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Abstract Transient global amnesia (TGA) often involves precipitating events associated with changes in autonomic nervous system (ANS), and heart rate variability (HRV) reflects the ANS state. This study aimed to investigate HRV changes after TGA. A retrospective analysis of HRV included patients diagnosed with TGA between January 2015 and May 2020. The time and frequency domains of HRV were compared among three groups: early (

Summary: Background: Early diagnosis and appropriate treatment are essential in meningitis and encephalitis management. We aimed to implement and verify an artificial intelligence (AI) model for early aetiological determination of patients with encephalitis and meningitis, and identify important variables in the classification process. Methods: In this retrospective observational study, patients older than 18 years old with meningitis or encephalitis at two centres in South Korea were enrolled for development (n = 283) and external validation (n = 220) of AI models, respectively. Their clinical variables within 24 h after admission were used for the multi-classification of four aetiologies including autoimmunity, bacteria, virus, and tuberculosis. The aetiology was determined based on the laboratory test results of cerebrospinal fluid conducted during hospitalization. Model performance was assessed using classification metrics, including the area under the receiver operating characteristic curve (AUROC), recall, precision, accuracy, and F1 score. Comparisons were performed between the AI model and three clinicians with varying neurology experience. Several techniques (eg, Shapley values, F score, permutation feature importance, and local interpretable model-agnostic explanations weights) were used for the explainability of the AI model. Findings: Between January 1, 2006, and June 30, 2021, 283 patients were enrolled in the training/test dataset. An ensemble model with extreme gradient boosting and TabNet showed the best performance among the eight AI models with various settings in the external validation dataset (n = 220); accuracy, 0.8909; precision, 0.8987; recall, 0.8909; F1 score, 0.8948; AUROC, 0.9163. The AI model outperformed all clinicians who achieved a maximum F1 score of 0.7582, by demonstrating a performance of F1 score greater than 0.9264. Interpretation: This is the first multiclass classification study for the early determination of the aetiology of meningitis and encephalitis based on the initial 24-h data using an AI model, which showed high performance metrics. Future studies can improve upon this model by securing and inputting time-series variables and setting various features about patients, and including a survival analysis for prognosis prediction. Funding: MD-PhD/Medical Scientist Training Program through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea.

ObjectiveInterest in sleep disorders among the elderly, especially those in Korea, has increased. We aimed to describe the overall sleep status of the elderly population in Korea using survey data and to determine the risk factors concerning different aspects of sleep status.MethodsWe conducted a cross-sectional survey on 271 respondents aged 65–86 years old. We performed multistage clustered random sampling according to the population and socioeconomic distribution of all Korean territories. The survey questionnaire was used to perform a structural assessment of sociodemographic characteristics; medical comorbidities; psychiatric comorbidities; and sleep status, including sleep duration, sleep quality, presence of insomnia, excessive daytime sleepiness, sleep apnea, and restless legs syndrome.ResultsApproximately 12.5, 22.%, and 51.3% of the elderly population had poor sleep quality, excessive daytime sleepiness, and insomnia, respectively. Hypertension, dyslipidemia, insomnia, anxiety, and depression predicted poor sleep quality. Female sex, insomnia, and sleep apnea predicted excessive daytime sleepiness. Poor sleep quality and depression predicted insomnia.ConclusionA substantial proportion of the elderly Korean population have sleep problems, including poor sleep quality, excessive daytime sleepiness, and insomnia. Sleep status is influenced by various factors, including age, sex, and metabolic and psychiatric comorbidities.

