Optimizing Surgical Planning for Epilepsy Patients With Multimodal Neuroimaging and Neurophysiology Integration: A Case Study.

SUMMARY: Current preoperative evaluation of epilepsy can be challenging because of the lack of a comprehensive view of the network's dysfunctions. To demonstrate the utility of our multimodal neurophysiology and neuroimaging integration approach in the presurgical evaluation, we present a proof-of-concept for using this approach in a patient with nonlesional frontal lobe epilepsy who underwent two resective surgeries to achieve seizure control. We conducted a post-hoc investigation using four neuroimaging and neurophysiology modalities: diffusion tensor imaging, resting-state functional MRI, and stereoelectroencephalography at rest and during seizures. We computed region-of-interest-based connectivity for each modality and applied betweenness centrality to identify key network hubs across modalities. Our results revealed that despite seizure semiology and stereoelectroencephalography indicating dysfunction in the right orbitofrontal region, the maximum overlap on the hubs across modalities extended to right temporal areas. Notably, the right middle temporal lobe region served as an overlap hub across diffusion tensor imaging, resting-state functional MRI, and rest stereoelectroencephalography networks and was only included in the resected area in the second surgery, which led to long-term seizure control of this patient. Our findings demonstrated that transmodal hubs could help identify key areas related to epileptogenic network. Therefore, this case presents a promising perspective of using a multimodal approach to improve the presurgical evaluation of patients with epilepsy.

MRI evidence for material-specific encoding deficits and mesial-temporal alterations in presurgical frontal lobe epilepsy patients.

OBJECTIVE: Neuroimaging studies reveal frontal lobe (FL) contributions to memory encoding. Accordingly, memory impairments are documented in frontal lobe epilepsy (FLE). Still, little is known about the structural or functional correlates of such impairments. Particularly, material specificity of functional changes in cerebral activity during memory encoding in FLE is unclear. METHODS: We compared 24 FLE patients (15 right-sided) undergoing presurgical evaluation with 30 healthy controls on a memory fMRI-paradigm of learning scenes, faces, and words followed by an out-of-scanner recognition task as well as regarding their mesial temporal lobe (mTL) volumes. We also addressed effects of FLE lateralization and performance level (normal vs. low). RESULTS: FLE patients had poorer memory performance and larger left hippocampal volumes than controls. Volume increase seemed, however, irrelevant or even dysfunctional for memory performance. Further, functional changes in FLE patients were right-sided for scenes and faces and bilateral for words. In detail, during face encoding, FLE patients had, regardless of their performance level, decreased mTL activation, while during scene and word encoding only low performing FLE patients had decreased mTL along with decreased FL activation. Intact verbal memory performance was associated with higher right frontal activation in FLE patients but not in controls. SIGNIFICANCE: Pharmacoresistant FLE has a distinct functional and structural impact on the mTL. Effects vary with the encoded material and patients' performance levels. Thus, in addition to the direct effect of the FL, memory impairment in FLE is presumably to a large part due to functional mTL changes triggered by disrupted FL networks. PLAIN LANGUAGE SUMMARY: Frontal lobe epilepsy (FLE) patients may suffer from memory impairment. Therefore, we asked patients to perform a memory task while their brain was scanned by MRI in order to investigate possible changes in brain activation during learning. FLE patients showed changes in brain activation during learning and also structural changes in the mesial temporal lobe, which is a brain region especially relevant for learning but not the origin of the seizures in FLE. We conclude that FLE leads to widespread changes that contribute to FLE patients' memory impairment.

White matter alterations in MR-negative temporal and frontal lobe epilepsy using fixel-based analysis.

