Characterizing Frontal Lobe Seizure Semiology in Children.

OBJECTIVE: The objective was to analyze seizure semiology in pediatric frontal lobe epilepsy patients, considering age, to localize the seizure onset zone for surgical resection in focal epilepsy. METHODS: Fifty patients were identified retrospectively, who achieved seizure freedom after frontal lobe resective surgery at Great Ormond Street Hospital. Video-electroencephalography recordings of preoperative ictal seizure semiology were analyzed, stratifying the data based on resection region (mesial or lateral frontal lobe) and age at surgery (≤4 vs >4). RESULTS: Pediatric frontal lobe epilepsy is characterized by frequent, short, complex seizures, similar to adult cohorts. Children with mesial onset had higher occurrence of head deviation (either direction: 55.6% vs 17.4%; p = 0.02) and contralateral head deviation (22.2% vs 0.0%; p = 0.03), ictal body-turning (55.6% vs 13.0%; p = 0.006; ipsilateral: 55.6% vs 4.3%; p = 0.0003), and complex motor signs (88.9% vs 56.5%; p = 0.037). Both age groups (≤4 and >4 years) showed hyperkinetic features (21.1% vs 32.1%), contrary to previous reports. The very young group showed more myoclonic (36.8% vs 3.6%; p = 0.005) and hypomotor features (31.6% vs 0.0%; p = 0.003), and fewer behavioral features (36.8% vs 71.4%; p = 0.03) and reduced responsiveness (31.6% vs 78.6%; p = 0.002). INTERPRETATION: This study presents the most extensive semiological analysis of children with confirmed frontal lobe epilepsy. It identifies semiological features that aid in differentiating between mesial and lateral onset. Despite age-dependent differences, typical frontal lobe features, including hyperkinetic seizures, are observed even in very young children. A better understanding of pediatric seizure semiology may enhance the accuracy of onset identification, and enable earlier presurgical evaluation, improving postsurgical outcomes. ANN NEUROL 2024;95:1138-1148.

Multimodal neurocognitive markers of frontal lobe epilepsy: Insights from ecological text processing.

The pressing call to detect sensitive cognitive markers of frontal lobe epilepsy (FLE) remains poorly addressed. Standard frameworks prove nosologically unspecific (as they reveal deficits that also emerge across other epilepsy subtypes), possess low ecological validity, and are rarely supported by multimodal neuroimaging assessments. To bridge these gaps, we examined naturalistic action and non-action text comprehension, combined with structural and functional connectivity measures, in 19 FLE patients, 19 healthy controls, and 20 posterior cortex epilepsy (PCE) patients. Our analyses integrated inferential statistics and data-driven machine-learning classifiers. FLE patients were selectively and specifically impaired in action comprehension, irrespective of their neuropsychological profile. These deficits selectively and specifically correlated with (a) reduced integrity of the anterior thalamic radiation, a subcortical structure underlying motoric and action-language processing as well as epileptic seizure spread in this subtype; and (b) hypoconnectivity between the primary motor cortex and the left-parietal/supramarginal regions, two putative substrates of action-language comprehension. Moreover, machine-learning classifiers based on the above neurocognitive measures yielded 75% accuracy rates in discriminating individual FLE patients from both controls and PCE patients. Briefly, action-text assessments, combined with structural and functional connectivity measures, seem to capture ecological cognitive deficits that are specific to FLE, opening new avenues for discriminatory characterizations among epilepsy types.

How cerebral cortex protects itself from interictal spikes: The alpha/beta inhibition mechanism.

Interactions between interictal epileptiform discharges (IEDs) and distant cortical regions subserve potential effects on cognition of patients with focal epilepsy. We hypothesize that "healthy" brain areas at a distance from the epileptic focus may respond to the interference of IEDs by generating inhibitory alpha and beta oscillations. We predict that more prominent alpha-beta oscillations can be found in patients with less impaired neurocognitive profile. We performed a source imaging magnetoencephalography study, including 41 focal epilepsy patients: 21 with frontal lobe epilepsy (FLE) and 20 with mesial temporal lobe epilepsy. We investigated the effect of anterior (i.e., frontal and temporal) IEDs on the oscillatory pattern over posterior head regions. We compared cortical oscillations (5-80 Hz) temporally linked to 3,749 IEDs (1,945 frontal and 1,803 temporal) versus an equal number of IED-free segments. We correlated results from IED triggered oscillations to global neurocognitive performance. Only frontal IEDs triggered alpha-beta oscillations over posterior head regions. IEDs with higher amplitude triggered alpha-beta oscillations of higher magnitude. The intensity of posterior head region alpha-beta oscillations significantly correlated with a better neuropsychological profile. Our study demonstrated that cerebral cortex protects itself from IEDs with generation of inhibitory alpha-beta oscillations at distant cortical regions. The association of more prominent oscillations with a better cognitive status suggests that this mechanism might play a role in determining the cognitive resilience in patients with FLE.

