Search

Epilepsy’s impact on cardiovascular function and autonomic regulation, including heart-rate variability, is complex and may contribute to sudden unexpected death in epilepsy (SUDEP). Lateralization of autonomic control in the brain remains the subject of debate; nevertheless, ultra-short-term heart-rate variability (HRV) analysis is a useful tool for understanding the pathophysiology of autonomic dysfunction in epilepsy patients. A retrospective study reviewed medical records of patients with temporal lobe epilepsy who underwent presurgical evaluations. Data from 75 patients were analyzed and HRV indices were extracted from electrocardiogram recordings of preictal, ictal, and postictal intervals. Various HRV indices were calculated, including time domain, frequency domain, and nonlinear indices, to assess autonomic function during different seizure intervals. The study found significant differences in HRV indices based on hemispheric laterality, language dominancy, hippocampal atrophy, amygdala enlargement, sustained theta activity, and seizure frequency. HRV indices such as the root mean square of successive differences between heartbeats, pNN50, normalized low-frequency, normalized high-frequency, and the low-frequency/high-frequency ratio exhibited significant differences during the ictal period. Language dominancy, hippocampal atrophy, amygdala enlargement, and sustained theta activity were also found to affect HRV. Seizure frequency was correlated with HRV indices, suggesting a potential relationship with the risk of SUDEP.

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) has been widely used as an effective treatment for refractory temporal lobe epilepsy. Despite its promising clinical outcome, the exact mechanism of how ANT-DBS alleviates seizure severity has not been fully understood, especially at the cellular level. To assess effects of DBS, the present study examined electroencephalography (EEG) signals and locomotor behavior changes and conducted immunohistochemical analyses to examine changes in neuronal activity, number of neurons, and neurogenesis of inhibitory neurons in different hippocampal subregions. ANT-DBS alleviated seizure activity, abnormal locomotor behaviors, reduced theta-band, increased gamma-band EEG power in the interictal state, and increased the number of neurons in the dentate gyrus (DG). The number of parvalbumin- and somatostatin-expressing inhibitory neurons was recovered to the level in DG and CA1 of naïve mice. Notably, BrdU-positive inhibitory neurons were increased. In conclusion, ANT-DBS not only could reduce the number of seizures, but also could induce neuronal changes in the hippocampus, which is a key region involved in chronic epileptogenesis. Importantly, our results suggest that ANT-DBS may lead to hippocampal subregion-specific cellular recovery of GABAergic inhibitory neurons.

OBJECTIVE The anterior thalamic nucleus (ATN) is a common target for deep brain stimulation (DBS) for the treatment of drug-refractory epilepsy. However, no atlas-based optimal DBS (active contacts) target within the ATN has been definitively identified. The object of this retrospective study was to analyze the relationship between the active contact location and seizure reduction to establish an atlas-based optimal target for ATN DBS. METHODS From among 25 patients who had undergone ATN DBS surgery for drug-resistant epilepsy between 2016 and 2018, those who had follow-up evaluations for more than 1 year were eligible for study inclusion. After an initial stimulation period of 6 months, patients were classified as responsive (≥ 50% median decrease in seizure frequency) or nonresponsive (< 50% median decrease in seizure frequency) to treatment. Stimulation parameters and/or active contact positions were adjusted in nonresponsive patients, and their responsiveness was monitored for at least 1 year. Postoperative CT scans were coregistered nonlinearly with preoperative MR images to determine the center coordinate and atlas-based anatomical localizations of all active contacts in the Montreal Neurological Institute (MNI) 152 space. RESULTS Nineteen patients with drug-resistant epilepsy were followed up for at least a year following bilateral DBS electrode implantation targeting the ATN. Active contacts located more adjacent to the center of gravity of the anterior half of the ATN volume, defined as the anterior center (AC), were associated with greater seizure reduction than those not in this location. Intriguingly, the initially nonresponsive patients could end up with much improved seizure reduction by adjusting the active contacts closer to the AC at the final postoperative follow-up. CONCLUSIONS Patients with stimulation targeting the AC may have a favorable seizure reduction. Moreover, the authors were able to obtain additional good outcomes after electrode repositioning in the initially nonresponsive patients. Purposeful and strategic trajectory planning to target this optimal region may predict favorable outcomes of ATN DBS.

