Predictors Of Seizure Outcome Research Articles

1132 Phase 1 Correlates of Seizure Onset Zone for Prediction of sEEG Placement and Clinical Outcomes

INTRODUCTION: Approximately 20 million people worldwide suffer from drug resistant epilepsy. Treatment of the seizure onset zone (SOZ) can reduce seizure burden. When phase 1 testing fails to identify a clear surgical lesion, stereo-electroencephalography (sEEG) offers a high-resolution spatial map of cortical and subcortical activity. However, each additional lead placed also increases the chances of a complication. Preoperative identification of optimal targets is crucial to minimizing the risk-benefit ratio of sEEG placement. METHODS: We studied epilepsy patients that underwent sEEG placement followed by resection, stimulation, or laser ablation at a single institution from 1/2012 to 11/2021. Leads were identified by their respective Phase 1 indications. Preoperative and 1-year postoperative clinical outcomes were compared. Hypothesis testing was performed via the Wilcoxon rank sum test and Fisher’s exact test. A logistic generalized linear mixed effect model was used for multivariate analysis. RESULTS: 101 patients had 1752 leads placed with 239 SOZs found and treated. Mean weekly seizure frequency decreased from 25.2 to 7.8 (p < 0.001). SOZ leads were more likely to have concordant findings (p < 0.001) across studies. Lesions with PET hypometabolism (OR 1.4), MRI abnormalities (OR 1.9), MEG Clusters (OR 1.9) and calcifications (OR 3.2) were significantly more likely to predict SOZ, though PET hypometabolism was not significant in multivariate analysis. While the reason for lead placement in the SOZ did not predict seizure outcomes, patients with other lesions that had MEG Clusters or Calcifications had an average 15% worse seizure reduction than those without (p < 0.005). CONCLUSIONS: Certain Phase 1 aspects of a putative lesion, such as MRI abnormalities, the presence of calcifications, or MEG clusters can predict SOZ and clinical outcomes.

Amygdala enlargement in temporal lobe epilepsy: Histopathology and surgical outcomes.

Amygdala enlargement is detected on magnetic resonance imaging (MRI) in some patients with drug-resistant temporal lobe epilepsy (TLE), but its clinical significance remains uncertain We aimed to assess if the presence of amygdala enlargement (1) predicted seizure outcome following anterior temporal lobectomy with amygdalohippocampectomy (ATL-AH) and (2) was associated with specific histopathological changes. This was a case-control study. We included patients with drug-resistant TLE who underwent ATL-AH with and without amygdala enlargement detected on pre-operative MRI. Amygdala volumetry was done using FreeSurfer for patients who had high-resolution T1-weighted images. Mann-Whitney U test was used to compare pre-operative clinical characteristics between the two groups. The amygdala volume on the epileptogenic side was compared to the amygdala volume on the contralateral side among cases and controls. Then, we used a two-sample, independent t test to compare the means of amygdala volume differences between cases and controls. The chi-square test was used to assess the correlation of amygdala enlargement with (1) post-surgical seizure outcomes and (2) histopathological changes. Nineteen patients with and 19 patients without amygdala enlargement were studied. Their median age at surgery was 38 years for cases and 39 years for controls, and 52.6% were male. There were no statistically significant differences between the two groups in their pre-operative clinical characteristics. There were significant differences in the means of volume difference between cases and controls (Diff = 457.2 mm3, 95% confidence interval [CI] 289.6-624.8; p < .001) and in the means of percentage difference (p < .001). However, there was no significant association between amygdala enlargement and surgical outcome (p = .72) or histopathological changes (p = .63). The presence of amygdala enlargement on the pre-operative brain MRI in patients with TLE does not affect the surgical outcome following ATL-AH, and it does not necessarily suggest abnormal histopathology. These findings suggest that amygdala enlargement might reflect a secondary reactive process to seizures in the epileptogenic temporal lobe.

Multimodal non-invasive evaluation in MRI-negative epilepsy patients.

