Apoptosis after traumatic brain injury has been shown to be a major factor influencing prognosis and outcome. Endoplasmic reticulum stress may be involved in mitochondrial mediated neuronal apoptosis. Therefore, endop...Apoptosis after traumatic brain injury has been shown to be a major factor influencing prognosis and outcome. Endoplasmic reticulum stress may be involved in mitochondrial mediated neuronal apoptosis. Therefore, endoplasmic reticulum stress has become an important mechanism of secondary injury after traumatic brain injury. In this study, a rat model of traumatic brain injury was established by lateral fluid percussion injury. Fluorescence assays were used to measure reactive oxygen species content in the cerebral cortex. Western blot assays were used to determine expression of endoplasmic reticulum stress-related proteins. Hematoxylin-eosin staining was used to detect pathological changes in the cerebral cortex. Transmission electron microscopy was used to measure ultrastructural changes in the endoplasmic reticulum and mitochondria. Our results showed activation of the endoplasmic reticulum stress-related unfolded protein response. Meanwhile, both the endoplasmic reticulum stress response and mitochondrial apoptotic pathway were activated at different stages post-traumatic brain injury. Furthermore, pretreatment with the endoplasmic reticulum stress inhibitor, salubrinal（1 mg/kg）, by intraperitoneal injection 30 minutes before injury significantly inhibited the endoplasmic reticulum stress response and reduced apoptosis. Moreover, salubrinal promoted recovery of mitochondrial function and inhibited activation of the mitochondrial apoptotic pathway post-traumatic brain injury. These results suggest that endoplasmic reticulum stress might be a key factor for secondary brain injury post-traumatic brain injury.展开更多
Polydatin is thought to protect mitochondria in different cell types in various diseases.Mitochondrial dysfunction is a major contributing factor in secondary brain injury resulting from traumatic brain injury.To inve...Polydatin is thought to protect mitochondria in different cell types in various diseases.Mitochondrial dysfunction is a major contributing factor in secondary brain injury resulting from traumatic brain injury.To investigate the protective effect of polydatin after traumatic brain injury,a rat brain injury model of lateral fluid percussion was established to mimic traumatic brain injury insults.Rat models were intraperitoneally injected with polydatin(30 mg/kg)or the SIRT1 activator SRT1720(20 mg/kg,as a positive control to polydatin).At 6 hours post-traumatic brain injury insults,western blot assay was used to detect the expression of SIRT1,endoplasmic reticulum stress related proteins and p38 phosphorylation in cerebral cortex on the injured side.Flow cytometry was used to analyze neuronal mitochondrial superoxide,mitochondrial membrane potential and mitochondrial permeability transition pore opened.Ultrastructural damage in neuronal mitochondria was measured by transmission electron microscopy.Our results showed that after treatment with polydatin,release of reactive oxygen species in neuronal mitochondria was markedly reduced;swelling of mitochondria was alleviated;mitochondrial membrane potential was maintained;mitochondrial permeability transition pore opened.Also endoplasmic reticulum stress related proteins were inhibited,including the activation of p-PERK,spliced XBP-1 and cleaved ATF6.SIRT1 expression and activity were increased;p38 phosphorylation and cleaved caspase-9/3 activation were inhibited.Neurological scores of treated rats were increased and the mortality was reduced compared with the rats only subjected to traumatic brain injury.These results indicated that polydatin protectrd rats from the consequences of traumatic brain injury and exerted a protective effect on neuronal mitochondria.The mechanisms may be linked to increased SIRT1 expression and activity,which inhibits the p38 phosphorylation-mediated mitochondrial apoptotic pathway.This study was approved by the Animal Care and Use Committee of the Southern Medical University,China(approval number:L2016113)on January 1,2016.展开更多
BACKGROUND Hypertrophic neuropathy of the cauda equina(HNCE)is a rare disease,especially in children.It can be caused by different etiological agents such as inflammation,tumor or hereditary factors.Currently,there is...BACKGROUND Hypertrophic neuropathy of the cauda equina(HNCE)is a rare disease,especially in children.It can be caused by different etiological agents such as inflammation,tumor or hereditary factors.Currently,there is no uniform standard for clinical treatment of HNCE.Furthermore,it is unclear whether spinal canal decompression is beneficial for patients with HNCE.CASE SUMMARY We report the case of a 13-year-old boy with enlargement of the cauda equina.The onset of the disease began at the age of 6 years and was initially marked by radiating pain in the buttocks and thighs after leaning over and weakness in the lower limbs when climbing a ladder.The child did not receive any medical treatment.As the disease slowly progressed,the child needed the help of others to walk,and he had a trendelenburg gait.He underwent spinal canal decompression and a nerve biopsy during his hospital stay.A diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy was made based on electrophysiological findings and pathological examination results.Immunoglobulin or hormone therapy was recommended during hospitalization,but his mother refused.After discharge,the boy’s mother helped him carry out postoperative rehabilitation training at home.His lower-limb muscle strength gradually increased,and he could stand upright and take steps.Six mo after surgery,the child was readmitted and began immunoglobulin therapy.Long-term oral steroid treatment was initiated after discharge.The movement and sensation of the lower limbs were further improved,and the boy could walk normally 1 year after surgery.CONCLUSION Spinal canal decompression can improve the clinical symptoms of HNCE caused by inflammation,even in children.When combined with specific etiological interventions,spinal cord decompression can lead to optimal outcomes.展开更多
Dear Editor,Electrophysiological studies have found that the entorhinal cortex(EC)contains grid cells that fire at the vertices of equilateral triangles tiling the entire environment[1-3].Theoretical models[4]and empi...Dear Editor,Electrophysiological studies have found that the entorhinal cortex(EC)contains grid cells that fire at the vertices of equilateral triangles tiling the entire environment[1-3].Theoretical models[4]and empirical studies[5]suggest that they are a key neural substrate for spatial navigation.In humans,grid cells can be indirectly measured by gridlike representations(GLRs)at the level of fMRI BOLD responses[6]and local field potentials[7].展开更多