Treatments for epilepsy include pharmacotherapy or surgery. Recently, focused ultrasound stimulation has been investigated as a promising non-invasive neuromodulation tool for neurological disorders, including epilepsy. To investigate the neuronal dynamics in epilepsy, we acutely stimulated 29 Sprague–Dawley rats to low-intensity focused ultrasound stimulation (LIFUS) three times for 3 minutes. Pentylenetetrazol (PTZ) was injected into the abdominal cavity of the anesthetized rats to induce epilepsy. During the anesthesia, the electroencephalography (EEG) signal was measured and analyzed for 1 h in groups of animals untreated (sham) and treated with LIFUS. The EEG signal was quantitatively processed to show the different characteristics of the frequency change over time and of the band power between sham and treated groups. Histological analyses (Nissl, Iba1, c-Fos, and GAD65) measured the degree of staining of expression factors to confirm the effect of the stimulation on seizure suppression. These results suggest that repetitive LIFUS can effectively reduce epileptic seizure activity by attenuating theta and beta-band oscillation in a PTZ-induced rat model. LIFUS can potentially facilitate hippocampal and cortical cellular recovery by augmenting GABAergic inhibitory neurons via its anti-seizure effect.

This study aims to compare directed transfer function (DTF), which is an effective connectivity analysis, derived from scalp EEGs between responder and nonresponder groups implanted with vagus-nerve stimulation (VNS). Twelve patients with drug-resistant epilepsy (six responders and six nonresponders) and ten controls were recruited. A good response to VNS was defined as a reduction of ≥50% in seizure frequency compared with the presurgical baseline. DTF was calculated in five frequency bands (delta, theta, alpha, beta, and broadband) and seven grouped electrode regions (left and right frontal, temporal, parieto-occipital, and midline) in three different states (presurgical, stimulation-on, and stimulation-off states). Responders showed presurgical nodal strength close to the control group in both inflow and outflow, whereas nonresponders exhibited increased inward and outward connectivity measures. Nonresponders also had increased inward and outward connectivity measures in the various brain regions and various frequency bands assessed compared with the control group when the stimulation was on or off. Our study demonstrated that the presurgical DTF profiles of responders were different from those of nonresponders. Moreover, a presurgical normal DTF profile may predict good responsiveness to VNS.

BackgroundConventional neurostimulations to treat epilepsy have adverse effects caused by post-inhibitory rebound excitations. Although ultrasound brain stimulation is feasible in inducing anticonvulsant effects, its association with paradoxical rebound excitations is unknown.ObjectiveThis study aimed at demonstrating rebound excitations with transcranial focused ultrasound. The modulations of epileptiform activities toward both suppressive and excitatory responses were investigated by changing ultrasonic transmit sequences.MethodsIn a pentylenetetrazol-injected acute epilepsy rat model, transcranial focused ultrasound stimulation was applied on the thalamus to modulate epileptiform activities. The parameters differentiated for pulse sequences were the pulse length, pulse pressure, and interval between the pulses. Sonication effects were assessed by electroencephalography (n=38), immuno-histochemical analysis (n=24), and optical measurement of cerebral blood volume changes (n=18).ResultsWhile ultrasonic patterns of stimuli at long intervals showed antiepileptic effects on electroencephalography, those at short intervals showed rebound excitatory responses followed by inhibitory activities. Further, suppressive states induced by inhibitory stimulations were transformed into excitatory states by applying a consecutive series of short bursts at higher acoustic pressure. Cerebral blood volume changes demonstrated consistent results with electroencephalography. Immunohistochemistry revealed that both inhibitory and excitatory neuronal cells were activated to generate rebound excitatory conditions, while inhibitory cells were activated for suppressive conditions.ConclusionsIn our study, variations in ultrasound stimulation patterns could modulate epileptiform activities in both upregulated and downregulated directions.