Presurgical evaluation is still challenging for MRI-negative epilepsy patients. As non-invasive modalities are the easiest acceptable and economic methods in determining the epileptogenic zone, we analyzed the localization value of common non-invasive methods in MRI-negative epilepsy patients. In this study, we included epilepsy patients undergoing presurgical evaluation with presurgical negative MRI. MRI post-processing was performed using a Morphometric Analysis Program (MAP) on T1-weighted volumetric MRI. The relationship between MAP, magnetoencephalography (MEG), scalp electroencephalogram (EEG), and seizure outcomes was analyzed to figure out the localization value of different non-invasive methods. Eighty-six patients were included in this study. Complete resection of the MAP-positive regions or the MEG-positive regions was positively associated with seizure freedom (p = 0.028 and 0.007, respectively). When an area is co-localized by MAP and MEG, the resection of the area was significantly associated with seizure freedom (p = 0.006). However, neither the EEG lateralization nor the EEG localization showed statistical association with the surgical outcome (p = 0.683 and 0.505, respectively). In conclusion, scalp EEG had a limited role in presurgical localization and predicting seizure outcome, combining MAP and MEG results can significantly improve the localization of epileptogenic lesions and have a positive association with seizure-free outcome. PLAIN LANGUAGE SUMMARY: Due to the lack of obvious structure abnormalities on neuroimaging examinations, the identification of epilepsy lesions in MRI-negative epilepsy patients can be difficult. In this study, we intended to use non-invasive examinations to explore the potential epileptic lesions in MRI-negative epilepsy patients and to determine the results accuracy by comparing the neuroimaging results with the epilepsy surgery outcomes. A total of 86 epilepsy patients without obvious structure lesions on MRI were included, and we found that the combinations of different non-invasive examinations and neuroimaging post-processing methods are significantly associated with the seizure freedom results of epilepsy surgery.

Clinical and pathologic features of Sturge-Weber syndrome in patients with refractory epilepsy.

We aimed to investigate the clinicopathologic features of and genetic changes in Sturge-Weber syndrome (SWS) in patients with refractory epilepsy. Clinical data were retrospectively analyzed. H&E and immunohistochemistry were performed to assess pathologic changes. Targeted amplicon sequencing was applied to investigate the somatic GNAQ (c.548G>A) mutation. The potential predictors of seizure outcomes were estimated by univariate and multivariate statistical analyses. Forty-eight patients with SWS and refractory epilepsy were enrolled. According to the imaging data and pathologic examination, ipsilateral hippocampal sclerosis (HS), calcification of leptomeningeal arteries, and focal cortical dysplasia were found in 14 (29.2%), 31 (64.6%), and 37 (77.1%) patients, respectively. A high frequency of GNAQ alteration was detected in both cerebral cortex (57.7%) and ipsilateral hippocampus (50.0%) from patients with SWS. During follow-up, 43 of 48 patients (85.4%) had achieved seizure control (Engel class I). Statistically, HS signs on imaging were found to be independent predictors of unfavorable seizure outcomes (P = .015). Calcification of leptomeningeal arteries, focal cortical dysplasia, and GNAQ alteration are common features in SWS pathology. Patients with refractory epilepsy caused by SWS can achieve satisfactory seizure control after surgery, but seizure control was compromised in patients with comorbid HS.

Predictors of seizure outcomes in stereo-electroencephalography-guided radio-frequency thermocoagulation for MRI-negative epilepsy.

One-third of intractable epilepsy patients have no visually identifiable focus for neurosurgery based on imaging tests [magnetic resonance imaging (MRI)-negative cases]. Stereo-electroencephalography-guided radio-frequency thermocoagulation (SEEG-guided RF-TC) is utilized in the clinical treatment of epilepsy to lower the incidence of complications post-open surgery. This study aimed to identify prognostic factors and long-term seizure outcomes in SEEG-guided RF-TC for patients with MRI-negative epilepsy. This was a single-center retrospective cohort study. We included 30 patients who had undergone SEEG-guided RF-TC at Sanbo Brain Hospital, Capital Medical University, from April 2015 to December 2019. The probability of remaining seizure-free and the plotted survival curves were analyzed. Prognostic factors were analyzed using log-rank tests in univariate analysis and the Cox regression model in multivariate analysis. With a mean time of 31.07 ± 2.64 months (median 30.00, interquartile range: 18.00-40.00 months), 11 out of 30 patients (36.7%) were classified as International League Against Epilepsy class 1 in the last follow-up. The mean time of remaining seizure-free was 21.33 ± 4.55 months [95% confidence interval (CI) 12.41-30.25], and the median time was 3.00 ± 0.54 months (95% CI 1.94-4.06). Despite falling in the initial year, the probability of remaining seizure-free gradually stabilizes in the subsequent years. The patients were more likely to obtain seizure freedom when the epileptogenic zone was located in the insular lobe or with one focus on the limbic system (p = 0.034, hazard ratio 5.019, 95% CI 1.125-22.387). Our findings may be applied to guide individualized surgical interventions and help clinicians make better decisions.

