open-loop system that can be used in the management of treatment-resistant epilepsy. In contrast, the responsive neurostimulation (RNS) system is a closed-loop device that delivers treatment in response to prespecified electrocorticographic triggers. The efficacy and safety of RNS targeting the ANT is unknown. We describe 3 patients with treatment-resistant multifocal epilepsy who were implanted with an RNS system, which included unilateral stimulation of the ANT. After >33 months of follow-up, there were no adverse effects on mood, memory or behavior. Two patients had ≥50% reduction in disabling seizures and one patient had a 50% reduction compared to pretreatment baseline. Although reduction in seizure frequency has been modest to date, these findings support responsive neurostimulation of the ANT as feasible, safe, and well-tolerated. Further studies are needed to determine optimal stimulation parameters.

Association of Seizure Spread With Surgical Failure in Epilepsy.

Abstract: Importance Seizures recur in as many as half of patients who undergo surgery for drug-resistant temporal lobe epilepsy (TLE). Understanding why TLE is resistant to surgery in some patients may reveal insights into epileptogenic networks and direct new therapies to improve outcomes. Objective To characterize features of surgically refractory TLE. Design, Setting, and Participants Medical records from a comprehensive epilepsy center were retrospectively reviewed for 131 patients who received a standard anteromedial temporal resection by a single surgeon from January 1, 2000, to December 31, 2015. Thirteen patients were excluded for having less than 1 year of follow-up. Patients at the highest risk for seizure recurrence were identified. Intracranial electroencephalogram (iEEG) analyses generated 3-dimensional seizure spread representations and quantified rapid seizure spread. The final analyses of seizure outcome and follow-up data were performed in June 2017. Main Outcomes and Measures The Engel class seizure outcome following surgery was evaluated for all patients, defining seizure recurrence as Engel class II or greater. Intracranial recordings of neocortical grids/strips and depth electrodes were analyzed visually for seizure spread. Fast β power was projected onto reconstructions of patients’ brain magnetic resonance imaging scans to visualize spread patterns and was quantified to compare power within vs outside resective margins. Results Of 118 patients with 1 year of follow-up or more (mean [SD], 6.5 [4.6] years), 66 (55.9%) were women and 52 (44.1%) were men (median age, 39 years [range, 4-66 years]). The cumulative probability of continuous Engel class I seizure freedom since surgery at postoperative year 10 and afterward was 65.6%, with 92% of recurrences in years 1 to 3. Multivariable statistical analyses found that the selection for iEEG study was the most reliable predictor of seizure recurrence, with a mixed-effects model estimating that the Engel score in the iEEG cohort was higher by a mean (SD) of 1.1 (0.33) (P = .001). In patients with iEEG results, rapid seizure spread in less than 10 seconds was associated with recurrence (hazard ratio, 5.99; 95% CI, 1.7-21.1;P Conclusions and significance Rapid seizure spread outside anteromedial temporal resection resective margins plays a significant role in the surgical failure of drug-resistant TLE. Seizure control after epilepsy surgery might be improved by investigating areas of early spread as candidates for resection or neuromodulation.

Referral to evaluation for epilepsy surgery: Reluctance by epileptologists and patients.

Abstract: OBJECTIVE Despite the obvious advantages of resective surgery in patients with drug-resistant focal epilepsy, namely high probability of seizure freedom, decreased mortality, and increased quality of life, referral rates from physicians and approval rates by patients for presurgical assessment remain constantly low. METHODS In the outpatient clinics of a tertiary epilepsy center, checklists were implemented asking treating epileptologists whether they recommended presurgical evaluation with noninvasive video-electroencephalographic monitoring to adult patients with drug-resistant focal epilepsy and asking respective patients whether they followed this recommendation. RESULTS Of 185 eligible patients, 80 (43%) were recommended presurgical evaluation by their epileptologists, and 24 (30%) of these patients consented. Nineteen of all patients (10%) actually underwent noninvasive presurgical assessment, and nine of these eventually proceeded to resection. The most frequent reason for nonreferral by epileptologists was their subjective appraisal of seizure frequency as low (31%), whereas patients declined most often due to overall fear of brain surgery (50%). Variables independently associated with nonreferral by epileptologists comprised older age of patients at questioning (odds ratio [OR] = 1.03), no previous evaluation for epilepsy surgery (OR = 4.04), the presence of legal guardianship (OR = 4.29), and ≥11 years of professional experience by the treating epileptologist (OR = 4.62). Independent predictors for patients' rejection of presurgical evaluation were older age at questioning (OR = 1.08), lifetime number of antiepileptic drugs ≥ 5 (OR = 4.47), presence of focal aware seizures (OR = 4.37), and absence of focal seizures with impaired awareness (OR = 11.24). SIGNIFICANCE In both epileptologists and patients with difficult-to-treat epilepsy, we found high decision rates against presurgical assessment. Some reasons given by physicians for not recommending presurgical evaluation to patients may be understandable; others need further exploration. On the patients' side, early and thorough counseling on risks and benefits of epilepsy surgery is necessary to increase understanding and acceptance.

