Acta Epileptologica最新文献

{"title":"Prevalence and factors associated with intellectual impairment in children with epilepsy in two national referral hospitals in Uganda.","authors":"Anita Arinda, Molly McVoy, Joan Abaatyo, Mark Kaddumukasa, Martha Sajatovic, Elly Katabira","doi":"10.1186/s42494-026-00265-3","DOIUrl":"10.1186/s42494-026-00265-3","url":null,"abstract":"<p><strong>Background: </strong>Epilepsy is a common neurological condition in children and is often associated with intellectual impairment. However, there is limited information on the intellectual impairment among children with epilepsy in Uganda. This study assessed the prevalence and associated factors of intellectual impairment among children and adolescents with epilepsy attending two national referral hospitals in Uganda.</p><p><strong>Methods: </strong>This cross-sectional study included children and adolescents aged 5 to 17 years who had a diagnosis of epilepsy. Intellectual functioning was assessed using the Raven's Progressive Matrices. Logistic regression analysis was performed to determine demographic and clinical factors associated with intellectual impairment.</p><p><strong>Results: </strong>Of 386 participants, 34.7% had intellectual impairment. Older age (adjusted odds ratio [aOR] = 6.94, P = 0.001), being in a special needs school (aOR = 14.50, P = 0.016), not being in school (aOR = 26.01, P < 0.001), delayed speech (aOR = 3.26, P = 0.030), and anti-seizure medication polypharmacy (aOR = 3.08, P = 0.020) were positively associated with intellectual impairment, while adolescent-onset epilepsy (aOR = 0.05, P = 0.030) was negatively associated.</p><p><strong>Conclusions: </strong>Intellectual impairment is common among Ugandan children and adolescents with epilepsy and is associated with older age, school non-attendance, special-needs school placement, delayed speech, and anti-seizure medication polypharmacy. These findings underscore the need for routine assessment of intellectual functioning and targeted interventions, including academic support, speech therapy, and optimization of treatment regimens.</p>","PeriodicalId":33628,"journal":{"name":"Acta Epileptologica","volume":"8 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148362747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Taenia solium development and host interactions in neurocysticercosis: a narrative mini review on mechanistic pathways to epileptogenesis.","authors":"Franck Katembo Sikakulya, Hervé Monka Lekuya, Larry Kasereka Kamabu, Mathieu Katembo Manzekele, Eric Ochen, Fatuma Djuma Sonia, Jeannot Munihire Baanitse, Furaha Nzanzu Blaise Pascal, Rishi A Shah, Shitu Hauwa Balarabe, Olivier Kambere Kavulikirwa, David Kitya, Malcolm K Jones","doi":"10.1186/s42494-026-00261-7","DOIUrl":"10.1186/s42494-026-00261-7","url":null,"abstract":"<p><p>Neurocysticercosis (NCC), a central nervous system infection caused by the larval stage of Taenia solium, remains a leading cause of acquired epilepsy in endemic regions. Mounting evidence indicates that seizure development in NCC is not solely driven by host inflammatory responses but reflects complex, dynamic interactions between parasite development, host neuroimmune processes, and neuronal network remodeling. This narrative mini-review integrates experimental and clinical data to demonstrate that T. solium larvae actively shape the cerebral microenvironment through stage-specific immune modulation, blood-brain barrier disruption, and the release of neuroactive excretory-secretory products. During cyst degeneration, parasite antigens and excitatory amino acids drive microglial and astrocytic activation, amplify glutamatergic signaling, and destabilize inhibitory neurotransmission, collectively reducing seizure thresholds. These acute events are followed by chronic structural alterations, including perilesional gliosis, synaptic reorganization, and persistent network hyperexcitability, particularly around parenchymal and calcified lesions that serve as enduring epileptogenic foci. Integrating parasite developmental biology with neuroimmune and neuroexcitatory mechanisms, this review reconceptualizes NCC epileptogenesis as an active, multilevel dialogue between parasite, host, and neuron, rather than a passive, inflammation-driven consequence of infection. This integrated mechanistic framework highlights opportunities for biomarker discovery and therapeutic strategies that look beyond mere parasite eradication to address sustained neural dysfunction. It further underscores the critical need for One Health-oriented interventions to disrupt the T. solium transmission cycle and alleviate the long-term burden of NCC-associated epilepsy.