Frontal Epilepsy Research Articles

Electrocorticographic Patterns in Frontal Epilepsy and Long-Term Outcomes [RETRACTED

The prognostic significance of tailored resection guided with intraoperative electrocorticography (iECoG) in frontal lobe epilepsy surgery has not been fully elucidated. To analyze influence of preresection and postresection iECoG patterns on long-term seizure control of adults with frontal lobe epilepsy undergoing epilepsy surgery. We retrospectively analyzed 27 patients undergoing epilepsy surgery from two centers with preresection and postresection iECoG and reported clinical variables, preresection and postresection iECoG patterns, and outcome using the Engel Outcome Scale. Descriptive statistics, Kaplan-Meier, the logistic regression model, and analysis of variance tests were used. Fifteen males (55.6%), a mean and mode follow-up after surgery of 43 (range 2-117) and 19 months, respectively. At 6 months, seizure frequency outcome according to Engel Scale was I 74.1% (20/27), II 7.4% (2/27), III 3.7% (1/27), and IV 14.8% (4/27). We found that 51.9% (14/27) and 40.8% (11/27) of patients without residual epileptiform discharges in postresective iECoG become seizure-free at 6 and 12 months of follow-up, respectively, compared with other postresective iECoG patterns. Disregarding the presence of lack of residual epileptiform discharges (interictal epileptiform discharges) after resection, Engel I outcome was seen between 74.1% and 63% at 6- and 12-month postresection follow-up, suggesting the outcome might be in relation with other factors.

Post-Ictal Mania: A Case Report with Literature Revue

IntroductionWhile postictal mania is a well-recognized clinical condition, it has received less research attention compared to other postictal manifestations.ObjectivesDrawing upon an analysis of a case report that underscores the clinical and therapeutic challenges associated with comorbid epilepsy and mania, a literature review was carried out to investigate the connection between these two disorders.MethodsWe illustrate a case of comorbidity between mania and epilepsy and provide a concise review of the literature summarizing the key characteristics of this association.ResultsThis case pertains to Mr. M, a 44-year-old male with a history of frontal epilepsy characterized by secondary partial generalization, which was partially controlled with sodium valproate. He was admitted to our service due to acute agitation following a loss of consciousness lasting a few minutes.Upon admission, the patient exhibited symptoms of mental confusion. A neurological examination did not uncover any abnormalities. Brain computed tomography revealed mild frontal atrophy. Video electroencephalography conducted during the interictal period and outside the episodes of confusion did not reveal any abnormalities. The patient was restarted on sodium valproate (20 mg/kg/day) and clonazepam (2 mg/day). Following a lucid interval of ten days, the patient started to manifest psychiatric symptoms, which included irritability, hostility towards his spouse, increased talkativeness, thought pressure, and an unusual sense of familiarity, raising suspicion of post-ictal mania.ConclusionsBased on this clinical case and the existing scientific literature, post-ictal mania occupies a distinct position among the mental disorders observed in the post-ictal period. Therefore, clinicians must be aware of these conditions to facilitate accurate diagnosis and appropriate management.Disclosure of InterestNone Declared

Multitarget deep brain stimulation for epilepsy.

Deep brain stimulation (DBS) is a rapidly growing surgical option for patients with drug-resistant epilepsy who are not candidates for resective/ablative surgery. Recent randomized controlled trials have demonstrated efficacy of DBS of the anterior nucleus of the thalamus (ANT), particularly in frontal or temporal epilepsy, whereas DBS of the centromedian (CM) nucleus appears to be most suitable in well-defined generalized epilepsy syndromes. At the authors' institution, DBS candidates who did not fit the populations represented in these trials were managed with DBS of multiple distinct targets, which included ANT, CM, and less-studied nuclei-i.e., mediodorsal nucleus, pulvinar, and subthalamic nucleus. The goal of this study was to present the authors' experience with these types of cases, and to motivate future investigations that can determine the long-term efficacy of multitarget DBS. This single-center retrospective study of adult patients with drug-resistant epilepsy who underwent multitarget DBS was performed to demonstrate the feasibility and safety of this approach, and to present seizure outcomes. Patients in this cohort had epilepsy with features that were difficult to treat with DBS of the ANT or CM nucleus alone, including multifocal/multilobar, diffuse-onset, and/or posterior-onset seizures; or both generalized and focal seizures. Eight patients underwent DBS of 2-3 distinct thalamic/subthalamic nuclei. DBS was performed with 2 electrodes in each hemisphere. All leads in each patient were implanted with either frontal or parietal trajectories. There were no surgical complications. Among those with > 6 months of follow-up (n = 5; range 7-21 months), all patients were responders in terms of overall seizure frequency and/or convulsive seizure frequency (i.e., ≥ 50% reduction). Two patients had adverse stimulation effects, which resolved with further programming. Multitarget DBS is a procedurally feasible and safe treatment strategy to maximize outcomes in patients with complex epilepsy. The authors highlight their approach to inform future studies that are sufficiently powered to assess its efficacy.

