Focal Epilepsy Patients Research Articles

In pursuit of the epileptogenic zone in focal epilepsy:a dynamical network biomarker approach

The success of resection surgery for drug-resistant epilepsy patients hinges on the correct identification of the epileptogenic zone (EZ) consisting of the subnetwork of brain regions that underlies seizure genesis in focal epilepsy. The dynamical network biomarker (DNB) method is a dynamical systems-based network analysis approach for identifying subnetworks that are the first to exhibit the transition as a complex system undergoes a bifurcation. The approach was devised and validated in the context of complex disease onset where the dynamics is known to be nonlinear and high-dimensional. We here adapt and implement the DNB approach for the identification of the EZ from the analysis of Stereoelectroencephalography (SEEG) data. The method is first successfully tested on simulated data generated with a large-scale brain network model of epilepsy using The Virtual Brain neuroinformatic platform and then applied to clinical SEEG data from focal epilepsy patients. The results are compared with those obtained by expert clinicians that designate the EZ using the Epileptogenicity Index (EI) method. High average precision values are obtained and posit the presented approach as a promising candidate tool for the pursuit of EZ in focal epilepsy.

Levetiracetam versus Oxcarbazepine as monotherapy in newly diagnosed focal epilepsy: A systematic review and meta‐analysis

To compare the efficacy and safety of Levetiracetam (LEV) and Oxcarbazepine (OXC) as monotherapy for the treatment of newly diagnosed focal epilepsy. We searched PubMed, Cochrane Library, EMBASE, and Google Scholar from January 1, 2000 to May 11, 2022, with no language restrictions along with The ClinicalTrials.gov website and the WHO International Controlled Trials Registry platforms. We pooled the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for the efficacy and safety outcomes. The quality of included trials was assessed using the Cochrane Collaboration's tool. Two RCTs included a total of 574 newly diagnosed focal epilepsy patients (the LEV group [282 patients] and the OXC group [292 patients]). LEV group when compared with the OXC group had no significant difference in the pooled estimate of seizure freedom at week 24. (RR: 0.81; 95% CI: 0.62-1.05, p = .11). Similarly, there was no significant difference in the pooled estimate of withdrawal due to adverse events (AEs) (RR: 0.87; 95% CI: 0.34-2.23, p = .77). The commonly reported AEs in both trials were dizziness, headache, rash, somnolence, and nasopharyngitis with zero medication-related death and few serious AEs. LEV is noninferior to OXC in terms of seizure freedom at week 24 and treatment withdrawal rate due to AEs among adults but long-term treatment data is still missing. Future multicentric double-blinded RCTs and real-world studies are of great need.

EMHapp: a pipeline for the automatic detection, localization and visualization of epileptic magnetoencephalographic high-frequency oscillations

Objective. High-frequency oscillations (HFOs) are promising biomarkers for localizing epileptogenic brain tissue. Previous studies have revealed that HFOs that present concurrence with interictal epileptic discharges (IEDs) better delineate epileptogenic brain tissue, particularly for epilepsy patients with multitype interictal discharges. However, the analysis of noninvasively recorded epileptic HFOs involves many complex procedures, such as data preprocessing, detection and source localization, impeding the translation of this approach to clinical practice. Approach. To address these problems, we developed a graphical user interface (GUI)-based pipeline called EMHapp, which can be used for the automatic detection, source localization and visualization of HFO events concurring with IEDs in magnetoencephalography (MEG) signals by using a beamformer-based virtual sensor (VS) technique. An improved VS reconstruction method was developed to enhance the amplitudes of both HFO and IED VS signals. To test the capability of our pipeline, we collected MEG data from 11 complex focal epilepsy patients with surgical resections or seizure onset zones (SOZs) that were identified by intracranial electroencephalography. Main results. Our results showed that the HFO sources of eight patients were concordant with their resection margins or SOZs. Our proposed VS signal reconstruction approach achieved an 83.2% improvement regarding the number of detected HFO events and a 17.3% improvement in terms of the spatial overlaps between the HFO sources and the resection margins or SOZs in comparison with conventional VS reconstruction approaches. Significance. EMHapp is the first GUI-based pipeline for the analysis of epileptic magnetoencephalographic HFOs, which conveniently obtains HFO source locations using clinical data and enables direct translation to clinical applications.

