OBJECTIVE:Tuberous sclerosis complex (TSC) is a genetic multisystem disorder with a high prevalence of drug-resistant epilepsy (DRE), significantly affecting patients' quality of life. For patients with TSC lacking localizing epileptogenic tuber, resective surgery is often not feasible. Vagus nerve stimulation (VNS) has been proposed as an alternative surgical therapy, although robust evidence in TSC-related DRE remains limited. METHODS:A prospective cohort study was conducted between December 2019 and July 2024 across multiple epilepsy centers in China. Seventy patients with TSC-related DRE were enrolled, all lacking resectable epileptogenic tubers on multidisciplinary evaluation and ineligible for resective surgery. Participants were divided into VNS (n = 20) and medication-only (n = 50) groups based on actual treatment, and followed for up to 3 years. Seizure outcomes, anti-seizure medication use, IQ, and quality of life were evaluated longitudinally. RESULTS:The VNS group demonstrated significantly higher response rates at 1-, 2-, and 3-year follow-ups (65%-75%) compared to the medical treatment group (31%-36%). Median and average seizure frequency reductions were also greater in the VNS group. VNS was associated with significantly higher treatment response than medication, with the relative risk (RR) of response being 1.81 (95% confidence interval [CI]: 1.22-2.67), 2.21 (95% CI: 1.42-3.44), and 2.42 (95% CI: 1.49-3.93) at 1-, 2-, and 3-year follow-ups (p < 0.01). Seizure recurrence was significantly lower in the VNS group (p < 0.01). Moreover, VNS treatment led to significant reductions in anti-seizure medication (ASM) use and improvement in intelligence quotient and quality of life at the 2-year follow-up. Treatment modality was the only independent predictor of clinical response. VNS was well tolerated, with only mild surgical complications and no permanent adverse events reported. SIGNIFICANCE:VNS significantly improves seizure control, cognitive outcomes, and quality of life, with a favorable safety profile. These findings support VNS as an effective and safe alternative for this specific TSC population. Future randomized controlled trials are warranted to further validate these results.

Epilepsy with its complex seizure mechanisms and diverse clinical manifestations, presents numerous challenges for clinical diagnosis and treatment, while electroencephalography (EEG) plays a crucial and irreplaceable role in its diagnosis. Although general-purpose foundation models have demonstrated some capability in knowledge processing, they still face challenges in capturing specific disease features and dealing with data scarcity in highly specialized domains such as epilepsy. To address these issues, we propose a domain-specific foundation model for epilepsy-EpilepsyFM, designed to learn generalized representations of epilepsy to support various downstream tasks. EpilepsyFM utilizes self-supervised pre-training, integrating clinical EEG data from top-tier hospital neurosurgery departments with large-scale public datasets such as TUH EEG Corpus, covering a variety of patient conditions to enhance the model's representation capacity. The model employs a discrete neural tokenizer to construct a domain-specific neural codebook for epilepsy and proposes a brain region masking strategy based on the mechanisms of clustered neuronal discharges during seizures, allowing for more effective capture of the spatiotemporal features of seizures. Furthermore, EpilepsyFM integrates temporal, spectral, and spatial encoding modules to fully exploit the multidimensional propagation patterns of epilepsy. Experimental results show that EpilepsyFM achieves state-of-the-art performance in six downstream tasks, including seizure detection, seizure type detection, short- and long-term signal forecasting, frequency-phase forecasting, anti-seizure medication efficacy analysis, and radiofrequency thermocoagulation surgery analysis, demonstrating outstanding generalization ability and broad clinical application potential.

High-performance methods for automated detection of epileptic stereo-electroencephalography (SEEG) have important clinical research implications, improving the diagnostic efficiency and reducing physician burden. However, few studies have been able to consider the process of seizure propagation, thus failing to fully capture the deep representations and variations of SEEG in the temporal, spatial, and spectral domains. In this paper, we construct a novel long-term SEEG seizure dataset (XJSZ dataset), and propose Signal Embedding Temporal-Spatial-Spectral Transformer (SE-TSS-Transformer) framework. Firstly, we design signal embedding module to reduce feature dimensions and adaptively construct optimal representation for subsequent analysis. Secondly, we integrate unified multi-scale temporal-spatial-spectral analysis to capture multi-level, multi-domain deep features. Finally, we utilize the transformer encoder to learn the global relevance of features, enhancing the network's ability to express SEEG features. Experimental results demonstrate state-of-the-art detection performance on the XJSZ dataset, achieving sensitivity, specificity, and accuracy of 99.03 %, 99.34 %, and 99.03 %, respectively. Furthermore, we validate the scalability of the proposed framework on two public datasets of different signal sources, demonstrating the power of the SE-TSS-Transformer framework for capturing diverse multi-scale temporal-spatial-spectral patterns in seizure detection.