</p>","PeriodicalId":33628,"journal":{"name":"Acta Epileptologica","volume":"8 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13231682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148151517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term effects of carbamazepine on bone-related biochemical markers in patients with epilepsy.","authors":"Alqassem Y Hakami, Azzam A Althagafi, Abdulla S Alkhayat, Belal A Alturkistani, Hesham E Mawar, Ibrahim H Ibrahim, Haneen Abualhamail, Mohamed Eldigire Ahmed","doi":"10.1186/s42494-026-00262-6","DOIUrl":"10.1186/s42494-026-00262-6","url":null,"abstract":"<p><strong>Background: </strong>Carbamazepine (CBZ) is a commonly prescribed antiseizure medication frequently prescribed for epilepsy, trigeminal neuralgia, and mood disorders. However, CBZ is a strong inducer of cytochrome P450 enzymes, which can accelerate the catabolism of vitamin D and potentially alter bone metabolism. This study aimed to evaluate the effects of long-term CBZ administration on bone health in patients with epilepsy.</p><p><strong>Methods: </strong>An observational study involving 226 patients was conducted at King Abdulaziz Medical City in Jeddah, Saudi Arabia. We analyzed the pre- and post-treatment serum levels of vitamin D (nmol/L), alkaline phosphatase (U/L), sodium (mmol/L), and calcium (mmol/L) to assess biochemical changes associated with prolonged CBZ therapy.</p><p><strong>Results: </strong>The analysis of vitamin D revealed a significant decrease after CBZ treatment (mean ± SD= 36.6 ± 15.68 nmol/L) compared to pre-treatment (45 ± 23.25 nmol/L) with a 95% CI of -14.47 to -2.37 and P = 0.007. Additionally, following the administration of CBZ, serum levels of calcium and sodium were both significantly reduced with P < 0.001 and P = 0.019, respectively. However, alkaline phosphatase levels showed no significant change.</p><p><strong>Conclusions: </strong>The study outcomes suggest a potential association between long-term CBZ use and bone health, as supported by the presence of biochemical abnormalities. Furthermore, these findings underscore the importance of proactive clinical screening and bone-preserving interventions. Moreover, further studies are recommended to address the management of epilepsy patients with impaired bone health.</p>","PeriodicalId":33628,"journal":{"name":"Acta Epileptologica","volume":"8 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13227868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148144921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First corpus callosotomy for medically refractory epilepsy in The Gambia: an international cooperation case report and historical review.","authors":"Zsombor T Gal, Ebrima K Manneh, Saksham Gupta, Gabrielle A Luiselli, Makumba Cham, Ancha Ceesay, Mai Nyassi, Yusupha Jobe, Richard Oguocha, Musa Barry, Mary F Gomez, Malick Jammeh, Oley Bojang, Tida Jagne, Fatoumata Jallow, Adama Njie, Cherno S Jallow, Mustapha Bittaye, Mariam Joof, Kebba S Marenah, Yohana C Sanchez, Maguette Mbaye, Nantenin Doumbia, Sabina Kangakan, Pokua Sarpong, Mhd A Alkhateeb, Eduardo R Cobas, Lamin Janneh, John D Rolston, John N Jabang","doi":"10.1186/s42494-026-00258-2","DOIUrl":"10.1186/s42494-026-00258-2","url":null,"abstract":"<p><strong>Background: </strong>Epilepsy affects over 50 million people worldwide, with the majority residing in low- and middle-income countries (LMICs) where access to specialized care is often constrained. Surgical intervention represents a crucial therapeutic modality for patients with medically refractory epilepsy, yet epilepsy surgery remains markedly underutilized in sub-Saharan Africa.</p><p><strong>Case presentation: </strong>We report the case of a 10-year-old boy in The Gambia with medically refractory epilepsy characterized by daily drop attacks. Despite optimized and adequately trialed therapy with carbamazepine and sodium valproate, he continued to experience disabling seizures, leading to recurrent head trauma. Computed tomography (CT) and magnetic resonance imaging (MRI) did not reveal an identifiable structural lesion. Given the intractability of seizures and significant associated morbidity, he underwent a corpus callosotomy. The procedure was performed via a standard microsurgical approach and concurrently addressed the resection of traumatic calcified scalp hematomas. The patient's postoperative recovery was uneventful, and he was discharged on postoperative day 13 and remained seizure-free. At the six-month postoperative follow-up, the patient achieved complete freedom from drop attacks, with generalized tonic-clonic seizures (GTCS) occurring only during periods of antiseizure medication (ASM) interruption.