Precision medicine in pediatric temporal epilepsy surgery: optimization of outcomes through functional MRI memory tasks and tailored surgeries.

The goal of epilepsy surgery is both seizure cessation and maximal preservation of function. In temporal lobe (TL) cases, the lack of functional MRI (fMRI) tasks that effectively activate mesial temporal structures hampers preoperative memory risk assessment, especially in children. This study evaluated pediatric TL surgery outcome optimization associated with tailored resection informed by an fMRI memory task. The authors identified focal onset TL epilepsy patients with 1) TL resections; 2) viable fMRI memory scans; and 3) pre- and postoperative neuropsychological (NP) evaluations. They retrospectively evaluated preoperative fMRI memory scans, available Wada tests, pre- and postoperative NP scores, postoperative MRI scans, and postoperative Engel class outcomes. To assess fMRI memory task outcome prediction, the authors 1) overlaid preoperative fMRI activation onto postoperative structural images; 2) classified patients as having "overlap" or "no overlap" of activation and resection cavities; and 3) compared these findings with memory improvement, stability, or decline, based on Reliable Change Index calculations. Twenty patients met the inclusion criteria. At a median of 2.1 postoperative years, 16 patients had Engel class IA outcomes and 1 each had Engel class IB, ID, IIA, and IID outcomes. Functional MRI activation was linked to NP memory outcome in 19 of 20 cases (95%). Otherwise, heterogeneity characterized the cohort. Functional MRI memory task activation effectively predicted individual NP outcomes in the context of tailored TL resections. Patients had excellent seizure and overall good NP outcomes. This small study adds to extant literature indicating that pediatric TL epilepsy does not represent a single clinical syndrome. Findings support individualized surgical intervention using fMRI memory activation to help guide this precision medicine approach.

QT interval alterations in epilepsy: A thorough investigation between epilepsy subtypes

ObjectivesCardiac disturbances and rhythm abnormalities which potentially lead sudden unexpected death in epilepsy, have been extensively studied in focal epilepsies. However, studies including generalized epilepsies are scarce and it is not clear whether electrocardiogram parameters reflecting vulnerability to ventricular arrhythmias differ between these groups. MethodsMedical records of patients who were followed in epilepsy department of a tertiary center between October 2015 and September 2016 were retrospectively reviewed. 66 generalized and 64 focal epilepsy patients with eligible electrophysiological data were analyzed. QTc interval, QTcd and other electrocardiographic indices were compared between patients with focal vs generalized epilepsy. Another analysis was performed in order to disclose any difference between patients with epilepsy (n:130) and psychogenic non-epileptic seizures. A two-tailed p value < 0.05 was considered significant. ResultsThere was no difference in terms of QTc and QTcd between patients with focal and generalized epilepsy [median: 406 ms vs 404 ms, p = 0.119; and median: 46 ms vs 44 ms, p = 0.497, respectively]. However patients with epilepsy were found to have longer QTc and QTcd when compared to ones with psychogenic non-epileptic seizures (p = 0.035 and p < 0.001, respectively). ConclusionCurrent findings demonstrate that patients with epilepsy have longer QTc and QTcd than patients with pure psychogenic non-epileptic seizures. Since there was no difference between patients with focal and generalized epilepsy; QTc interval, QTcd and potential susceptibility to cardiac arrhythmias as a result, could be a consequence of epilepsy itself regardless of origin.

Brain network analysis of interictal epileptiform discharges from ECoG to identify epileptogenic zone in pediatric patients with epilepsy and focal cortical dysplasia type II: A retrospective study.

