Long-term seizure outcome with the surgically remediable syndrome of frontal lobe epilepsy associated with superior frontal sulcus-related dysplasia.

Objective: To assess the long-term outcome of the surgically remediable syndrome of frontal lobe epilepsy (FLE) associated with superior frontal sulcus (SFS)-related dysplasia. Methods: We retrospectively reviewed the medical charts and surgical features of 31 patients with drug-resistant frontal lobe epilepsy in our centers between 2016 and 2018. All patients underwent surgical resection. According to the epileptogenic zone (EZ), localization and resection extent were classified as (1) pure SFS group (PS group), (2) associated SFS group (AS group), and (3) no SFS group (NS group). The general characteristics, neuroradiological findings, morbidity, pathology, and long-term seizure outcome after surgery were analyzed to extract the potential value of the surgery for SFS-related dysplasia. Results: Of 31 patients with FLE who underwent epilepsy surgery, 15 patients (nine men) were included PS group, five patients (five men) in the AS group, and 11 patients (eight men) in the NS group. Eleven patients detected abnormal focal signals in the presurgical MRI. Six patients in the PS group demonstrated the suspected focal cortical dysplasia (FCD) in the SFS detected with MRI. All patients demonstrated focal abnormal hypometabolism foci in the PET-MR co-registration. Twenty-five patients (80.6%) were seizure-free since surgery, including all 15 patients (100%) of the PS group, three in five patients (60%) of the AS group, and seven in 11 patients (63.6%) of the NS group. The difference in outcome between different groups was significant (p = 0.004, PS vs. AS group; p = 0.005, PS vs. NS group). As of the last follow-up (mean 66.2 ± 9.7months), 25 patients (80.6%) were seizure-free since surgery (Engel's class I). In addition, antiseizure medication was withdrawn in 19 patients (61.3%). Histologic examination of resected specimens revealed FCD in all 31 patients. The percentage of FCD II type was 100, 60, and 63.6% in the three different groups, respectively. Conclusion: SFS-related dysplasia is a neuropathologic entity with a favorable postoperative outcome. FCD II is the most common type of SFS-related dysplasia. FDG-PET co-registered with MRI should be performed in patients with suspected SFS-related dysplasia, since it may depict areas of hypometabolism suggestive of dysplasia in the absence of MRI abnormalities.

Preoperative Heart Rate Variability During Sleep Predicts Vagus Nerve Stimulation Outcome Better in Patients With Drug-Resistant Epilepsy.

Objective: Vagus nerve stimulation (VNS) is an adjunctive and well-established treatment for patients with drug-resistant epilepsy (DRE). However, it is still difficult to identify patients who may benefit from VNS surgery. Our study aims to propose a VNS outcome prediction model based on machine learning with multidimensional preoperative heart rate variability (HRV) indices. Methods: The preoperative electrocardiography (ECG) of 59 patients with DRE and of 50 healthy controls were analyzed. Responders were defined as having at least 50% average monthly seizure frequency reduction at 1-year follow-up. Time domain, frequency domain, and non-linear indices of HRV were compared between 30 responders and 29 non-responders in awake and sleep states, respectively. For feature selection, univariate filter and recursive feature elimination (RFE) algorithms were performed to assess the importance of different HRV indices to VNS outcome prediction and improve the classification performance. Random forest (RF) was used to train the classifier, and leave-one-out (LOO) cross-validation was performed to evaluate the prediction model. Results: Among 52 HRV indices, 49 showed significant differences between DRE patients and healthy controls. In sleep state, 35 HRV indices of responders were significantly higher than those of non-responders, while 16 of them showed the same differences in awake state. Low-frequency power (LF) ranked first in the importance ranking results by univariate filter and RFE methods, respectively. With HRV indices in sleep state, our model achieved 74.6% accuracy, 80% precision, 70.6% recall, and 75% F1 for VNS outcome prediction, which was better than the optimal performance in awake state (65.3% accuracy, 66.4% precision, 70.5% recall, and 68.4% F1). Significance: With the ECG during sleep state and machine learning techniques, the statistical model based on preoperative HRV could achieve a better performance of VNS outcome prediction and, therefore, help patients who are not suitable for VNS to avoid the high cost of surgery and possible risks of long-term stimulation.

