Epilepsy is a neurological disorder with marked genetic heterogeneity， and genetic factors play an important role in the development and progression of epilepsy. High-throughput sequencing， genome-wide association studies， and large-scale genomic databases have greatly accelerated the discovery of epilepsy-associated genes and precision medicine； however， the pathogenic interpretation of low-frequency variants， complex inheritance patterns， and variants with mild functional impairment remains challenging. The gene dependency principle addresses how life activities depend on gene function and proposes the key concepts including functional dependency， genetic dependent nature， genetic dependent quantity， and genetic dependent stage， which provides a new medical genetics framework for understanding gene-disease relationship and the pathogenicity of variants.Based on this principle， the 3-Ⅰ approach emphasizes individualized phenotype analysis， individualized case analysis， and individualized gene analysis， integrating whole-exome sequencing， gene dependency assessment， and the China Epilepsy Gene 1.0 Project cohort， and this framework has facilitated the discovery or identification of more than 40 novel pathogenic genes or candidate pathogenic genes for epilepsy， thereby providing a theoretical basis for precise diagnosis， individualized therapy， genetic counseling，and disease prevention.Recently， the new pathogenic gene phenotypes including USP25， ZFHX3， and ATP6V0C have been recognized by OMIM， which fully reflects the application value of the gene dependency principle in the discovery of novel epilepsy-associated genes.

This article summarizes the research advances in the clinical manifestations， related factors， and underlying mechanisms of cognitive impairment in elderly adults with epilepsy. The prevalence rate of cognitive impairment ranges from 26% to 87% in elderly adults with epilepsy， with the main manifestations of impairment in short- and long-term visual memory， verbal memory， executive function， attention， and psychomotor speed. Cognitive function in elderly adults with epilepsy shows a progressive decline over time， which can be explained by the parallel decline model， the two-hit model， and the accelerated aging model. Epilepsy comorbid with cognitive impairment in elderly adults may result from the combined effect of epilepsy itself， brain structural and functional changes， comorbidity burden， anti-seizure medications， and pathological changes associated with Alzheimer disease. Frequent seizures and subclinical epileptiform discharges may accelerate cognitive decline by disrupting neural network activity and memory consolidation processes. The bidirectional relationship between epilepsy and dementia suggests the existence of shared pathological mechanisms leading to cognitive impairment.

Electroencephalography（EEG） is a fundamental tool in the diagnosis and management of epilepsy， and in recent years， its role in epilepsy associated with malformations of cortical development（MCD） has expanded from a conventional tool for adjunctive diagnosis to one used to reveal structural etiologies and assess prognosis. This article systematically reviews the scalp EEG features of patients with MCD， summarizes the electrophysiological manifestations of common MCD subtypes， and highlights the value of EEG in the diagnosis of MCD and the potential significance of its discharge patterns in prognostic evaluation， in order to provide a reference for clinical diagnosis and treatment.

Epilepsy is a common chronic nervous system disease worldwide， affecting approximately 50 million people around the world. Some patients have shown poor response to existing anti-seizure medications and neuromodulation therapies， and therefore， it is urgently needed to explore new treatment strategies. Polyunsaturated fatty acid（PUFA） have become a research hotspot in the field of nutritional intervention for epilepsy due to their roles in neural signaling， cell membrane stability， and inflammation regulation. Studies have shown that ω-3 fatty acids can reduce neuronal excitability， inhibit inflammatory response， and improve mitochondrial energy metabolism， whereas metabolic imbalance of ω-6 fatty acids may activate inflammatory pathways and exacerbate neuronal injury. PUFA may regulate the PPARγ/AMPK/NF-κB signaling axis， thereby coordinating inflammation and energy metabolism through immunometabolic coupling， maintaining neuroimmune homeostasis， and optimizing cerebral energy supply.On this basis， optimizing the composition of PUFA and ω-6/ω-3 ratio in ketogenic diet may become an effective supplementary strategy for epilepsy management， particularly offering a new nutritional intervention approach for medically intractable epilepsy， with important clinical and translational value.