This study focuses on white matter alterations in pharmacoresistant epilepsy patients with no visible lesions in the temporal and frontal lobes on clinical MRI (i.e. MR-negative) with lesions confirmed by resective surgery. The aim of the study was to extend the knowledge about group-specific neuropathology in MR-negative epilepsy. We used the fixel-based analysis (FBA) that overcomes the limitations of traditional diffusion tensor image analysis, mainly within-voxel averaging of multiple crossing fibres. Group-wise comparisons of fixel parameters between healthy controls (N = 100) and: (1) frontal lobe epilepsy (FLE) patients (N = 9); (2) temporal lobe epilepsy (TLE) patients (N = 13) were performed. A significant decrease of the cross-section area of the fixels in the superior longitudinal fasciculus was observed in the FLE. Results in TLE reflected widespread atrophy of limbic, thalamic, and cortico-striatal connections and tracts directly connected to the temporal lobe (such as the anterior commissure, inferior fronto-occipital fasciculus, uncinate fasciculus, splenium of corpus callosum, and cingulum bundle). Alterations were also observed in extratemporal connections (brainstem connection, commissural fibres, and parts of the superior longitudinal fasciculus). To our knowledge, this is the first study to use an advanced FBA method not only on the datasets of MR-negative TLE patients, but also MR-negative FLE patients, uncovering new common tract-specific alterations on the group level.

Patterns of hypometabolism in frontal lobe epilepsy originating in different frontal regions.

OBJECTIVES: Analysis of FDG-PET imaging commonly shows that hypometabolism extends into extra-epileptogenic zones (extra-EZ). This study investigates the distribution patterns of hypometabolism in frontal lobe epilepsy (FLE) originating in different frontal regions. METHODS: Sixty-four patients with FLE were grouped by EZ localization according to Brodmann areas (BAs): Group 1 (the frontal motor and premotor area), BAs 4, 6, and 8; Group 2 (the inferior frontal gyrus and opercular area), BAs 44, 45, and 47; Group 3 (the dorsal prefrontal area), BAs 9, 10, 11, and 46; and Group 4 (the medial frontal and anterior cingulate gyrus), BAs 32 and 24. Regions of extra-EZ hypometabolism were statistically analyzed between FLE groups and healthy controls. Correlation analysis was performed to identify relationships between the intensity of hypometabolism and clinical characteristics. RESULTS: Significant hypometabolism in the ipsilateral (Groups 1 and 4) or bilateral (Groups 2 and 3) anterior insulae was found. Groups 1 and 4 presented with limited distribution of extra-EZ hypometabolism, whereas Groups 2 and 3 showed widely distributed extra-EZ hypometabolism in the rectus gyrus, cingulate gyrus, and other regions. Additionally, the intensity of hypometabolism was correlated with epilepsy duration in Groups 2 and 3. CONCLUSIONS: All FLE groups showed hypometabolism in the anterior insula. In addition, distinct patterns of extra-EZ hypometabolism were identified for each FLE group. This quantitative FDG-PET analysis expanded our understanding of the topography of epileptic networks and can guide EZ localization in the future.

Brain structural differences in temporal lobe and frontal lobe epilepsy patients: A voxel-based morphometry and vertex-based surface analysis.

PURPOSE: Exploration of the effect of chronic recurrent seizures in focal epilepsy on brain volumes has produced many conflicting reports. To determine differences in brain structure in temporal lobe epilepsy (TLE) and extratemporal epilepsy (using frontal lobe epilepsy (FLE) a surrogate) further, we performed a retrospective analysis of a large cohort of patients with seizure-onset zone proven by intracranial monitoring. METHODS: A total of 120 TLE patients, 86 FLE patients, and 54 healthy controls were enrolled in this study. An analysis of variance of voxel-based morphometry (VBM) was used to seek morphometric brain differences among TLE patients, FLE patients, and healthy controls. Additionally, a vertex-based surface analysis was utilized to analyze the hippocampus and thalamus. Significant side-specific differences in hippocampal gray matter volume were present between the left TLE (LTLE), right TLE RTLE (RTLE), and control groups (p<0.05, family-wise error (FWE) corrected). RESULTS: Vertex analyses revealed significant volume reduction in inferior parts of the left hippocampus in the LTLE group and lateral parts of the right hippocampus in the RTLE group compared to controls (p<0.05, FWE corrected). Significant differences were also detected between the LTLE and control group in the bilateral medial and inferior thalamus (p<0.05, FWE corrected). FLE patients did not exhibit focal atrophy of gray matter across the brain. CONCLUSION: Our results highlight the variation in morphometric lateralized changes in the brain between different epilepsy onset zones, providing critical insight into the natural history of people with drug-resistant focal epilepsies.

