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Objectives: We aimed to investigate the clinicopathologic features of and genetic changes in Sturge-Weber syndrome (SWS) in patients with refractory epilepsy., Methods: Clinical data were retrospectively analyzed. H&E and immunohistochemistry were performed to assess pathologic changes. Targeted amplicon sequencing was applied to investigate the somatic GNAQ (c.548G>A) mutation. The potential predictors of seizure outcomes were estimated by univariate and multivariate statistical analyses., Results: Forty-eight patients with SWS and refractory epilepsy were enrolled. According to the imaging data and pathologic examination, ipsilateral hippocampal sclerosis (HS), calcification of leptomeningeal arteries, and focal cortical dysplasia were found in 14 (29.2%), 31 (64.6%), and 37 (77.1%) patients, respectively. A high frequency of GNAQ alteration was detected in both cerebral cortex (57.7%) and ipsilateral hippocampus (50.0%) from patients with SWS. During follow-up, 43 of 48 patients (85.4%) had achieved seizure control (Engel class I). Statistically, HS signs on imaging were found to be independent predictors of unfavorable seizure outcomes (P = .015)., Conclusions: Calcification of leptomeningeal arteries, focal cortical dysplasia, and GNAQ alteration are common features in SWS pathology. Patients with refractory epilepsy caused by SWS can achieve satisfactory seizure control after surgery, but seizure control was compromised in patients with comorbid HS., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: This protocol describes the design of a multicenter randomized controlled trial of robot-assisted stereotactic lesioning versus epileptogenic foci resection. Typical causes of focal epilepsy include hippocampal sclerosis and focal cortical dysplasia. These patients usually present with drug resistance and require surgical treatment. Although epileptogenic foci resection is still the most commonly used treatment for such focal epilepsy, there is increasing evidence that epileptogenic focus resection may lead to neurological impairment. The treatment of epilepsy with a robot-assisted stereotactic lesioning mainly includes two new minimally invasive surgical methods: radiofrequency thermocoagulation (RF-TC) and laser interstitial thermal therapy (LITT). Seizure-free is less likely to be achieved by these two procedures, but neurologic preservation is better. In this study, we aimed to compare the safety and efficacy of RF-TC, LITT, and epileptogenic foci resection for focal drug-resistant epilepsy., Methods: This is a multicenter, three-arm, randomized controlled clinical trial. The study will include patients older than 3 years of age with epilepsy who have had medically refractory seizures for at least 2 years and are eligible for surgical treatment with an epileptogenic focus as determined by multidisciplinary evaluation prior to randomization. The primary outcome measure is seizure outcome (quantified by seizure remission rate) at 3-month, 6-month, and 1-year follow-up after treatment. Postoperative neurologic impairment, spectrum distribution change of video electroencephalogram, quality of life, and medical costs will also be assessed as secondary outcomes., Trial Registration: Chinese Clinical Trials Registry ChiCTR2200060974. Registered on June 14, 2022. The status of the trial is recruiting, and the estimated study completion date is December 31, 2024., (© 2023. The Author(s).)