Objective To analyze the changing trends of the incidence and mortality of epilepsy in China from 1994 to 2023， and to provide a basis for the formulation of prevention and control strategies. Methods Based on the research database of the Global Burden of Disease Study 2023（GBD 2023）， the data on the incidence and mortality of epilepsy in China from 1994 to 2023 were extracted， and the age-period-cohort model was used to estimate the age， period， and cohort effects on the risk of onset and mortality of epilepsy. Meanwhile， the ARIMA model was used to predict the changing trends of the incidence and mortality rates of epilepsy from 2024 to 2030. Results The results of age effect analysis showed that the incidence rate of epilepsy in China from 1994 to 2023 first decreased and then increased with the increase in age， while the mortality rate of epilepsy tended to decrease from 5-9 years of age to 65-69 years of age and slightly increase from 70-74 years of age to 85-89 years of age. The highest incidence and mortality rates of epilepsy were observed in the population aged 5-9 years in China， with a peak incidence rate of 34.10/100 000 and a peak mortality rate of 3.9/100 000. The results of period effect analysis showed that the risk of onset first increased， then decreased， and increased again from 1994-1998 to 2009-2013， followed by a reduction from 2009-2013 to 2019-2023； the risk of death tended to decrease from 1994 to 2023， decreasing from 1.30（95%CI 1.26‒1.34） in the period of 1994-1998 to 0.62（95%CI 0.60‒0.64） in the period of 2019-2023. The results of cohort effect analysis showed that the mortality risk of epilepsy in China tended to decrease across successive birth cohorts， with more recent birth cohorts experiencing lower mortality risk. The prediction results showed that the incidence and mortality rates of epilepsy would decrease slowly from 2024 to 2030. Conclusion The incidence and mortality of epilepsy in China are influenced by age effects， period effects， and cohort effects to varying degrees. It is important to focus on the younger and older age groups and implement targeted public health interventions， so as to further reduce disease burden.

Sengers syndrome is a rare autosomal recessive mitochondrial DNA depletion syndrome and a highly malignant disease. Acylglycerol kinase（AGK） is an mitochondrial inner membrane protein that performs both kinase-independent and kinase-dependent functions within the mitochondria， and loss-of-function mutations in AGK are pathogenic factors for Sengers syndrome. This article reports the first case of adult-onset Sengers syndrome comorbid with epilepsy caused by an AGK gene mutation in China and explores the potential mechanisms of seizures， so as to further deepen the understanding and research of the AGK gene and provide a reference for clinical diagnosis and treatment.

Temporal lobe epilepsy（TLE） is one of the most prevalent types of focal epilepsy in clinical practice， and 30%‒40% of these patients progress to refractory temporal lobe epilepsy（RTLE）， while electroencephalography（EEG） is an important cornerstone for the diagnosis and preoperative evaluation of epilepsy. With the continuous advances in neurophysiology and signal analysis technologies in recent years， the understanding of EEG characteristics in RTLE has gradually evolved from traditional spike identification to new dimensions such as high-frequency oscillation analysis and network dynamics interpretation. This article systematically reviews the features of RTLE on scalp and intracranial EEG， clarifies their clinical value in localization of epileptic foci， pathological correlation， and prognostic assessment， and discusses the future developmental trends of related technologies.

Burst suppression is a serious abnormal phenomenon on electroencephalogram（EEG），which often indicates a poor prognosis for patients. This article reports the evolution of EEG burst suppression in a patient with advanced malignant tumor complicated by epilepsy secondary to Listeria meningoencephalitis in the intensive care unit， as well as the diagnosis and treatment process of this patient. This case shows that EEG plays an important role in monitoring the condition of critically ill patients and can provide guidance for diagnosis and treatment.

