Predictors of therapeutic response following thalamic neuromodulation for drug-resistant pediatric epilepsy: A systematic review and individual patient data meta-analysis.

We sought to perform a systematic review and individual participant data meta-analysis to identify predictors of treatment response following thalamic neuromodulation in pediatric patients with medically refractory epilepsy. Electronic databases (MEDLINE, Ovid, Embase, and Cochrane) were searched, with no language or data restriction, to identify studies reporting seizure outcomes in pediatric populations following deep brain stimulation (DBS) or responsive neurostimulation (RNS) implantation in thalamic nuclei. Studies featuring individual participant data of patients with primary or secondary generalized drug-resistant epilepsy were included. Response to therapy was defined as >50% reduction in seizure frequency from baseline. Of 417 citations, 21 articles reporting on 88 participants were eligible. Mean age at implantation was 13.07 ± 3.49 years. Fifty (57%) patients underwent DBS, and 38 (43%) RNS. Sixty (68%) patients were implanted in centromedian nucleus and 23 (26%) in anterior thalamic nucleus, and five (6%) had both targets implanted. Seventy-four (84%) patients were implanted bilaterally. The median time to last follow-up was 12 months (interquartile range = 6.75-26.25). Sixty-nine percent of patients achieved response to treatment. Age, target, modality, and laterality had no significant association with response in univariate logistic regression. Until thalamic neuromodulation gains widespread approval for use in pediatric patients, data on efficacy will continue to be limited to small retrospective cohorts and case series. The inherent bias of these studies can be overcome by using individual participant data. Thalamic neuromodulation appears to be a safe and effective treatment for epilepsy. Larger, prolonged prospective, multicenter studies are warranted to further evaluate the efficacy of DBS over RNS in this patient population where resection for curative intent is not a safe option.

Postoperative shunt failure following hemispherectomy in pediatric patients with pre-existing hydrocephalus.

OBJECTIVE: The risk of hydrocephalus following hemispherectomy for drug resistant epilepsy (DRE) remains high. Patients with pre-existing hydrocephalus pose a postoperative challenge, as maintaining existing shunt patency is necessary but lacks a clearly defined strategy. This study examines the incidence and predictors of shunt failure in pediatric hemispherectomy patients with pre-existing ventricular shunts. METHODS: We performed a retrospective chart review at our center to identify pediatric patients diagnosed with DRE who were treated with ventricular shunt prior to their first hemispherectomy surgery. Demographic and perioperative data were obtained including shunt history, hydrocephalus etiology, epilepsy duration, surgical technique, and postoperative outcomes. Univariate analysis was performed using Fisher's exact test and Pearson correlation, with Bonferroni correction to a = 0.00625 and a = 0.01, respectively. RESULTS: Five of nineteen (26.3%) patients identified with ventriculoperitoneal shunting prior to hemispherectomy experienced postoperative shunt malfunction. All 5 of these patients underwent at least 1 shunt revision prior to hemispherectomy, with a significant association between pre- and post-hemispherectomy shunt revisions. There was no significant association between post-hemispherectomy shunt failure and valve type, intraoperative shunt alteration, postoperative external ventricular drain placement, hemispherectomy revision, lateralization of shunt relative to resection, postoperative complications, or postoperative aseptic meningitis. There was no significant correlation between number of post-hemispherectomy shunt revisions and age at shunt placement, age at hemispherectomy, epilepsy duration, or shunt duration prior to hemispherectomy. CONCLUSIONS: Earlier shunt revision surgery may portend a subsequent need for shunt revision following hemispherectomy. These findings may guide neurosurgeons in counseling patients with pre-existing ventricular shunts prior to hemispherectomy surgery.

Beyond seizure freedom: Dissecting long-term seizure control after surgical resection for drug-resistant epilepsy.

