Tall gastrodis tuber combined with antiepileptic drugs repairs abnormal perfusion foci in focal epilepsy

One hundred patients with focal epilepsy were recruited for the present study and their seizures controlled with antiepileptic drugs. The patients then orally received a capsule of tall gastrodis tuber powder, a traditional Chinese drug, and underwent single photon emission computed tomography, long-term electroencephalogram, and CT/MRI. Blood drug levels were monitored throughout the study. Before treatment with tall gastrodis tuber, 35 of the 100 cases had abnormal CT/MRI scans; 79 cases had abnormal single photon emission computed tomography images; 86 cases had abnormal electroencephalogram; and a total of 146 abnormal perfusion foci were observed across the 100 subjects. After treatment, the number of patients with normal single photon emission computed tomography images increased by 12; normal electroencephalogram was observed in an additional 27 cases and the number of patients with epileptiform discharge decreased by 29 （34% of 86）; the total number of abnormal perfusion foci decreased by 52 （36%） and changes in abnormal loci were visible in 65 patients. These changes indicate that the administration of tall gastrodis tuber in combination with antiepileptic drugs repairs abnormal perfusion foci in patients with focal epilepsy Our results demonstrate that traditional Chinese drugs can repair abnormal perfusion foci and, as such, are a promising new pathway in the treatment of focal epilepsy.

Reproducibility of Test-Retest Cortical Evoked Responses in Patients with Focal Epilepsy

This exploratory study examined the short-term reliability of cortical auditory evoked responses recorded from patients undergoing whole-head scalp elec-troencephalography (EEG) monitoring to assess their candidacy for surgical treatment of intractable focal seizures. Participants were 26 patients with either left-sided (N = 13) or right-sided focal epilepsy admitted to the hospital for continuous scalp EEG monitoring for possible epilepsy surgery planning. Cortical auditory evoked responses were recorded over multiple days from scalp EEG electrodes using tones presented binaurally in a passive oddball paradigm. Test-retest intervals were 1 - 6 days (mean 2 days). Test-retest reproducibility of the auditory N1 response was assessed by paired t-test (latency) and cross-correlation analysis (amplitude and latency). Within-patient comparisons of test-retest auditory N1 peak latencies revealed no significant differences. The cross-correlation coefficient indicated high test-retest reproducibility of the N1 waveform (rcc = 0.88). Seizure lateralization was not associated with asymmetries in N1 latencies or amplitudes. An N1 amplitude asymmetry (right > left) in patients with focal seizures originating from the left hemisphere was initially observed, but disappeared when patients with prior resections were excluded, suggesting that reduced left hemisphere tissue volume may account for the smaller N1 amplitudes. Test-retest reliability of cortical auditory evoked responses was unexpectedly high in patients with focal epilepsy regardless of seizure lateralization or localization. These findings challenge the view that neural responses are intrinsically unstable (unreliable) in patients with seizures.

Dedicated Magnetic Resonance Imaging Sequences:Contribution in the Diagnosis of Focal Epilepsy in the Lebanese Population

There have been many advances in the diagnosis and management of focal epilepsies particularly with neuroimaging techniques and magnetic resonance imaging(MRI).Special MRI sequences can be employed to localize and resect the epileptogenic lesions responsible for focal epilepsy.This study aims to show the benefit of dedicated epilepsy MRI sequences in the diagnosis of focal epilepsies.A general electric 1.5 Tesla MRI machine was used with standard and special sequences.Also,a Nihon Kohden electroencephalography(EEG)machine was used.This is a prospective observational study that included 51 patients with focal epilepsies who had an initial negative brain imaging.They underwent epilepsy MRI sequences along with a prolonged video EEG monitoring to localize the lesion,and then results were analyzed statistically using SPSS 22 program.The majority of patients were males(62.75%)with a mean age of 30 years.The grand majority of patients(74.5%,p value of 0.001)had their lesion localized by the epilepsy MRI.The most commonly found pathology was mesial temporal sclerosis.A significant number of patients(23.5%)were sent for an epilepsy surgery(p value 0.002).This study shows the significant impact of dedicated epilepsy MRI sequences on the diagnosis and management of focal epilepsy in the Lebanese population.

