A longitudinal cohort study of mediators of health-related quality of life after pediatric epilepsy surgery or medical treatment.

OBJECTIVES: The purpose of this longitudinal cohort study was to examine the variables that influence health-related quality of life (HRQOL) after epilepsy surgery in children. We examined whether treatment type (surgical vs medical therapy) and seizure control are related to other variables that have been shown to influence HRQOL, namely depressive symptoms in children with epilepsy or their parents, and the availability of family resources. METHODS: In total, 265 children with drug-resistant epilepsy were recruited from eight epilepsy centers across Canada at the time of their evaluation for candidacy for epilepsy surgery and were assessed at baseline, 6-month, 1-year, and 2-year follow-up. Parents completed the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) and measures of family resources and depression; children completed depression inventories. Causal mediation analyses using natural effect models were used to evaluate the extent to which the relationship between treatment and HRQOL was explained by seizure control, child and parent depressive symptoms, and family resources. RESULTS: Overall, 111 children underwent surgery and 154 were treated with medical therapy only. The HRQOL scores of surgical patients were 3.4 points higher (95% confidence interval [CI]: -0.2, 7.0) relative to medical patients at the 2-year follow-up after adjusting for baseline covariates, with 66% of the effect of surgery attributed to seizure control. Child or parent depressive symptoms and family resources had negligible mediation effects between treatment and HRQOL. The effect of seizure control on HRQOL was not mediated by child or parent depressive symptoms, or by family resources. SIGNIFICANCE: The findings demonstrate that seizure control is on the causal pathway between epilepsy surgery and improved HRQOL in children with drug-resistant epilepsy. However, child and parent depressive symptoms and family resources were not significant mediators. The results highlight the importance of achieving seizure control to improve HRQOL.

Antiseizure medication use and medical resource utilization after resective epilepsy surgery in children in the United States: A contemporary nationwide cross-sectional cohort analysis.

OBJECTIVE: Antiseizure drug (ASD) therapy can significantly impact quality of life for pediatric patients whose epilepsy remains refractory to medications and who experience neuropsychological side effects manifested by impaired cognitive and social development. Contemporary patterns of ASD reduction after pediatric epilepsy surgery across practice settings in the United States are sparsely reported outside of small series. We assessed timing and durability of ASD reduction after pediatric epilepsy surgery and associated effects on health care utilization. METHODS: We performed a retrospective analysis of 376 pediatric patients who underwent resective epilepsy surgery between 2007 and 2016 in the United States using the Truven MarketScan database. Filled ASD prescriptions during the pre- and postoperative periods were compared. Univariate and multivariate analyses identified factors associated with achieving a stable discontinuation of or reduction in number of ASDs. Health care utilization and costs were systematically compared. RESULTS: One hundred seventy-one patients (45.5%) achieved a >90-day ASD-free period after surgery, and 84 (22.3%) additional patients achieved a stable reduction in number of ASDs. Achieving ASD freedom was more common in patients undergoing total hemispherectomy (n = 21, p = .002), and less common in patients with tuberous sclerosis (p = .003). A higher number of preoperative ASDs was associated with a greater likelihood of achieving ASD reduction postoperatively (hazard ratio [HR]: 1.85, 95% confidence interval [CI]: 1.50-2.28), but was not associated with a significant difference in the likelihood of achieving ASD freedom (0.83, 95% CI: 0.49-1.39). Achieving an ASD-free period was associated with fewer hospital readmissions within the first year after surgery. SIGNIFICANCE: Patterns of ASD use and discontinuation after pediatric epilepsy surgery provide an unbiased surgical outcome endpoint extractable from administrative databases, where changes in seizure frequency are not captured. This quantitative measure can augment traditional surgical outcome scales, incorporating a significant clinical parameter associated with improved quality of life.

Outcome of epilepsy surgery in lesional epilepsy: Experiences from a developing country.