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.

Heart rate variability in frontal lobe epilepsy: Association with SUDEP risk.

OBJECTIVES: Frontal lobe epilepsy (FLE) may impair autonomic heart rate modulation. Decreased heart rate variability (HRV) may enhance risk of sudden death. Our objective was to describe whole day and wakefulness/sleep HRV parameters from FLE patients in comparison with those of healthy controls and correlate HRV parameters to SUDEP-7 scores. METHODS: Ten patients with FLE and 15 healthy controls underwent a 24-hour electrocardiogram holter. The SUDEP-7 score was calculated for patients. Subgroups were identified according to active epilepsy, number of generalized seizures, cognitive deficit, medication load, and time-length of epilepsy. Time-domain SDNN, SDNNi, SDANN, rMSDD, and pNN50 and frequency-domain LF, HF, and LF/HF parameters were analyzed. Wilcoxon and Spearman correlation tests were used. A P < .05 was considered significant. RESULTS: Patients SDNN, SDNNi, rMSSD, and pNN50 were decreased in 24-hour recordings. Although a tendency for a protective effect of sleep was seen for both patients and controls, intragroup comparisons of sleeping/waking states revealed a significant increase in sleep rMSSD (P = .046) and pNN50 (P = .041) only for controls. All 24-hour time-domain parameters and LF were inversely and significantly correlated to SUDEP-7, particularly SDANN (ρ = -0.896, P = .00019), known to deteriorate with diminished physical activity and decreased in patients with more generalized seizures. Wakefulness parameters did not correlate to SUDEP-7, whereas correlations to sleep parameters were very strong, particularly with rMSSD (ρ = -0.945, P = .00012). Cognitive deficit was associated with decreased pNN50, sleep pNN50, and LH. CONCLUSION: HRV is impaired in patients with FLE. Low HRV scores are associated with increased risk for SUDEP as measured by the SUDEP-7 score.

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.

The understanding of mental states and the cognitive phenotype of frontal lobe epilepsy.

OBJECTIVE: Previous studies of frontal lobe epilepsy (FLE) have documented different impairments of theory of mind (ToM), while the study of frontal lobe (FL) lesion without seizures has produced inconsistent results. Given the role played by the FLs in ToM, we evaluated this and other functions in patients with FLE with and without FL lesions. The main objective was to clarify the salience of ToM impairment in the cognitive pattern of FLE and its capacity to discriminate these patients from healthy subjects. The effects of FL lesions on ToM were also explored. METHODS: Seventy-five adult patients with FLE (40 cases with FL lesions) were compared with 42 healthy controls. The Faux Pas Task (FPT) and other neuropsychological tests were utilized to assess ToM, reasoning, language, memory, praxis, attention, and executive abilities. RESULTS: The patients obtained lower z scores for the FPT than for other tests. The ToM, Executive, and Verbal factors discriminated patients from healthy subjects. The patients with or without FL lesion showed significant impairments in recognizing and understanding others' epistemic and affective mental states, but adequate capacity to exclude inexistent mental states was retained. In comparison with controls, the patients with FL lesions obtained lower scores for lexical, memory, praxis, attention, and executive functions, whereas those without lesion only showed attention and initiative deficits. Schooling was the major predictor of ToM, whereas the capacity to exclude inexistent mental states was related to seizure onset age and epilepsy duration. Other cognitive functions were related to schooling, age, or FLE laterality. SIGNIFICANCE: Impaired understanding of real mental states is a specific, salient, and discriminating cognitive aspect of FLE. Poor education is a risk factor for ToM deficit, whereas the clinical variables and FL lesions have no impact. These results suggest that impaired ToM may be a marker of FLE neurobehavioral phenotype.

Semiologic subgroups of insulo-opercular seizures based on connectional architecture atlas.