OBJECTIVE: This study was undertaken to better understand the long-term palliative and disease-modifying effects of surgical resection beyond seizure freedom, including frequency reduction and both late recurrence and remission, in patients with drug-resistant epilepsy. METHODS: This retrospective database-driven cohort study included all patients with >9 years of follow-up at a single high-volume epilepsy center. We included patients who underwent lobectomy, multilobar resection, or lesionectomies for drug-resistant epilepsy; we excluded patients who underwent hemispherectomies. Our main outcomes were (1) reduction in frequency of disabling seizures (at 6 months, each year up to 9 years postoperatively, and at last follow-up), (2) achievement of seizure remission (>6 months, >1 year, and longest duration), and (3) seizure freedom at last follow-up. RESULTS: We included 251 patients; 234 (93.2%) achieved 6 months and 232 (92.4%) experienced 1 year of seizure freedom. Of these, the average period of seizure freedom was 10.3 years. A total of 182 (72.5%) patients were seizure-free at last follow-up (defined as >1 year without seizures), with a median 11.9 years since remission. For patients not completely seizure-free, the mean seizure frequency reduction at each time point was 76.2%, and ranged from 66.6% to 85.0%. Patients decreased their number of antiseizure medications on average by .58, and 53 (21.2%) patients were on no antiseizure medication at last follow-up. Nearly half (47.1%) of those seizure-free at last follow-up were not seizure-free immediately postoperatively. SIGNIFICANCE: Patients who continue to have seizures after resection often have considerable reductions in seizure frequency, and many are able to achieve seizure freedom in a delayed manner.

Comparative Effectiveness of Stereotactic Electroencephalography Versus Subdural Grids in Epilepsy Surgery.

OBJECTIVE: The aim was to compare the outcomes of subdural electrode (SDE) implantations versus stereotactic electroencephalography (SEEG), the 2 predominant methods of intracranial electroencephalography (iEEG) performed in difficult-to-localize drug-resistant focal epilepsy. METHODS: The Surgical Therapies Commission of the International League Against Epilepsy created an international registry of iEEG patients implanted between 2005 and 2019 with ≥1 year of follow-up. We used propensity score matching to control exposure selection bias and generate comparable cohorts. Study endpoints were: (1) likelihood of resection after iEEG; (2) seizure freedom at last follow-up; and (3) complications (composite of postoperative infection, symptomatic intracranial hemorrhage, or permanent neurological deficit). RESULTS: Ten study sites from 7 countries and 3 continents contributed 2,012 patients, including 1,468 (73%) eligible for analysis (526 SDE and 942 SEEG), of whom 988 (67%) underwent subsequent resection. Propensity score matching improved covariate balance between exposure groups for all analyses. Propensity-matched patients who underwent SDE had higher odds of subsequent resective surgery (odds ratio [OR] = 1.4, 95% confidence interval [CI] 1.05, 1.84) and higher odds of complications (OR = 2.24, 95% CI 1.34, 3.74; unadjusted: 9.6% after SDE vs 3.3% after SEEG). Odds of seizure freedom in propensity-matched resected patients were 1.66 times higher (95% CI 1.21, 2.26) for SEEG compared with SDE (unadjusted: 55% seizure free after SEEG-guided resections vs 41% after SDE). INTERPRETATION: In comparison to SEEG, SDE evaluations are more likely to lead to brain surgery in patients with drug-resistant epilepsy but have more surgical complications and lower probability of seizure freedom. This comparative-effectiveness study provides the highest feasible evidence level to guide decisions on iEEG. ANN NEUROL 2021;90:927-939.

Cognitive phenotypes in frontal lobe epilepsy.

OBJECTIVE: Neuropsychological profiles are heterogeneous both across and within epilepsy syndromes, but especially in frontal lobe epilepsy (FLE), which has complex semiology and epileptogenicity. This study aimed to characterize the cognitive heterogeneity within FLE by identifying cognitive phenotypes and determining their demographic and clinical characteristics. METHOD: One hundred and six patients (age 16-66; 44% female) with FLE completed comprehensive neuropsychological testing, including measures within five cognitive domains: language, attention, executive function, processing speed, and verbal/visual learning. Patients were categorized into one of four phenotypes based on the number of impaired domains. Patterns of domain impairment and clinical and demographic characteristics were examined across phenotypes. RESULTS: Twenty-five percent of patients met criteria for the Generalized Phenotype (impairment in at least four domains), 20% met criteria for the Tri-Domain Phenotype (impairment in three domains), 36% met criteria for the Domain-Specific Phenotype (impairment in one or two domains), and 19% met criteria for the Intact Phenotype (no impairment). Language was the most common domain-specific impairment, followed by attention, executive function, and processing speed. In contrast, learning was the least impacted cognitive domain. The Generalized Phenotype had fewer years of education compared to the Intact Phenotype, but otherwise, there was no differentiation between phenotypes in demographic and clinical variables. However, qualitative analysis suggested that the Generalized and Tri-Domain Phenotypes had a more widespread area of epileptogenicity, whereas the Intact Phenotype most frequently had seizures limited to the lateral frontal region. SIGNIFICANCE: This study identified four cognitive phenotypes in FLE that were largely indistinguishable in clinical and demographic features, aside from education and extent of epileptogenic zone. These findings enhance our appreciation of the cognitive heterogeneity within FLE and provide additional support for the development and use of cognitive taxonomies in epilepsy.