ObjectiveFor patients with drug–resistant focal epilepsy, intracranial monitoring remains the gold standard for surgical intervention. Focal cortical dysplasia (FCD) is the most common cause of pharmacoresistant focal epilepsy in pediatric patients who usually develop seizures in early childhood. Timely removal of the epileptogenic zone (EZ) is necessary to achieve lasting seizure freedom and favorable developmental and cognitive outcomes to improve the quality of life. We applied brain network analysis to investigate potential biomarkers for the diagnosis of EZ that will aid in the resection for pediatric focal epilepsy patients with FCD type II.MethodsTen pediatric patients with focal epilepsy diagnosed as FCD type II and that had a follow–up after resection surgery (Engel class I [n = 9] and Engel class II [n = 1]) were retrospectively included. Time–frequency analysis of phase transfer entropy, graph theory analysis, and power spectrum compensation were combined to calculate brain network parameters based on interictal epileptiform discharges from ECoG.ResultsClustering coefficient, local efficiency, node out–degree, and node out–strength with higher values are the most reliable biomarkers for the delineation of EZ, and the differences between EZ and margin zone (MZ), and EZ and normal zone (NZ) were significant (p < 0.05; Mann–Whitney U-test, two–tailed). In particular, the difference between MZ and NZ was significant for patients with frontal FCD (MZ > NZ; p < 0.05) but was not significant for patients with extra–frontal FCD.ConclusionsBrain network analysis, based on the combination of time–frequency analysis of phase transfer entropy, graph theory analysis, and power spectrum compensation, can aid in the diagnosis of EZ for pediatric focal epilepsy patients with FCD type II.

Interictal epileptiform discharges show distinct spatiotemporal and morphological patterns across wake and sleep.

Presurgical evaluation of mesial temporal and neocortical focal pharmacoresistant epilepsy patients using intracranial EEG recordings has led to the generation of extensive data on interictal epileptiform discharges, located within or remotely from seizure onset zones. In this study, we used this data to investigate how interictal epileptiform discharges are modulated and how their spatial distribution changes during wake and sleep and analysed the relationship between these discharge events and seizure onset zones. Preoperative evaluation data from 11 adult patients with focal pharmacoresistant epilepsy were extracted from the Epilepsiae database. Interictal epileptiform discharges were automatically detected during wakefulness and over several hours of continuous seizure-free sleep (total duration of EEG recordings:106.7 h; mean per patient: 9.7 h), and analysed across four brain areas (mesial temporal, lateral neocortical, basal cortical and the temporal pole). Sleep stages were classified manually from scalp EEG. Discharge events were characterized according to their rate and morphology (amplitude, sharpness and duration). Eight patients had a seizure onset zone over mesial areas and three patients over lateral neocortical areas. Overall, discharge rates varied across brain areas during wakefulness and sleep [wake/sleep stages × brain areas interaction; Wald χ 2(df = 6) = 31.1, P < 0.0001]. N2-N3 non-rapid eye movement sleep increased interictal epileptiform discharges in mesial areas compared with wakefulness and rapid eye movement sleep (P < 0.0001), and to other areas (P < 0.0001 for all comparisons). This mesial pattern was observed both within and outside of seizure onset zones. During wakefulness, the rate of interictal epileptiform discharges was significantly higher than during N2-N3 non-rapid eye movement sleep (P = 0.04), and rapid eye movement sleep (P = 0.01) in lateral neocortical areas (referred to as lateral neocortical pattern), a finding that was more pronounced in seizures onset zones (P = 0.004). The morphological characteristics of the discharge events were modulated during wakefulness and sleep stages across brain areas. The effect of seizure onset zones on discharge morphology was conditioned by brain area and was particularly marked in temporal pole areas. Our analysis of discharge patterns in relation to cerebral localization, vigilance state and the anatomical affiliation of seizure onset zones revealed the global and local aspects of the complex relationship between interictal discharges, sleep and seizure onset zones. This novel approach may lead to a better understanding of cognitive decline and responses to therapy, as well as to adaptation of surgical interventions for epileptic patients.