</p><p><strong>Conclusions: </strong>This case highlights the feasibility and therapeutic potential of epilepsy surgery in the context of a surgical program within a resource-limited setting. Scaling up access to epilepsy surgery in comparable environments could contribute to mitigating the global epilepsy treatment gap.</p>","PeriodicalId":33628,"journal":{"name":"Acta Epileptologica","volume":"8 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13224592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148139107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overtreatment and therapeutic nihilism in chronic epilepsy: a call to action!","authors":"Bernhard J Steinhoff, John Paul Leach","doi":"10.1186/s42494-026-00257-3","DOIUrl":"10.1186/s42494-026-00257-3","url":null,"abstract":"<p><p>Despite the use of appropriately selected antiseizure medications (ASMs), seizure freedom remains elusive for some patients at each treatment line, and those failing two ASMs are then classified with drug-resistant epilepsy (DRE). Living with long-term uncontrolled epilepsy can lead to discouragement and disillusionment for both people with epilepsy and clinicians. In the context of potential treatment failure, maximizing seizure control while minimizing adverse events becomes even more critical, necessitating continual symptom surveillance and consideration of therapeutic trials of ASMs where appropriate. This requires truly individualized care, and in this pursuit, physicians will encounter the diametrically opposed challenges of overtreatment (or a burdensome drug load) and therapeutic nihilism (caused by missing consideration of treatment possibilities). This paper presents a detailed review of these issues and the influence of patient- and physician-related factors. Diagnostic and treatment strategies include ensuring accurate diagnosis and epilepsy classification for optimization of ASM treatment, considering the risk-to-benefit ratio when choosing treatment, encouraging treatment adherence, considering the initiation of alternative therapies, adjusting concomitant medications when needed, maintaining awareness of variations in patient characteristics, re-framing emotions effectively, and engaging in effective communication with patients and their families. All will have to be undertaken in conjunction with cognitive and psychological approaches. Seizure freedom is an important and worthwhile goal, and patients and families should be aware that increased therapeutic options available today can make seizure freedom possible even in the context of a challenging a priori prognosis or after previous ASM failures.</p>","PeriodicalId":33628,"journal":{"name":"Acta Epileptologica","volume":"8 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13224403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148139017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of Brivaracetam as an adjunctive therapy in patients with focal-onset seizures: a phase III, multi-center, randomized, double-blind, placebo-controlled trial.","authors":"Peimin Yu, Ting Zhao, Weihong Lin, Xiong Han, Feng Li, Zhen Hong","doi":"10.1186/s42494-026-00253-7","DOIUrl":"10.1186/s42494-026-00253-7","url":null,"abstract":"<p><strong>Background: </strong>Preclinical experiments have revealed that Brivaracetam (BRV) exhibited a significant anti-seizure function in animal models and was more effective and safer than other synaptic vesicle protein 2A (SV2A) ligands, including levetiracetam (LEV), this study aims to evaluate the efficacy and safety of generic BRV tablets in Chinese patients with focal-onset seizure.</p><p><strong>Methods: </strong>This phase III, randomized, double-blind, placebo-controlled clinical trial conducted in 21 medical centers evaluated BRV (200 mg/day) as an adjunctive therapy in Chinese adult patients with focal-onset seizures, with or without secondary generalization, despite treatment with one or two permitted concomitant anti-seizure medications (ASMs). After an 8-week screening baseline, patients were 1:1 randomized to BRV 200 mg/day or placebo for a 12-week treatment period. The primary efficacy endpoint was the percent reduction in seizure frequency per 28 days from baseline. Safety evaluations included the adverse events (AEs), side effects, and the regular monitoring of clinical symptoms, vital signs, physical examinations, laboratory tests, electrocardiograms, and mood.