Ictal semiology of epileptic seizures with insulo-opercular genesis.

OBJECTIVE: Epileptic seizures with insular genesis are often difficult to distinguish from those originating in the temporal lobe due to their complex and variable semiology. Here, we analyzed differentiating characteristics in the clinical spectrum of insulo-opercular seizures. METHODS: Ictal semiology in patients with a diagnosis of insulo-opercular epilepsy (IOE) based on imaging of epileptogenic lesions or electrophysiological evidence of an insulo-opercular seizure origin was retrospectively analyzed and compared to age-matched controls with mesial temporal lobe epilepsy (MTE). RESULTS: Forty-six IOE and 46 matched MTE patients were included. The most prominent ictal features in IOE were focal motor phenomena in 80.4% of these patients. Somatosensory sensations, version, tonic and clonic features, when present, were more frequent contralateral to the SOZ in MTE patients, while they occurred about equally often ipsilateral and contralateral to the SOZ in IOE patients. Ipsilateral manual automatisms were significantly more frequent in MTE patients than in IOE (p = 0.010). Multivariate analysis correctly identified IOE in 78.3% and MTE in 84.8% using five semiologic features (Chi-square = 53.79 with 5 degrees of freedom, p < 0.0001). A subanalysis comparing patients with purely insular lesions with MTE patients using only the earliest ictal signs showed that somatosensory sensations are significantly more frequent in insular epilepsy (p = 0.010), while automatisms were significantly more frequent in MTE patients (p = 0.06). SIGNIFICANCE: Our study represents the first in-depth analysis of ictal semiology in IOE compared to MTE. Use of these differentiating characteristics can serve for a correct syndrome classification and to steer appropriate diagnostic and local therapeutic procedures.

Magnetic resonance imaging findings and clinical characteristics in mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy in a predominantly adult cohort.

OBJECTIVE: We aimed to better characterize the magnetic resonance imaging (MRI) findings of mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE), a rare clinicopathological entity associated with pharmacoresistance recently described in patients with frontal lobe epilepsy. METHODS: We studied 12 patients who underwent epilepsy surgery and whose surgical specimens showed histopathological findings of MOGHE, characterized by preserved cortical lamination, blurred gray-white matter interface due to increased number of oligodendrocytes, and heterotopic neurons in the white matter. The age at MRI evaluation ranged from 11 to 58 years, except for one 4.5-year-old patient. RESULTS: Following a detailed MRI analysis using an in-house protocol, we found abnormalities in all cases. The lesion was circumscribed in the frontal lobe in six (50%) and in the temporal lobe in three (25%) patients. In the remaining three patients (25%), the lesion was multilobar (frontotemporal and temporoparieto-occipital). Cortical thickening was mild in all patients, except in the 4.5-year-old patient, who had pronounced cortical thickening and white matter blurring. We also identified cortical/subcortical hyperintense T2/fluid-attenuated inversion recovery signal associated with gray/white matter blurring in all but one patient. When present, cleft cortical dimple, and deep sulci aided in localizing the lesion. Overall, the MRI findings were like those in focal cortical dysplasia (FCD) Type IIa. Surgical outcome was excellent in five patients (Engel Class I in 25% and II in 17%). The remaining seven patients (58%) had worthwhile seizure reduction (Engle Class III). Incomplete lesion resection was significantly associated with worse outcomes. SIGNIFICANCE: MRI findings associated with MOGHE are similar to those described in FCD Type IIa. Although more frequent in the frontal lobe, MOGHE also occurred in the temporal lobe or involved multiple lobes. Multilobar or extensive MOGHE MRI lesions are associated with less favorable surgical outcomes. Because this is a rare condition, multicenter studies are necessary to characterize MOGHE further.

Automated analysis of cortical volume loss predicts seizure outcomes after frontal lobectomy.