Quality of life after epilepsy surgery: How domain-specific cognitive changes impact QOL within the context of seizure outcome.

PURPOSE: Neurosurgery is an effective treatment option for pharmacoresistant epilepsy. Although post-surgical seizure freedom is considered the primary goal of epilepsy surgery, other factors that impact Quality of Life (QOL) are also important to consider, including post-surgical cognitive changes. This study aimed to examine the impact of post-surgical cognitive changes on QOL in the context of seizure outcomes. METHODS: Participants were 196 adults with focal epilepsy who underwent either frontal (n = 27) or temporal (n = 169) lobe resection. Each participant completed pre- and post-surgical neuropsychological evaluations, and cognitive composites were constructed for the following domains: language, attention/processing speed, memory, executive function, and visuospatial skill. The Quality of Life in Epilepsy (QOLIE-10) questionnaire was used to assess QOL. Seizure outcome was determined by seizure status six months post-surgery. RESULTS: Eighty-one percent of patients were seizure-free post-surgery and generally reported improved QOL. While a significant portion of patient's demonstrated declines in language and verbal memory following surgery, only a decline in verbal memory was associated with worse QOL; however, this relationship was no longer significant after controlling for seizure outcome. Instead, reduced post-surgical QOL was primarily observed in those who experienced both seizure recurrence and a decline in executive function. Notably, depression was a significant covariate in all of the models. CONCLUSIONS: The findings from this study improve our ability to counsel patients about the trade-off between cognitive decline and seizure remittance in the greater context of overall QOL. Reassuringly, it appears that QOL is improved regardless of cognitive changes when patients have good seizure outcomes. However, for those that experience a "double hit" (i.e., cognitive decline without seizure remission), post-surgical QOL may be reduced. Changes in depression also appear to play a crucial role in QOL outcomes.

Mother knows best or does she? Perceptions of the memory abilities of pediatric patients with epilepsy as reported by patients and their parents across time.

PURPOSE: This study compared the self-reported and parent-reported memory of children with epilepsy across time and explored the relationships between these measures of subjective memory and the children's actual performance on objective neuropsychological tests. METHOD: One-hundred and nineteen children with epilepsy who were surgical candidates underwent comprehensive neuropsychological testing that included the Everyday Verbal Memory Questionnaire (EVMQ). Each child's parent and 82 of the children themselves completed the appropriate version of this subjective memory measure. After 9 months, the children returned for a second neuropsychological evaluation with 71 parents and 39 children completing the same questionnaire. Approximately one-third of the children in the study underwent surgery between the two evaluations. Standardized regression-based norms were used to quantify change in cognitive abilities across assessments. RESULTS: Results revealed significant relationships between parent reports and child reports of the children's memory abilities. Parent reports, but not child reports, correlated with the children's objective test scores at baseline. In contrast, children were more attuned to changes in their memory across time. CONCLUSIONS: These findings demonstrate the importance of considering both parent and child perceptions of everyday cognitive functioning when evaluating cognition and cognitive changes over time in pediatric patients with epilepsy.

Glucocorticoid Receptor ß Isoform Predominates in the Human Dysplastic Brain Region and Is Modulated by Age, Sex, and Antiseizure Medication.