In recent years, electroceuticals have been spotlighted as an emerging treatment for various severe chronic brain diseases, owing to their intrinsic advantage of electrical interaction with the brain, which is the most electrically active organ. However, the majority of research has verified only the short-term efficacy through acute studies in laboratory tests owing to the lack of a reliable miniaturized platform for long-term animal studies. The construction of a sufficient integrated system for such a platform is extremely difficult because it requires multi-disciplinary work using state-of-the-art technologies in a wide range of fields. In this study, we propose a complete system of an implantable platform for long-term preclinical brain studies. Our proposed system, the extra-cranial brain activator (ECBA), consists of a titanium-packaged implantable module and a helmet-type base station that powers the module wirelessly. The ECBA can also be controlled by a remote handheld device. Using the ECBA, we performed a long-term non-anesthetic study with multiple canine subjects, and the resulting PET-CT scans demonstrated remarkable enhancement in brain activity relating to memory and sensory skills. Furthermore, the histological analysis and high-temperature aging test confirmed the reliability of the system for up to 31 months. Hence, the proposed ECBA system is expected to lead a new paradigm of human neuromodulation studies in the near future.

The significance of interictal epileptiform discharges (IEDs) observed in the extratemporal lobe has not been fully evaluated in patients with mesial temporal lobe epilepsy (MTLE). This study aimed to evaluate the surgical outcomes, clinical features, and functional neuroimaging characteristics of patients in relation to the presence or absence of extratemporal IED in MTLE with hippocampal sclerosis (HS).A total of 165 patients with HS-induced MTLE who had undergone anterior temporal lobectomy were enrolled and stratified into the extratemporal interictal epileptiform discharges (ETD) and the temporal lobe discharges (TD) groups. We analyzed the differentiating features of pre- and postsurgical evaluation data between the two groups. For outcome assessment, only patients with a follow-up of at least 2 years were enrolled, and the outcomes were classified based on Engel classification.The ETD group showed extensive glucose hypometabolism involving the temporal lobe and extratemporal regions (p 0.001), and IEDs were observed bilaterally or contralateral to the ictal focus (p = 0.02). However, there was no difference in the surgical outcomes between the two groups. On multivariate analysis, statistically significant variables related to ETD occurrence including seizure onset age were not identified nevertheless.Our results indicate that ETD had a surgical outcome comparable to that of TD. Therefore, a surgical intervention need not be delayed even if extratemporal IED may be found in presurgical long-term scalp EEG monitoring.

Understanding the neurovascular coupling (NVC) underlying hemodynamic changes in epilepsy is crucial to properly interpreting functional brain imaging signals associated with epileptic events. However, how excitatory and inhibitory neurons affect vascular responses in different epileptic states remains unknown. We conducted real-time in vivo measurements of cerebral blood flow (CBF), vessel diameter, and excitatory and inhibitory neuronal calcium signals during recurrent focal seizures. During preictal states, decreases in CBF and arteriole diameter were closely related to decreased γ-band local field potential (LFP) power, which was linked to relatively elevated excitatory and reduced inhibitory neuronal activity levels. Notably, this preictal condition was followed by a strengthened ictal event. In particular, the preictal inhibitory activity level was positively correlated with coherent oscillating activity specific to inhibitory neurons. In contrast, ictal states were characterized by elevated synchrony in excitatory neurons. Given these findings, we suggest that excitatory and inhibitory neurons differentially contribute to shaping the ictal and preictal neural states, respectively. Moreover, the preictal vascular activity, alongside with the γ-band, may reflect the relative levels of excitatory and inhibitory neuronal activity, and upcoming ictal activity. Our findings provide useful insights into how perfusion signals of different epileptic states are related in terms of NVC.

Transcranial electrical stimulation (TES) is a widely accepted neuromodulation modality for treating brain disorders. However, its clinical efficacy is fundamentally limited due to the current shunting effect of the scalp and safety issues. A newer electrical stimulation technique called subcutaneous electrical stimulation (SES) promises to overcome the limitations of TES by applying currents directly at the site of the disorder through the skull. While SES seems promising, the electrophysiological effect of SES compared to TES is still unknown, thus limiting its broader application. Here we comprehensively analyze the SES and TES to demonstrate the effectiveness and advantages of SES. Beagles were bilaterally implanted with subdural strips for intracranial electroencephalography and electric field recording. For the intracerebral electric field prediction, we designed a 3D electromagnetic simulation framework and simulated TES and SES. In the beagle model, SES induces three to four-fold larger cerebral electric fields compared to TES, and significant changes in power ratio of brainwaves were observed only in SES. Our prediction framework suggests that the field penetration of SES would be several-fold larger than TES in human brains. These results demonstrate that the SES would significantly enhance the neuromodulatory effects compared to conventional TES and overcome the TES limitations.