OBJECTIVE: Patients undergoing frontal lobectomy demonstrate lower seizure-freedom rates than patients undergoing temporal lobectomy and several other resective interventions. We attempted to utilize automated preoperative quantitative analysis of focal and global cortical volume loss to develop predictive volumetric indicators of seizure outcome after frontal lobectomy. METHODS: Ninety patients who underwent frontal lobectomy were stratified based on seizure freedom at a mean follow-up time of 3.5 (standard deviation [SD] 2.5) years. Automated quantitative analysis of cortical volume loss organized by distinct brain region and laterality was performed on preoperative T1-weighted magnetic resonance imaging (MRI) studies. Univariate statistical analysis was used to select potential predictors of seizure freedom. Backward variable selection and multivariate logistical regression were used to develop models to predict seizure freedom. RESULTS: Forty-eight of 90 (53.3%) patients were seizure-free at the last follow-up. Several frontal and extrafrontal brain regions demonstrated statistically significant differences in both volumetric cortical volume loss and volumetric asymmetry between the left and right sides in the seizure-free and non-seizure-free cohorts. A final multivariate logistic model utilizing only preoperative quantitative MRI data to predict seizure outcome was developed with a c-statistic of 0.846. Using both preoperative quantitative MRI data and previously validated clinical predictors of seizure outcomes, we developed a model with a c-statistic of 0.897. SIGNIFICANCE: This study demonstrates that preoperative cortical volume loss in both frontal and extrafrontal regions can be predictive of seizure outcome after frontal lobectomy, and models can be developed with excellent predictive capabilities using preoperative MRI data. Automated quantitative MRI analysis can be quickly and reliably performed in patients with frontal lobe epilepsy, and further studies may be developed for integration into preoperative risk stratification.

Different faces of frontal lobe epilepsy: The clinical, electrophysiologic, and imaging experience of a tertiary center.

OBJECTIVE: Frontal lobe epilepsy (FLE) is the second most common epilepsy among drug-resistant focal epilepsies. Semiologic and electrophysiologic features of FLE present some difficulties because frontal lobe seizures are brief, accompanied by complex motor activities and emotional signs. The rich connectivity of the frontal lobe with other areas leads to the rapid and widespread propagation of seizure activity, which contribute to the difficulty of evaluating the semiologic and EEG patterns of the seizure. In this study, we investigated semiologic, interictal, ictal, and postictal EEG characteristics; the imaging data of patients with FLE and the possible contribution of these data to localization and lateralization of seizures. MATERIALS AND METHODS: The medical records of patients who were diagnosed as having FLE between 2010 and 2019 in our clinic were evaluated retrospectively. The diagnosis of FLE was considered either when patients had a structural lesion in the frontal region or seizure semiology and EEG characteristics were compatible with FLE. Clinical, electrophysiologic, and imaging features were investigated in these patients. RESULTS: We have evaluated 146 seizures in 36 patients (17 lesional and 19 non-lesional according to MRI). There were 110 focal motor or nonmotor seizures, 18 bilateral tonic-clonic seizures, and 18 subclinical seizures. There were 16 patients with aura. The most common semiologic feature was hyperkinetic movements. Among the interictal EEGs, 30.5 % included focal anomalies. Among the ictal EEGs, 69.1 % were non-localizing or lateralizing. The most common ictal pattern was rhythmic theta activity (21.2 %). In four patients, who had non-localizing or lateralizing EEG, the postictal EEG was informative. Our study showed a low percentage of localized FDG-PET, which, however, involved visual analysis. CONCLUSION: Our results support the previously known difficulties in the determination of the epileptogenic zone of FLE. Semiologic and electrophysiologic correlation studies, longer postictal records, and quantitative analysis of FDG-PET may contribute to a better characterization of the disease.

Hyperkinetic Seizures with Ictal Fear as Localizing Ictal Signs in MRI-Negative Medial Frontal Lobe Epilepsy.