Monitoring neural population activity at single-cell resolution is essential for driving fundamental research and clinical innovations. However, translating advanced recording techniques from animal models to humans remains a significant challenge. Flexible neural electrodes have recently emerged as powerful tools for large-scale single-unit recordings due to their superior biocompatibility and high recording density. Here, we demonstrate reliable, high-density single-unit recordings during intraoperative procedures in human patients using u ltra- F lexible I mplantable N eural E lectrode (uFINE) arrays. The uFINE array exhibited sufficient mechanical robustness to maintain structural integrity throughout surgical operations. We successfully recorded 616 single units from 10 patients, with up to 135 single units simultaneously recorded. The flexibility of uFINE array minimized signal disturbances from brain pulsations, enabling stable and continuous single-unit detection. Stimulus and response tuning were observed at the level of individual neurons in awake patients. This uFINE-based recording approach offers unique opportunities to investigate human-specific cognitive functions and develop next-generation brain-machine interfaces. ### Competing Interest Statement Z.Z. and X.L are the founders of Shanghai Stairmed Technology Co., Ltd.. Z.Z., X.L are co-inventors on a patent (CN202210689990.9, 2022) on the electrode related to this study. The other authors declare no competing interest.

[This corrects the article DOI: 10.3389/fnins.2019.00254.].

High-performance methods for automated detection of epileptic stereo-electroencephalography (SEEG) have important clinical research implications, improving the diagnostic efficiency and reducing physician burden. However, few studies have been able to consider the process of seizure propagation, thus failing to fully capture the deep representations and variations of SEEG in the temporal, spatial, and spectral domains. In this paper, we construct a novel long-term SEEG seizure dataset (LTSZ dataset), and propose channel embedding temporal-spatial-spectral transformer (CE-TSS-Transformer) framework. Firstly, we design channel embedding module to reduce feature dimensions and adaptively construct optimal representation for subsequent analysis. Secondly, we integrate unified multi-scale temporal-spatial-spectral analysis to capture multi-level, multi-domain deep features. Finally, we utilize the transformer encoder to learn the global relevance of features, enhancing the network’s ability to express SEEG features. Experimental results demonstrate state-of-the-art detection performance on the LTSZ dataset, achieving sensitivity, specificity, and accuracy of 99.48 https://github.com/lizhuoyi-eve/CE-TSS-Transformer .

Background Genetic generalized epilepsy (GGE) accounts for nearly one-third of all epilepsies. The feature of status epilepticus (SE) in patients with GGE has been rarely studied. We aimed to determine the electroclinical characteristics of SE in patients with GGE. Methods In this retrospective study, nine patients with GGE were enrolled at Xijing Hospital, Xi’an, China from May 2014 to May 2020. SE was confirmed by 24-h video-EEG recording. The demography, clinical manifestation, brain MRI and SE pattern were analyzed. Results Of the nine patients in the study, seven were female. The mean age of the patients at the time of inclusion was 16.8 years (range 7–31 years), and the mean age at the onset of epilepsy was 10.9 years (range 6–17 years). The follow-up time ranged from 3 months to 6 years. Myoclonic absence status was identified in four patients showing eyelid myoclonia with absence and one patient showing perioral myoclonia with absences. Myoclonic SE was identified in three patients showing juvenile myoclonic epilepsy. Autonomic SE was found in one patient with eyelid myoclonia with absence. SE was terminated by oral midazolam in four patients. In the other five patients, SE terminated spontaneously. Conclusions The seizure type of SE in patients with GGE is often consistent with their major symptoms. Oral midazolam may be an option to terminate SE in patients with GGE.

Most seizures in critical ill patients are non-convulsive, and some patients may develop non-convulsive status epilepticus (NCSE), a state of continuous or repetitive seizures without convulsions. With the growing use of continuous electroencephalogram (EEG) monitoring in neuro-intensive care units, non-convulsive seizure (NCS) and NCSE are increasingly diagnosed in patients with impaired consciousness, and progress has been made in identifying various EEG characteristics of NCS/NCSE. Epidemiological studies have contributed to a better understanding of etiologies and risk factors for NCS and NCSE. However, sufficient clinical trials about the treatment of NCS and NCSE are still lacking. The appropriate level of aggressiveness in the treatment of NCSE is still debated, particularly with regard to the use of anesthetics in patients with refractory NCSE. In this review, we summarize the EEG, clinical, epidemiological, diagnostic and therapeutic knowledge of NCS and NCSE in the neuro-intensive care setting in detail.