Involvement of the Anterior Nucleus of the Thalamus during Focal Automatisms in Epileptic Seizures: A First Evidence Study.

The Anterior Nucleus of Thalamus (ANT) Deep Brain Stimulation (DBS) has long been touted as the most effective DBS-target for interrupting seizures in focal refractory epilepsy patients. The ANT is primarily involved in cognitive tasks but has extensive reciprocal connections with motor-related regions, suggesting that it is also involved in motor-cognitive tasks. In this work, we aimed to assess the involvement of the ANT during voluntary upper limbs movements. For this purpose, we analyzed Local Field Potentials (LFPs) signals recorded during a movement protocol from one of the first epilepsy patients implanted with a Percept™ PC system, who performed a 5-day period of simultaneous video electroencephalography (vEEG) and Percept PC-LFPs recordings. We estimated time-frequency maps and performed event-related desynchronization (ERD) or synchronization (ERS) analysis and we found that synchronizations found in left hemisphere 7-17 Hz map corresponded to maximum hand rotations. Positive peaks on the ERD/ERS curve occurred at a similar frequency of the hand movements ([Formula: see text] against [Formula: see text]). These results suggested that the ANT may be involved in the execution of automatisms. Moreover, we found that ERD/ERS appeared approximately 2 seconds before the movement onset, as it was found on the EEG of healthy subjects performing the same protocol.

Is the left hemisphere more prone to epilepsy and poor prognosis than the right hemisphere?

Objective: The central nervous system is known to have asymmetric immune system modulation. Thus far, no clinical study has examined asymmetric immune modulation between hemispheres in focal epilepsy patients. We aimed to compare the prognosis of epilepsy patients lateralized to the right hemisphere with epilepsy patients lateralized to the left hemisphere using clinic and demographic data.Method: Ninety-nine patients with focal epilepsy with all seizures originating in only one hemisphere, between the ages of 18–and 86 years were included. We included patients with focal epilepsy whose seizures were lateralized to only one hemisphere. Age, gender, marital status, education, mental retardation, hand dominance, etiology, trauma, central nervous system infection, febrile convulsion, parental relationships, seizure onset age, seizure frequency (per month), systemic disease, and biochemical parameters were recorded. To evaluate lateralization, we used positron emission tomography (PET/CT), long-term video-electroencephalography (EEG), and magnetic resonance imaging (MRI) investigations.Results: Thirty-seven patients (37.4%) patients were right-lateralized, whereas 62 patients (62.6%) were left-lateralized (p = 0.01). Seizures frequency seizures were higher in patients lateralized to the left hemisphere than in the right. (p = 0.001). In patients with epilepsy lateralized to the left hemisphere, epilepsy onset age was lower (p = 0.003), numbers of antiepileptic medicines were higher (p = 0.04), and epilepsy durations and longest seizure-free periods were longer (p = 0.001 and p = 0.04, respectively).Conclusion: We have shown that compared to the right hemisphere, the left hemisphere is far more prone to seizures and has a poorer prognosis.

Secondary motor areas for response inhibition: an epicortical recording and stimulation study.