Objective To investigate the efficacy and safety of tenecteplase versus alteplase in the treatment of acute ischemic stroke（AIS）， as well as the value of neutrophil-to-lymphocyte ratio（NLR）， lymphocyte-to-monocyte ratio（LMR）， platelet-to-lymphocyte ratio（PLR）， and systemic inflammation response index（SIRI） before thrombolysis in predicting functional prognosis on day 90 after onset. Methods A total of 278 patients with AIS treated at Inner Mongolia People's Hospital between May 2024 and November 2024 were enrolled. Patients were divided into a tenecteplase group and an alteplase group according to thrombolytic agents， and the therapeutic efficacy and safety were compared between the two groups. All subjects were categorized into a good prognosis subgroup（mRS ≤ 2） and a poor prognosis subgroup（mRS > 2） based on the modified Rankin Scale（mRS） scores assessed at 90 days after stroke onset. Logistic regression analysis was performed to explore the predictive value of pre-thrombolysis inflammatory markers for clinical prognosis. Results Compared with the alteplase group， the tenecteplase group had significantly better improvement in NIHSS score at 24 hours after thrombolysis， on day 7 after thrombolysis， and at discharge， as well as significantly higher cure rate and overall response rate（P<0.05）， and there were no significant differences between the two groups in the distribution of mRS score and the incidence rate of intracerebral hemorrhage events on day 90 after onset（P>0.05）. The multivariate Logistic regression analysis showed that elevated neutrophil count，high NLR， and high SIRI before thrombolysis were independent risk factors for poor 90-day prognosis（P<0.05），among which SIRI showed the stronger predictive effect（with the higher odds ratio）. Conclusion Tenecteplase has better efficacy in promoting early neurological recovery， with comparable functional prognosis to alteplase on day 90 after onset.Neutrophil count， NLR， and SIRI before thrombolysis can be used as independent risk factors for predicting poor prognosis on day 90 after onset.

Objective To investigate the association of biological aging acceleration estimated by the Klemera-Doubal method（KDM-AA） with the clinical prognosis of patients with acute ischemic stroke（AIS） receiving reperfusion therapy. Methods The patients with AIS who received reperfusion therapy in Zhejiang Provincial People’s Hospital from 2018 to 2024 were enrolled in this study. The biological age（BA） of patients was estimated using a BA model constructed based on the healthy population. KDM-AA was defined as the BA higher than chronological age（CA）. The clinical endpoints included parenchymal hematoma（PH） within 24 hours after reperfusion therapy， malignant cerebral edema within 5 days， and poor prognosis at 90 days， 6 months， and 12 months. Poor prognosis was defined as a modified Rankin Scale（mRS） score of 3-6. The Logistic regression analysis was used to investigate the association between KDM-AA and endpoint events， and the predictive performance of the models was compared using the area under the receiver operating characteristic curve（AUC）， net reclassification improvement（NRI）， and integrated discrimination improvement（IDI）. Results A total of 864 patients were enrolled， among whom 214（24.8%） had KDM aging acceleration. The multivariable analysis showed that KDM-AA was significantly associated with all endpoint events. After KDM-AA was incorporated into the baseline models， there was a significant increase in the predictive ability for each endpoint event. Conclusion KDM-AA is an independent predictive factor for short- and long-term endpoint events after reperfusion therapy in patients with AIS and has a good potential application value in clinical practice.

Objective To investigate the correlation between the serum levels of folic acid and homocysteine（Hcy） in acute stroke patients and their value in predicting prognosis. Methods A total of 180 acute stroke patients who were treated in The Second Central Hospital of Baoding from January 2020 to January 2025 were enrolled as subjects， and according to the level of folic acid， they were divided into normal folic acid group（102 patients with a folic acid level of ≥3.0 ng/ml） and folic acid deficiency group（78 patients with a folic acid level of <3.0 ng/ml）. On day 90 after disease onset， 108 patients with a modified Rankin Scale（mRS） score of ≤2 were enrolled in the good prognosis group， while 72 patients with an mRS score of >2 were enrolled in the poor prognosis group. The multiple linear regression analysis was used to investigate the correlation between folic acid and Hcy； Locally Weighted Scatterplot Smoothing（LOWESS） was used to analyze the two-dimensional curve relationship between folic acid and Hcy； the Logistic regression model analysis was used to investigate the independent association between folic acid/Hcy and poor prognosis； the restricted cubic spline model was used to investigate the dose-response relationship between folic acid/Hcy and poor prognosis； a two-factor analysis of variance was used to investigate the impact of folic acid and Hcy on mRS score； the receiver operating characteristic（ROC） curve was used to analyze the value of folic acid and Hcy in predicting the prognosis of acute stroke patients. Results There was a significant nonlinear negative correlation between the levels of folic acid and Hcy（P<0.05）， and the levels of folic acid and Hcy were independently associated with the poor prognosis of patients. The two-factor analysis of variance showed that regardless of the level of Hcy， there was a significant difference in mRS score between different folic acid groups（F=12.645， P<0.001）， and for patients with different levels of Hcy， mRS score gradually decreased with the increase in the level of folic acid. Combined measurement of folic acid and Hcy had a significantly larger area under the ROC curve（AUC） than the measurement of folic acid alone（P<0.001） or Hcy alone（P=0.029）， while there was no significant difference in AUC between the measurement of folic acid or Hcy alone（P=0.075）. Conclusion The level of folic acid is significantly negatively correlated with that of Hcy， and combined measurement of folic acid and Hcy has a relatively high value in predicting prognosis.