Clinical studies have demonstrated that deep brain stimulation of the anterior nucleus of the thalamus (ANT) is a safe and effective treatment for focal epilepsy and drug-resistant epilepsy. However, the mechanism of action of ANT deep brain stimulation, especially in terms of neuromodulatory circuits, is not fully understood. In this study, we evaluated the anatomical and functional connectivity of the ANT in rats. For anatomical connectivity, herpes simplex virus (HSV) and pseudorabies virus (PRV; Bartha stain) were focally injected into the ANT of rats to label the connected brain structures in the retrograde and anterograde directions, respectively. For functional connectivity, we used c-Fos mapping in conjunction with electrical stimulation of the ANT to map the brain structures functionally connected to the ANT. Circuit connectivity mapping revealed that the ANT was connected to the hippocampus, the nucleus accumbens, the dorsal part of the lateral septal nucleus (LSD), the amygdala, the secondary motor cortex (M2), the cingulate cortex, the substantia nigra, the hypothalamus, and other regions. The ipsilateral connections were stronger than the contralateral connections. Deep brain stimulation of the ANT resulted in c-fos expression in the cortex, hippocampus, amygdala, striatum and hypothalamus, with the strongest activation in the hippocampus. These results suggest that the ANT has a wide range of structural and functional connections, which may underlie the effectiveness of deep brain stimulation in treating epilepsy. DATA AVAILABILITY STATEMENT: The datasets generated for this study are available on request to the corresponding author., Competing Interests: Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The aim of the study was to evaluate the clinicopathological features, as well as the surgical prognosis, of epilepsy-associated glioneuronal tumors (GNT) with CD34 expression and BRAF mutation. Clinical data of patients who underwent epilepsy surgery for GNT were retrospectively studied. Univariate and multivariate analyses were performed to evaluate the correlations of clinical and pathological factors with molecular markers of CD34 expression and BRAF V600E mutation in GNT. A total of 247 patients with GNT had immunohistochemical detection of CD34 expression (CD34 positive vs. negative: 198/49), and among them, 102 patients had immunohistochemical detection of BRAF V600E mutation (BRAF positive vs. negative: 59/43). Univariate analysis found that tumor types (P < 0.001), patient population (P = 0.015), seizure aura (P = 0.007), drug-resistant epilepsy (P = 0.036), concordance of ictal electroencephalogram (EEG) findings (P = 0.032), surgical resection extent (P = 0.045), tumor location (P = 0.007) and duration of epilepsy (P = 0.027) were related to CD34 expression, and that concordance of ictal EEG findings (P = 0.031) and age at surgery (P = 0.015) were related to BRAF V600E mutation. In addition, history of generalized tonic-clonic seizure (HR 0.12; P = 0.035), drug-resistant epilepsy (HR 0.13; P = 0.030) and concordance of interictal EEG findings (HR 8.01; P = 0.039) were associated with tumor progression-free survival (PFS). However, CD34 expression or BRAF V600E mutation in GNT was not associated with surgical outcomes of seizure control and tumor PFS. The CD34 expression or BRAF V600E mutation in GNT may partly influence the distribution of clinicopathological features of patients with epilepsy, but they may be not able to predict the surgical prognosis of seizure outcome and tumor recurrence., (© 2022. The Author(s).)

Epilepsy surgery is the treatment of choice for patients with drug-resistant seizures. A timely evaluation for surgical candidacy can be life-saving for patients who are identified as appropriate surgical candidates, and may also enhance the care of nonsurgical candidates through improvement in diagnosis, optimization of therapy, and treatment of comorbidities. Yet, referral for surgical evaluations is often delayed while palliative options are pursued, with significant adverse consequences due to increased morbidity and mortality associated with intractable epilepsy. The Surgical Therapies Commission of the International League Against Epilepsy (ILAE) sought to address these clinical gaps and clarify when to initiate a surgical evaluation. We conducted a Delphi consensus process with 61 epileptologists, epilepsy neurosurgeons, neurologists, neuropsychiatrists, and neuropsychologists with a median of 22 years in practice, from 28 countries in all six ILAE world regions. After three rounds of Delphi surveys, evaluating 51 unique scenarios, we reached the following Expert Consensus Recommendations: (1) Referral for a surgical evaluation should be offered to every patient with drug-resistant epilepsy (up to 70 years of age), as soon as drug resistance is ascertained, regardless of epilepsy duration, sex, socioeconomic status, seizure type, epilepsy type (including epileptic encephalopathies), localization, and comorbidities (including severe psychiatric comorbidity like psychogenic nonepileptic seizures [PNES] or substance abuse) if patients are cooperative with management; (2) A surgical referral should be considered for older patients with drug-resistant epilepsy who have no surgical contraindication, and for patients (adults and children) who are seizure-free on 1-2 antiseizure medications (ASMs) but have a brain lesion in noneloquent cortex; and (3) referral for surgery should not be offered to patients with active substance abuse who are noncooperative with management. We present the Delphi consensus results leading up to these Expert Consensus Recommendations and discuss the data supporting our conclusions. High level evidence will be required to permit creation of clinical practice guidelines., (© 2022 International League Against Epilepsy.)