BACKGROUND: Our aim was to report the postoperative seizure outcome and associated factors in patients with lesional epilepsy, in a low-income setting. METHODS: This longitudinal prospective study included patients who underwent epilepsy surgery at Kashani Comprehensive Epilepsy Center between 2014 and 2019. Post-surgical outcomes were reported according to the Engel score, and patients were classified into two groups of seizure free (SF) and not-seizure free (NSF). RESULTS: A total of 148 adult patients, with a mean age of 30.45 ±â€¯9.23 years were included. The SF outcome was reported in 86.5% of patients and antiepileptic drugs (AEDs) were reduced or discontinued in 45.9%. The mean follow-up duration was 26.7 ±â€¯14.9 months. Temporal lobe lesions (76.3%) and mesial temporal sclerosis (MTS) (56.7%) were the most frequent etiologies. Temporal lesion (Incidence relative risk (IRR): 1.76, 95% CI [1.08-2.87], p = 0.023), prior history of CNS infection (IRR:1.18, 95% CI [1.03-1.35], p = 0.019), use of intra-operative ECoG (IRR:1.73, 95% CI [1.06-2.81], p = 0.028), and absence of IEDs in postoperative EEG (IRR: 1.41, 95% CI [1.18-1.70], p < 0.001) were positive predictors for a favorable outcome. CONCLUSION: Many patients with drug-resistant lesional epilepsy showed a favorable response to surgery. We believe that resective epilepsy surgery in low-income settings is a major treatment option. The high frequency of patients with drug-resistant epilepsy in developing countries is associated with high rates of morbidity and mortality. Hence, strategies to increase access to epilepsy surgery in these settings are urgently needed.

Are psychogenic nonepileptic seizures risk factors for a worse outcome in patients with refractory mesial temporal epilepsy submitted to surgery? Results of a retrospective cohort study.

OBJECTIVE: The objective of this study was to verify if the presence of psychogenic nonepileptic seizures (PNES) could be a risk factor precluding corticoamygdalohippocampectomy (CAH) in patients with refractory temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS) (TLE-MTS). METHODS: This retrospective cohort study analyzed medical data of patients with refractory TLE-MTS accompanied in a Brazilian epilepsy surgery center. Presurgical psychiatric evaluations were performed using the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. Engel's I classification two years after surgery was considered as a favorable outcome. RESULTS: Of the 81 patients initially included (65 females; 56.5%), 49 (60.5%) had TLE-MTS without PNES, 24 (29.7%) with TLE-MTS and PNES, and eight (9.8%) with PNES only, who were excluded from further statistical comparisons. Nine patients with PNES (37.5%) underwent CAH versus 35 (71.4%) without PNES (p = 0.005). Five patients (55.5%) with PNES versus 26 (74.3%) without PNES presented Engel I (p = 0.54). The relative risk (RR) was of 1.90 for patients without PNES to undergo CAH and of 1.33 to be at Engel I. CONCLUSIONS: In this study, PNES were associated with less CAH. There were no differences, however, regarding favorable postsurgical outcomes. These results highlight that the sole presence of PNES should not preclude CAH in patients with TLE-MTS, despite the necessity of careful presurgical psychiatric evaluation.

PET hypermetabolism in medically resistant childhood epilepsy: Incidence, associations, and surgical outcome.

OBJECTIVE: We observed several children with medically resistant epilepsy demonstrating focal positron emission tomography (PET) hypermetabolism, a finding rarely reported and of questionable significance. We therefore retrospectively reviewed the incidence of hypermetabolic PET, and its relationship to electroencephalography (EEG) and magnetic resonance imaging (MRI) findings, and to the outcome of epilepsy surgery. METHODS: We retrospectively reviewed 498 PET brain studies in patients with medically resistant childhood epilepsy for evidence of hypermetabolism. In patients with PET hypermetabolism, we correlated metabolic abnormality with the scalp EEG and MRI findings. In a subset of patients who underwent surgical resection, we further correlated the PET findings with histopathologic and surgical outcomes. RESULTS: Focal PET hypermetabolism was identified in 33 (6.6%) of 498 studies. The region of hypermetabolism correlated with a spike count of ≥10 per minute in 26 of 32 concomitant scalp EEG studies and 18 of 21 lesions evident on MRI. In 17 patients who underwent surgical resection, PET hypermetabolism further correlated with regions revealing almost continuous epileptiform discharges on the intracranial EEG and with histopathologically malformative tissue. At a minimum follow-up of 1 year postsurgery (median 33 months), 7 (50%) of 14 patients had Engel's class I outcome, 4 patients had class II, and 2 had class III outcome, whereas one patient was unchanged. At last follow-up, seizure freedom was noted in five of seven patients with focal PET hypermetabolism alone versus three of eight patients with PET hypometabolism. SIGNIFICANCE: Focal PET hypermetabolism is associated with high spike frequency on scalp EEG and can occur in the absence of ictal events during the peri-injection period. Correlation with intracranial EEG usually corroborates the highly epileptogenic pathophysiologic state. Cortical malformations constitute the most common pathologic substrate, and resection of the hypermetabolic PET region may facilitate favorable outcomes. These observations indicate that focal PET hypermetabolism is an important marker of the epileptogenic zone and may represent its epicenter.