High frequency oscillations in relation to interictal spikes in predicting postsurgical seizure freedom

We evaluate whether interictal spikes, epileptiform HFOs and their co-occurrence (Spike + HFO) were included in the resection area with respect to seizure outcome. We also characterise the relationship between high frequency oscillations (HFOs) and propagating spikes. We analysed intracranial EEG of 20 patients that underwent resective epilepsy surgery. The co-occurrence of ripples and fast ripples was considered an HFO event; the co-occurrence of an interictal spike and HFO was considered a Spike + HFO event. HFO distribution and spike onset were compared in cases of spike propagation. Accuracy in predicting seizure outcome was 85% for HFO, 60% for Spikes, and 79% for Spike + HFO. Sensitivity was 57% for HFO, 71% for Spikes and 67% for Spikes + HFO. Specificity was 100% for HFO, 54% for Spikes and 85% for Spikes + HFO. In 2/2 patients with spike propagation, the spike onset included the HFO area. Combining interictal spikes with HFO had comparable accuracy to HFO. In patients with propagating spikes, HFO rate was maximal at the onset of spike propagation.

Hemimegalencephaly: A Systematic Comparison of Functional and Anatomic Hemispherectomy for Drug-Resistant Epilepsy.

Hemimegalencephaly (HME) is a rare diffuse malformation of cortical development characterized by unihemispheric hypertrophy, drug-resistant epilepsy (DRE), hemiparesis, and developmental delay. Definitive treatment for HME-related DRE is hemispheric surgery through either anatomic (AH) or functional hemispherectomy (FH). This individual patient data meta-analysis assessed seizure outcomes of AH and FH for HME with pharmacoresistant epilepsy, predictors of Engel I, and efficacy of different FH approaches. PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature were searched from inception to Jan 13th, 2023, for primary literature reporting seizure outcomes in >3 patients with HME receiving AH or FH. Demographics, neurophysiology findings, and Engel outcome at the last follow-up were extracted. Postsurgical seizure outcomes were compared through 2-tailed t -test and Fisher exact test. Univariate and multivariate Cox regression analyses were performed to identify independent predictors of Engel I outcome. Data from 145 patients were extracted from 26 studies, of which 89 underwent FH (22 vertical, 33 lateral), 47 underwent AH, and 9 received an unspecified hemispherectomy with a median last follow-up of 44.0 months (FH cohort) and 45.0 months (AH cohort). Cohorts were similar in preoperative characteristics and at the last follow-up; 77% (n = 66) of the FH cohort and 81% (n = 38) and of the AH cohort were Engel I. On multivariate analysis, only the presence of bilateral ictal electroencephalography abnormalities (hazard ratio = 11.5; P = .002) was significantly associated with faster time-to-seizure recurrence. A number-needed-to-treat analysis to prevent 1 additional case of posthemispherectomy hydrocephalus reveals that FH, compared with AH, was 3. There was no statistical significance for any differences in time-to-seizure recurrence between lateral and vertical FH approaches (hazard ratio = 2.59; P = .101). We show that hemispheric surgery is a highly effective treatment for HME-related DRE. Unilateral ictal electroencephalography changes and using the FH approach as initial surgical management may result in better outcomes due to significantly lower posthemispherectomy hydrocephalus probability. However, larger HME registries are needed to further delineate the predictors of seizure outcomes.

Hemispheric epilepsy surgery for hemimegalencephaly: The UCLA experience.