The glucocorticoid receptor (GR) at the blood−brain barrier (BBB) is involved in the pathogenesis of drug-resistant epilepsy with focal cortical dysplasia (FCD); however, the roles of GR isoforms GRα and GRß in the dysplastic brain have not been revealed. We utilized dysplastic/epileptic and non-dysplastic brain tissue from patients who underwent resective epilepsy surgery to identify the GRα and GRß levels, subcellular localization, and cellular specificity. BBB endothelial cells isolated from the dysplastic brain tissue (EPI-ECs) were used to decipher the key BBB proteins related to drug regulation and BBB integrity compared to control and transfected GRß-overexpressed BBB endothelial cells. GRß was upregulated in dysplastic compared to non-dysplastic tissues, and an imbalance of the GRα/GRß ratio was significant in females vs. males and in patients > 45 years old. In EPI-ECs, the subcellular localization and expression patterns of GRß, Hsp90, CYP3A4, and CYP2C9 were consistent with GRß+ brain endothelial cells. Active matrix metalloproteinase levels and activity increased, whereas claudin-5 levels decreased in both EPI-ECs and GRß+ endothelial cells. In conclusion, the GRß has a major effect on dysplastic BBB functional proteins and is age and gender-dependent, suggesting a critical role of brain GRß in dysplasia as a potential biomarker and therapeutic target in epilepsy.

Predicting mood decline following temporal lobe epilepsy surgery in adults.

OBJECTIVE: To develop a model to predict the probability of mood decline in adults following temporal lobe resection for the treatment of pharmacoresistant epilepsy. METHODS: Variable selection was performed on 492 patients from the Cleveland Clinic using best subsets regression. After completing variable selection, a subset of variables was requested from four epilepsy surgery centers across North America (n = 100). All data were combined to develop a final model to predict postoperative mood decline (N = 592). Internal validation with bootstrap resampling was performed. A clinically significant increase in depressive symptoms was defined as a 15% increase in Beck Depression Inventory-Second Edition score and a postoperative raw score > 11. RESULTS: Fourteen percent of patients in the Cleveland Clinic cohort and 22% of patients in the external cohort experienced clinically significant increases in depressive symptoms following surgery. The final prediction model included six predictor variables: psychiatric history, resection side, relationship status, verbal fluency score, age at preoperative testing, and presence/absence of malformation of cortical development on magnetic resonance imaging. The model had an optimism-adjusted c-statistic of .70 and good calibration, with slight probability overestimation in higher risk patients. SIGNIFICANCE: Clinicians can utilize our nomogram via a paper tool or online calculator to estimate the risk of postoperative mood decline for individual patients prior to temporal lobe epilepsy surgery.

Effective connectivity differs between focal cortical dysplasia types I and II.

OBJECTIVE: To determine whether brain connectivity differs between focal cortical dysplasia (FCD) types I and II. METHODS: We compared cortico-cortical evoked potentials (CCEPs) as measures of effective brain connectivity in 25 FCD patients with drug-resistant focal epilepsy who underwent intracranial evaluation with stereo-electroencephalography (SEEG). We analyzed the amplitude and latency of CCEP responses following ictal-onset single-pulse electrical stimulation (iSPES). RESULTS: In comparison to FCD type II, patients with type I demonstrated significantly larger responses in the electrodes near the ictal-onset zone (<50 mm). These findings persisted when controlling for the location of the epileptogenic zone, as noted in patients with temporal lobe epilepsies, as well as controlling for seizure type, as noted in patients with focal to bilateral tonic-clonic seizures (FBTCS). In type II, the root mean square (RMS) of CCEP responses dropped substantially from the early segment (10-60 ms) to the middle and late segments (60-600 ms). The middle and late CCEP latency segments showed the largest differences between FCD types I and II. SIGNIFICANCE: Focal cortical dysplasia type I may have a greater degree of cortical hyperexcitability as compared with FCD type II. In addition, FCD type II displays a more restrictive area of hyperexcitability in both temporal and spatial domains. In patients with FBTCS and type I FCD, the increased amplitudes of RMS in the middle and late CCEP periods appear consistent with the cortico-thalamo-cortical network involvement of FBTCS. The notable differences in degree and extent of hyperexcitability may contribute to the different postsurgical seizure outcomes noted between these two pathological substrates.

Automated analysis of cortical volume loss predicts seizure outcomes after frontal lobectomy.

