Focal Epilepsy Patients Research Articles

Deep learning based source imaging provides strong sublobar localization of epileptogenic zone from MEG interictal spikes

Electromagnetic source imaging (ESI) offers unique capability of imaging brain dynamics for studying brain functions and aiding the clinical management of brain disorders. Challenges exist in ESI due to the ill-posedness of the inverse problem and thus the need of modeling the underlying brain dynamics for regularizations. Advances in generative models provide opportunities for more accurate and realistic source modeling that could offer an alternative approach to ESI for modeling the underlying brain dynamics beyond equivalent physical source models. However, it is not straightforward to explicitly formulate the knowledge arising from these generative models within the conventional ESI framework. Here we investigate a novel source imaging framework based on mesoscale neuronal modeling and deep learning (DL) that can learn the sensor-source mapping relationship directly from MEG data for ESI. Two DL-based ESI models were trained based on data generated by neural mass models and either generic or personalized head models. The robustness of the two DL models was evaluated by systematic computer simulations and clinical validation in a cohort of 29 drug-resistant focal epilepsy patients who underwent intracranial EEG (iEEG) evaluation or surgical resection. Results estimated from pre-operative MEG interictal spikes were quantified using the overlap with resection regions and the distance to the seizure-onset zone (SOZ) defined by iEEG recordings. The DL-based ESI provided robust results when no personalized head geometry is considered, reaching a spatial dispersion of 21.90 ± 19.03 mm, sublobar concordance of 83 %, and sublobar sensitivity and specificity of 66 and 97 % respectively. When using personalized head geometry derived from individual patients’ MRI in the training data, personalized DL-based ESI model can further improve the performance and reached a spatial dispersion of 8.19 ± 8.14 mm, sublobar concordance of 93 %, and sublobar sensitivity and specificity of 77 and 99 % respectively. When compared to the SOZ, the localization error of the personalized approach is 15.78 ± 5.54 mm, outperforming the conventional benchmarks. This work demonstrates that combining generative models and deep learning enables an accurate and robust imaging of epileptogenic zone from MEG recordings with strong sublobar precision, suggesting its added value to enhancing MEG source localization and imaging, and to epilepsy source localization and other clinical applications.

Organization of the epileptogenic zone and signal analysis at seizure onset in patients with drug-resistant epilepsy due to focal cortical dysplasia with mTOR pathway gene mutations-An SEEG study.

Epilepsy surgery in genetic drug-resistant epilepsy is a debated subject as more histological and molecular data are available. We retrospectively collected data from focal drug-resistant epilepsy patients that underwent stereoelectroencephalography (SEEG) invasive recordings. Patients with nonlesional brain imaging or in whom a first epilepsy surgery failed to control seizures were selected. We computed and displayed the intracranial ictal onset activity pattern on structural imaging. Patients underwent epilepsy gene panel testing, next generation sequencing-NGS. Of 113 patients, 13 underwent genetic testing, and in 6 patients, a mechanistic target of rapamycin pathway gene germline mutation (mTOR) was identified. Brain imaging was nonlesional except for one patient in whom two abnormalities suggestive of focal cortical dysplasia (FCD) were found. Patients underwent tailored brain surgery based on SEEG data, tissue analysis revealed FCD and postsurgical outcome was favorable. Our findings are similar to previous case series suggesting that epilepsy surgery can be a treatment option in patients with mTOR pathway mutation. In patients with mTOR pathway mutation, the postsurgical outcome is favorable if complete resection of the epileptogenic zone is performed. Electrophysiological seizure onset patterns in FCDs associated with mTOR pathway mutations display low-voltage fast activity as previously described.

Peri-ictal heart rate changes in patients with epilepsy.