Hemimegalencephaly (HME) is a rare congenital brain malformation presenting predominantly with drug-resistant epilepsy. Hemispheric disconnective surgery is the mainstay of treatment; however, little is known about how postoperative outcomes compare across techniques. Thus we present the largest single-center cohort of patients with HME who underwent epilepsy surgery and characterize outcomes. This observational study included patients with HME at University of California Los Angeles (UCLA) from 1984 to 2021. Patients were stratified by surgical intervention: anatomic hemispherectomy (AH), functional hemispherectomy (FH), or less-than-hemispheric resection (LTH). Seizure freedom, functional outcomes, and operative complications were compared across surgical approaches. Regression analysis identified clinical and intraoperative variables that predict seizure outcomes. Of 56 patients, 43 (77%) underwent FH, 8 (14%) underwent AH, 2 (4%) underwent LTH, 1 (2%) underwent unknown hemispherectomy type, and 2 (4%) were managed non-operatively. At median last follow-up of 55 months (interquartile range [IQR] 20-92 months), 24 patients (49%) were seizure-free, 17 (30%) required cerebrospinal fluid (CSF) shunting for hydrocephalus, 9 of 43 (21%) had severe developmental delay, 8 of 38 (21%) were non-verbal, and 15 of 38 (39%) were non-ambulatory. There was one (2%) intraoperative mortality due to exsanguination earlier in this cohort. Of 12 patients (29%) requiring revision surgery, 6 (50%) were seizure-free postoperatively. AH, compared to FH, was not associated with statistically significant improved seizure freedom (hazard ratio [HR] = .48, p = .328), although initial AH trended toward greater odds of seizure freedom (75% vs 46%, p = .272). Younger age at seizure onset (HR = .29, p = .029), lack of epilepsia partialis continua (EPC) (HR = .30, p = .022), and no contralateral seizures on electroencephalography (EEG) (HR = .33, p = .039) independently predicted longer duration of seizure freedom. This study helps inform physicians and parents of children who are undergoing surgery for HME by demonstrating that earlier age at seizure onset, absence of EPC, and no contralateral EEG seizures were associated with longer postoperative seizure freedom. At our center, initial AH for HME may provide greater odds of seizure freedom with complications and functional outcomes comparable to those of FH.

High-rate leading spikes in propagating spike sequences predict seizure outcome in surgical patients with temporal lobe epilepsy.

Inter-ictal spikes aid in the diagnosis of epilepsy and in planning surgery of medication-resistant epilepsy. However, the localizing information from spikes can be unreliable because spikes can propagate, and the burden of spikes, often assessed as a rate, does not always correlate with the seizure onset zone or seizure outcome. Recent work indicates identifying where spikes regularly emerge and spread could localize the seizure network. Thus, the current study sought to better understand where and how rates of single and coupled spikes, and especially brain regions with high-rate and leading spike of a propagating sequence, informs the extent of the seizure network. In 37 patients with medication-resistant temporal lobe seizures, who had surgery to treat their seizure disorder, an algorithm detected spikes in the pre-surgical depth inter-ictal EEG. A separate algorithm detected spike propagation sequences and identified the location of leading and downstream spikes in each sequence. We analysed the rate and power of single spikes on each electrode and coupled spikes between pairs of electrodes, and the proportion of sites with high-rate, leading spikes in relation to the seizure onset zone of patients seizure free (n = 19) and those with continuing seizures (n = 18). We found increased rates of single spikes in mesial temporal seizure onset zone (ANOVA, P < 0.001, η2 = 0.138), and increased rates of coupled spikes within, but not between, mesial-, lateral- and extra-temporal seizure onset zone of patients with continuing seizures (P < 0.001; η2 = 0.195, 0.113 and 0.102, respectively). In these same patients, there was a higher proportion of brain regions with high-rate leaders, and each sequence contained a greater number of spikes that propagated with a higher efficiency over a longer distance outside the seizure onset zone than patients seizure free (Wilcoxon, P = 0.0172). The proportion of high-rate leaders in and outside the seizure onset zone could predict seizure outcome with area under curve = 0.699, but not rates of single or coupled spikes (0.514 and 0.566). Rates of coupled spikes to a greater extent than single spikes localize the seizure onset zone and provide evidence for inter-ictal functional segregation, which could be an adaptation to avert seizures. Spike rates, however, have little value in predicting seizure outcome. High-rate spike sites leading propagation could represent sources of spikes that are important components of an efficient seizure network beyond the clinical seizure onset zone, and like the seizure onset zone these, too, need to be removed, disconnected or stimulated to increase the likelihood for seizure control.

Factors predicting seizure outcome after surgical excision of meningioma: SOLID-C guideline for prophylactic AED