Objective To investigate the clinical and myopathological features of child-onset mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes（MELAS） and the results of post-treatment follow-up. Methods Clinical data were collected from 18 patients with child-onset MELAS， and a confirmed diagnosis was made based on the results of muscle biopsy and genetic testing， and all patients were followed up after treatment. Results Of all 18 patients， there were 10 male patients and 8 female patients， with a mean age of onset of（12.3±3.3） years（range 6-17 years）， a mean age of（19.5±5.4） years（range 12-33 years） at the time of confirmed diagnosis， and a mean course of disease of（7.2±5.8） years（range 0.3-20 years）. As for clinical manifestations， there were 15 patients with epileptic seizures， 10 with stroke-like episodes， 4 with headache， and 5 with psychiatric symptoms. Physical examination showed short stature in 14 patients， hirsutism in 3 patients， cognitive impairment in 15 patients， hearing loss in 9 patients， aphasia in 8 patients， and hemianopsia in 4 patients. There were 4 patients with a reduction in limb muscle strength， 5 patients with an increase in muscle tension， and 4 patients with positive pathological signs. Brain MRI showed abnormal long T₁ and long T₂ signals in unilateral or bilateral cerebral cortex in all 18 patients， and brain atrophy was observed in 7 patients. Brain CT showed basal ganglia calcification in 3 patients. Among the 15 patients who underwent muscle biopsy， 13 had typical ragged red fiber， and 9 had ragged blue fiber and strongly succinate dehydrogenase-reactive blood vessels. Genetic testing was performed for 12 patients， and the results showed mtDNA3243A>G mutation in 11 patients and mtDNA13513G>A mutation in 1 patient. Fifteen patients were followed up for 2-9 years， among whom 4 had a stable disease， 2 experienced deterioration， and 9 died， and the main causes of death were persistent seizures and pulmonary infection. Conclusion Epileptic seizures and stroke-like episodes are the most common clinical symptoms in patients with child-onset MELAS， with the important clinical signs of cognitive impairment， short stature， and hirsutism. Most patients have a poor prognosis， and early confirmed diagnosis and comprehensive treatment can delay the progression of the disease.

Spinal and bulbar muscular atrophy， also known as Kennedy disease（KD）， is an X-linked recessive neurological disorder with the core pathogenesis of abnormal expansion of CAG repeat sequences in the androgen receptor gene. The main clinical manifestations of KD include progressive limb weakness and muscular atrophy， frequently accompanied by endocrine disorders and neuroelectrophysiological abnormalities. KD is easily confused with other neuromuscular diseases， leading to the high rates of missed diagnosis and misdiagnosis in clinical practice. This article analyzes one patient with suspected KD and his family members and reports this familial case based on the clinical data and genetic testing results of the family members， and performs a literature review， in order to increase awareness of this disease and its familial genetic characteristics among clinical workers and improve their ability to diagnose and differentiate this condition.

Dyke-Davidoff-Masson syndrome（DDMS） is a clinical syndrome characterized by unilateral cerebral hemiatrophy and compensatory calvarial changes. This article reports a DDMS patient carrying an ATP1A3 gene mutation. The patient was a 27-year-old young male， with the clinical manifestations of seizures， hemiplegia， facial asymmetry， and mild cognitive impairment. Cranial magnetic resonance imaging revealed an encephalomalacic lesion in the left frontoparietal lobe with dilation of the ipsilateral lateral ventricle， left hippocampal atrophy， and FLAIR hyperintensity. Genetic testing identified a heterozygous mutation of c.2458G>A（p.Asp820Asn） in the ATP1A3 gene. Seizures were controlled after adjustment of the treatment regimen， and now the patient is still under ongoing follow-up. This is the first case of DDMS reported in China in which an ATP1A3 mutation was identified by comprehensive genetic testing. Although the pathogenicity of this mutation requires further validation， the results suggest that ATP1A3 dysfunction may be involved in abnormal brain structural development or neural injury in DDMS. Genetic testing can help expand our understanding of the etiology of DDMS.

