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Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous syndrome, with 75.6%-83.5% and 54.1% patients presenting with epilepsy and drug-resistant epilepsy (DRE), respectively. Clinical studies on TSC, particularly surgical interventions, have achieved rapid and substantial progress. The TSC-Task Force Committee of the China Association Against Epilepsy (CAAE-TFTSC) was founded in 2012, and annual academic conferences on the surgical treatment of TSC-related epilepsy have been held since 2013. 'China experts' consensus on surgical treatment of TSC-related epilepsy' was published in 2019. This review focuses on surgical treatment, including resective surgery, neuromodulations, corpus callosotomy and mini-invasive ablations, as well as studies on phenotype, genotype and anti-seizure therapies of mammalian target of rapamycin inhibitor, vigabatrin and ketogenic diet in patients with TSC-related DRE in China.

Delineation of the epileptogenic zone (EZ) is crucial during resective surgery in patients with epilepsy. In recent years, high-frequency oscillations, including fast ripples and ripples, have been considered promising biomarkers of the EZ. The objective of this study was to perform a systematic review and meta-analysis to evaluate the diagnostic accuracy of fast ripples and ripples in identifying EZs.The PubMed, Embase, and Cochrane databases were searched systematically. The review process followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A bivariate mixed-effects regression approach was used to obtain summary estimates of the sensitivity and specificity of fast ripples and ripples.Thirteen studies were included in this review (12 for fast ripples and eight for ripples). Fast ripples had a pooled sensitivity of 0.80 (95% confidence interval [CI], 0.62-0.91), a specificity of 0.72 (95% CI, 0.55-0.85), and a summary area under the curve of 0.82 (95% CI, 0.79-0.86). The threshold effect was detected for ripples, and the summary area under the curve was 0.75 (95% CI, 0.71-0.79), with a sensitivity of 0.38 (95% CI, 0.18-0.64) and specificity of 0.90 (95% CI, 0.70-0.97).Fast ripples are a biomarker of the EZ with moderate diagnostic accuracy; in contrast, ripples are not as effective.

Background: Focal cortical dysplasia (FCD) is one of the most important pathogenic findings in patients with extratemporal lobe epilepsy. Magnetic resonance imaging (MRI)-negative is the most important negative factor to predict postoperative seizure freedom; however, FCD-I and part of FCD-IIa are MRI-negative on routine MRI. Objectives: To explore the diagnostic values of 7T MRI and its new scan sequences in epilepsy patients with FCD-IIa. Methods: To include patients with focal seizure and suspicious focal abnormal imaging on 3T MRI during preoperative evaluation and perform a 7T MRI scan with white matter-suppressed (WMS) and gray-white matter tissue border enhancement (GWBE) sequences, resective epilepsy surgery, and postoperative pathological finding of FCD-IIa. The preoperative qualitative and localization significance of 7T MRI and 3T MRI in lesions with FCD-IIa was compared, and then, the imaging characteristics of lesions with FCD-IIa on 7T MRI were analyzed. Results: Ten cases were enrolled in this study. Seven tesla MRI presented high spatial resolutions and a high signal-to-noise ratio. WMS and GWBE could selectively suppress the signal of special tissue and improved the possibility of FCD findings. FCD-IIa showed abnormal thickness of gray matter and a blurring border and was hypointense on 7T MRI compared with 3T MRI. Seven patients showed improvement in the qualitative diagnosis strength grade of FCD, and 6 subjects showed improvement in the localization strength grade of the lesion border after careful reading of the 7T MR images. Significant differences were found in the qualitative diagnosis of FCD (p < 0.05) and localization of the lesion border (p < 0.05) between the neuroimaging diagnoses based on 3T MRI and the findings based on 7T MRI. Conclusion: 7T MRI with WMS and GWBE sequences shows application value in the preoperative imaging diagnosis of lesions with FCD-IIa in epilepsy patients.

This paper proposes a compact bioelectronics sensing platform, including a multi-channel electrode, intracranial electroencephalogram (iEEG) recorder, adjustable galvanometer, and shunt-current conduction circuit pathway. The developed implantable electrode made of polyurethane-insulated stainless-steel materials is capable of recording iEEG signals and shunt-current conduction. The electrochemical impedance of the conduction, ground/reference, and working electrode were characterized in phosphate buffer saline solution, revealing in vitro results of 517.2 Ω@1 kHz (length of 0.1 mm, diameter of 0.8 mm), 1.374 kΩ@1 kHz (length of 0.3 mm, diameter of 0.1 mm), and 3.188 kΩ@1 kHz (length of 0.1 mm, diameter of 0.1 mm), respectively. On-bench measurement of the system revealed that the input noise of the system is less than 2 μVrms, the signal frequency bandwidth range is 1 Hz~10 kHz, and the shunt-current detection range is 0.1~3000 μA with an accuracy of above 99.985%. The electrode was implanted in the CA1 region of the right hippocampus of rats for the in vivo experiments. Kainic acid (KA)-induced seizures were detected through iEEG monitoring, and the induced shunt-current was successfully measured and conducted out of the brain through the designed circuit-body path, which verifies the potential of current conduction for the treatment of epilepsy.