OBJECTIVE: Patients undergoing frontal lobectomy demonstrate lower seizure-freedom rates than patients undergoing temporal lobectomy and several other resective interventions. We attempted to utilize automated preoperative quantitative analysis of focal and global cortical volume loss to develop predictive volumetric indicators of seizure outcome after frontal lobectomy. METHODS: Ninety patients who underwent frontal lobectomy were stratified based on seizure freedom at a mean follow-up time of 3.5 (standard deviation [SD] 2.5) years. Automated quantitative analysis of cortical volume loss organized by distinct brain region and laterality was performed on preoperative T1-weighted magnetic resonance imaging (MRI) studies. Univariate statistical analysis was used to select potential predictors of seizure freedom. Backward variable selection and multivariate logistical regression were used to develop models to predict seizure freedom. RESULTS: Forty-eight of 90 (53.3%) patients were seizure-free at the last follow-up. Several frontal and extrafrontal brain regions demonstrated statistically significant differences in both volumetric cortical volume loss and volumetric asymmetry between the left and right sides in the seizure-free and non-seizure-free cohorts. A final multivariate logistic model utilizing only preoperative quantitative MRI data to predict seizure outcome was developed with a c-statistic of 0.846. Using both preoperative quantitative MRI data and previously validated clinical predictors of seizure outcomes, we developed a model with a c-statistic of 0.897. SIGNIFICANCE: This study demonstrates that preoperative cortical volume loss in both frontal and extrafrontal regions can be predictive of seizure outcome after frontal lobectomy, and models can be developed with excellent predictive capabilities using preoperative MRI data. Automated quantitative MRI analysis can be quickly and reliably performed in patients with frontal lobe epilepsy, and further studies may be developed for integration into preoperative risk stratification.

Improving the prediction of epilepsy surgery outcomes using basic scalp EEG findings.

OBJECTIVE: This study aims to evaluate the role of scalp electroencephalography (EEG; ictal and interictal patterns) in predicting resective epilepsy surgery outcomes. We use the data to further develop a nomogram to predict seizure freedom. METHODS: We retrospectively reviewed the scalp EEG findings and clinical data of patients who underwent surgical resection at three epilepsy centers. Using both EEG and clinical variables categorized into 13 isolated candidate predictors and 6 interaction terms, we built a multivariable Cox proportional hazards model to predict seizure freedom 2 years after surgery. Harrell's step-down procedure was used to sequentially eliminate the least-informative variables from the model until the change in the concordance index (c-index) with variable removal was less than 0.01. We created a separate model using only clinical variables. Discrimination of the two models was compared to evaluate the role of scalp EEG in seizure-freedom prediction. RESULTS: Four hundred seventy patient records were analyzed. Following internal validation, the full Clinical + EEG model achieved an optimism-corrected c-index of 0.65, whereas the c-index of the model without EEG data was 0.59. The presence of focal to bilateral tonic-clonic seizures (FBTCS), high preoperative seizure frequency, absence of hippocampal sclerosis, and presence of nonlocalizable seizures predicted worse outcome. The presence of FBTCS had the largest impact for predicting outcome. The analysis of the models' interactions showed that in patients with unilateral interictal epileptiform discharges (IEDs), temporal lobe surgery cases had a better outcome. In cases with bilateral IEDs, abnormal magnetic resonance imaging (MRI) predicted worse outcomes, and in cases without IEDs, patients with extratemporal epilepsy and abnormal MRI had better outcomes. SIGNIFICANCE: This study highlights the value of scalp EEG, particularly the significance of IEDs, in predicting surgical outcome. The nomogram delivers an individualized prediction of postoperative outcome, and provides a unique assessment of the relationship between the outcome and preoperative findings.

Epilepsy surgery in infants up to 3 months of age: Safety, feasibility, and outcomes: A multicenter, multinational study.

