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.

DIAGNOSTIC VALUE OF INTERICTAL DIFFUSION-WEIGHTED IMAGING IN EVALUATION OF INTRACTABLE TEMPORAL LOBE EPILEPSY

Objective To explore the ability of interictal diffusion-weighted imaging(DWI)to localize the temporal lobe of seizure origin and to predict postoperative seizure control in patients with temporal lobe epilepsy(TLE).Methods Twenty-seven patients with intractable TLE considered for surgery and 19 healthy volunteers were studied with conventional magnetic resonance imaging(MRI)and DWI.Apparent diffusion coefficients(ADCs)of bilateral hippocampi in both TLE patients and control subjects were obtained.Lateralization to either temporal lobe with hippocampal ADC was based on the threshold values derived from ±1SD of right/left ratios in normal subjects.And the postoperative pathology was reviewed.Results Hippocampal ADCs were higher on the side of surgery compared with those on the contralateral side as well as the ipsilateral side in control subjects [resected side(109.8±7.3)×10-5 cm2/s,contralateral side(91.7±4.7)×10-5 cm2/s,control subjects(81.6±5.2)×10-5 cm2/s,all P<0.01].Right/left hippocampal ADC ratio and conventional MRI lateralized to the operated temporal lobe in 21 of 27(77.8%)and in 18 of 27(66.7%)patients.Lateralization to the surgical side was not associated with postoperative seizure control with right/left hippocampal ADC ratio(P>0.05).Conclusions Conventional MRI is a sensitive method to detect hippocampal sclerosis.Accuracy of the right/left hippocampal ADC ratio for lateralizing to the side of surgery is very high,but it isn't a better predictor of surgical outcome.

Preliminary analysis of the effect of vagus nerve stimulation in the treatment of children with intractable epilepsy

BACKGROUND Implant vagus nerve stimulation is an adjunctive treatment for intractable epilepsy when patients are not suitable for resective surgery.AIM To identify the safety and efficacy of vagus nerve stimulation in children with intractable epilepsy and analyze the effects on different epilepsy syndromes.METHODS Eligible children with intractable epilepsy were admitted to the study.We collected data from preoperative assessments as the baseline.During the followup time,we recorded the process of seizures(frequency,duration,and seizure type),the changes of drugs or parameters,the complications,etc.The mean reduction rate of seizures,response rate,and McHugh scale were chosen as the outcomes.RESULTS A total of 213 patients were implanted with Tsinghua Pins vagus nerve stimulators,and the average age was 6.6 years.In the follow-up time of postoperative 3 mo,6 mo,12 mo,18 mo,and 24 mo,the average reduction rate was 30.2%,49.5%,56.3%,59.4%,and 63.2%,while the response rate was 21.8%,62.5%,57.1%,69.2%,and 70.7%.In addition,implanted vagus nerve stimulation had different effects on epilepsy syndromes.The reduction rate of West syndrome increased from 36.4%(postoperative 6 m)to 74.3%(postoperative 24 m).The reduction rate of Lennox-Gastaut syndrome improved from 25.4%to 73.1%in 24 mo.The chi-square test of the five efficacy grades showed P<0.05.The comparison between the 3-mo follow-up and the 6-mo follow-up showed P<0.05,and the comparison between the 6-mo follow-up and the 24-mo follow-up showed P>0.05.CONCLUSION Vagus nerve stimulation is safe and effective in children with intractable epilepsy,and the seizure reduction occurred in a time-dependent manner.Moreover,patients with West syndrome may get the most benefits.

Expression of multidrug resistance 1 gene and C3435T genetic polymorphism in peripheral blood of patients with intractable epilepsy

