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 characteristics of choroid plexus volume （CPV） in Alzheimer disease （AD） and mild cognitive impairment （MCI）， as well as its association with cognitive function and the pathological burden of β-amyloid （Aβ） and tau. Methods The data of this study consisted of two parts. The first part of the data were collected from the individuals who attended the memory clinic of The First Hospital of Jilin University from January 2018 to July 2024， among whom there were 142 patients with AD， 95 with MCI， and 85 healthy controls. All individuals underwent neuropsychological assessments and three-dimensional T₁-weighted magnetic resonance imaging. FreeSurfer 7.4.1 combined with a Gaussian mixture model was used to measure CPV， which was then normalized by intracranial volume （ICV）， and the regression analysis and the generalized linear mixed model were used to investigate the association between CPV and cognitive function， as well as longitudinal cognitive changes. The second part of the data were longitudinal data obtained from the Alzheimer Disease Neuroimaging Initiative （ADNI） database； CPV and standardized uptake value ratios （SUVR） of Aβ and tau on PET-CT were extracted， and the generalized linear mixed model was used to observe the effect of CPV on the dynamic changes of Aβ and tau deposition. Results The AD and MCI groups had a significantly higher CPV/ICV ratio than the healthy control group， and the AD group had a significantly higher ratio than the MCI group （P<0.001）.After adjustment for confounding factors， CPV was negatively correlated with Mini-Mental State Examination score and Montreal Cognitive Assessment （MoCA） score and was positively correlated with Clinical Dementia Rating-Sum of Boxes score（P<0.001）. Right-side CPV predicted a longitudinal reduction in MoCA score （β=-2.596， P=0.041） and showed a significant interaction with time （β=-0.166，P=0.013）. In the ADNI cohort， CPV was correlated with Aβ across multiple brain regions and Braak stage and was positively correlated with the SUVR of tau （P<0.05）. Conclusion CPV increases with progression of AD continuum and is associated with cognitive impairment and the deposition of Aβ and tau，suggesting that CPV may be used as a potential low-cost imaging biomarker for AD.

Alzheimer disease （AD） is mainly characterized by progressive cognitive decline， with the core pathological changes of abnormal deposition of amyloid-β（Aβ） and tau protein in the brain. There are currently limited treatment methods for AD， with an urgent need for early risk biomarkers that can be targeted. Triglyceride-glucose （TyG） index is calculated based on fasting blood glucose and triglyceride， and it is an easily accessible surrogate marker for insulin resistance and can reflect metabolic stress load associated with glucose-lipid toxicity. Existing studies have shown that an increase in TyG is associated with cognitive decline and an increase in the risk of dementia or AD， and it may also be associated with core AD biomarkers such as Aβ42 and tau and p-tau in cerebrospinal fluid and atrophy in susceptible brain regions such as the hippocampus.Potential mechanisms may involve the pathways such as impaired brain energy metabolism， blood-brain barrier/neurovascular unit dysfunction， and amplification of neuroinflammation. This article reviews the advances in the clinical and mechanistic research on the association of TyG index with the clinical manifestations and pathological changes of AD and explores its application prospect in longitudinal risk stratification and early prevention of AD.

Objective To comprehensively assess the efficacy， biomarker changes， and safety of Lecanemab in the treatment of Chinese patients with Alzheimer disease in real-world clinical practice. Methods A retrospective analysis was performed for the data of patients who received Lecanemab treatment in The First Hospital of Hebei Medical University from 2024 to 2025， including cognitive-related neuropsychological assessment scales， radiological examination， and plasma biomarkers at baseline and at 6 and 12 months of treatment， and adverse events were recorded. The linear mixed-effects model and individual change trajectory plots were used for description and comparison of the above indicators. Results The results of MoCA and CDR-SB scales deteriorated with disease progression after Lecanemab treatment， while there were no significant changes in the results of MMSE scale. In addition， radiological examination and plasma biomarkers showed improvements in pathology， with amyloid PET showing a reduction in CL value， increases in plasma Aβ42 and Aβ42/Aβ40 ratio， and reductions in the levels of p-tau217 and GFAP. Of all patients， 24.1% reported adverse events， and a rare case of severe adverse drug reaction was recorded， with no events of symptomatic ARIA. Conclusion Lecanemab shows a clear effect of pathological clearance in Chinese patients with Alzheimer’s disease in a real-world setting and can effectively reduce Aβ load in the brain and regulate the levels of plasma-related biomarkers. Lecanemab has a good overall safety profile and can delay disease progression. This study provides real-world evidence-based support for the clinical application of Lecanemab in the Chinese population.