Salivary proteins serve multifaceted roles in maintaining oral health and hold significant potential for diagnosing and monitoring diseases due to the non-invasive nature of saliva sampling.However,the clinical utilit...Salivary proteins serve multifaceted roles in maintaining oral health and hold significant potential for diagnosing and monitoring diseases due to the non-invasive nature of saliva sampling.However,the clinical utility of current saliva biomarker studies is limited by the lack of reference intervals(RIs)to correctly interpret the testing result.Here,we developed a rapid and robust saliva proteome profiling workflow,obtaining coverage of>1,200 proteins from a 50-μL unstimulated salivary flow with 30 min gradients.With the workflow,we investigated protein variation in a cohort of 1,743 healthy individuals.The significant differences in non-linear saliva proteomes among age groups resulted in the establishment of age-related RIs covering 1,123 salivary protein variations.We then utilized a cohort of 30 epilepsy patients as a case study to illustrate the practical application of RIs in identifying disease-enriched outlier proteins,elucidating their cellular origins,determining disease diagnosis,and visualizing outlier proteins in each epilepsy patient.Our study showed the classification model based on the RI achieved PR-AUC of 0.815(95%CI:0.813–0.826).Additionally,we validated these results in an independent test set.Furthermore,the epilepsy cohort could be further stratified into 2 major subtypes,with one subtype characterized by disrupted metabolic proteins and containing mostly Focal Cortical Dysplasia(FCD)type III epilepsy patients.Overall,our study provided a proof-of-principle workflow for the use of salivary proteome for health monitoring,epilepsy diagnosis and subtyping.展开更多
Importance:Perampanel(PER)is used less extensively in children than in adults.Currently,there is a lack of data from PER clinical studies with large sample sizes in Chinese children and adolescents with epilepsy,espec...Importance:Perampanel(PER)is used less extensively in children than in adults.Currently,there is a lack of data from PER clinical studies with large sample sizes in Chinese children and adolescents with epilepsy,especially those with refractory epilepsy.Objective:To evaluate the effectiveness,retention,and safety of PER in the treatment of children and adolescents with epilepsy in China.Methods:This was a multicenter,prospective,observational study.Children and adolescents with epilepsy who received PER as adjunctive therapy were included.The primary effectiveness endpoint was the proportion of patients achieving a≥50%reduction in seizure frequency after 6 months of treatment compared to baseline.The secondary effectiveness endpoints included retention and seizure-free rates.The safety outcome was the incidence of treatment-emergent adverse events(TEAEs).Results:A total of 240 patients with epilepsy were enrolled in the study.Prior to initiating PER treatment,approximately 87.9%of them took two or more antiseizure medications.After a 6-month treatment regimen with PER,70.4%of the patients experienced a reduced seizure frequency of at least 50%,and 22.1%achieved complete seizure freedom.The retention rate was 90.2%.TEAEs were reported by 89 patients,leading to the discontinuation of PER in seven cases.No severe TEAEs were observed in this study.Interpretation:Under routine clinical conditions,PER demonstrated good effectiveness and retention in Chinese children with epilepsy,particularly in those with refractory epilepsy.展开更多
Background： Epilepsy is a chronic disorder characterized by recurrent seizures and has significant psychological and social consequence for everyday living. Epilepsy affects various aspects of ones＇ social life. The...Background： Epilepsy is a chronic disorder characterized by recurrent seizures and has significant psychological and social consequence for everyday living. Epilepsy affects various aspects of ones＇ social life. The present study aimed to investigate the influence of marital status on the quality of life of adult Chinese patients with epilepsy. Methods： This study surveyed 805 Chinese adults who have been clinically diagnosed with epilepsy for longer than 1 year in 11 hospitals in Beijing. In this survey, 532 （66.1%） participants were married. All of them completed the case report form with enquiries on demographic data, social factors, and illness. The marriage status of adult epileptic quality of life was the dependent variable, and demographic data and clinical data were independent variables, analyzed through the multiple linear regression analysis methods. The patients＇ quality of life was assessed using the Quality of Life in patients with Epilepsy-31 items （QOLIE-31） questionnaire, the Patient Health Questionnaire-9 items （PHQ-9）, and the Generalized Anxiety Disorder-7 items （GAD-7）. Results： The PHQ-9 and GAD-7 scores in the unmarried group （PHQ-9 = 6.0 and GAD-7 = 5.0） were significantly higher than that of the married group （PHQ-9 = 4.0 and GAD-7 =3.0）. The scores of married adult patients with epilepsy on QOLIE （61.8 ±15.3） and social function （70.9 ± 22.7） were higher than the scores of the unmarried patients aged between 20 and 44 years. The scores of married adult epileptics on the QOLIE （58,4 ± 14.6） and the energy/fatigue （62.1 ± 20.4） were higher than the scores of the unmarried patients （QOLIE = 58.4 ± 14.6 and the energy/fatigue = 62.1 ±20.4） aged between 45 and 59 years. For the adult epilepsy patients, depression, anxiety, seizures within the last year, disease course, medical expense category, and marriage＊ age are negatively correlated with the quality of life. Occupation, educational level, and average monthly income are closely related to the quality of life. Conclusions： Married adult epileptic patients have better quality of life than that of unmarried adult patients in young and middle-aged age groups. Unmarried adult patients with epilepsy are more anxious and depressed than married adult patients.展开更多
Background： Epilepsy is one of the most common serious neurological disorders. The present study aimed to investigate the influence of occupational status on the quality of life of Chinese adult patients with epileps...Background： Epilepsy is one of the most common serious neurological disorders. The present study aimed to investigate the influence of occupational status on the quality of life of Chinese adult patients with epilepsy. Methods： This study surveyed 819 subjects clinically diagnosed with epilepsy for more than 1 year in 11 hospitals in Beijing; 586 were employed （71.55%）. All subjects completed the case report form with inquiries on demographic data, social factors, and illness. The patients＇ quality of life was assessed using the quality of life in patients with epilepsy-31 items （QOLIE-31） questionnaire. Results： The QOLIE-31 score in the employed group was significantly higher than that in the unemployed group. Furthermore, the scores in all the sections （overall quality of life, energy/fatigue, emotional well-being, seizure worry, cognition, social function, and medication effects） of the employed group were higher than those of the unemployed group. Both the employed and unemployed groups achieved the highest difference in social function. The QOLIE-31 score of students was higher than those of farmers and workers. Both the students and workers scored higher in the quality of life compared with the adult peasants living with epilepsy. The students and farmers showed significant differences in QOL1E-31 score, cognition, emotional well-being, overall quality of life, energy/fatigue, and social function. In contrast, no significant difference was noted in seizure worry and medication effects across the three different kinds of occupation. Conclusion： Occupational status might affect the quality of life of Chinese adult patients with epilepsy, and social function is the most important contributing factor.展开更多
