Electroclinical and Multimodality Neuroimaging Characteristics and Predictors of Post-Surgical Outcome in Focal Cortical Dysplasia Type IIIa

Focal cortical dysplasia (FCD) type IIIa is an easily ignored cause of intractable temporal lobe epilepsy. This study aimed to analyze the clinical, electrophysiological, and imaging characteristics in FCD type IIIa and to search for predictors associated with postoperative outcome in order to identify potential candidates for epilepsy surgery. We performed a retrospective review including sixty-six patients with FCD type IIIa who underwent resection for drug-resistant epilepsy. We evaluated the clinical, electrophysiological, and neuroimaging features for potential association with seizure outcome. Univariate and multivariate analyses were conducted to explore their predictive role on the seizure outcome. We demonstrated that thirty-nine (59.1%) patients had seizure freedom outcomes (Engel class Ia) with a median postsurgical follow-up lasting 29.5 months. By univariate analysis, duration of epilepsy (less than 12 years) (p = 0.044), absence of contralateral insular lobe hypometabolism on PET/MRI (pLog-rank = 0.025), and complete resection of epileptogenic area (pLog-rank = 0.004) were associated with seizure outcome. The incomplete resection of the epileptogenic area (hazard ratio = 2.977, 95% CI 1.218–7.277, p = 0.017) was the only independent predictor for seizure recurrence after surgery by multivariate analysis. The results of past history, semiology, electrophysiological, and MRI were not associated with seizure outcomes. Carefully included patients with FCD type IIIa through a comprehensive evaluation of their clinical, electrophysiological, and neuroimaging characteristics can be good candidates for resection. Several preoperative factors appear to be predictive of the postoperative outcome and may help in optimizing the selection of ideal candidates to benefit from epilepsy surgery.

Value of ultra-high field MRI in patients with suspected focal epilepsy and negative 3 T MRI (EpiUltraStudy): protocol for a prospective, longitudinal therapeutic study

Purpose Resective epilepsy surgery is a well-established, evidence-based treatment option in patients with drug-resistant focal epilepsy. A major predictive factor of good surgical outcome is visualization and delineation of a potential epileptogenic lesion by MRI. However, frequently, these lesions are subtle and may escape detection by conventional MRI (≤ 3 T). Methods We present the EpiUltraStudy protocol to address the hypothesis that application of ultra-high field (UHF) MRI increases the rate of detection of structural lesions and functional brain aberrances in patients with drug-resistant focal epilepsy who are candidates for resective epilepsy surgery. Additionally, therapeutic gain will be addressed, testing whether increased lesion detection and tailored resections result in higher rates of seizure freedom 1 year after epilepsy surgery. Sixty patients enroll the study according to the following inclusion criteria: aged ≥ 12 years, diagnosed with drug-resistant focal epilepsy with a suspected epileptogenic focus, negative conventional 3 T MRI during pre-surgical work-up. Results All patients will be evaluated by 7 T MRI; ten patients will undergo an additional 9.4 T MRI exam. Images will be evaluated independently by two neuroradiologists and a neurologist or neurosurgeon. Clinical and UHF MRI will be discussed in the multidisciplinary epilepsy surgery conference. Demographic and epilepsy characteristics, along with postoperative seizure outcome and histopathological evaluation, will be recorded. Conclusion This protocol was reviewed and approved by the local Institutional Review Board and complies with the Declaration of Helsinki and principles of Good Clinical Practice. Results will be submitted to international peer-reviewed journals and presented at international conferences. Trial registration number www.trialregister.nl: NTR7536.

Interictal SEEG resting-state connectivity localizes seizure onset zone and predicts seizure outcome

Stereotactic-electroencephalography (SEEG) is a common neurosurgical method to localize epileptogenic zone in drug resistant epilepsy patients and inform treatment recommendations. In the current clinical practice, localization of epileptogenic zone typically requires prolonged recordings to capture seizure, which may take days to weeks. Although epilepsy surgery has been proven to be effective in general, the percentage of unsatisfactory seizure outcomes is still concerning. We developed a method to identify the seizure onset zone (SOZ) and predict seizure outcome using short-time resting-state SEEG data. In a cohort of 43 drug resistant epilepsy patients, we estimated the information flow via directional connectivity and inferred the excitation-inhibition ratio from the 1/f power slope. We hypothesized that the antagonism of information flow at multiple frequencies between SOZ and non-SOZ underlying the relatively stable epilepsy resting state could be related to the disrupted excitation-inhibition balance. We found higher excitability in non-SOZ regions compared to the SOZ, with dominant information flow from non-SOZ to SOZ regions, probably reflecting inhibitory input from non-SOZ to prevent seizure initiation. Greater differences in information flow between SOZ and non-SOZ regions were associated with favorable seizure outcome. By integrating a balanced random forest model with resting-state connectivity, our method localized the SOZ with an accuracy of 85% and predicted the seizure outcome with an accuracy of 77% using clinically determined SOZ. Overall, our study suggests that brief resting-state SEEG data can significantly facilitate the identification of SOZ and may eventually predict seizure outcomes without requiring long-term ictal recordings.