Objective: Insomnia and depression are prevalent disorders that often co-occur. This study aimed to investigate the impact of clinically significant insomnia symptoms on the prevalence and clinical presentation of clinically significant depressive symptoms and vice versa.Methods: This study used data from the Korean Headache-Sleep Study (KHSS), a nationwide cross-sectional population-based survey regarding headache and sleep. Clinically significant insomnia symptoms were defined as Insomnia Severity Index (ISI) scores ≥ 10 and clinically significant depressive symptoms were defined as Patient Health Questionnaire-9 (PHQ-9) scores ≥ 10, respectively. We referred clinically significant insomnia symptoms and clinically significant depressive symptoms as insomnia symptoms and depressive symptoms, respectively.Results: Of 2,695 participants, 290 (10.8%) and 116 (4.3%) were classified as having insomnia and depressive symptoms, respectively. The prevalence of depressive symptoms was higher among participants with insomnia symptoms than in those without insomnia symptoms (25.9 vs. 1.7%, respectively, P < 0.001). Among participants with depressive symptoms, the PHQ-9 scores were not significantly different between participants with and without insomnia symptoms (P = 0.124). The prevalence of insomnia symptoms was significantly higher among participants with depressive symptoms than in those without depressive symptoms (64.7 vs. 8.3%, respectively, P < 0.001). The ISI scores were significantly higher among participants with insomnia and depressive symptoms than in participants with insomnia symptoms alone (P < 0.001).Conclusions: Participants with depressive symptoms had a higher risk of insomnia symptoms than did those without depressive symptoms. The severity of depressive symptoms did not significantly differ based on insomnia symptoms among participants with depressive symptoms; however, the severity of insomnia symptoms was significantly higher in participants with depressive symptoms than in those without depressive symptoms.

Background Cerebral air embolism is uncommon but potentially causes catastrophic events such as cardiac damage or even death. However, due to a low overall incidence, it may go undiagnosed. Case Report A 56-year-old man with a medical history of right upper lobectomy due to lung cancer showed changes in mental status after the Valsalva maneuver, followed by status epilepticus during admission. Brain and chest computed tomography showed cerebral air embolism and accidental pneumothorax in the right major fissure. After antiepileptic drug infusion and oxygen therapy, he recovered completely. Conclusion Since cerebral air embolism may result in fatal outcomes, it should be suspected in patients with sudden neurological deterioration after routine medical procedures.

STUDY OBJECTIVES:Insomnia is the most common sleep disorder with significant psychiatric/physical comorbidities in the general population. The aim of this study is to investigate whether socioeconomic and demographic factors are associated with gender differences in insomnia and subtypes in Korean population. METHOD:The present study used data from the nationwide, cross-sectional study on sleep among all Koreans aged 19 to 69 years. The Insomnia Severity Index (ISI) was used to classify insomnia symptoms and their subtypes (cutoff value: 9.5). The Pittsburgh Sleep Quality Index (PSQI), Goldberg Anxiety Scale (GAS) and Patient Health Questionnaire-9 (PHQ-9) were used to measure sleep quality, anxiety and depression. RESULTS:A total of 2695 participants completed the survey. The overall prevalence of insomnia symptoms was 10.7%, including difficulty in initiating sleep (DIS) (6.8%), difficulty in maintaining sleep (DMS) (6.5%) and early morning awakening (EMA) (6.5%), and these symptoms were more prevalent in women than in men. Multivariate analysis showed that female gender, shorter sleep time and psychiatric complications were found to be independent predictors for insomnia symptoms and subtypes. After adjusting for covariates among these factors, female gender remained a significant risk factor for insomnia symptoms and their subtypes. As for men, low income was related to insomnia. CONCLUSION:Approximately one-tenth of the sample from the Korean general population had insomnia symptoms. The prevalence of insomnia symptom and the subtypes were more prevalent in women than men. Gender is an independent factor for insomnia symptoms.

Abstract Background Insomnia and migraine are closely related; insomnia aggravates migraine symptoms. This study was conducted to investigate the impact of migraine on the clinical presentation of insomnia symptoms. Methods The data of the Korean Headache-Sleep Study (KHSS) were used in the present study. The KHSS is a nation-wide cross-sectional population-based survey regarding headache and sleep in Korean adults aged 19 to 69 years. If a participant’s Insomnia Severity Index (ISI) score ≥ 10, she/he was classified as having insomnia. The clinical presentation of insomnia symptoms was assessed using total and subcomponent scores of the ISI. Results Of 2695 participants, 290 (10.8%) and 143 (5.3%) individuals were assigned as having insomnia and migraine, respectively. The proportions of migraine (12.8% vs. 4.4%, p

