Importance:Perampanel (PER) is used less extensively in children than in adults. Currently, there is a lack of data from PER clinical studies with large sample sizes in Chinese children and adolescents with epilepsy, especially those with refractory epilepsy. Objective:To evaluate the effectiveness, retention, and safety of PER in the treatment of children and adolescents with epilepsy in China. Methods:This was a multicenter, prospective, observational study. Children and adolescents with epilepsy who received PER as adjunctive therapy were included. The primary effectiveness endpoint was the proportion of patients achieving a ≥50% reduction in seizure frequency after 6 months of treatment compared to baseline. The secondary effectiveness endpoints included retention and seizure-free rates. The safety outcome was the incidence of treatment-emergent adverse events (TEAEs). Results:A total of 240 patients with epilepsy were enrolled in the study. Prior to initiating PER treatment, approximately 87.9% of them took two or more antiseizure medications. After a 6-month treatment regimen with PER, 70.4% of the patients experienced a reduced seizure frequency of at least 50%, and 22.1% achieved complete seizure freedom. The retention rate was 90.2%. TEAEs were reported by 89 patients, leading to the discontinuation of PER in seven cases. No severe TEAEs were observed in this study. Interpretation:Under routine clinical conditions, PER demonstrated good effectiveness and retention in Chinese children with epilepsy, particularly in those with refractory epilepsy.

To enhance deep learning-based automated interictal epileptiform discharge (IED) detection, this study proposes a multimodal method, vEpiNet, that leverages video and electroencephalogram (EEG) data. Datasets comprise 24 931 IED (from 484 patients) and 166 094 non-IED 4-second video-EEG segments. The video data is processed by the proposed patient detection method, with frame difference and Simple Keypoints (SKPS) capturing patients' movements. EEG data is processed with EfficientNetV2. The video and EEG features are fused via a multilayer perceptron. We developed a comparative model, termed nEpiNet, to test the effectiveness of the video feature in vEpiNet. The 10-fold cross-validation was used for testing. The 10-fold cross-validation showed high areas under the receiver operating characteristic curve (AUROC) in both models, with a slightly superior AUROC (0.9902) in vEpiNet compared to nEpiNet (0.9878). Moreover, to test the model performance in real-world scenarios, we set a prospective test dataset, containing 215 h of raw video-EEG data from 50 patients. The result shows that the vEpiNet achieves an area under the precision–recall curve (AUPRC) of 0.8623, surpassing nEpiNet's 0.8316. Incorporating video data raises precision from 70% (95% CI, 69.8%–70.2%) to 76.6% (95% CI, 74.9%–78.2%) at 80% sensitivity and reduces false positives by nearly a third, with vEpiNet processing one-hour video-EEG data in 5.7 min on average. Our findings indicate that video data can significantly improve the performance and precision of IED detection, especially in prospective real clinic testing. It suggests that vEpiNet is a clinically viable and effective tool for IED analysis in real-world applications.

The aim of the study is to analyze microstate patterns in GLUT1-DS, both before and after the ketogenic diet (KD). We conducted microstate analysis of a patient with GLUT-1 DS and 27 healthy controls. A systematic literature review and meta-analysis was done. We compared the parameters of the patients with those of healthy controls and the incorporating findings in literature. The durations of the patient were notably shorter, and the occurrence rates were longer than those of healthy controls and incorporating findings from the review. After 10 months of KD, the patient’s microstate durations exhibited an increase from 53.05 ms, 57.17 ms, 61.80 ms, and 49.49 ms to 60.53 ms, 63.27 ms, 71.11 ms, and 66.55 ms. The occurrence rates changed from 4.0774 Hz, 4.9462 Hz, 4.8006 Hz, and 4.0579 Hz to 3.3354 Hz, 3.7893 Hz, 3.5956 Hz, and 4.1672 Hz. In healthy controls, the durations of microstate class A, B, C, and D were 61.86 ms, 63.58 ms, 70.57 ms, and 72.00 ms, respectively. Our findings suggest EEG microstates may be a promising biomarker for monitoring the effect of KD. Administration of KD may normalize the dysfunctional patterns of temporal parameters.