</p><p><strong>Results: </strong>Of 179 randomized patients, 178 were included in the final analysis (90 in BRV; 88 in placebo), while one patient in placebo group was excluded for not receiving the study drug. The percent reduction in seizure frequency per 28 days from baseline was 40.67% in the BRV group compared to the placebo group. The 12-week responder rate was significantly higher with BRV than placebo [48.89% vs. 23.86%, Odds Ratio (OR) = 3.12, 95% Confidence Interval (CI): 1.63-5.99, P = 0.0006]. There's no statistical significance of reported AEs in the BRV and placebo groups. Seizure freedom was achieved by 10 (11.11%) and 2 (2.27%) patients in the BRV and placebo groups, respectively (P = 0.0325). Discontinuations due to AEs (6.67% vs. 0, P = 0.0287) and special concern AEs (32.22% vs. 9.09%, P = 0.0002) were higher with BRV than placebo. Dizziness, somnolence, and nausea were reported more frequently with BRV than placebo.</p><p><strong>Conclusions: </strong>Generic BRV demonstrated a better efficacy and comparable safety in treating focal-onset seizure in Chinese patients.</p>","PeriodicalId":33628,"journal":{"name":"Acta Epileptologica","volume":"8 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knockdown of Gasdermin D protects hippocampal neurons by regulating both pyroptosis and ferroptosis in a rat model of status epilepticus.","authors":"Fan Feng, Haijiao Wang, Yanmei Tian, Rong Luo, Qianyun Cai","doi":"10.1186/s42494-026-00255-5","DOIUrl":"10.1186/s42494-026-00255-5","url":null,"abstract":"<p><strong>Background: </strong>Pyroptosis and ferroptosis may be implicated in status epilepticus (SE)-induced neuronal damage. This study aimed to elucidate the effects of Gasdermin D (GSDMD) on pyroptosis and ferroptosis after SE, and to determine whether GSDMD inhibition ameliorates SE-induced neuronal damage and cognitive dysfunction.</p><p><strong>Methods: </strong>In the lithium-pilocarpine-induced SE rat model, we measured GSDMD and glutathione peroxidase 4 (GPX4) expression in the hippocampus via western blotting to evaluate the involvement of pyroptosis and ferroptosis after SE. After GSDMD knockdown by RNA interference, we performed Nissl staining to detect neuronal loss; quantitative reverse transcription polymerase chain reaction (qRT-PCR) to detect the hippocampal expressions of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α); Prussian blue staining to detect iron deposition; and western blotting and enzyme-linked immunosorbent assay to detect the expressions of the ferroptosis-related molecules GPX4, malonaldehyde (MDA), and glutathione (GSH). Finally, cognitive and behavioral functions were evaluated using the spontaneous-activity test and novel object-recognition test.</p><p><strong>Results: </strong>Western blotting showed a marked increase in GSDMD expression (P < 0.050) and a notable decrease in GPX4 levels in (P < 0.050) the hippocampus of rats, providing evidence that both pyroptosis and ferroptosis are activated following SE. In addition, GSDMD knockdown significantly improved hippocampal neuronal survival and improved cognitive and behavioral functions of SE rats. Meanwhile, knockdown of GSDMD led to a significant reduction in the mRNA expression of IL-1β, IL-6, and TNF-α (pyroptosis products) (P = 0.021, 0.010, and 0.015, respectively), a decrease in iron deposition (P = 0.000) and MDA levels (ferroptosis product) (P = 0.000), and increased GSH and GPX4 expression (negative ferroptosis regulators) (P = 0.000 and 0.004, respectively).</p><p><strong>Conclusions: </strong>Pyroptosis and ferroptosis may jointly contribute to SE-induced neuronal damage. GSDMD may regulate both pyroptosis and ferroptosis, and inhibiting GSDMD could improve cognitive and behavioral function in SE rats.</p>","PeriodicalId":33628,"journal":{"name":"Acta Epileptologica","volume":"8 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case report: precise mapping and epilepsy surgery of the Broca's area after a comprehensive OPM-MEG investigation of Broca's area localization.","authors":"Yuanfeng Zhou, Yanjiong Zhang, Luo Tian, Tianshuang Wang, Min Wang, Renqing Zhu, Hao Li, Zhongwei Qiao, Zhigang Cao, Yuming Peng, Ming Ding, Yi Wang","doi":"10.1186/s42494-026-00245-7","DOIUrl":"10.1186/s42494-026-00245-7","url":null,"abstract":"<p><strong>Background: </strong>Optically pumped magnetometers magnetoencephalography (OPM-MEG) have demonstrated their value in the diagnosis and mapping of epilepsy, as well as their advantages in pediatric applications.</p><p><strong>Case presentation: </strong>We present a case of 8-year-old boy with drug-resistant epilepsy, whose epileptogenic lesion is in left Broca's region. The boy underwent language function evaluation and localization by on-scalp OPM-MEG before surgery. Dipole clusters and Dipole Density of epileptogenic signals by OPM-MEG were located in the left inferior frontal gyrus, though language verbal generation mapping of OPM-MEG signals were mainly located in left frontal orbital gyrus, indicating a localization of the language function area. Seizure freedom and no loss of language function were achieved after MRI-guided laser interstitial thermal therapy.