Objectives: The mechanisms underlying the anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS) for the treatment of drug-resistant epilepsy (DRE) have not been fully explored. The present study aimed to measure the changes in whole-brain activity generated by ANT DBS using interictal electroencephalography (EEG)., Materials and Methods: Interictal EEG signals were retrospectively collected in 20 DRE patients who underwent ANT DBS surgery. Patients were classified as responders or non-responders depending on their response to ANT DBS treatment. The power spectrum (PS) and Phase Lag Index (PLI) were determined and data analyzed using a paired sample t-test to evaluate activity differences between pre-and-post-treatment on different frequency categories. Student's t-test, Mann-Whitney test (non-parametric test) and Fisher exact test were used to compare groups in terms of clinical variables and EEG metrics. P values < 0.05 were considered statistically significant, and FDR-corrected values were used for multiple testing., Results: PS analysis revealed that whole-brain spectral power had a significant decrease in the beta (p = 0.005) and gamma (p = 0.037) bands following ANT DBS treatment in responders. The analysis of scalp topographic images of all patients showed that ANT DBS decreases PS in the beta band at the F3, F7 and Cz electrode sites. The findings indicated a decrease in PS in the gamma band at the Fp2, F3, Cz, T3, T5 and Oz electrode sites. After ANT DBS treatment, PLI analysis showed a significant decrease in PLI between Fp1 and T3 in the gamma band in responders., Conclusion: The findings showed that ANT DBS induces a decrease in power in the left frontal lobe, left temporal lobe and midline areas in the beta and gamma bands. Lower whole-brain power in the beta and gamma bands can be used as biomarkers for a favorable therapeutic response to ANT DBS, and decreased synchronization between the left frontal pole and temporal lobe in the gamma band can also be used as a biomarker for effective clinical stimulation to guide postoperative programming., (Copyright © 2022 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: This study investigated the dynamic and long-term efficacy of vagus nerve stimulation (VNS) in patients with drug-resistant epilepsy (DRE) induced by tuberous sclerosis complex (TSC). In addition, the impact of VNS on cognition and emotion after a one-year follow-up was evaluated., Methods: A total of 17 patients diagnosed with DRE induced by TSC were retrospectively recruited between 2008 and 2019. Dynamic changes in seizure frequency were observed in the responders (≥50% reduction of seizure frequency at last follow-up) and non-responders. Clinical characteristics and seizure outcomes were comprehensively analyzed to determine factors associated with seizure outcomes. The Wechsler intelligence scale was applied in a subgroup of six pediatric patients, whereas the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) were assessed in a subgroup of nine patients to determine the impact of VNS therapy on cognitive performance and emotional state., Results: The follow-up duration for the 17 patients who underwent VNS treatment ranged from 0.5 to 10 years (mean ± SD: 4.1 ± 3.2 years). Monthly seizures decreased significantly from three months to four years post-treatment (p < 0.05). At the last follow-up, 70.6% of the patients achieved at least a 50% reduction in seizure frequency, and three patients were completely seizure free. Comparatively, non-responder patients experienced deterioration of seizure frequency after the first year. Notably, after one-year follow-up the mean standard score of full-scale intelligence quotient increased from 67.33 to 69.5 (p = 0.078) while the mean, standard score of SDS decreased from 49.22 to 45.67 (p = 0.003) compared to preoperative neuropsychological evaluation results., Conclusion: VNS is a safe and effective treatment for patients with DRE caused by TSC. Although early outcomes were encouraging, a follow-up of at least one-year was required to predict long-term outcomes in patients receiving VNS treatment. Moreover, VNS may improve depressive mood in patients with DRE caused by TSC. Further investigations are needed to validate the present results., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

