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Focused ultrasound (FUS) has the potential to modulate regional brain excitability and possibly aid seizure control; however, effects on behavior of FUS used as a seizure therapy are unknown. This study explores behavioral effects and hippocampal restoration induced by pulsed FUS in a kainic acid (KA) animal model of temporal lobe epilepsy. Twenty-nine male Sprague–Dawley rats were observed for 20 weeks with anatomical magnetic resonance imaging (MRI) and behavioral performance evaluations, comprising measures of anxiety, limb usage, sociability, and memory. FUS targeted to the right hippocampus was given 9 and 14 weeks after KA was delivered to the right amygdala. Ultrasound pulsations were delivered with the acoustic settings of 0.25 of mechanical index, 0.5 W/cm2 of intensity spatial peak temporal average (ISPTA), 100 Hz of pulse repetition frequency, and 30% of duty cycle, during three consecutive pulse trains of 10 min separated by 5-min rests. Controls included normal animals with sham injections and KA-exposed animals without FUS exposure. Longitudinal MRI observations showed that FUS substantially protected hippocampal and striatal structures from KA-induced atrophy. KA alone increased anxiety, impaired contralateral limb usage, and reduced sociability and learning. Two courses of FUS sonications partially ameliorated these impairments by enhancing exploring and learning, balancing limb usage, and increasing social interaction. The histology results indicated that two sonications enhanced neuroprotection effect and decreased the inflammation markers induced by KA. This study supports existence of both neuroprotective and beneficial behavioral effects from low-intensity pulsed ultrasound in the KA animal model of epilepsy.

Neuronal intranuclear inclusion disease (NIID), caused by an expansion of GGC repeats in the 5′-untranslated region of NOTCH2NLC, is an important but underdiagnosed cause of adult-onset leukoencephalopathies. The present study aimed to investigate the prevalence, clinical spectrum and brain MRI characteristics of NIID in adult-onset nonvascular leukoencephalopathies and assess the diagnostic performance of neuroimaging features. One hundred and sixty-one unrelated Taiwanese patients with genetically undetermined nonvascular leukoencephalopathies were screened for the NOTCH2NLC GGC repeat expansions using fragment analysis, repeat-primed PCR, Southern blot analysis and/or nanopore sequencing with Cas9-mediated enrichment. Among them, 32 (19.9%) patients had an expanded NOTCH2NLC allele and were diagnosed with NIID. We enrolled another two affected family members from one patient for further analysis. The size of the expanded NOTCH2NLC GGC repeats in the 34 patients ranged from 73 to 323 repeats. Skin biopsies from five patients all showed eosinophilic, p62-positive intranuclear inclusions in the sweat gland cells and dermal adipocytes. Among the 34 NIID patients presenting with nonvascular leukoencephalopathies, the median age at symptom onset was 61 years (range, 41–78 years) and the initial presentations included cognitive decline (44.1%; 15/34), acute encephalitis-like episodes (32.4%; 11/34), limb weakness (11.8%; 4/34) and parkinsonism (11.8%; 4/34). Cognitive decline (64.7%; 22/34) and acute encephalitis-like episodes (55.9%; 19/34) were also the most common overall manifestations. Two-thirds of the patients had either bladder dysfunction or visual disturbance. Comparing the brain MRI features between the NIID patients and individuals with other undetermined leukoencephalopathies, corticomedullary junction curvilinear lesions on diffusion weighted images were the best biomarkers for diagnosing NIID with high specificity (98.4%) and sensitivity (88.2%). However, this diffusion weighted imaging abnormality was absent in 11.8% of the NIID patients. When only fluid-attenuated inversion recovery images were available, the presence of white matter hyperintensity lesions either in the paravermis or middle cerebellar peduncles also favoured the diagnosis of NIID with a specificity of 85.3% and sensitivity of 76.5%. Among the MRI scans of 10 patients, performed within 5 days of the onset of acute encephalitis-like episodes, five showed cortical hyperintense lesions on diffusion weighted images and two revealed focal brain oedema. In conclusion, NIID accounts for 19.9% (32/161) of patients with adult-onset genetically undiagnosed nonvascular leukoencephalopathies in Taiwan. Half of the NIID patients developed encephalitis-like episodes with restricted diffusion in the cortical regions on diffusion weighted images at the acute stage. Corticomedullary junction hyperintense lesions, white matter hyperintensities in the paravermis or middle cerebellar peduncles, bladder dysfunction and visual disturbance are useful hints to diagnosing NIID.