Heart rate (HR) changes associated with seizures are promising biomarkers in epilepsy. The aim of our study is to reveal possible HR changes in the peri-ictal period. Long-term video-EEG monitorization records of generalized and focal epilepsy patients were reviewed. HRs were calculated in the pre-ictal (2 min before the first seizure activity in EEG), ictal (the time from the first seizure activity on the EEG to the end of the seizure), and in the interictal period (at least 2 h before or 12 h after the seizure). Interictal, pre-ictal, and ictal HRs were compared with each other. In addition, it was investigated whether peri-ictal HR changes differ between generalized and focal seizure patients. Focal motor seizures were observed in 21, and generalized tonic-clonic seizures were observed in 18 of 39 (22 female and 17 male) patients studied. HRs in the pre-ictal and ictal periods were significantly higher than in the interictal period. This significant increase in HR was validated separately in both focal and generalized seizure groups and was not different between the two groups. Our study supports previous studies showing the presence of increased peri-ictal HR and also provides new insights by comparing focal and generalized motor seizures. We think that our findings may contribute to the development of early warning signs in epilepsy patients.

Identifying sources of human interictal discharges with travelling wave and white matter propagation.

Interictal epileptiform discharges have been shown to propagate from focal epileptogenic sources as travelling waves or through more rapid white matter conduction. We hypothesize that both modes of propagation are necessary to explain interictal discharge timing delays. We propose a method that, for the first time, incorporates both propagation modes to identify unique potential sources of interictal activity. We retrospectively analysed 38 focal epilepsy patients who underwent intracranial EEG recordings and diffusion-weighted imaging for epilepsy surgery evaluation. Interictal discharges were detected and localized to the most likely source based on relative delays in time of arrival across electrodes, incorporating travelling waves and white matter propagation. We assessed the influence of white matter propagation on distance of spread, timing and clinical interpretation of interictal activity. To evaluate accuracy, we compared our source localization results to earliest spiking regions to predict seizure outcomes. White matter propagation helps to explain the timing delays observed in interictal discharge sequences, underlying rapid and distant propagation. Sources identified based on differences in time of receipt of interictal discharges are often distinct from the leading electrode location. Receipt of activity propagating rapidly via white matter can occur earlier than more local activity propagating via slower cortical travelling waves. In our cohort, our source localization approach was more accurate in predicting seizure outcomes than the leading electrode location. Inclusion of white matter in addition to travelling wave propagation in our model of discharge spread did not improve overall accuracy but allowed for identification of unique and at times distant potential sources of activity, particularly in patients with persistent postoperative seizures. Since distant white matter propagation can occur more rapidly than local travelling wave propagation, combined modes of propagation within an interictal discharge sequence can decouple the commonly assumed relationship between spike timing and distance from the source. Our findings thus highlight the clinical importance of recognizing the presence of dual modes of propagation during interictal discharges, as this may be a cause of clinical mislocalization.

Focal epilepsy without overt epileptogenic lesions: no evidence of microstructural brain tissue damage in multi-parametric quantitative MRI.

In patients with epilepsies of structural origin, brain atrophy and pathological alterations of the tissue microstructure extending beyond the putative epileptogenic lesion have been reported. However, in patients without any evidence of epileptogenic lesions on diagnostic magnetic resonance imaging (MRI), impairment of the brain microstructure has been scarcely elucidated. Using multiparametric quantitative (q) magnetic resonance imaging MRI, we aimed to investigate diffuse impairment of the microstructural tissue integrity in MRI-negative focal epilepsy patients. 27 MRI-negative patients with focal epilepsy (mean age 33.1 ± 14.2 years) and 27 matched healthy control subjects underwent multiparametric qMRI including T1, T2, and PD mapping at 3 T. After tissue segmentation based on synthetic anatomies, mean qMRI parameter values were extracted from the cerebral cortex, the white matter (WM) and the deep gray matter (GM) and compared between patients and control subjects. Apart from calculating mean values for the qMRI parameters across the respective compartments, voxel-wise analyses were performed for each tissue class. There were no significant differences for mean values of quantitative T1, T2, and PD obtained from the cortex, the WM and the deep GM between the groups. Furthermore, the voxel-wise analyses did not reveal any clusters indicating significant differences between patients and control subjects for the qMRI parameters in the respective compartments. Based on the employed methodology, no indication for an impairment of the cerebral microstructural tissue integrity in MRI-negative patients with focal epilepsy was found in this study. Further research will be necessary to identify relevant factors and mechanisms contributing to microstructural brain tissue damage in various subgroups of patients with epilepsy.

Multi-scale structural alterations of the thalamus and basal ganglia in focal epilepsy using 7T MRI.