Epileptogenic network of focal epilepsies mapped with cortico-cortical evoked potentials.

OBJECTIVE: The goal of this study was to investigate the spatial extent and functional organization of the epileptogenic network through cortico-cortical evoked potentials (CCEPs) in patients being evaluated with intracranial stereoelectroencephalography. METHODS: We retrospectively included 25 patients. We divided the recorded sites into three regions: epileptogenic zone (EZ); propagation zone (PZ); and noninvolved zone (NIZ). The root mean square of the amplitudes was calculated to reconstruct effective connectivity network. We also analyzed the N1/N2 amplitudes to explore the responsiveness influenced by epileptogenicity. Prognostic analysis was performed by comparing intra-region and inter-region connectivity between seizure-free and non-seizure-free groups. RESULTS: Our results confirmed that stimulation of the EZ caused the strongest responses on other sites within and outside the EZ. Moreover, we found a hierarchical connectivity pattern showing the highest connectivity strength within EZ, and decreasing connectivity gradient from EZ, PZ to NIZ. Prognostic analysis indicated a stronger intra-EZ connection in the seizure-free group. CONCLUSION: The EZ showed highest excitability and dominantly influenced other regions. Quantitative CCEPs can be useful in mapping epileptic networks and predicting surgical outcome. SIGNIFICANCE: The generated computational connectivity model may enhance our understanding of epileptogenic networks and provide useful information for surgical planning and prognosis prediction.

Superior Frontal Sulcus Focal Cortical Dysplasia Type II: An MRI, PET, and Quantified SEEG Study.

Purpose: The superior frontal sulcus (SFS), located in the prefrontal and premotor cortex, is considered as one of the common locations of focal cortical dysplasia (FCD). However, the characteristics of seizures arising from this area are incompletely known. The primary purpose of this study was to investigate the clinical features and the epileptic networks of seizures originating from the SFS. Methods: We included seventeen patients with type II FCD within the SFS. SFS was identified both visually and automatically. Semiological features were evaluated and grouped. Interictal 18FDG-PET imaging in all patients was compared to controls using statistical parametric mapping (SPM-PET). In those subjects with stereoelectroencephalography (SEEG), two different quantitative intracranial electroencephalography analyses were applied. Finally, the locations of the SFS-related hypometabolic regions and epileptogenic zones (EZs) were transformed into standard space for group analysis. Results: We identified two semiological groups. Group 1 (9/17) showed elementary motor signs (head version and tonic posturing), while group 2 (8/17) exhibited complex motor behavior (fear, hypermotor, and ictal pouting). Based on SPM-PET, an SFS-supplementary motor area (SMA) epileptic propagation network was found in group 1, and an SFS-middle cingulate cortex (MCC)-pregenual anterior cingulate cortex (pACC) propagation network was discovered in group 2. Intracranial EEG analysis suggested similar affected structures with high epileptogenicity. The SFS-related hypometabolic regions and EZs in these groups showed a posterior-anterior spatial relationship. Conclusions: Even though originating from the spatially restricted cortex, SFS seizures can be divided into two groups based on semiological features. The SFS-SMA and SFS-MCC-pACC epileptic propagation networks may play pivotal roles in the generation of different semiologies. The posterior-anterior spatial relationship of both hypometabolic regions and EZs provides potentially useful information for distinguishing different types of SFS seizures and surgical evaluation.

Use of an Automated Quantitative Analysis of Hippocampal Volume, Signal, and Glucose Metabolism to Detect Hippocampal Sclerosis.