BACKGROUND： Increased expression of multidrug resistance 1 （MDR1） mRNA in peripheral blood of patients with intractable epilepsy is not due to epilepsy drugs, but epilepsy behavior. Monitoring MDR1 expression in peripheral blood is a target for MDR1 gene evaluation. OBJECTIVE： To investigate the influence of antiepileptic drugs and seizures on MDR expression in intractable epilepsy, and to analyze the genetic polymorphisms of C3435T in the MDRl gene. DESIGN, TIME AND SETTING： Factorial designs and comparative observations at the experimental center of the Affiliated Hospital of Qingdao Medical College, Qingdao University between October 2003 and October 2004. PARTICIPANTS： A total of 120 subjects were recruited from the epilepsy clinical department of the Affiliated Hospital of Qingdao Medical College. Four groups （n = 30） were classified according to statistical factorial design： intractable epilepsy, treatment response, no treatment, and normal control groups. METHODS： One-step semi-quantitative reverse-transcription polymerase chain reaction technology was used to test expressions of the MDR1 gene in 120 subjects. C3435T polymorphisms in intractable epilepsy group and normal control groups were analyzed by polymerase chain reaction-restriction fragment length polymorphism. MAIN OUTCOME MEASURES： Expression of MDR1 mRNA in the four groups, and C3435T genetic polymorphisms in intractable epilepsy and normal control groups. RESULTS： MDRl gene expression was increased in the intractable epilepsy group, due to the factor seizures, but not the antiepileptic drugs. However, the interaction between the two factors was not statistically significant. Of the 30 subjects in the intractable epilepsy group, the following genotypes were exhibited： 3 （10%） C/C genotype, 9 （30%） C/T genotype, and 18 （60%） T/T genotype at the site of C3435T, while 4 （13%）, 10 （33%）, and 16 （53%） subjects were determined to express these genotypes in the normal control group, respectively. C and T allele frequency were 25% and 75% in the intractable epilepsy group, and 30% and 70% in the normal control group, respectively. However, there was no statistical difference between the groups. CONCLUSION： Results demonstrated that seizures, not antiepileptic drugs, induced MDR1 gene expression in intractable epilepsy. Genetic polymorphisms of C3435T in the MDR1 gene did not contribute to the development of multidrug resistance in patients with intractable epilepsy.

Electrocorticography with Direct Cortical Stimulation for a Left Temporal Glioma with Intractable Epilepsy

ELECTROCORTICOGRAPHY (ECoG), the intraoperative recording of cortical potentials, has played an important role in the surgical management of patients with medically intractable epilepsy. This technique is useful in epilepsy surgery to delineate margins of epileptogenic zones, guide resection,

The influence of immunomodulator on the immunoglobulin and T cell subsets in children with intractable epilepsy

Objective:To observe the influence of immunomodulator on the immunoglobulin and T cell subsets in children with intractable epilepsy.Method:A total of 82 children with intractable epilepsy in our hospital were selected and randomly divided into 2 groups: the control group (41 cases) and the observation group (41 cases). Routine antiepileptic drugs were given to the control group. Medication regimen was that more than 2 kinds of anti epileptic drugs were be combined used. But the immunomodulator wasn't used. Treatment of immune globulin was given to the control group on the basis of observation group. By taking the 400 mg/kg/d as the standard of dosage, for 5 d every course of treatment. One course of treatment was carried out every month, 3 months in total. The changes of IgA, IgG, IgM and CD3+, CD4+, CD8+, CD4+/CD8+ were compared in 2 groups before and after treatment.Result: The comparison of IgA, IgG, IgM in the two groups before treatment was not statistically significant. After treatment, IgA, IgG in observation group were significantly higher than that before treatment and the difference was statistically significant. However, there was no significant difference on the IgM. There was no significant difference on the IgA, IgG, IgM in the control group compared with that before treatment. IgA, IgG in observation group was significant higher than that in the control group. The comparison of IgM between 2 groups was not statistically significant. The comparison of CD3+, CD4+, CD8+, CD4+/CD8+ in the two groups before treatment was not statistically significant. After treatment, CD3+, CD4+, CD4+/CD8+ in observation group were significantly higher than that before treatment;CD8+ in observation group was significantly lower than that before treatment. The difference was statistically significant. There was no significant difference on the CD3+, CD4+, CD8+, CD4+/CD8+ in the control group compared with that before treatment. CD3+, CD4+, CD4+/CD8+ in observation group was significant higher than that in the control group. CD8+ in observation group was significant lower than that in the control group. The difference was statistically significant.Conclusion:Compared with using routine antiepileptic drugs , application of immune globulin as an immunomodulator combined with conventional antiepileptic drug in children with refractory epilepsy can effectively improve the expression of IgA, IgG, IgM and T cell subsets, which has a positive effect on the immune function of the children.

Correlation analysis of Toll-like receptor 3 content in peripheral blood with electroencephalogram parameters and neurotransmitter content in children with intractable epilepsy

Objective:To detect the content of Toll-like receptor 3 (TLR3) in peripheral blood of children with intractable epilepsy, explore the correlation between TLR3 content and EEG parameters, neurotransmitter contents.Methods:37 cases of Intractable epilepsy children in our hospital during September 2016to June 2018 were chosen as Intractable epilepsy group, 30 cases of healthy volunteers who underwent physical examination in our hospital were treated as Normal control group. The levels of TLR3, neurotransmitter [5-hydroxytryptamine (5-HT), dopamine (DA), epinephrine (E), norepinephrine (NE)] and electroencephalogram parameters [alpha, beta, delta, theta] in peripheral blood of two groups were compared. Pearson test was used to evaluate the correlation of TLR3 content in peripheral blood with EEG parameters and neurotransmitter content in children with intractable epilepsy.Results: Content of TLR3 in peripheral blood of Intractable epilepsy group was significantly higher than that of Normal control group;the alpha power and theta power of EEG parameters were lower than those of Normal control group;contents of neurotransmitters such as 5-HT, DA, E and NE were significantly lower than those of Normal control group (P<0.05). The correlation analysis showed that content of TLR3 in peripheral blood of children with intractable epilepsy was negatively correlated with levels of alpha and theta power of EEG, positively correlated with content of neurotransmitters such as 5-HT, DA, E and NE (P<0.05), but had no significant correlation was found with level of beta and delta power (P>0.05).Conclusion: The abnormal increase of TLR3 in peripheral blood of children with intractable epilepsy may be one of the direct causes of neurological impairment in children with intractable epilepsy.