Identification of epileptic networks with graph convolutional network incorporating oscillatory activities and evoked synaptic responses

Stereoelectroencephalography (SEEG) offers unique neural data from in-depth brain structures with fine temporal resolutions to better investigate the origin of epileptic brain activities. Although oscillatory patterns from different frequency bands and functional connectivity computed from the SEEG datasets are employed to study the epileptic zones, direct electrical stimulation-evoked electrophysiological recordings of synaptic responses, namely cortical-cortical evoked potentials (CCEPs), from the same SEEG electrodes are not explored for the localization of epileptic zones. Here we proposed a two-stream model with unsupervised learning and graph convolutional network tailored to the SEEG and CCEP datasets in individual patients to perform localization of epileptic zones. We compared our localization results with the clinically marked electrode sites determined for surgical resections. Our model had good classification capability when compared to other state-of-the-art methods. Furthermore, based on our prediction results we performed group-level brain-area mapping analysis for temporal, frontal and parietal epilepsy patients and found that epileptic and non-epileptic brain networks were distinct in patients with different types of focal epilepsy. Our unsupervised data-driven model provides personalized localization analysis for the epileptic zones. The epileptic and non-epileptic brain areas disclosed by the prediction model provide novel insights into the network-level pathological characteristics of epilepsy.

The effect of cannabidiol on seizure features and quality of life in drug-resistant frontal lobe epilepsy patients: a triple-blind controlled trial.

Treatment-resistant epileptic seizures are associated with reduced quality of life (QoL). As polypharmacy with routine antiseizure medications has many side effects, novel add-on treatments are necessary. Recent research showed the efficacy of add-on therapy by cannabidiol (CBD) on refractory epilepsy. We attempted to extend data on the efficacy and safety profile of CBD in patients with frontal lobe treatment-resistant epilepsy. A total of 27 patients were recruited into two CBD (n = 12) and placebo (n = 15) groups. The CBD group received a highly purified liposomal preparation of the drug in addition to routine antiseizure medications. The placebo group only received antiseizure medications. This experiment followed a triple-blinding protocol. Outcome measures were seizure frequency, the Chalfont seizure severity scale (CSSS), and the quality of life questionnaire score (QOLIE-31) assessed at baseline, 4 weeks, and 8 weeks. At 4 weeks, results indicated that a higher fraction of patients in the CBD group (66.67%) showed improvement in seizure, compared to the placebo group (20.00%). Before-after comparison revealed that CBD, unlike routine ADEs, was effective in reducing the occurrence of seizures at the study's final timepoint [mean difference 45.58, 95% CI (8.987 to 82.18), p = 0.009]. Seizure severity was not affected by study groups or time intervals (repeated-measures ANOVA p > 0.05). Post-hoc tests found that the QoLI-31 score was improved at 8 weeks compared to baseline [mean diff. -5.031, 95% CI (-9.729 to -0.3328), p = 0.032]. The difference in cases who experienced enhanced QoL was meaningful between the CBD and placebo groups at 8 weeks [RR: 2.160, 95% CI (1.148 to 4.741), p = 0.018] but not at 4 weeks (p = 0.653). A positive finding for QoL improvement was associated with a positive finding for seizure frequency reduction [r = 0.638, 95% CI (0.296 to 0.835), p = 0.001]. Interestingly, limiting the correlation analysis to cases receiving CBD indicated that QoL improvement was not linked with seizure parameters such as severity and frequency (p > 0.05). The present study suggests the benefit of a purified and highly efficient preparation of CBD for seizure frequency reduction and improvement of QoL in refractory frontal lobe epilepsy. Further study with longer follow-ups and larger sample size is advised. https://www.irct.ir/trial/56790, identifier: IRCT20210608051515N1.

Multiparametric mapping of white matter reorganizations in patients with frontal glioma-related epilepsy.