OBJECTIVE: Insulo-opercular seizures are characterized by diverse semiology, related to the insula's multiple functional roles and extensive connectivity. We aimed to identify semiologic subgroups and correlate these with insulo-opercular subregions based on connectional architecture. METHODS: We retrospectively collected a large series of 37 patients with insulo-opercular seizures explored by stereoelectroencephalography (SEEG) from three epilepsy centers. A new human brain atlas (Brainnetome Atlas, BNA) based on both anatomic and functional connections was employed to segment insulo-opercular cortex. Semiology and SEEG changes were carefully reviewed and quantified. Principal component analysis and cluster analysis were used to correlate semiologic characteristics with insulo-opercular subregions. RESULTS: Four main semiologic subgroups were identified, organized along an anteroventral to posterodorsal axis based on BNA. Group 1 was characterized by epigastric sensation and/or integrated gestural motor behaviors with or without feelings of fear or rage, involving the anteroventral insular regions and mesial temporal lobes. Group 2 was characterized by auditory sensations and symmetric proximal/axial tonic signs involving the posteroventral temporal operculum. The characteristics of group 3 were orofacial and laryngeal signs, involving the intermediate insulo-opercular regions. The features of group 4 were somatosensory signs followed by nonintegrated gestural motor behaviors and/or asymmetric tonic signs involving the posterodorsal insulo-opercular regions with propagation to the mesial frontal lobes. Thus anteroventral seizure organizations predominantly showed limbic system semiology, whereas more posterodorsal regions were associated with semiology involving mainly the sensorimotor system. Subjective symptoms proved to be particularly discriminating factors. SIGNIFICANCE: Insulo-opercular seizures can be categorized in terms of clinical semiology and correlate with connectional architecture subregions along an anteroventral-posterodorsal axis in line with the cytoarchitectonic gradient rather than the gyral anatomy of the insula cortex. This provides new insights into facilitating differential diagnosis and presurgical localization but also highlights the importance of considering connectional architecture in determining neural correlates of complex semiologic patterns.

Association between lack of functional connectivity of the frontal brain region and poor response inhibition in children with frontal lobe epilepsy.

PURPOSE: We investigated the relationship between electroencephalographic (EEG) functional connectivity and executive function in children with frontal lobe epilepsy (FLE). METHODS: We enrolled 24 children with FLE (mean age, 11.0 years; 13 boys) and 22 sex-, age-, and intelligence-matched typically developing children (TDC) to undergo 19-channel EEG during light sleep. We estimated functional connectivity using the phase lag index (PLI) that captures the synchronization of EEG. We also performed continuous performance tests (CPTs) on the children and obtained questionnaire responses on attention deficit hyperactivity disorder and oppositional defiant disorder (ODD). RESULTS: The average gamma PLI was lower in the FLE group than in the TDC group, especially between long-distance frontoparietal pairs, between interhemispheric frontal pairs, and between interhemispheric parietotemporal pairs. Gamma PLIs with long-distance frontoparietal and interhemispheric frontal pairs were positively associated with inattention, ODD scores, omission error, and reaction time in the FLE group but not in the TDC group. Conversely, they were negatively associated with age, hyperactivity score, and commission error. CONCLUSIONS: A lack of functional connectivity of the frontal brain regions in children with FLE was associated with poor response inhibition.

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.

Revisiting autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) mutations in the nicotinic acetylcholine receptor reveal an increase in efficacy regardless of stochiometry.

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a genetic form of epilepsy that is caused by mutations in several genes, including genes encoding for the α4 and ß2 subunits of the nicotinic acetylcholine (nACh) receptor. Pentameric α4ß2 nACh receptors are the most abundant nicotinic receptor in the mammalian brain and form two stoichiometries, the (α4)3(ß2)2 and (α4)2(ß2)3 receptors that differ in their physiological and pharmacological properties. The purpose of this study was to investigate how ADNFLE mutations ß2V287M, ß2V287L or α4T293I manifest themselves in different receptor stoichiometries. We expressed wild-type and mutant receptors in Xenopus oocytes and measured the response to ACh and other agonists at both receptor stoichiometries. For all three mutations, the efficacy of ACh at (α4)2(ß2)3 receptors was increased. At (α4)3(ß2)2 receptors, the efficacy of activation was increased both when two molecules of agonist, either ACh or the site-selective agonist sazetidine-A, were bound at the α4-ß2 interfaces, and when a third ACh molecule was bound at the α4-α4 site. Regardless of stoichiometry, the mutations increased the current elicited by low concentrations of ACh. Further, the smoking cessation agents, nicotine, varenicline and cytisine increased activation of mutant (α4)3(ß2)2 receptors, while only nicotine increased activation of mutant (α4)2(ß2)3 receptors. Chronic exposure of all agonists reduced ACh-activation levels at low and high ACh concentrations. From this, we concluded that mutations that cause ADNFLE manifest themselves in a change in efficacy regardless of the stoichiometry of the receptor.