New network and synchronization approaches in focal epilepsy research and treatment

Traditional approaches to focal epileptic surgery rely in the identification and resection of the epileptic zone. However, a significant minority of epileptic patients continue to experience seizures after surgery, a fact that shows how difficult it is to define this concept. In this work we will review some of the recent advances in the use of complex network theory and synchronization analysis in the study of neurophysiological epileptic records which shed new light on fragmented understanding of the epilepsy dynamic we have today. More important would be the potential treatments which could be implemented from the new information and change of perspective gathered by using this methodology, particularly the substitution of the traditional resective surgery in temporal lobe epilepsy patients.

Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

The role of axon guidance molecules in the pathogenesis of epilepsy

Current treatments for epilepsy can only manage the symptoms of the condition but cannot alter the initial onset or halt the progression of the disease. Consequently, it is crucial to identify drugs that can target novel cellular and molecular mechanisms and mechanisms of action. Increasing evidence suggests that axon guidance molecules play a role in the structural and functional modifications of neural networks and that the dysregulation of these molecules is associated with epilepsy susceptibility. In this review, we discuss the essential role of axon guidance molecules in neuronal activity in patients with epilepsy as well as the impact of these molecules on synaptic plasticity and brain tissue remodeling. Furthermore, we examine the relationship between axon guidance molecules and neuroinflammation, as well as the structural changes in specific brain regions that contribute to the development of epilepsy. Ample evidence indicates that axon guidance molecules, including semaphorins and ephrins, play a fundamental role in guiding axon growth and the establishment of synaptic connections. Deviations in their expression or function can disrupt neuronal connections, ultimately leading to epileptic seizures. The remodeling of neural networks is a significant characteristic of epilepsy, with axon guidance molecules playing a role in the dynamic reorganization of neural circuits. This, in turn, affects synapse formation and elimination. Dysregulation of these molecules can upset the delicate balance between excitation and inhibition within a neural network, thereby increasing the risk of overexcitation and the development of epilepsy. Inflammatory signals can regulate the expression and function of axon guidance molecules, thus influencing axonal growth, axon orientation, and synaptic plasticity. The dysregulation of neuroinflammation can intensify neuronal dysfunction and contribute to the occurrence of epilepsy. This review delves into the mechanisms associated with the pathogenicity of axon guidance molecules in epilepsy, offering a valuable reference for the exploration of therapeutic targets and presenting a fresh perspective on treatment strategies for this condition.

Safety and efficacy of a novel responsive neurostimulation system in China for drug-refractory focal epilepsy:The first-in-man study

To the Editor:Recent studies have characterized drugresistant epilepsy(DRE)as essentially a neural network disease.[1]Detection and disconnection of this pathological epileptic connectome or network can greatly improve seizure outcomes.Our team also proposes the development of the newly emerging branch of epileptic networks neurosurgery(ENN).Responsive neurostimulation(RNS)is an ENN-oriented emerging treatment option without the resection of the seizure-onset zone or epileptic focus and aims to control the seizure or other epileptic manifestations by modulating or disrupting the network’s key nodes(epileptic hubs)in a self-responsive way.

Treadmill exercise improves hippocampal neural plasticity and relieves cognitive deficits in a mouse model of epilepsy

Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains controversial.Here,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of epilepsy.Cognitive assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical exercise.Investigations of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain barrier.In summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.

Flexible,high-density,laminated ECoG electrode array for high spatiotemporal resolution foci diagnostic localization of refractory epilepsy

High spatiotemporal resolution brain electrical signals are critical for basic neuroscience research and high-precision focus diagnostic localization,as the spatial scale of some pathologic signals is at the submillimeter or micrometer level.This entails connecting hundreds or thousands of electrode wires on a limited surface.This study reported a class of flexible,ultrathin,highdensity electrocorticogram(ECoG)electrode arrays.The challenge of a large number of wiring arrangements was overcome by a laminated structure design and processing technology improvement.The flexible,ultrathin,high-density ECoG electrode array was conformably attached to the cortex for reliable,high spatial resolution electrophysiologic recordings.The minimum spacing between electrodes was 15μm,comparable to the diameter of a single neuron.Eight hundred electrodes were prepared with an electrode density of 4444 mm^(-2).In focal epilepsy surgery,the flexible,high-density,laminated ECoG electrode array with 36 electrodes was applied to collect epileptic spike waves inrabbits,improving the positioning accuracy of epilepsy lesions from the centimeter to the submillimeter level.The flexible,high-density,laminated ECoG electrode array has potential clinical applications in intractable epilepsy and other neurologic diseases requiring high-precision electroencephalogram acquisition.