Epilepsy is a common symptom in diffuse lower-grade glioma (DLGG). The specific role of white matter (WM) alteration in patients with glioma-related epilepsy (GRE) is largely unknown. This study aims to investigate the reorganization of WM tracts and changes in structural networks related to GRE. Diffusion-weighted images were collected from 70 patients with left frontal DLGG (GRE = 33, non-GRE = 37) and 41 healthy controls (HC). Tractometry with TractSeg was applied to segment tracts and quantify fractional anisotropy (FA) along each tract. Structural network was constructed using constrained spherical deconvolution and probabilistic tractography. FA and network properties were compared among three groups. Compared with HC, both GRE and non-GRE showed decreased FA in contralateral inferior fronto-occipital fasciculus, superior longitudinal fasciculus II and arcuate fasciculus, increased nodal efficiency in contralateral nodes of frontal-parietal and limbic networks, whereas decreased degree centrality and betweenness centrality in nodes of dorsal temporal lobe and rostral middle frontal gyrus (rMFG). Additionally, when compared GRE with non-GRE, increased FA in contralateral corticospinal tract (CST) and lower betweenness centrality in paracentral lobule (PCL) in GRE (all p < 0.05 after Bonferroni correction). This study indicates that patients with left frontal DLGG exhibit complex WM reorganization, and the altered regions mainly concentrated in the language, frontal-parietal and limbic networks. Moreover, the preserved integrity in contralateral CST and server decreased nodal betweenness in PCL may be potential neuroimaging markers underlying the occurrence of presurgical seizures of GRE.

Auditory verbal hallucination can be evoked by prefrontal epileptic seizure

Auditory verbal hallucinations (AVHs) have been reported in neocortical temporal epileptic seizures and have been considered highly associated with implication of auditory cortex by epileptic discharges or electrical stimulation. Herein, we report two rare frontal epilepsy cases in which AVHs featured the habitual seizures. The epileptogenic zones of these two patients were localized in the dorsal and orbitomedial prefrontal cortex, respectively by stereoelectroencephalography (SEEG) monitoring. Comparing with the AVHs in schizophrenia, we postulated that the phenomenological similarities between the two sets of AVHs imply homology in mechanisms. Ictal SEEG confirmed that the wide involvement of prefrontal–cingulate–auditory cortical network by low-voltage fast activity corresponded the occurrence with AVHs during frontal epileptic seizures. Electrical stimulation study of one of the two cases highlighted the causal role of prefrontal–cingulate cortex in the emergence of AVHs. Based on our clinical observation, SEEG findings, and electrical cortical stimulation, we supposed that wide implication of prefrontal–cingulate–auditory cortical network during epileptic seizure underlie the emergence of AVHs, and further hypothesized that AVHs could be yielded by transient deficit of self-monitoring for inner speech in focal epileptic seizures.

Characteristics of Microstructural Changes Associated with Glioma Related Epilepsy: A Diffusion Tensor Imaging (DTI) Study.

(1) Background: Glioma is the most common primary tumor in the central nervous system, and glioma-related epilepsy (GRE) is one of its common symptoms. The abnormalities of white matter fiber tracts are involved in attributing changes in patients with epilepsy (Rudà, R, 2012).This study aimed to assess frontal lobe gliomas’ effects on the cerebral white matter fiber tracts. (2) Methods: Thirty patients with frontal lobe glioma were enrolled and divided into two groups (Ep and nEep). Among them, five patients were excluded due to apparent insular or temporal involvement. A set of 14 age and gender-matched healthy controls were also included. All the enrolled subjects underwent preoperative conventional magnetic resonance images (MRI) and diffusion tensor imaging (DTI). Furthermore, we used tract-based spatial statistics to analyze the characteristics of the white matter fiber tracts. (3) Results: The two patient groups showed similar patterns of mean diffusivity (MD) elevations in most regions; however, in the ipsilateral inferior fronto-occipital fasciculus (IFOF), superior longitudinal fasciculus (SLF), and superior corona radiata, the significant voxels of the EP group were more apparent than in the nEP group. No significant fractional anisotropy (FA) elevations or MD degenerations were found in the current study. (4) Conclusions: Gliomas grow and invade along white matter fiber tracts. This study assessed the effects of GRE on the white matter fiber bundle skeleton by TBSS, and we found that the changes in the white matter skeleton of the frontal lobe tumor-related epilepsy were mainly concentrated in the IFOF, SLF, and superior corona radiata. This reveals that GRE significantly affects the white matter fiber microstructure of the tumor.

Altered Structural and Functional Patterns Within Executive Control Network Distinguish Frontal Glioma-Related Epilepsy.