Focal epilepsy is characterized by repeated spontaneous seizures that originate from cortical epileptogenic zone networks (EZN). Analysis of intracerebral recordings showed that subcortical structures, and in particular the thalamus, play an important role in seizure dynamics as well, supporting their structural alterations reported in the neuroimaging literature. Nonetheless, between-patient differences in EZN localization (e.g., temporal vs. non-temporal lobe epilepsy) as well as extension (i.e., number of epileptogenic regions) might impact the magnitude as well as spatial distribution of subcortical structural changes. Here we used 7 Tesla MRI T1 data to provide an unprecedented description of subcortical morphological (volume, tissue deformation, and shape) and longitudinal relaxation (T1 ) changes in focal epilepsy patients and evaluate the impact of the EZN and other patient-specific clinical features. Our results showed variable levels of atrophy across thalamic nuclei that appeared most prominent in the temporal lobe epilepsy group and the side ipsilateral to the EZN, while shortening of T1 was especially observed for the lateral thalamus. Multivariate analyses across thalamic nuclei and basal ganglia showed that volume acted as the dominant discriminator between patients and controls, while (posterolateral) thalamic T1 measures looked promising to further differentiate patients based on EZN localization. In particular, the observed differences in T1 changes between thalamic nuclei indicated differential involvement based on EZN localization. Finally, EZN extension was found to best explain the observed variability between patients. To conclude, this work revealed multi-scale subcortical alterations in focal epilepsy as well as their dependence on several clinical characteristics.

The role of superficial and deep layers in the generation of high frequency oscillations and interictal epileptiform discharges in the human cortex

Describing intracortical laminar organization of interictal epileptiform discharges (IED) and high frequency oscillations (HFOs), also known as ripples. Defining the frequency limits of slow and fast ripples. We recorded potential gradients with laminar multielectrode arrays (LME) for current source density (CSD) and multi-unit activity (MUA) analysis of interictal epileptiform discharges IEDs and HFOs in the neocortex and mesial temporal lobe of focal epilepsy patients. IEDs were observed in 20/29, while ripples only in 9/29 patients. Ripples were all detected within the seizure onset zone (SOZ). Compared to hippocampal HFOs, neocortical ripples proved to be longer, lower in frequency and amplitude, and presented non-uniform cycles. A subset of ripples (≈ 50%) co-occurred with IEDs, while IEDs were shown to contain variable high-frequency activity, even below HFO detection threshold. The limit between slow and fast ripples was defined at 150 Hz, while IEDs’ high frequency components form clusters separated at 185 Hz. CSD analysis of IEDs and ripples revealed an alternating sink-source pair in the supragranular cortical layers, although fast ripple CSD appeared lower and engaged a wider cortical domain than slow ripples MUA analysis suggested a possible role of infragranularly located neural populations in ripple and IED generation. Laminar distribution of peak frequencies derived from HFOs and IEDs, respectively, showed that supragranular layers were dominated by slower (< 150 Hz) components. Our findings suggest that cortical slow ripples are generated primarily in upper layers while fast ripples and associated MUA in deeper layers. The dissociation of macro- and microdomains suggests that microelectrode recordings may be more selective for SOZ-linked ripples. We found a complex interplay between neural activity in the neocortical laminae during ripple and IED formation. We observed a potential leading role of cortical neurons in deeper layers, suggesting a refined utilization of LMEs in SOZ localization.