During the noninvasive evaluation phase for refractory epilepsy, the localization of the epileptogenic zone (EZ) is essential for the surgical protocols. Confirmation of laterality is required when the preoperative evaluation limits the EZ to bilateral anterior temporal lobes or bilateral frontal lobes. High-frequency oscillations (HFOs) are considered to be promising biological markers for the EZ. However, a large number of studies on HFOs stem from intracranial research. There were few quantitative measures for scalp HFOs, so we proposed a new method to quantify and analyze scalp HFOs. This method was called the "scalp-HFO index" (HI) and calculated in both the EZ and non-EZ. The calculation was based on the numbers and spectral power of scalp HFOs automatically detected. We labeled the brain lobes involved in the EZ as regions of interest (ROIs). The HIs based on the ripple numbers (n-HI) and spectral power (s-HI) were significantly higher in the ROI than in the contra-ROI ( P = 0.012, P = 0.003), indicating that HIs contributed to the lateralization of EZ. The sensitivity and specificity of n-HI for the localization of the EZ were 90% and 79.58%, respectively, suggesting that n-HI was valuable in localizing the EZ. HI may contribute to the implantation strategy of invasive electrodes. However, few scalp HFOs were recorded when the EZ was located in the medial cortex region. NEW & NOTEWORTHY We proposed the scalp-high-frequency oscillation (HFO) index (HI) as a quantitative assessment method for scalp HFOs to locate the epileptogenic zone (EZ). Our results showed that the HI in regions of interest (ROIs) was significantly higher than in contra-ROIs. Sensitivity and specificity of HI based on ripple rates (n-HI) for EZ localization were 90% and 79.58%, respectively. If the n-HI of the brain region was >1.35, it was more likely to be an epileptogenic region. Clinical application of HIs as an indicator may facilitate localization of the EZ.

Objective: Vagus nerve stimulation (VNS) is an alternative treatment option for individuals with refractory epilepsy, with nearly 40% of patients showing no benefit after VNS and only 6%-8% achieving seizure freedom. It is presently unclear why some patients respond to treatment and others do not. Therefore, identification of biomarkers to predict efficacy of VNS is of utmost importance. The objective of this study was to explore whether genetic variations in genes involved in adenosine kinase (ADK), ecto-5'-nucleotidase (NT5E), and adenosine A1 receptor (A1R) are linked to outcome of VNS in patients with refractory epilepsy., Methods: Thirty single-nucleotide polymorphisms (SNPs), including 9 in genes encoding ADK, 3 in genes encoding NT5E, and 18 in genes encoding A1R, were genotyped in 194 refractory epilepsy patients who underwent VNS. The chi-square test and binary logistic regression were used to determine associations between genetic differences and VNS efficacy., Results: A significant association between ADK SNPs rs11001109, rs7899674, and rs946185 and seizure reduction with VNS was found. Regardless of sex, age, seizure frequency and type, antiseizure drug use, etiology, and prior surgical history, all patients (10/10 patients [100%]) with minor allele homozygosity at rs11001109 (genotype AA) or rs946185 (AA) achieved > 50% seizure reduction and 4 patients (4/10 [40%]) achieved seizure freedom. VNS therapy demonstrated higher efficacy among carriers of minor allele rs7899674 (CG + GG) (68.3% vs 48.8% for patients with major allele homozygosity)., Conclusions: Homozygous ADK SNPs rs11001109 (AA) and rs946185 (AA), as well as minor allele rs7899674 (CG + GG), may serve as useful biomarkers for prediction of VNS therapy outcome.