Background Glioma‐related epilepsy (GRE) is defined as symptomatic epileptic seizures secondary to gliomas, it brings both heavy financial and psychosocial burdens to patients with diffuse glioma and significantly decreases their quality of life. To date, there have been no clinical guidelines that provide recommendations for the optimal diagnostic and therapeutic procedures for GRE patients. Methods In March 2017, the Joint Task Force for GRE of China Association Against Epilepsy and Society for Neuro‐Oncology of China launched the guideline committee for the diagnosis and treatment of GRE. The guideline committee conducted a comprehensive review of relevant domestic and international literatures that were evaluated and graded based on the Oxford Centre for Evidence‐Based Medicine Levels of Evidence, and then held three consensus meetings to discuss relevant recommendations. The recommendations were eventually given according to those relevant literatures, together with the experiences in the diagnosis and treatment of over 3000 GRE cases from 24 tertiary level hospitals that specialize in clinical research of epilepsy, glioma, and GRE in China. Results The manuscript presented the current standard recommendations for the diagnostic and therapeutic procedures of GRE. Conclusions The current work will provide a framework and assurance for the diagnosis and treatment strategy of GRE to reduce complications and costs caused by unnecessary treatment. Additionally, it can serve as a reference for all professionals involved in the management of patients with GRE.

International audience; Identifying a structural brain lesion on MRI has important implications in epilepsy and is the most important factor that correlates with seizure freedom after surgery in patients with drug-resistant focal onset epilepsy. However, at conventional magnetic field strengths (1.5 and 3T), only approximately 60%–85% of MRI examinations reveal such lesions. Over the last decade, studies have demonstrated the added value of 7T MRI in patients with and without known epileptogenic lesions from 1.5 and/or 3T. However, translation of 7T MRI to clinical practice is still challenging, particularly in centers new to 7T, and there is a need for practical recommendations on targeted use of 7T MRI in the clinical management of patients with epilepsy. The 7T Epilepsy Task Force—an international group representing 21 7T MRI centers with experience from scanning over 2,000 patients with epilepsy—would hereby like to share its experience with the neurology community regarding the appropriate clinical indications, patient selection and preparation, acquisition protocols and setup, technical challenges, and radiologic guidelines for 7T MRI in patients with epilepsy. This article mainly addresses structural imaging; in addition, it presents multiple nonstructural MRI techniques that benefit from 7T and hold promise as future directions in epilepsy. Answering to the increased availability of 7T MRI as an approved tool for diagnostic purposes, this article aims to provide guidance on clinical 7T MRI epilepsy management by giving recommendations on referral, suitable 7T MRI protocols, and image interpretation.

Epilepsy and seizures can have dramatic effects on cardiac function. The aim of the present study was to investigate deceleration capacity, acceleration capacity and their 24-h fluctuations of heart rate variability in patients with drug-resistant epilepsy. Deceleration capacity, acceleration capacity of heart rate and their 24-h dynamics derived from the phase rectified signal averaging method as well as traditional measures were analyzed in 39 patients with drug-resistant epilepsy and 33 healthy control subjects using 24-h electrocardiogram recordings. The discriminatory power of heart rate variability measures were validated by assessment of the area under the receiver operating characteristic curve. Net reclassification improvement and integrated discrimination improvement models were also estimated. Both deceleration capacity and absolute values of acceleration capacity were significantly lower in patients with drug-resistant epilepsy. The abnormal suppression of absolute deceleration capacity and acceleration capacity values were observed throughout the 24-h recording time (peaked at about 3 to 5 A.M.). Deceleration capacity had the greatest discriminatory power to differentiate the patients from the healthy controls. Moreover, in both net reclassification improvement and integrated discrimination improvement models, the combination of acceleration capacity or deceleration capacity with traditional heart rate variability measures has greater discriminatory power than any of the single heart rate variability features. Drug-resistant epilepsy was associated with a significant inhibition of vagal modulation of heart rate, which was more pronounced during the night than during the day. These findings indicate that phase rectified signal averaging method may serve as a complementary approach for characterizing and understanding the neuro-pathophysiology in epilepsy, and may provide a new clue to sudden unexpected death in epilepsy.