Background Knowledge of the genetic etiology of epilepsy can provide essential prognostic information and influence decisions regarding treatment and management, leading us into the era of precision medicine. However, the genetic basis underlying epileptogenesis or epilepsy pharmacoresistance is not well-understood, particularly in non-familial epilepsies with heterogeneous phenotypes that last until or start in adulthood. Methods We sought to determine the contribution of known epilepsy-associated genes (EAGs) to the causation of non-familial epilepsies with heterogeneous phenotypes and to the genetic basis underlying epilepsy pharmacoresistance. We performed a multi-center study for whole exome sequencing-based screening of 178 selected EAGs in 243 non-familial adult patients with primarily focal epilepsy (122 drug-resistant and 121 drug-responsive epilepsies). The pathogenicity of each variant was assessed through a customized stringent filtering process and classified according to the American College of Medical Genetics and Genomics guidelines. Results Possible causal genetic variants of epilepsy were uncovered in 13.2% of non-familial patients with primarily focal epilepsy. The diagnostic yield according to the seizure onset age was 25% (2/8) in the neonatal and infantile period, 11.1% (14/126) in childhood and 14.7% (16/109) in adulthood. The higher diagnostic yields were from ion channel-related genes and mTOR pathway-related genes, which does not significantly differ from the results of previous studies on familial or early-onset epilepsies. These potentially pathogenic variants, which were identified in genes that have been mainly associated with early-onset epilepsies with severe phenotypes, were also linked to epilepsies that start in or last until adulthood in this study. This finding suggested the presence of one or more disease-modifying factors that regulate the onset time or severity of epileptogenesis. The target hypothesis of epilepsy pharmacoresistance was not verified in our study. Instead, neurodevelopment-associated epilepsy genes, such as TSC2 or RELN, or structural brain lesions were more strongly associated with epilepsy pharmacoresistance. Conclusions We revealed a fraction of possible causal genetic variants of non-familial epilepsies in which genetic testing is usually overlooked. In this study, we highlight the importance of earlier identification of the genetic etiology of non-familial epilepsies, which leads us to the best treatment options in terms of precision medicine and to future neurobiological research for novel drug development. This should be considered a justification for physicians determining the hidden genetics of non-familial epilepsies that last until or start in adulthood.

Excessive daytime sleepiness (EDS) is a prevalent sleep-related complaint across the general population and has been reported to be associated with headache. Tension-type headache (TTH) is the most commonly encountered headache and accounts for a significant amount of disease burden. However, the association between EDS and TTH is currently scarce. In the present study, we investigated the impact of EDS on the prevalence and clinical presentation of TTH. We utilized data from the Korean Headache-Sleep Study, a national survey that sought to identify headache and sleep characteristics in Korean adults. Participants with an Epworth sleepiness scale score greater or equal to 11 were considered as having EDS. Of the 2,695 participants enrolled, 570 (21.2%) and 313 (11.6%) had TTH and EDS, respectively. EDS was highly prevalent in individuals with chronic tension-type headache (CTTH) than in those without headache (35.7 vs. 9.4%, p < 0.001). The prevalence of EDS in episodic tension-type headache (ETTH) individuals with a headache frequency

Abstract Background Probable migraine (PM) is a subtype of migraine that is prevalent in the general population. Previous studies have shown that poor sleep quality is common among migraineurs and is associated with an exacerbation of migraine symptoms. However, information on the prevalence and clinical implication of poor sleep quality among individuals with PM is scarce. Thus, the aim of this study was to assess the prevalence and clinical impact of poor sleep quality in individuals with PM in comparison with those with migraine. Methods Two-stage cluster random sampling was used to perform the survey for sleep and headache in Korean general population. Participants with Pittsburgh Sleep Quality Index > 5 were considered as having poor sleep quality. Results Of 2695 participants, 379 (14.1%) had PM and 715 (26.5%) had poor sleep quality. Prevalence of poor sleep quality was 35.4% in the PM group, which was lower than that in the migraine group (47.6%, p = 0.011), but higher than that in the non-headache group (21.4%, p