Seizure Outcome After Surgery for MRI-Diagnosed Focal Cortical Dysplasia: A Systematic Review and Meta-analysis

Objective:Focal cortical dysplasia (FCD) has been associated with poorer post-surgical seizure outcomes compared to other pathologies. FCD surgical series have been assembled on the basis of a histological diagnosis, including patients with abnormal as well as normal pre-operative MRI. However, in clinical workflow, patient selection for surgery is based on pre-operative findings, including MRI. We performed a systematic review and meta-analysis of the literature to determine the rate and predictors of favorable seizure outcome after surgery for MRI-detected FCD.Methods:We devised our study protocol in accordance with PRISMA guidelines and registered the protocol with PROSPERO. We searched MEDLINE, EMBASE, and Web of Science for studies of patients followed for ≥12 months after resective surgery for drug-resistant epilepsy with MRI-detected FCD. Random-effects meta-analysis was used to calculate the proportion of patients attaining a favorable outcome, defined as Engel Class I, ILAE Classes 1-2, or “seizure-free” status. Meta-regression was performed to investigate sources of heterogeneity.Results:Our search identified 3,745 references. Of these, 35 studies (total of 1,353 patients) were included. Most studies (89%) followed patients for ≥24 months post-surgery. The overall post-surgical favorable outcome rate was 70% (95% CI: 64-75). There was high inter-study heterogeneity. Favorable outcome was associated with complete resection of the FCD lesion [risk ratio, RR=2.42 (95% CI: 1.55-3.76), p<0.001] and location of the FCD lesion in the temporal lobe [RR=1.38 (95% CI: 1.07-1.79), p=0013], but not lesion extent, intracranial EEG use, or FCD histological type. The number of FCD histological types included in the same study accounted for 7.6% of the observed heterogeneity.Conclusions:70% of patients with drug-resistant epilepsy and MRI features of FCD attain a favorable seizure outcome following resective surgery. Our findings can be incorporated in routine pre-operative counselling and reinforce the importance of resecting completely the MRI-detected FCD where this is safe and feasible.

Predictors of postoperative seizure outcome in supratentorial meningioma

OBJECTIVE Meningiomas are the most common primary intracranial tumor. Seizures are common sequelae of meningioma development. Meningioma patients with seizures can be effectively treated with resection, with reports of seizure freedom of 60%–90%. Still, many patients manifest persistent epilepsy. Determining factors associated with worsened seizure outcomes remains critical in improving the quality of life for these patients. The authors sought to identify clinical, radiological, and histological factors associated with worse seizure outcomes in patients with supratentorial meningioma and preoperative seizures. METHODS The authors retrospectively reviewed the charts of 384 patients who underwent meningioma resection from 2008 to 2020. The charts of patients with a documented history of preoperative seizures were further reviewed for clinical, radiological, operative, perioperative, histological, and postoperative factors associated with seizures. Engel class at last follow-up was retrospectively assigned by the authors and further grouped into favorable (class I) and worse (class II–IV) outcomes. Factors were subsequently compared by group using comparative statistics. Univariable and multivariable regression models were utilized to identify independent predictors of worse seizure outcome. RESULTS Fifty-nine patients (15.4%) were found to have preoperative seizures, of whom 57 had sufficient postoperative data to determine Engel class outcome. Forty-two patients (74%) had Engel class I outcomes. The median follow-up was 17 months. Distinct margins on preoperative imaging (p = 0.012), Simpson grade I resection (p = 0.004), postresection ischemia (p = 0.019), WHO grade (p = 0.019), and recurrent disease (p = 0.015) were found to be the strongest predictors of Engel class outcome in univariable logistic regression. MIB-1 index (p = 0.001) and residual volume (p = 0.014) at last follow-up were found to be the strongest predictors of Engel class outcome in univariable generalized linear regression. Postresection ischemia (p = 0.012), WHO grade (p = 0.022), recurrent disease (p = 0.038), and MIB-1 index (p = 0.002) were found to be the strongest independent predictors of Engel class outcomes in multivariable analysis. CONCLUSIONS Postresection ischemia, higher WHO grade, elevated MIB-1 index, and disease recurrence independently predict postresection seizure persistence in patients with supratentorial meningioma. Further understanding of the etiology of these markers may aid in elucidation of this complex disease process and guide management to prevent worse outcomes.

