IDH1 mutation predicts seizure occurrence and prognosis in lower-grade glioma adults.

Epileptic seizures are frequently the first symptom in glioma patients. However, the causal relationship between glioma and epilepsy is not yet fully understood, as it cannot be explained solely by tumor mass effect or peritumoral factors. In this study, we retrospectively enrolled 320 patients with grade 2-4 glioma who received treatment between January 2019 and July 2022, and explored the biomarkers of seizure occurrence and seizure outcome prediction using univariate and multivariate logistic regression analyses. Our results showed that IDH1 R132H mutation was an independent risk factor for seizure occurrence in lower-grade glioma (LGG) patients (OR = 4.915, 95%CI = 1.713 - 14.103, P = 0.003). Additionally, IDH1 R132H mutation predicted higher seizure-free ratios in LGG patients with intact ATRX expression (OR = 6.793, 95%CI = 1.217 - 37.923, P = 0.029) one year after diagnosis. Therefore, our findings suggest that IDH1 mutation can predict seizure occurrence and control in LGG patients, providing further insights into the relationship between glioma and epilepsy.

Cavernoma-Related Epilepsy: Postoperative Epilepsy Outcome and Analysis of the Predictive Factors, Case Series.

BACKGROUND: Epilepsy is common in patients harboring cavernous malformation, and surgery is reported to be an effective treatment. However, few patients still experience seizures after surgery. We analyzed the outcome and predictive factors after cavernoma-related epilepsy (CRE) surgery. METHODS: A database was created for all patients with CRE treated surgically from 2003 to 2020 at a university hospital. A chart review, perioperative epilepsy workup, surgical strategies, and postoperative and follow-up notes were analyzed. Postoperative seizure outcome was evaluated according to the Engel classification. RESULTS: Thirty-seven patients (40.5% women; mean age 39.1 ± 14.5 years) were studied. The mean follow-up time was 5.6 ± 3.9 years. Among 37 patients, 32 (86.5%) achieved Engel class I at the last follow-up. Engel class II was found in 1 (2.7%), Engel class III in 1 (2.7%), and Engel class IV in 3 (8.1%) cases. Engel class Ia was observed in 23 patients (62.2%). None of the patients had a worse seizure outcome after the operation (Engel class IVc). Univariate and multivariate analysis showed that short-standing, sporadic, or low-frequent (≤3) seizures were the only variables significantly associated with seizure freedom, whereas longstanding, drug-resistant, or high-frequent seizure history were associated with worse seizure outcomes. CONCLUSIONS: Surgical treatment results in favorable seizure control in most patients after CRE surgery. Long duration of epilepsy before surgery, high seizure frequency, and drug-resistant epilepsy could have a negative effect on seizure outcome (Engel class II-IV). Therefore, early surgical resection of the cavernoma after careful presurgical planning is recommended to achieve an optimal result.

Utility of magnetoencephalography combined with stereo-electroencephalography in resective epilepsy surgery: A 2-year follow-up.

PURPOSE: Precise and accurate implantation of stereo-electroencephalography (SEEG) electrodes is critical for the localization of the seizure onset zone (SOZ), which plays a leading role in the prognosis of resective epilepsy surgery. Magnetoencephalography (MEG) is a noninvasive technique which can delineate the epilepsy focus by visualizing interictal spikes into dipole clusters. MEG may provide supporting information for guiding SEEG electrode implantation and improve the long-term outcomes of epilepsy surgery. In this study, we evaluated the accuracy of MEG in determining the SOZ. METHODS: We retrospectively analyzed patients with refractory epilepsy who underwent MEG examination and SEEG implantation before resective epilepsy surgery in the Shanghai Ruijin Hospital. The SEEG plan was designed according to the dipole clusters and the resections were operated according to the SEEG recordings. We investigated the relationships of the pattern of MEG dipole clusters and SEEG sampling to the final resective surgery prognosis. RESULTS: We included 42 patients with a postoperative follow-up of at least 2 years (mean 34.1 months). Eighteen (42%) patients who showed concordant localization between MEG and SEEG evaluation had a higher probability of seizure-free outcome (p=0.046, χ2=4.835, odds ratio=5.00, 95% CI=1.12-22.30). Complete sampling of MEG dipole clusters by SEEG electrodes was found in 23 (54%) patients, who had higher probability of seizure-free outcome that those with incomplete sampling (p<0.001, odds ratio=16.67, 95% CI=3.11-89.28). MEG results showing a single, tight cluster or stable orientation were associated to better seizure outcomes after resective surgery. CONCLUSION: MEG dipole cluster helps SEEG implantation in localizing the SOZ for better long-term epilepsy surgery outcome. The MEG results can play a role as prognostic predictors of epilepsy surgery.