OBJECTIVE: Drug-resistant epilepsy (DRE) during the first few months of life is challenging and necessitates aggressive treatment, including surgery. Because the most common causes of DRE in infancy are related to extensive developmental anomalies, surgery often entails extensive tissue resections or disconnection. The literature on "ultra-early" epilepsy surgery is sparse, with limited data concerning efficacy controlling the seizures, and safety. The current study's goal is to review the safety and efficacy of ultra-early epilepsy surgery performed before the age of 3 months. METHODS: To achieve a large sample size and external validity, a multinational, multicenter retrospective study was performed, focusing on epilepsy surgery for infants younger than 3 months of age. Collected data included epilepsy characteristics, surgical details, epilepsy outcome, and complications. RESULTS: Sixty-four patients underwent 69 surgeries before the age of 3 months. The most common pathologies were cortical dysplasia (28), hemimegalencephaly (17), and tubers (5). The most common procedures were hemispheric surgeries (48 procedures). Two cases were intentionally staged, and one was unexpectedly aborted. Nearly all patients received blood products. There were no perioperative deaths and no major unexpected permanent morbidities. Twenty-five percent of patients undergoing hemispheric surgeries developed hydrocephalus. Excellent epilepsy outcome (International League Against Epilepsy [ILAE] grade I) was achieved in 66% of cases over a median follow-up of 41 months (19-104 interquartile range [IQR]). The number of antiseizure medications was significantly reduced (median 2 drugs, 1-3 IQR, p < .0001). Outcome was not significantly associated with the type of surgery (hemispheric or more limited resections). SIGNIFICANCE: Epilepsy surgery during the first few months of life is associated with excellent seizure control, and when performed by highly experienced teams, is not associated with more permanent morbidity than surgery in older infants. Thus surgical treatment should not be postponed to treat DRE in very young infants based on their age.

Disparities in the nationwide distribution of epilepsy centers.

BACKGROUND: Prior studies in the field of epilepsy surgical disparities have examined barriers in undergoing epilepsy surgical resections in disadvantaged populations involving trust in health providers, education level, social support, and fear of treatment. Few studies have analyzed the geographical locations of specialized epilepsy centers and their role in nationwide epilepsy surgical access and disparities. OBJECTIVE: To better visualize the locations of epilepsy level IV centers in the United States with respect to epilepsy prevalence and socioeconomic disadvantage. METHODS: We created heat maps of the United States to visualize geographical locations of level IV epilepsy centers with respect to the 2015 state-wide epilepsy prevalence and 2017 county-wide Area Deprivation Index (ADI) scores, a composite measure of socioeconomic disadvantage. Univariate logistic regression was used to test for associations between the presence or absence of epilepsy centers and socioeconomic disadvantage. RESULTS: We found eight states within the United States without any level IV epilepsy centers. In states with level IV centers, centers were clustered in populated and metropolitan regions. Disadvantaged counties (with increased ADI scores) were less likely to have level IV centers compared to counties that were less disadvantaged (lower ADI scores) (p < 0.00001). CONCLUSION: Further work is required to remedy the decreased access to specialized epilepsy care due to geographical disparities, and to better understand its contribution to overall disparities affecting epilepsy surgery referrals.

Cognitive outcomes following frontal lobe resection for treatment of epilepsy in children and adolescents.

OBJECTIVE: To use reliable change indices (RCIs) developed specifically for pediatric patients with epilepsy to examine cognitive outcomes after frontal lobe resection for pharmacoresistant epilepsy. METHODS: Forty-one pediatric patients (25 male, Mage = 10 years) completed comprehensive neuropsychological evaluations before and an average of 6.5 months after frontal lobe resections for treatment of epilepsy. Evaluations included tests of intelligence, attention/working memory, processing speed, language, visuospatial skills, executive function, and episodic memory. Practice effect-adjusted RCIs were used to determine clinically significant postoperative cognitive change. Demographic, disease, and surgical variables were examined to identify factors associated with postoperative cognitive decline or improvement. RESULTS: Within each cognitive domain, there was a large proportion of patients (51-84%) who did not exhibit significant cognitive change. In terms of overall cognitive profile, 44% demonstrated improvement in at least one domain and 69% declined in at least one domain. Postoperative cognitive improvement occurred most commonly in the domain of processing speed, whereas postoperative cognitive decline occurred most frequently in the domain of visuospatial skills. Younger age at surgery was associated with cognitive improvement. Older age at seizure onset and higher baseline cognitive performance were associated with cognitive decline. SIGNIFICANCE: Approximately 6.5 months after frontal lobe resection, only 15% of our sample showed stable performance across all cognitive domains. Seventeen percent of patients showed improvements without declines, 42% showed declines without improvements, and 27% showed a mix of improvements and declines across different cognitive domains. Age and baseline abilities were associated with postoperative cognitive change on multiple measures. With 1 in 8 children demonstrating postoperative decline across three or more domains, further research is needed to identify factors associated with cognitive decline in order to inform clinical decision-making and patient/family counseling.