Association of intraoperative end-tidal carbon dioxide level with ablation volume during magnetic resonance–guided laser interstitial thermal therapy for mesial temporal lobe epilepsy

OBJECTIVE Maximal safe ablation of target structures during magnetic resonance–guided laser interstitial thermal therapy (MRgLiTT) is critical to achieving good seizure outcome in patients with mesial temporal lobe epilepsy (mTLE). The authors sought to determine whether intraoperative physiological variables are associated with ablation volume during MRgLiTT. METHODS Patients with mTLE who underwent MRgLiTT at our institution from 2014 to 2019 were retrospectively analyzed. Ablation volume was determined with volumetric analysis of intraoperative postablation MR images. Physiological parameters (systolic blood pressure [SBP], diastolic blood pressure [DBP], mean arterial pressure [MAP], end-tidal carbon dioxide [ETCO2]) measured 40 minutes prior to ablation were analyzed. Univariate and multivariate regression analyses were performed to determine independent predictors of ablation volume. RESULTS Forty-four patients met the inclusion criteria. The median (interquartile range) ablation volume was 4.27 (2.92–5.89) cm3, and median ablation energy was 7216 (6402–8784) J. The median MAP, SBP, DBP, and ETCO2 values measured during the 40-minute period leading up to ablation were 72.8 (66.2–81.5) mm Hg, 104.4 (96.4–114.4) mm Hg, 62.4 (54.1–69.8) mm Hg, and 34.1 (32.0–36.2) mm Hg, respectively. In univariate analysis, only total laser energy (r = 0.464, p = 0.003) and 40-minute average ETCO2 (r = −0.388, p = 0.012) were significantly associated with ablation volume. In multivariate analysis, only ETCO2 ≤ 33 mm Hg (p = 0.001) was significantly associated with ablation volume. CONCLUSIONS Total ablation energy and ETCO2, but not blood pressure, may significantly affect ablation volume in mTLE patients undergoing MRgLiTT. Mild hypocapnia was associated with increased extent of ablation. Intraoperative monitoring and modulation of ETCO2 may help improve extent of ablation, prediction of ablation volume, and potentially seizure outcome.

Focal Cortical Dysplasia Type Ⅲ Related Medically Refractory Epilepsy: MRI Findings and Potential Predictors of Surgery Outcome

This study aims to explore the relationship between neuropathologic and the post-surgical prognosis of focal cortical dysplasia (FCD) typed-Ⅲ-related medically refractory epilepsy. A total of 266 patients with FCD typed-Ⅲ-related medically refractory epilepsy were retrospectively studied. Presurgical clinical data, type of surgery, and postsurgical seizure outcome were analyzed. The minimum post-surgical follow-up was 1 year. A total of 266 patients of FCD type Ⅲ were included in this study and the median follow-up time was 30 months (range, 12~48 months). Age at onset ranged from 1.0 years to 58.0 years, with a median age of 12.5 years. The number of patients under 12 years old was 133 (50%) in patients with FCD type Ⅲ. A history of febrile seizures was present in 42 (15.8%) cases. In the entire postoperative period, 179 (67.3%) patients were seizure-free. Factors with p < 0.15 in univariate analysis, such as age of onset of epilepsy (p = 0.145), duration of epilepsy (p = 0.004), febrile seizures (p = 0.150), being MRI-negative (p = 0.056), seizure type (p = 0.145) and incomplete resection, were included in multivariate analysis. Multivariate analyses revealed that MRI-negative findings of FCD (OR 0.34, 95% CI 0.45–0.81, p = 0.015) and incomplete resection (OR 0.12, 95% CI 0.05–0.29, p < 0.001) are independent predictors of unfavorable seizure outcomes. MRI-negative finding of FCD lesions and incomplete resection were the most important predictive factors for poor seizure outcome in patients with FCD type Ⅲ.

Epilepsy surgery for low-grade epilepsy-associated neuroepithelial tumor of temporal lobe: a single-institution experience of 61 patients

Background Low-grade epilepsy-associated neuroepithelial tumor (LEAT) is highly responsive to surgery in general. The appropriate surgical strategy remains controversial in temporal LEAT. The aim of this study is to analyze the surgical seizure outcome of temporal LEAT, focusing on the aspects of surgical strategy. Methods Sixty-one patients from a single epilepsy center with temporal LEAT underwent surgery. The surgical strategy was according to the multidisciplinary presurgical evaluation. Electrocorticogram (ECoG)-assisted resection was utilized. Surgical extent including lesionectomy and extended resection was described in detail. Seizure outcome was classified as satisfactory (Engel class I) and unsatisfactory (Engel classes II–IV). Results After a median follow-up of 36.0 (30.0) months, 83.6% of patients achieved satisfactory outcome, including 72.1% with Engel class Ia. There was 39.3% (24/61) of patients with antiepileptic drug (AED) withdrawal. Use of ECoG (χ2 = 0.000, P > 0.1), preresection spike (χ2 = 0.000, P = 0.763), or spike residue (P = 0.545) was not correlated with the seizure outcome. For lateral temporal LEAT, outcome from lesionectomy was comparable to extended resection (χ2 = 0.499, P > 0.1). For mesial temporal LEAT, 94.7% (18/19) of patients who underwent additional hippocampectomy were satisfactory, whereas only 25% (1/4) of patients who underwent lesionectomy were satisfactory (P = 0.009). Conclusion Surgical treatment was highly effective for temporal LEAT. ECoG may not influence the seizure outcome. For lateral temporal LEAT, lesionectomy with or without cortectomy was sufficient in most patients. For mesial temporal LEAT, extended resection was recommended.