ObjectiveTo observe the dynamic changes of neuroglobin (NGB) expression in hippocampus after status epilepticus(SE) in rats, and to explore the role of NGB in epileptic seizures.Methods40 healthy male Sprague Dawley rats were randomly divided into two group according to random number table method:control group (n=5) and epilepsy model group(n=35).Epilepsy model group according to observation time was divided into:0h, 1h, 3h, 12h, 24h, 10d and 30d.Intraperitoneal injection Lithium-pilocarpine (20 mg/kg~127 mg/kg, Li-PC) to establish the rat model of SE.Observe the behavioral changes in rats with epilepsy.Nissl staining was used to detect the neuronal damage in hippocampus. Streptavidin-biotin-peroxidase complex immunohistochemical method was used to detect the expression level of NGB in hippocampus;ResultsAfter SE, the neurons in hippocampus were severely damaged with the progress of epileptic seizures, the number of surviving neurons in CA1, CA3 regions showed a near linear decline.Among them, the number of surviving neurons in (12h, 24h, 10d, 30d)CA1, (0h, 12h, 24h, 10d, 30d)CA3 and(12h, 24h, 10d, 30d) DG area were significantly lower than that of the control group (P < 0.05).The expression level of NGB in CA1, CA3 and DG region of hippocampus were increased after SE, and both of CA1 and DG were reached peak in 24h after SE, but was still higher than the control group.And the CA3 area showed a continue rising trend.Among them, CA1(24h, 10d, 30d), CA3(24h, 10d, 30d) and DG(12h, 24h, 10d, 30d) were higher than that of control group significantly (P < 0.05).In addition, it was found that there was a positive correlation between the number of surviving neurons in CA3 area and the expression level of NGB (R=0.306, P=0.011).ConclusionUp-regulation of NGB expression in hippocampus after status epilepticus, and was positively correlated with the number of neurons in the CA3 area, suggesting that up regulation of NGB expression may be a compensatory protective mechanism of ischemic injury induced by seizures, and participate in the protection of epilepsy related neuronal damage.
ObjectiveTo explore the dynamic expression changes of neuronal growth and differentiation-associated miR-124a and miR-9 in the process of epileptogenesis. MethodsEstablish the lithium-pilocarpine induced status epilepticus (SE) rat model. Animal behavior change induced by SE as well as in the period of chronic epilepsy was observed by naked-eye or video-recording. Major time points for the study were chosen at 1d, 7d, 14d and 28d post-SE, on which the post-SE rats were decapitated and their hippocampal specimens were obtained. Total RNA from each specimen was extracted and qPCR was exploited to detect miR-124a and miR-9 expression in the specimens. Statistical analysis was used to show the dynamic expressional changes of miR-124a and miR-9 in rat hippocampus at 1d, 7d, 14d and 28d post-SE during the process of epileptogenesis. ResultsCompared with normal rats, the expression level of miR-124a in rat hippocampus did not show a significant difference at 1d post-SE, but it had shown markedly differences at 7d, 14d and 28d post-SE(P < 0.05), with a declining trend. Compared with normal rats, the expression level of miR-9 had demonstrated significant differences at 1d, 7d, 14d and 28d post-SE(P < 0.05)with a generally increasing trend, although there was slight fluctuation of expressional up-regulation at 7d post-SE. ConclusionNeuronal growth and differentiation-associated miR-124a and miR-9 had shown dynamic changes of down-regulation or up-regulation in the process of epileptogenesis. It can be suspected that miR-124a and miR-9 take part in hippocampal neurogenesis post-SE and be involved in epileptogenesis process.
Objective To investigate the diagnosis and treatment of status epilepticus in hospitals of different levels and the knowledge of status epilepticus in clinical physicians, in order to better guide clinical education in the future. Methods From August 2014 to August 2015, a questionnaire was designed and used to investigate the general situation of the hospital, the diagnosis of status epilepticus and the clinical practice among trainee doctors and students in the epilepsy training class in the Neurological Intensive Care Unit and the Department of Neurology of West China Hospital, Sichuan University. The results of the investigation were statistically analyzed. Results Ninety questionnaires were distributed, and all the questionnaires were retrieved with validity. The number of investigated physicians was 42 (46.7%) from the Department of Neurology, 6 (6.7%) from the Department of Neurosurgery, 30 (33.3%) from the Intensive Care Unit and 12 (13.3%) from other departments. Twenty-seven (30.0%) physicians were from class Ⅲ grade A hospitals, 31 (34.4%) from class Ⅲ grade B hospitals, and 32 (35.6%) from class Ⅱ grade A hospitals. All the class Ⅲ hospitals and 53.1% of class Ⅱ hospitals had electroencephalograph monitoring facilities. The proportion of status epilepticus patients ranged from 0.5% to 10.0% in different hospitals. There were great differences in the identification and treatment of convulsive status epilepticus among different hospitals. Conclusions Status epilepticus is a common emergency. Questionnaire survey is an effective means to reflect the difference in identifying and treating the emergency among different departments and hospitals. It can guide clinical education and promote the identification and treatment of the emergency more accurately in doctors of all levels.