During economic choice, evidence from monkeys and humans suggest that activity in the orbitofrontal cortex (OFC) encodes the subjective values of options under consideration. Monkey data further suggests that value representations in the OFC are context dependent, representing subjective value in a way influenced by the decision makers’ recent experience. Using stereo electroencephalography (sEEG) in human subjects, we investigated the neural representations of both past and present subjective values in the OFC, insula, cingulate and parietal cortices, amygdala, hippocampus and striatum. Patients with epilepsy (n=20) reported their willingness to pay—a measure of subjective value—for snack food items in a Becker-DeGroot-Marschack (BDM) auction task. We found that the high frequency power (gamma and high-gamma bands) in the OFC positively correlated with the current subjective value but negatively correlated with the subjective value of the good offered on the last trial – a kind of temporal context dependency not yet observed in humans. These representations were observed at both the group level (across electrode contacts and subjects) and at the level of individual contacts. Noticeably, the majority of significant contacts represented either the present or past subjective value, but not both. A dynamic dimensionality-reduction analysis of OFC population trajectories suggested that the past trial begin to influence activity early in the current trial after the current offer was revealed, and that these two properties—current and past subjective values—dominate the electrophysiological signals. Together, these findings indicate that information about the value of the past and present rewards are simultaneously represented in the human OFC, and offer insights into the algorithmic structure of context-dependent computation during human economic choice.

Neuroimaging studies suggest cross-sensory visual influences in human auditory cortices (AC). Whether these influences reflect active visual processing in human ACs, which drives neuronal firing and concurrent broadband high-frequency activity (BHFA; >70 Hz), or whether they merely modulate sound processing is still debatable. Here, we presented auditory, visual, and audiovisual stimuli to 16 participants with stereo-EEG depth electrodes implanted near ACs for presurgical monitoring. Anatomically normalized group analyses were facilitated by inverse modeling of intracranial source currents. Cross-correlation and spatiotemporal pattern similarity analyses suggested cross-sensory visual influences, which lagged auditory responses by several tens of milliseconds in ACs. Visual stimuli also modulated the phase of intrinsic low-frequency oscillations and triggered 15–30-Hz event-related desynchronization in ACs. However, BHFA, a putative correlate of neuronal firing, was not significantly increased in ACs after visual stimuli, not even when they coincided with auditory stimuli. Intracranial recordings demonstrate cross-sensory modulations, but no indication of active visual processing in human ACs.

Objectives We investigated hippocampal-sparing lesionectomy (HSL) outcomes in temporal lobe epilepsy (TLE) and the significance of high-frequency oscillations (HFOs) detected by hippocampography in HSL. Methods We retrospectively reviewed data from patients who underwent HSL for lesional TLE. Patients were included when MRI confirmed (i) a lesion limited to the temporal lobe with normal hippocampi preoperatively and (ii) hippocampal integrity postoperatively. Factors possibly related to outcomes were collected. Intraoperative hippocampography was reviewed, and spikes, ripples, and fast ripples were marked. Seizure outcomes were tracked ≥ 2 years. Postoperative neuropsychological tests were performed and analyzed. Results We included 67 patients (35 males/32 females, median age at surgery 28 years, 57 seizure-free). Complete resection was significantly associated with being seizure-free without aura, an outcome achieved by 32 (69.6%) patients with complete resection vs 1 (12.5%) with incomplete resection (p = 0.004). Spikes/ripples/fast ripples appeared frequently in the hippocampus, occurring in 86.4%/82.4%/75.0% of cases before resection and 76.7%/78.1%/63.0% after resection. The presence and rate were unconnected to seizure outcome. Postoperative neuropsychological outcomes in intelligence and visual memory improved overall. Conclusions HSL in lesional TLE can produce satisfactory seizure and cognitive outcomes. Intraoperative hippocampography-guided resection of apparently normal hippocampi should be performed cautiously and might not be necessary. Significance This study provided evidence in decision making for patients with lesional TLE with a radiologically normal hippocampus.