Altered structural and causal connectivity in frontal lobe epilepsy.

BACKGROUND: Albeit the few resting-state fMRI neuroimaging studies in frontal lobe epilepsy (FLE) patients, these studies focused on functional connectivity. The aim of this current study was to examine the effective connectivity based on voxel-based morphometry in FLE patients. METHODS: Resting-state structural and functional magnetic resonance imaging (fMRI) data were acquired from 19 FLE patients and 19 age and gender-matched healthy controls using the 3.0 Tesla magnetic resonance imaging (3.0 T MRI). The investigations were done by acquiring the structural information through voxel-based morphometry, then based on the seed obtained, Granger causality analysis was used to evaluate the causal flow of the designated seed to and from other significant voxels. RESULTS: Our results showed altered structural and effective connectivity. Compared with healthy controls, FLE patients showed reduced grey matter volume in bilateral putamen and right caudate as well as altered causality with increased, and decreased causal outflow from the right caudate (seed region) to inferior frontal gyrus-triangular, from bilateral putamen (seed regions) to right middle frontal gyrus and frontal gyrus medial-orbital representing the frontal executive areas, respectively. Also, significantly increased and decreased inflow from left calcarine to right caudate and from cerebellum_6 and vermis_6 to bilateral putamen, respectively. Moreover, we found that the causal alterations to and from the seed regions (from vermis_6 to right putamen and from left putamen to right middle frontal gyrus) negatively correlated with clinical scores (duration of epilepsy). CONCLUSIONS: The findings point to the impairment within the executive and motor-controlled system including the cerebellum, frontal, caudate and putamen regions in FLE patients. These results would therefore enhance our understanding of structural and effective mechanisms in FLE.

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.

Altered Dynamic Functional Network Connectivity in Frontal Lobe Epilepsy.

Frontal lobe epilepsy has recently been associated with disrupted brain functional connectivity; variations among various resting-state networks (RSNs) across time remains largely unclear. This study applied dynamic functional network connectivity (dFNC) analysis to investigate functional patterns in the temporal and spatial domains of various functional systems in FLE. Resting-state fMRI data were acquired from 19 FLE patients and 18 controls. Independent component analysis was used to decompose RSNs, which were grouped into seven functional systems. Sliding windows and clustering approach were used to identify the dFNC patterns. Then, state-specific connectivity pattern and dynamic functional state interactions (dFSIs) were evaluated. Compared with healthy controls, FLE patients exhibited decreased dFNC in almost all four patterns, changes that were mostly related to the frontoparietal system, suggesting a disturbed communication of the frontoparietal system with other systems in FLE. Additionally, regarding the fundamental connectivity pattern (state 3 in this study), FLE showed decreased time spent in this state. Moreover, the duration positively correlated with seizure onset. Furthermore, significantly reduced dynamic connections in this state were observed in the frontoparietal system linked to the cerebellar and subcortical systems. These findings imply abnormal fundamental dynamic interactions and dysconnectivity associated with the subcortical and cerebellar regulation of dysfunctions in frontoparietal regions in FLE. Finally, based on the developed FSI analysis, temporal dynamic abnormalities among states were observed in FLE. Therefore, this altered dynamic FNC extended our understanding of the abnormalities in the frontoparietal system in FLE. The dynamic FNC provided novel insight into the fundamental pathophysiological mechanisms in FLE.

Are frontal and temporal lobe epilepsy dissociable in their memory functioning?

There is controversy in the literature as to how dissociable frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE) are in terms of memory deficits. Some researchers have demonstrated that FLE is associated with greater executive dysfunction including working memory, whereas TLE is associated with greater memory impairment. Others have found the two groups to be comparable in memory functioning. Hence, we examined this question in children with FLE and TLE versus typically developing controls. We found most of the expected effects when the groups with focal onset epilepsy were compared to controls. Specifically, children with left TLE performed worse on verbal short-term memory/learning and long-term memory measures. In contrast, children with right TLE exhibited a more global pattern of difficulty on short-term memory/learning measures but performed worse than controls on long-term memory for faces. Children with FLE performed worse than controls on verbal working memory. Nevertheless, laterality effects were mild, as children with right and left TLE did not differ significantly from each other. Further, children with FLE did not differ from those with TLE on most measures except delayed facial recognition, where children with right TLE performed worse. In addition, attention problems and poor behavioral regulation were related to encoding problems in both the total epilepsy sample and in children with TLE specifically. Hence, our findings overall are consistent with prior studies indicating that children with TLE and FLE are commensurate in most aspects of memory impairment when compared to each other, likely related to rapid propagation between the frontal and temporal lobes, as would be expected with an excitatory lesion.