Purpose: Magnetic resonance imaging (MRI) and positron emission tomography (PET) with 18F-fluorodeoxyglucose (18FDG) are valuable tools for evaluating hippocampal sclerosis (HS); however, bias may arise during visual analyses. The aim of this study was to evaluate and compare MRI and PET post-processing techniques, automated quantitative hippocampal volume (Q-volume), and fluid-attenuated inversion-recovery (FLAIR) signal (Q-FLAIR) and glucose metabolism (Q-PET) analyses in patients with HS. Methods: We collected MRI and 18FDG-PET images from 54 patients with HS and 22 healthy controls and independently performed conventional visual analyses (CVA) of PET (CVA-PET) and MRI (CVA-MRI) images. During the subsequent quantitative analyses, the hippocampus was segmented from the 3D T1 image, and the mean volumetric, FLAIR intensity and standardized uptake value ratio (SUVR) values of the left and right hippocampus were assessed in each subject. Threshold confidence levels calculated from the mean volumetric, FLAIR intensity and SUVR values of the controls were used to identify healthy subjects or subjects with HS. The performance of the three methods was assessed using receiver operating characteristic (ROC) curves, and the detection rates of CVA-MRI, CVA-PET, Q-volume, Q-FLAIR, and Q-PET were statistically compared. Results: The areas under the curves (AUCs) for the Q-volume, Q-FLAIR, and Q-PET ROC analyses were 0.88, 0.41, and 0.98, which suggested a diagnostic method with moderate, poor, and high accuracy, respectively. Although Q-PET had the highest detection rate among the two CVA methods and three quantitative methods, the difference between Q-volume and Q-PET did not reach statistical significance. Regarding the HS subtypes, CVA-MRI, CVA-PET, Q-volume, and Q-PET had similar detection rates for type 1 HS, and Q-PET was the most sensitive method for detecting types 2 and 3 HS. Conclusions: In MRI or 18FDG-PET images that have been visually assessed by experts, the quantification of hippocampal volume or glucose uptake can increase the detection of HS and appear to be additional valuable diagnostic tools for evaluating patients with epilepsy who are suspected of having HS.

Multimodality Image Post-processing in Detection of Extratemporal MRI-Negative Cortical Dysplasia.

Purpose: To determine the diagnostic value of individual image post-processing techniques in a series of patients who underwent extratemporal operations for histologically proven, MRI-negative focal cortical dysplasia (FCD). Methods: The morphometric analysis program (MAP), PET/MRI co-registration and statistical parametric mapping (SPM) analysis of PET (SPM-PET) techniques were analyzed in 33 consecutive patients. The epileptogenic zone (EZ) assumed by MAP, PET/MRI, and SPM-PET was compared with the location of the FCD lesions determined by stereoelectroencephalography (SEEG) and histopathological study. The detection rate of each modality was statistically compared. Results: Three lesions were simultaneously detected by the three post-processing methods, while two lesions were only MAP positive, and 8 were only PET/MRI positive. The detection rate of MAP, PET/MRI, SPM-PET and the combination of the three modalities was 24.2, 90.9, 57.6, and 97.0%, respectively. Taking the pathological subtype into account, no type I lesions were detected by MAP, and PET/MRI was the most sensitive method for detecting FCD types II and IIA. During a mean follow-up period of 22.94 months, seizure freedom was attained in 26/33 patients (78.8%) after focal corticectomy. Conclusions: MAP, PET/MRI, and SPM-PET provide complementary information for FCD detection, intracranial electrode design, and lesion resection. PET/MRI was particularly useful, with the highest detection rate of extratemporal MRI-negative FCD.

Preoperative Heart Rate Variability as Predictors of Vagus Nerve Stimulation Outcome in Patients with Drug-resistant Epilepsy.