Functional near infrared spectroscopy (fNIRS) is an emerging non-invasive technique that allows bedside measurement of blood oxygenation level-dependent hemodynamic signals. We aimed to examine the efficacy of resting-state fNIRS in detecting the residual functional networks in patients with disorders of consciousness (DOC). We performed resting-state fNIRS in 23 DOC patients of whom 12 were in minimally conscious state (MCS) and 11 were in unresponsive wakefulness state (UWS). Ten regions of interest (ROIs) in the prefrontal cortex (PFC) were selected: both sides of Brodmann area (BA) 9, BA10, BA44, BA45, and BA46. Graph-theoretical analysis and seed-based correlation analyses were used to investigate the network topology and the strength of pairwise connections between ROIs and channels. MCS and UWS exhibited varying degrees of the loss of topological architecture, and the regional nodal properties of BA10 were significantly different between them (Nodal degree, PLeft BA10 = 0.01, PRight BA10 < 0.01; nodal efficiency, PLeft BA10 = 0.03, PRight BA10 < 0.01). Compared to healthy controls, UWS had impaired functions in both short- and long-distance connectivity, however, MCS had significantly impaired functions only in long-distance connectivity. The functional connectivity of right BA10 (AUC = 0.88) and the connections between left BA46 and right BA10 (AUC = 0.86) had excellent performance in differentiating MCS and UWS. MCS and UWS have different patterns of topological architecture and short- and long-distance connectivity in PFC. Intraconnections within BA10 and interhemispheric connections between BA10 and 46 are excellent resting-state fNIRS classifiers for distinguishing between MCS and UWS.

Purpose: Eating epilepsy was previously known as a kind of focal reflex epilepsy. However, the development of eating-induced multiple generalized seizures and the associated EEG changes were rarely reported. Herein, we present a 13-year-old generalized epilepsy patient with eating-induced generalized seizures since the age of 5. Case presentation: The 13-year-old male patient had suffered from late-onset eating-induced epileptic spasms during the meal since the age of 5. Meanwhile, he also experienced spontaneous epileptic spasms during the period of sleep. The seizure frequency and type gradually increased from 7 years of age. In addition to epileptic spasms, he started experiencing atypical absence with myoclonic jerks during the meal. Ictal EEG presented as the appearance of an irregular slow-wave mixed with generalized polyspike wave with the intake of food, and gradually evolved to bursts of generalized polyspike wave complexes. At the end of the meal, the EEG returned to normal. Nevertheless, at the age of 13, his seizure frequency increased and appeared new seizure type, and besides epileptic spasm and atypical absence, he began to experience myoclonic seizure during sleep and awaking-generalized tonic-clonic seizure in the morning. In this period he started taking valproic acid, topiramate and clonazepam, and his seizure frequency was reduced. Conclusion: In conclusion, this case demonstrated the variability of eating induced multiple generalized seizure types, and eight years follow-up also indicates that generalized epilepsy progressed with age. The EEG and clinical changes of our patient contribute to a better understanding of the electro-clinical features of eating-induced multiple generalized seizures and the course of generalized epilepsy with such seizures. (C) 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reservedy.

A seizure is one of the leading neurological disorders. NMDA receptor-mediated neuronal excitation has been thought to be essential for epileptogenesis. As an endogenous co-agonist of the NMDA receptor, D-serine has been suggested to play a role in epileptogenesis. However, the underlying mechanisms remain unclear. In the current study, we investigated the effects of antagonizing two key enzymes in D-serine metabolism on the development of seizures and the downstream signaling. Our results showed that serine racemase (SR), a key enzyme in regulating the L-to-D-serine conversion, was significantly up-regulated in hippocampal astrocytes in rats and patients who experienced seizure, in comparison with control rats and patients. L-aspartic acid β-hydroxamate (LaaβH), an inhibitor of SR, significantly prolonged the latencies of seizures, shortened the durations of seizures, and decreased the total EEG power in rats. In contrast, D-amino acid oxidase inhibitor 5-chlorobenzo[d]isoxazol-3-ol (CBIO), which can increase D-serine levels, showed the opposite effects. Furthermore, our data showed that LaaβH and CBIO significantly affected the phosphorylation of Extracellular Signal-regulated Kinase (ERK). Antagonizing or activating ERK could significantly block the effects of LaaβH/CBIO on the occurrence of seizures. In summary, our study revealed that D-serine is involved in the development of epileptic seizures, partially through ERK signaling, indicating that the metabolism of D-serine may be targeted for the treatment of epilepsy.