Brain pH is thought to be important in epilepsy. The regulation of brain pH is, however, still poorly understood in animal models of chronic seizures (SZ) as well as in patients with intractable epilepsy. We used chemical exchange saturation transfer (CEST) MRI to noninvasively determine if the pH is alkaline shifted in a rodent model of the mesial temporal lobe (MTL) epilepsy with chronic SZ. Taking advantage of its high spatial resolution, we determined the pH values in specific brain regions believed to be important in this model produced by lithium-pilocarpine injection. All animals developed status epilepticus within 90 min after the lithium-pilocarpine administration, but one animal died within 24 hrs. All the surviving animals developed chronic SZ during the first 2 months. After SZ developed, brain pH was determined in the pilocarpine and control groups (n = 8 each). Epileptiform activity was documented in six pilocarpine rats with scalp EEG. The brain pH was estimated using two methods based on magnetization transfer asymmetry and amide proton transfer ratio. The pH was alkaline shifted in the pilocarpine rats (one outlier excluded) compared to the controls in the hippocampus (7.29 vs 7.17, t-test, p < 0.03) and the piriform cortex (7.34 vs. 7.06, p < 0.005), marginally more alkaline in the thalamus (7.13 vs. 7.01, p < 0.05), but not in the cerebral cortex (7.18 vs. 7.08, p > 0.05). Normalizing the brain pH may lead to an effective non-surgical method for treating intractable epilepsy as it is known that SZ can be eliminated by lowering the pH., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purposes: This study was to further explore the adenosine dysfunction in refractory epilepsy in Sturge-Weber Syndrome (SWS), to evaluate the neuronal-level effect of the A1 receptor (A1R) agonist on both excitatory pyramidal neurons and inhibitory interneurons, to discuss the possibility of adenosine augmentation therapy (AAT) using A1R agonist for treating refractory epilepsy in SWS., Materials and Methods: The intrinsic excitatory properties of pyramidal cells (PCs) and fast-spiking (FS) interneurons from human brain tissues with SWS cases and malformations of cortical development (MCD) cases were compared using electrophysiology. With application of either A1R agonist or antagonist, the neuronal-level effect of A1R agonist was evaluated in vitro in PCs and FS interneurons from SWS cases and MCD cases., Results: No significant difference of passive excitatory properties of PCs and FS interneurons was found between SWS cases and MCD cases. In terms of the neuronal-level effect of A1R agonist, with 22.88 ± 1.12% percentage of decreased frequency, FS interneurons showed relatively highest sensitivity of A1R agonist application, compared with PCs from SWS cases and FS interneurons and PCs from MCD cases., Conclusion: Our results supported the potential of AATs using A1R agonist to be a novel therapy for reducing life burden from patients with refractory epilepsy in SWS, with application to epileptic generation region but not propagation region., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The authors of this study aimed to investigate surgical outcomes and prognostic factors in older patients with drug-resistant temporal lobe epilepsy (TLE) who had undergone resective surgery., Methods: Data on patients older than 45 years of age with drug-resistant TLE who had undergone resective surgery at Sanbo Brain Hospital, Capital Medical University, between January 2009 and August 2017 were retrospectively collected. Postoperative seizure outcomes were evaluated according to the International League Against Epilepsy (ILAE) classification. Patients belonging to ILAE classes 1 and 2 were classified as having a favorable outcome, whereas patients belonging to ILAE classes 3-6 were classified as having an unfavorable outcome. Univariate analysis and multivariate logistic regression analysis were used to identify the potential predictors of seizure outcomes., Results: A total of 45 patients older than 45 years of age who had undergone resective epilepsy surgery for TLE were included in the present study. Eight (17.8%) of 45 patients had preoperative comorbidity in addition to seizures. The average age at the time of surgery was 51.76 years, and the average duration of epilepsy at the time surgery was 18.01 years. After an average follow-up period of 4.53 ± 2.82 years (range 2-10 years), 73.3% (33/45) of patients were seizure free. Surgical complications were observed in 13.3% of patients. Univariate and multivariate analyses revealed that an MRI-negative finding is the only independent predictor of unfavorable seizure outcomes (OR 0.06, 95% CI 0.01-0.67, p = 0.023)., Conclusions: Resective surgery is a safe and effective treatment for older patients with drug-resistant TLE. An MRI-negative finding independently predicts unfavorable seizure outcomes.