BackgroundThe tumor invasion of the frontal lobe induces changes in the executive control network (ECN). It remains unclear whether epileptic seizures in frontal glioma patients exacerbate the structural and functional alterations within the ECN, and whether these changes can be used to identify glioma-related seizures at an early stage. This study aimed to investigate the altered structural and functional patterns of ECN in frontal gliomas without epilepsy (non-FGep) and frontal gliomas with epilepsy (FGep) and to evaluate whether the patterns can accurately distinguish glioma-related epilepsy.MethodsWe measured gray matter (GM) volume, regional homogeneity (ReHo), and functional connectivity (FC) within the ECN to identify the structural and functional changes in 50 patients with frontal gliomas (29 non-FGep and 21 FGep) and 39 healthy controls (CN). We assessed the relationships between the structural and functional changes and cognitive function using partial correlation analysis. Finally, we applied a pattern classification approach to test whether structural and functional abnormalities within the ECN can distinguish non-FGep and FGep from CN subjects.ResultsWithin the ECN, non-FGep and FGep showed increased local structure (GM) and function (ReHo), and decreased FC between brain regions compared to CN. Also, non-FGep and FGep showed differential patterns of structural and functional abnormalities within the ECN, and these abnormalities are more severe in FGep than in non-FGep. Lastly, FC between the right superior frontal gyrus and right dorsolateral prefrontal cortex was positively correlated with episodic memory scores in non-FGep and FGep. In particular, the support vector machine (SVM) classifier based on structural and functional abnormalities within ECN could accurately distinguish non-FGep and FGep from CN, and FGep from non-FGep on an individual basis with very high accuracy, area under the curve (AUC), sensitivity, and specificity.ConclusionTumor invasion of the frontal lobe induces local structural and functional reorganization within the ECN, exacerbated by the accompanying epileptic seizures. The ECN abnormalities can accurately distinguish the presence or absence of epileptic seizures in frontal glioma patients. These findings suggest that differential ECN patterns can assist in the early identification and intervention of epileptic seizures in frontal glioma patients.

Safety and efficacy of responsive neurostimulation in the pediatric population: Evidence from institutional review and patient-level meta-analysis

BackgroundResponsive neurostimulation (RNS) is a novel technology for drug-resistant epilepsy rising from bilateral hemispheres or eloquent cortex. Although recently approved for adults, its safety and efficacy for pediatric patients is under investigation. MethodsA comprehensive literature search (Pubmed/Medline, Scopus, Cochrane) was conducted for studies on RNS for pediatric epilepsy (<18 y/o) and supplemented by our institutional series (4 cases). Reduction in seizure frequency at last follow-up compared to preoperative baseline comprised the primary endpoint. ResultsA total of 8 studies (49 patients) were analyzed. Median age at implant was 15 years (interquartile range [IQR] 12–17) and 63% were males. A lesional MRI was noted in 64% (14/22). Prior invasive EEG recording was performed in the majority of patients (90%) and the most common modality was stereoelectroencephalography (57%). The most common implant location (total of 94 RNS leads) was the frontal lobe (27%), followed by mesial temporal structures (23%) and thalamus (17%). At a median follow-up of 22 months, median seizure frequency reduction was 75% (IQR: 50–88%) and 80% were responders (>50% seizure reduction). Responses ranged from 50% for temporal lobe epilepsy to 81–93% for frontal, parietal, and multilobar epilepsy. Four infections were observed (8%) and there were no hematomas or postoperative neurological deficits. ConclusionCurrent evidence, albeit limited by potential publication bias, supports the promising safety and efficacy profile of RNS for medically refractory pediatric epilepsy. Randomized controlled trial data are needed to further establish the role of this intervention in preoperative discussions with patients and their families.

Postoperative striatal degeneration: a hitherto unrecognized impact of frontal disconnection surgery for drug-resistant epilepsy. Illustrative cases.

BACKGROUNDFrontal disconnection surgery is a useful surgical option for patients with frontal epilepsy whose seizure onset zones are exceedingly large and thus are not amenable to conventional resective surgery. While it has the advantage of avoiding sequelae stemming from a large resection cavity, the impact of radical anatomofunctional disconnection of such a vast frontal region is not fully understood.OBSERVATIONSThe authors have identified secondary degeneration in the striatum ipsilateral to the frontal disconnection surgery in two adult patients who had otherwise favorable postoperative outcomes following the surgery. On serial postoperative magnetic resonance imaging, the striatum showed transient restricted diffusion in the caudate head and rostral putamen around several weeks postoperatively and subsequent atrophy in the caudate head. The affected striatal regions (i.e., the anterior portion of the striatum) were congruent with the known fronto-striatal connectivity corresponding to the disconnected frontal regions anterior to the primary and supplementary motor areas. Both patients achieved 1-year seizure freedom without apparent disability related to the surgery.LESSONSThe benign postoperative course despite the marked degenerative changes in the ipsilateral striatum supports the feasibility of the frontal disconnection surgery in otherwise inoperable patients with broad frontal epileptogenicity.