BackgroundSeizures are commonly seen among meningioma patients and may cause impaired quality of life. These patients can be effectively treated with surgery. Still, many patients have persistent seizure episodes after surgery. The factors which are associated with worsening of seizure episodes remain critical in improving the quality of life for such patients. In this study, we aim to analyze the clinical and histopathological factors to predict the post excision seizure-outcome in meningioma and need of antiepileptic prophylaxis for these patients. MethodsAdult patients who underwent primary resection of meningioma at our institute between 2007 and 2020 were included in the study. Eligibility criteria were as follows: (i) Surgery for newly-diagnosed biopsy proven meningioma, (ii) Presence of pre-operative seizure (iii) A follow-up period ≥ 12 months. ResultsOf the 1145 patients in this series, 333 patients were recruited in study. The major determinants of prophylactic anti-epileptic were tumour size (S), Oedema (O), location (L), inclusion body (I), antiepileptic drugs (D) and surgical complication (C). The factors independently associated with poor seizure control after surgical resection were presence of brain parenchyma invasion (p < 0.001), pre-operative use of > 2 antiepileptics (p = 0.016) and presence of intranuclear inclusion bodies (p = 0.001). ConclusionsThe identification and consideration of factors associated with prolonged seizure control after surgery may help us to guide treatment strategies aimed at improving the quality of life for patients with meningiomas. Authors have proposed a SOLID-C guideline to avoid the blanket approach of prophylactic AED in patients undergoing for meningioma resection.

Long-term seizure and developmental outcomes of epilepsy surgery in children under 3 years old: A single-center study of 113 patients.

To investigate the clinical characteristics, surgical strategy, developmental and seizure outcomes, and predictors of surgical outcome in children with drug-resistant epilepsy (DRE) under 3 years old. One hundred thirteen consecutive children younger than 3 years of age with DRE underwent curative surgical treatment after multidisciplinary preoperative evaluation using the strategy developed in the pediatric epilepsy center of Peking University First Hospital (PKFHPEC) between 2014 and 2018. These patients were selected for retrospective study. The relevant clinical data were collected and analyzed. The surgical prognoses were classified using the Engel classification, and the developmental assessment results were collected. Statistical analysis of the clinical data was performed to analyze the predictors of seizure outcomes and their correlation with developmental outcomes. All the patients were followed up for more than 3 years, and 98 (86.7%) patients had no seizure recurrence. One year after surgery, the seizure-free rate was 86.7%, which was as high as that at the last follow-up. Cortical dysplasia was the most frequent etiology of DRE in this cohort, accounting for 77.0%. According to the Engel classification, acute postoperative seizure (APOS; p < 0.001) was a predictor of seizure recurrence. No deaths occurred. No unpredicted long-term severe complications occurred except for one ventricular peritoneal shunt. The patients' neurodevelopmental statuses were improved after successful surgery, while the scores of the pre- and postoperative developmental assessments were closely correlated. For children who are younger than 3 years old and have DRE and structural abnormalities, early curative treatment can lead to long-term good seizure outcomes and a low complication rate. The development of appropriate strategies for both presurgical evaluation and resection is crucial for the success of surgery.

Seizure outcomes after resection of primary brain tumors in pediatric patients: a systematic review and meta-analysis.

Primary brain neoplasms are the most common solid tumors in pediatric patients and seizures are a common presenting symptom. Surgical intervention improves oncologic outcomes and seizure burden. A better understanding of factors that influence seizure outcomes in the surgical management of primary brain tumors of childhood can guide treatment approach thereby improving patient quality of life. We performed a systematic analysis using articles queried from PubMed, EMBASE, and Cochrane published from January 1990 to August 2022 to determine predictors of seizure outcomes in pediatric patients undergoing resection of primary brain tumors. We identified 24 retrospective cohort studies, one prospective cohort study, and one mixed retrospective and prospective study for the systematic analysis. A total of 831 pediatric patients were available for analysis. 668 (80.4%) patients achieved seizure freedom after surgery. Complete tumor resection increased the likelihood of a seizure-free (Engel I) outcome compared to subtotal resection (OR 7.1, 95% CI 2.3-21.9). Rates of Engel I seizure outcomes did not significantly differ based on factors such as age at seizure onset, duration of epilepsy, gender, tumor laterality, or age at surgery, but trended towards significance for improved outcomes in temporal lobe tumors. Primary brain tumors in the pediatric population are commonly associated with seizures. Resection of these lesions reduces seizure burden and is associated with high rates of seizure freedom. Complete resection, compared to subtotal resection, significantly increases the likelihood of seizure-free outcomes.

Identifying sources of human interictal discharges with travelling wave and white matter propagation.