Background:Vagus nerve stimulation(VNS)is an effective treatment for patients with refractory epilepsy,yet with varied predictive factors and heterogeneous long-term outcomes.Adjustment of VNS parameters is critical f...Background:Vagus nerve stimulation(VNS)is an effective treatment for patients with refractory epilepsy,yet with varied predictive factors and heterogeneous long-term outcomes.Adjustment of VNS parameters is critical for obtaining favorable efficacy.In this study,we aimed to investigate the long-term outcomes and the possible predictive factors of VNS in patients with refractory epilepsy.Methods:Eighty-six patients(59 males and 27 females)who underwent VNS implantation for treatment of refractory epilepsy between May 2016 and May 2017 at five Epilepsy Centers were enrolled.The clinical data,including sex,age at epilepsy onset,VNS implantation,epilepsy duration,seizure type,MRI findings,history of neurosurgical operations,and responder rate(responders were those with≥50%seizure reduction),were analyzed.Results:Four-year follow-up data were available for 76 patients(53 males and 23 females).The mean current intensity at the last follow-up was 1.8±0.3 mA(range:0.75–2.5 mA).The mean seizure reduction was 36.2%at 6 months,38.5%at 1 year,69.4%at 3 years,and 56.7%at 4 years.A favorable outcome of≥50%reduction in seizure frequency occurred in 40.0%of the patients at 6 months,55.9%at 1 year with 4 patients being seizure-free,63.2%at 3 years with 5 patients being seizure-free,and 68.4%at 4 years with 5 patients being seizure-free.Earlier onset age(P<0.001)and shorter duration(P=0.042)were associated with favorable prognosis.Compared with generalized tonicclonic seizures,tonic seizures had a favorable outcome(P=0.026).Twenty-three patients underwent neurosurgical operations before VNS implantation,and the responder rate was 60.9%at the last follow-up.Conclusions:VNS is an adjunctive and effective treatment for patients with refractory epilepsy who are not good candidates for surgical resection or have failed to respond to surgical treatment.The stimulation efficacy increases over time after implantation,and earlier exposure to VNS improves the prognosis.展开更多
Encephalitis is an acute inflammatory process of the brain parenchyma,which is often caused by viral infection.It is an vital cause of acute symptomatic seizures and subsequent epilepsy.The incidence of unprovoked and...Encephalitis is an acute inflammatory process of the brain parenchyma,which is often caused by viral infection.It is an vital cause of acute symptomatic seizures and subsequent epilepsy.The incidence of unprovoked and recurrent seizures after previous infections of the central nervous system is high and accounts for1%~5%of the cases of epilepsy.Viral encephalitis(VE)is directly caused by viral infection.The occurrence of seizures after VE is associated with poor prognosis.In survivors of VE,among other neurological sequelae,the risk of developing epilepsy is increased10-fold.The risk of severe neurological sequelae after VE is particularly high in very young children.Studies on seizure occurrence,possible underlying mechanisms,clinical characteristics,and clinical treatment(especially surgical treatment)of VE have yielded only limited detailed data.We reviewed the most recent literature on the clinical features and surgical treatment of post-VE epilepsy.展开更多
Background Temporal lobe epilepsy is the most common type of focal epilepsy,but hereditary factors are usually overlooked.Reelin(RELN)is considered to be the second most common pathogenic gene implicated in autosomal ...Background Temporal lobe epilepsy is the most common type of focal epilepsy,but hereditary factors are usually overlooked.Reelin(RELN)is considered to be the second most common pathogenic gene implicated in autosomal dominant lateral temporal epilepsy(ADLTE).However,this mutation is not frequently discovered in the Chinese population.Additionally,there are few clinical studies regarding the connection between RELN and glioma.Case presentation The healthcare records of an 8-year-old child who experienced generalized tonic-clonic seizures(GTCS)during sleep for 7 years were retrospectively analyzed.In addition to experiencing his first seizure at the age of one,his mother also suffered from GTCS during her pregnancy,and a glioma was discovered.An investigation involving gene sequencing was conducted on the proband and his parents.He was diagnosed with ADLTE once a missense mutation in RELN(c.1799 C>T)was identified as the causal factor.The mutation was inherited from his mother.He was taking levetiracetam(500 mg twice a day)to avoid seizures,but his mother died of status epilepticus caused by glioma recurrence two years earlier.Conclusions Genetic issues should be given more consideration in cases of temporal lobe epilepsy.If the source of the seizures is determined to be inherited,anti-seizure medications should be used for prolonged periods.Furthermore,more research is required to determine whether mutations in RELN are related to the occurrence and progression of gliomas.展开更多
Background The KCNT1 gene encodes a Na+-activated K+channel.Gain-of-function mutations of KCNT1 lead to autosomal dominant sleep-related hypermotor epilepsy,early-onset epileptic encephalopathy,focal epilepsy and othe...Background The KCNT1 gene encodes a Na+-activated K+channel.Gain-of-function mutations of KCNT1 lead to autosomal dominant sleep-related hypermotor epilepsy,early-onset epileptic encephalopathy,focal epilepsy and other epileptic encephalopathies.In this paper,we report a boy carrying a KCNT1 gene mutation,who presented with drug-resistant focal-onset seizures.He had decreased seizure frequency and improvement of background changes in electroencephalography(EEG)after vagus nerve stimulation(VNS).Case presentation The case was a nonverbal 9-year-old male who presented with drug-resistant focal-onset seizures since age 3 and had underwent VNS therapy for 2 years.He had hypermotor symptoms,automatism and bilateral asymmetric tonic seizures with cognitive decline and aphasis from age 3.The patient had a variety of seizure types that only occurred at night.The most common seizure type was automatisms,and ictal video EEG showed high-amplitude delta waves,followed by a fast rhythmic sharp activity in the mesial frontal and bitemporal regions.The patient was diagnosed with KCNT1-related epilepsy,epileptic encephalopathy and cognitive disorder.He was refractory to multiple anti-seizure medicines(ASM)and ketogenic diet.After VNS treatment at age 7,the frequency of seizures was reduced significantly and EEG was improved in background slowing.Conclusions Children with KCNT1-related epilepsy usually have early onset of disease,are nonverbal,and are refractory to ASM.This boy with drug-resistant KCNT1-related epilepsy showed significantly reduced seizure frequency after VNS.This report may provide reference for management of cases of KCNT1-related epilepsy.展开更多