Outcome after resective epilepsy surgery in the elderly.

OBJECTIVE: The objective of this study was to compare complications, seizures, and neuropsychological outcomes after resective epilepsy surgery in patients ≥ 60 years of age who underwent operations to younger and matched controls. METHODS: Charts of 2243 patients were screened for operated patients in the authors' center between 2000 and 2015. Patients with available postsurgical follow-up data who were operated on at the age of 60 years or older and matched (by gender, histopathology, and side of surgery) controls who were between 20 and 40 years of age at the time of surgery were included. Outcomes regarding postoperative seizure control were scored according to the Engel classification and group comparisons were performed by using chi-square statistics. RESULTS: Data of 20 older patients were compared to those of 60 younger controls. Postoperative seizure control was favorable in the majority of the elderly patients (Engel classes I and II: 75% at 12 months, 65% at last follow-up), but the proportion of patients with favorable outcome tended to be larger in the control group (Engel classes I and II: 90% at 12 months, p = 0.092; 87% at last follow-up, p = 0.032, chi-square test). The surgical complication rate was higher in the elderly population (65% vs 27%, p = 0.002), but relevant persistent deficits occurred in 2 patients of each group only. Neuropsychological and behavioral assessments displayed considerable preoperative impairment and additional postoperative worsening, particularly of verbal skills, memory (p < 0.05), and mood in the elderly. CONCLUSIONS: The overall favorable postsurgical outcome regarding seizure control and the moderate risk of disabling persistent neurological deficits in elderly patients supports the view that advanced age should not be a barrier per se for resective epilepsy surgery and underscores the importance of an adequate presurgical evaluation and of referral of elderly patients to presurgical assessment.

Comorbid impulsivity after one year of epilepsy surgery.

BACKGROUND: Psychiatric comorbidities in patients with drug-resistant epilepsy (DRE) are frequently observed before and after epilepsy surgery. Impulsivity, defined as behaviors that are poorly conceived, are also frequent among patients with epilepsy. The aim of this study was to determine the presence of comorbid impulsivity in patients with DRE after one year of epilepsy surgery. METHODS: Patients who underwent epilepsy surgery for DRE and completed the postsurgical assessment protocol one year after surgery were included. All patients underwent a presurgical protocol comprising of neurological, psychiatric, neuropsychological, video-EEG and MRI assessments. The psychiatric evaluation was performed before and one year after surgery using SCID-I, SCID-II, GAF scale of DSM IV, and Beck Depression Inventory II. One year after surgery, Barratt Impulsiveness Scale 11, and Engel classification of seizures, were administered. RESULTS: A total of 38 patients were included in this study, 21 women (55.3%) and 17 men (44.7%), mean age 36 years (SD = 9.4). Higher impulsivity was associated with a worse epilepsy seizure outcome (p < 0.05), one year after surgery. According to the multiple linear regression analysis, a worse epilepsy seizure outcome was associated with higher levels of nonplanning impulsivity (p < 0.05) (p < 0.05, ß -0.5, r2 0.25). The GAF score was negatively associated with motor score (p < 0.05, ß -0.584, r2 0.42) and with the total BIS-11 score (p < 0.05, ß -0.557, r2 0.39). CONCLUSIONS: Impulsivity has been associated with a worse post-surgical seizure outcome. Larger studies about impulsivity might confirm these preliminary findings.

Post-Surgical Outcome and Its Determining Factors in Patients Operated on With Focal Cortical Dysplasia Type II-A Retrospective Monocenter Study.