Interictal epileptiform discharges have been shown to propagate from focal epileptogenic sources as travelling waves or through more rapid white matter conduction. We hypothesize that both modes of propagation are necessary to explain interictal discharge timing delays. We propose a method that, for the first time, incorporates both propagation modes to identify unique potential sources of interictal activity. We retrospectively analysed 38 focal epilepsy patients who underwent intracranial EEG recordings and diffusion-weighted imaging for epilepsy surgery evaluation. Interictal discharges were detected and localized to the most likely source based on relative delays in time of arrival across electrodes, incorporating travelling waves and white matter propagation. We assessed the influence of white matter propagation on distance of spread, timing and clinical interpretation of interictal activity. To evaluate accuracy, we compared our source localization results to earliest spiking regions to predict seizure outcomes. White matter propagation helps to explain the timing delays observed in interictal discharge sequences, underlying rapid and distant propagation. Sources identified based on differences in time of receipt of interictal discharges are often distinct from the leading electrode location. Receipt of activity propagating rapidly via white matter can occur earlier than more local activity propagating via slower cortical travelling waves. In our cohort, our source localization approach was more accurate in predicting seizure outcomes than the leading electrode location. Inclusion of white matter in addition to travelling wave propagation in our model of discharge spread did not improve overall accuracy but allowed for identification of unique and at times distant potential sources of activity, particularly in patients with persistent postoperative seizures. Since distant white matter propagation can occur more rapidly than local travelling wave propagation, combined modes of propagation within an interictal discharge sequence can decouple the commonly assumed relationship between spike timing and distance from the source. Our findings thus highlight the clinical importance of recognizing the presence of dual modes of propagation during interictal discharges, as this may be a cause of clinical mislocalization.

Predictors of seizure outcomes of autoimmune encephalitis: A clinical and morphometric quantitative analysis study

ObjectiveAutoimmune encephalitis can be followed by treatment-resistant epilepsy. Understanding its predictors and mechanisms are crucial to future studies to improve autoimmune encephalitis outcomes. Our objective was to determine the clinical and imaging predictors of postencephalitic treatment-resistant epilepsy. MethodsWe performed a retrospective cohort study (2012–2017) of adults with autoimmune encephalitis, both antibody positive and seronegative but clinically definite or probable. We examined clinical and imaging (as defined by morphometric analysis) predictors of seizure freedom at long term follow-up. ResultsOf 37 subjects with adequate follow-up data (mean 4.3 yrs, SD 2.5), 21 (57 %) achieved seizure freedom after a mean time of 1 year (SD 2.3), and one third (13/37, 35 %) discontinued ASMs. Presence of mesial temporal hyperintensities on the initial MRI was the only independent predictor of ongoing seizures at last follow-up (OR 27.3, 95 %CI 2.48–299.5). Morphometric analysis of follow-up MRI scans (n = 20) did not reveal any statistically significant differences in hippocampal, opercular, and total brain volumes between patients with postencephalitic treatment-resistant epilepsy and those without. SignificancePostencephalitic treatment-resistant epilepsy is a common complication of autoimmune encephalitis and is more likely to occur in those with mesial temporal hyperintensities on acute MRI. Volume loss in the hippocampal, opercular, and overall brain on follow-up MRI does not predict postencephalitic treatment-resistant epilepsy, so additional factors beyond structural changes may account for its development.

Predicting seizure outcome after epilepsy surgery: Do we need more complex models, larger samples, or better data?

The accurate prediction of seizure freedom after epilepsy surgery remains challenging. We investigated if (1) training more complex models, (2) recruiting larger sample sizes, or (3) using data-driven selection of clinical predictors would improve our ability to predict postoperative seizure outcome using clinical features. We also conducted the first substantial external validation of a machine learning model trained to predict postoperative seizure outcome. We performed a retrospective cohort study of 797 children who had undergone resective or disconnective epilepsy surgery at a tertiary center. We extracted patient information from medical records and trained three models-a logistic regression, a multilayer perceptron, and an XGBoost model-to predict 1-year postoperative seizure outcome on our data set. We evaluated the performance of a recently published XGBoost model on the same patients. We further investigated the impact of sample size on model performance, using learning curve analysis to estimate performance at samples up to N = 2000. Finally, we examined the impact of predictor selection on model performance. Our logistic regression achieved an accuracy of 72% (95% confidence interval [CI] = 68%-75%, area under the curve [AUC] = .72), whereas our multilayer perceptron and XGBoost both achieved accuracies of 71% (95% CIMLP  = 67%-74%, AUCMLP  = .70; 95% CIXGBoost own  = 68%-75%, AUCXGBoost own  = .70). There was no significant difference in performance between our three models (all p > .4) and they all performed better than the external XGBoost, which achieved an accuracy of 63% (95% CI = 59%-67%, AUC = .62; pLR  = .005, pMLP  = .01, pXGBoost own  = .01) on our data. All models showed improved performance with increasing sample size, but limited improvements beyond our current sample. The best model performance was achieved with data-driven feature selection. We show that neither the deployment of complex machine learning models nor the assembly of thousands of patients alone is likely to generate significant improvements in our ability to predict postoperative seizure freedom. We instead propose that improved feature selection alongside collaboration, data standardization, and model sharing is required to advance the field.