Disorders of consciousness (DOC) are neuropsychiatric disorders with causes that include traumatic brain injury, hypoxia, and stroke. The possibility of spontaneous recovery is low, and treatment remains a difficult p...Disorders of consciousness (DOC) are neuropsychiatric disorders with causes that include traumatic brain injury, hypoxia, and stroke. The possibility of spontaneous recovery is low, and treatment remains a difficult problem in the frontier challenge of neuroscience and medicine. With progress in neurocritical care, the number of patients with DOC is growing. Spinal cord stimulation (SCS) can improve the level of consciousness in patients with DOC. The present article reviews the current research status and development trends of SCS in promoting consciousness recovery in patients with DOC. It also seeks to identify the frontier problems and challenges associated with this neuroregulatory technology. Through a systematic review of the relevant literature, criteria for inclusion and exclusion in SCS therapy were established, suitable patients with DOC were identified, and the effects of different stimulation frequencies on consciousness and motor function were examined. Additionally, the optimal SCS mode was investigated, and evaluation criteria, treatment mechanisms, and factors influencing effectiveness were summarized. The present review aims to guide the clinical application and research development of SCS. Although SCS has demonstrated efficacy in the treatment of DOC, responses to SCS exhibit significant individual variation. Consequently, further studies are necessary to expand the sample size for continued exploration and enhancement.展开更多
Researchers have widely acknowledged the therapeutic value of epilepsy surgery for drug-resistant epilepsy.None-theless,there is a substantial gap in the surgical treatment for appropriate candidates owing to several ...Researchers have widely acknowledged the therapeutic value of epilepsy surgery for drug-resistant epilepsy.None-theless,there is a substantial gap in the surgical treatment for appropriate candidates owing to several factors,particularly in the population of young children.To standardize the protocols of preoperative evaluation and sur-gery of young children for epilepsy surgery,the China Association Against Epilepsy has appointed an expert task force to standardize the protocols of preoperative evaluation and surgery in pediatric epilepsy patients.It adopted the modifed Delphi method and performed two rounds of surveys through an anonymous inquiry among 75 experts from four subgroups including pediatric neurologists,epileptologists,pediatric epilepsy surgeons,and functional neurosurgeons.The survey contents contained:(1)the participants,comprising children aged≤6 years;(2)adopted DRE definition proposed by the International League Against Epilepsy in 2010;and(3)investigated epilepsy surgery,principally referring to curative epilepsy surgeries.The neuromodulation therapies were excluded because of the differences in treatment mechanisms from the above-mentioned surgeries.According to the Delphi process,a con-sensus was achieved for most aspects by incorporating two rounds of surveys including preoperative assessment,sur-gical strategies and techniques,and perioperative and long-term postoperative management,despite controversial opinions on certain items.We hope the results of this consensus will improve the level of surgical treatment and man-agement of intractable epilepsy in young children.展开更多
Background Temporal lobe epilepsy is one of the most common types of partial epilepsy.Although surgical treatment has led to signifcant improvements in seizure-free rates,nearly one-third of patients still have poor s...Background Temporal lobe epilepsy is one of the most common types of partial epilepsy.Although surgical treatment has led to signifcant improvements in seizure-free rates,nearly one-third of patients still have poor seizure control after surgery.Moreover,the long-term outcome is less favorable compared to short-term outcome,with 48-58%of patients experiencing seizures fve years after surgery.The aim of this study was to investigate the surgical outcomes and the predictive value of prognostic factors associated with poor surgical outcomes in temporal lobe epilepsy patients receiving surgery.Methods We retrospectively reviewed 94 patients undergoing temporal resective surgery in the Epilepsy Center of Guangdong Provincial Hospital of Traditional Chinese Medicine between July 2016 and July 2020.Patient information including age,gender,personal and family history,as well as preoperative and postoperative clinical data(clinical type and duration of disease)was collected.Results The diferences of postoperative clinical efcacy in both seizure free group and non-seizure free group patients were observed.A log-rank test was used for univariate analysis,and a Cox proportional hazard model was used for multivariate analysis.Ninety-four patients were followed up for at least 1 years.At 12 months of followup,71(75.5%)patients achieved Engel class I,5(5.3%)patients were classifed as Engel class II,5(5.3%)patients were classifed as Engel class Ⅲ,and 13(13.8%)patients were classifed as Engel class IV.Univariate analysis and multivariate Cox regression analysis indicated that the postoperative EEG abnormalities were signifcantly correlated with seizure recurrence and were signifcant independent predictive factors,with a hazard ratio of 12.940.Conclusions The relapse rate in our study was similar to commonly reported overall rates in temporal lobe epilepsy patients receiving surgery.Anterior temporal lobectomy is a reliable treatment option for temporal lobe epilepsy patients.Postoperative electroencephalograph abnormalities are independent risk factors for poor surgical prognosis.展开更多
The multiple PDZ domain crumbs cell polarity complex component gene(MPDZ;MIM:603785),is highly expressed in the brain across the whole lifespan.It encodes the multiple PDZ domain protein,which is a member of the NMDAR...The multiple PDZ domain crumbs cell polarity complex component gene(MPDZ;MIM:603785),is highly expressed in the brain across the whole lifespan.It encodes the multiple PDZ domain protein,which is a member of the NMDAR signaling complex that may play a role in the control of AMPAR potentiation and synaptic plasticity in excitatory synapses."Previously,MPDZ variants have been demonstrated to be associated with autosomal recessive congenital hydrocephalus-2(HYC2;MIM:615219)which is commonly complicated by brain abnormalities and developmental delay.Seizures were reported in only one case.The association between MPDz and epilepsy requires clarification.展开更多