Rates and predictors of seizure outcome after corpus callosotomy for drug-resistant epilepsy: a meta-analysis.

Abstract: OBJECTIVECorpus callosotomy is a palliative surgery for drug-resistant epilepsy that reduces the severity and frequency of generalized seizures by disconnecting the two cerebral hemispheres. Unlike with resection, seizure outcomes remain poorly understood. The authors systematically reviewed the literature and performed a meta-analysis to investigate rates and predictors of complete seizure freedom and freedom from drop attacks after corpus callosotomy.METHODSPubMed, Web of Science, and Scopus were queried for primary studies examining seizure outcomes after corpus callosotomy published over 30 years. Rates of complete seizure freedom or drop attack freedom were recorded. Variables showing a potential relationship to seizure outcome on preliminary analysis were subjected to formal meta-analysis.RESULTSThe authors identified 1742 eligible patients from 58 included studies. Overall, the rates of complete seizure freedom and drop attack freedom after corpus callosotomy were 18.8% and 55.3%, respectively. Complete seizure freedom was significantly predicted by the presence of infantile spasms (OR 3.86, 95% CI 1.13-13.23), normal MRI findings (OR 4.63, 95% CI 1.75-12.25), and shorter epilepsy duration (OR 2.57, 95% CI 1.23-5.38). Freedom from drop attacks was predicted by complete over partial callosotomy (OR 2.90, 95% CI 1.07-7.83) and idiopathic over known epilepsy etiology (OR 2.84, 95% CI 1.35-5.99).CONCLUSIONSThe authors report the first systematic review and meta-analysis of seizure outcomes in both adults and children after corpus callosotomy for epilepsy. Approximately one-half of patients become free from drop attacks, and one-fifth achieve complete seizure freedom after surgery. Some predictors of favorable outcome differ from those in resective epilepsy surgery.

Indications and expectations for neuropsychological assessment in epilepsy surgery in children and adults.

Abstract: In our first paper in this series (Epilepsia 2015; 56(5): 674-681), we published recommendations for the indications and expectations for neuropsychological assessment in routine epilepsy care. This partner paper provides a comprehensive overview of the more specialist role of neuropsychological assessment in the pre and postoperative evaluation of epilepsy surgery patients. The paper is in two parts. The first part presents the framework for the mandatory role of neuropsychologists in the presurgical evaluation of epilepsy surgery candidates. A preoperative neuropsychological assessment should be comprised of standardised measures of cognitive function in addition to wider measures of behavioural and psychosocial function. The results from the presurgical assessment are used to: (1) establish a baseline against which change can be measured following surgery; (2) provide a collaborative contribution to seizure characterization, lateralization and localization; (3) provide evidence-based predictions of cognitive risk associated with the proposed surgery; and (4) provide the evidence base for comprehensive preoperative counselling, including exploration of patient expectations of surgical treatment. The second part examines the critical role of the neuropsychologist in the evaluation of postoperative outcomes. Neuropsychological changes following surgery are dynamic and a comprehensive, long-term assessment of these changes following surgery should form an integral part of the postoperative follow-up. The special considerations with respect to pre and postoperative assessment when working with paediatric populations and those with an intellectual disability are also discussed. The paper provides a summary checklist for neuropsychological involvement throughout the epilepsy surgery process, based on the recommendations discussed.