Levetiracetam is a new antiepileptic drug (AED) used for treating and preventing partial or generalized seizures. The usefulness of levetiracetam therapeutic drug monitoring (TDM) is related to inter- or intra-individual pharmacokinetic variability, drug interactions, and patient noncompliance. We aimed to investigate the levetiracetam TDM status in Korean epilepsy patients. Serum trough levetiracetam concentrations were measured using liquid chromatography–tandem mass spectrometry in 710 samples from 550 patients. The median (range) daily and weight-adjusted levetiracetam doses were 1500 (20–5000) mg and 25.5 (3.03–133.0) mg/kg, respectively. Patients on levetiracetam monotherapy constituted only 19.5% of the population, while 30.1% were on co-medication with valproate and 56.0% with enzyme-inducing AEDs (EIAEDs). Observed levetiracetam concentrations were widely distributed, ranging 0.8–95 mg/L, with a median of 17.3 mg/L. Levetiracetam concentrations were therapeutic, supra-therapeutic, and sub-therapeutic in 58.5% (n = 393), 11.6% (n = 78), and 29.9% (n = 201) of samples, respectively. There was a strong correlation between weight-adjusted levetiracetam dosage and concentrations (ρ = 0.6896, p < 0.0001). In this large-scale clinical study, a large inter-individual difference in levetiracetam pharmacokinetics was observed, and levetiracetam concentrations were influenced by EIAEDs. For individual dose adjustments and monitoring compliance, routine levetiracetam TDM is needed in epilepsy patients.

Deep brain stimulation (DBS) has provided new treatment options for refractory epilepsy; however, treatment outcomes of DBS in refractory epilepsy patients previously treated with vagus nerve stimulation (VNS) have not been clarified. Herein, treatment outcomes of DBS of the anterior nucleus of the thalamus (ANT-DBS) in patients who had previously experienced VNS failure are reported. Seven patients who had previously experienced VNS failure underwent ANT-DBS device implantation. VNS was turned off before DBS device implantation. Monthly seizure counts starting from baseline to 12–18 months after DBS were analyzed. Five (71.3%) of the 7 patients experienced a >50% reduction of seizure counts after DBS; 1 responder reached a seizure-free status after DBS therapy. Of the 2 nonresponders, 1 subject showed improvement in seizure strength and duration, which lessened the impact of the seizures on the patient’s quality of life. This is the first study in which favorable outcomes of ANT-DBS surgery were observed in individual patients with refractory epilepsy who had not responded to prior VNS. Further studies with a larger number of subjects and longer follow-up period are needed to confirm the feasibility of ANT-DBS in patients who have previously experienced VNS failure.

Background and Objectives: Abnormal epileptic discharges in the brain can affect the central brain regions that regulate autonomic activity and produce cardiac symptoms, either at onset or during propagation of a seizure. These autonomic alterations are related to cardiorespiratory disturbances, such as sudden unexpected death in epilepsy. This study aims to investigate the differences in cardiac autonomic function between patients with temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE) using ultra-short-term heart rate variability (HRV) analysis around seizures. Materials and Methods: We analyzed electrocardiogram (ECG) data recorded during 309 seizures in 58 patients with epilepsy. Twelve patients with FLE and 46 patients with TLE were included in this study. We extracted the HRV parameters from the ECG signal before, during and after the ictal interval with ultra-short-term HRV analysis. We statistically compared the HRV parameters using an independent t-test in each interval to compare the differences between groups, and repeated measures analysis of variance was used to test the group differences in longitudinal changes in the HRV parameters. We performed the Tukey–Kramer multiple comparisons procedure as the post hoc test. Results: Among the HRV parameters, the mean interval between heartbeats (RRi), normalized low-frequency band power (LF) and LF/HF ratio were statistically different between the interval and epilepsy types in the t-test. Repeated measures ANOVA showed that the mean RRi and RMSSD were significantly different by epilepsy type, and the normalized LF and LF/HF ratio significantly interacted with the epilepsy type and interval. Conclusions: During the pre-ictal interval, TLE patients showed an elevation in sympathetic activity, while the FLE patients showed an apparent increase and decrease in sympathetic activity when entering and ending the ictal period, respectively. The TLE patients showed a maintained elevation of sympathetic and vagal activity in the pos-ictal interval. These differences in autonomic cardiac characteristics between FLE and TLE might be relevant to the ictal symptoms which eventually result in SUDEP.