Abstract A 23-year-old man with drug-resistant epilepsy was admitted for presurgical evaluation. The epileptogenic zone could not be derived from seizure semiology and scalp electroencephalographic monitoring definitely. MRI showed periventricular nodular heterotopia in occipital horn of left lateral ventricle with high FDG uptake on interictal 18F-FDG PET scan, whereas the hypometabolic zone in the left medial temporal lobe was also found on PET with no abnormality on MRI. Stereoelectroencephalographic implantation was performed to identify the seizure-onset zone. Two independent epileptogenic foci located in periventricular nodular heterotopia and left hippocampus were validated by stereoelectroencephalographic monitoring and the outcome of subsequent thermocoagulation.

Diagnosis of non-convulsive status epilepticus (NCSE) is challenging and outcomes during follow-up are not clear. This study aimed to conduct power spectrum analysis in NCSE and measure outcomes of patients. We searched continuous EEG monitoring (cEEG) recordings to identify patients of NCSE. An artifact-free cEEG epoch of continuous 60 s was chosen for spectral power analysis. We also collected electronic medical records of the patients for extracting clinical information. Patients recruited were followed up at least every half a year. There were 48 patients with 64 independent NCSE episodes during different course of disease recruited in the study, with a mean age of 40.3 ± 19.1 years (range, 12–72 years), including 24 males (50

Objective To evaluate the clinical and paraclinical features of Chinese patients with anti- LGI1 encephalitis. Methods Patients with memory deficits, psychiatric symptoms, seizures or altered level of consciousness, suspicious of encephalitis, at presentation to Peking Union Medical College Hospital were recruited between July 2013 and January 2018, and tested for anti-LGI1 antibodies in their serum and/or cerebrospinal fluid(CSF) samples. Patients with anti-LGI1 antibodies were enrolled. The demographic characteristics, clinical manifestations, laboratory examination results, neuroimaging features, immunotherapy, follow-up practices and outcomes for included patients were registered and analyzed. Results The study enrolled 120 patients, of whom 66.7% were male. The median age was 61 years (interquartile range [IQR]: 49-66 years). Seizures(65.0%) were the most common initial symptoms. Most patients developed seizures (95.0%), including faciobrachial dystonic seizures (54.2%), memory deficits (92.5%), and psychiatric symptoms (69.1%). Brain MRI and 18F-FDG PET / CT showed that the lesions were mainly located in unilateral or bilateral medial temporal lobes, and (or) basal ganglia. Of the patients, 95.0% received intravenous immunoglobulin (IVIg) or corticosteroids, 47.5% received mycophenolate mofetil as long-term immunotherapy, and no one received second-line immunotherapy. The median follow-up was 34.2 months(IQR: 22.0-45.6 months). 91.2% had a good outcome (modified Rankin Scale score≤2 points). Residual mild memory deficits were present in 47.8% of the patients. Nine deaths were documented. Relapses occurred in 24.8% of the patients in the first year. In total, 24 (20%)cases were young patients(onset age ≤45 years).There were fewer males among the younger patients(37.5% vs. 74.0%, P < 0.01). Besides, there were fewer younger patients with psychiatric symptoms(50.0% vs. 74.0%, P=0.02), hyponatremia(33.3% vs. 68.8%, P < 0.01), and abnormalities on brain 18F-FDG PET/CT(20.8% vs. 47.9%, P=0.02). The relapse-free survival rate was significantly higher in the young patients. Conclusions Elderly males were predominant in patients with anti-LGI1 encephalitis. Most patients developed symptoms of limbic encephalitis and/or FDBS during the disease course. Several patients were young adults and lacked typical symptoms. Neuroimaging features were consistent with the involvement of limbic system or basal ganglia. Patients with anti-LGI1 encephalitis respond well to immunotherapy, irrespective of the age.