Novel variants in established epilepsy genes in focal epilepsy

IntroductionNext generation sequencing (NGS) has greatly expanded our understanding of genetic contributors in multiple epilepsy syndromes, including focal epilepsy. Describing the genetic architecture of common syndromes promises to facilitate the diagnostic process as well as aid in the identification of patients who stand to benefit from genetic testing, but most studies to date have been limited to examining children or adults with intellectual disability. Our aim was to determine the yield of targeted sequencing of 5 established epilepsy genes (DEPDC5, LGI1, SCN1A, GRIN2A, and PCHD19) in an extensively phenotyped cohort of focal epilepsy patients with normal intellectual function or mild intellectual disability, as well as describe novel variants and determine the characteristics of variant carriers. Patients and methodsTargeted panel sequencing was performed on 96 patients with a strong clinical suspicion of genetic focal epilepsy. Patients had previously gone through a comprehensive diagnostic epilepsy evaluation in The Neurology Clinic, University Clinical Center of Serbia. Variants of interest (VOI) were classified using the American College of Medical Genetics and the Association for Molecular Pathology criteria. ResultsSix VOI in eight (8/96, 8.3%) patients were found in our cohort. Four likely pathogenic VOI were determined in six (6/96, 6.2%) patients, two DEPDC5 variants in two patients, one SCN1A variant in two patients and one PCDH19 variant in two patients. One variant of unknown significance (VUS) was found in GRIN2A in one (1/96, 1.0%) patient. Only one VOI in GRIN2A was classified as likely benign. No VOI were detected in LGI1. ConclusionSequencing of only five known epilepsy genes yielded a diagnostic result in 6.2% of our cohort and revealed multiple novel variants. Further research is necessary for a better understanding of the genetic basis in common epilepsy syndromes in patients with normal intellectual function or mild intellectual disability.

N°291 – ERC Galvani – Pilot study 2: Impact of transcranial current stimulation on brain networks by simultaneous stereoelectroencephalography recordings in drug-resistant focal epilepsy patients

N°291 – ERC Galvani – Pilot study 2: Impact of transcranial current stimulation on brain networks by simultaneous stereoelectroencephalography recordings in drug-resistant focal epilepsy patients

Real-World Evaluation of Serum Sodium Levels in Patients With Focal Seizures Treated With Eslicarbazepine Acetate (P4-1.010)

<h3>Objective:</h3> Here we report serum sodium values in patients treated with adjunctive eslicarbazepine acetate (ESL) that were collected in an electronic health record database to assess the effect of ESL on sodium levels in a U.S. real world clinical setting. <h3>Background:</h3> ESL is approved for focal seizure treatment in patients ≥4 years in the US. ESL is a member of the dibenzazepine carboxamide class, a class associated with the development of hyponatremia. In a pooled analysis of 3 clinical trials, incidence of clinically meaningful post-dose sodium levels (≤125 mEq/L) was 1.0% (ESL 800mg), 1.5% (ESL 1200mg) vs 0% (placebo). <h3>Design/Methods:</h3> The electronic health record database was queried to identify patients with a diagnosis of epilepsy (ICD-10 G40*; N=99) or focal epilepsy (ICD-10 G40.0*-G40.2*; n=55), aged ≥4 years, currently treated with ESL, and sodium values available within 3 months prior to ESL initiation (baseline). Serum sodium levels obtained during baseline were compared to levels during ESL treatment (6 months, 1 year). These levels were summarized as the average of all lab values for all patients up to the date of interest and as the single lab value closest to the date of interest (max event) per individual patient. <h3>Results:</h3> Most patients started ESL at 400 or 800 mg/day. The mean serum sodium level for epilepsy patients during baseline was 138.9±8.6 mEq/L and remained stable through 12 months of ESL treatment (138.8±6.2 mEq/L), similar to focal epilepsy patients (baseline, 139.2±9.6 mEq/L; 12 months, 137.5±6.6 mEq/L). These results remained when assessing the max event. 4 focal epilepsy patients demonstrated serum sodium level ≤125 mEq/L at ≥1 timepoints during 12 months of ESL treatment. All observations were made in the context of routine delivery of care. <h3>Conclusions:</h3> Mean serum sodium values in patients treated with ESL did not change from baseline in a real-world clinical setting over 12 months. <b>Disclosure:</b> Mr. Mitchell has received personal compensation for serving as an employee of Sumitovant. Mr. Mitchell has received personal compensation for serving as an employee of Real Chemistry. Mr. Mitchell has stock in Citius Pharmaceuticals Inc. Mr. Mitchell has stock in Spectrum Pharmaceuticals. Mr. Mitchell has received publishing royalties from a publication relating to health care. Mr. Mitchell has received personal compensation in the range of $0-$499 for serving as a Chaplain Candidate with US Army Reserve. Dr. Cantu has received personal compensation for serving as an employee of Sunovion Pharmaceuticals Inc.. Darshan Mehta has received personal compensation for serving as an employee of Sunovion Pharmaceuticals Inc. . Todd Grinnell, PhD has received personal compensation for serving as an employee of Sunovion Pharmaceuticals Inc.. Mr. Smith has nothing to disclose.