The areas that directly inhibit motor responses in the human brain remain not fully clarified, although the pre-supplementary motor area and lateral premotor areas have been implicated. The objective of the present study was to delineate the critical areas for response inhibition and the associated functional organization of the executive action control system in the frontal lobe. The subjects were eight intractable focal epilepsy patients with chronic subdural or depth electrode implantation for presurgical evaluation covering the frontal lobe (five for left hemisphere, three for right). We recorded event-related potentials to a Go/No-Go task. We then applied a brief 50 Hz electrical stimulation to investigate the effect of the intervention on the task. Brief stimulation was given to the cortical areas generating discrete event-related potentials specific for the No-Go trials (1–3 stimulation sites/patient, a total of 12 stimulation sites). We compared the locations of event-related potentials with the results of electrical cortical stimulation for clinical mapping. We also compared the behavioural changes induced by another brief stimulation with electrical cortical stimulation mapping. As the results, anatomically, No-Go-specific event-related potentials with relatively high amplitude, named ‘large No-Go event-related potentials’, were observed predominantly in the secondary motor areas, made up of the supplementary motor area proper, the pre-supplementary motor area, and the lateral premotor areas. Functionally, large No-Go event-related potentials in the frontal lobe were located at or around the negative motor areas or language-related areas. Brief stimulation prolonged Go reaction time at most stimulation sites (66.7%) [P < 0.0001, effect size (d) = 0.30, Wilcoxon rank sum test], and increased No-Go error at some stimulation sites (25.0%: left posterior middle frontal gyrus and left pre-supplementary motor area). The stimulation sites we adopted for brief stimulation were most frequently labelled ‘negative motor area’ (63.6%), followed by ‘language-related area’ (18.2%) by the electrical cortical stimulation mapping. The stimulation sites where the brief stimulation increased No-Go errors tended to be labelled ‘language-related area’ more frequently than ‘negative motor area’ [P = 0.0833, Fisher’s exact test (two-sided)] and were located more anteriorly than were those without a No-Go error increase. By integrating the methods of different modality, namely, event-related potentials combined with brief stimulation and clinical electrical cortical stimulation mapping, we conducted a novel neuroscientific approach, providing direct evidence that secondary motor areas, especially the pre-supplementary motor area and posterior middle frontal gyrus, play an important role in response inhibition.

EFFICACY AND TOLERABILITY OF ESLICARBAZEPINE ACETATE AS MONOTHERAPY IN PATIENTS OF NEWLY DIAGNOSED FOCAL EPILEPSY

This study was conducted at Department of Psychiatry, Teerthanker Mahaveer University, Moradabad. The aim of our study was to determine the efficacy and safety of Eslicarbazepine Acetate, observe its well-tolerated use and monitor adverse effects in newly diagnosed patients of focal epilepsy. A total of 30 newly diagnosed cases of focal epilepsy between 18-60 years, were studied for 6 months, using a semi-structured interview and Liverpool Adverse Events Profile. Majority of patients were males (58%), between 21-30 years. Patients with partial/focal seizures (63%) were more common than those of generalized seizures (37%).Majority of the participants had 1-2 episodes of focal seizures weekly (48%), while some had almost daily (32%). Majority were on Eslicarbazepine Acetate 800mg in two divided doses daily (64%), while the others received 1200 mg in divided doses (32%). The mean Liverpool Adverse Events Profile score initially was 28.34 ± 6.28 which significantly improved after 4 weeks treatment to 22.80 ± 4.35 (p &lt; 0.05). The improvement in newly diagnosed focal seizures patients was significantly more than other patients (p &lt; 0.05).No major side effects were observed.Therefore, better results of this drug are found in newly diagnosed focal epilepsy patients.

Elevated peripheral Neuregulin-1 protein levels in non-medicated focal epilepsy patients

IntroductionThe Neuregulin-1 (NRG-1) gene has been identified as a susceptibility gene for schizophrenia. Schizophrenia and epilepsy shared some common clinical manifestations and common pathogenesis. Therefore, it is necessary to explore whether there is a relationship between NRG-1 and epilepsy. This study aimed to investigate the expression level of NRG-1 in peripheral blood of non-medicated patients with first-onset focal epilepsy. MethodsA total of 83 non-medicated first-onset focal epilepsy patients and 80 healthy controls were involved in this study. Serum NRG-1 protein levels were determined by ELISA. ResultsCompared to healthy controls (mean ± SD, 3.97 ± 2.37), NRG-1 protein levels were statistically significantly higher in patients (mean ± SD, 5.37 ± 3.48) (P = 0.006). ConclusionsOur findings suggest that NRG-1 protein may play a role in the pathogenesis of focal epilepsy, which provides insights into the search for epilepsy potential therapeutic markers and new drug treatment targets.