Tuberous scleroses complex (TSC) is a rare neurocutaneous syndrome and has autosomal dominant inheritance. However, larger family with TSC is very rare. Here, we report the first five generations family with TSC from China, and localize the pathogenic gene. A boy with TSC and epilepsy underwent preoperative evaluation and epileptic surgery. His TSC family history was gotten, and the clinical data of a Chinese family with TSC were collected in 2016. Complete exons sequencing was performed in the proband and his parents, and whole exons sequence of TSC was performed in the other family members. The family showed autosomal dominant inheritance, and it was the largest reported family with TSC. In this pedigree, there were 14 patients in 5 generations, but only 1 case with epilepsy in them. All of examined patients had TSC 1 gene exon 15 c.1846delG p.A616Pfs*13 mutation. In conclusion, TSC patients with TSC 1 deletion presented mild neurological symptom and rendered larger family.

Objective Epilepsy and seizures can have dramatic effects on the cardiac function. The aim of this study was to investigate the heart rhythm complexity in patients with drug-resistant epilepsy (DRE). Methods Ambulatory 24-h electrocardiograms (ECG) from 70 DRE patients and 50 healthy control subjects were analyzed using conventional heart rate variability (HRV) and multiscale entropy (MSE) methods The variation of complexity indices (CI), which was calculated from MSE profile, was determined. Results DRE patients had significantly lower time domain (Mean RR, SDNN, RMSSD, pNN50) and frequency domain (VLF, LF, HF, TP) HRV measurements than healthy controls. Of the MSE analysis, MSE profile, CI including Slope 5, Area 1–5, Area 6–15 and Area 6–20 were significantly lower than those in the healthy control group. In receiver operating characteristic (ROC) curve analysis, VLF had the greatest discriminatory power for the two groups. In both net reclassification improvement (NRI) model and integrated discrimination improvement (IDI) models, CI derived from MSE profiles significantly improved the discriminatory power of Mean RR, SDNN, RMSSD, pNN50, VLF, LF, HF and TP. Significance The heart rate complexity is impaired for DRE patients. CI are useful to discriminate DRE patients from subjects with normal cardiac complexity. These findings indicate that MSE method may serve as a complementary approach for characterizing and understanding abnormal heart rate dynamics in epilepsy. Furthermore, the CI may potentially be used as a biomarker in monitoring epilepsy.

Objectives: Patients with tuberous sclerosis complex (TSC) present multiple cortical tubers in the brain, which are responsible for epilepsy. It is still difficult to localize the epileptogenic tuber. The value of cortico-cortical evoked potentials (CCEPs) was assessed in epileptogenic tuber localization in patients with TSC using stereo-electroencephalography (SEEG). Methods: Patients with TSC who underwent SEEG and CCEP examination in preoperative evaluation during 2014-2017 and reached postoperative seizure freedom at 1-year follow-up were enrolled in this study (n = 11). CCEPs were conducted by stimulating every two adjacent contacts of SEEG electrodes and recording on other contacts of SEEG electrodes in one epileptogenic tuber and its early-stage propagating tuber, and their perituberal cortexes in each patient. The CCEP was defined as positive when N1 and/or N2 wave presented, and then the occurrence rates of positive CCEPs were then compared among different tubers and perituberal regions. Results: Occurrence rates of positive CCEP from epileptogenic tubers to early propagating tubers and epileptogenic tubers to perituberal cortexes were 100%, which were significantly higher than the occurrence rates of CCEP between other locations. The occurrence rates of CCEP from peripheral portions of epileptogenic tubers to peripheral portions of early propagating tubers or perituberal cortexes were 100%, which were significant higher than the occurrence rates of CCEP from peripheral regions of early propagating tubers to peripheral portions of epileptogenic tubers, from the central part of early propagating tuber to central portions of epileptogenic tubers, or from perituberal cortexes to the center part of epileptogenic tubers. Conclusion: Epileptogenic tubers presented much more diffusive connectivity with other tubers and perituberal cortexes than any other connectivity relationships across propagating tubers, and the peripheral region of epileptogenic tubers presented the greatest connectivity with propagating tubers and perituberal cortexes. CCEP can be an effective tool in epileptogenic tuber localization in patients with TSC.