Effects of lamotrigine + sodium valproate therapy on the nerve cell nutrition and apoptosis status as well as inflammatory response in patients with intractable epilepsy

Objective: To investigate the effects of lamotrigine + sodium valproate therapy on the nerve cell nutrition and apoptosis as well as inflammatory response in patients with intractable epilepsy. Methods: A total of 70 patients with intractable epilepsy who were treated in our hospital between August 2013 and October 2016 were divided into routine group (n=35) and study group (n=35) by random number table method, routine group received sodium valproate therapy and study group received lamotrigine combined with sodium valproate therapy. The differences in serum levels of neurotrophy indexes, nerve apoptosis indexes and inflammatory factors were compared between the two groups before and after treatment. Results: Before treatment, there was no statistically significant difference in serum levels of neurotrophy indexes, nerve apoptosis indexes and inflammatory factors between the two groups. After treatment, serum BDNF and NGF levels of study group were higher than those of routine group;serum Bcl-2, Fas and FasL levels of study group were lower than those of routine group whereas Bax level was higher than that of routine group;serum IL-1β, IL-6 and PGE2 levels of study group were lower than those of routine group. Conclusion: Lamotrigine combined with sodium valproate therapy can effectively increase the neurotrophy, inhibit the nerve apoptosis and reduce the systemic inflammatory response in patients with intractable epilepsy.

Bipolar electrocoagulation on functional cortex(BCFC)for intractable epilepsy involving eloquent cortex:a review

Twenty percent to forty percent of patients with epilepsy are medically refractory.For these patients,epilepsy surgeries such as resecting the epileptogenic focus may provide an alternative option.However,when the epileptogenic focus is located in the eloquent cortex,the resection of epileptogenic focus may lead to unacceptable functional deficits.Bipolar electrocoagulation on functional cortex(BCFC)is a surgical technique that holds the same principles with multiple subpial transections(MST)and aims to benefit patients with epilepsy whose epileptogenic zone is located in the eloquent cortex.It uses thermal injury to interrupt the horizontal fibers in the cortex while mechanical injury is used in MST.Here,we reviewed the rationale,surgical procedure,laboratory research,and clinical application of BCFC.We also discussed the ongoing challenges of BCFC.

Microscopic Anterior Callosotomy for Management of Intractable Epilepsy (Al-Azhar Experience)

Background: Anterior Corpus Callosotomy is a palliative treatment for drug-resistant generalized or multifocal epilepsy patients where focus excision is not an option for management. Callosotomy prevents propagation of epileptic discharge from one cerebral hemisphere to the other. Objective: To describe Al-Azhar University Hospitals experience and clinical outcome of Anterior Corpus Callosotomy for management of drug-resistant generalized epilepsy patients as an inexpensive palliative method. Patients and Methods: In this study, there are 15 patients admitted to Neurosurgery Department in Al-Azhar University Hospitals with drug-resistant generalized epilepsy. These patients were not candidates for lesionectomy. They were managed by anterior two thirds Corpus Callosotomy between February 2017 and December 2019. They were followed at outpatient clinic for at least 14 months. Clinical outcome regarding seizure control was assessed using Engel classification. Results: All 15 patients in this study underwent anterior two thirds corpus callosotomy and followed for at least 14 months. The post-operative improvement of seizure frequency has been evaluated using Engel outcome scale with 12 patients (80%) of the patients becoming Engel class II and 3 patients (20%) becoming Engel class III. Only 3 patients (20%) had minor transient postoperative complications;one patient (6.67%) had contra-lateral lower limb heaviness Grade 4 which was transient, one patient (6.67%) had contra-lateral lower limb Jacksonian focal fits and one patient (6.67%) had behavioral changes for one month. Conclusion: Corpus callosotomy is a palliative procedure and inexpensive method for management of patients with intractable focal with generalization and generalized drug-resistant epilepsy who are not suitable for resective surgery and with good outcome.

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.

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.

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.