Comparison of Hemispheric Surgery Techniques for Pediatric Drug-Resistant Epilepsy: An Individual Patient Data Meta-analysis.

Hemispheric surgery effectively treats unihemispheric pediatric drug-resistant epilepsy (DRE) by resecting and/or disconnecting the epileptic hemisphere. Modifications to the original anatomic hemispherectomy have generated multiple functionally equivalent, disconnective techniques for performing hemispheric surgery, termed functional hemispherotomy. While a myriad of hemispherotomy variants exist, all of them can be categorized according to the anatomic plane they are performed in, which includes vertical approaches at or near the interhemispheric fissure and lateral approaches at or near the Sylvian fissure. This meta-analysis of individual patient data (IPD) aimed to compare seizure outcomes and complications between the hemispherotomy approaches to better characterize their relative efficacy and safety in the modern neurosurgical treatment of pediatric DRE, given emerging evidence that outcomes may differ between them. CINAHL, Embase, PubMed, and Web of Science were searched from inception to September 9, 2020, for studies reporting IPD from pediatric patients with DRE who underwent hemispheric surgery. Outcomes of interest were seizure freedom at last follow-up, time-to-seizure recurrence, and complications including hydrocephalus, infection, and mortality. The χ2 test compared the frequency of seizure freedom and complications. Multivariable mixed-effects Cox regression controlling for predictors of seizure outcome was performed on propensity score-matched patients to compare time-to-seizure recurrence between approaches. Kaplan-Meier curves were made to visualize differences in time-to-seizure recurrence. Fifty-five studies reporting on 686 unique pediatric patients treated with hemispheric surgery were included for meta-analysis. Among the hemispherotomy subgroup, vertical approaches resulted in a greater proportion of seizure free patients (81.2% vs 70.7%, p = 0.014) than lateral approaches. While there were no differences in complications, lateral hemispherotomy had higher rates of revision hemispheric surgery due to incomplete disconnection and/or recurrent seizures than vertical hemispherotomy (16.3% vs 1.2%, p < 0.001). After propensity score matching, vertical hemispherotomy approaches independently conferred longer time-to-seizure recurrence than lateral hemispherotomy approaches (hazard ratio 0.44, 95% CI 0.19-0.98). Among functional hemispherotomy techniques, vertical hemispherotomy approaches confer more durable seizure freedom than lateral approaches without compromising safety. Future prospective studies are required to definitively determine whether vertical approaches are indeed superior and how it should influence clinical guidelines for performing hemispheric surgery.

Multivariate analysis of seizure outcomes after resective surgery for focal epilepsy: a single-center study on 833 patients

The predictors of seizure outcomes after resective surgery for focal epilepsy, for an update on the features of good and poor outcomes, are investigated. A retrospective study of patients with focal epilepsy undergoing resective surgery from March 2011 to April 2019 was performed. There were 3 groups according to the seizure outcomes: seizure freedom, seizure improvement, and no improvement. Predictors of seizure outcomes were identified by multivariate logistic regression analysis. Of all 833 patients, 561 (67.3%) patients remained seizure-free at the last follow-up, 203 (24.4%) patients had seizure improvement, and 69 (8.3%) had no improvement. The mean follow-up duration was 5.2years (range: 2.7 to 9.6). Predictors of better outcomes included epilepsy duration < 5years, localized discharge, no. of antiepileptic drugs at surgery < 3, and temporal lobe resection. However, predictors of worse outcomes included intracranial hemorrhage in infancy, interictal abnormal discharge, intracranial electrode monitoring, and acute postoperative seizure. Our study suggests that resective surgery for focal epilepsy has satisfactory outcomes. Short epilepsy duration, localized discharge, and temporal lobe resection are positive predictors of seizure freedom. Patients with these predictors are intensively recommended for surgery.