PURPOSE: Hyperkinetic seizures are described as seizure onset in the frontal or temporal lobe. Additional localizing information is important for diagnostic workup and surgical therapy. We describe diagnostic workup and surgical outcomes in three patients with pharmacoresistant focal emotional seizures with hyperkinetic elements. METHODS/RESULTS: High-resolution 3 Tesla (T) magnetic resonance imaging (MRI) did not reveal clear-cut lesions. Invasive video-electroencephalography (EEG) with depth electrodes along the cingulate sulcus (bilateral; patients 1 and 3), right; patient 2 provided congruent results for a circumscribed seizure onset zone within the medial frontal lobe (right: patients 1 and 2; left: patient 3). Topectomies were performed in all patients. Histopathology revealed a small focal cortical dysplasia in the three cases (focal cortical dysplasia [FCD] IIA: patient 1; FCD IIB: patients 2 and 3). All patients remained completely seizure-free since surgery (Engel 1A; follow-up: 9-28 months). CONCLUSION: Ictal fear associated with hyperkinetic semiology points to a seizure-onset zone within the anteromedial frontal lobe (anterior cingulate gyrus). Ictal semiology is crucial for the placement of depth electrodes, especially in MRI-negative cases. These cases illustrate a clinical advantage to the new International League against Epilepsy (ILAE) seizure classification, emphasizing initial clinical symptoms.

Temporal variability profiling of the default mode across epilepsy subtypes.

OBJECTIVE: Epilepsies are a group of neurological disorders sharing certain core features, but also demonstrate remarkable pathogenic and symptomatic heterogeneities. Various subtypes of epilepsy have been identified with abnormal shift in the brain default mode network (DMN). This study aims to evaluate the fine details of shared and distinct alterations in the DMN among epileptic subtypes. METHODS: We collected resting-state functional magnetic resonance imaging (MRI) data from a large epilepsy sample (n = 371) at a single center, including temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE), and genetic generalized epilepsy with generalized tonic-clonic seizures (GGE-GTCS), as well as healthy controls (HC, n = 150). We analyzed temporal dynamics profiling of the DMN, including edge-wise and node-wise temporal variabilities, and recurrent dynamic states of functional connectivity, to identify abnormalities common to epilepsies as well as those specific to each subtype. RESULTS: The analyses revealed that hypervariable edges within the specific DMN subsystem were shared by all subtypes (all PNBS  < .005), and deficits in node-wise temporal variability were prominent in TLE (all t(243) ≤ 2.51, PFDR  < .05) and FLE (all t(302) ≤ -2.65, PFDR  < .05) but relatively weak in GGE-GTCS. Moreover, dynamic states were generally less stable in patients than controls (all P's < .001). SIGNIFICANCE: Collectively, these findings demonstrated general DMN abnormalities common to different epilepsies as well as distinct dysfunctions to subtypes, and provided insights into understanding the relationship of pathophysiological mechanisms and brain connectivity.

Prefrontal seizure classification based on stereo-EEG quantification and automatic clustering.

PURPOSE: Frontal seizures are organized according to anatomo-functional subdivisions of the frontal lobe. Prefrontal seizures have been the subject of few detailed studies to date. The objective of this study was to identify subcategories of prefrontal seizures based on seizure onset quantification and to look for semiological differences. METHODS: Consecutive patients who underwent stereoelectroencephalography (SEEG) for drug-resistant prefrontal epilepsy between 2000 and 2018 were included. The different prefrontal regions investigated in our patients were dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), dorsomedial prefrontal cortex (DMPFC), ventromedial prefrontal cortex (VMPFC), and orbitofrontal cortex (OFC). The seizure onset zone (SOZ) was determined from one or two seizures in each patient, using the epileptogenicity index (EI) method. The presence or absence of 16 clinical ictal manifestations was analyzed. Classification of prefrontal networks was performed using the k-means automatic classification method. RESULTS: A total of 51 seizures from 31 patients were analyzed. The optimal clustering was 4 subgroups of prefrontal seizures: a "pure DLPF" group, a "pure VMPF" group, a "pure OFC" group, and a "global prefrontal" group. The first 3 groups showed a mean EI considered epileptogenic (>0.4) only in one predominant structure, while the fourth group showed a high mean EI in almost all prefrontal structures. The median number of epileptogenic structures per seizure (prefrontal or extrafrontal) was 5 for the "global prefrontal" group and 2 for the other groups. We found that the most common signs were altered consciousness, automatisms/stereotypies, integrated gestural motor behavior, and hyperkinetic motor behavior. We found no significant difference in the distribution of ictal signs between the different groups. CONCLUSION: Our study showed that although most prefrontal seizures manifest as a network of several anatomically distinct structures, we were able to determine a sublobar organization of prefrontal seizure onset with four groups.