Stroke is one of the leading causes of death and disability among Chinese residents， and ischemic stroke is often caused by carotid artery stenosis. Therefore， accurate assessment of carotid artery stenosis lesions to provide guidance for interventional treatment is of great significance for improving the prognosis of patients. Although traditional imaging techniques， such as intravascular ultrasound， computed tomography angiography， and digital subtraction angiography， can assess the degree of carotid artery stenosis， they fail to clearly display the microstructure of the responsible carotid artery and have significant limitations in assessment. In recent years， optical coherence tomography（OCT）， with its advantages of ultra-high resolution and real-time imaging， has gradually been applied in the diagnosis and treatment of cerebrovascular diseases， especially in determining the nature of carotid artery stenosis， formulating interventional treatment regimens， and monitoring postoperative treatment outcomes， thereby showing a unique and significant clinical value. This article systematically reviews the core advantages of OCT， its specific application scenarios in the diagnosis and treatment of carotid artery stenosis， technical limitations， and development prospects， in order to provide a reference for the standardized application of this technique in clinical practice.

Myelin oligodendrocyte glycoprotein antibody-associated disorders（MOGAD） are a group of autoimmune inflammatory demyelinating diseases involving the central nervous system， characterized by marked clinical heterogeneity and a tendency toward recurrence.Although conventional immunotherapy can improve symptoms in the acute stage， some patients still experience issues such as glucocorticoid dependence， recurrence after dose reduction， and insufficient treatment response. Studies have shown that interleukin-6（IL-6） participates in the immunopathogenesis of MOGAD by regulating humoral immunity， affecting the Th17/Treg balance， and increasing blood-brain barrier permeability. In recent years， treatment strategies targeting the IL‑6/IL‑6 receptor（IL‑6R） signaling pathway have attracted more and more attention. IL‑6R antagonists can inhibit both cis- and trans-signal transduction of IL‑6 and have shown certain application prospects in reducing the risk of recurrence and improving the outcome of some patients with refractory diseases. This article reviews the immunopathogenesis of MOGAD and the recent advances in therapies targeting the IL‑6/IL‑6R pathway， in order to provide a reference for the individualized treatment of MOGAD.

Objective To investigate the application effect of a hierarchical progressive problem-based learning（PBL） teaching model in developing clinical decision-making ability among refresher physicians engaged in vascular ultrasound， and to provide a reference for improving the teaching quality of vascular ultrasound specialty. Methods A total of 77 refresher physicians engaged in vascular ultrasound in Xuanwu Hospital， Capital Medical University， from January 2023 to December 2024 were enrolled and randomly divided into observation group（38 physicians receiving hierarchical progressive PBL teaching） and control group（39 physicians receiving traditional teaching）. The two groups were compared in terms of theoretical assessment， case analysis assessment， and operation assessment at the end of rotation， as well as the degree of satisfaction among both refresher physicians and instructors. Results Compared with the control group， the observation group achieved significantly higher scores of case analysis [（89.6±4.9） vs（86.0±4.9），P<0.05] and theoretical assessment [（91.8±4.1） vs（88.9±3.8），P<0.05]， and there was no significant difference in operation assessment score between the two groups（P>0.05）.An analysis of covariance showed that the observation group had significantly better performance than the control group at department examination in terms of theoretical assessment score（F=12.165，P<0.001） and case analysis score（F=9.463，P=0.003），while there was no significant difference in the score of hands-on operation assessment between the two groups（F=1.893，P=0.173）. Compared with the control group， the observation group had a significantly higher degree of satisfaction among the refresher physicians [（97.5±4.3） vs（92.6±6.6），P<0.05] and the instructors [（90.1±7.3） vs（85.3±7.8），P<0.05]. Conclusion The hierarchical progressive PBL teaching model can effectively improve the case analysis and diagnostic decision-making abilities of refresher physicians engaged in vascular ultrasound and enhance teaching interaction and satisfaction， and therefore， it is suitable for the training of specialized vascular ultrasound talents.