Objective Voxel-based morphometry（VBM）has been used to study gray matter volume （GMV） changes in patients with mild cognitive impairment （MCI），but with great differences in current research findings. This study aims to investigate the brain regions showing the most consistently reported GMV differences between MCI patients and healthy controls through a meta-analysis. Methods CNKI， Wanfang Data， Embase， PubMed， and Web of Science were searched for articles on the difference in GMV between MCI patients and healthy controls based on VBM published over the past 10 years， and the articles were screened based on inclusion and exclusion criteria. Signed differential mapping software was used to compare the difference in GMV between MCI patients and healthy controls. Results A total of 13 studies were included， involving 506 MCI patients and 435 healthy controls. Compared with the healthy control group， the MCI group had a significant reduction in GMV in the right superior temporal gyrus， the left postcentral gyrus， the left putamen， the left medial superior frontal gyrus， the left fusiform gyrus， and the bilateral hippocampus （P<0.005， peak height Z>1， cluster range ≥10 voxels）. Conclusion The meta-analysis confirmed the most relevant core brain structural regions in MCI patients. These findings not only provide a potential biomarker for MCI， but also help to gain a better understanding of its neuropathological basis.

Objective To investigate the clinical and radiological features of patients with moyamoya syndrome （MMS）and the influence of cerebral hypoperfusion on cognitive function in MMS. Methods A total of 153 patients with MMS who were consecutively admitted to Henan Provincial People’s Hospital from June 2023 to December 2024 were enrolled，and according to the presence or absence of cognitive impairment， they were divided into cognitive impairment group with 73 patients and normal cognitive function group with 80 patients. The two groups were compared in terms of clinical data， cranial MRI data， and perfusion-weighted magnetic resonance imaging （PWI-MRI） data， and the Logistic regression analysis was used to investigate the influencing factors for cognitive impairment in MMS patients. Results Based on the results of Montreal Cognitive Assessment （MoCA） and Mini-Mental State Examination （MMSE）， the incidence rate of cognitive impairment in MMS patients was 47.71%（73/153）.PWI-MRI showed that in the cognitive impairment group， the patients with local cerebral hypoperfusion （a reduction in relative blood volume） accounted for 49.32% （36/73）， while in the normal cognitive function， the patients with local hypoperfusion accounted for 31.25% （25/80）， and there was a significant difference between the two groups（χ²=5.196，P<0.05）.Frontal hypoperfusion（OR=2.098， 95%CI 1.049‒4.196，P=0.036） was a risk factor for cognitive impairment in MMS patients. Conclusion Cognitive impairment is common in MMS patients， and MMS patients with frontal hypoperfusion are more likely to develop cognitive impairment.