At least 50% of patients with tuberous sclerosis complex present with intractable epilepsy; for these patients, resective surgery is a treatment option. Here, we report a nationwide multicentre retrospective study and analyse the long-term seizure and neuropsychological outcomes of epilepsy surgery in patients with tuberous sclerosis complex. There were 364 patients who underwent epilepsy surgery in the study. Patients’ clinical data, postoperative seizure outcomes at 1-, 4-, and 10-year follow-ups, preoperative and postoperative intelligence quotients, and quality of life at 1-year follow-up were collected. The patients’ ages at surgery were 10.35 ± 7.70 years (range: 0.5–47). The percentage of postoperative seizure freedom was 71% (258/364) at 1-year, 60% (118/196) at 4-year, and 51% (36/71) at 10-year follow-up. Influence factors of postoperative seizure freedom were the total removal of epileptogenic tubers and the presence of outstanding tuber on MRI at 1- and 4-year follow-ups. Furthermore, monthly seizure (versus daily seizure) was also a positive influence factor for postoperative seizure freedom at 1-year follow-up. The presence of an outstanding tuber on MRI was the only factor influencing seizure freedom at 10-year follow-up. Postoperative quality of life and intelligence quotient improvements were found in 43% (112/262) and 28% (67/242) of patients, respectively. Influence factors of postoperative quality of life and intelligence quotient improvement were postoperative seizure freedom and preoperative low intelligence quotient. The percentage of seizure freedom in the tuberectomy group was significantly lower compared to the tuberectomy plus and lobectomy groups at 1- and 4-year follow-ups. In conclusion, this study, the largest nationwide multi-centre study on resective epilepsy surgery, resulted in improved seizure outcomes and quality of life and intelligence quotient improvements in patients with tuberous sclerosis complex. Seizure freedom was often achieved in patients with an outstanding tuber on MRI, total removal of epileptogenic tubers, and tuberectomy plus. Quality of life and intelligence quotient improvements were frequently observed in patients with postoperative seizure freedom and preoperative low intelligence quotient.

Background Electronic conduction, a new treatment approach for epilepsy, has been confirmed to reduce epileptiform discharge on EEG and convulsive behaviors, particularly epileptic discharge propagation and serious behavioral seizures, in rats with kainic acid (KA)-induced acute temporal lobe epilepsy (TLE). Objective Hippocampal cell apoptosis was examined to confirm the neuroprotective effect of electronic conduction therapy in rats with KA-induced acute TLE. Methods Rats were divided into four groups: control group (right CA3 injection of saline), KA group (right CA3 injection of KA), sham conduction group (KA rats with sham conduction), and conduction group (KA rats with electric conduction). Apoptotic cells were evaluated by flow cytometry, TUNEL staining, and mRNA expression levels of caspase-3, tumor necrosis factor-alpha, and glial fibrillary acidic protein measured by real-time quantitative PCR (qRT-PCR). Results The frequency of convulsive behaviors in the conduction group decreased significantly compared with the KA group and the sham conduction group. Significantly fewer apoptotic cells were detected in rats with conduction based on flow cytometry and TUNEL staining results. The qRT-PCR results indicated that KA-induced up-regulation of hippocampal caspase-3 mRNA expression was reduced 24 hours after KA injection in rats that received conduction treatment. Conclusion Electronic conduction treatment can reduce seizure frequency and hippocampal cell apoptosis in rats with KA-induced acute TLE.

Hippocampal theta cycles provide a means to maintain and segregate different goal representations during human wayfinding., Humans are adept in simultaneously following multiple goals, but the neural mechanisms for maintaining specific goals and distinguishing them from other goals are incompletely understood. For short time scales, working memory studies suggest that multiple mental contents are maintained by theta-coupled reactivation, but evidence for similar mechanisms during complex behaviors such as goal-directed navigation is scarce. We examined intracranial electroencephalography recordings of epilepsy patients performing an object-location memory task in a virtual environment. We report that large-scale electrophysiological representations of objects that cue for specific goal locations are dynamically reactivated during goal-directed navigation. Reactivation of different cue representations occurred at stimulus-specific hippocampal theta phases. Locking to more distinct theta phases predicted better memory performance, identifying hippocampal theta phase coding as a mechanism for separating competing goals. Our findings suggest shared neural mechanisms between working memory and goal-directed navigation and provide new insights into the functions of the hippocampal theta rhythm.

This study was conducted to determine the benefit of magnetic resonance imaging (MRI) at 7 T in detecting structural lesions and previously unidentified abnormalities in patients with tuberous sclerosis complex (TSC). Thirteen patients with TSC (8–36 years, seven males) previously diagnosed by 3 T MRI underwent additional imaging at 7 T, which included T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE), T2-weighted turbo spin echo (TSE), SPACE fluid attenuated inversion recovery (FLAIR), susceptibility weighted imaging (SWI), white matter suppressed (WM-suppressed), and gray-white matter tissue border enhancement (GW-TBE) MPRAGE sequences. Subtle lesions, tuberal morphology, and perituberal cortex abnormalities were examined and compared to those observed at 3 T MRI using standard sequences. Improved visualization of TSC lesions was achieved in all subjects at 7 T compared to 3 T imaging, and three subjects received resective surgery. The 7 T T1- and T2-weighted images had high spatial resolution and provided a clear delineation of the perituberal cortex. SWI revealed abnormal blood vessel morphology. WM-suppressed and GW-TBE protocols, adjusted specifically for TSC imaging, aided in visualizing lesions and uncovered more extensive subtle lesions and abnormalities beyond the conventionally detected tubers. Due to its high spatial resolution and powerful new imaging protocols, 7 T MRI provided a better evaluation of subtle lesions and perituberal details compared with conventional MRI at 3 T, with potential implications for diagnosis and operative treatment of TSC and its related epilepsy.