Significance of Polyspikes on Electroencephalography in Children with Focal Epilepsy

Purpose: Epilepsy is one of the most common neurological disorders in both adults and children. After detailed history-taking, electroencephalography (EEG) is the most important investigation in the evaluation of epilepsy patients. Polyspikes, defined as a sequence of two or more spikes, are among the findings that can be seen on EEGs of epilepsy patients, but the literature on their significance in focal epilepsy patients is scarce. Therefore, in the current study, we investigated the significance of polyspikes on EEG in childhood focal epilepsy. Methods: A retrospective analysis was conducted of data from children who were diagnosed with focal epilepsy and received anti-seizure medications at Pusan National University Children’s Hospital. Results: Among the 1,125 children included in this study, 468 (41.6%) showed interictal polyspikes on their EEGs. In the multivariate analysis, only the presence of brain magnetic resonance imaging (MRI) abnormalities was significantly associated with the presence of interictal polyspikes on EEGs. Among patients with brain MRI abnormalities, localized polyspikes were significantly associated with focal cortical dysplasia, while multifocal polyspikes were significantly associated with perinatal insults (hypoxic-ischemic encephalopathy and destructive encephalomalacia). Conclusion: Focal epilepsy patients with interictal polyspikes were more likely to have a structural etiology. Furthermore, patients with localized polyspikes were more likely to have focal cortical dysplasia as the structural etiology, while patients with multifocal polyspikes were more likely to have perinatal insults as the structural etiology. This study demonstrates that focal polyspikes can be used as markers of the possible presence of a structural etiology in routine practice.

Sleep-wake states change the interictal localization of candidate epileptic source generators.

To compare estimated epileptic source localizations from 5 sleep-wake states (SWS): wakefulness (W), rapid eye movement sleep (REM), and non-REM 1-3. Electrical source localization (sLORETA) of interictal spikes from different SWS on surface EEG from the epilepsy monitoring unit at spike peak and take-off, with results mapped to individual brain models for 75% of patients. Concordance was defined as source localization voxels shared between 2 and 5 SWS, and discordance as those unique to 1 SWS against 1-4 other SWS. 563 spikes from 16 prospectively recruited focal epilepsy patients across 161 day-nights. SWS exerted significant differences at spike peak but not take-off. Source localization size did not vary between SWS. REM localizations were smaller in multifocal than unifocal patients (28.8% vs. 54.4%, p = .0091). All five SWS contributed about 45% of their localizations to converge onto 17.0 ± 15.5% voxels. Against any one other SWS, REM was least concordant (54.4% vs. 66.9%, p = .0006) and most discordant (39.3% vs. 29.6%, p = .0008). REM also yielded the most unique localizations (20.0% vs. 8.6%, p = .0059). REM was best suited to identify candidate epileptic sources. sLORETA proposes a model in which an "omni-concordant core" of source localizations shared by all five SWS is surrounded by a "penumbra" of source localizations shared by some but not all SWS. Uniquely, REM spares this core to "move" source voxels from the penumbra to unique cortex not localized by other SWS. This may reflect differential intra-spike propagation in REM, which may account for its reported superior localizing abilities.

Interictal epileptiform discharges in focal epilepsy are preceded by increase in low-frequency oscillations

ObjectiveInterictal epileptiform discharges (IEDs) constitute a diagnostic signature of epilepsy. These events reflect epileptogenic hypersynchronization. Previous studies indicated that IEDs arise from slow neuronal activation accompanied by metabolic and hemodynamic changes. These might induce cortical inhibition followed hypersynchronization at IED onset. As cortical inhibition is mediated by low-frequency oscillations, we aimed to analyze the role of low-frequency oscillations prior the IED using magnetencephalography (MEG). MethodsLow-frequency (1–8 Hz) oscillations pre-IED ([-1000 milliseconds (ms), IED onset]) were analyzed using MEG in 14 focal epilepsy patients (median age = 23 years, range = 7–46 age). Occurrence of local pre-IED oscillations was analyzed using Beamformer Dynamical Imaging of Coherent Sources (DICS) and event-related desynchronization/synchronization (ERD-ERS) maps constructed using cluster-based permutation tests. The development of pre-IED oscillations was characterized using Hilbert transformation. ResultsAll patients exhibited statistically significant increase in delta (1–4 Hz) and/or theta (4–8 Hz) oscillations pre-IED compared to baseline [-2000 ms, −1000 ms]. Furthermore, all patients exhibited low-frequency power increase up to IED onset. ConclusionsWe demonstrated consistently occurring, low-frequency oscillations prior to IED onset. SignificanceAs low-frequency activity mediates cortical inhibition, our study demonstrates that a focal inhibition precedes hypersynchronization at IED onset.