Cerebral cavernous malformations (CCMs) present variably, and epileptic seizures are the most common symptom. The factors contributing to cavernoma-related epilepsy (CRE) and drug resistance remain inconclusive. The outcomes of CRE after different treatment modalities have not yet been fully addressed. This study aimed to characterize the clinical features of patients with CRE and the long-term seizure outcomes of medical and surgical treatment strategies.This was a retrospective cohort of 135 patients with CCM who were diagnosed in 2007-2011 and followed up for 93.6 months on average. The patients were divided into drug-resistant epilepsy (DRE; n = 29), non-DRE (n = 45), and no epilepsy (NE; n = 61).Temporal CCM was the factor most strongly associated with the development of both CRE and DRE. The majority of patients with single temporal CCMs had CRE (86.8%, n = 33), and 50% had DRE, whereas only 14.7% (n = 5) with a nontemporal supratentorial CCM had DRE (p .05). The most common lesion site in the DRE group was the mesiotemporal lobe (50%). Multiple CCMs were more frequently observed in the CRE (29.2%) than the NE (11.5%) group (p .05). In patients with CRE, multiple lesions were associated with a higher rebleeding rate (odds ratio = 11.1), particularly in those with DRE (odds ratio = 15.4). The majority of patients who underwent resective surgery for DRE (76.5%, n = 13) achieved International League Against Epilepsy Class I and II seizure outcomes even after a long disease course.Temporal CCM not only predisposes to CRE but also is a major risk factor for drug resistance. The mesiotemporal lobe is the most epileptogenic zone. Multiple CCMs are another risk factor for CRE and increase the rebleeding risk in these patients. Surgical resection could provide beneficial long-term seizure outcomes in patients with DRE.

Satisfaction with epilepsy surgery in Mandarin-speaking countries remains unknown. We aimed to validate in our Taiwanese patients an existing instrument to measure patient satisfaction with epilepsy surgery, the 19-item Epilepsy Surgery Satisfaction Questionnaire (ESSQ-19).Consecutive patients with epilepsy who received epilepsy surgery one year earlier in Taipei Veterans General Hospital were recruited and provided clinical and demographic data. The Mandarin version of the ESSQ-19 for the Taiwanese population and eight other questionnaires were completed to assess construct validity. To evaluate the validity and reliability of the tool, the data were analyzed by confirmatory factor analysis, Spearman's rank correlation, and internal consistency analysis.The study involved 120 patients (70 F/50 M, median age 35 years [IQR = 28-41]). The mean summary score (±SD) of the Tw-ESSQ-19 was 82.5 ± 14.5. The mean scores of the four domains were 90.3 ± 15.4 (surgical complications), 83.2 ± 16.7 (seizure control), 80.1 ± 17.3 (recovery from surgery), and 76.6 ± 18.3 (psychosocial functioning). The questionnaire was shown to have good construct validity with satisfactory goodness-of-fit of the data (standardized root mean square residual = 0.0492; comparative fit index = 0.946). It also demonstrated good discriminant validity (being seizure free [AUC 0.78; 95% CI 0.68-0.89], endorsing depression [AUC 0.84; 95% CI 0.76-0.91], self-rating epilepsy as disabling [AUC 0.71; 95% CI 0.58-0.84], and self-rating epilepsy as severe [AUC 0.78; 95% CI 0.64-0.93]), high internal consistency in four domains (Cronbach's alpha = 0.83-0.96), and no significant floor/ceiling effects of the summary score.The Mandarin version of the ESSQ-19 adapted for the Taiwanese population is a reliable and valid self-reported questionnaire for assessing patient satisfaction with epilepsy surgery.

Cognitive control involves flexibly combining multiple sensory inputs with task-dependent goals during decision making. Several tasks have been proposed to examine cognitive control, including Stroop, Eriksen-Flanker, and the Multi-source interference task. Because these tasks have been studied independently, it remains unclear whether the neural signatures of cognitive control reflect abstract control mechanisms or specific combinations of sensory and behavioral aspects of each task. To address this question, here we recorded invasive neurophysiological signals from 16 subjects and directly compared the three tasks against each other. Neural activity patterns in the theta and high-gamma frequency bands differed between incongruent and congruent conditions, revealing strong modulation by conflicting task demands. These neural signals were specific to each task, generalizing within a task but not across tasks. These results highlight the complex interplay between sensory inputs, motor outputs, and task demands and argue against a universal and abstract representation of conflict.