Pre-Treatment Seizure Intervals in a Large Prospective Observational Cohort (S44.007)

Pre-Treatment Seizure Intervals in a Large Prospective Observational Cohort (S44.007)

Teaching Neuro Images : A spiritual visual hallucination from a right parieto-occipital seizure

A 59-year-old woman with epilepsy reported episodes of dizziness, blurred vision, and an occasional stereotyped visual hallucination of a guardian angel. She had experienced this recurrent hallucination since childhood, and could draw it in detail (figure 1). MRI brain revealed a right parieto-occipital lesion (figure 2A). Inpatient EEG monitoring captured multiple seizures evolving over the right posterior quadrant. With one typical electrographic seizure (figure 2B), she awakened from stage II sleep, reporting seeing her guardian angel at bedside within 10 seconds of electrographic seizure offset. Among focal epilepsy patients, 0.4%–3.1% report ictal religious experiences.1

Lacosamide as the first add-on therapy in adult patients with focal epilepsy: A multicenter real-world study.

Prospective observations on the effectiveness, safety, tolerance, and influence of comorbidity of add-on lacosamide (LCM) therapy are still lacking, especially for domestic generic LCM in China. In this multicenter real-world study, we aimed to evaluate lacosamide (LCM) as the first add-on therapy in adult Chinese patients with focal epilepsy that had initially been treated with monotherapy. A cohort of consecutive focal epilepsy patients aged over 16 years were enrolled and followed at the multi-epilepsy centers in China. LCM was prescribed as the first add-on therapy. The main outcome measures included seizure frequency and response rate. Data on seizure-free rate, retention rate, scales of depression and anxiety, and adverse events were also collected as additional outcome measures. A total number of 107 adult subjects (60 men, 56.07%) were enrolled. The mean age was 37.16 ± 15.01 years, and the mean age at seizure onset was 312.35 ± 199.97 months. After the LCM add-on therapy, the ≥50% response rates were 76.19, 81.73, 94.12, and 95.79% at the visit at 4 weeks (visit 2), 8 weeks (visit 3), 16 weeks (visit 4), and 24 weeks (visit 5), respectively, compared to the baseline (visit 1). A total of 34 patients (31.78%) had no seizures during the whole follow-up period. The posttreatment emotional performance of the 97 subjects, defined as generalized anxiety disorder (GAD) and Neurological Disorders Depression Inventory (NDDI) scores, was significantly better than the baseline one. Only one patient suffered from mild dizziness. LCM as the first add-on therapy in adult focal epilepsy in China was effective and safe. Further prospective studies with long-term follow-up periods are needed to confirm our present findings. http://www.chictr.org.cn, ChiCTR2100042485.

Sevoflurane-induced high-frequency oscillations, effective connectivity and intraoperative classification of epileptic brain areas

ObjectiveTo determine how sevoflurane anesthesia modulates intraoperative epilepsy biomarkers on electrocorticography, including high-frequency oscillation (HFO) effective connectivity (EC), and to investigate their relation to epileptogenicity and anatomical white matter. MethodsWe studied eight pediatric drug-resistant focal epilepsy patients who achieved seizure control after invasive monitoring and resective surgery. We visualized spatial distributions of the electrocorticography biomarkers at an oxygen baseline, three time-points while sevoflurane was increasing, and at a plateau of 2 minimum alveolar concentration (MAC) sevoflurane. HFO EC was combined with diffusion-weighted imaging, in dynamic tractography. ResultsIntraoperative HFO EC diffusely increased as a function of sevoflurane concentration, although most in epileptogenic sites (defined as those included in the resection); their ability to classify epileptogenicity was optimized at sevoflurane 2 MAC. HFO EC could be visualized on major white matter tracts, as a function of sevoflurane level. ConclusionsThe results strengthened the hypothesis that sevoflurane-activated HFO biomarkers may help intraoperatively localize the epileptogenic zone. SignificanceOur results help characterize how HFOs at non-epileptogenic and epileptogenic networks respond to sevoflurane. It may be warranted to establish a normative HFO atlas incorporating the modifying effects of sevoflurane and major white matter pathways, as critical reference in epilepsy presurgical evaluation.