Long-term outcomes of reoperations in epilepsy surgery.

OBJECTIVE: To analyze longitudinal seizure outcomes following epilepsy surgery, including reoperations, in patients with intractable focal epilepsy. METHODS: Clinicoradiological characteristics of patients who underwent epilepsy surgery from 1995 to 2016 with follow-up of ≥1 year were reviewed. In patients undergoing reoperations, the latest resection was considered the index surgery. The primary outcome was complete seizure freedom (Engel I) at last follow-up. Potentially significant outcome variables were first identified using univariate analyses and then fit in multivariate Cox proportional hazards models. RESULTS: Of 898 patients fulfilling study criteria, 110 had reoperations; 92 had one resection prior to the index surgery and 18 patients had two or more prior resective surgeries. Two years after the index surgery, 69% of patients with no prior surgeries had an Engel score of I, as opposed to only 42% of those with one prior surgery, and 33% of those with two or more prior resections (P < .001). Among surgical outcome predictors, the number of prior epilepsy surgeries, female sex, lesional initial magnetic resonance imaging, no prior history of generalization, and pathology correlated with better seizure outcomes on univariate analysis. However, only sex (P = .011), history of generalization (P = .016), and number of prior surgeries (P = .002) remained statistically significant in the multivariate model. SIGNIFICANCE: Although long-term seizure control is possible in patients with failed prior epilepsy surgery, the chances of success diminish with every subsequent resection. Outcome is additionally determined by inherent biological markers (sex and secondary generalization tendency), rather than traditional outcome predictors, supporting a hypothesis of "surgical refractoriness."

Value of 7T MRI and post-processing in patients with nonlesional 3T MRI undergoing epilepsy presurgical evaluation.

OBJECTIVE: Ultra-high-field 7-Tesla (7T) magnetic resonance imaging (MRI) offers increased signal-to-noise and contrast-to-noise ratios, which may improve visualization of cortical malformations. We aim to assess the clinical value of in vivo structural 7T MRI and its post-processing for the noninvasive identification of epileptic brain lesions in patients with pharmacoresistant epilepsy and nonlesional 3T MRI who are undergoing presurgical evaluation. METHODS: Sixty-seven patients were included who had nonlesional 3T MRI by official radiology report. Epilepsy protocols were used for the 3T and 7T acquisitions. Post-processing of the 7T T1-weighted magnetization-prepared two rapid acquisition gradient echoes sequence was performed using the morphometric analysis program (MAP) with comparison to a normal database consisting of 50 healthy controls. Review of 7T was performed by an experienced board-certified neuroradiologist and at the multimodal patient management conference. The clinical significance of 7T findings was assessed based on intracranial electroencephalography (ICEEG) ictal onset, surgery, postoperative seizure outcomes, and histopathology. RESULTS: Unaided visual review of 7T detected previously unappreciated subtle lesions in 22% (15/67). When aided by 7T MAP, the total yield increased to 43% (29/67). The location of the 7T-identified lesion was identical to or contained within the ICEEG ictal onset in 13 of 16 (81%). Complete resection of the 7T-identified lesion was associated with seizure freedom (P = .03). Histopathology of the 7T-identified lesions encountered mainly focal cortical dysplasia (FCD). 7T MAP yielded 25% more lesions (6/24) than 3T MAP, and showed improved conspicuity in 46% (11/24). SIGNIFICANCE: Our data suggest a major benefit of 7T with post-processing for detecting subtle FCD lesions for patients with pharmacoresistant epilepsy and nonlesional 3T MRI.

Quality of life before and after epilepsy surgery: Age is just a number.