Cirugía de zona epileptogénica localizada en un área elocuente dellóbulo frontal en un adolescente con epilepsia / Epileptogenic zone surgery located in an eloquent area of the frontal lobe in an adolescent with epilepsy

Objetivo: Describir los resultados de la evaluación prequirúrgica, transquirúrgica y postquirúrgica, en un adolescente con epilepsia farmacorresistente con zona epileptogénica estimada en un área elocuente del lóbulo frontal izquierdo.Caso clínico: Paciente masculino, de 18 años, con epilepsia frontal izquierdafarmacorresistente desde los tres años, con una frecuencia de crisis de desconexión, atónicas y, en ocasiones, tónico clónico bilateral entre 30 y 40 diarias, previo a la cirugía. Laevaluación prequirúrgica identificó la zona de inicio ictal frontal izquierda, no lesional por imagen de resonancia magnética de 3 tesla. Se indicó tomografía computarizada por emisiónde fotón único interictal / ictal corregistrada con resonancia magnética, donde se identificó hiperperfusión frontal izquierda. Se realizó la cirugía con el uso de potenciales evocadossomatosensoriales para identificar el surco central, la estimulación cortical directa para mapear el área motora primaria, y la electrocorticografía transoperatoria para delimitar la zona de resección. Se empleó la técnica combinada desconectiva (callosotomía anterior) y resectiva del giro frontal superior y medio izquierdos, con modificación del patrón eléctrico en la electrocorticografía posterior a la cirugía. El resultado anatomopatológico fue displasia cortical focal tipo IA. En el seguimiento postquirúrgico, el paciente presenta solo entre 2-3 crisis semanales.Conclusiones: La cirugía de epilepsia extratemporal no lesional y con zona epileptogénica que incluye áreas elocuentes del lóbulo frontal es factible de realizar en nuestro país con mínima invasividad y buenos resultados(AU)

Objective: To describe the results of pre-surgical, trans-surgical and post-surgical assessment of an adolescent with drug-resistant epilepsy and an estimated epileptogenic zone in an eloquent area of the left frontal lobe.Clinical case: Male patient, 18 years old, who had drug-resistant left frontal epilepsy since the age of three. Before surgery, the patient suffered 30 and 40 daily disconnection episodes, atonic and, occasionally, daily bilateral clonic tonic. The pre-surgical evaluation identifiedthe left frontal, non-lesional ictal onset zone using 3-tesla magnetic resonance imaging. An interictal / ictal single photon emission computed tomography corrected with magnetic resonance imaging was indicated, which identified left frontal hyperperfusion. Surgery wasperformed using somatosensory-evoked potentials to identify the central sulcus, direct cortical stimulation to map the primary motor area, and intraoperative electrocorticography to delimit the resection area. Combined disconnective technique (anterior callosotomy) andresective technique of the left superior and middle left gyrus was used, modifying the electrical pattern in the electrocorticography after surgery. The pathological result was type IA focal cortical dysplasia. In the post-surgical follow-up, the patient only has 2-3 weekly crises.Conclusions: Surgery is feasible in a non-lesional extra-temporal epilepsy with an epileptogenic zone that includes eloquent frontal lobe areas in our country with minimal invasiveness and good results(AU)

Neuroimaging of memory in frontal lobe epilepsy.