Aberrant adult neurogenesis in intractable epilepsy:can GABAergic progenitor transplantation normalize this process?

Temporal lobe epilepsy(TLE) is a common type of focal epilepsy characterized by seizure foci within the temporal lobes.While surgical resection of the foci is an established and effective approach for controlling seizures,both temporal lobes cannot be removed,due to their prominent roles in learning and memory.Additionally,seizures induce changes to the temporal lobes that contribute to hyperexcitability,including mossy fiber sprouting,astrogliosis.

Astrocyte chloride,excitatory-inhibitory balance and epilepsy

Excitation and inhibition are at the core of brain function and malfunction.To sustain the activity of neuronal networks over time and space,glutamatergic excitation is balanced by GABAergic inhibition.The equipoise of excitation and inhibition,known as the excitation/inhibition(E/I)balance,is crucial for proper brain function.The E/I balance is highly dynamic and shifts across different brain states:wakefulness primarily augments excitatory activity,while sleep promotes a decrease in excitation and an increase in inhibition(Bridi et al.,2020).Neuronal activity during various brain states is primarily regulated by neurotransmitters(Schiemann et al.,2015),alongside non-synaptic mechanisms that operate on a slower timescale.The non-synaptic mechanisms are many,with the ionic composition of the extracellular space playing a significant role;altering extracellular ion concentrations affects sleep,arousal,electroencephalogram patterns,and behavioral states(Ding et al.,2016).

Psychiatric comorbidities in epilepsy:population co-occurrence,genetic correlations and causal effects

Background Psychiatric comorbidities are common in patients with epilepsy.Reasons for the co-occurrence of psychiatric conditions and epilepsy remain poorly understood.Aim We aimed to triangulate the relationship between epilepsy and psychiatric conditions to determine the extent and possible origins of these conditions.Methods Using nationwide Swedish health registries,we quantified the lifetime prevalence of psychiatric disorders in patients with epilepsy.We then used summarydata from genome-wide association studies to investigate whether the identified observational associations could be attributed to a shared underlying genetic aetiology using cross-trait linkage disequilibrium score regression.Finally,we assessed the potential bidirectional relationships using two-sample Mendelian randomisation.Results In a cohort of 7628495 individuals,we found that almost half of the 94435 individuals diagnosed with epilepsy were also diagnosed with a psychiatric condition in their lifetime(adjusted lifetime prevalence,44.09%;95%confidence interval(Cl)43.78%to 44.39%).We found evidence for a genetic correlation between epilepsy and some neurodevelopmental and psychiatric conditions.For example,we observed a genetic correlation between epilepsy and attention-deficit/hyperactivity disorder(r,=0.18,95%Cl 0.09 to 0.27,p<0.001)—a correlation that was more pronounced in focal epilepsy(r=0.23,95%CI 0.09 to 0.36,p<0.001).Findings from Mendelian randomisation using common genetic variants did not support bidirectional effects between epilepsy and neurodevelopmental or psychiatric conditions.Conclusions Psychiatric comorbidities are common in patients with epilepsy.Genetic correlations may partially explain some comorbidities;however,there is little evidence of a bidirectional relationship between the genetic liability of epilepsy and psychiatric conditions.These findings highlight the need to understand the role of environmental factors or rare genetic variations in the origins of psychiatric comorbidities in epilepsy.

Nrf2 as a potential target for the treatment of epilepsy

Epilepsy is a prevalent chronic brain disorder that is characterized by a persistent predisposition to recurrently generate epileptic seizures and is often associated with cognitive and psychological consequences.Epilepsy affects approximately 65 million individuals,including both males and females of all ages worldwide,and poses a significant burden on patients,their families,and the health system(Vezzani et al.,2019).