ObjectiveTo systematically review the efficacy and safety of second-line medications for status epilepticus (SE). MethodsThe Cochrane Library, PubMed, EMbase, CNKI, CBM, and WanFang Data databases were electronically searched to collect randomized controlled trials (RCTs) of second-line medications for SE from inception to May, 2021. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Network meta-analysis was then performed using Stata 15.1 software and R 4.1.0 software. ResultsA total of 23 RCTs were included and 4 regimens were involved: levetiracetam (LEV), phenytoin/fosphenytoin (PHT), valproate (VPA), and phenobarbital (PHB). The results of network meta-analysis showed SE control rate validity sorting to be PHB>LEV>VPA>PHT, the epilepsy recurrence rate in 24 hour validity sorting to be VPA>PHB>LEV>PHT, those requiring further antiepileptic drug treatment rate validity sorting to be LEV>PHT>VPA, and drug safety security sorting to be VPA>LEV>PHT>PHB. Subgroup analysis showed PHB was optimal for SE control in children and adults, VPA had the optimal effect on other efficacy indicators in children, LEV was the safest in children and elderly patients, and VPA was the safest in adults. ConclusionsCurrent evidence suggests that PHB is the optimal for SE control, however, the safety is unsatisfactory; VPA and LEV have their own advantages in the treatment of SE, and their safety is satisfactory. VPA is recommended for adult patients, and LEV is recommended for children and elderly patients.
Objective To study the factors that affect the prognosis of status epilepticus (SE) and to improve the understanding of clinicians. Methods A retrospective analysis of 57 patients with SE witch from the General Hospital of Ningxia Medical University and Cardio-cerebrovascular Disease Hospital were carried out to collect their clinical data. The data were analyzed by SPSS 17.0 software. The prognosis of the patients was assessed by the Status epilepticus severity score (STESS) scale. Results A total of 57 patients were included, 53 cases improved, 4 cases were automatically discharged. Telephone follow-up showed that 4 cases of automatic discharge were dead. The mortality rate of SE was 7.02%. The most common cause of SE was acute cerebrovascular disease (17.54%), followed by intracranial infection (10.53%); The most common incidence were the occasional medication, self-medication, withdrawal (15.79%). Age, state of consciousness and concurrent infection were associated with prognosis (improvement/death) (P<0.05). STESS score of 0 to 2 points were 45 patients, all improved; score of 3 to 5 points were 12 patients, 8 patients improved, 4 patients died. There were significant differences in the prognosis between the two groups (P<0.05). Conclusions Age, state of consciousness, concurrent infection were related to prognosis, more than 65 years, the state of consciousness for the sleeping or coma had the poor prognosis. STESS scale can predict the prognosis of patients effectively.
Epilepsy is one of the most common neurological disorders, and status epilepticus (SE) can lead to permanent neuronal brain damage in the central nervous system, but the mechanism is not clear. Solving this problem will help to find more SE therapeutic targets, benefiting tens of millions of epilepsy patients. The pathway of SE leading to neuronal damage in the brain has made new progress in neuroinflammation, autophagy, apoptosis and pyroptosis, glial cell hyperplasia and category transformation, and changes in neurotransmitters in the brain, which will be beneficial to the discovery of new targets for the treatment of SE, thus laying a foundation for the development of new anti-epileptic drugs.
ObjiectiveTo explore the efficacy and safety of ketogenic diet therapy (KDT) in the rapidly progressive stage of childhood developmental epileptic encephalopathy Dravet syndrome (DS). Methods The clinical data of all patients who added KDT in the Children’s Hospital of Fudan University from 2011 to 2022 were retrospectively collected, and the age of <6 years was used as the criterion for the rapid progression of the disease. The clinica data, genotype and the efficacy of KDT were analyzed in DS patients who met the criteria. Results A total of 32 patients met the criteria for rapid disease progress, including 22 males and 10 females. The age at onset was (5.69±2.10) months. All patients had multiple seizure phenotypes and monthly seizures despite reasonable Antiseizure medications treatment. After 3, 6, 12, and ≥24 months, 93.8% (30/32), 87.5% (28/32), 53.1% (17/32), 34.4% (11/32) remained on the KDT, while 76.7% (23/30), 75.0% (21/28), 70.6% (12/17), 54.5% (6/11) showed >50% reduction in seizure. Status epileptius (SE) was reduced by 100% at 3 months, 71.0% at 6 months, 86.0% at 12 months. After 12 months, 14 patients experienced efficacy degradation. After 3 months, the EEG background rhythm showed improvement in 75.0% patients, interictal epileptic discharges was decreased in 54.5% patients and cognitive function was improved in 78.6% patients. At the initial stage of KDT, 62.5% (20/32) patients had transisent adverse reactions, including diarrhea, vomiting, fatigue, lethargy, hypoglycemia, and metabolic acidosis, but no mid- and long-term adverse reactions were found. ConclusionKDT is an efficective and safe treatment for DS. KDT can effectively control seizures, reduce the incidence of Status SE and shorten the duration of SE. With the prolongation of the KDT course, some patients experienced a degraded effect. KDT can improve abnormal EEG and cognitive function in DS patients. Pharmoco-resistant DS patients are suggested to receive KDT in the early stage of disease progression.