Purpose: Focal cortical dysplasias (FCDs) are a frequent cause of drug-resistant focal epilepsies. These lesions are in many cases amenable to epilepsy surgery. We examined 12-month and long-term post-surgical outcomes and its predictors including positive family history of epilepsy. Methods: Twelve-month and long-term outcomes regarding seizure control after epilepsy surgery in patients operated on with FCD type II between 2002 and 2019 in the Epilepsy Center of Bonn were evaluated based on patient records and telephone interviews. Results: Overall, 102 patients fulfilled the inclusion criteria. Seventy-one percent of patients at 12 months of follow-up (FU) and 54% of patients at the last available FU (63 ± 5.00 months, median 46.5 months) achieved complete seizure freedom (Engel class IA), and 84 and 69% of patients, respectively, displayed Engel class I outcome. From the examined variables [histopathology: FCD IIA vs. IIB, lobar lesion location: frontal vs. non-frontal, family history for epilepsy, focal to bilateral tonic-clonic seizures (FTBTCS) in case history, completeness of resection, age at epilepsy onset, age at surgery, duration of epilepsy], outcomes at 12 months were determined by interactions of age at onset, duration of epilepsy, age at surgery, extent of resection, and lesion location. Long-term post-surgical outcome was primarily influenced by the extent of resection and history of FTBTCS. Positive family history for epilepsy had a marginal influence on long-term outcomes only. Conclusion: Resective epilepsy surgery in patients with FCD II yields very good outcomes both at 12-month and long-term follow-ups. Complete lesion resection and the absence of FTBTCS prior to surgery are associated with a better outcome.

Stereotactic MRI-guided laser interstitial thermal therapy for extratemporal lobe epilepsy.

OBJECTIVE: Magnetic resonance imaging (MRI)-guided laser interstitial thermal therapy (MRg-LITT) is an alternative to open epilepsy surgery. We assess safety and effectiveness of MRg-LITT for extratemporal lobe epilepsy (ETLE) in patients who are considered less favorable for open resection. METHODS: We retrospectively reviewed sequential cases of patients with focal ETLE who underwent MRg-LITT between 2012 and 2019. Epileptogenic zones were determined from standard clinical and imaging data ± stereoelectroencephalography (SEEG). Standard stereotactic techniques, MRI thermometry, and a commercial laser thermal therapy system were used for ablations. Anatomic MRI was used to calculate ablation volumes. Clinical outcomes were determined longitudinally. RESULTS: Thirty-five patients with mean epilepsy duration of 21.3 ± 12.2 years underwent MRg-LITT for focal ETLE at a mean age 36.4 ± 12.7 years. A mean 2.59 ± 1.45 trajectories per patient were used to obtain ablation volumes of 8.8 ± 7.5 cm3 . Mean follow-up was 27.3 ± 19.5 months. Of 32 patients with >12 months of follow-up, 17 (53%) achieved good outcomes (Engel class I + II) of whom 14 (44%) were Engel class I. Subgroup analysis revealed better outcomes for patients with lesional ETLE than for those who were nonlesional, multifocal, or who had failed prior interventions (P = .02). Of 13 patients showing favorable seizure-onset patterns (localized low voltage fast activity or rhythmic spiking on SEEG) prior to ablation, 9 (69%) achieved good outcomes, whereas only 3 of 11 (27%) who show other slower onset patterns achieved good outcomes. Minor adverse events included six patients with transient sensorimotor neurologic deficits and four patients with asymptomatic hemorrhages along the fiber tract. Major adverse events included one patient with a brain abscess that required stereotactic drainage and one patient with persistent hypothalamic obesity. Three deaths-two seizure-associated and one suicide-were unrelated to surgical procedures. SIGNIFICANCE: MRI-guided laser interstitial thermal therapy (or MRg-LITT) was well-tolerated and yielded good outcomes in a heterogeneous group of ETLE patients. Lesional epilepsy and favorable seizure-onset patterns on SEEG predicted higher likelihoods of success.

Outcomes of tumour related epilepsy in a specialised epilepsy surgery unit.