Aims: To prospectively study the surgical outcomes of unilateral anterior temporal lobectomy (ATL) in patients with intractable bilateral temporal lobe epilepsy (TLE) as well as two-staged contralateral hippocampal stimulation in patients after failed unilateral ATL. Methods: Eighteen carefully selected patients with bilateral TLE underwent unilateral ATL. Five cases with failed ATL underwent two-staged contralateral hippocampal stimulation. Seizure control and changes in intelligence quotient (IQ), memory quotient, and quality of life (QOL) were analyzed 2-5 years after treatment. Results: In the patients with unilateral ATL, the percentages seizure free were 55.6% (10/18), 50.0% (9/18), and 44.4% (4/9) at the 1-, 2-, and 5-year follow-up visits, respectively. There were significant difference in seizure control between the patients with unilateral ATL and the 12 cases in the medication group. Significant differences were also found in changes in the patients' QOL and full-scale IQ at the 2-year follow-up between the surgical and medication groups. Five patients who underwent contralateral hippocampal stimulation after failed unilateral ATL experienced 80-100% seizure reductions, and 80% were seizure free 1 year after hippocampal stimulation. Conclusion: Unilateral ATL provides good seizure control and does not cause serious memory or IQ injury in carefully selected patients with true bilateral TLE. Contralateral hippocampal stimulation is a useful approach for patients who experience unilateral ATL failure.

Vagus nerve stimulation (VNS) is an adjunctive treatment for drug-resistant epilepsy (DRE). However, it is still difficult to predict which patients will respond to VNS treatment and to what extent. We aim to explore the relationship between preoperative heart rate variability (HRV) and VNS outcome. 50 healthy control subjects and 63 DRE patients who had received VNS implants and had at least one year of follow up were included. The preoperative HRV were analyzed by traditional linear methods and heart rhythm complexity analyses with multiscale entropy (MSE). DRE patients had significantly lower complexity indices (CI) as well as traditional linear HRV measurements than healthy controls. We also found that non-responders0 had significantly lower preoperative CI including Area 1–5, Area 6–15 and Area 6–20 than those in the responders0 while those of the non-responders50 had significantly lower RMSSD, pNN50, VLF, LF, HF, TP and LF/HF than the responders50. In receiver operating characteristic (ROC) curve analysis, Area 6–20 and RMSSD had the greatest discriminatory power for the responders0 and non-responders0, responders50 and non-responders50, respectively. Our results suggest that preoperative assessment of HRV by linear and MSE analysis can help in predicting VNS outcomes in patients with DRE.

Approximately 50% of patients with tuberous sclerosis complex (TSC) present intractable epilepsy, and surgery is an option for those patients. Hereby, we analyze long-term seizure control and neuropsychological outcomes of epilepsy surgery in patients with TSC. Clinical data were retrospectively collected from 66 patients with TSC and epilepsy followed up over 5 years, 51 of whom underwent epilepsy surgery between 2001 and 2011. Reductions in the number of seizures were analyzed at 1-year (1FU), 5-year (5FU), and 10-year (10FU) follow-ups visits after the operation. Influential factors on postoperative seizure free and intelligence quotient (IQ) and quality-of-life (QOL) outcomes were evaluated at 5FU. Resective procedures included 26 tuber resections, 15 lobectomies, and 10 tuber resections and lobectomies. Corpus callosotomies were performed as the adjunctive approach in 11 cases with low IQ. The percentages of seizure-free cases were 74.5% at 1FU, 58.8% at 5FU, and 47.8% at 10FU, and the predictive factor for long-term postoperative seizure freedom was the history of preoperative seizures and preoperative full-scale IQ. Significant improvements were found in performance IQ, full-scale IQ, and QOL in patients from the surgery group, particularly those who were seizure free after the operation. Our study showed that epilepsy surgery in TSC with epilepsy rendered improvements in seizure control, full-scale IQ, and QOL. Satisfactory long-term seizure control was often achieved with an early operation and without mental retardation, and improvements in QOL and IQ were frequently observed in postoperative patients who remained seizure free.