A novel minimally invasive wirelessly powered medical device, a magnetic induction extra-cranial brain stimulation (MI-ECBS) system is implemented for treating neurological disorders, Alzheimer’s disease (AD) and Epilepsy. The proposed system provides 2 different types of clinically significant stimulation waveforms for the therapy. For high frequency stimulation (HFS), we used 1mA, 10Hz, rectangular, charge balanced (0.5msec pulse width) pulses for 3sec with 21sec rest (total 600 pulses). Subsequently, under same configuration, a low frequency stimulation (LFS; 1Hz, 600 pulses) protocol was applied to canine-animal models. As a result, complementary neuro-modulation, facilitation and an inhibition are successfully demonstrated with an EEG power spectrum monitoring and the stimulation delivery efficacy is enhanced to 39.57x comparing to conventional transcutaneous direct current stimulation (tDCS).

Background and Objective: Epilepsy is one of the most common neurologic diseases worldwide, and 30% of the patients live with uncontrolled seizures. For the safety of patients with epilepsy, an automatic seizure detection algorithm for continuous seizure monitoring in daily life is important to reduce risks related to seizures, including sudden unexpected death. Previous researchers applied machine learning to detect seizures with EEG, but the epileptic EEG waveform contains subtle changes that are difficult to identify. Furthermore, the imbalance problem due to the small proportion of ictal events caused poor prediction performance in supervised learning approaches. This study aimed to present a personalized deep learning-based anomaly detection algorithm for seizure monitoring with behind-the-ear electroencephalogram (EEG) signals. Methods: We collected behind-the-ear EEG signals from 16 patients with epilepsy in the hospital and used them to develop and evaluate seizure detection algorithms. We modified the variational autoencoder network to learn the latent representation of normal EEG signals and performed seizure detection by measuring the anomalies in EEG signals using the trained network. To personalize the algorithm, we also proposed a method to calibrate the anomaly score for each patient by comparing the representations in the latent space. Results: Our proposed algorithm showed a sensitivity of 90.4% with a false alarm rate of 0.83 per hour without personal calibration. On the other hand, the one-class support vector machine only showed a sensitivity of 84.6% with a false alarm rate of 2.17 per hour. Furthermore, our proposed model with personal calibration achieved 94.2% sensitivity with a false alarm rate of 0.29 while detecting 49 of 52 ictal events. Conclusion: We proposed a novel seizure detection algorithm with behind-the-ear EEG signals via semi-supervised learning of an anomaly detecting variational autoencoder and personalization method of anomaly scoring by comparing latent representations. Our approach achieved improved seizure detection with high sensitivity and a lower false alarm rate.

Background and purpose Implantation of deep brain stimulation (DBS) electrodes in the anterior nucleus of the thalamus (ANT) or the centromedian nucleus (CM), for the treatment of refractory epilepsy, is technically demanding. To enhance the accuracy of electrode placement within the ANT and CM, we analyzed our experience with electrode revision surgery in ANT and CM DBS and investigated the cause of misplacement and verifying methods for accurate placement. Methods A retrospective analysis of the medical records of 23 patients who underwent DBS for refractory epilepsy during the period from 2013 to 2016 was performed. Results Misplacement of the electrode occurred in 1 (25%) of 4 ANT DBS and 2 (14.3%) of 14 patients with CM DBS performed in our institute, and revision surgery was performed in three patients. During this period, we performed three revision surgeries for misplaced electrodes in ANT DBS that were performed at another hospital. Therefore, we performed six revision surgeries (four in ANT, two in CM) for mistargeted DBS electrodes for thalamic DBS. Transventricular lead placement and an anatomical targeting of the ANT was the cause of misplacement in the ANT and intraoperative brain shift was found to be the cause in the CM. For verification of the location of lead placement, magnetic resonance imaging (MRI) was superior to computed tomography and electroencephalography (EEG). Conclusions To reduce the rate of electrode misplacement for refractory epilepsy, image-based targeting of the ANT according to individual anatomical variation, and efforts to minimize intraoperative brain shift are essential. To verify the location of the electrode, MRI examination is mandatory in DBS for refractory epilepsy.