Electroencephalogram findings in 10 patients with post-stroke epilepsy:A retrospective study

BACKGROUND Post-stroke epilepsy is a common and easily overlooked complication of acute cerebrovascular disease.Long-term seizures can seriously affect the prognosis and quality of life of patients.Electroencephalogram(EEG)is the simplest way to diagnose epilepsy,and plays an important role in predicting seizures and guiding medication.AIM To explore the EEG characteristics of patients with post-stroke epilepsy and improve the detection rate of inter-seizure epileptiform discharges.METHODS From January 2017 to June 2020,10 patients with post-stroke epilepsy in our hospital were included.The clinical,imaging,and EEG characteristics were collected.The stroke location,seizure type,and ictal and interictal EEG manifestations of the patients with post-stroke epilepsy were then retrospectively analyzed.RESULTS In all 10 patients,epileptiform waves occurred in the side opposite to the stroke lesion during the interictal stage;these manifested as sharp wave,sharp-wave complex,or spike discharges in the anterior head lead of the side opposite to the lesion.CONCLUSION In EEG,epileptiform waves can occur in the side opposite to the stroke lesion in patients with post-stroke epilepsy.

Cognitive Disorders, Depression and Anxiety in Temporal Lobe Epilepsy: An Overview

Partial epilepsies, originating in a specific brain region, affect about 60% of adults with epilepsy. Temporal lobe epilepsy (TLE) is the most prevalent subtype within this category, often necessitating surgical intervention due to its refractoriness to antiepileptic drugs (AEDs). Hippocampal sclerosis, a common underlying pathology, often exacerbates the severity by introducing cognitive and emotional challenges. This review delves deeper into the cognitive profile of TLE, along with the risk factors for cognitive disorders, depression, and anxiety in this population.

Bibliometric analysis of research in epilepsy and comorbid depression from 2014 to 2023

BACKGROUND Epilepsy and depression have complicated bidirectional relationships.Our study aimed to explore the field of epilepsy comorbid with depression in a bibliometric perspective from 2014-2023.AIM To improve our understanding of epilepsy and depression by evaluating the relationship between epilepsy and depression,bibliometric analyses were performed.METHODS Epilepsy and depression-related publications from the last decade were retrieved from the Web of Science Core Collection.We conducted bibliometric and visual analysis using VOSviewer and CiteSpace,examining authorships,countries,institutions,journals of publication,co-citations of references,connections between keywords,clusters of keywords,and keywords with citation bursts.RESULTS Over the past ten years,we collected 1045 research papers focusing on the field of epilepsy and comorbid depression.Publications on epilepsy and depression have shown a general upward trend over time,though with some fluctuations.The United States,with 287 articles,and the University of Melbourne,contributing 34 articles,were the top countries and institutions,respectively.In addition,in the field of epilepsy and depression,Professor Lee,who has published 30 articles,was the most contributing author.The hot topics pay attention to the quality of life in patients with epilepsy and depression.CONCLUSION We reported that quality of life and stigma in patients with epilepsy comorbid with depression are possible future hot topics and directions in the field of epilepsy and depression research.

The role of exercise in modulating the HP pathway to reduce glioma-induced epilepsy

Background:Glioma-induced refractory epilepsy can be alleviated through conventional exercise,providing a potential therapeutic approach to manage this condition.This study aims to investigate the underlying mechanisms.Methods:Bioinformatics methodologies were employed to scrutinize gene expression data from public repositories such as GEO,with a specific focus on mobility-related genes in epilepsy.Through differential and enrichment analyses,differentially expressed genes(DEGs)were identified,while protein-protein interaction networks elucidated pivotal hub genes.Results:Our analysis revealed 32 DEGs,comprising 23 upregulated and 9 downregulated genes.Enrichment analysis underscored significant alterations in immune pathways in epilepsy.Two central hub genes,haptoglobin(HP)and prostaglandin-endoperoxide synthase 2(PTGS2),were found to be modulated by Arginase 1(ARG1)and Chemokine(C-X-C motif)ligand 8(CXCL8).GSVA analysis associated elevated PTGS2 expression with metabolic pathways,while increased HP expression was correlated with angiogenesis and inflammation.Subsequent experiments validated HP’s role in tumor cell proliferation,emphasizing its potential as a therapeutic target.Conclusion:This study highlights the crucial involvement of HP and PTGS2 genes in the etiology of epilepsy,linked to discrepancies in the immune system.These findings offer fresh perspectives on the management of epilepsy,emphasizing the neuroprotective possibilities of targeting specific gene pathway.