Purpose: To analyze the impact of magnetoencephalography (MEG) results on surgical outcomes in patients with drug-resistant epilepsy secondary to encephalomalacia., Methods: We retrospectively reviewed 121 patients with drug-resistant epilepsy associated with encephalomalacia who underwent MEG followed by resection surgery. Patients were subdivided into concordant MEG group and dis-concordant MEG group for analysis based on whether the MEG results were in concordance with epileptogenic zones or not., Results: 121 patients were included in the present study. The MEG spike sources of 73 (60.33%) patients were in concordance with epileptogenic zones while the MEG spike sources of the other 48 (39.67%) were in dis-concordance with epileptogenic zones. Favorable seizure outcomes were achieved in 79.45% (58 of 73) of patients with concordant MEG results while only 62.50% (30 of 48) of patients with dis-concordant MEG results were seizure free with a follow-up of 2-10 years. The differences of seizure-free rate between patients with concordant MEG results and dis-concordant MEG results were statistically significant. For patients with concordant MEG results, bilateral lesions on MRI are the only independent predictor of unfavorable seizure outcomes. For patients with discordant MEG results, duration of seizures is the only independent predictor of unfavorable seizure outcomes., Conclusions: Concordant MEG results are associated with favorable seizure outcomes. Bilateral lesions on MRI independently predict unfavorable seizure outcomes in patients with concordant MEG results while longer seizure durations independently predict unfavorable seizure outcomes in patients with dis-concordant MEG results.

Objective: To evaluate long-term outcomes and prognostic factors in patients who underwent surgical resection for drug-resistant epilepsy secondary to encephalomalacia., Methods: A total of 143 patients with drug-resistant epilepsy who underwent surgical resection with a follow-up of at least 5 years were included. Seizure outcomes were evaluated based on the International League Against Epilepsy classification. Univariate analysis and a multivariate logistic regression model in a backward fashion were used to identify the potential predictors of seizure outcomes., Results: Three months after surgery, 102 of 143 (71.3%) patients had achieved favorable seizure outcomes. Five years after surgery, 107 of 143 (74.8%) patients had achieved favorable seizure outcomes. Changes in the postoperative seizure status were observed in 22 of 143 (15.4%) patients during follow-up, but the difference in the seizure-free rate between 3 months and 5 years after surgery was not significant. Univariate and multivariate analyses revealed that only a monthly seizure frequency of >30 seizures (odds ratio = 3.42, 95% confidence interval = 1.19-9.76) and bilateral ictal onset rhythms (odds ratio = 4.46, 95% confidence interval = 1.61-12.39) were independent predictors of unfavorable seizure outcomes., Significance: Surgical resection is an effective treatment for patients with drug-resistant epilepsy secondary to encephalomalacia. Knowledge of the predictors of seizure outcomes may help during preoperative counseling and selection of optimal candidates for epilepsy surgery among patients with drug-resistant epilepsy secondary to encephalomalacia., (Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)

Objective: 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., Methods: 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., Results: 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., Interpretation: 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.