Barques are generated in posterior hippocampus and phase reverse over lateral posterior hippocampal surface

ObjectiveTo investigate whether barques can be localized across the hippocampal longitudinal axis with sufficient specificity. MethodsWe identified 51 focal epilepsy patients implanted with a minimum of two electrodes – unilateral anterior and posterior - in either hippocampus. We used visual inspection of the intracranial electroencephalogram (iEEG) and 3D brain volume spectrum-based statistical parametric mapping (SPM) to localize barques. ResultsIn 18/51 patients (35.29%), barques were identified in 22/70 (31.42%) hippocampi. In all hippocampi (100%), barques were present in the posterior hippocampus, while 9 (40.90%) showed concurrent non-independent barque activity anteriorly (P < 0.0001). Statistical parametric mapping confirmed the posterior barque localization, with significant differences in t-values (t(27) = 8.08, P < 0.0001) and z-scores (t(24) = 6.85, P < 0.0001) between anterior and posterior hippocampal barque activity. Posterior lateral extrahippocampal contacts demonstrated phase reversals of positive polarity during barque activity (P = 0.0092, compared to anterior extrahippocampal contacts). ConclusionsThis study highlights the posterior hippocampal predominance of barques. Our findings are concordant with the posterior distribution of the scalp manifestation of barques as “14&6/sec positive spikes”. The posterio-lateral hippocampal barque phase reversal can explain the positive polarity of scalp 14&6/sec spikes. SignificanceUnderstanding the properties of barques is critical for the iEEG interpretation in epilepsy surgery evaluations that include the hippocampus.

A neuromorphic spiking neural network detects epileptic high frequency oscillations in the scalp EEG

Interictal High Frequency Oscillations (HFO) are measurable in scalp EEG. This development has aroused interest in investigating their potential as biomarkers of epileptogenesis, seizure propensity, disease severity, and treatment response. The demand for therapy monitoring in epilepsy has kindled interest in compact wearable electronic devices for long-term EEG recording. Spiking neural networks (SNN) have emerged as optimal architectures for embedding in compact low-power signal processing hardware. We analyzed 20 scalp EEG recordings from 11 pediatric focal lesional epilepsy patients. We designed a custom SNN to detect events of interest (EoI) in the 80–250 Hz ripple band and reject artifacts in the 500–900 Hz band. We identified the optimal SNN parameters to detect EoI and reject artifacts automatically. The occurrence of HFO thus detected was associated with active epilepsy with 80% accuracy. The HFO rate mirrored the decrease in seizure frequency in 8 patients (p = 0.0047). Overall, the HFO rate correlated with seizure frequency (rho = 0.90 CI [0.75 0.96], p < 0.0001, Spearman’s correlation). The fully automated SNN detected clinically relevant HFO in the scalp EEG. This study is a further step towards non-invasive epilepsy monitoring with a low-power wearable device.

Common functional connectivity alterations in focal epilepsies identified by machine learning.