INTRODUCTION: Seizures are an important cause of morbidity in patients with low grade gliomas with approximately 40% of cases drug resistant. The pathogenesis is quite complex and poorly understood. The treatment aims vary between almost purely epilepsy considerations and those that are primarily oncologic. AIM: To determine whether patients who present with seizures and are found to have a low grade glioma have better outcomes when managed through a specialized epilepsy unit compared to the general neurosurgical service. METHODS: A review of the prospectively collected database was performed over a 10 year period to identify 48 adult patients who present with a seizure and were subsequently found to have a low grade glioma. These patients were analysed with respect to management through the specialized epilepsy service or the general neurosurgical service. The primary outcome was Engel classification between the two groups. Secondary outcomes included recurrence, postoperative deficits, delay to surgery, histology, grade and extent of resection. OUTCOMES: The patients managed through the epilepsy service had significantly higher rate of favourable Engel outcomes (I and II) compared to the general neurosurgery service (OR: 13.2, 95% CI: 1.239-140.679; P = 0.033). The epilepsy surgery group patients had a significantly higher delay to surgery (P < 0.001). The patients in the epilepsy service had a significantly higher resection ratio compared to the general neurosurgery service (73% vs 127%, P = 0.014). Rates of recurrence were not different between the two groups. CONCLUSION: Patients with tumour related epilepsy who undergo an intensive presurgical evaluation may obtain better seizure related outcomes.

An extent of resection threshold for seizure freedom in patients with low-grade gliomas.

OBJECTIVE Seizures are the most common presenting symptom of newly diagnosed WHO Grade II gliomas (low-grade glioma [LGG]) and significantly impair quality of life. Although gross-total resection of LGG is associated with better seizure control, it remains unclear whether an extent of resection (EOR) "threshold" exists for long-term seizure control. Specifically, what proportion of FLAIR-positive tissue in patients with newly diagnosed LGG must be removed to achieve Engel Class I seizure freedom? To clarify the EOR threshold for long-term seizure control, the authors analyzed data from a consecutive series of patients with newly diagnosed LGG who presented with seizures and subsequently underwent microsurgical resection. METHODS The authors identified consecutive patients with newly diagnosed LGG who presented with seizures and were treated at the Barrow Neurological Institute between 2002 and 2012. Patients were dichotomized into those who were seizure free postoperatively and those who were not. The EOR was calculated by quantitative comparison of pre- and postoperative MRI. Univariate analysis of these 2 groups included the chi-square test and the Mann-Whitney U-test, and a multivariate logistic regression was constructed to predict the impact of multiple independent variables on the likelihood of postoperative seizure freedom. To determine a threshold of EOR that optimizes seizure freedom, a receiver operating characteristic curve was plotted and the optimal point of discrimination was determined. RESULTS Data from 128 patients were analyzed (male/female ratio 1.37:1; mean age 40.8 years). All 128 patients presented with seizures, usually generalized (n = 57, 44.5%) or simple partial (n = 57, 44.5%). The median EOR was 90.0%. Of 128 patients, 46 (35.9%) had 100% volumetric tumor resection, 64 (50.0%) had 90%-99% volumetric tumor resection, and 11 (8.6%) had 80%-89% volumetric tumor resection. Postoperatively, 105 (82%) patients were seizure free (Engel Class I); 23 (18%) were not (Engel Classes II-IV). The proportion of seizure-free patients increased in proportion to the EOR. Predictive variables included in the regression model were preoperative Karnofsky Performance Scale score, seizure type, time from diagnosis to surgery, preoperative number of antiepileptic drugs, and EOR. Only EOR significantly affected the likelihood of postoperative Engel Class I status (OR 11.5, 95% CI 2.4-55.6; p = 0.002). The receiver operating characteristic curve generated based on Engel Class I status showed a sensitivity of 0.65 and 1 - specificity of 0.175, corresponding to an EOR of 80%. CONCLUSIONS For adult patients with LGG who suffer seizures, the results suggest that seizure freedom can be attained when EOR > 80% is achieved. Improvements in both the proportion of seizure-free patients and the durability of seizure freedom were observed beyond this 80% threshold. Interestingly, this putative EOR seizure-freedom threshold closely approximates that reported for the overall survival benefit in newly diagnosed hemispheric LGGs, suggesting that a minimum level of residual tumor burden is necessary for both disease and symptomatic progression.

Pediatric epilepsy surgery: could age be a predictor of outcomes?