In a large percentage of epilepsies, seizures have focal onset. These epilepsies are associated with a wide range of behavioral and cognitive deficits sometimes limited to the functions encompassed within the ictal onset zone but, more frequently, expanding beyond it. The presence of impairments associated with neuroanatomical areas outside of the ictal onset zone suggests distal propagation of epileptic activity via brain networks and interconnected whole-brain neural circuitry. In patients with frontal lobe epilepsy (FLE), using functional magnetic resonance imaging (fMRI) to identify deficits in working, semantic, and episodic memory may provide a lens through which to understand typical and atypical network organization. A network approach to focal epilepsy is relevant in these patients because of the frequently noted early age of seizure onset. Early seizure-related disruption in healthy brain development may result in a significant brain reorganization, development of compensation-related mechanisms of dealing with function abnormalities and disruptions, and the propagation of epileptic activity from the focus to widespread brain areas (functional deficit zones). Benefits of a network approach in the study of focal epilepsy are discussed along with considerations for future neuroimaging studies of patients with FLE.

Evaluation of cortical thickness and brain volume on 3 Tesla magnetic resonance imaging in children with frontal lobe epilepsy.

BACKGROUND: Frontal lobe epilepsy (FLE) is the most common epilepsy syndrome in the pediatric population; however, brain magnetic resonance imaging (MRI) of the children with FLE is frequently normal. We use both cortical thickness and brain volume measurements to report on cortical changes in children with FLE. Our aim was to determine cortical thickness and brain volume changes on 3 Tesla MRI of children with FLE and normal brain magnetic resonance imaging. METHODS: Twenty-seven children with FLE and 27 healthy controls received brain magnetic resonance imaging. Cortical thickness and regional brain volumes were assessed using three-dimensional volumetric T1-weighted imaging and patients were compared with controls. RESULTS: In children with FLE, statistically significant (p < 0.05) cortical thinning were found in the bilateral middle frontal gyrus, bilateral occipitotemporal and medial lingual gyrus, left subcallosal gyrus, left short insular gyrus, and right long insular gyrus. Statistically significant volume reductions in right and left hemisphere cortical white matter, total cortical white matter, bilateral thalamus, bilateral putamen, bilateral globus pallidus, right caudate nucleus, brain stem, and right cerebellar cortex were found. CONCLUSION: Cortical thinning in frontal and extra-frontal lobes and volume loss in a variety of brain regions were found in children with FLE.

Surgical Technique and Outcome of Extensive Frontal Lobectomy for Treatment of Intracable Non-lesional Frontal Lobe Epilepsy.

Although extensive frontal lobectomy (eFL) is a common surgical procedure for intractable frontal lobe epilepsy (FLE), there have been very few reports regarding surgical techniques for eFL. This article provides step-by-step descriptions of our surgical technique for non-lesional FLE. Sixteen patients undergoing eFL were included in this study. The goals were to maximize gray matter removal, including the orbital gyrus and subcallosal area, and to spare the primary motor and premotor cortexes and anterior perforated substance. The eFL consists of three steps: (1) positioning, craniotomy, and exposure; (2) lateral frontal lobe resection; and (3), resection of the rectus gyrus and orbital gyrus. Resection ahead of bregma allows preservation of motor and premotor area function. To remove the orbital gyrus preserving anterior perforated substance, it is essential to visualize the olfactory trigone beneath the pia. It is important to observe the surface of the contralateral medial frontal lobe for complete removal of the subcallosal area of the frontal lobe. Thirteen patients (81.25%) became seizure-free and three patients (18.75%) continued to have seizures. None of the patients showed any complications. The eFL is a good surgical technique for the treatment of intractable non-lesional FLE. For treatment of epilepsy by eFL, it is important to resect the non-eloquent area of the frontal lobe as much as possible with preservation of the eloquent cortex.

Electroclinical features of insulo-opercular epilepsy: an SEEG and PET study.