Clinical features of sleep-related hypermotor epilepsy in relation to the seizure-onset zone: A review of 135 surgically treated cases

Abstract: Objectives Sleep-related hypermotor epilepsy (SHE), formerly nocturnal frontal lobe epilepsy, is characterized by abrupt and typically sleep-related seizures with motor patterns of variable complexity and duration. They seizures arise more frequently in the frontal lobe than in the extrafrontal regions but identifying the seizure onset-zone (SOZ) may be challenging. In this study, we aimed to describe the clinical features of both frontal and extrafrontal SHE, focusing on ictal semiologic patterns in order to increase diagnostic accuracy. Methods We retrospectively analyzed the clinical features of patients with drug-resistant SHE seen in our center for epilepsy surgery. Patients were divided into frontal and extrafrontal SHE (temporal, operculoinsular, and posterior SHE). We classified seizure semiology according to four semiology patterns (SPs): elementary motor signs (SP1), unnatural hypermotor movements (SP2), integrated hypermotor movements (SP3), and gestural behaviors with high emotional content (SP4). Early nonmotor manifestations were also assessed. Results Our case series consisted of 91 frontal SHE and 44 extrafrontal SHE cases. Frontal and extrafrontal SHE shared many features such as young age at onset, high seizure-frequency rate, high rate of scalp electroencephalography (EEG) and magnetic resonance imaging (MRI) abnormalities, similar histopathologic substrates, and good postsurgical outcome. Within the frontal lobe, SPs were organized in a posteroanterior gradient (SP1-4) with respect to the SOZ. In temporal SHE, SP1 was rare and SP3-4 frequent, whereas in operculoinsular and posterior SHE, SP4 was absent. Nonmotor manifestations were frequent (70%) and some could provide valuable localizing information. Significance Our study shows that the presence of certain SP and nonmotor manifestations may provide helpful information to localize seizure onset in patients with SHE.

Presurgical epilepsy evaluation and epilepsy surgery.

Abstract: With a prevalence of 0.8 to 1.2%, epilepsy represents one of the most frequent chronic neurological disorders; 30 to 40% of patients suffer from drug-resistant epilepsy (that is, seizures cannot be controlled adequately with antiepileptic drugs). Epilepsy surgery represents a valuable treatment option for 10 to 50% of these patients. Epilepsy surgery aims to control seizures by resection of the epileptogenic tissue while avoiding neuropsychological and other neurological deficits by sparing essential brain areas. The most common histopathological findings in epilepsy surgery specimens are hippocampal sclerosis in adults and focal cortical dysplasia in children. Whereas presurgical evaluations and surgeries in patients with mesial temporal sclerosis and benign tumors recently decreased in most centers, non-lesional patients, patients requiring intracranial recordings, and neocortical resections increased. Recent developments in neurophysiological techniques (high-density electroencephalography [EEG], magnetoencephalography, electrical and magnetic source imaging, EEG-functional magnetic resonance imaging [EEG-fMRI], and recording of pathological high-frequency oscillations), structural magnetic resonance imaging (MRI) (ultra-high-field imaging at 7 Tesla, novel imaging acquisition protocols, and advanced image analysis [post-processing] techniques), functional imaging (positron emission tomography and single-photon emission computed tomography co-registered to MRI), and fMRI significantly improved non-invasive presurgical evaluation and have opened the option of epilepsy surgery to patients previously not considered surgical candidates. Technical improvements of resective surgery techniques facilitate successful and safe operations in highly delicate brain areas like the perisylvian area in operculoinsular epilepsy. Novel less-invasive surgical techniques include stereotactic radiosurgery, MR-guided laser interstitial thermal therapy, and stereotactic intracerebral EEG-guided radiofrequency thermocoagulation.

Accuracy of Interictal and Ictal Electric and Magnetic Source Imaging: A Systematic Review and Meta-Analysis

Abstract: Background: Electric and magnetic source imaging methods (ESI, MSI) estimate the location in the brain of the sources generating the interictal epileptiform discharges (II-ESI, II-MSI) and the ictal activity (IC-ESI, IC-MSI). These methods provide potentially valuable clinical information in the presurgical evaluation of patients with drug-resistant focal epilepsy, evaluated for surgical therapy. In spite of the significant technical advances in this field, and the numerous papers published on clinical validation of these methods, ESI and MSI are still underutilized in most epilepsy centers performing a presurgical evaluation. Our goal was to review and summarize the published evidence on the diagnostic accuracy of interictal and ictal ESI and MSI in epilepsy surgery. Methods: We searched the literature for papers on ESI and MSI that specified the diagnostic reference standard as the site of resection and the postoperative outcome (seizure-freedom). We extracted data from the selected studies, to calculate the diagnostic accuracy measures. Results: Our search resulted in 797 studies; 48 studies fulfilled the selection criteria (25 ESI and 23 MSI studies), providing data from 1,152 operated patients (515 for II-ESI, 440 for II-MSI, 159 for IC-ESI, and 38 for IC-MSI). The sensitivity of source imaging methods was between 74 and 90% (highest for IC-ESI). The specificity of the source imaging methods was between 20 and 54% (highest for II-MSI). The overall accuracy was between 50 and 75% (highest for IC-ESI). Diagnostic Odds Ratio was between 0.8 (IC-MSI) and 4.02–7.9 (II-ESI < II-MSI < IC-ESI). Conclusions: Our systematic review and meta-analysis provides evidence for the accuracy of source imaging in presurgical evaluation of patients with drug-resistant focal epilepsy. These methods have high sensitivity (up to 90%) and diagnostic odds ratio (up to 7.9), but the specificity is lower (up to 54%). ESI and MSI should be included in the multimodal presurgical evaluation.