Status epilepticus (SE) is one of the most common neurological emergencies. Prolonged seizures can cause permanent neuronal death in the central nervous system, necessitating early recognition and timely intervention. Although there is some consensus on the diagnosis and treatment of SE, the high heterogeneity of SE patients presents a significant challenge for standardized management and prognosis prediction. This review summarizes the current research progress on the diagnosis, treatment, and prognosis of SE, aiming to provide references for early diagnosis, early treatment, and early prediction of prognosis.
ObjectiveTo investigate the etiology, clinical features, treatment, and prognosis of Partial status epilepticus (PSE). MethodsSeventeen PSE patients were hospitalized in the Department of Neurology at the First Hospital of Jilin University from April 2013 to June 2015. Clinical data were retrospectively analyzed. ResultsA total of 17 patients, 8 male and 9 female, 18~91years old, at mean age (48.90±21.17) years were included. About 12 cases (70.59%) had acute symptomatic status epilepticus, the etiologies including central nervous system inflammation (5 cases), cortical infarction (3 cases), metabolic disorder (1 case), hypoxic-ischemic encephalopathy (1 case), space-occupying lesions(1 case) and degeneration (1 case); four cases (23.53%) were diagnosed with epilepsy, one case (5.88%) had no definite pathogenesis. The seizure types included complex partial status epilepticus (8 cases, 47.06%), complex part of the secondary comprehensive status epilepticus (3 cases, 17.65%), supplementary motor area (SMA) status epilepticus (4 cases, 23.53%), epilepsia partialis continua (EPC) (1case, 5.88%)and complex partial status epilepticus & aura continua (1case, 5.88%). Nine cases (52.94%) were effective after one hour treament, eight cases (47.06%) were negative. 17 cases are followed-up and 4 cases lost, the average follow-up time is (10.89±8.64) months. 8 cases are completely seizure free, and 3 cases have experience less seizures or the symptom is relived; the other 2 cases die from Creutzfeldt-Jacob desease(case No.10) and Respiratory failure(case No.12). ConclusionsThe inpatients of partial status epilepticus are mostly "situation related". Patients with clinical suspect should be administrated with long term video-Electroencephalogram(EEG) monitoring timely. Early diagnosis, treatment and the aggressive treatment can help to improve the prognosis. Patients of encephalitis usually progress into refractory status epilepticus, the anesthetic drugs should be used as soon as possible.
ObjectiveTo investigate the effect of electroacupuncture on the apoptosis of hippocampal neurons in C57BL/6J mice with status epilepticus by observing the changes of hippocampal subtle neuron pathology and apoptosis.MethodsMale C57BL/6J mice were used to prepare epileptic status models of lithium-pilocarpine mice, and then 7-day electroacupuncture stimulation (Baihui, Fengfu) were given to the mice model. Open field experiment and new object recognition experiment were performed to observe the changes of cognitive abilities. The pathological changes of hippocampal neurons were detected by HE staining. Hippocampal apoptosis protein (Caspase-3) and microtubule-associated protein (MAP-2) were detected by immunohistochemistry. Effect of electroacupuncture on apoptosis of hippocampal neurons in C57BL/6J mice with status epilepticus were recorded.Results① Compared with the control group, the vertical movement, modification times, and number of crossings of the model group all decreased significantly (P<0.000 1,P<0.000 1,P<0.000 1), and their cognitive ability decreased significantly (P<0.01). Compared with the model group, vertical movements, modification times, and number of crossings were increased in the electroacupuncture (EA) group (P<0.01,P<0.05,P<0.05), and the cognitive ability of new objects was increased (P<0.01). ② HE staining showed that the model group had significant damage to the hippocampal neurons of mice, and the cells swelled, nuclear collapsed and vacuoles appeared. In the EA group, the injury of hippocampal neurons was alleviated, and cell edema and vacuolization were alleviated. ③ Immunohistochemistry showed that compared with the control group, the IOD of the Caspase-3 positive cells in the hippocampus of the model group increased significantly (P<0.000 1), and the IOD of the MAP-2 positive cells decreased significantly (P<0.01); Compared with the electroacupuncture, the IOD of the Caspase-3 positive cells in the hippocampus of the mice decreased (P<0.05), and the IOD of the MAP-2 positive cells increased (P<0.05).ConclusionsElectroacupuncture can improve the pathological changes of hippocampal neurons in C57BL/6J mice with status epilepticus, promote cytoskeletal repair, reduce neuronal apoptosis in hippocampus, and antagonize the damage of hippocampal neurons induced by status epilepticus.