Managing epilepsy in the elderly remains complicated largely due to factors related to aging. In this population, management practices are increasingly shifting towards the use of newer-generation anti-seizure medications (ASMs) as they are generally associated with better tolerability and safety profiles than older ones. Perampanel is a new ASM with broad-spectrum efficacy and a favorable safety profile. However, because of the lack of information and experience in its use, the prescription of perampanel has not been optimized in the elderly in the real-world setting in Asia. A group of epilepsy experts across the region convened at a series of virtual meetings to share their experience and discuss recommendations on perampanel use in elderly patients, including dose optimization, considerations with treatment initiation, and strategies to manage adverse events and maximize tolerability. This article summarizes key clinical and real-world evidence for perampanel in the elderly and consolidates the experts' opinions on optimizing perampanel use in elderly Asian patients with epilepsy, providing practical guidance for clinicians to address challenges related to treatment initiation and tolerance.

Tuberous sclerosis complex (TSC) is mainly caused by variants in TSC1 and TSC2, which encodes hamartin protein and tuberin protein, respectively. Here, we report clinical and molecular characteristics of 18 families with TSC. High-throughput DNA sequencing was employed to detect variants in all the exons and flanking region of TSC1 and TSC2. TA clone and real-time PCR were performed to verify the pathogenicity of candidate variants. A total of 17 mutations were identified, including 13 mutations in TSC2 and 4 mutations in TSC1. Fifty-six percent (10/18) of the families carried de novo mutations, and 8 of these mutations were not reported previously. Most mutations detected were loss-of-function mutations (15/17). One splice-site mutation (TSC2 c.599 + 5G > A) caused abnormal splicing and was confirmed by in vitro analysis. Facial angiofibromas (94%) and epilepsy (89%) were the most prevalent clinical features in our patients. Treatment with anti-seizure medication (ASM) or in combination with rapamycin results in clinical remission in most patients with TSC-associated seizures (14/15). For genotype–phenotype correlation, patients in our cohort with TSC2 mutations had an earlier onset age and patients with TSC1 showed better response to ASM. Our study has expanded the spectrum of TSC1 and TSC2 causing TSC.

Temporal lobe epilepsy (TLE) is the most common form of adult epilepsy, frequently accompanied with cognitive deficits. The present study aims to investigate functional network alterations affected by cognitive impairments in drug-resistant TLE. Patients with drug-resistant TLE were divided into normal cognition (NC) and abnormal cognition (AC) groups based on their primary medical history and completed the Wechsler intelligence scale. Thirty-one patients in the NC group and 30 in the AC group had mean intelligence quotients (IQ) of 107 (96-137) and 71 (60-85), respectively. Eighteen controls were enrolled in the study. Graph theory analysis showed decreased alpha small world index (SWI) in the AC group compared to that in the NC group and controls. Increased SWI in the fast rhythm was observed in both TLE groups compared with controls. But the gamma SWI in the AC group declined and was significantly lower than in the NC group at 50–70 Hz. A lower IQ is associated with a decreased SWI in alpha and 50-70Hz. Spectral analysis revealed reduced alpha power and increased delta power in the TLE groups compared to the controls. Immunofluorescence analysis revealed more severe amyloid-β (Aβ) and phosphorylated Tau (p-Tau) loads in the resected hippocampus of the AC group than that of NC group. Cognitive deficits in drug-resistant TLE are associated with general EEG activity slowing, loss of efficiency in gamma connectivity, and increased Aβ and p-Tau expression. These alterations are potential markers and intervention targets for concomitant cognitive decline in drug-resistant epilepsy.