Vagus nerve stimulation (VNS) is an adjunctive treatment for drug-resistant epilepsy (DRE). However, it is still difficult to predict which patients will respond to VNS treatment and to what extent. We aim to explore the relationship between preoperative heart rate variability (HRV) and VNS outcome. 50 healthy control subjects and 63 DRE patients who had received VNS implants and had at least one year of follow up were included. The preoperative HRV were analyzed by traditional linear methods and heart rhythm complexity analyses with multiscale entropy (MSE). DRE patients had significantly lower complexity indices (CI) as well as traditional linear HRV measurements than healthy controls. We also found that non-responders0 had significantly lower preoperative CI including Area 1-5, Area 6-15 and Area 6-20 than those in the responders0 while those of the non-responders50 had significantly lower RMSSD, pNN50, VLF, LF, HF, TP and LF/HF than the responders50. In receiver operating characteristic (ROC) curve analysis, Area 6-20 and RMSSD had the greatest discriminatory power for the responders0 and non-responders0, responders50 and non-responders50, respectively. Our results suggest that preoperative assessment of HRV by linear and MSE analysis can help in predicting VNS outcomes in patients with DRE.

Vagus Nerve Stimulation for Pediatric and Adult Patients with Pharmaco-resistant Epilepsy.

BACKGROUND: Over past two decades, vagus nerve stimulation (VNS) has been widely used and reported to alleviate seizure frequency worldwide, however, so far, only hundreds of patients with pharmaco-resistant epilepsy (PRE) have been treated with VNS in mainland China. The study aimed to evaluate the effectiveness of VNS for Chinese patients with PRE and compare its relationship with age cohort and gender. METHODS: We retrospectively assessed the clinical outcome of 94 patients with PRE, who were treated with VNS at Beijing Fengtai Hospital and Beijing Tiantan Hospital between November 2008 and April 2014 from our database of 106 consecutive patients. The clinical data analysis was retrospectively examined. RESULTS: Seizure frequency significantly decreased with VNS therapy after intermittent stimulation of the vagus nerve. At last follow-up, we found McHugh classifications of Class I in 33 patients (35.1%), Class II in 27 patients (28.7%), Class III in 20 patients (21.3%), Class IV in 3 patients (3.2%), and Class V in 11 patients (11.7%). Notably, 8 (8.5%) patients were seizure-free while ≥50% seizure frequency reduction occurred in as many as 60 patients (63.8%). Furthermore, with regard to the modified Engel classification, 12 patients (12.8%) were classified as Class I, 11 patients (11.7%) were classified as Class II, 37 patients (39.4%) were classified as Class III, 34 patients (36.2%) were classified as Class IV. We also found that the factors of gender or age are not associated with clinical outcome. CONCLUSIONS: This comparative study confirmed that VNS is a safe, well-tolerated, and effective treatment for Chinese PRE patients. VNS reduced the seizure frequency regardless of age or gender of studied patients.

Melatonin as an effective protector against doxorubicin-induced cardiotoxicity.

The present study was designed to explore the protective effects of melatonin and its analogs, 6-hydroxymelatonin and 8-methoxy-2-propionamidotetralin, on the survival of doxorubicin-treated mice and on doxorubicin-induced cardiac dysfunction, ultrastructural alterations, and apoptosis in mouse hearts. Whereas 60% of the mice treated with doxorubicin (25 mg/kg ip) died in 5 days, almost all the doxorubicin-treated mice survived when melatonin or 6-hydroxymelatonin (10 mg/l) was administered in their drinking water. Perfusion of mouse hearts with 5 microM doxorubicin for 60 min led to a 50% suppression of heart rate x left ventricular developed pressure and a 50% reduction of coronary flow. Exposure of hearts to 1 microM melatonin or 6-hydroxymelatonin reversed doxorubicin-induced cardiac dysfunction. 8-Methoxy-2-propionamidotetralin had no protective effects on animal survival and on in vitro cardiac function. Infusion of melatonin or 6-hydroxymelatonin (2.5 microg/h) significantly attenuated doxorubicin-induced cardiac dysfunction, ultrastructural alterations, and apoptosis in mouse hearts. Neither melatonin nor 6-hydroxymelatonin compromised the antitumor activity of doxorubicin in cultured PC-3 cells. These results suggest that melatonin protect against doxorubicin-induced cardiotoxicity without interfering with its antitumor effect.