Low IQ predicts worse long-term seizure outcome after resective epilepsy surgery – A propensity score matched analysis

ObjectiveTo describe long-term seizure outcomes in patients with IQ < 70 undergoing resective epilepsy surgery and to analyse whether baseline IQ predicts seizure outcome. MethodsPatients undergoing focal resective epilepsy surgery 1995–2017 at age ≥ 4 years were identified in the population-based Swedish National Epilepsy Surgery Register. Two-year, five-year and long-term (10–20-year follow-up) outcomes were analysed. Seizure outcomes of patients with IQ ≥ 70 and IQ < 70 at baseline were compared in the full cohort and between propensity score matched groups. ResultsFollow-up data were available for 884 patients, 79 of whom had IQ < 70. Matched controls were found for 74 of the IQ < 70 patients. Preoperative MRI pathology was unifocal in 54 % and 79 % of IQ < 70 and IQ ≥ 70 patients before matching compared to 58 % and 62 % after matching, respectively. Patients with IQ < 70 achieved significantly worse seizure outcomes at all time points both when analysing the full cohort and the matched groups. After matching, the proportions of seizure-free patients in the IQ < 70 group were 28 %, 32 % and 32 % at the 2-year, 5-year and long-term follow-ups, respectively. Corresponding figures in the IQ ≥ 70 group were 54 %, 62 % and 60 % (p for difference between IQ groups 0.004, 0.002 and 0.049). In the IQ < 70 group, 36 %, 29 % and 45 % had a ≥ 75 % reduction in seizure frequency at the respective three follow-ups. ConclusionLow preoperative IQ predicts lower chances of seizure freedom after resective epilepsy surgery and few patients with IQ < 70 remain completely seizure-free in the long term. Nevertheless, a significant proportion had a reduction in seizure frequency of at least 75 % at long-term follow-up, indicating an important palliative potential of resective surgery for epilepsy patients with intellectual disability.

Ablation of apparent diffusion coefficient hyperintensity clusters in mesial temporal lobe epilepsy improves seizure outcomes after laser interstitial thermal therapy.

Laser interstitial thermal therapy (LiTT) is a minimally invasive surgical procedure for intractable mesial temporal epilepsy (mTLE). LiTT is safe and effective, but seizure outcomes are highly variable due to patient variability, suboptimal targeting, and incomplete ablation of the epileptogenic zone. Apparent diffusion coefficient (ADC) is a magnetic resonance imaging (MRI) sequence that can identify potential epileptogenic foci in the mesial temporal lobe to improve ablation and seizure outcomes. The objective of this study was to investigate whether ablation of tissue clusters with high ADC values in the mesial temporal structures is associated with seizure outcome in mTLE after LiTT. Twenty-seven patients with mTLE who underwent LiTT at our institution were analyzed. One-year seizure outcome was categorized as complete seizure freedom (International League Against Epilepsy [ILAE] Class I) and residual seizures (ILAE Class II-VI). Volumes of hippocampus and amygdala were segmented from the preoperative T1 MRI sequence. Spatially distinct hyperintensity clusters were identified in the preoperative ADC map. Proportion of cluster volume and number ablated were associated with seizure outcomes. The mean age at surgery was 37.5 years and the mean follow-up duration was 1.9 years. Proportions of hippocampal cluster volume (p=.013) and number (p=.03) ablated were significantly higher in patients with seizure freedom. For amygdala clusters, the proportion of cluster number ablated was significantly associated with seizure outcome (p=.026). In the combined amygdalohippocampal complex, ablation of amygdalohippocampal clusters reliably predicted seizure outcome by their volume ablated (area under the curve [AUC]=0.7670, p=.02). Seizure outcome after LiTT in patients with mTLE was associated significantly with the extent of cluster ablation in the amygdalohippocampal complex. The results suggest that preoperative ADC analysis may help identify high-yield pathological tissue clusters that represent epileptogenic foci. ADC-based cluster analysis can potentially assist ablation targeting and improve seizure outcome after LiTT in mTLE.

[Neuroimaging in the Diagnosis of Epilepsy].

Neuroimaging is commonly used for presurgical evaluation in epilepsy surgery. Neuroimaging for epilepsy includes structural and functional neuroimaging. Lesions detected by structural neuroimaging are crucial to determine the indication of epilepsy surgery, as well as to predict seizure outcomes, as patients with MRI-visible lesions are likely to have better seizure outcomes. However, MRI lesions sometimes show very faint findings; therefore, the diagnosis of structural neuroimaging requires sophisticated skills. Moreover, the epilepsy focus should not only involve the MRI-visible lesion, but also the surrounding tissue with abnormal neuronal function. The MRI-lesion, which is almost the same as that epileptogenic lesion, is a part of the epileptogenic zone. Surgical strategy should be conducted by comprehensive evaluation including neuroimaging in addition to other modalities.