Epileptic spasm(ES)is one of the most common types of seizures in children.It is primarily characterized by brief axial contractions lasting less than 2 s and recurring in short clusters.It usually occurs in children ...Epileptic spasm(ES)is one of the most common types of seizures in children.It is primarily characterized by brief axial contractions lasting less than 2 s and recurring in short clusters.It usually occurs in children of 3 to 12 months of age,although it can also occur after the age of 1 year.In general,children with ES develop other symptoms of epilepsy,such as tonic,tonic-clonic,or focal seizures,after 3 to 5 years of age.ES in children is often damaging and usually results in developmental regression.First-line treatments for spasm seizures include adrenocorticotropic hormone(ACTH)and vigabatrin.However,many patients fail to respond to these medications,and continued to have spasms associated with progressive neurodevelopmental degeneration.Therefore,it is important to consider whether children with drug resistance meet surgical indications to consider surgical treatment in such conditions.In this study,we reviewed and summarized the importance of preoperative evaluation in order to provide surgical options for treatment of children with ES.展开更多
文摘Apoptosis after traumatic brain injury has been shown to be a major factor influencing prognosis and outcome. Endoplasmic reticulum stress may be involved in mitochondrial mediated neuronal apoptosis. Therefore, endoplasmic reticulum stress has become an important mechanism of secondary injury after traumatic brain injury. In this study, a rat model of traumatic brain injury was established by lateral fluid percussion injury. Fluorescence assays were used to measure reactive oxygen species content in the cerebral cortex. Western blot assays were used to determine expression of endoplasmic reticulum stress-related proteins. Hematoxylin-eosin staining was used to detect pathological changes in the cerebral cortex. Transmission electron microscopy was used to measure ultrastructural changes in the endoplasmic reticulum and mitochondria. Our results showed activation of the endoplasmic reticulum stress-related unfolded protein response. Meanwhile, both the endoplasmic reticulum stress response and mitochondrial apoptotic pathway were activated at different stages post-traumatic brain injury. Furthermore, pretreatment with the endoplasmic reticulum stress inhibitor, salubrinal（1 mg/kg）, by intraperitoneal injection 30 minutes before injury significantly inhibited the endoplasmic reticulum stress response and reduced apoptosis. Moreover, salubrinal promoted recovery of mitochondrial function and inhibited activation of the mitochondrial apoptotic pathway post-traumatic brain injury. These results suggest that endoplasmic reticulum stress might be a key factor for secondary brain injury post-traumatic brain injury.
基金supported by the National Natural Science Foundation of China,No.81501690(to ZTG)the Scientific Research Staring Foundation for Talent Introduction for Southern Medical University(to MM)
文摘Polydatin is thought to protect mitochondria in different cell types in various diseases.Mitochondrial dysfunction is a major contributing factor in secondary brain injury resulting from traumatic brain injury.To investigate the protective effect of polydatin after traumatic brain injury,a rat brain injury model of lateral fluid percussion was established to mimic traumatic brain injury insults.Rat models were intraperitoneally injected with polydatin(30 mg/kg)or the SIRT1 activator SRT1720(20 mg/kg,as a positive control to polydatin).At 6 hours post-traumatic brain injury insults,western blot assay was used to detect the expression of SIRT1,endoplasmic reticulum stress related proteins and p38 phosphorylation in cerebral cortex on the injured side.Flow cytometry was used to analyze neuronal mitochondrial superoxide,mitochondrial membrane potential and mitochondrial permeability transition pore opened.Ultrastructural damage in neuronal mitochondria was measured by transmission electron microscopy.Our results showed that after treatment with polydatin,release of reactive oxygen species in neuronal mitochondria was markedly reduced;swelling of mitochondria was alleviated;mitochondrial membrane potential was maintained;mitochondrial permeability transition pore opened.Also endoplasmic reticulum stress related proteins were inhibited,including the activation of p-PERK,spliced XBP-1 and cleaved ATF6.SIRT1 expression and activity were increased;p38 phosphorylation and cleaved caspase-9/3 activation were inhibited.Neurological scores of treated rats were increased and the mortality was reduced compared with the rats only subjected to traumatic brain injury.These results indicated that polydatin protectrd rats from the consequences of traumatic brain injury and exerted a protective effect on neuronal mitochondria.The mechanisms may be linked to increased SIRT1 expression and activity,which inhibits the p38 phosphorylation-mediated mitochondrial apoptotic pathway.This study was approved by the Animal Care and Use Committee of the Southern Medical University,China(approval number:L2016113)on January 1,2016.
基金Supported by the Yunnan Provincial Department of Science and Technology Kunming Medical University Application Foundation Research Joint Fund Project,No.202001AY070001-273the Epilepsy Research Fund of China Anti-Epilepsy Association,No.CQ-B-2021-04the Kunming Health Science and Technology Talent Training Project and“100 thousand”Project Training Plan,No.2021-SW(province)-23.
文摘BACKGROUND Hypertrophic neuropathy of the cauda equina(HNCE)is a rare disease,especially in children.It can be caused by different etiological agents such as inflammation,tumor or hereditary factors.Currently,there is no uniform standard for clinical treatment of HNCE.Furthermore,it is unclear whether spinal canal decompression is beneficial for patients with HNCE.CASE SUMMARY We report the case of a 13-year-old boy with enlargement of the cauda equina.The onset of the disease began at the age of 6 years and was initially marked by radiating pain in the buttocks and thighs after leaning over and weakness in the lower limbs when climbing a ladder.The child did not receive any medical treatment.As the disease slowly progressed,the child needed the help of others to walk,and he had a trendelenburg gait.He underwent spinal canal decompression and a nerve biopsy during his hospital stay.A diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy was made based on electrophysiological findings and pathological examination results.Immunoglobulin or hormone therapy was recommended during hospitalization,but his mother refused.After discharge,the boy’s mother helped him carry out postoperative rehabilitation training at home.His lower-limb muscle strength gradually increased,and he could stand upright and take steps.Six mo after surgery,the child was readmitted and began immunoglobulin therapy.Long-term oral steroid treatment was initiated after discharge.The movement and sensation of the lower limbs were further improved,and the boy could walk normally 1 year after surgery.CONCLUSION Spinal canal decompression can improve the clinical symptoms of HNCE caused by inflammation,even in children.When combined with specific etiological interventions,spinal cord decompression can lead to optimal outcomes.
基金supported by STI2030-Major Projects(2022ZD0205000)the National Natural Science Foundation of China(32020103009 and 32200861)+1 种基金a Ministry Key Project(GW0890006)NA acknowledges funding via DFG grant Project number 429281110.