Objective To report the clinical manifestations, EEG characteristics, diagnosis and treatment of 3 children with "benign epileptic discharge", and analyze the causes of misdiagnosis and treatment. Methods and Results The clinical data of 3 children with centrotemporal spikes (CTS) in EEG treated in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences from December 2008 to October 2020 were retrospectively analyzed. Case 1 presented with non-epileptic seizure, which was misdiagnosed as "epilepsy" due to episodic events and CTS, and was eventually diagnosed as night fright based on clinical manifestations and EEG. Case 2 did not have clinical seizures, but was misdiagnosed as "epilepsy" due to CTS, and took antiepileptic drugs (AEDs) for several years. Although benign childhood epilepsy with central-temporal spikes (BECTS) was diagnosed in Case 3, the dosage and types of AEDs were increased even when the clinical seizures were well controlled. After diagnosis, AEDs was not performed in Case 1, AEDs were gradually stopped in Cases 2 and Case 3, and no epileptic seizure was observed. Conclusions "Benign epileptic discharge" is common in children's EEG examination. It is the key point to avoid the misdiagnosis and mismanagement to determine whether there is a causal relationship between EEG abnormalities and clinical seizures. For children with "benign epileptic discharge", the antiepileptic therapy is aimed at controlling clinical seizures rather than eliminating EEG abnormalities.

对患者人际互动过程的会话分析在临床诊断中的作用已获证实,其中最具代表性的是,对患者会话中互动特征、话题特征和语言特征的分析能够有效鉴别临床上不易鉴别的痫性发作和心因性非痫性发作.对汉语痫性发作和心因性非痫性发作患者的会话特征分析证实:患者会话中提供发作信息的主动性、陈述的努力程度、否定性表达的使用等特征对于鉴别诊断痫性发作与心因性非痫性发作具有重要价值.研究也进一步表明,会话分析在医学临床诊断中具有实际的应用价值,通过病史记录阶段的医患沟通特征的会话分析,能够为某些神经系统疾病的鉴别诊断提供借鉴.

Multimodal image integration (MMII) is a promising tool to help delineate the epileptogenic zone (EZ) in patients with medically intractable focal epilepsies undergoing presurgical evaluation. We report here the detailed methodology of MMII and an overview of the utility of MMII at the Cleveland Clinic Epilepsy Center from 2014 to 2018, exemplified by illustrative cases. The image integration was performed using the Curry platform (Compumedics Neuroscan ™ , Charlotte, NC, USA), including all available diagnostic modalities such as Magnetic resonance imaging (MRI), Positron Emission Tomography (PET), single-photon emission computed tomography (SPECT) and Magnetoencephalography (MEG), with additional capability of trajectory planning for intracranial EEG (ICEEG), particularly stereo-EEG (SEEG), as well as surgical resection planning. In the 5-year time span, 467 patients underwent MMII; of them, 98 patients (21%) had a history of prior neurosurgery and recurring seizures. Of the 467 patients, 425 patients underwent ICEEG implantation with further CT co-registration to identify the electrode locations. A total of 351 patients eventually underwent surgery after MMII, including 197 patients (56%) with non-lesional MRI and 223 patients (64%) with extra-temporal lobe epilepsy. Among 269 patients with 1-year post-operative follow up, 134 patients (50%) had remained completely seizure-free. The most common histopathological finding is focal cortical dysplasia. Our study illustrates the usefulness of MMII to enhance SEEG electrode trajectory planning, assist non-invasive/invasive data interpretation, plan resection strategy, and re-evaluate surgical failures. Information presented by MMII is essential to the understanding of the anatomo-functional-electro-clinical correlations in individual cases, which leads to the ultimate success of presurgical evaluation of patients with medically intractable focal epilepsies.