OBJECTIVE: To report clinical experience with presurgical evaluation in patients with insulo-opercular epilepsy. Quantitative analysis on PET imaging and stereoelectroencephalography (SEEG) signals was used to summarize their electroclinical features. METHODS: Twenty-two patients with focal epilepsy arising from the insular and/or opercular cortex according to SEEG were retrospectively analyzed. Presurgical noninvasive data were analyzed in detail. Interictal PET data of patients were then statistically compared with those of healthy controls to identify the interictal hypometabolic network. The epileptogenicity index (EI) of ictal SEEG signal was computed to identify areas of spread at the beginning of seizure onset. RESULTS: Focal tonic seizures of the face and/or neck (16/22, 73%) were the most prevalent early objective signs. Epileptic discharges in the interictal and ictal scalp-EEG mostly showed an ipsilateral perisylvian distribution. Statistical analysis of interictal PET showed significant hypometabolism in the insular lobe, central operculum, supplementary motor area, middle cingulate cortex, bilateral caudate nuclei, and putamen. According to the EI analysis, insulo-opercular epilepsy could be classified as insulo-opercular epilepsy (50%), opercular epilepsy (41%), and insular cortex epilepsy (9%). SIGNIFICANCE: Clinical diagnosis of insulo-opercular epilepsy is challenging because of its complex seizure semiology and nonlocalizing discharges on scalp-EEG. A common hypometabolic network involving the insulo-opercular cortex, mesial frontal cortex and subcortical nuclei may be involved in the organization of the insulo-opercular epilepsy network. Furthermore, quantified SEEG analysis suggested that pure insular epilepsy is rare, and the close connection between insular and opercular cortex necessitates SEEG implantation to define the epileptogenic zone.

Seizure outcome and its predictors after frontal lobe epilepsy surgery.

OBJECTIVES: Frontal lobe epilepsy (FLE) surgery is the second most common focal resective surgery for drug-resistant epilepsy. Not many studies are available regarding the long-term surgical outcome of FLE. We studied the longitudinal outcome and predictors of seizure outcome following FLE surgery in a sizeable cohort of patients. MATERIALS & METHODS: A total of 73 consecutive patients who underwent FLE surgery between January 1997 and May 2015 with a minimum follow-up of 1 year (range 1-16 years) were studied. Primary outcome was seizure freedom at last follow-up (Engel Class IA). "Seizure freedom" separately was defined as absence of seizures till last follow-up. Outcome predictors were subjected to multivariate analysis. Using Kaplan-Meier curve, we assessed the post-operative seizure freedom over time. RESULTS: Twenty-five patients (34%) were seizure-free till last follow-up. The seizure freedom was 45%, 34%, 26%, 20% and 14% at the end of 1st, 2nd, 3rd, 4th and 5th post-operative year, respectively. Engel class I outcomes were 48%, 41%, 56%, 57% and 53% at end of 1st, 2nd, 3rd, 4th and 5th post-operative year, respectively. Predictors of seizure recurrence on multivariate analysis were older age at surgery (P = 0.032), longer duration of epilepsy (P = 0.031), presence of interictal epileptiform discharges in post-operative EEG on 7th day (P = 0.005), 3 months (P = 0.005) and 1 year (P = 0.0179). In subgroup analysis, duration of epilepsy of less than 2 years before surgery was a significant predictor for achieving seizure freedom (P = 0.029). CONCLUSIONS: These results emphasize early surgery for better outcome in frontal lobe epilepsy. Post-operative EEG remained a good predictor for long-term outcome.

Effective connectivity analysis of iEEG and accurate localization of the epileptogenic focus at the onset of operculo-insular seizures.

Recognition of insular epilepsy may sometimes be challenging due to the rapid speed at which insular seizures can spread throughout the cortex via extensive connections to surrounding cortices. The spectrum weighted adaptive directed transfer function, a multivariate causality-based effective connectivity measure, was applied to intracranial electroencephalography recordings to identify generators of seizure activity. A non-parametric test based on surrogate data testing was used to validate statistical significance of causal relations. Outflow and inflow of seizure activity were extracted from the computed transfer matrix. Recorded data of 21 seizures from seven patients were analyzed including five who were rendered seizure-free after operculo-insular resection. Effective connectivity analysis of 7 s following electrical onset confirmed an operculo-insular seizure origin in 5 patients with a good post-operative seizure outcome, and for whom the resected region was sampled by intracranial electroencephalography contacts. Different or additional seizure foci were identified in 2 patients with a bad post-operative seizure outcome. Findings highlight the feasibility of accurate operculo-insular seizure foci localization based on quantitative approaches.