Seong Hoon Kim,1 Sung Chul Lim,1 Dong Won Yang,1 Jeong Hee Cho,1 Byung-Chul Son,2 Jiyeon Kim,3 Seung Bong Hong,4 Young-Min Shon4 1Department of Neurology, 2Department of Neurosurgery, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seoul, 3Department of Neurology, Korea University Ansan Hospital, College of Medicine, Korea University, Ansan, 4Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Objective: Deep brain stimulation (DBS) of the centromedian thalamic nucleus (CM) can be an alternative treatment option for intractable epilepsy patients. Since CM may be involved in widespread cortico-subcortical networks, identification of the cortical sub-networks specific to the target stimuli may provide further understanding on the underlying mechanisms of CM DBS. Several brain structures have distinguishing brain connections that may be related to the pivotal propagation and subsequent clinical effect of DBS.Methods: To explore core structures and their connections relevant to CM DBS, we applied electroencephalogram (EEG) and diffusion tensor imaging (DTI) to 10 medically intractable patients – three generalized epilepsy (GE) and seven multifocal epilepsy (MFE) patients unsuitable for resective surgery. Spatiotemporal activation pattern was mapped from scalp EEG by delivering low-frequency stimuli (5Hz). Structural connections between the CM and the cortical activation spots were assessed using DTI.Results: We confirmed an average 72% seizure reduction after CM DBS and its clinical efficiency remained consistent during the observation period (mean 21months). EEG data revealed sequential source propagation from the anterior cingulate, followed by the frontotemporal regions bilaterally. In addition, maximal activation was found in the left cingulate gyrus and the right medial frontal cortex during the right and left CM stimulation, respectively. From DTI data, we confirmed concrete structural connections between CM and those maximal activation spots identified from EEG data.Conclusion: These results suggest that the anterior cingulate can be a core cortical structure for the bilateral propagation of CM stimulation. Our DTI findings also indicate that the propagation of CM stimulation may rely upon integrity of structural connections between CM and these key cortical regions. Structures and their connections found in this study may be relevant in the interpretation of the clinical outcomes of CM DBS. Keywords: deep brain stimulation, intractable epilepsy, centromedian thalamic nucleus, structural connectivity, cortical recruiting response, anterior cingulate

As transcranial electrical stimulation (tES) is an emerging and promising technique for neuromodulation, we developed a novel device; wirelessly-powered, extracranial brain activator (ECBA), which is mounted subcutaneously, and its neuromodulation effect was investigated. The oscillatory changes in electrocorticography (EcoG) were analyzed from two types of stimulation. Two weeks prior to the recording experiment, we underwent surgery for implantation of subdural strips and ECBA module over centroparietal regions of anesthetized beagles. Low-frequency stimulation (LFS) and subsequent high-frequency stimulation (HFS) protocols (600 pulses respectively) were applied. Then, the power changes before and after each stimulation in five different bands were compared. A significantly larger voltage difference with subcutaneous than transcutaneous stimulation measured at EcoG channels indicated a substantial current attenuation between the skin and skull. Compared with the baseline, all subjects showed consistently decreased delta power and increased gamma power after HFS. LFS also induced a similar, but opposite, pattern of power change in four beagles. The results from this study indicate that LFS and HFS with our novel ECBA can consistently and effectively modulate neural activity of the cortex, inducing neural inhibition and facilitation functions, respectively. Future studies are necessary to further ensuring a consistent efficacy and long-term safety.

Objective Focal cortical dysplasia (FCD) represents a heterogeneous group of disorders of the cortical formation and is one of the most common causes of epilepsy. Magnetic resonance imaging (MRI) is the modality of choice for detecting structural lesions, and the surgical prognosis in patients with MR lesions is favorable. However, the surgical prognosis of patients with MR-negative FCD is unknown. We aimed to evaluate the long-term surgical outcomes and prognostic factors in MR-negative FCD patients through comprehensive presurgical data. Methods We retrospectively reviewed data from 719 drug-resistant epilepsy patients who underwent resective surgery and selected cases in which surgical specimens were pathologically confirmed as FCD Type I or II. If the epileptogenic focus and surgical specimens were obtained from brain areas with a normal MRI appearance, they were classified as MR-negative FCD. Surgical outcomes were evaluated at 2 and 5 years, and clinical, neurophysiological, and neuroimaging data of MR-negative FCD were compared to those of MR-positive FCD. Results Finally, 47 MR-negative and 34 MR-positive FCD patients were enrolled in the study. The seizure-free rate after surgery (Engel classification I) at postoperative 2 year was 59.5% and 64.7% in the MR-negative and positive FCD groups, respectively (p = 0.81). This rate decreased to 57.5% and 44.4% in the MR-negative and positive FCD groups (p = 0.43) at postoperative 5 years. MR-negative FCD showed a higher proportion of FCD type I (87.2% vs. 50.0%, p = 0.001) than MR-positive FCD. Unilobar cerebral perfusion distribution (odds ratio, OR 5.41) and concordance of interictal epileptiform discharges (OR 5.10) were significantly associated with good surgical outcomes in MR-negative FCD. Conclusion In this study, MR-negative and positive FCD patients had a comparable surgical prognosis, suggesting that comprehensive presurgical evaluations, including multimodal neuroimaging studies, are crucial for obtaining excellent surgical outcomes even in epilepsy patients with MR-negative FCD.