Decreasing Shortest Path Length of the Sensorimotor Network Induces Frontal Glioma-Related Epilepsy.

BackgroundGlioma-related epilepsy (GRE) is a common symptom in patients with prefrontal glioma. Epilepsy onset is associated with functional network alterations. This study investigated alterations of functional networks in patients with prefrontal glioma and GRE.MethodsSixty-five patients with prefrontal lobe gliomas were retrospectively assessed and classified into GRE and non-GRE groups. Additionally, 25 healthy participants were enrolled after matching for general information. Imaging data were acquired within 72 h in pre-operation. The sensorimotor network was used to delineate alterations in functional connectivity (FC) and topological properties. One-way analysis of variance and post-hoc analysis with Bonferroni correction were used to calculate differences of FC and topological properties.ResultsAll significant alterations were solely found in the sensorimotor network. Irrespective of gliomas located in the left or right prefrontal lobes, the edge between medial Brodmann area 6 and caudal ventrolateral Brodmann area 6 decreased FC in the GRE group compared with the non-GRE group [p < 0.0001 (left glioma), p = 0.0002 (right glioma)]. Moreover, the shortest path length decrease was found in the GRE group compared with the non-GRE group [p = 0.0292 (left glioma) and p = 0.0129 (right glioma)].ConclusionsThe reduction of FC between the medial BA 6 (supplementary motor area) and caudal ventrolateral BA 6 in the ipsilateral hemisphere and the shortening of the path length of the sensorimotor network were characteristics alterations in patients with GRE onset. These findings fill in the gap which is the relationship between GRE onset and the alterations of functional networks in patients with prefrontal glioma.Significance StatementGlioma related epilepsy is the most common symptom of prefrontal glioma. It is important to identify characteristic alterations in functional networks in patients with GRE. We found that all significant alterations occurred in the sensorimotor network. Moreover, a decreased FC in the supplementary motor area and a shortening of the path’s length are additional characteristics of glioma-related epilepsy. We believe that our findings indicate new directions of research that will contribute to future investigations of glioma-related epilepsy onset.

Resective surgery for patients with frontal lobe diffuse low-grade glioma-related epilepsy: predictors of seizure outcomes

Diffuse low-grade gliomas (DLGGs) are prone to invade the frontal lobes, with seizures being the most common symptom. However, limited attention has been paid to surgical outcomes and their predictors in patients with frontal DLGG-related epilepsy. This study aimed to analyze predictors of postoperative seizure outcomes in patients with frontal DLGG-related epilepsy. This is a single-center retrospective study. This study retrospectively collected data of 115 patients with frontal DLGG-related epilepsy who underwent resective surgery between January 2014 and January 2021. Patients were categorized into favorable and unfavorable seizure outcome groups based on the International League Against Epilepsy (ILAE) classification. Univariate and multivariate analyses were used to identify potential predictors of seizure outcomes. The mean follow-up was 4.11 ± 2.06 years, and 77.4% (89 of 115) of patients were seizure-free. Permanent neurological deficits were observed in 7.0% (8 of 115) of patients. Univariate and multivariate analyses revealed that total tumor removal [odds ratio (OR), 0.31; 95% confidence interval (CI), 0.12-0.82; p = 0.018] and older age at seizure onset (OR, 0.96; 95% CI, 0.93-0.99; p = 0.042) were independent predictors of favorable seizure outcomes. Surgical resection is an effective treatment for frontal DLGG-related epilepsy. Favorable seizure outcomes are more likely to be achieved in patients with complete tumor removal and those with older age at seizure onset.

Variations in Seizure Frequency During Pregnancy and Postpartum by Epilepsy Type.