Short and long term prediction of seizure freedom in drug-resistant focal epilepsy surgery.

BACKGROUND: The selection of candidates for drug-resistant focal epilepsy surgery is essential to achieve the best post-surgical outcomes. OBJECTIVE: To develop two prediction models for seizure freedom in the short and long-term follow-up and from them to create a risk calculator in order to individualize the selection of candidates for surgery and future therapies in each patients. METHODS: A sample of 64 consecutive patients who underwent epilepsy surgery at two Cuban tertiary health institutions between 2012 and 2020 constituted the basis for the prediction models. Two models were obtained through the novel methodology, based on biomarker selection reached by resampling methods, cross-validation and high-accuracy index measured through the area under the receiving operating curve (ROC) procedure. RESULTS: The first, to pre-operative model included five predictors: epilepsy type, seizures per month, ictal pattern, interictal EEG topography and normal or abnormal magnetic resonance imaging,. it's precision was 0.77 at one year, and with four years and more 0.63. The second model including variables from the trans-surgical and post-surgical stages: the interictal discharges in the post-surgical EEG, incomplete or complete resection of the epileptogenic zone, the surgical techniques employed and disappearance of the discharge in post-resection electrocorticography; the precision of this model was 0.82 at one year, and with four years and more 0.97. CONCLUSIONS: The introduction of trans-surgical and post-surgical variables increase the prediction of the pre-surgical model. A risk calculator was developed using these prediction models, which could be useful as an accurate tool to improve the prediction in epilepsy surgery.

Focal to bilateral motor seizures in temporal lobe epilepsy during video-EEG monitoring: effects on surgical outcome.

The aim of this study was to determine whether the occurrence of focal to bilateral motor seizures in the course of partial drug withdrawal during video-EEG monitoring (FTBMS-M) had a predictive value for seizure recurrence in surgically treated patients with mesial temporal lobe epilepsy (MTLE). We analyzed the outcomes of 59 patients who underwent temporal lobe resection at 12 month postoperative follow up. In total, 48 out of 59 patients were rendered seizure free (81.4%). We analyzed seizure recurrence after surgery with reference to: (i) occurrence of seizures after partial drug withdrawal during video-EEG monitoring (FTBMS-M); (ii) history of secondarily generalized seizures during antiepileptic drug treatment prior to presurgical evaluation (FTBMS-H) and (iii) other possible confounding factors (sex, age, epilepsy duration, side of surgery, presence of hippocampal sclerosis, and history of febrile seizures). We found no differences in the frequency of seizure recurrences between patients with FTBMS-M and patients without FTBMS-M (4/20 vs. 7/39; p = 0.848). Conversely, the frequency of seizure recurrence was significantly higher among the patients with FTBMS-H than among the patients without FTBMS-H (7/20 vs. 4/39; p = 0.021). The predictive value of FTBMS-H for postoperative seizure recurrence was confirmed in logistic regression analysis. We found a statistically significant influence of FTBMS-H on poor outcome after surgery, but not of FTBMS-M or other confounding variables, which suggests that withdrawal seizures do not affect postsurgical seizure control.

Incorporation of quantitative MRI in a model to predict temporal lobe epilepsy surgery outcome.

Quantitative volumetric brain MRI measurement is important in research applications, but translating it into patient care is challenging. We explore the incorporation of clinical automated quantitative MRI measurements in statistical models predicting outcomes of surgery for temporal lobe epilepsy. Four hundred and thirty-five patients with drug-resistant epilepsy who underwent temporal lobe surgery at Cleveland Clinic, Mayo Clinic and University of Campinas were studied. We obtained volumetric measurements from the pre-operative T1-weighted MRI using NeuroQuant, a Food and Drug Administration approved software package. We created sets of statistical models to predict the probability of complete seizure-freedom or an Engel score of I at the last follow-up. The cohort was randomly split into training and testing sets, with a ratio of 7:3. Model discrimination was assessed using the concordance statistic (C-statistic). We compared four sets of models and selected the one with the highest concordance index. Volumetric differences in pre-surgical MRI located predominantly in the frontocentral and temporal regions were associated with poorer outcomes. The addition of volumetric measurements to the model with clinical variables alone increased the model's C-statistic from 0.58 to 0.70 (right-sided surgery) and from 0.61 to 0.66 (left-sided surgery) for complete seizure freedom and from 0.62 to 0.67 (right-sided surgery) and from 0.68 to 0.73 (left-sided surgery) for an Engel I outcome score. 57% of patients with extra-temporal abnormalities were seizure-free at last follow-up, compared to 68% of those with no such abnormalities (P-value = 0.02). Adding quantitative MRI data increases the performance of a model developed to predict post-operative seizure outcomes. The distribution of the regions of interest included in the final model supports the notion that focal epilepsies are network disorders and that subtle cortical volume loss outside the surgical site influences seizure outcome.