Jiyeon Kim,1 Seong Hoon Kim,2 Sung Chul Lim,2 Woojun Kim,2 Young-Min Shon3 1Department of Neurology, Korea University Ansan Hospital, College of Medicine, Korea University, Ansan, 2Department of Neurology, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seocho-gu, 3Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Purpose: To evaluate the evolution of nonlesional temporal lobe epilepsy (TLE-NL) in patients treated exclusively with antiepileptic drugs and to elucidate clinical phenotypes related to the prognosis of these patients.Methods: Clinical, radiological, and electroencephalographic (EEG) findings in 84 patients with TLE-NL were reviewed. A good response group (GRG) and a poor response group (PRG) were defined if the duration of their seizure-free period was >1 year, or

Background and Objective: Epilepsy is a neurological disorder of the brain, which involves recurrent seizures. An encephalogram (EEG) is a gold standard method in the detection and analysis of epileptic seizures. However, the standard EEG recording system is too obstructive to be used in daily life. Behind-the-ear EEG is an alternative approach to record EEG conveniently. Previous researchers applied machine learning to automatically detect seizures with EEG, but the epileptic EEG waveform contains subtle changes that are difficult to be identified. Furthermore, the extremely small proportion of ictal events in the long-term monitoring may cause the imbalance problem and, consequently, poor prediction performance in supervised learning approaches. In this study, we present an automatic seizure detection algorithm with a generative adversarial network (GAN) trained by unsupervised learning and evaluated it with behind-the-ear EEG. Methods: We recorded behind-the-ear EEGs from 12 patients who have various types of epilepsy. Data were reviewed separately by two epileptologists, who determined the onsets and ends of seizures. First, we conducted unsupervised learning with the normal records for the GAN to learn the representation of normal states. Second, we performed automatic seizure detection with the trained GAN as an anomaly detector. Last, we combined the Gram matrix with other anomaly losses to improve detection performance. Results: The proposed approach achieved detection performance with an area under the receiver operating curve of 0.939 and sensitivity of 96.3% with a false alarm rate of 0.14 per hour in the test dataset. In addition, we confirmed distinguishability with the distribution of the anomaly scores in terms of EEG frequency bands. Conclusions: It is expected that the proposed anomaly detection via GAN with the behind-the-ear EEG can be effectively used for long-term seizure monitoring in daily life.

The effects of repetitive transcranial magnetic stimulation (rTMS) on epilepsy remain unclear. This study was performed to investigate the effects of low-frequency rTMS on non-lesional focal epilepsy. This was a prospective open-label longitudinal study with four patients with multi-drug-resistant non-lesional focal epilepsy and no control group. The patients received daily doses of 900 pulses of 0.5-Hz stimulation for 10 days over the epileptic foci in neocortical areas determined by electrical source analysis. The outcomes were measured in terms of seizure reduction. The incidences of seizures were measured at baseline (4 weeks), intervention (2 weeks), and follow up (8 weeks). Seizure reduction was observed in three of four subjects. The effects of rTMS persisted over a follow-up period of 8 weeks. One of the four patients did not respond to rTMS and showed no seizure reduction. The low frequency rTMS would be an effective treatment for non-lesional focal refractory epilepsy, may be an adjunctive treatment with conventional medical treatment for refractory epilepsy. These results are therefore useful for planning treatment strategies for patients with refractory epilepsy, as well as for treatment of epilepsy.