Narcolepsy is a life-long neurological disorder characterized by excessive daytime sleepiness (EDS) and cataplexy. At present, Sodium oxybate, modafinil, methylphenidate and other stimulants are recommended first-line therapies for narcolepsy but are difficult to obtain in China. One hundred forty-eight patients with narcolepsy were treated with antidepressants and administered the Epworth Sleepiness Scale (ESS) and the Maintenance of Wakefulness Test (MWT) before and after treatment from August 2012 to August 2017. The subjects were followed for 1-6 years after treatment. Improvement in sleepiness, cataplexy, cataplexy-like episodes, and antidepressant side effects were assessed. There were significant differences in the mean sleep latency (MSL) and sleep onset rapid eye movement periods (SOREMP5) in MWT and ESS scores, cataplexy and cataplexy-like episodes before and after treatment (p < 0.01). Venlafaxine demonstrated significantly greater improvements in MSL in the MWT (p < 0.01). Early awakenings and dry mouth were the most common adverse effects. (C) 2019 Elsevier Ltd. All rights reserved.

Photosensitive is probably caused by multiple factors including gender, familiar, etc. We aim to study the clinical and EEG features of Chinese Han patients with photosensitivity. A total of 5482 consecutive patients with possible epilepsy from 3 center in China. Of the 73 patients with PPR to IPS, 48 were female. 69.9% patients were evoked by frequency ranged 8 Hz-25 Hz, with accompanying seizures in 13 patients. 6 of 9 patients with eyes closure sensitivity experienced epileptic seizures during IPS. We found some new features: 1) The patients with eyes closure sensitivity apt to experience electro-clinical seizures provoked by IPS; 2) Female epilepsy patients with PPR and ECS maybe difficult to be seizure free. Preventive measures for related seizures should be performed to the patients with generalized PPR, upper threshold evoking frequency, and eyes closure sensitivity when they received the IPS. (C) 2019 The Authors. Published by Elsevier Ltd.

ABSTRACT Aims . To determine the electroclinical features of fixation‐off sensitivity (FOS) in patients with idiopathic generalized epilepsy (IGE). Methods . We searched the EEG database using the terms “fixation‐off sensitivity” and “idiopathic generalized epilepsy” over a four‐year period from March 2014 to April 2018 in the Xijing Hospital, Xi’an, China. FOS was evaluated according to the technique proposed by Panayiotopoulos. Photic stimulation procedure and neuropsychological testing were performed during video‐EEG monitoring. Results . FOS was observed in eight patients with several different IGE syndromes, including four with eyelid myoclonia/Jeavons syndrome, two with juvenile myoclonic epilepsy, one with photosensitivity epilepsy, and one with epilepsy with generalized tonic‐clonic seizures only. FOS was associated with seizures in five patients manifesting with eyelid myoclonic, myoclonic, and myoclonic‐tonic‐clonic seizures, and eyelid myoclonic status. FOS coexisted with photosensitivity in six patients as independent EEG features. Neuropsychological testing revealed transitory cognitive impairments associated with FOS. Conclusions . FOS is associated with several different IGE syndromes and may coexist with photosensitivity in the same patient as independent EEG features. FOS may be associated with both clinical seizures and cognitive impairments. Intermittent photic stimulation and registration of different eye conditions with and without fixation will aid the study of the dynamics of the visual system in epilepsy patients. [ Published with video sequences on www.epilepticdisorders.com ]

Most sleep-related seizures occur during non-rapid eye movement (NREM) sleep, particularly during stage changes. Sleep-related hypermotor epilepsy (SHE) is a rare epileptic syndrome characterized by paroxysmal motor seizures, mainly arising from NREM sleep. Here, we report a patient with SHE who had seven seizures captured on video-EEG-polysomnography during REM sleep. Ictal semiology of this patient ranged from brief paroxysmal arousals to hypermotor seizures. On EEG-polysomnography, the spontaneous arousals were more frequent during REM than NREM sleep, with a considerably higher arousal index in REM sleep (20/hour). While the reason for seizures during REM sleep in this patient is unclear, we speculate that the threshold and mechanisms of arousal during different sleep stages may be related to the occurrence of seizures. [Published with video sequences on www.epilepticdisorders.com].