Emotional asymmetries in refractory medial temporal and frontal lobe epilepsy: Their impact on predicting lateralization and localization of seizures.

BACKGROUND: Emotional disturbances have been reported in patients with epilepsy. Although conflicting results emanate from relevant studies, depressive symptoms are seen more often in temporal lobe epilepsy (TLE) whereas, hypomanic/manic symptoms usually accompany frontal lobe epilepsy (FLE); the above psychiatric symptoms are especially seen in refractory epilepsy. However, neocortical TLE and medial TLE are considered as distinct epileptic syndromes, and there is limited literature on comparison of affective traits in medial TLE (MTLE) and FLE. AIM: In the present study, we sought to investigate affective traits among epilepsy surgery candidates suffering refractory left medial TLE (LMTLE), right medial TLE (RMTLE), left FLE (LFLE), and right FLE (RFLE). RESULTS: Our results revealed that patients with MTLE scored significantly higher than the ones with FLE in depression, anxiety, asthenia, and melancholia as measured by the Symptoms Rating Scale for Depression and Anxiety (SRSDA), while patients with FLE scored significantly higher in mania than those with MTLE. Moreover, patients with MTLE scored significantly higher than their FLE counterparts on the anxiety scale of the State Trait Personality Inventory (STPI)-trait version. When laterality of the seizure focus was taken into account, no differences were found among both patients with MTLE and patients with FLE, with exception for the Trail Making Test part B (TMT-B) in which patients with RMTLE performed significantly worse than patients with LMTLE. Seizure frequency was higher for FLE. CONCLUSIONS: We provide evidence for an anterior-frontal versus a posterior-medial temporal cerebral functional asymmetry with regard to the manifestation of manic and depressive emotional traits in FLE and MTLE, respectively. Our results are mainly discussed within the frame of their contribution in localizing and to a lesser extent in lateralizing seizures foci in epilepsy surgery candidates. We suggest that this is of great importance in the context of preoperative monitoring of epilepsy surgery, especially when neuropsychologists are called upon to provide anatomical information in defining the functional deficit zone.

Clinical and electroencephalographic correlates of psychiatric features in children with frontal lobe epilepsy.

BACKGROUND AND OBJECTIVE: Frontal lobe epilepsy (FLE) is often associated with psychiatric features, although the factors predisposing to the concurrence of these conditions have yet to be determined, especially in younger children. We aimed at defining possible clinical and electroencephalography (EEG) features that may enhance the psychiatric risk in pediatric FLE. METHOD: We performed a structured psychiatric assessment of 59 children with FLE, using both categorical and dimensional approaches, correlated psychopathology with epilepsy data, and cognitive development. RESULTS: About 1/3 of patients with FLE displayed intellectual disability (ID), and more than 2/3 displayed psychiatric disorders, including depression, disruptive behaviors, anxiety, and bipolar/psychotic disorders. Psychiatric dimensions such as impulse control problems, attentional deficits, social problems, and aggressive behaviors were frequent features of FLE. Intellectual disability was associated with an earlier onset of psychiatric disorders and more frequent disruptive behavior disorders and aggressiveness. Long-standing epilepsy and bilateral or anterior frontal EEG abnormalities also increased the risk of psychopathology. Finally, right-hemisphere lesions were associated with disruptive behavior disorders, fast EEG rhythms with attention/memory problems, and phases of seizure remission with impulse control problems. CONCLUSIONS: Clinical and EEG markers of increased psychopathological risk may help in defining consistent at-risk subgroups within FLE and improving early diagnosis, prognosis, and treatment. Categorical and dimensional approaches to psychiatric diagnosis may generate new research hypotheses and support the investigation of the complex pathophysiological bases shared by different neurodevelopmental disturbances.

Long-term seizure outcome in frontal lobe epilepsy surgery.