OBJECTIVE Like adults, many children suffering from intractable seizures benefit from surgical therapy. Although various reports indicate that early intervention may avoid severe developmental consequences often associated with intractable epilepsy, surgery is still considered a last option for many children. In this retrospective study, the authors aimed to determine whether pediatric epilepsy surgery, in particular during the first years of life, relates to measurable benefits. METHODS Data from 78 patients (age range 5 months to 17 years) who underwent epilepsy surgery at the Geneva and Lausanne University Hospitals between 1997 and 2012 were reviewed retrospectively. Patients were dichotomized into 2 groups: infants (≤ 3 years of age, n = 19), and children/adolescents (4-17 years of age, n = 59). Compared with children/adolescents, infants more often had a diagnosis of dysplasia (37% vs 10%, respectively; p < 0.05, chi-square test). RESULTS The overall seizure-free rate was 76.9%, with 89.5% in infants and 72.9% in the children/adolescents group. Infants were 2.76 times as likely to achieve seizure-free status as children/adolescents. Postoperative antiepileptic medication was reduced in 67.9% of patients. Only 11.4% of the patients were taking more than 2 antiepileptic drugs after surgery, compared with 43% before surgery (p < 0.0001). The overall complication rate was 15.1% (6.4% transient hemiparesis), and no major complications or deaths occurred. CONCLUSIONS The data show a high seizure-free rate in children ≤ 3 years of age, despite a higher occurrence of dysplastic, potentially ill-defined lesions. Pediatric patients undergoing epilepsy surgery can expect a significant reduction in their need for medication. Given the excellent results in the infant group, prospective studies are warranted to determine whether age ≤ 3 years is a predictor for excellent surgical outcome.

Long-term outcome and predictors of resective surgery prognosis in patients with refractory extratemporal epilepsy.

PURPOSE: We analyzed the long-term postoperative outcome and possible predictive factors of the outcome in surgically treated patients with refractory extratemporal epilepsy. METHODS: We retrospectively analyzed 73 patients who had undergone resective surgery at the Epilepsy Center Brno between 1995 and 2010 and who had reached at least 1 year outcome after the surgery. The average age at surgery was 28.3±11.4 years. Magnetic resonance imaging (MRI) did not reveal any lesion in 24 patients (32.9%). Surgical outcome was assessed annually using Engel's modified classification until 5 years after surgery and at the latest follow-up visit. RESULTS: Following the surgery, Engel Class I outcome was found in 52.1% of patients after 1 year, in 55.0% after 5 years, and in 50.7% at the last follow-up visit (average 6.15±3.84 years). Of the patients who reached the 5-year follow-up visit (average of the last follow-up 9.23 years), 37.5% were classified as Engel IA at each follow-up visit. Tumorous etiology and lesions seen in preoperative MRI were associated with significantly better outcome (p=0.035; p<0.01). Postoperatively, 9.6% patients had permanent neurological deficits. CONCLUSION: Surgical treatment of refractory extratemporal epilepsy is an effective procedure. The presence of a visible MRI-detected lesion and tumorous etiology is associated with significantly better outcome than the absence of MRI-detected lesion or other etiology.

Ki-67 overexpression in WHO grade II gliomas is associated with poor postoperative seizure control.

PURPOSE: Seizures are the most common initial symptom in patients with low-grade gliomas, and approximately 30% of these patients still suffer from epilepsy after gross-total resection of the tumour. We examined the relationship between the overexpression of ki-67 in WHO grade II gliomas and seizure control. METHODS: A series of 93 histologically confirmed WHO grade II glioma tissues were analysed through immunohistochemical staining for ki-67 expression. Follow-up visits regarding seizure control were scheduled at 12 months. The Engel classification was used to categorise patients' seizure status. RESULTS: Of the 93 patients analysed, 65 (66.3%) patients initially presented with seizures. A total of 36 patients were diagnosed with WHO grade II oligodendrogliomas, 29 patients had oligoastrocytomas and 28 patients had astrocytomas. Ki-67 was over-expressed in 15 patients. One year after surgery poor seizure control was observed in 11 of these patients. In contrast, low ki-67 expression (<10%) was found in 78 patients. Poor seizure control was observed in 36 patients (difference between ki-67 over- and low expression groups P = 0.002). Logistic regression analysis revealed that patients with gross-total resection achieved better seizure control while ki-67 overexpression and age below 38 years were poor seizure control factors explained of the variance of seizure outcome (OR: 0.382, 4.354 and 1.822, respectively). CONCLUSIONS: In WHO grade II gliomas, Ki-67 is a molecular marker which predicts poor seizure control of glioma patients after the resection of the tumour. Gross-total resection, ki-67 overexpression and age below 38 years significantly affect seizure prognosis.