To investigate the opinions and attitudes of neurologists on the counseling about sudden unexpected death in epilepsy (SUDEP) worldwide.Practicing neurologists from around the world were invited to participate in an online survey. On February 18th, 2021, we emailed an invitation including a questionnaire (using Google-forms) to the lead neurologists from 50 countries. The survey anonymously collected the demographic data of the participants and answers to the questions about their opinions and attitudes toward counseling about SUDEP.In total, 1123 neurologists from 27 countries participated; 41.5% of the respondents reported they discuss the risk of SUDEP with patients and their care-givers only rarely. Specific subgroups of patients who should especially be told about this condition were considered to be those with poor antiseizure medication (ASM) adherence, frequent tonic-clonic seizures, or with drug-resistant epilepsy. The propensity to tell all patients with epilepsy (PWE) about SUDEP was higher among those with epilepsy fellowship. Having an epilepsy fellowship and working in an academic setting were factors associated with a comfortable discussion about SUDEP. There were significant differences between the world regions.Neurologists often do not discuss SUDEP with patients and their care-givers. While the results of this study may not be representative of practitioners in each country, it seems that there is a severe dissociation between the clinical significance of SUDEP and the amount of attention that is devoted to this matter in daily practice by many neurologists around the world.

Objective The neuromodulatory effects of focused ultrasound (FUS) have been demonstrated in animal epilepsy models; however, the safety and efficacy of FUS in humans with epilepsy have not been well established. Patients with drug-resistant epilepsy (DRE) undergoing stereo-electroencephalography (SEEG) provide an opportunity to investigate the neuromodulatory effects of FUS in humans. Methods Patients with DRE undergoing SEEG for localization of the seizure onset zone (SOZ) were prospectively enrolled. FUS was delivered to the SOZ using a neuronavigation-guided FUS system (ceiling spatial-peak temporal-average intensity level = 2.8 W/cm2 , duty cycle = 30%, modulating duration = 10 min). Simultaneous SEEG recordings were obtained during sonication and for 3 days after treatment. Seizures, interictal epileptiform discharges, and adverse events after FUS were monitored. Results Six patients met the eligibility criteria and completed FUS treatment. A decrease in seizure frequency was observed in two patients within the 3-day follow-up; however, one patient presented an increase in the frequency of subclinical seizures. Posttreatment magnetic resonance imaging revealed neither lesion nor brain edema. Significant changes in spectral power of SEEG were noted at the targeted electrodes during FUS treatment. One patient reported subjective scalp heating during FUS, and one patient developed transient naming and memory impairment that resolved within 3 weeks after FUS. Significance FUS can be safely delivered to the SOZ of patients with DRE, resulting in significant changes in spectral power of SEEG. A larger sample cohort and pursuing optimal sonication parameters will be required to elucidate the neuromodulatory effects of FUS when used for seizure control.

OBJECTIVEIn this study, the authors investigated high-frequency oscillation (HFO) networks during seizures in order to determine how HFOs spread from the focal cerebral cortex and become synchronized across various areas of the brain.METHODSAll data were obtained from stereoelectroencephalography (SEEG) signals in patients with drug-resistant temporal lobe epilepsy (TLE). The authors calculated intercontact cross-coefficients between all pairs of contacts to construct HFO networks in 20 seizures that occurred in 5 patients. They then calculated HFO network topology metrics (i.e., network density and component size) after normalizing seizure duration data by dividing each seizure into 10 intervals of equal length (labeled I1–I10).RESULTSFrom the perspective of the dynamic topologies of cortical and subcortical HFO networks, the authors observed a significant increase in network density during intervals I5–I10. A significant increase was also observed in overall energy during intervals I3–I8. The results of subnetwork analysis revealed that the number of components continuously decreased following the onset of seizures, and those results were statistically significant during intervals I3–I10. Furthermore, the majority of nodes were connected to a single dominant component during the propagation of seizures, and the percentage of nodes within the largest component grew significantly until seizure termination.CONCLUSIONSThe consistent topological changes that the authors observed suggest that TLE is affected by common epileptogenic patterns. Indeed, the findings help to elucidate the epileptogenic network that characterizes TLE, which may be of interest to researchers and physicians working to improve treatment modalities for epilepsy, including resection, cortical stimulation, and neuromodulation treatments that are responsive to network topologies.