To study postoperative seizure control of hemispherectomy in adults with epilepsy and evaluate changes of movement and speech function, intelligence quotient (IQ) and quality of life (QOL) after hemispherectomy.We retrospectively analyzed 25 adults who presented severe unilateral epilepsy and hemiplegia and underwent anatomic or functional hemispherectomy in between 2006 and 2011. Surgical outcomes, including seizure-control at last follow-up, changes of aphasia quotient, hemiplegic side motor function, IQ and QOL from pre-operative to 2 years follow-up, were investigated. Results were statistically analyzed with SPSS 18.0.Nine functional hemispherectomies and 16 anatomic hemispherectomies were performed. Ninety-two percent of patients were seizure-free and 8% displayed Engel II grade seizure control after the procedure. Impaired movement function was present in 9 (36%) adults' upper limbs and 5 (20%) patients' lower limbs. The patients with age at seizure onset3 years showed improvement in mean motor function of the upper limbs. Impaired speech was seen in 7 patients with left hemispherectomies. There was an overall improvement in the mean aphasia quotient and significant difference was found in amount of change in aphasia quotients between patients with different ages of onset. All of the patients' postoperative scores of overall QOL, full IQ, verbal IQ and performance IQ improved compared with pretreatment scores and those improvements were not associated with patient's age at seizure onset or surgical approach. However, significant difference was found in change of verbal IQ between patients with right hemispherectomies and those with left hemispherectomies. Surgical complications included a single case of hydrocephalus, and 6 transient complications.Hemispherectomy presented good seizure control and improvement in QOL and IQ, and impairment on motor and speech function were mild. Furthermore, patients with early seizure onset could maintain movement function of upper limb and speech function improvement. Therefore, it is worth pursuing hemispherectomy in well-selected adults with severe unilateral epilepsy and hemiplegia.

Nuclear receptor subfamily 4 group A member 1 (NR4A1), a downstream target of CREB that is a key regulator of epileptogenesis, has been implicated in a variety of biological processes and was previously identified as a seizure-associated molecule. However, the relationship between NR4A1 and epileptogenesis remains unclear. Here, we showed that NR4A1 protein was predominantly expressed in neurons and up-regulated in patients with epilepsy as well as pilocarpine-induced mouse epileptic models. NR4A1 knockdown by lentivirus transfection (lenti-shNR4A1) alleviated seizure severity and prolonged onset latency in mouse models. Moreover, reciprocal coimmunoprecipitation of NR4A1 and NR2B demonstrated their interaction. Furthermore, the expression of p-NR2B (Tyr1472) in epileptic mice and the expression of NR2B in the postsynaptic density (PSD) were significantly reduced in the lenti-shNR4A1 group, indicating that NR4A1 knockdown partly decreased surface NR2B by promoting NR2B internalization. These results are the first to indicate that the expression of NR4A1 in epileptic brain tissues may provide new insights into the molecular mechanisms underlying epilepsy.

Summary Grid cells and theta oscillations are fundamental components of the brain’s navigation system. Grid cells provide animals [ 1 , 2 ] and humans [ 3 , 4 ] with a spatial map of the environment by exhibiting multiple firing fields arranged in a regular grid of equilateral triangles. This unique firing pattern presumably constitutes the neural basis for path integration [ 5 , 6 , 7 , 8 ] and may also enable navigation in visual and conceptual spaces [ 9 , 10 , 11 , 12 ]. Theta frequency oscillations are a prominent mesoscopic network phenomenon during navigation in both rodents and humans [ 13 , 14 ] and encode movement speed [ 15 , 16 , 17 ], distance traveled [ 18 ], and proximity to spatial boundaries [ 19 ]. Whether theta oscillations may also carry a grid-like signal remains elusive, however. Capitalizing on previous fMRI studies revealing a macroscopic proxy of sum grid cell activity in human entorhinal cortex (EC) [ 20 , 21 , 22 ], we examined intracranial EEG recordings from the EC of epilepsy patients (n = 9) performing a virtual navigation task. We found that the power of theta oscillations (4–8 Hz) exhibits 6-fold rotational modulation by movement direction, reminiscent of grid cell-like representations detected using fMRI. Modulation of theta power was specific to 6-fold rotational symmetry and to the EC. Hexadirectional modulation of theta power by movement direction only emerged during fast movements, stabilized over the course of the experiment, and showed sensitivity to the environmental boundary. Our results suggest that oscillatory power in the theta frequency range carries an imprint of sum grid cell activity potentially enabled by a common grid orientation of neighboring grid cells [ 23 ].