To assess whether increased seizure frequency during pregnancy and postpartum is influenced by epilepsy type, seizure location, and antiseizure medications. Clinical data were collected in a longitudinal prospective database of pregnant women with epilepsy at Brigham and Women's Hospital. Within each individual participant, baseline seizure frequency was calculated for the 9 months before conception, and whether seizure frequency increased during pregnancy or the postpartum period was determined. Seizure frequency was calculated for each 4-week interval during pregnancy. Generalized estimating equations for logistic regression were applied. Ninety-nine patients contributing 114 pregnancies were included from 2013 to 2018. Increased seizure frequency occurred more often during pregnancies of women with focal vs generalized epilepsy (21.1% vs 5.3%, odds ratio [OR] 4.70, 95% confidence interval [CI] 1.00-22.00; p = 0.0497). Among women with focal epilepsy, increased seizure frequency occurred more often in those with frontal lobe epilepsy (OR 8.00, 95% CI 2.19-29.21; p = 0.0017). There was no difference in seizure worsening in the postpartum period between the focal and generalized (11.1% vs 9.1%; p = 0.4478) or frontal and other focal (18.8% vs 6.0%; p = 0.1478) epilepsy groups. Pregnancies on polytherapy had higher odds of seizure worsening compared to monotherapy (OR 8.36, 95% CI 2.07-33.84; p = 0.0029), regardless of the medication or epilepsy type. A lack of preconception seizure freedom was also associated with increased seizure frequency during pregnancy (OR 6.418; p = 0.0076). Women with focal epilepsy have higher likelihood of seizure worsening during pregnancy compared to women with generalized epilepsy; frontal lobe epilepsy poses an especially elevated risk. Polytherapy and lack of preconception seizure freedom are additional predictors for an increased likelihood of seizure worsening.

Radiomics for the Prediction of Epilepsy in Patients With Frontal Glioma.

ObjectiveThis study was conducted in order to investigate the association between radiomics features and frontal glioma-associated epilepsy (GAE) and propose a reliable radiomics-based model to predict frontal GAE.MethodsThis retrospective study consecutively enrolled 166 adult patients with frontal glioma (111 in the training cohort and 55 in the testing cohort). A total 1,130 features were extracted from T2 fluid-attenuated inversion recovery images, including first-order statistics, 3D shape, texture, and wavelet features. Regions of interest, including the entire tumor and peritumoral edema, were drawn manually. Pearson correlation coefficient, 10-fold cross-validation, area under curve (AUC) analysis, and support vector machine were adopted to select the most relevant features to build a clinical model, a radiomics model, and a clinical–radiomics model for GAE. The receiver operating characteristic curve (ROC) and AUC were used to evaluate the classification performance of the models in each cohort, and DeLong’s test was used to compare the performance of the models. A two-sided t-test and Fisher’s exact test were used to compare the clinical variables. Statistical analysis was performed using SPSS software (version 22.0; IBM, Armonk, New York), and p <0.05 was set as the threshold for significance.ResultsThe classification accuracy of seven scout models, except the wavelet first-order model (0.793) and the wavelet texture model (0.784), was <0.75 in cross-validation. The clinical–radiomics model, including 17 magnetic resonance imaging-based features selected among the 1,130 radiomics features and two clinical features (patient age and tumor grade), achieved better discriminative performance for GAE prediction in both the training [AUC = 0.886, 95% confidence interval (CI) = 0.819–0.940] and testing cohorts (AUC = 0.836, 95% CI = 0.707–0.937) than the radiomics model (p = 0.008) with 82.0% and 78.2% accuracy, respectively.ConclusionRadiomics analysis can non-invasively predict GAE, thus allowing adequate treatment of frontal glioma. The clinical–radiomics model may enable a more precise prediction of frontal GAE. Furthermore, age and pathology grade are important risk factors for GAE.

Functional Connectivity as a Potential Mechanism for Language Plasticity.

Task fMRI is a clinical tool for language lateralization, but has limitations, and cannot provide information about network-level plasticity. Additional methods are needed to improve the precision of presurgical language mapping. We investigate language resting-state functional connectivity (RS fMRI; FC) in typically developing children (TD) and children with epilepsy. Our objectives were to (1) understand how FC components differ between TD children and those with epilepsy; (2) elucidate how the location of disease (frontal/temporal epilepsy foci) affects FC; and (3) investigate the relationship between age and FC. Our sample included 55 TD children (mean age 12 years, range 7-18) and 31 patients with focal epilepsy (mean age 13 years, range 7-18). All participants underwent RS fMRI. Using a bilateral canonical language map as target, vertex-wise intrahemispheric FC map and interhemispheric FC map for each participant were computed and thresholded at top 10% to compute an FC laterality index (FCLI; [(L - R)/(L + R)]) of the frontal and temporal regions for both integration (intrahemispheric FC; FCLIi) and segregation (interhemispheric FC; FCLIs) maps. We found FC differences in the developing language network based on disease, seizure foci location, and age. Frontal and temporal FCLIi was different between groups (t[84] = 2.82, p < 0.01; t[84] = 4.68, p < 0.01, respectively). Frontal epilepsy foci had the largest differences from TD (Cohen d frontal FCLIi = 0.84, FCLIs = 0.51; temporal FCLIi = 1.29). Development and disease have opposing influences on the laterality of FC based on groups. In the frontal foci group, FCLIi decreased with age (r = -0.42), whereas in the temporal foci group, FCLIi increased with age (r = 0.40). Within the epilepsy group, increases in right frontal integration FCLI relates to increased right frontal task activation in our mostly left language dominant group (r = 0.52, p < 0.01). Language network connectivity is associated with higher verbal intelligence in children with epilepsy (r = 0.45, p < 0.05). These findings lend preliminary evidence that FC reflects network plasticity in the form of adaptation and compensation, or the ability to recruit support and reallocate resources within and outside of the traditional network to compensate for disease. FC expands on task-based fMRI and provides complementary and potentially useful information about the language network that is not captured using task-based fMRI alone.