Background Selective amygdalohippocampectomy (SAH) is designed to treat patients with mesial temporal lobe epilepsy (MTLE). Objective To determine the volume and impact of temporal lobe infarction after retractorless transsylvian SAH (en bloc resection of the hippocampus) that have not been reported. Methods A retrospective analysis of patients treated with retractorless transsylvian SAH. Infarctions were detected by magnetic resonance imaging (MRI) within the first week after the operation. Neuropsychological testing was performed preoperatively and 6 mo later. Seizure outcome was evaluated 2 yr after epilepsy surgery. Results Between 2010 and 2014, a total of 30 patients were included in this study. Analysis of postoperative MRI showed the following: (1) mean removal volume of the hippocampus-parahippocampus was 5.72 cm3, and (2) mean volumes of temporal and insular infarctions were 1.71 and 0.25 cm3, respectively. Twenty-five patients (83.3%) were free of disabling seizures (Engel class I) at 2 yr of outcome. Neuropsychological testing revealed improvement in Perceptual Organization Index (P = .036) and verbal paired associates II (P = .014) after the operation. Neither infarction volume nor removal volume was related to epilepsy outcome in linear regression model. Conclusion Transsylvian SAH has comparable seizure outcomes but bears inherent risks of vasospasm/vascular injury. Immediate postoperative small infarction volume around resection cavity or along surgical corridor was noticed after retractorless transsylvian SAH, which did not cause neuropsychological deteriorations, in contrast to previous study with the use of self-sustaining rigid retraction system. Further study should be performed to compare procedure-related infarctions and their impacts on neuropsychological outcomes in different selective approaches.

Intracranial stereoelectroencephalography (sEEG) provides unsurpassed sensitivity and specificity for human neurophysiology. However, functional mapping of brain functions has been limited because the implantations have sparse coverage and differ greatly across individuals. Here, we developed a distributed, anatomically realistic sEEG source-modeling approach for within- and between-subject analyses. In addition to intracranial event-related potentials (iERP), we estimated the sources of high broadband gamma activity (HBBG), a putative correlate of local neural firing. Our novel approach accounted for a significant portion of the variance of the sEEG measurements in leave-one-out cross-validation. After logarithmic transformations, the sensitivity and signal-to-noise ratio were linearly inversely related to the minimal distance between the brain location and electrode contacts (slope≈−3.6). The signa-to-noise ratio and sensitivity in the thalamus and brain stem were comparable to those locations at the vicinity of electrode contact implantation. The HGGB source estimates were remarkably consistent with analyses of intracranial-contact data. In conclusion, distributed sEEG source modeling provides a powerful neuroimaging tool, which facilitates anatomically-normalized functional mapping of human brain using both iERP and HBBG data.

Introduction Acute withdrawal of antiepileptic drugs (AEDs) is a safe and effective approach to provoking seizures in order to complete video-electroencephalogram (V-EEG) studies in a timely manner. Previous studies have focused only on withdrawal from conventional AEDs, and the effects of withdrawal from new-generation AEDs have not been extensively studied. Materials and Methods This study examined adult patients with drug-resistant epilepsy admitted to an epilepsy monitoring unit between 2015 and 2018. Patients were classified according to whether they received conventional AEDs (Con; n = 13) or new-generation AEDs (N-Gen; n = 26). We then compared the effects of withdrawing these two types of AEDs over a period of one week in terms of efficacy (time to complete V-EEG monitoring) and safety, including the incidence of cluster seizures (CS), focal to bilateral tonic-clonic seizures (FBTCS) and status epilepticus (SE). Results In both groups, approximately one week was required to complete V-EEG analysis: N-Gen group (5.6 days) and Con group (6.3 days). No differences were observed between the two groups in terms of the median number of seizures, the onset of the 1st seizure, the distribution of CS, FBTCS, or SE. Following acute withdrawal of medication, a high percentage of patients with a history of CS or FBTCS, respectively, presented CS or FBTCS. Conclusions We did not observe significant differences between patients taking new-generation AEDs and those taking conventional AEDs following withdrawal during V-EEG recording. In the current study, we employed a standard protocol for the rapid withdrawal of AEDs (daily dose reduction of 50%), which was sufficient for 80% of patients to complete V-EEG monitoring within one week.