Impact of an optimized epilepsy surgery imaging protocol for focal epilepsy: A monocentric prospective study.

To evaluate in a real clinical scenario the impact of the ILAE-recommended "Harmonized neuroimaging of epilepsy structural sequences"- HARNESS protocol in patients affected by focal epilepsy. We prospectively enrolled focal epilepsy patients who underwent a structural brain MRI between 2020 and 2021 at Modena University Hospital. For all patients, MRIs were: (a) acquired according to the HARNESS-MRI protocol (H-MRI); (b) reviewed by the same neuroradiology team. MRI outcomes measures were: the number of positive (diagnostic) and negative MRI; the type of radiological diagnosis classified in: (1) Hippocampal Sclerosis; (2) Malformations of cortical development (MCD); (3) Vascular malformations; (4) Glial scars; (5) Low-grade epilepsy-associated tumors; (6) Dual pathology. For each patient we verified for previous MRI (without HARNESS protocol, noH-MRI) and the presence of clinical information in the MRI request form. Then the measured outcomes were reviewed and compared as appropriate. A total of 131 patients with H-MRI were included in the study. 100 patients out from this cohort had at least one previous noH-MRI scan. Of those, 92/100 were acquired at the same Hospital than H-MRI and 71/92 on a 3T scanner. The HARNESS protocol revealed 81 (62%) positive and 50 (38%) negative MRI, and MCD was the most common diagnosis (60%). Among the entire pool of 100 noH-MRI, 36 resulted positive with a significant difference (p < .001) compared to H-MRI. Similar findings were observed when accounting for the expert radiologists (H-MRI = 57 positive; noH-MRI = 33, p < .001) and the scanner field strength (H-MRI 43 = positive, noH-MRI = 23, p < .001), while clinical information were more present in H-MRI (p < .002). The adoption of a standardized and optimized MRI acquisition protocol together with adequate clinical information contribute to identify a higher number of potentially epileptogenic lesions (especially FCD) thus impacting concretely on the clinical management of patients with focal epilepsy.

Periictal water drinking revisited: Occurrence and lateralizing value in surgically confirmed patients with focal epilepsy.

Periictal water drinking (PIWD), which is a rare seizure-related autonomic behavior, has been reported in temporal lobe epilepsy (TLE) but only rarely in extra-TLE. Additionally, the lateralizing value of PIWD is controversial. We aimed to clarify the occurrence and lateralizing value of PIWD in patients with focal epilepsy. This retrospective study included 240 focal epilepsy patients aged >10 years with a favorable postoperative seizure outcome (Engel class I). PIWD was defined as water drinking behavior during a seizure or within 2 min in the postictal phase. The occurrence of PIWD documented on video-electroencephalogram monitoring was assessed. The lateralizing value of PIWD was analyzed among patients whose language dominant hemisphere was identified. Twenty-three (9.5%) patients exhibited PIWD. PIWD occurred more frequently in frontal lobe epilepsy (FLE; eight of 41 patients, 19.5%) than in TLE (15 of 188 patients, 8%). The occurrence of PIWD was significantly different between FLE and extra-FLE (P=0.035), with a low positive predictive value (34.8%). In FLE with PIWD, all but one patient underwent resective surgery involving the medial frontal lobe. In 194 patients whose language dominant hemisphere was determined, the lateralizing value of PIWD in FLE and TLE showed no statistical significance (P=0.69 and P=0.27, respectively). Periictal water drinking occurred more often in FLE than TLE. Thus, PIWD might not be a specific periictal symptom in TLE. There was no evidence for the lateralizing value of PIWD in FLE and TLE. These findings can provide useful clinical clues for preoperative evaluations to estimate the epileptogenic zone based on seizure semiology and allow for a better understanding of pathophysiological insights into PIWD.

Responsive neurostimulation with low-frequency stimulation.