PURPOSE: The purpose of this study was to report long-term seizure outcome in patients who underwent frontal lobe epilepsy (FLE) surgery. METHOD: This retrospective study included 44 consecutive subjects who underwent resective surgery for intractable FLE at IRCCS NEUROMED (period 2001-2014), followed up for at least 2 years (mean: 8.7 years). All patients underwent noninvasive presurgical evaluation and/or invasive electroencephalography (EEG) monitoring when nonconcordant data were obtained or epileptogenic zone was hypothesized to be close to the eloquent cortex. Electroclinical, neuroimaging, surgical data, and histology were compared to seizure outcome. RESULTS: Mean epilepsy duration was 19 years; mean age at surgery was 31.6 years. Preoperative magnetic resonance imaging (MRI) showed a frontal lesion in 86.4 % of cases. Scalp video-electroencephalography (VEEG) monitoring detected a focal ictal onset in 90% of cases. Twenty-seven patients (61.4%) underwent invasive recordings. Resections involved dorsolateral (47.7%), medial (9%), orbital (13.6%), and rolandic (13.6%) region. Lobectomy within functional boundaries was performed in the remaining 7 cases (16%). Transient and permanent neurological deficits were observed in 2 and 3 cases, respectively. Histology revealed focal cortical dysplasia (45.5%), World Health Organization (WHO) I-II grade tumors (15.9%), gliosis (22.7%), vascular malformations (4.5%), Rasmussen encephalitis (6.8%), and normal tissue (4.5%). At last observation 68.1% of patients were in Engel's class I, 11.4% in class II, 9% in class III, and 11.4% in class IV. A favorable outcome was associated with focal ictal scalp EEG onset (p = 0.0357). CONCLUSION: Surgery is a safe treatment option in drug-resistant FLE with a satisfying long-term outcome. These data highlight the importance of an appropriate selection of potential surgical candidates.

Frontal lobe epileptic seizures are accompanied by elevated pitch during verbal communication.

The objective of our study was to assess alterations in speech as a possible localizing sign in frontal lobe epilepsy. Ictal speech was analyzed in 18 patients with frontal lobe epilepsy (FLE) during seizures and in the interictal period. Matched identical words were analyzed regarding alterations in fundamental frequency (ƒo) as an approximation of pitch. In patients with FLE, ƒo of ictal utterances was significantly higher than ƒo in interictal recordings (p = 0.016). Ictal ƒo increases occurred in both FLE of right and left seizure origin. In contrast, a matched temporal lobe epilepsy (TLE) group showed less pronounced increases in ƒo, and only in patients with right-sided seizure foci. This study for the first time shows significant voice alterations in ictal speech in a cohort of patients with FLE. This may contribute to the localization of the epileptic focus. Increases in ƒo were interestingly found in frontal lobe seizures with origin in either hemisphere, suggesting a bilateral involvement to the planning of speech production, in contrast to a more right-sided lateralization of pitch perception in prosodic processing.

Insulo-opercular cortex generates oroalimentary automatisms in temporal seizures.

OBJECTIVE: Oroalimentary automatisms (OAAs) resembling normal alimentary behavior are stereotyped complex movements that may occur during epileptic seizures. They are considered common clinical signs in temporal lobe seizures, but their anatomofunctional mechanisms are not established. We took the opportunity of presurgical intracerebral recordings to study the relations between the occurrence of OAAs and temporal/spatial features of ictal activities. METHODS: We retrospectively reviewed patients with medically intractable medial temporal lobe epilepsy who underwent stereoelectroencephalography (SEEG) at Cleveland Clinic between 2009 and 2016. Patients presenting oroalimentary automatisms during seizures, with intracerebral electrodes spanning temporal and extratemporal areas, were selected. SEEG-clinical correlations with latency measurements were done. Coherence analyses were performed on regions of interest as defined by the areas involved at the onset of oroalimentary automatisms. RESULTS: Fifteen patients (115 seizures) were analyzed. Sixty-nine seizures exhibited overt oroalimentary automatisms. Only insulo-opercular cortex ictal involvement was consistently related to the occurrence of OAAs, with a linear correlation between OAA onset and ictal oscillatory activity onset in the insulo-opercular cortex. SEEG signal processing showed an increase in theta coherence preceding oroalimentary automatism onset between mediobasal-temporal structures and insulo-opercular cortex, as well as between the 2 insulo-opercular regions. SIGNIFICANCE: The underlying mechanism for the production of oroalimentary automatisms in medial temporal seizures is based on temporal-insulo-opercular theta coherence leading to a synchronous state generating rhythmic patterned outputs from the cortical masticatory area.