文摘Dear Editor,Electrophysiological studies have found that the entorhinal cortex(EC)contains grid cells that fire at the vertices of equilateral triangles tiling the entire environment[1-3].Theoretical models[4]and empirical studies[5]suggest that they are a key neural substrate for spatial navigation.In humans,grid cells can be indirectly measured by gridlike representations(GLRs)at the level of fMRI BOLD responses[6]and local field potentials[7].
基金supported by the National Natural Science Foundation of China(32088101,32271498)the National Key Research and Development Program of China(2022YFA1303200)+3 种基金State Key Laboratory of Proteomics(SKLP-K202002)State Key Laboratory of Dampness Syndrome of Chinese Medicine,The Second Affiliated Hospital of Guangzhou University of Chinese Medicine(SZ2021ZZ06,SZ2021ZZ3205)Key-Area Research and Development Program of Guangdong Province(2020B1111100009)Guangzhou Science and Technology Plan Project(202102010275,202201020499).
文摘Salivary proteins serve multifaceted roles in maintaining oral health and hold significant potential for diagnosing and monitoring diseases due to the non-invasive nature of saliva sampling.However,the clinical utility of current saliva biomarker studies is limited by the lack of reference intervals(RIs)to correctly interpret the testing result.Here,we developed a rapid and robust saliva proteome profiling workflow,obtaining coverage of>1,200 proteins from a 50-μL unstimulated salivary flow with 30 min gradients.With the workflow,we investigated protein variation in a cohort of 1,743 healthy individuals.The significant differences in non-linear saliva proteomes among age groups resulted in the establishment of age-related RIs covering 1,123 salivary protein variations.We then utilized a cohort of 30 epilepsy patients as a case study to illustrate the practical application of RIs in identifying disease-enriched outlier proteins,elucidating their cellular origins,determining disease diagnosis,and visualizing outlier proteins in each epilepsy patient.Our study showed the classification model based on the RI achieved PR-AUC of 0.815(95%CI:0.813–0.826).Additionally,we validated these results in an independent test set.Furthermore,the epilepsy cohort could be further stratified into 2 major subtypes,with one subtype characterized by disrupted metabolic proteins and containing mostly Focal Cortical Dysplasia(FCD)type III epilepsy patients.Overall,our study provided a proof-of-principle workflow for the use of salivary proteome for health monitoring,epilepsy diagnosis and subtyping.
文摘Importance:Perampanel(PER)is used less extensively in children than in adults.Currently,there is a lack of data from PER clinical studies with large sample sizes in Chinese children and adolescents with epilepsy,especially those with refractory epilepsy.Objective:To evaluate the effectiveness,retention,and safety of PER in the treatment of children and adolescents with epilepsy in China.Methods:This was a multicenter,prospective,observational study.Children and adolescents with epilepsy who received PER as adjunctive therapy were included.The primary effectiveness endpoint was the proportion of patients achieving a≥50%reduction in seizure frequency after 6 months of treatment compared to baseline.The secondary effectiveness endpoints included retention and seizure-free rates.The safety outcome was the incidence of treatment-emergent adverse events(TEAEs).Results:A total of 240 patients with epilepsy were enrolled in the study.Prior to initiating PER treatment,approximately 87.9%of them took two or more antiseizure medications.After a 6-month treatment regimen with PER,70.4%of the patients experienced a reduced seizure frequency of at least 50%,and 22.1%achieved complete seizure freedom.The retention rate was 90.2%.TEAEs were reported by 89 patients,leading to the discontinuation of PER in seven cases.No severe TEAEs were observed in this study.Interpretation:Under routine clinical conditions,PER demonstrated good effectiveness and retention in Chinese children with epilepsy,particularly in those with refractory epilepsy.
文摘Background： Epilepsy is a chronic disorder characterized by recurrent seizures and has significant psychological and social consequence for everyday living. Epilepsy affects various aspects of ones＇ social life. The present study aimed to investigate the influence of marital status on the quality of life of adult Chinese patients with epilepsy. Methods： This study surveyed 805 Chinese adults who have been clinically diagnosed with epilepsy for longer than 1 year in 11 hospitals in Beijing. In this survey, 532 （66.1%） participants were married. All of them completed the case report form with enquiries on demographic data, social factors, and illness. The marriage status of adult epileptic quality of life was the dependent variable, and demographic data and clinical data were independent variables, analyzed through the multiple linear regression analysis methods. The patients＇ quality of life was assessed using the Quality of Life in patients with Epilepsy-31 items （QOLIE-31） questionnaire, the Patient Health Questionnaire-9 items （PHQ-9）, and the Generalized Anxiety Disorder-7 items （GAD-7）. Results： The PHQ-9 and GAD-7 scores in the unmarried group （PHQ-9 = 6.0 and GAD-7 = 5.0） were significantly higher than that of the married group （PHQ-9 = 4.0 and GAD-7 =3.0）. The scores of married adult patients with epilepsy on QOLIE （61.8 ±15.3） and social function （70.9 ± 22.7） were higher than the scores of the unmarried patients aged between 20 and 44 years. The scores of married adult epileptics on the QOLIE （58,4 ± 14.6） and the energy/fatigue （62.1 ± 20.4） were higher than the scores of the unmarried patients （QOLIE = 58.4 ± 14.6 and the energy/fatigue = 62.1 ±20.4） aged between 45 and 59 years. For the adult epilepsy patients, depression, anxiety, seizures within the last year, disease course, medical expense category, and marriage＊ age are negatively correlated with the quality of life. Occupation, educational level, and average monthly income are closely related to the quality of life. Conclusions： Married adult epileptic patients have better quality of life than that of unmarried adult patients in young and middle-aged age groups. Unmarried adult patients with epilepsy are more anxious and depressed than married adult patients.
文摘Background： Epilepsy is one of the most common serious neurological disorders. The present study aimed to investigate the influence of occupational status on the quality of life of Chinese adult patients with epilepsy. Methods： This study surveyed 819 subjects clinically diagnosed with epilepsy for more than 1 year in 11 hospitals in Beijing; 586 were employed （71.55%）. All subjects completed the case report form with inquiries on demographic data, social factors, and illness. The patients＇ quality of life was assessed using the quality of life in patients with epilepsy-31 items （QOLIE-31） questionnaire. Results： The QOLIE-31 score in the employed group was significantly higher than that in the unemployed group. Furthermore, the scores in all the sections （overall quality of life, energy/fatigue, emotional well-being, seizure worry, cognition, social function, and medication effects） of the employed group were higher than those of the unemployed group. Both the employed and unemployed groups achieved the highest difference in social function. The QOLIE-31 score of students was higher than those of farmers and workers. Both the students and workers scored higher in the quality of life compared with the adult peasants living with epilepsy. The students and farmers showed significant differences in QOL1E-31 score, cognition, emotional well-being, overall quality of life, energy/fatigue, and social function. In contrast, no significant difference was noted in seizure worry and medication effects across the three different kinds of occupation. Conclusion： Occupational status might affect the quality of life of Chinese adult patients with epilepsy, and social function is the most important contributing factor.