Focal-to-bilateral motor seizures in temporal lobe epilepsy during video-EEG monitoring: effects on surgical outcome.

The aim of this study was to determine whether the occurrence of focal-to-bilateral motor seizures in the course of partial drug withdrawal during video-EEG monitoring (FTBMS-M) had a predictive value for seizure recurrence in surgically treated patients with mesial temporal lobe epilepsy (MTLE). We analyzed the outcomes of 59 patients who underwent temporal lobe resection and had postoperative follow-up from 6 to 58 months. In total, 48 out of 59 patients were rendered seizure free (81.4%). We analyzed seizure recurrence after surgery with reference to: (i) occurrence of seizures after partial drug withdrawal during video-EEG monitoring (FTBMS-M); (ii) history of secondarily generalized seizures during antiepileptic drug treatment prior to presurgical evaluation (FTBMS-H) and (iii) other possible confounding factors (sex, age, epilepsy duration, side of surgery, presence of hippocampal sclerosis, and history of febrile seizures). We found no differences in the frequency of seizure recurrences between patients with FTBMS-M and patients without FTBMS-M (4/20 vs. 7/39; p = 0.848). Conversely, the frequency of seizure recurrence was significantly higher among the patients with FTBMS-H than among the patients without FTBMS-H (7/20 vs. 4/39; p = 0.021). The predictive value of FTBMS-H for postoperative seizure recurrence was confirmed in logistic regression analysis. We found a statistically significant influence of FTBMS-H on poor outcome after surgery, but not of FTBMS-M or other confounding variables, which suggests that withdrawal seizures do not affect post-surgical seizure control.

Morphological changes of cerebellar substructures in temporal lobe epilepsy: A complex phenomenon, not mere atrophy.

PURPOSE: To evaluate cerebellar volume changes in temporal lobe epilepsy (TLE) patients in greater detail. We aimed to determine which discrete substructures significantly differ in patients with TLE compared to controls and the nature of this difference. Correlations with age at epilepsy onset, epilepsy duration, seizure frequency, and total number of antiepileptic drugs (AED) in the patient's history were studied. We analyzed the potential association between cerebellar atrophy and epilepsy surgery outcome. METHODS: Study participants were 36 TLE patients; 22 hippocampal sclerosis (HS) only and 38 healthy controls. All patients later underwent temporal lobe resection. All subjects were examined using 1.5T MRI. Cerebellar volume was adjusted for total intracranial volume, age, and gender, and measured using voxel-based morphometry. Cerebellar substructures were defined using the AAL atlas. Data processing was performed automatically. Separate analyses for HS only subset were performed. RESULTS: Total cerebellar gray matter volume (GMV) appeared non-significantly smaller in epilepsy patients. Within the substructures, the GMV of the selected vermian segments were significantly larger in patients. The GMV of the whole cerebellum and of all individual cerebellar substructures non-significantly decreased with increasing complex partial seizure frequency and total number of AEDs in the patient's history. Total cerebellar GMV was significantly smaller in patients with persistent seizures after epilepsy surgery than in seizure-free patients. CONCLUSION: Cerebellar atrophy is a complex phenomenon, the character of changes differs significantly within the cerebellar substructures. Total cerebellar GMV reduction is associated with worse outcome of temporal lobe resection.

Improvement of intellectual outcomes in 20 children with refractory epilepsy after individualized surgery.

BACKGROUND: Refractory epilepsy is a common and troublesome neurosurgical disease. This study is designed to compare seizure control and degrees in intellectual outcome in children with refractory epilepsy after surgical treatment. METHODS: 20 children with refractory epilepsy were treated with tailored epilepsy surgery or vagus nerve stimulation (VNS). We used the Engel Epilepsy Surgery Outcome Scale to evaluate seizure control and the Wechsler Intelligence Scale for Children, fourth edition (WISC-IV), to test the children's intellectual outcomes 7-day preoperative and 3-, 6-, and 12-month postoperative. RESULTS: In total, 14 cases were seizure free (Engel I) and 2 cases to have suffered few attacks since surgery (Engel II). In two cases, the frequency of seizures decreased by >90% (Engel III). In the remaining two cases, the effects of surgery on seizure control were not obvious (Engel IV). All children completed the WISC-IV test. On average, postoperative intelligence quotient (IQ) increased by 6.35 points 12-month postsurgery compared with the results of the preoperative tests (P < 0.01). Second, intellectual outcomes after surgery in the Engel I and II groups increased by >3.88 points compared with in the Engel III and IV groups (P < 0.05). Finally, there were no fatal complications over the long-term follow-up except for intracranial infection of two cases; postoperative subcutaneous hematoma occurred in one case and hoarseness in one case. CONCLUSION: Individualized epilepsy surgery is safe and effective for children with refractory epilepsy. It can control or reduce the frequency of postoperative attacks as well as improve postoperative intellectual outcomes to different degrees.