The immune-acquired responses after vaccination vary depending on the type of vaccine and the individual. The purpose of this study was to investigate the relationship between the acquisition of immunity and the side effects, health status, and lifestyle after completion of the second dose of AZD1222. Blood samples were collected after a second dose of AZD1222. The Euroimmun Anti-SARS-CoV-2 ELISA (IgG) for anti-S1 antibody, the cPASS SARS-CoV-2 neutralizing antibody detection kit for the surrogate virus neutralization test, and the T-spot Discovery SARS-CoV-2 kit were used to identify cellular immunogenicity. Patient experience of adverse effects was investigated using questionnaires. Information on health status and lifestyle were collected from the most recent health checkup data. Generally, females experience more reactogenicity in both intensity and duration. The rash of the first shot and chills of the second shot were associated with humoral immunity. However, comprehensive adverse effects had no correlation with humoral and cellular immunity. The T-spot-positive group had a higher creatinine level, which reflects muscle mass, than the T-spot-negative group. Males presented a higher level of T-spot assays. Body mass index and age were negatively correlated with the T-spot assay and anti-S1 antibody, respectively. Immune acquisition after the second AZD1222 shot was not associated with reactogenicity. However, individuals’ sex, age, and BMI were found to be associated with immunogenicity after vaccination.

Abstract Background Tension-type headache (TTH) represents the most common type of headache among the general population. Although such headaches are usually mild in severity, some individuals with TTH experience severe symptoms and psychiatric comorbidities. Such patients may also experience sleep disturbances, which have been associated with headache exacerbation. Nevertheless, information regarding the prevalence and impact of insomnia among individuals with TTH in a population-based setting is limited. Therefore, the aim of the present study was to evaluate the prevalence and impact of insomnia among individuals with TTH using data from the Korean Headache-Sleep Study (KHSS). Methods We analysed data from the KHSS—a nation-wide, cross-sectional, population-based survey on headache and sleep involving Korean adults aged 19 to 69 years. Insomnia was defined as an Insomnia Severity Index score ≥ 10. Results Among 2695 participants, 570 (21.2%) and 290 (10.8%) were classified as having TTH and insomnia, respectively. Among individuals with TTH, 113 (19.8%) met the criteria for probable migraine (PM). The prevalence of insomnia among individuals with TTH was significantly higher than that among individuals without headache (13.2% vs. 5.8%, p

Abstract Background Sleep disorder and sleep complaints are common in subjects with migraine. Although the association between sleep disorders and migraine has been reported, the association between perceived insufficient sleep and migraine has rarely reported. The aim of this study is to evaluate the association between insufficient sleep and migraine using the data of the Korean Headache-Sleep Study (KHSS). Methods The KHSS is a nation-wide cross-sectional population-based survey regarding headache and sleep for Korean adults aged 19 to 69 years. A difference of one hour or more between sleep need and average sleep time indicated insufficient sleep. Results Of 2,695 participants, 727 (27.0%) individuals were classified as having insufficient sleep. The prevalence of insufficient sleep among individuals with migraine (45.5%) was significantly higher compared to that among individuals with non-migraine headache (32.9%, p = 0.004) or among non-headache (20.4%, p

Abstract Background Recent studies have shown a significant association between restless legs syndrome (RLS) and primary headache disorders. Nevertheless, information regarding the association between tension-type headache (TTH) and RLS is limited. This study aimed to investigate the association between RLS and TTH in a population-based sample. Methods We selected a stratified random population sample of Koreans aged 19–69 years and assessed them using a semi-structured interview designed to identify RLS, headache type, and clinical characteristics of TTH. We determined the prevalence and clinical impact of RLS in participants with TTH. Results Of the 2695 participants, 570 (21.2%) and 142 (5.3%) were classified as having TTH and RLS, respectively. Among the 570 individuals with TTH, 113 (19.8%) also met the criteria for probable migraine (PM). The prevalence of RLS was significantly higher among individuals with TTH than among those with non-headache (6.0% vs 3.6%, p = 0.018). The prevalence of RLS was significantly higher in subjects with TTH who fulfilled PM criteria than in those with non-headache participants (8.0% vs. 3.6%, p = 0.018). However, RLS prevalence in individuals with TTH who did not fulfil PM criteria did not differ from that of participants with non-headache (5.5% vs. 3.6%, p = 0.063). TTH participants with RLS had higher visual analogue scale scores for headache intensity (5.1 ± 2.0 vs. 4.3 ± 1.8, p = 0.038), and higher prevalence of anxiety (20.6% vs. 8.8%, p = 0.022) and depression (14.7% vs. 3.5%, p = 0.002) than TTH participants without RLS. Multivariable analyses revealed that headache aggravation by movement (odds ratio [OR] = 2.4, 95% confidence interval [CI] = 1.1–5.2) and depression (OR = 3.5, 95% CI = 1.1–11.4) were significant indicators of RLS among individuals with TTH. Conclusions The prevalence of RLS was higher among individuals with TTH than among those with non-headache. Some clinical presentations varied in accordance with the presence of RLS among participants with TTH.