Objective: The aim of this study was to investigate the variations and the circadian rhythm of multi-domain parameters of heart rate variability (HRV) in patients with drug-resistant epilepsy., Methods: Time domain HRV parameters of 24-hour data, frequency and non-linear domain HRV parameters were calculated using a 24-hour ambulatory electrocardiogram (ECG) from subjects in a resting and awake state (5-min data from 9:00-10:00 a.m.). Circadian fluctuation (24 one-hour segments) and the night (00:00 - 05:00)/ day (07:30 - 09:30) ratio of each HRV parameter were measured in (i) refractory epilepsy (n = 51) and (ii) healthy, age and sex matched controls (n = 50). Cosinor fit method was used to quantify the pattern of the circadian rhythm of HRV., Results: Compared to healthy controls, patients with drug-resistant epilepsy had significantly decreased time domain (mean&#95;RR, STDRR, RMSSD, pNN50, HRV&#95;triangular&#95;index), frequency domain (VLF&#95;power, LF&#95;power, HF&#95;power, Total&#95;power) and non-linear domain (Poincaré SD 1 , SD 2 , D 2 ) HRV measurements. There were also overall reductions in amplitude and the baseline of circadian curves of HRV parameter in the patients group, especially nocturnal inhibition of cardiac autonomic modulations was stronger than that in daytime. The majority of differences in HRV values between the two groups reached a maximum in early morning (usually 5:00 or 6:00 a.m.). No significant differences were found in the night/day ratios of multi-domain HRV measurements between patients and healthy controls (p = 0.862)., Conclusions: The significant suppression of HRV parameters in patients with refractory epilepsy may reflect the inhibitions of both sympathetic and parasympathetic activities. This is notably the first time that marked circadian diversity of HRV measurments between the patient and control groups were found and quantified by cosinor fit method. The difference in amplitude increased during night with peak occurrence between 5:00 or 6:00 a.m. These findings may be linked to cardiac autonomic dysfunction and subsequent sudden unexpected death in epilepsy (SUDEP), which is reported to often occur during night or early morning. Taken together, HRV parameters may be potential bio-markers for predicting SUDEP., (Copyright © 2018. Published by Elsevier B.V.)

Background: Hemispherectomy is useful for treating patients with intractable epilepsy caused by diffuse unilateral hemispheric disease. Few patients develop recurrent seizures after hemispherectomy, but managing epilepsy by medical means alone is challenging for these patients, and it is also difficult to determine the treatment options and assess the need for reoperation., Objective: To present the treatment strategies and outcomes of patients who developed recurrent intractable epilepsy after initial hemispherectomies that were performed at a single institution by a single surgeon between 2004 and 2014., Method: The preoperative medical records, operative reports, imaging findings, and follow-up data for patients with recurrent epilepsy who underwent hemispherectomy for intractable epilepsy between 2004 and 2014 at Sanbo Brain Hospital Capital Medical University were retrospectively reviewed. The baseline characteristics, cause of seizures, imaging findings, electrophysiological findings, primary surgery-related complications, treatments for recurrent epilepsy and long-term seizure outcomes were evaluated. A reduction of seizure frequency greater than 90% was considered a favorable outcome., Results: In the cohort of 17 patients who suffered recurrent epilepsy after primary hemispherectomy, 11 had undergone reoperative surgery, whereas 6 patients took medication alone. No major complications occurred in this series. At the last follow-up, favorable outcome was noted in 10 (91%) patients who underwent reoperative surgery and in 1 (17%) patient who received only medication for treatment (Table 1, p = 0.005). Patients with malformation of cortical development tended to have worse seizure outcomes., Conclusions: Reoperative hemispherectomy is an effective and safe treatment for patients who still have seizures after primary hemispherectomy for epilepsy caused by unilateral cortical lesion., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To investigate the clinicopathologic characteristics of intractable epilepsy. Methods: Based on the classification criteria