Intracranial stereoelectroencephalography (sEEG) provides unsurpassed sensitivity and specificity for human neurophysiology. However, sEEG group analyses are complicated because the electrode implantations differ greatly across individuals. Here, using an auditory experiment as the test case, we developed a distributed, anatomically realistic sEEG source-modeling approach for within- and between-subject analyses. In addition to intracranial event-related potentials (iERP), we also estimated the sources of high broadband gamma activity (HBBG), a putative correlate of local neural firing. The source models accounted for a significant portion of the variance of the sEEG measurements in leave-one-out cross-validation. After logarithmic transformations, the sensitivity and signal-to-noise ratio were linearly inversely related to the minimal distance between the brain location and electrode contacts (slope≈-3.6). The HGGB source estimates were remarkably consistent with analyses of intracranial-contact data. In conclusion, distributed sEEG source modeling provides a powerful neuroimaging tool, which facilitates anatomically-normalized group analyses of both iERP and HBBG.

Depression is the most commonly seen psychiatric co-morbidity of epilepsy. Depression in patients with epilepsy (PWE) is underrecognized. The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) is a useful tool to screen for major depressive episodes (MDEs) in PWE. This study validated the Taiwanese version of the NDDI-E using data from adult PWE in our hospital.PWE were recruited from the Taipei Veterans General Hospital from April 2017 to December 2019. The Chinese version of the NDDI-E for the Taiwanese population and the Beck Depression Inventory-II (BDI-II) were completed as part of the self-rated psychiatric assessments. The mood disorder module of the Mini International Neuropsychiatric Interview (MINI) was completed as part of the psychiatric assessment before the self-rated assessment. Internal consistency, external validation, and receiver operator characteristic (ROC) curve analysis were used to assess the utility of the Taiwanese version of the NDDI-E.We recruited 109 patients during the 33-month study period. The mean age was 33.1 ± 8.94 years old. The mean NDDI-E score was 12.32 ± 4.96. The mean BDI-II score was 13.26 ± 12.77. All NDDI-E items were significantly positively associated with the corrected overall NDDI-E score (Cronbach's alpha = 0.902, r = 0.825, p 0.0001). The cut-off point for the NDDI-E determined with receiver operating characteristic (ROC) curve analysis is 15 (sensitivity = 85.0%, specificity = 87.64%).The Chinese version of the NDDI-E adapted for the Taiwanese population is a reliable and valid self-reported questionnaire for detecting MDE in Taiwanese PWE.

Sporadic hemiplegic migraine (SHM) is characterized by a prolonged motor aura that accompanies a migraine attack, and its underlying pathophysiology remains unclear. Functional image during the event can help to explore the mechanism.We report a finding of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) in a 15-year-old female with SHM. She presented with recurrent right arm weakness and pain with migrainous headache. A video electroencephalogram showed no evidence of epilepsy during the events. Subtraction of ictal-interictal FDG-PET coregistered to magnetic resonance imaging was performed for the image analysis. In comparison with the interictal state, the FDG-PET image showed decreased glucose metabolism in the bilateral dorsal lateral frontal cortices and bilateral occipital cortices, whereas increased metabolism in the left precentral motor cortex and right premotor cortex.These findings reveal an increase in metabolism in the motor cortex during general cortical dysfunction in the frontal and occipital cortices in SHM. Key words: FDG-PET, hemiplegic migraine, migraine, positron emission tomography, SISCOM.

Human-machine interaction (HMI) safety for cyber-physical systems (CPSs) is critical and its analysis is mandatory in many domains such as SCADA, autonomous cars, and medical devices. Generation of dynamic accident scenarios is the cornerstone of safety analysis. This paper presents a platform and associated methodology to effectively generate accident scenarios by modeling HMI errors using model-level fault injection, followed by simulation to produce dynamic evolutions of accident scenarios. An HMI fault tree template is proposed to guide the simulation. Results show that human mode confusion triggered by false displays may lead to severe accidents. Run-time assertions play a crucial role to detect HMI errors. A case study is described. The methodology expands Ptolemy II's modeling and simulation capabilities for CPS applications.