A 43-year-old male presented with daytime sleepiness at work and indifferent behavior like never before. Two weeks prior to hospital admission, he had episodic memory loss with well preserved remote memory. Brain MRI showed a dural arteriovenous fistula (DAVF) in the right lateral transverse sinus with a bilateral thalamic venous infarction. Cerebral angiography confirmed a right transverse sigmoid dural arteriovenous fistula with a feeding artery of the right occipital artery and left posterior meningeal artery. The DAVF was completely eliminated through multiple endovascular interventions. Recently, endovascular treatment has become one of the main therapeutic options to obliterate a fistulous site, which has led to a rapid diagnostic approach and management of DAVFs with high curative rates. We report a rare case of posterior fossa located at a dural arteriovenous fistula that caused rapid progressive dementia and was successfully eliminated through only endovascular treatment.

To determine the prevalence, sleep characteristics, and comorbidities associated with a high risk for obstructive sleep apnea (OSA) in the Korean adult population.We analyzed data from 2,740 subjects who responded to a nationwide questionnaire survey of sleep characteristics. Those who qualified under two or more symptom categories of the Berlin questionnaire were defined as "at high risk for OSA". We investigated their socio-demographic information, sleep habits, and medical and psychiatric comorbidities. Logistic regression analyses were performed to identify factors and consequences significantly associated with a high risk for OSA.The prevalence of a high risk for OSA was 15.8% (95% confidence interval [CI] 14.5-17.2%). Multiple logistic regression analysis showed that old age (≥ 70 years, odds ratio [OR] 2.68) and body mass index ≥ 25 kg/m2 (OR 10.75) were significantly related with a high risk for OSA, whereas regular physical activity (OR 0.70) had a protective effect. Subjective sleep characteristics associated with a high risk for OSA were perceived insufficient sleep (OR 1.49), excessive daytime sleepiness (OR 1.88), and insomnia (OR 3.70). In addition, hypertension (OR 5.83), diabetes mellitus (OR 2.54), hyperlipidemia (OR 2.85), and anxiety (OR 1.63) were comorbid conditions independently associated with a high risk for OSA.This is the first study to demonstrate the prevalence of a high risk for OSA in a nationwide representative sample of the Korean adult population. These findings elucidate the epidemiology and clinical characteristics of those at high risk for OSA.

Background: Chemical meningitis results from foreign materials causing inflammation to the meninges covering the brain and spinal cord. Cerebrospinal fluid (CSF) study of chemical meningitis mimics bacterial meningitis. Case Report: We report three cases of chemical meningitis after spinal or epidural anesthesia with mepivacaine or bupivacaine. They experienced mental change or seizure. The results of CSF study revealed increased polymorphonuclear cell count and protein level and decreased glucose concentration. Gram staining and bacterial culture of CSF were all negative. We started empirical antibiotics and corticosteroids immediately and the patients were rapidly improved. Concclusion: The chemical meningitis should be differentiated in bacterial meningitis because bacterial meningitis is life-threatening and requires immediate antibiotic therapy. Chemical meningitis dramatically responds to steroid. The results of CSF study improved shortly after steroid administration.

The multidrug resistance protein 2 (MRP2, ABCC2) gene may determine individual susceptibility to adverse drug reactions (ADRs) in the central nervous system (CNS) by limiting brain access of antiepileptic drugs, especially valproic acid (VPA). Our objective was to investigate the effect of ABCC2 polymorphisms on ADRs caused by VPA in Korean epileptic patients. We examined the association of ABCC2 single-nucleotide polymorphisms and haplotype frequencies with VPA related to adverse reactions. In addition, the association of the polymorphisms with the risk of VPA related to adverse reactions was estimated by logistic regression analysis. A total of 41 (24.4%) patients had shown VPA-related adverse reactions in CNS, and the most frequent symptom was tremor (78.0%). The patients with CNS ADRs were more likely to have the G allele (79.3% vs. 62.7%, p = 0.0057) and the GG genotype (61.0% vs. 39.7%, p = 0.019) at the g.-1774delG locus. The frequency of the haplotype containing g.-1774Gdel was significantly lower in the patients with CNS ADRs than without CNS ADRs (15.8% vs. 32.3%, p = 0.0039). Lastly, in the multivariate logistic regression analysis, the presence of the GG genotype at the g.-1774delG locus was identified as a stronger risk factor for VPA related to ADRs (odds ratio, 8.53; 95% confidence interval, 1.04 to 70.17). We demonstrated that ABCC2 polymorphisms may influence VPA-related ADRs. The results above suggest the possible usefulness of ABCC2 gene polymorphisms as a marker for predicting response to VPA-related ADRs.