Alzheimer disease （AD）is a neurodegenerative disease with the core pathological features of β-amyloid （Aβ） deposition and abnormal tau phosphorylation， and it is often comorbid with sleep disturbance， with the presence of bidirectional interactions between the two diseases. orexin is a key neurotransmitter in the regulation of sleep-wake cycles， and the potential of orexin receptor antagonists （ORAs） in improving insomnia has attracted more and more attention. This article reviews the mechanism of interaction between AD and sleep disturbance， with a focus on the effect on ORAs， especially dual orexin receptor antagonists （DORAs） such as Suvorexant and Lemborexant， on AD pathology and sleep disturbance by regulating the orexin signaling pathway. Clinical studies have shown that DORAs can significantly improve sleep quality in AD patients by increasing total sleep time and reducing nocturnal awakenings and may reduce the levels of Aβ and phosphorylated tau protein in cerebrospinal fluid for a short period of time. However， current studies have the limitations of a small sample size and a short follow-up time， with insufficient evidence on the improvement in cognitive function and the presence of adverse reactions including somnolence. Future research should further explore the long-term efficacy and safety of ORAs in AD， in order to clarify the clinical value of ORAs in the comprehensive treatment of AD.

Alzheimer disease （AD） is a neurodegenerative disease characterized by cognitive dysfunction， and its pathogenesis remains unclear. More and more studies have shown that gut microbiota may be involved in the development and progression of AD through the “gut-brain axis”. This article reviews the association between gut microbiota and AD and discusses the pathogenic mechanisms and therapeutic prospects of gut microbiota in AD.

Objective To investigate the surface electromyography （sEMG） characteristics of drug-induced tremor， and to identify electrophysiological biomarkers for differentiating it from tremor caused by Parkinson disease （PD）. Methods A total of 50 patients with drug-induced tremor and 71 patients with PD were enrolled. The sEMG signals from bilateral radial wrist extensors and flexors，along with accelerometer signals， were recorded under resting and postural conditions.Tremor frequency，amplitude，contraction pattern，and harmonic resonance were analyzed. Results The patients in the drug-induced tremor group exhibited symmetrical bilateral tremor， with a higher proportion of patients with mandibular tremor compared with the PD group（70% vs 42.25%，χ²=9.09，P=0.003）.Compared with the PD group， the drug-induced tremor group had a significantly higher tremor frequency under both resting and postural conditions[（6.43±0.41）Hz/（6.57±0.33）Hz vs （4.68±0.27）Hz，F=620.64，P<0.001]， while there was no significant difference in tremor amplitude. Compared with the PD group， the drug-induced tremor group had a significantly lower proportion of patients with alternating contraction pattern under both resting （χ²=23.20，P<0.001） and postural（χ²=27.52，P<0.001） conditions， as well as a significantly lower proportion of patients with harmonic resonance under both resting（χ²=26.64，P<0.001） and postural（χ²=22.32，P<0.001） conditions. Conclusion Drug-induced tremor has the following electrophysiological features：bilateral symmetry，a higher prevalence rate of mandibular tremor， a higher tremor frequency，and a lower proportion of patients with alternating contraction pattern and harmonic resonance， which can provide objective evidence for differentiating drug-induced tremor from PD in clinical practice.

Objective To compare the differences in non-motor symptoms between the patients with Parkinson disease （PD） carrying LRRK2 G2385R mutation and those without such mutation， and to identify key clinical features. Methods The patients who were consecutively admitted to Xuanwu Hospital， Capital Medical University， from January to November 2025 and were diagnosed with PD were enrolled. According to the results of genetic testing， the patients were divided into carrier group and non-carrier group， and other known pathogenic mutations were excluded. Demographic data and the results of multiple clinical scales were collected， including UPDRS-Ⅲ，NMSS，MMSE，MoCA，HAMA，HAMD， RBDQ-HK， and olfactory questionnaire. Traditional statistical methods and Elastic Net regression were used for comparison between the two groups. Results A total of 292 PD patients were enrolled，among whom there were 27 carriers and 265 non-carriers， and there were no significant differences between the two groups in sex， age of onset， disease duration， and motor symptoms （all P>0.05）. The univariate analysis showed that the carrier group had a significantly lower RBDQ-HK score than the non-carrier group （P<0.05）. The Elastic Net analysis further revealed that RBD symptoms， olfactory function， and overall non-motor symptom burden were negatively correlated with the carrier status， while anxiety score was positively correlated with the carrier status，suggesting a relatively milder burden of non-motor symptoms in carriers. Conclusion There are no significant differences in motor symptoms between LRRK2 G2385R carriers and non-carriers， but LRRK2 G2385R carriers have a distinctive non-motor symptom phenotype， especially milder RBD symptoms.The multivariate analysis suggests that the carrier status may be associated with a lower burden of non-motor symptoms， which may help to deepen the understanding of clinical heterogeneity in genetic subtypes of PD and provide a reference for individualized assessment.