BACKGROUND: In a rapidly aging population, it is critical to analyze if the quality of life (QOL) in patients with drug-resistant epilepsy (DRE) and the change in it after epilepsy surgery is dependent on the age at operation. METHODS: A prospective registry-based retrospective cohort study including adults with a completed pre- and post-surgery Quality of Life in Epilepsy 10 (QOLIE-10) survey. Multivariable linear regression models analyzed the baseline, postoperative, or change in QOLIE-10 score. RESULTS: We analyzed 416 patients (51% females) with the mean age of 39.6 (SD = 12.6) years at the time of surgery, including 100 (24%) individuals 50 years or older. The younger and older adults (dichotomized as <50 vs. ≥50 and <60 vs. ≥60) had comparable pre- and post-surgery QOLIE 10 total scores. The change in total and individual QOLIE-10 items score were comparable between the groups as well. Within group improvements in total QOLIE-10 score post-surgery was in younger as well as older groups. The linear regression models showed that age, regardless of parameterization (linear or dichotomized), was not related to pre-surgery, post-surgery, and change in QOLIE-10 score, both before and after adjustment for covariates. The change in QOLIE-10 score did not show correlation with age, whether seizure freedom or relative seizure reduction was used in the model. CONCLUSION: With QOL, before or after surgery, being independent of a patient's age, our findings suggest that well-selected older adults and the elderly should be offered epilepsy surgery without concern for an inferior improvement in QOL compared to their younger counterparts.

(Re)Defining success in epilepsy surgery: The importance of relative seizure reduction in patient-reported quality of life.

OBJECTIVE: Previous work has suggested that seizure outcome is the most important predictor of quality of life (QoL) after epilepsy surgery, but it is unknown which specific seizure outcome measure should be used in judging surgical success. We assess three different seizure outcome measures (relative seizure reduction, absolute seizure reduction, and seizure freedom [yes/no]) to investigate which measure best predicts postoperative QoL. METHODS: We prospectively surveyed patients at outpatient visits before and after epilepsy surgery (n = 550). The QoL measure was the Quality of Life in Epilepsy (QOLIE-10) score at the patient's most recent office visit. We created multivariate regression models to predict postoperative QOLIE-10, with a different seizure outcome measure in each model. We compared models using adjusted R2 values and Akaike information criteria (AIC). RESULTS: Our cohort had a high level of disease severity and complexity (17% repeat surgery, 39% extratemporal, and 18% nonlesional). For the cohort as a whole, mean absolute seizure frequency decreased from 1 per day to 0.1 per day (P < .001), and mean reduction was 73% (95% confidence interval [CI] 66%-81%). Average improvement in QoL score was 5.3 (95% CI 4.1-6.5) points. Of patients who reported an improvement in QoL, 27% had persistent seizures. Comparison of regression models to predict QoL showed that the worst model was provided when using "absolute seizure reduction," but that models using "relative seizure reduction" and "seizure freedom (yes/no)" were equally strong. SIGNIFICANCE: In our high severity and complexity cohort, a substantial subset of patients (27%) reported improved QoL despite persistent seizures. Relative seizure reduction was at least as good a predictor of QoL as seizure freedom. A yes/no seizure freedom variable may be a suboptimal measure of surgical success, especially in high complexity cohorts.

Risk analysis of hemorrhage in stereo-electroencephalography procedures.

OBJECTIVE: To examine the true incidence of hemorrhage related to stereo-electroencephalography (SEEG) procedures. To analyze risk factors associated with the presence of different types of hemorrhage in SEEG procedures. METHODS: This was a retrospective, single-center observational study examining every SEEG implantation performed at our center from 2009 to 2017. This consisted of 549 consecutive SEEG implantations using a variety of stereotactic and imaging techniques. A hemorrhage grading system was applied by a blinded neuroradiologist to every postimplant and postexplant computed tomography (CT) scan. Hemorrhages were classified as asymptomatic or symptomatic based on neurologic deficit seen on examination. Statistical analysis included multivariate regression using relevant preoperative variables to predict the presence of hemorrhage. RESULTS: One hundred five implantations (19.1%) had any type of hemorrhage seen on postimplant CT. Of these, 93 (16.9%) were asymptomatic and 12 (2.2%) were symptomatic, with 3 implantations (0.6%) resulting in either a permanent deficit (2, 0.4%) or death (1, 0.2%). Male sex, increased number of electrodes, and increasing age were associated with increased risk of postimplant hemorrhage on multivariate analysis. Increasing score in the grading system was related to a statistically significant increase in the likelihood of a symptomatic hemorrhage. SIGNIFICANCE: Detailed examination of every postimplant CT reveals that the total hemorrhage rate appears higher than previously reported. Most of these hemorrhages are small and asymptomatic. Our grading system may be useful to risk stratify these hemorrhages and awaits prospective validation.