基金This work was supported by the Rishena Medical Device Co.,Ltd。
文摘Background:Vagus nerve stimulation(VNS)is an effective treatment for patients with refractory epilepsy,yet with varied predictive factors and heterogeneous long-term outcomes.Adjustment of VNS parameters is critical for obtaining favorable efficacy.In this study,we aimed to investigate the long-term outcomes and the possible predictive factors of VNS in patients with refractory epilepsy.Methods:Eighty-six patients(59 males and 27 females)who underwent VNS implantation for treatment of refractory epilepsy between May 2016 and May 2017 at five Epilepsy Centers were enrolled.The clinical data,including sex,age at epilepsy onset,VNS implantation,epilepsy duration,seizure type,MRI findings,history of neurosurgical operations,and responder rate(responders were those with≥50%seizure reduction),were analyzed.Results:Four-year follow-up data were available for 76 patients(53 males and 23 females).The mean current intensity at the last follow-up was 1.8±0.3 mA(range:0.75–2.5 mA).The mean seizure reduction was 36.2%at 6 months,38.5%at 1 year,69.4%at 3 years,and 56.7%at 4 years.A favorable outcome of≥50%reduction in seizure frequency occurred in 40.0%of the patients at 6 months,55.9%at 1 year with 4 patients being seizure-free,63.2%at 3 years with 5 patients being seizure-free,and 68.4%at 4 years with 5 patients being seizure-free.Earlier onset age(P<0.001)and shorter duration(P=0.042)were associated with favorable prognosis.Compared with generalized tonicclonic seizures,tonic seizures had a favorable outcome(P=0.026).Twenty-three patients underwent neurosurgical operations before VNS implantation,and the responder rate was 60.9%at the last follow-up.Conclusions:VNS is an adjunctive and effective treatment for patients with refractory epilepsy who are not good candidates for surgical resection or have failed to respond to surgical treatment.The stimulation efficacy increases over time after implantation,and earlier exposure to VNS improves the prognosis.
文摘Encephalitis is an acute inflammatory process of the brain parenchyma,which is often caused by viral infection.It is an vital cause of acute symptomatic seizures and subsequent epilepsy.The incidence of unprovoked and recurrent seizures after previous infections of the central nervous system is high and accounts for1%~5%of the cases of epilepsy.Viral encephalitis(VE)is directly caused by viral infection.The occurrence of seizures after VE is associated with poor prognosis.In survivors of VE,among other neurological sequelae,the risk of developing epilepsy is increased10-fold.The risk of severe neurological sequelae after VE is particularly high in very young children.Studies on seizure occurrence,possible underlying mechanisms,clinical characteristics,and clinical treatment(especially surgical treatment)of VE have yielded only limited detailed data.We reviewed the most recent literature on the clinical features and surgical treatment of post-VE epilepsy.
文摘Background Temporal lobe epilepsy is the most common type of focal epilepsy,but hereditary factors are usually overlooked.Reelin(RELN)is considered to be the second most common pathogenic gene implicated in autosomal dominant lateral temporal epilepsy(ADLTE).However,this mutation is not frequently discovered in the Chinese population.Additionally,there are few clinical studies regarding the connection between RELN and glioma.Case presentation The healthcare records of an 8-year-old child who experienced generalized tonic-clonic seizures(GTCS)during sleep for 7 years were retrospectively analyzed.In addition to experiencing his first seizure at the age of one,his mother also suffered from GTCS during her pregnancy,and a glioma was discovered.An investigation involving gene sequencing was conducted on the proband and his parents.He was diagnosed with ADLTE once a missense mutation in RELN(c.1799 C>T)was identified as the causal factor.The mutation was inherited from his mother.He was taking levetiracetam(500 mg twice a day)to avoid seizures,but his mother died of status epilepticus caused by glioma recurrence two years earlier.Conclusions Genetic issues should be given more consideration in cases of temporal lobe epilepsy.If the source of the seizures is determined to be inherited,anti-seizure medications should be used for prolonged periods.Furthermore,more research is required to determine whether mutations in RELN are related to the occurrence and progression of gliomas.
文摘Background The KCNT1 gene encodes a Na+-activated K+channel.Gain-of-function mutations of KCNT1 lead to autosomal dominant sleep-related hypermotor epilepsy,early-onset epileptic encephalopathy,focal epilepsy and other epileptic encephalopathies.In this paper,we report a boy carrying a KCNT1 gene mutation,who presented with drug-resistant focal-onset seizures.He had decreased seizure frequency and improvement of background changes in electroencephalography(EEG)after vagus nerve stimulation(VNS).Case presentation The case was a nonverbal 9-year-old male who presented with drug-resistant focal-onset seizures since age 3 and had underwent VNS therapy for 2 years.He had hypermotor symptoms,automatism and bilateral asymmetric tonic seizures with cognitive decline and aphasis from age 3.The patient had a variety of seizure types that only occurred at night.The most common seizure type was automatisms,and ictal video EEG showed high-amplitude delta waves,followed by a fast rhythmic sharp activity in the mesial frontal and bitemporal regions.The patient was diagnosed with KCNT1-related epilepsy,epileptic encephalopathy and cognitive disorder.He was refractory to multiple anti-seizure medicines(ASM)and ketogenic diet.After VNS treatment at age 7,the frequency of seizures was reduced significantly and EEG was improved in background slowing.Conclusions Children with KCNT1-related epilepsy usually have early onset of disease,are nonverbal,and are refractory to ASM.This boy with drug-resistant KCNT1-related epilepsy showed significantly reduced seizure frequency after VNS.This report may provide reference for management of cases of KCNT1-related epilepsy.