proposed by the International League Against Epilepsy (ILAE), a retrospective analysis of the pathological characteristics was done in 822 patients who underwent epilepsy surgery in Sanbo Brain Hospital, Capital Medical University, from June 2008 to December 2012. Results: The mean age of epilepsy onset was 9.9 years, mean duration of epilepsy was 11.9 years. Complex partial seizures were the main presenting features. Histopathological study showed 33 cases (4.01%) with mild forms of cortical malformations, 690 cases (83.94%) with focal cortical dysplasia (FCD) and 99 cases with others (including 39 pure hippocampal sclerosis, 20 cystosclerosis, 19 Sturge-Weber syndrome, 8 tuberous sclerosis complex, 6 without significant pathological changes, 5 gyral malformations and 2 hamartoma). Among the 690 FCD cases, 106 were FCD typeⅠ, 91 were FCD typeⅡ and 493 were FCDⅢ(Ⅲa: 160, Ⅲb: 106, Ⅲc: 26 and Ⅲd: 201). Conclusions: FCDⅢd is the most common histopathological subtype causing intractable epilepsy, mainly due to focal hypoxia/ischemia in the perinatal period, which results in scarring of local brain tissue; this is followed by other isolated forms of FCD (FCDⅠand FCDⅡ), and then FCD Ⅲa and FCD Ⅲb. The reason to distinguish isolated forms of FCD (types Ⅰ and Ⅱ) from FCD Ⅲ and to subclassify FCD Ⅲ is to allow better definition of cortical dyslamination. Therefore, the pathogenic factors of intractable epilepsy can be grouped in greater details, and facilitate the diagnosis and potential curative treatment of intractable epilepsy.

Rasmussen encephalitis (RE) is a rare neurological disorder of childhood characterized by uni-hemispheric inflammation, progressive neurological deficits and intractable focal epilepsy. The pathogenesis of RE is still enigmatic. Activation of endogenous high-mobility group box-1 (HMGB1) and Toll-like receptor (TLR) has been proved to be with pro-inflammatory as well as pro-convulsant effects. We hypothesized that the epileptogenic mechanisms underlying RE are related to activation of HMGB1/TLR signaling. Immunnohistochemistry approach was used to examine the expression of HMGB1, TLR2, TLR4, receptor for advanced glycation end products (RAGE) in surgically resected human epileptic cortical specimens from RE (n=12), and compared that with control cortical issue (n=6). HMGB1 was ubiquitously detected in nuclei of astrocytes while its receptors were not detected in control cortex specimens. Marked expression of the receptors were observed in the lesions of RE. In particular, HMGB1 was in stead detected in cytoplasm of reactive astrocytes in RE cortex, predictive its release from glial cells. Significant greater HMGB1 and its receptors expression in RE vs. control was demonstrated by western blot. These results provide the novel evidence of intrinsic activation of these pro-inflammation pathways in RE, which suggest the specific targets in the treatment of epilepsy associated with RE., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background/aims: We have demonstrated previously that bipolar electrocoagulation on functional cortex (BCFC) is a safe and effective approach for epilepsy involving eloquent areas. Here, we report the results of BCFC with lesionectomy for patients with epileptogenic foci partially overlapping eloquent areas., Methods: Forty patients who had been treated with lesionectomy with BCFC were retrospectively reviewed with regard to seizure outcome and neurological deficits. Ten similar patients who had received lesionectomy with multiple subpial transections (MST) were examined as a control group., Results: In the lesionectomy group with BCFC, Engel class I was achieved in 18 (45%) patients, class II in 8 (20%) patients, class III in 8 (20%) patients and class IV in 6 (15%) patients. Five (12.5%) patients developed mild hemiparesis and 1 (2.5%) patient mild sensory dysphasia. In the lesionectomy group with MST, Engel class I was achieved in 3 (30%) patients, class II in 2 (20%) patients, class III in 3 (30%) patients and class IV in 2 (20%) patients. Two (20%) patients developed mild hemiparesis and 1 (10%) patient moderate hemiparesis. All these complications recovered within 1-12 months., Conclusions: Compared with MST, the outcome of BCFC with lesionectomy is similar. But since MST leads to mechanical injury, while BCFC causes thermal injury, the complications of BCFC seem less severe., (© 2014 S. Karger AG, Basel.)