A monolithic integrated medium wave Mercury Cadmium Telluride polarimetric focal plane array

A medium wave(MW)640×512(25μm)Mercury Cadmium Telluride(HgCdTe)polarimetric focal plane array(FPA)was demonstrated.The micro-polarizer array(MPA)has been carefully designed in terms of line grating structure optimization and crosstalk suppression.A monolithic fabrication process with low damage was explored,which was verified to be compatible well with HgCdTe devices.After monolithic integration of MPA,NETD<9.5 mK was still maintained.Furthermore,to figure out the underlying mechanism that dominat⁃ed the extinction ratio(ER),specialized MPA layouts were designed,and the crosstalk was experimentally vali⁃dated as the major source that impacted ER.By expanding opaque regions at pixel edges to 4μm,crosstalk rates from adjacent pixels could be effectively reduced to approximately 2%,and promising ERs ranging from 17.32 to 27.41 were implemented.

Regulation of specific abnormal calcium signals in the hippocampal CA1 and primary cortex M1 alleviates the progression of temporal lobe epilepsy

Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and is not fully understood.Intracellular calcium dynamics have been implicated in temporal lobe epilepsy.However,the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown,and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice.In this study,we used a multichannel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process.We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes.In particular,cortical spreading depression,which has recently been frequently used to represent the continuously and substantially increased calcium signals,was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from gradeⅡto gradeⅤ.However,vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures.Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to gradeⅠepisodes.In addition,the latency of cortical spreading depression was prolonged,and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced.Intriguingly,it was possible to rescue the altered intracellular calcium dynamics.Via simultaneous analysis of calcium signals and epileptic behaviors,we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced,and that the end-point behaviors of temporal lobe epilepsy were improved.Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding to different grades.Furthermore,the selective regulation of abnormal calcium signals in CA1 pyramidal neurons appears to effectively alleviate temporal lobe epilepsy,thereby providing a potential molecular mechanism for a new temporal lobe epilepsy diagnosis and treatment strategy.

Towards fast focal mechanism inversion of shallow crustal earthquakes in the Chinese mainland

We have developed an automatic regional focal mechanism inversion system based on the Earthquake Rapid Report(ERR) system and the real-time three-component seismic waveform stream of 1 000 broadband seismic stations provided by the China Earthquake Networks Center(CENC). The system can rapidly provide a double couple solution and centroid depth within 5–15 min after receiving earthquake information from the ERR system.The data processing is triggered by earthquake information obtained from the ERR system. The system is capable of determining the focal mechanism of all shallow-depth earthquakes in the Chinese mainland with a magnitude of 5.5–6.5. It utilizes waveform data recorded by seismic stations located within 500 km from the epicenter,enabling the reporting of a focal mechanism solution within 5–15 min of an earthquake occurrence. Additionally,the system can assign a corresponding grade(A B C) to the focal mechanism solution. We processed a total of 301earthquakes that occurred from 2021 to June 2022, and after the quality control, 166 of them were selected.These selected solutions were manually checked, and 160 of them were compiled in a focal mechanism catalog.This catalog can be conveniently downloaded online via the Internet. The automatic focal mechanism solution of earthquakes in eastern China exhibits a good agreement with that provided by the Global Centroid Moment Tensor(GCMT), when available. The average Kagan angle between this catalog and GCMT is 22°, and the average difference in MWis 0.17. Furthermore, compared with GCMT, the minimum magnitude of our catalog has been reduced from approximately 5.0 to 4.0. The correlation between the centroid depth and crustal thickness in the Chinese mainland confirms the distribution of the centroid depth.