Phase-Amplitude Coupling and Epileptogenic Zone Localization of Frontal Epilepsy Based on Intracranial EEG.

Objective: This study aimed to explore the characteristics of phase-amplitude coupling in patients with frontal epilepsy based on their electrocorticography data, in order to identify the localization of epileptic regions and further guide clinical resection surgery.Methods: We adopted the modulation index based on the Kullback-Leibler distance, phase-amplitude coupling co-modulogram, and time-varying phase-amplitude modulogram to explore the temporal-spatial patterns and characterization of PAC strength during the period from inter- seizure to post-seizure. Taking the resected area as the gold standard, the epileptogenic zone was located based on MI values of 7 different seizure periods, and the accuracy of localization was measured by the area under the receiver operating curve.Results: (1) The PAC in the inter- and pre-seizure periods was weak and paroxysmal, but strong PAC channels were confined more to the seizure-onset zone and resection region. PAC during the seizure period was intense and persistent, but gradually deviated from the seizure-onset zone. (2) The characteristics of coupling strength of the inter- and pre-seizure EEG can be used to accurately locate the epileptogenic zone, which is better than that in periods after the beginning of a seizure. (3) In an epileptic seizure, the preferred phases of coupling were usually in the rising branches at the pre- and early-seizure stages, while those in the middle- and terminal-seizure were usually in the falling branch. We thus speculate that the coupling occurred in the rising branch can promote the recruitment of abnormal discharge, while the coupling occurred in the falling branch can inhibit the abnormal discharge.Conclusion: The findings suggest that the phase-amplitude coupling during inter- and pre-seizure is a promising marker of epileptic focus location. The preferred phase of coupling changed regularly with the time of epileptic seizure, suggesting that the surge and suppression of abnormal discharges are related to different phases.

Peripheric smell regions in patients with temporal and frontal lobe epilepsies: An MRI evaluation

ObjectivesWe investigated peripheric smell regions of olfactory bulb (OB) volume and olfactory sulcus (OS) depth in temporal and frontal lobe epilepsy patients by cranial magnetic resonance imaging (MRI). MethodsIn this retrospective study, cranial MRI images of 150 adult patients were included. Group 1 was consisted of 50 adult patients with temporal lobe epilepsy (TLE). Group 2 was consisted of 50 adult patients with frontal lobe epilepsy (FLE). The control group (Group 3) was consisted of 50 healthy subjects without epilepsy. OB volume and OS depth were measured in all groups. ResultsOB volumes of the temporal and frontal epilepsy groups were significantly lower than those of the control group (padjusted < 0.0175). However, OS depths were not different between groups 1–3 (p > 0.05). In the temporal and frontal epilepsy groups, there were positive correlations between OB volumes; OS depths; left OB volume and bilateral OS depths p < 0.05). There were no significant correlations between OB volume and OS depth; and age and gender of the epilepsy group (p > 0.05). ConclusionWe concluded that temporal and frontal epilepsy maybe related to decrease in OB volume and may cause olfactory impairment. Olfactory deficit maybe related to central epileptic focus. Therefore, early diagnosis and appropriate treatment of epilepsy are important to prevent olfactory impairment.

Повторювана та стереотипна поведінка при розладах аутистичного спектра та лобних епілепсіях: обговорення клінічного випадку.