AimsTo investigate the surgical outcomes of anterior corpus callosotomy (aCCT) combined with anterior temporal lobectomy (ATL) in patients with intractable temporal lobe epilepsy (TLE) and mental retardation (MR).MethodsSixty patients with TLE and MR were carefully selected and randomly divided into two equal groups: ATL and aCCT, in which they were treated with ATL or ATL combined with aCCT, respectively. Surgical outcomes, including seizure control, IQ and quality of life (QOL) changes, as well as complications were recorded and analyzed 2 years after operation.ResultsSeizure-free status had been achieved in 66.7% of all patients. The aCCT group had higher percentage in Engle Classes I–II than the ATL group (96.7% vs. 80.0%, P

PURPOSE: To examine the effects of current shunt on rats with temporal lobe epilepsy and neocortex epilepsy. EXPERIMENTAL DESIGN: A kainic acid (KA)-induced model of temporal lobe seizure and a penicillin-induced model of neocortical partial seizure were used in this study. Rats of each model were randomly allocated into two groups: control and model groups. The model group was further divided into the KA or penicillin group, sham conduction group and conduction group. The current shunt was realized through the implantation of a customized conduction electrode. After surgery, electroencephalogram (EEG) was recorded for two hours for each rat under anesthesia. Subsequently, the rats were video monitored for 72 h to detect the occurrence of behavioral seizures upon awakening. The average number and duration of seizures on EEG and the number of behavioral seizures were measured. RESULTS: In KA model, the number of total EEG seizures in conduction group (9.57±2.46) was significantly less than that in sham conduction group (15.13±3.45) (p

A large number of epileptic patients suffer from refractory epilepsy, despite optimal treatment; thus these patients require new therapeutic approaches. Focal seizure activity is typically initiated in a fixed and localized region, which subsequently spreads to neighboring regions or more distant areas. At the initial onset of a seizure, the epileptic discharge will generate a relatively high voltage in seizure focus, and the discharge subsequently spreads to other relatively low-voltage regions. However, it is unknown whether seizure can be controlled through current shunt using a conduction microelectrode to conduct the epileptic discharge with a relatively high voltage in the seizure focus outside the brain. The current therapies for epilepsy, including drugs, resective surgery and neuromodulation, focus on inhibiting abnormal excessive or synchronous neuronal activity to control seizures; thus, the basic mechanism underlying these therapies is “inhibition”. In contrast, we proposed a “conduction” mechanism, whereby a current shunt with conduction electrode is used to control seizures. To our knowledge, this therapeutic strategy has not been previously reported, and we propose that this approach might be an alternative choice for the treatment of refractory partial epilepsy in the future.

Aim: This study aimed to report the first case of deep brain stimulation (DBS) in a preschool-aged child with hypothalamic hamartoma (HH) and discuss the rationale and outcome of this treatment. Methods: A 5.5-year-old girl was diagnosed with HH and intractable epilepsy, including laughing seizures, tonic seizures, and atypical absence seizures, using magnetic resonance imaging and electroencephalograph examination, quality of life (QOL), intelligence quotient (IQ), and memory quotient (MQ) tests. A right trans-temporal lobe approach HH stimulation was performed with a quadripolar electrode along the axial plane of the lesion. The initial stimulation parameters were a wave width of 90 μs, a stimulating frequency of 130 Hz, a voltage of 0.5 V, and a maintenance stimulation voltage of 2.0 V. Results: The girl achieved freedom from tonic seizure after 4 months of stimulation (1.5 V), freedom from laughing seizure after 7 months of stimulation (1.8 V), and a reduction by more than 80% of atypical absence seizure after implantation of the stimulation electrode. At the 18-month follow-up visit, the postoperative QOL, IQ, and MQ scores of the girl had improved more than 10% compared with the preoperative scores. There were no surgical- or stimulation-related complications. Conclusion: DBS is a safe and efficient approach in older preschool-aged patients with HH, and it provided freedom from tonic and laughing seizures, as well as a significant reduction of atypical absence seizure and improvement of IQ, MQ. and QOL.

OBJECTIVE: To perform a systematic review and individual participant data meta-analysis to identify preoperative factors associated with a good seizure outcome in children with Tuberous Sclerosis Complex undergoing resective epilepsy surgery. DATA SOURCES: Electronic databases (MEDLINE, EMBASE, CINAHL and Web of Science), archives of major epilepsy and neurosurgery meetings, and bibliographies of relevant articles, with no language or date restrictions. STUDY SELECTION: We included case-control or cohort studies of consecutive participants undergoing resective epilepsy surgery that reported seizure outcomes. We performed title and abstract and full text screening independently and in duplicate. We resolved disagreements through discussion. DATA EXTRACTION: One author performed data extraction which was verified by a second author using predefined data fields including study quality assessment using a risk of bias instrument we developed. We recorded all preoperative factors that may plausibly predict seizure outcomes. DATA SYNTHESIS: To identify predictors of a good seizure outcome (i.e. Engel Class I or II) we used logistic regression adjusting for length of follow-up for each preoperative variable. RESULTS: Of 9863 citations, 20 articles reporting on 181 participants were eligible. Good seizure outcomes were observed in 126 (69%) participants (Engel Class I: 102(56%); Engel class II: 24(13%)). In univariable analyses, absence of generalized seizure semiology (OR = 3.1, 95%CI = 1.2-8.2, p = 0.022), no or mild developmental delay (OR = 7.3, 95%CI = 2.1-24.7, p = 0.001), unifocal ictal scalp electroencephalographic (EEG) abnormality (OR = 3.2, 95%CI = 1.4-7.6, p = 0.008) and EEG/Magnetic resonance imaging concordance (OR = 4.9, 95%CI = 1.8-13.5, p = 0.002) were associated with a good postoperative seizure outcome. CONCLUSIONS: Small retrospective cohort studies are inherently prone to bias, some of which are overcome using individual participant data. The best available evidence suggests four preoperative factors predictive of good seizure outcomes following resective epilepsy surgery. Large long-term prospective multicenter observational studies are required to further evaluate the risk factors identified in this review.