Objective To investigate the feasibility and efficacy of bilateral globus pallidus internus deep brain stimulation （GPi-DBS） as a rescue treatment strategy after failed subthalamic nucleus deep brain stimulation （STN-DBS） in the management of Parkinson disease （PD）. Methods A retrospective analysis was conducted on two patients who had undergone STN-DBS treatment at another hospital for Parkinson’s disease （PD） but showed poor therapeutic response. After evaluation at the Central Hospital affiliated with Shandong First Medical University confirmed that efficacy could not be restored through parameter optimization or medication adjustment， both patients underwent a procedure to retain their original STN-DBS system and implant bilateral GPi-DBS systems. Following the deactivation of the STN-DBS， surgical outcomes were assessed by comparing preoperative and postoperative Unified Parkinson's Disease Rating Scale Part Ⅲ（UPDRS-Ⅲ） scores under conditions of active GPi-DBS， as well as during "on" and "off" medication periods. Results Both patients successfully retained their original STN-DBS systems and underwent uneventful implantation of bilateral GPi-DBS systems， without complications such as bleeding or infection. Six months postoperatively， Patient 1 showed a UPDRS-Ⅲ improvement rate of 61.21% during the "on" medication phase and 68.92% during the "off" medication phase with GPi-DBS activated. Patient 2 demonstrated an improvement rate of 55.81% during the "on" medication phase and 59.34% during the "off" medication phase under GPi-DBS activation. Both patients exhibited significant improvements in dyskinesia， speech， and balance. Conclusion Retaining the original STN system with simultaneous bilateral GPi-DBS reimplantation may be a safe and effective rescue treatment strategy for PD patients who experience a decline in efficacy or severe complications following STN-DBS surgery that cannot be improved by optimizing medication or programming parameters.

Rigidity is a core motor symptom of Parkinson disease（PD），characterized by uniformly increased resistance during passive muscle stretching. It can be classified into two types：lead-pipe rigidity and cogwheel rigidity. This review systematically summarizes the pathophysiological mechanisms underlying rigidity in PD，including enhanced long-latency stretch reflexes， the combined effects of shortening reaction and stretch-induced inhibition，functional abnormalities in brainstem and cortico-basal ganglia-cerebellar circuit， and alterations in muscle biomechanical properties.This review also summarizes recent advances in objective assessment methods such as electromyography，ultrasound elastography， servo motors， and inertial sensors.Studies indicate that rigidity in PD results from the interaction between abnormal neural regulation and changes in muscle biomechanical properties，with assessment methods evolving from subjective clinical scoring toward multimodal objective quantification.A deeper understanding of the mechanisms and assessment methods of rigidity is crucial for the diagnosis and treatment of PD.

The pathological mechanism of neurogenic orthostatic hypotension （nOH） in Parkinson disease （PD） is shifting from peripheral sympathetic denervation to central network dysfunction. This article explores the core role of locus coeruleus （LC） degeneration and abnormalities in the central autonomic network （CAN） and the somato-cognitive action network （SCAN） in the pathogenesis of nOH. A current research challenge lies in determining whether network hyperconnectivity is physiological compensation or a pathological marker， with a lack of longitudinal multimodal imaging data. Based on the novel understanding of CAN/SCAN impairment， the treatment of PD with nOH is transitioning towards precise neuromodulation paradigms， including SCAN-targeted cortical stimulation， epidural spinal cord stimulation， and closed-loop neuromodulation， which provides new perspectives for individualized management in clinical practice.