基金funded by the 2023 Hebei Provincial Key R&D Program Project“Research and Development of Brain Health Assessment and Auxiliary Intervention Technology and Its Application in Beidaihe Health Care Industry”(No.23377709D).
文摘Disorders of consciousness (DOC) are neuropsychiatric disorders with causes that include traumatic brain injury, hypoxia, and stroke. The possibility of spontaneous recovery is low, and treatment remains a difficult problem in the frontier challenge of neuroscience and medicine. With progress in neurocritical care, the number of patients with DOC is growing. Spinal cord stimulation (SCS) can improve the level of consciousness in patients with DOC. The present article reviews the current research status and development trends of SCS in promoting consciousness recovery in patients with DOC. It also seeks to identify the frontier problems and challenges associated with this neuroregulatory technology. Through a systematic review of the relevant literature, criteria for inclusion and exclusion in SCS therapy were established, suitable patients with DOC were identified, and the effects of different stimulation frequencies on consciousness and motor function were examined. Additionally, the optimal SCS mode was investigated, and evaluation criteria, treatment mechanisms, and factors influencing effectiveness were summarized. The present review aims to guide the clinical application and research development of SCS. Although SCS has demonstrated efficacy in the treatment of DOC, responses to SCS exhibit significant individual variation. Consequently, further studies are necessary to expand the sample size for continued exploration and enhancement.
文摘Researchers have widely acknowledged the therapeutic value of epilepsy surgery for drug-resistant epilepsy.None-theless,there is a substantial gap in the surgical treatment for appropriate candidates owing to several factors,particularly in the population of young children.To standardize the protocols of preoperative evaluation and sur-gery of young children for epilepsy surgery,the China Association Against Epilepsy has appointed an expert task force to standardize the protocols of preoperative evaluation and surgery in pediatric epilepsy patients.It adopted the modifed Delphi method and performed two rounds of surveys through an anonymous inquiry among 75 experts from four subgroups including pediatric neurologists,epileptologists,pediatric epilepsy surgeons,and functional neurosurgeons.The survey contents contained:(1)the participants,comprising children aged≤6 years;(2)adopted DRE definition proposed by the International League Against Epilepsy in 2010;and(3)investigated epilepsy surgery,principally referring to curative epilepsy surgeries.The neuromodulation therapies were excluded because of the differences in treatment mechanisms from the above-mentioned surgeries.According to the Delphi process,a con-sensus was achieved for most aspects by incorporating two rounds of surveys including preoperative assessment,sur-gical strategies and techniques,and perioperative and long-term postoperative management,despite controversial opinions on certain items.We hope the results of this consensus will improve the level of surgical treatment and man-agement of intractable epilepsy in young children.
文摘Background Temporal lobe epilepsy is one of the most common types of partial epilepsy.Although surgical treatment has led to signifcant improvements in seizure-free rates,nearly one-third of patients still have poor seizure control after surgery.Moreover,the long-term outcome is less favorable compared to short-term outcome,with 48-58%of patients experiencing seizures fve years after surgery.The aim of this study was to investigate the surgical outcomes and the predictive value of prognostic factors associated with poor surgical outcomes in temporal lobe epilepsy patients receiving surgery.Methods We retrospectively reviewed 94 patients undergoing temporal resective surgery in the Epilepsy Center of Guangdong Provincial Hospital of Traditional Chinese Medicine between July 2016 and July 2020.Patient information including age,gender,personal and family history,as well as preoperative and postoperative clinical data(clinical type and duration of disease)was collected.Results The diferences of postoperative clinical efcacy in both seizure free group and non-seizure free group patients were observed.A log-rank test was used for univariate analysis,and a Cox proportional hazard model was used for multivariate analysis.Ninety-four patients were followed up for at least 1 years.At 12 months of followup,71(75.5%)patients achieved Engel class I,5(5.3%)patients were classifed as Engel class II,5(5.3%)patients were classifed as Engel class Ⅲ,and 13(13.8%)patients were classifed as Engel class IV.Univariate analysis and multivariate Cox regression analysis indicated that the postoperative EEG abnormalities were signifcantly correlated with seizure recurrence and were signifcant independent predictive factors,with a hazard ratio of 12.940.Conclusions The relapse rate in our study was similar to commonly reported overall rates in temporal lobe epilepsy patients receiving surgery.Anterior temporal lobectomy is a reliable treatment option for temporal lobe epilepsy patients.Postoperative electroencephalograph abnormalities are independent risk factors for poor surgical prognosis.
基金funded by the National Natural Science Foundation of China(No.82201609)Shandong Medical and Health Science and Technology Development Plan(China)(No.202106010271)+2 种基金Scientific Research Project of Hunan Provincial Health Commission(China)(No.D202303077290)Guangdong Basic and Applied Basic Research Foundation(China)(No.2021A1515111064)Science and Technology Project of Guangzhou,Guangdong,China(No.202102021059,202201020106,202235395).
文摘The multiple PDZ domain crumbs cell polarity complex component gene(MPDZ;MIM:603785),is highly expressed in the brain across the whole lifespan.It encodes the multiple PDZ domain protein,which is a member of the NMDAR signaling complex that may play a role in the control of AMPAR potentiation and synaptic plasticity in excitatory synapses."Previously,MPDZ variants have been demonstrated to be associated with autosomal recessive congenital hydrocephalus-2(HYC2;MIM:615219)which is commonly complicated by brain abnormalities and developmental delay.Seizures were reported in only one case.The association between MPDz and epilepsy requires clarification.
文摘Epileptic spasm(ES)is one of the most common types of seizures in children.It is primarily characterized by brief axial contractions lasting less than 2 s and recurring in short clusters.It usually occurs in children of 3 to 12 months of age,although it can also occur after the age of 1 year.In general,children with ES develop other symptoms of epilepsy,such as tonic,tonic-clonic,or focal seizures,after 3 to 5 years of age.ES in children is often damaging and usually results in developmental regression.First-line treatments for spasm seizures include adrenocorticotropic hormone(ACTH)and vigabatrin.However,many patients fail to respond to these medications,and continued to have spasms associated with progressive neurodevelopmental degeneration.Therefore,it is important to consider whether children with drug resistance meet surgical indications to consider surgical treatment in such conditions.In this study,we reviewed and summarized the importance of preoperative evaluation in order to provide surgical options for treatment of children with ES.