Diagnosis of hyperkinetic movement disorders with an unknown cause is usually challenging. The objective of this study is to learn about video electroencephalogram (VEEG) combined with electromyography (EMG) in the diagnosis of hyperkinetic movement disorders with an unknown cause. We performed an observational cohort study by recruiting consecutive patients with hyperkinetic movements as the main manifestation with an unknown cause for VEEG combined with EMG evaluations. A total of 77 consecutive patients were enrolled for VEEG-EMG examination. Among them, 57 patients changed their diagnosis after VEEG-EMG assessment, with a mean final diagnosis age of 35.4 ± 20.3 years (range, 4–74 years). The mean duration between initial and final diagnosis was 54.8 ± 71.3 months (range 0.5–300 months). The most common misdiagnosed hyperkinetic movement disorders were myoclonus (40.4%), followed by tremors (24.6%), dystonia (15.8%), psychogenic movement disorders (10.5%), and periodic leg movement syndrome (PLMS) (7.0%). Outcomes of therapy were significantly improved after VEEG-EMG examination (p = 0.000). Simultaneous VEEG and EMG are important in the diagnosis of hyperkinetic movement disorders with an unknown cause.

Introduction: It remains controversial whether the periodic discharges (PDs) pattern is an ictal or interictal phenomenon. The aims of the study are to apply time-frequency and power spectrum analysis to study the PDs pattern and prediction of seizures.Methods: We retrospectively searched continuous electroencephalography (cEEG) recordings to identify patients exhibiting the PDs pattern. Artifact-free cEEG segments demonstrating the PDs pattern with stable baselines were chosen for time-frequency and power spectrum analysis.Results: In total, 72 patients (1.3%) exhibited the PDs pattern, with a mean age 36.0 ± 20.7 years (range, 8–76 years). The median spectral power of PDs with a length of 60 s was 70.94 μV2 and that of PDs with a length of 20 s was 195.80 μV2. During follow-up, patients with spectral power of PDs of length 60 and 20 s lower than 28.65 and 36.09 μV2, respectively, exhibited no seizure. For predicting seizures, when the spectral power for PDs of 60 and 20 s equaled to 17.26 and 21.40 μV2, respectively, the diagnostic sensitivity was 100% and specificity was 86%. The locations of maximal spectral power of PDs, crude seizure onset zone (SOZ) judged from scalp EEG, and the most prominent regions of hyper- or hypo-metabolism on FDG-PET were congruent.Conclusions: Spectral power might be a candidate seizure marker of the PDs pattern. High spectral power predicted a high risk of seizures, and low spectral power was associated with a low risk of seizures.

Background: This study aimed to investigate the semiology of seizure disorders, including electroencephalographic characteristics, and seizure outcomes in participants with anti-leucine-rich gliomainactivated 1 (LGI-1) encephalitis. Methods: Seventy participants who presented with seizures during the acute phase of anti-LGI-1 encephalitis at Peking Union Medical College Hospital from May 2013 to July 2020 were reviewed. All participants underwent follow-up for longer than 2 years. Results: At the time of presentation, 48 (68.6%) participants had generalized seizures and 57 (81.4%) had focal seizures. The most common focal motor seizures were faciobrachial dystonic seizures (FDS). The main manifestations of focal nonmotor seizures were dyscognitive features, goosebumps, and disorders of sensation. All participants received immunomodulatory therapy. Thirty-five (50%) participants were seizure free after 1 year of follow-up, and 48 (68.6%) participants were seizure free over a follow-up of 2 years. Participants with seizures continued longer than 1 year were older than participants whose seizure duration was shorter than 1 year (P = 0.021). However, after an extended follow-up period, the difference between the incidences of seizures based on age was not significant. The frequency of focal motor seizures was higher in participants who became seizure free within 1 year, compared to participants who had seizures for longer than 1 year (75% vs 54.3%, respectively; P = 0.015). Participants with seizures continued over 2 years tended to have focal nonmotor seizures, and tended to show an elevated incidence of abnormal EEG results. Participants receiving early corticosteroid and longer duration immunosuppressant treatments, tended to have a lower risk of persistent seizures and better seizure outcomes, with no statistical significance. Conclusions: Most participants obtained remission from seizures after immunomodulatory therapy. The seizure manifestation of anti-LGI1 encephalitis is diverse and variable. The type of focal seizures may affect the outcome of participants with seizures. Older age could lead to longer duration of the seizure disorder, but did not affect the rate of seizures over the long term. Early and prolonged administration of immunomodulatory therapy may be useful for shortening the time to becoming seizure free. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

[This corrects the article DOI: 10.3389/fneur.2020.00696.].