Seizure outcome following primary motor cortex-sparing resective surgery for perirolandic focal cortical dysplasia.

OBJECTIVES: We present a case series of patients who underwent perirolandic resection for medically refractory focal epilepsy due to focal cortical dysplasia (FCD). Our aim was to specifically evaluate the outcome of a surgical strategy intended for seizure freedom while preserving primary motor cortex function. MATERIALS AND METHODS: Thirteen patients undergoing perirolandic resection for pharmacoresistant focal epilepsy between 2010 and 2015 who demonstrated histological evidence of FCD were selected from a prospectively maintained database. Presurgical evaluation included video EEG telemetry and 3T MRI brain for all patients. Eight patients underwent interictal FDG PET scan. Intracranial EEG monitoring was done for 8 patients - six by conventional subdural grid and depth electrodes and two by Stereo EEG. Additional techniques included extraoperative cortical stimulation mapping, intraoperative electrocorticography (ECoG), intraoperative motor cortex mapping and awake surgery in various combinations. In all cases (lesional and nonlesional), resection was intentionally limited for anatomic preservation of the primary motor cortex. RESULTS: Amongst the thirteen patients with age ranging 14-44 years (mean 26.8 ± 9.2) 62% of them had daily seizures. MRI abnormalities were identified in 8 patients (62%), PET showed concordant findings in 7 patients (88%). When utilized, the mean duration of intracranial EEG recordings was 8.0 ± 7.2 days (range 2-23 days). All patients underwent a primary motor cortex-sparing resection of the suspected epileptogenic cortex. The mean postoperative follow up period was 23 months (range 7.5-62 months). Twelve out of 13 (92%) were seizure free (Engel 1) outcome at the last follow-up assessment; one patient had Engel 2a outcome at 28 months. Six patients (46%) had immediate new focal neurological deficits, however all six patients had recovered completely within three months. CONCLUSION: The surgical strategy of a primary motor cortex-sparing resective surgery for perirolandic FCD is associated with an excellent early seizure-freedom rate and no permanent neurological deficits. Since the ultimate goal of resective epilepsy surgery is seizure freedom with simultaneous functional preservation, similar long term outcome studies should ultimately guide the resection strategy.

The correlation of magnetoencephalography to intracranial EEG in localizing the epileptogenic zone: a study of the surgical resection outcome.

OBJECTIVES: To evaluate the agreement between magnetoencephalography (MEG) and intracranial electroencephalography (ICEEG) results, to determine the characteristics that lead to concordance, and to assess how these factors relate to favorable epilepsy surgery outcome. MATERIALS: This retrospective study reviewed 50 patients who had positive MEG findings and ICEEG recordings between 2008 and 2010. The anatomical concordance between MEG and ICEEG recordings, the features of the MEG focus, and the relationship between the MEG focus and the surgically resected regions were correlated with the epilepsy surgery outcome. RESULTS: Thirty-six of the 50 patients with positive MEG and ICEEG findings underwent epilepsy surgery, and 27 (75%) of the patients had an anatomical concordance of MEG/ICEEG. Among the patients with concordant MEG/ICEEG, the seizure free outcome rate was significantly higher compared to the discordant group [18/27 (66.7%) patients concordant vs. 1/9 (11.1%) patients discordant (p<0.006)]. Nineteen (53%) of the 36 patients had complete resection when the MEG focus overlapped with the resection area, and 15 (79%) of these 19 patients became seizure-free following surgery (p<0.001); 17 (47%) of the 36 patients had an MEG focus that was not completely resected (the MEG foci of 7 patients partially overlapped the resection areas, and 10 patients had MEG foci that were in a different area from the resection area), and 13/17 (76.5%) patients had seizure recurrences (p<0.001). CONCLUSIONS: Both the anatomical concordance of MEG/ICEEG and the complete resection of the MEG foci significantly increased the chance of seizure-free outcomes following epilepsy surgery.