This paper set out to demonstrate the clinical features of IGE patients coexisting with FOS, meanwhile to evaluate the consciousness and higher cognitive functions during the long term generalized epileptic discharges elicited by elimination of central vision and fixation. The database of EEG records was searched for FOS and IGE over 4 years from January 2014 to November 2017 at Xijing hospital, Xi’an, China. FOS was evaluated according to the technique proposed by Panayiotopoulos. Photic stimulation procedure was performed according the methodology of updated European algorithm for visual stimulation. In order to evaluate the degree of possible transient impaired consciousness and cognitive function caused by the epileptic discharges, neuropsychological evaluation was performed during video-EEG monitoring with eyes open and with eye closed according the procedure developed by the European taskforce. For comparison, performance during eye open period was set as the normal baseline. We identified five (four males and one female) young IGE patients with FOS (one GTCS-only; one JME, two EMA/JS, one IGPE photosensitivity epilepsy). Three of them had family history of epilepsy. All the patients presented with FOS, two of them manifest with FOS associated with seizures captured by video-EEG, four of them coexisted with photosensitivity (two confirmed, two probable). The GTCS was well managed on AED. Two patients complained the GTCS were only provoked by and emotional stress, one patient complained seizures were only triggered by television, the other two patients reported no precipitating factors. The EEG features of FOS presented as high amplitude generalized epileptic discharge predominantly over frontal and occipital regions. Consciousness (awareness and responsiveness) looked like well-preserved during longstanding generalized epileptic discharge induced by elimination of visual fixation, while mild transitory impairment of higher cognitive functions was observed when neuropsychological testing was performed. (1) The fixation-off phenomenon as a reflex EEG phenomenon in IGE may either manifest with seizures or represent an EEG abnormality associated with higher cortical cognitive impairment. (2) Neuropsychological assessment can make a highly contribution to the understanding of the mechanisms of consciousness and higher cortical cognitive function in epilepsy. Both concomitant Video-EEG and high-precision neuropsychological testing are necessary to detect the subtle symptom. (3) FOS may be not self-limiting, could occur in several different idiopathic generalized epilepsy syndromes, and therefore, their occurrence alone is not sufficient to characterize a definite epilepsy syndrome.

OBJECTIVE:The objective of this study was to assess the electroclinical aspects and treatment of Han patients with juvenile myoclonic epilepsy (JME) in northern China. METHODS:One hundred fifty-six outpatients with JME from six epilepsy centers, between January 2011 and June 2012, were followed up for at least two years. They underwent twenty-four-hour video-EEG recording. Brain imaging was performed using magnetic resonance imaging (MRI). Clinical aspects, electroencephalographic (EEG) features, and antiepileptic drugs (AEDs) received were reviewed. RESULTS:Generalized tonic-clonic seizures (GTCS) were found in 150/156 patients. Delay of diagnosis was 4.60±9.92years. Photosensitivity was more common in eye closure condition during IPS in patients with JME; in addition, patients with JME with myoclonic seizures (MS) and GTCS as seizure types were likely to present photoparoxysmal responses (PPRs). The 82 nontreated patients showed a median latency to first interictal or ictal generalized spike-wave discharge (GSWD) of 50min (IQR: 22-102min). The first GSWDs were recorded in 63%, 76%, 90%, and 98% patients within one, two, three, and 4h, respectively; only 2% of patients had first GSWDs after 4h. One hundred eleven patients (111/156) chose extended-release valproate (VPA) at daily doses ≤1000mg. The percentages of seizure-free patients among MS, GTCS, and absence seizure (AS) groups were 88.3%, 99.0%, and 94.9%, respectively. CONCLUSION:Photoparoxysmal responses were more common in patients with JME with MS and GTCS and rare in patients with JME with MS and AS in northern Chinese Han patients. Most patients with JME in northern China chose VPA as first therapeutic choice, and low dose (500 to 1000mg daily) of extended-release VPA may be an optimal choice for them. Video-EEG monitoring for at least 4h may be helpful in detecting the first interictal or ictal GSWD in patients with potential JME. Moreover, video-EEG monitoring performed at about 9 o'clock in the morning with patients in the awake state might be useful to find the first GSWD. For JME diagnosis, Class II criteria are more helpful than Class I counterparts, the latter yielding more missed diagnoses.