Objective. Electroencephalogram (EEG) is a sensitive method for evaluation of anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. The aim was to investigate the EEG and clinical features and correlations in patients with anti-NMDAR encephalitis. Methods. Anti-NMDAR encephalitis patients (n = 98) with at least 1 EEG recording in our hospital were recruited between January 2012 and October 2017. We reviewed and analyzed the EEG and clinical data. Results. In our cohorts, 79 patients underwent EEG in the disease acute stage, and 39 in the recovery stage. Of the 79 patients, 70 (88.6%) EEG recordings in acute period were abnormal. Symptoms, including consciousness, movement disorder, coma, were correlated to the degree of EEG abnormalities (P < .05). The patients with more severe EEG abnormalities also had longer hospitalized and intensive care unit stay time (P < .05). We found that the EEG pattern of abnormal occipital alpha rhythm had a correlation with the clinical severity, and the Spearman coefficient was 0.448 (P = .000). Neither delta activities distribution nor prevalence showed correlations with clinical severity in acute stage. However, delta activities significantly decreased in the disease recovery stage. The other findings of EEG records were extreme delta brush (7cases, 8.9%), excess delta activities (diffuse slowing 30 cases, 38.0%), and epileptiform discharge (10 cases, 14.3%). Conclusion. This is the largest study of EEG recording in patients with anti-NMDAR encephalitis patients in China. EEG abnormalities, particularly occipital alpha rhythm, are correlated with clinical severity. EEG is useful for diagnosis and monitoring of treatment response in conjunction with clinical improvement.

Objective:Sleep disorders are common in voltage-gated potassium channel complex antibody (VGKC-Ab) diseases. The aim was to investigate the sleep disturbances and polysomnography (PSG) characteristics in patients with VGKC-Ab-associated diseases. Methods:Twenty-seven patients with leucine-rich glioma-inactivated protein 1 antibody (LGI1-Ab) encephalitis, seven patients with contactin protein-like 2 antibody (Caspr2-Ab)-associated diseases, and 14 healthy controls with at least one PSG or actigraphy recording were recruited at Peking Union Medical College Hospital from January 2014 to July 2019. Results:Sleep disorders including insomnia, hypersomnia, rapid eye movement (REM) sleep behavior disorder (RBD), periodic limb movements in sleep (PLMS), agrypnia excitata, and obstructive sleep apnea syndrome were observed. Twenty-one PSG recordings from patients with LGI1-Ab encephalitis demonstrated a decrease in total sleep time (TST) (median 365.5, range 184.5-495.5 min), sleep efficiency (70.0%, 47-92%), N3 sleep (9.7%, 0-32.9%), and REM sleep (9.9%, 0.4-27.9%). Of five patients with Caspr2-Ab-associated diseases, TST was found to be 329.5 (167.0-377.5 min), and sleep efficiency was found to be 61.7% (34.6-71.7%). The percentage for N3 and REM sleep was found to be 15.0% (0-34.6%) and 12.7% (0-22.2%), respectively. Both RBD and PLMS were observed more frequently in patients with LGI1-Ab encephalitis. We identified status dissociatus (SD) in five (23.8%) patients with LGI1-Ab encephalitis and two (40%) patients with Caspr2-Ab diseases. The former is more likely to have simple limb movements rather than complex movements, which mimic the contents of their dreams. Continuous insomnia was more common in patients with Caspr2-Ab diseases than patients with LGI1-Ab encephalitis. Patients reported clinical and PSG improvements following immunotherapy. Conclusion:Sleep disorders in patients with VGKC-Ab-associated diseases include decreased TST and poor sleep efficiency. Our studies provide evidence of SD in patients with LGI1-Ab encephalitis.

[This corrects the article DOI: 10.3389/fneur.2020.00696.].