Background: Evidence for the comparative teratogenic risk of antiepileptic drugs is insufficient, particularly in relation to the dosage used. Therefore, we aimed to compare the occurrence of major congenital malformations following prenatal exposure to the eight most commonly used antiepileptic drugs in monotherapy. Methods: We did a longitudinal, prospective cohort study based on the EURAP international registry. We included data from pregnancies in women who were exposed to antiepileptic drug monotherapy at conception, prospectively identified from 42 countries contributing to EURAP. Follow-up data were obtained after each trimester, at birth, and 1 year after birth. The primary objective was to compare the risk of major congenital malformations assessed at 1 year after birth in offspring exposed prenatally to one of eight commonly used antiepileptic drugs (carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate, and valproate) and, whenever a dose dependency was identified, to compare the risks at different dose ranges. Logistic regression was used to make direct comparisons between treatments after adjustment for potential confounders and prognostic factors. Findings: Between June 20, 1999, and May 20, 2016, 7555 prospective pregnancies met the eligibility criteria. Of those eligible, 7355 pregnancies were exposed to one of the eight antiepileptic drugs for which the prevalence of major congenital malformations was 142 (10·3%) of 1381 pregnancies for valproate, 19 (6·5%) of 294 for phenobarbital, eight (6·4%) of 125 for phenytoin, 107 (5·5%) of 1957 for carbamazepine, six (3·9%) of 152 for topiramate, ten (3·0%) of 333 for oxcarbazepine, 74 (2·9%) of 2514 for lamotrigine, and 17 (2·8%) of 599 for levetiracetam. The prevalence of major congenital malformations increased with the dose at time of conception for carbamazepine (p=0·0140), lamotrigine (p=0·0145), phenobarbital (p=0·0390), and valproate (p

Purpose The purpose of this review was to investigate the prevalence of depression in people with epilepsy (PWE) in different countries in Asia. Methods We searched the electronic database PubMed on June 13, 2017 for articles in English that included the following search terms: "epilepsy" AND "depression" AND "country name" for all Asian countries since 1947. Relevant original studies from Asia were included if they reported the prevalence of depression in PWE. Papers studying special populations (e.g., elderly, veterans, etc.) were not included. In addition, experts in epilepsy field were invited from some Asian countries for an in-depth assessment. Results Six hundred eighty-seven papers were reviewed and 26 related studies were included in this study. Depression is highly prevalent in PWE in different countries in Asia and the prevalence rates are consistent with rates reported in the literature from other countries: overall, about 25% of PWE suffer from depression. Conclusion In Asian countries, as elsewhere, depression is common in PWE. High quality data is scarce in many countries and validated screening tools [e.g., Neurological Disorders Depression Inventory for Epilepsy (NDDI-E)] to appropriately investigate the prevalence of depression in PWE are still lacking in many languages. Considering the high prevalence of depression among PWE, routine and periodic screening of all PWE for early detection and appropriate management of depression would be a reasonable approach.

Purpose We conducted this study to compare the occurrence and prognostic significance of early postoperative interictal epileptiform discharges (IEDs) on seizure outcomes between corticoamygdalohippocampectomy (CAH) and selective amygdalohippocampectomy (SAH). Methods We reviewed our database of patients who had epilepsy surgery with hippocampus atrophy or signal changes on brain MRIs and pathology of mesial temporal sclerosis. One hundred and seventy-seven CAH and 39 SAH patients were enrolled. Postoperative EEG within 30days, other preoperative variables and seizure outcome 2years after surgery were obtained for analysis. Engel's IA and IB were defined as seizure-free. Results There was no significant difference in the seizure-free rate between the two procedures (127 (71.8%) of CAH vs 30 (76.9%) of SAH, p =0.51). Postoperative IEDs were more frequently seen in the SAH group (64.1%) than in the CAH group (29.9%), p 0.001. The IEDs in the SAH group did not show correlation with the seizure outcome 2 years after surgery. In the CAH group, patients who had no postoperative IEDs showed a higher seizure-free rate compared to those with IEDs (78.2% vs 56.6%, p =0.003; OR 2.267, 95% CI 1.09-4.73, p =0.029 in multivariate logistic regression). Conclusions Early postoperative IEDs are more frequently seen in SAH than in CAH. Unlike in patients with CAH, the presence of IEDs after SAH was not a predictor of seizure recurrence. The type of surgery should be considered while utilizing postoperative IEDs for evaluating the prognosis.