</p><p><strong>Conclusions: </strong>This article underscores the feasibility of using OPM-MEG to record abnormal discharges of seizure and assess language function area in children, especially in drug-resistant epilepsy surgery involving brain functional areas.</p>","PeriodicalId":33628,"journal":{"name":"Acta Epileptologica","volume":"8 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene variants in periventricular nodular heterotopia.","authors":"Jianping Song, Xiaoqin Sun, Chunqing Zhang","doi":"10.1186/s42494-026-00243-9","DOIUrl":"10.1186/s42494-026-00243-9","url":null,"abstract":"<p><p>Periventricular nodular heterotopia (PVNH) is a malformation of cortical development (MCD) mainly caused by aberrant neuronal migration, and a group of diseases sharing similar pathological manifestations, including the presence of nodular clusters of abnormal neurons in the subependymal region. PVNH is one of major causes that result in genetic epilepsy. Seizures can strike as early as a few days after birth but are more common at 10-20 years old, and among them, generalized tonic-clonic seizures are commonly observed. PVNH is a highly genetically heterogeneous disease associated with various rare single gene variants. However, despite the fact that the FLNA gene is identified to be closely correlated with the presence of PVNH, mutations in other genes were understudied and have not attracted as much attention due to the relatively low morbidity of PVNH. In consequence, an updated spectrum of PVNH-associated risk genes with potentially pathogenic changes that lead to PVNH in human patients is urgently needed. The risk genes that have already been clinically reported for PVNH are summarized here chronologically according to when the first patient was reported, and clinical manifestations of patients with each of these genes are described. Human cerebral organoids as well as animal models are subsequently discussed in this review to reveal alterations in risk gene products and the pathogenesis of PVNH.</p>","PeriodicalId":33628,"journal":{"name":"Acta Epileptologica","volume":"8 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The kynurenine pathway storm in epilepsy: mechanisms and therapeutic implications.","authors":"Yuxuan He, Jing Meng, Wen Luo, Mingxing Yu, Nana Zhang, Chunyan Chen, Liang Yu","doi":"10.1186/s42494-026-00250-w","DOIUrl":"10.1186/s42494-026-00250-w","url":null,"abstract":"<p><p>The kynurenine pathway (KP) is the main route for tryptophan (TRP) degradation and plays a crucial role in neuroinflammation, oxidative stress and neurotransmission, which holds significant clinical significance. The dysregulation of this pathway is closely related to neurological disorders such as epilepsy, and its metabolic products can promote the occurrence of epileptic seizures and comorbid depression. This review aims to clarify the complex mechanisms of the KP in the occurrence and development of epilepsy and to explore its potential as a therapeutic target for epilepsy and comorbid depression. This is a narrative review and synthesis of the current literature. We reviewed animal experiments and clinical studies, elaborating in detail on how metabolites of the KP and their key enzymes function in the context of epilepsy by regulating neuroinflammation, oxidative stress, glutamatergic signaling, and the gut-brain axis. We also explored the interaction between antiseizure medications (ASMs) and the KP, and evaluated the potential value of targeting key enzymes (such as indoleamine 2,3-dioxygenase, IDO) as a new therapeutic strategy for epilepsy. This review particularly focuses on the promoting effect of KP imbalance on comorbid depression, clarifying how IDO-mediated TRP metabolism changes constitute a common mechanism basis, jointly leading to the occurrence of epilepsy and depression-like behaviors. The occurrence and development of epilepsy are closely related to the imbalance of the KP, specifically manifested as a decrease in kynurenic acid (KYNA) level and an increase in quinolinic acid (QA) level. The IDO-mediated shift of TRP metabolism towards the KP is established as a critical mechanism underlying depression comorbidity in epilepsy. Therapeutic modulation of this pathway, through targeting key enzymes like IDO and restoring the KYNA/QA balance, presents a viable strategy for improving the cerebral microenvironment. This approach holds promise for enhancing seizure control, counteracting drug resistance, and concurrently alleviating comorbid depressive symptoms.</p>","PeriodicalId":33628,"journal":{"name":"Acta Epileptologica","volume":"8 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}