Deep brain stimulation and responsive neurostimulation (RNS) use high-frequency stimulation (HFS) per the pivotal trials and manufacturer-recommended therapy protocols. However, not all patients respond to HFS. In this retrospective case series, 10 patients implanted with the RNS System were programmed with low-frequency stimulation (LFS) to treat their seizures; nine of these patients were previously treated with HFS (100 Hz or greater). LFS was defined as frequency < 10Hz. Burst duration was increased to at least 1000 ms. With HFS, patients had a median seizure reduction (MSR) of 13% (interquartile range [IQR] = -67 to 54) after a median of 19 months (IQR=8-49). In contrast, LFS was associated with a 67% MSR (IQR=13-95) when compared to HFS and 76% MSR (IQR=43-91) when compared to baseline prior to implantation. Charge delivered per hour and pulses per day were not significantly different between HFS and LFS, although time stimulated per day was longer for LFS (228 min) than for HFS (7min). There were no LFS-specific adverse effects reported by any of the patients. LFS could represent an alternative, effective method for delivering stimulation in focal drug-resistant epilepsy patients treated with the RNS System.

Epileptic diathesis: An EEG-LORETA study

ObjectiveEpileptic diathesis is an inherited neurophysiological trait that contributes to the development of all types of epilepsy. The amount of resting-state electroencephalography (EEG) theta activity is proportional to the degree of cortical excitability and epileptic diathesis. Our aim was to explore the amount and topographic distribution of theta activity in epilepsy groups. We hypothesized that the anatomical distribution of increased theta activity is independent of the epilepsy type. MethodsPatients with unmedicated idiopathic generalized epilepsy (IGE, n = 92) or focal epilepsy (FE, n = 149) and non-seizure patients with mild to moderate cerebral lesions (NONEP, n = 99) were compared to healthy controls (NC, n = 114). We analysed artifact-free EEG activity and defined multiple distributed sources of theta activity in the source space via low resolution electromagnetic tomography software. Age-corrected and Z-transformed theta values were compared across the groups. ResultsThe rank of increased theta activity was IGE > FE > NONEP > NC. Both epilepsy groups showed significantly more theta activity than did the NC group. Maximum theta abnormality occurred in the medial-basal prefrontal and anterior temporal cortex in both epilepsy groups. ConclusionsWe confirmed the hypothesis outlined above. SignificanceThe common topographical pattern of increased EEG theta activity is correlated with epileptic diathesis, regardless of the epilepsy type.

Cognitive profiles in pediatric unilobar vs. multilobar epilepsy.

We aimed to determine how cognitive impairment relates to the extent of the presumed epileptogenic zone in pediatric focal epilepsies. We analyzed the cognitive functions in unilobar compared to multilobar focal epilepsy patients that underwent neuropsychological testing at a tertiary epilepsy center. We assessed cognitive functions of pediatric focal epilepsy patients with the German version of the Wechsler Intelligence Scales that measures full-scale IQ and subcategories. We assessed differences in IQ and epilepsy-related variables between unilobar and multilobar epilepsy patients. We included 62 patients (37 unilobar, 25 multilobar), aged 10.6±3.7 years. Full-scale IQ values were significantly higher in unilobar (93.6±17.7, 95% CI 87.7-99.6) than in multilobar epilepsy patients (77.3±17.2, 95% CI 69.3-85.0; p=0.001). In all but one IQ subcategory (working memory), significantly higher values were measured in unilobar than in multilobar epilepsy patients. The proportion of unilobar epilepsy patients with severe cognitive impairment (8.3%) and below-average intelligence (30.5%) was lower compared to multilobar epilepsy patients (47.6% and 61.9%; p=0.002 and p=0.021, respectively). Epilepsy onset occurred earlier in multilobar (4.0 years, 95% CI 2.6-5.5, SD±3.4 years) than in unilobar epilepsy patients (7.0 years, 95% CI 5.5-8.5, SD±4.4 years, p=0.008). Pediatric multilobar epilepsy patients face more cognitive issues than unilobar epilepsy patients on average. Our findings should help to identify children and adolescents who are most at risk for impaired cognitive development. A limitation of our study is the simple division into unilobar and multilobar epilepsies, with no specific account being taken of etiology/epilepsy syndrome, which can have a profound effect on cognition.

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.