Background Epilepsy is a neurological disorder characterized by abnormal neuron discharge, and one-third of epilepsy patients suffer from drug-resistant epilepsy (DRE). The current management for DRE includes epileptogenic lesion resection, disconnection, and neuromodulation. Neuromodulation is achieved through invasive electrical stimulus including deep brain stimulation, vagus nerve stimulation, or responsive neurostimulation (RNS). As an alternative therapy, transcranial focused ultrasound (FUS) can transcranially and non-invasively modulate neuron activity. Objective This study seeks to verify the use of FUS pulsations to suppress spikes in an acute epileptic small-animal model, and to investigate possible biological mechanisms by which FUS pulsations interfere with epileptic neuronal activity. Methods The study used a total of 76 Sprague-Dawley rats. For the epilepsy model, rats were administered pentylenetetrazol (PTZ) to induce acute epileptic-like abnormal neuron discharges, followed by FUS exposure. Various ultrasound parameters were set to test the epilepsy-suppressing effect, while concurrently monitoring and analyzing electroencephalogram (EEG) signals. Animal behavior was monitored and histological examinations were conducted to evaluate the hazard posed by ultrasound exposure and the expression of neuronal activity markers. Western blotting was used to evaluate the correlation between FUS-induced epileptic suppression and the PI3K-mTOR signaling pathway. Results We observed that FUS pulsations effectively suppressed epileptic activity and observed EEG spectrum oscillations; the spike-suppressing effect depended on the selection of ultrasound parameters and highly correlated with FUS exposure level. Expression level changes of c-Fos and GAD65 were confirmed in the cortex and hippocampus, indicating that FUS pulsations deactivated excitatory cells and activated GABAergic terminals. No tissue damage, inflammatory response, or behavioral abnormalities were observed in rats treated with FUS under these exposure parameters. We also found that the FUS pulsations down-regulated the S6 phosphorylation and decreased pAKT expression. Conclusion Our results suggest that pulsed FUS exposure effectively suppresses epileptic spikes in an acute epilepsy animal model, and finds that ultrasound pulsation interferes with neuronal activity and affects the PTZ-induced PI3K-Akt-mTOR pathway, which might help explain the mechanism underlying ultrasound-related epileptic spike control.

OBJECTIVEThe semiology of cingulate gyrus epilepsy is varied and may involve the paracentral area, the adjacent limbic system, and/or the orbitofrontal gyrus. Invasive electroencephalography (iEEG) recording is usually required for patients with deeply located epileptogenic foci. This paper reports on the authors’ experiences in the diagnosis and surgical treatment of patients with focal epilepsy originating in the cingulate gyrus.METHODSEighteen patients (median age 24 years, range 5–53 years) with a mean seizure history of 23 years (range 2–32 years) were analyzed retrospectively. The results of presurgical evaluation, surgical strategy, and postoperative pathology are reported, as well as follow-up concerning functional morbidity and seizures (median follow-up 7 years, range 2–12 years).RESULTSPatients with cingulate gyrus epilepsy presented with a variety of semiologies and scalp EEG patterns. Prior to ictal onset, 11 (61%) of the patients presented with aura. Initial ictal symptoms included limb posturing in 12 (67%), vocalization in 5, and hypermotor movement in 4. In most patients (n = 16, 89%), ictal EEG presented as widespread patterns with bilateral hemispheric origin, as well as muscle artifacts obscuring the onset of EEG during the ictal period in 11 patients. Among the 18 patients who underwent resection, the pathology revealed mild malformation of cortical development in 2, focal cortical dysplasia (FCD) Ib in 4, FCD IIa in 4, FCD IIb in 4, astrocytoma in 1, ganglioglioma in 1, and gliosis in 2. The seizure outcome after surgery was satisfactory: Engel class IA in 12 patients, IIB in 3, IIIA in 1, IIIB in 1, and IVB in 1 at the 2-year follow-up.CONCLUSIONSIn this study, the authors exploited the improved access to the cingulate epileptogenic network made possible by the use of 3D electrodes implanted using stereoelectroencephalography methodology. Under iEEG recording and intraoperative neuromonitoring, epilepsy surgery on lesions in the cingulate gyrus can result in good outcomes in terms of seizure recurrence and the incidence of postoperative permanent deficits.