Background: Autism spectrum disorders (ASD) have a prevalence of 1-2% among the world's child population and belong to the spectrum of neurodevelopmental disorders. ASD are characterized by significant genetic and clinical polymorphism, in particular comorbidity with neurological and mental disorders. In 15 - 30% of children with ASD, epilepsy is diagnosed throughout life. Repeated movements and vocalizations in ASD are often similar and require differential diagnosis with motor and vocal phenomena in the structure of epileptic seizures, with motor and vocal tics, in particular with Tourette's disorder, obsessions and compulsions in obsessive-compulsive disorder. The polymorbidity of ASD complicates the typology of recurring motor and vocal phenomena. Polymorphism of repetitive movements and vocalizations is also inherent in developmental encephalopathy. Objective : to investigate clinical polymorphism, variants of motor phenomena during 6 years of life in a child with dual diagnosis of ASD and frontal epilepsy. Materials and methods: A child with ASD and frontal focal epilepsy was observed for 6 years on the basis of the Department of Mental Disorders of Children and Adolescents of the Scientific Research Institute of Psychiatry of the Ministry of Health of Ukraine. The child underwent a comprehensive psychiatric and neurological examination every three months. For the diagnosis and assessment of the course of mental disorders, DAWBA and K-SADS-PL were used. To assess autistic symptoms, ADOS and ADI-R were used, and tics symptoms were YGTSS, and obsessive-compulsive disorders in children with ASD were CYBOCS ASD. The cognitive functioning of the child was assessed using PEP-R and the test WISC, the socially adaptive behavior of Vineland and SRS. Every six months and during unscheduled visits, an EEG study was conducted with a mathematical analysis of the results. Results: Child autism in a child was diagnosed in accordance with the ICD-10 diagnostic criteria, according to the results of a semi-structured interview with parents - ADI-R and assessment of current behavior by ADOS. During the period of controlled observation, epileptic paroxysms were characterized by the absence of complete loss of consciousness, polymorphism of seizures with numerous motor and vocal phenomena, which differentiated with symptoms of ASD, tics, obsessive-compulsive disorders. Stereotypic movements in the form of automatically repeated actions were observed in the proximal extremities, looked like a continuation and repetition of previous performed and daily performed automatic actions. The episodes of involuntary grimaces with distorted facial muscles during the first two years of observation looked like a violent act of activity, and not like epileptic paroxysms. EEG results also did not confirm the diagnosis of epilepsy. Dynamic, longitudinal monitoring of the clinical pathomorphism of repeated motor and vocal phenomena, analysis of therapeutic responses to treatment at different time periods: aripiprazole, guanfacin, sertraline, lamotrigine, analysis of symptoms that are qualified as comorbid, a gradual increase in focal epileptiform changes in the EEG allowed to diagnose frontal epilepsy with autism spectrum disorder. Conclusions: Most children with ASD have vocal and motor phenomena that may resemble symptoms of comorbid mental disorders. Repeated movements and vocalizations in ASD, as manifestations of tics, obsessive-compulsive disorders, are difficult to differentiate; they can be superimposed in the case of comorbidity disorders. With the appearance of specific epileptic activity and epileptic seizures in such patients, it is necessary to conduct differential diagnosis with developmental encephalopathy. The frontal form of epilepsy can be accompanied by seizures without complete loss of consciousness with characteristic automatic repeated stereotypic movements that have significant variability throughout life. The given clinical case supports the point of view that ASD and epilepsy are manifestations of a single pathological process - impaired neurodevelopment.

Acute effects of spaced cathodal transcranial direct current stimulation in drug resistant focal epilepsies

ObjectiveTo evaluate the safety and temporal dynamic of the antiepileptic effect of spaced transcranial direct current stimulation (tDCS) in different focal epilepsies. MethodsCathodal tDCS with individual electrode placement was performed in 15 adults with drug resistant focal epilepsy. An amplitude of 2 mA was applied twice for 9 minutes, with an interstimulation interval of 20 minutes. Tolerability was assessed via the Comfort Rating Questionnaire and the frequency of interictal epileptiform discharges (IEDs) was sequentially compared between the 24 hours before and after tDCS. ResultsTDCS led to a significant reduction in the total number of IEDs/24 h by up to 68% (mean ± SD: −30.4 ± 21.1%, p = 0.001) as well as in seizure frequency (p = 0.041). The maximum IED reduction was observed between the 3rd and 21st hour after stimulation. Favorable clinical response was associated with structural etiology and clearly circumscribed epileptogenic foci but did not differ between frontal and temporal epilepsies. Overall, the tDCS treatment was well tolerated and did not lead to severe adverse events. ConclusionsThe spaced stimulation approach proved to be safe and well-tolerated in patients with drug-resistant unifocal epilepsies, leading to sustained IED and seizure frequency reduction. SignificanceSpaced tDCS induces mediate antiepileptic effects with promising therapeutic potential.