The long-term (5-years) antiepileptic effect of deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) against refractory epilepsy has been reported. However, experience with ANT DBS for epilepsy is limited, and so hardware complications and technical problems related to ANT DBS are unclear. We report the case of a 57-year-old male who underwent re-implantation of a DBS lead in the left ANT because of lead migration into the third ventricle detected 8 years after the first DBS, and which was caused by the significant enlargement of the lateral and third ventricles. After re-implantation, the patient showed a mechanically-related antiepileptic effect and a prominent driving response of the electroencephalography was verified. We speculate that progressive dilatation of the ventricle and shallow, insufficient implantation of the lead during the initial ANT DBS may have caused migration of the DBS lead. Because dilatation of the ventricle could progress years after DBS in a patient with chronic epilepsy, regular follow-up imaging is warranted in ANT DBS patients with an injured, atrophied brain.

Background— Modern treatments have improved the survival rate following cardiac arrest, but prognostication remains a challenge. We examined the prognostic value of continuous electroencephalography according to time by performing amplitude-integrated electroencephalography on patients with cardiac arrest receiving therapeutic hypothermia. Methods and Results— We prospectively studied 130 comatose patients treated with hypothermia from September 2010 to April 2013. We evaluated the time to normal trace (TTNT) as a neurological outcome predictor and determined the prognostic value of burst suppression and status epilepticus, with a particular focus on their time of occurrence. Fifty-five patients exhibited a cerebral performance category score of 1 to 2. The area under the curve for TTNT was 0.97 (95% confidence interval, 0.92–0.99), and the sensitivity and specificity of TTNT36 hours. Burst suppression and status epilepticus predicted poor neurological outcome (positive predictive value of 98.3% and 96.4%, respectively). The combination of these factors predicted a negative outcome at a median of 6.2 hours after resuscitation (sensitivity and specificity of 92.0% and 96.4%, respectively). Conclusions— A TTNT

Seong Hoon Kim,1,* Sung-Chul Lim,1,2,* Woojun Kim,1,2 Oh-hun Kwon,3 Chan Mi Kim,3 Jong-Min Lee,3 Young-Min Shon1,2 1Department of Neurology, 2Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul, Republic of Korea; 3Department of Biomedical Engineering, Hanyang University, Seoul, Republic of Korea *These authors contributed equally to this work Abstract: The antiseizure efficacy and safety of levetiracetam (LEV) is well documented; however, few clinical studies have investigated the predictability of patient responsiveness to LEV, especially when the drug is first administered. The aim of this study was to ascertain the utility of clinical, electrophysiological, and neuroimaging parameters for assessing the early response to LEV treatment in focal epilepsy patients. Twelve confirmed focal epilepsy patients were included who had never taken LEV before. At baseline and 1 month after LEV administration, all subjects underwent 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and electroencephalography (EEG), and completed the Quality of Life in Epilepsy questionnaire (QOLIE-31). Participants were divided by drug response: good versus poor. The good response group (seven subjects) was defined by a >50% decrease in seizure frequency compared to baseline (3 months before LEV intake). The other five participants with a

Ictal automatism with preserved responsiveness (APR) has been reported, particularly in nondominant temporal lobe epilepsy (TLE), but its pathophysiology remains poorly understood. This study sought to investigate the relationship between APRs and increased cerebral blood flow (CBF) using ictal single photon emission computed tomography (SPECT) in TLE. Forty-seven subjects with right mesial TLE (15 with and 32 without APR) were enrolled. Patients with APR (APR +) were subdivided into four groups according to degree of responsiveness during seizures. Cerebral blood flow changes during these seizures were semiquantitatively assessed by subtraction ictal SPECT coregistered to MRI (SISCOM). Hyperperfusion in temporal regions did not vary significantly between the APR + and APR − groups. Cerebral blood flow changes in the frontal area, insula, cingulum, and occipital area were also nonsignificant. However, hyperperfusion in the ipsilateral parietal areas was more frequent in the APR − group than in the APR + group. Furthermore, hyperperfusion of the contralateral basal ganglia showed an inclination to be more common in the APR − group, but without statistical significance. The study suggested that the involvement of the parietal association cortex during seizure may play an important role in ictal loss of consciousness in TLE. Further studies will be needed to elucidate the pathophysiology of changes in consciousness during temporal lobe seizures.