Network-targeted approach and postoperative resting-state functional magnetic resonance imaging are associated with seizure outcome.

Abstract: OBJECTIVE Postoperative resting-state functional magnetic resonance imaging (MRI) in children with intractable epilepsy has not been quantified in relation to seizure outcome Therefore, its value as a biomarker for epileptogenic pathology is not well understood METHODS In a sample of children with intractable epilepsy who underwent prospective resting-state seizure onset zone (SOZ)-targeted epilepsy surgery, postoperative resting-state functional MRI (rs-fMRI) was performed 6 to 12 months later Graded normalization of the postoperative resting-state SOZ was compared to seizure outcomes, patient, surgery, and anatomical MRI characteristics RESULTS A total of 64 cases were evaluated Network-targeted surgery, followed by postoperative rs-fMRI normalization was significantly (p < 0001) correlated with seizure reduction, with a Spearman rank correlation coefficient of 083 Of 39 cases with postoperative rs-fMRI SOZ normalization, 38 (97%) became completely seizure free In contrast, of the 25 cases without complete rs-fMRI SOZ normalization, only 3 (5%) became seizure free The accuracy of rs-fMRI as a biomarker predicting seizure freedom is 94%, with 96% sensitivity and 93% specificity INTERPRETATION Among seizure localization techniques in pediatric epilepsy, network-targeted surgery, followed by postoperative rs-fMRI normalization, has high correlation with seizure freedom This study shows that rs-fMRI SOZ can be used as a biomarker of the epileptogenic zone, and postoperative rs-fMRI normalization is a biomarker for SOZ quiescence ANN NEUROL 2019;86:344-356

Laser ablation for mesial temporal epilepsy: a multi-site, single institutional series.

Abstract: OBJECTIVEAlthough it is still early in its application, laser interstitial thermal therapy (LiTT) has increasingly been employed as a surgical option for patients with mesial temporal lobe epilepsy. This study aimed to describe mesial temporal lobe ablation volumes and seizure outcomes following LiTT across the Mayo Clinic's 3 epilepsy surgery centers.METHODSThis was a multi-site, single-institution, retrospective review of seizure outcomes and ablation volumes following LiTT for medically intractable mesial temporal lobe epilepsy between October 2011 and October 2015. Pre-ablation and post-ablation follow-up volumes of the hippocampus were measured using FreeSurfer, and the volume of ablated tissue was also measured on intraoperative MRI using a supervised spline-based edge detection algorithm. To determine seizure outcomes, results were compared between those patients who were seizure free and those who continued to experience seizures.RESULTSThere were 23 patients who underwent mesial temporal LiTT within the study period. Fifteen patients (65%) had left-sided procedures. The median follow-up was 34 months (range 12-70 months). The mean ablation volume was 6888 mm3. Median hippocampal ablation was 65%, with a median amygdala ablation of 43%. At last follow-up, 11 (48%) of these patients were seizure free. There was no correlation between ablation volume and seizure freedom (p = 0.69). There was also no correlation between percent ablation of the amygdala (p = 0.28) or hippocampus (p = 0.82) and seizure outcomes. Twelve patients underwent formal testing with computational visual fields. Visual field changes were seen in 67% of patients who underwent testing. Comparing the 5 patients with clinically noticeable visual field deficits to the rest of the cohort showed no significant difference in ablation volume between those patients with visual field deficits and those without (p = 0.94). There were 11 patients with follow-up neuropsychological testing. Within this group, verbal learning retention was 76% in the patients with left-sided procedures and 89% in those with right-sided procedures.CONCLUSIONSIn this study, there was no significant correlation between the ablation volume after LiTT and seizure outcomes. Visual field deficits were common in formally tested patients, much as in patients treated with open temporal lobectomy. Further studies are required to determine the role of amygdalohippocampal ablation.