The pediatric epileptic spectrum and seizure control in surgical patients have been defined in developed countries. However, corresponding data on school-aged children from developing countries are insufficient. We summarized epileptic surgical data from four centers in China, to compare surgical outcomes of school-aged children with intractable partial epilepsy from China and those from developed countries, and introduce surgical candidate criteria. Data from 206 children (aged 6-14 years) undergoing surgical resection for epilepsy between September 2001 and January 2007 were selected. Postoperative freedom from seizures was achieved in 173 cases (84.0%) at 1 year, 149 (72.3%) at 3 years, and 139 (67.5%) at 5 years. Patients with focal magnetic resonance imaging abnormalities and a short history of seizure were most likely to become seizure-free postoperatively. Those with preoperative low intelligence quotients who became seizure-free postoperatively achieved improvements in full memory quotients, intelligence quotients, and overall quality of life at 2 years. Significant differences were evident in mean changes of full intelligence quotient, full memory quotient, and overall quality of life between patients with preoperative low intelligence quotients who received corpus callosotomies and those with a normal preoperative intelligence quotient, and between seizure-free children and those with continual seizures.

To discuss neuropsychological outcome and candidate of epilepsy surgery for tuberous sclerosis complex (TSC).To retrospectively analyze clinical data of 25 patients with TSC and epilepsy who underwent epilepsy surgery between 2001 and 2007. Seizure reduction was analyzed at 1-year (1FU), 2-year (2FU), and 5-year (5FU) follow-up visits after surgery, and outcomes of intelligence quotient (IQ) and quality of life (QOL) were evaluated at 2FU.Resective procedures included 14 tuber resections, 9 lobectomies, and 2 tuber resections and lobectomies. Corpus callosotomies (CCTs) were performed as the adjunctive approach in eight cases with low IQ and behavioral problems. The percentages of seizure-free cases were 72% at 1FU, 60% at 2FU, and 54.5% at 5FU, and the factors predicting seizure freedom included the course of seizures and ages of patients. Significant improvement was found in performance IQ in patients with preoperative low IQ or CCT. Significant improvement in mean QOL score was observed in all patients, especially patients with preoperative low IQ and CCT but postoperative seizure freedom.To be surgical candidates, patients with TSC and epilepsy should have identified epileptogenic tubers, and candidates should include patients with low IQ and multiple epileptogenic tubers. Satisfactory seizure control was often achieved with early operation, whereas improved QOL was observed frequently in postoperative seizure-free patients. CCT could be performed as an adjunctive approach to resective operation for TSC patients with epilepsy and low IQ and render improvement of performance IQ and QOL.

Aims: To prospectively study outcomes of anterior corpus callosotomy (aCCT) in patients with refractory generalized epilepsy (RGE) and mental retardation (MR), and estimate the effect of preoperative Wechsler Full Scale Intelligence Quotient (FIQ) on surgical outcomes. Methods: Selected patients with RGE were divided into a moderate MR group (MoMR), mild MR group (MiMR) and no MR group (NMR), and all of them were treated with aCCT. Seizure outcomes were evaluated at the 1-year follow-up (1FU) and 2-year follow-up (2FU), and changes of quality of life (QOL) and IQ were tested at 2FU. Results: Seizure control did not differ by group or follow-up period. Most seizure reduction was achieved in atonic or tonic seizures with 76–80% reduction at 1FU and 81–87% at 2FU; myoclonic epilepsy was the least likely to respond. QOL changes differed among groups, and 53.2% of total patients showed postoperative QOL improvement: 75% in the MoMR group, 65% in the MiMR group and 21.1% in the NMR group. No significant group difference was seen in FIQ change, although average postoperative performance IQ (PIQ) improvement in patients with MR exceeded 4 points. Conclusion: aCCT can reduce seizures and is a safe surgical procedure. Low IQ does not affect seizure outcome and can be associated with a good surgical outcome in PIQ and QOL improvement.