Background: Fluid-attenuated inversion recovery hyperintense vessels (FHVs) are known to reflect stagnant or slow blood flow within the cerebral artery. FHVs are frequently observed in patients with acute cerebral infarction accompanied by arterial occlusion or significant stenosis of the anterior cerebral circulation. However, FHVs have not been studied in the context of posterior cerebral circulation. Thus, we investigated the prevalence of FHVs and its clinical significance in patients with acute posterior cerebral artery (PCA) territory infarction. Methods: In this retrospective study, consecutive patients with PCA territory infarction who underwent MRI within 1 week after symptom onset were enrolled. Two neurologists who were blinded to the angiographic findings read the images and determined the presence of FHVs. Afterwards, FHVs were graded according to the extent (subtle or prominent) and location (proximal or distal) of the hyperintense vessels. Neurologic deficits of the patients were assessed by the National Institutes of Health Stroke Scale (NIHSS) upon admission and after 5 days. The clinical outcome between patient groups based on FHVs grading was compared using the NIHSS. Among the patients with PCA occlusion, infarction volume on the diffusion-weighted image was compared between the two groups with and without distal FHVs. Results: FHVs were observed in 25 of the 87 patients (28.7%) with PCA territory infarction and in 65.7% of the 35 patients with significant arterial stenosis (10 patients) or occlusion (25 patients) in the posterior cerebral circulation. Among the 18 patients with PCA occlusion, the NIHSS score was significantly improved in patients with distal FHVs compared to the others (2.00 ± 2.18 vs. 0.56 ± 1.01, p = 0.04). The infarction volume was smaller in the distal FHV group than in the others (8.3 ± 8.7 vs. 16.8 ± 17.6 ml), but the difference was not statistically significant. Conclusions: FHVs are detected in patients with PCA territory infarction, especially in those with an occlusive lesion in the PCA. FHVs can be used as an imaging marker of PCA occlusion. Although this study showed a better clinical improvement in patients with distal FHVs, further study is needed to elucidate the clinical meaning of FHVs in PCA infarction.

Although tension-type headache (TTH) is a frequent type of headache disorder and imposes a significant burden, there is scant information about the prevalence and impact of comorbid anxiety and depression among individuals with TTH. We investigated the prevalence and clinical impact of anxiety and depression among patients with TTH in the general population. We recruited Korean participants aged 19-69 years using a two-stage clustered random sampling method. To identify the presence of headache type, anxiety, and depression, we used a semi-structured interview using certain questionnaires. To assess the level of anxiety and depression, we used the Goldberg Anxiety Scale and Patient Health Questionnaire-9, respectively. Among 2,695 participants, 570 people (21.2%) had TTH during previous 1 year. In participants with TTH, the prevalence of anxiety (9.5% vs. 5.3%, p = 0.001) and depression (4.2% vs. 1.8%, p = 0.001) was significantly higher than that of non-headache participants. The prevalence of anxiety among TTH participants with >15 attacks per month [21.4%, odds ratio (OR): 4.0] and 1-14 attacks per month (13.1%, OR: 2.2) was higher than that in those with

Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE) because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs) for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. In vitro, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA)-ergic interneurons and released GABA in response to the depolarization induced by a high K+ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III+ neurons (∼34%), APC-CC1+ oligodendrocytes (∼28%), and GFAP+ astrocytes (∼8%). Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF) levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest that human fetal brain-derived NSPCs possess some therapeutic effect for TLE treatments although further studies to both increase the yield of NSPC grafts-derived functionally integrated GABAergic neurons and improve cognitive deficits are still needed.