This study was undertaken to identify shared functional network characteristics among focal epilepsies of different etiologies, to distinguish epilepsy patients from controls, and to lateralize seizure focus using functional connectivity (FC) measures derived from resting state functional magnetic resonance imaging (MRI). Data were taken from 103 adult and 65 pediatric focal epilepsy patients (with or without lesion on MRI) and 109 controls across four epilepsy centers. We used three whole-brain FC measures: parcelwise connectivity matrix, mean FC, and degree of FC. We trained support vector machine models with fivefold cross-validation (1) to distinguish patients from controls and (2) to lateralize the hemisphere of seizure onset in patients. We reported the regions and connections with the highest importance from each model as the common FC differences between the compared groups. FC measures related to the default mode and limbic networks had higher importance relative to other networks for distinguishing epilepsy patients from controls. In lateralization models, regions related to somatosensory, visual, default mode, and basal ganglia showed higher importance. The epilepsy versus control classification model trained using a 400-parcel connectivity matrix achieved a median testing accuracy of 75.6% (median area under the curve [AUC]=.83) in repeated independent testing. Lateralization accuracy using the 400-parcel connectivity matrix reached a median accuracy of 64.0% (median AUC=.69). Machine learning models revealed common FC alterations in a heterogeneous group of patients with focal epilepsies. The distribution of the most altered regions supports the hypothesis that shared functional alteration exists beyond the seizure onset zone and its epileptic network. We showed that FC measures can distinguish patients from controls, and further lateralize focal epilepsies. Future studies are needed to confirm these findings by using larger numbers of epilepsy patients.

Incidence and prevalence of major epilepsy-associated brain lesions.

Epilepsy surgery is an effective treatment option for drug-resistant focal epilepsy patients with associated structural brain lesions. However, little epidemiological data are available regarding the number of patients with these lesions. We reviewed data regarding (1) the prevalence and incidence of epilepsy; (2) the proportion of epilepsy patients with focal epilepsy, drug-resistant epilepsy, and drug-resistant focal epilepsies; and (3) the number of epilepsy presurgical evaluations and surgical resections. We also assessed the relative proportion of brain lesions using post-surgical histopathological findings from 541 surgical patients from the Cleveland Clinic and 9,523 patients from a European multi-center cohort. Data were combined to generate surgical candidate incidence and prevalence estimates and the first lesion-specific estimates for hippocampal sclerosis (HS), low-grade epilepsy-associated brain tumors (LEAT), malformations of cortical development (MCD), glial scars, vascular malformations, and encephalitis. The most frequently diagnosed brain lesions were HS (incidence=2.32±0.26 in 100,000, prevalence=19.40±2.16 in 100,000) for adults and MCD (incidence=1.15±0.34 in 100,000, prevalence=6.52±1.89 in 100,000) for children. Our estimates can guide patient advocacy groups, clinicians, researchers, policymakers in education, development of health care strategy, resource allocation, and reimbursement schedules.

7T versus 3T MRI in the presurgical evaluation of patients with drug-resistant epilepsy.

MRI has a crucial role in presurgical evaluation of drug-resistant focal epilepsy patients. Whether and how much 7T MRI further improves presurgical diagnosis compared to standard of care 3T MRI remains to be established. We investigate the added value 7T MRI offers in surgical candidates with remaining clinical uncertainty after 3T MRI. 7T brain MRI was obtained on sequential patients with drug-resistant focal epilepsy undergoing presurgical evaluation at a comprehensive epilepsy center, including patients with and without suspected lesions on standard 3T MRI. Clinical information and 3T images informed the interpretation of 7T images. Detection of a new lesion on 7T or better characterization of a suspected lesion was considered to add value to the presurgical workup. Interpretable 7T MRI was acquired in 19 patients. 7T MRI identified a lesion relevant to the seizures in three of eight patients (38%) without a lesion on 3T MRI; no lesion in 7/11 patients (64%) with at least one suspected lesion on 3T MRI, contributing to the final classification of all seven as nonlesional; and confirmed and better characterized the lesion suspected at 3T MR in the remaining 4/11 patients. 7T MRI detected new lesions in over a third of 3T MRI nonlesional patients, confirmed and better characterized a 3T suspected lesion in one third of patients, and helped exclude a 3T suspected lesion in the remainder. Our initial experience suggests that 7T MRI adds value to surgical planning by improving detection and characterization of suspected brain lesions in drug-resistant focal epilepsy patients.