SCN1A rs6732655A/T polymorphism:Diagnostic and therapeutic insights for drug-resistant epilepsy

BACKGROUND A significant subset of individuals with epilepsy fails to respond to currently available antiepileptic drugs,resulting in heightened mortality rates,psychosocial challenges,and a diminished quality of life.Genetic factors,particularly within the SCN1A gene,and the pro-inflammatory cytokine response is important in intricating the drug resistance in idiopathic epilepsy cases.In this extended study,we determined the correlation of rs6732655A/T single nucleotide polymorphism to understand the causative association of SCN1A gene with epilepsy drug resistance and inflammatory response.AIM To find the correlation of SCN1A gene rs6732655A/T polymorphism with the drug-resistant epilepsy and inflammatory response.METHODS The study enrolled 100 age and sex-matched patients of both drug-resistant and drug-responsive epilepsy cases.We analysed the rs6732655A/T polymorphism to study its association and causative role in drug-resistant epilepsy cases using restriction fragment length polymorphism technique.The diagnostic performance of interleukin(IL)-1β,IL-6,and high mobility group box 1(HMGB1)protein levels was evaluated in conjunction with genotypic outcome receiver operating characteristic analysis.RESULTS AT and AA genotypes of rs6732655 SCN1A gene polymorphism were associated with higher risk of drug resistance epilepsy.Serum biomarkers IL-6,IL1βand HMGB1 demonstrated diagnostic potential,with cutoff values of 4.63 pg/mL,59.52 pg/mL and 7.99 ng/mL,respectively,offering valuable tools for epilepsy management.Moreover,specific genotypes(AA and AT)were found to be linked to the elevated levels of IL-1βand IL-6 and potentially reflecting increased oxidative stress and neuro-inflammation in drug-resistant cases supporting the previous reported outcome of high inflammatory markers response in drug resistance epilepsy.CONCLUSION SCN1A genotypes AA and AT are linked to higher drug-resistant epilepsy risk.These findings underscore the potential influence of inflammation and genetics on epilepsy treatment resistance.

Did pediatric drug development advance epilepsy treatment in young patients?It is time for new research goals

Modern drugs have changed epilepsy,which affects people of all ages.However,for young people with epilepsy,the framework of drug development has stalled.In the wake of the thalidomide catastrophe,the misconception emerged that for people<18 years of age drugs,including antiseizure medications(ASMs),need separate proof of efficacy and safety,overall called"pediatric drug development".For ASMs,this has changed to some degree.Authorities now accept that ASMs are effective in<18 years as well,but they still require"extrapolation of efficacy,"as if minors were another species.As a result,some of the pediatric clinical epilepsy research over the past decades was unnecessary.Even more importantly,this has hampered research on meaningful research goals.We do not need to confirm that ASMs work before as they do after the 18th birthday.Instead,we need to learn how to prevent brain damage in young patients by preventing seizures and optimize ASMs’uses.Herein we discuss how to proceed in this endeavor.

Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

Association of single nucleotide polymorphisms of brain-derived neurotrophic factor gene and multidrug resistance 1 gene to refractory epilepsy in Chinese Han children

BACKGROUND： There are two hypotheses for the underlying cause of refractory epilepsy： ＂target＂ and ＂transport＂. Studies have shown that brain-derived neurotrophic factor （BDNF） is over-expressed in refractory epilepsy. Multidrug resistance 1 （MDR1） gene encodes for P-glycoprotein, the primary ATP-binding cassette transporter in the human body. Some single nucleotide polymorphisms of the MDR1 gene have been associated with refractory epilepsy. OBJECTIVE： To investigate the association between BDNF gene C270T polymorphism and MDR1 T-129C polymorphism with refractory epilepsy in Chinese Han children through the use of polymerase chain reaction （PCR）-restriction fragment length polymorphism analysis. DESIGN, TIME AND SETTING： A case-control, genetic association study was performed at the Central Laboratory, Third Xiangya Hospital of Central South University from June 2005 to November 2007. PARTICIPANTS： A total of 84 cases of unrelated children with epilepsy, including 41 cases of refractory epilepsy and 43 cases of drug-responsive epilepsy, were enrolled. An additional 30 healthy, Chinese Han children, whose ages and gender matched the refractory epilepsy patients, were selected as normal controls. METHODS： Venous blood was collected and genomic DNA was extracted from the blood specimens. C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene were genotyped using PCR-restriction fragment length polymorphism analysis. Association analysis using the Ftest and Chi-square test was statistically performed between C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene and refractory epilepsy. MAIN OUTCOME MEASURES： The distribution of genotypes and allele frequencies of C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene. RESULTS： The distribution of CC, CT, and TT genotypes, as well as C and T allele frequencies, in the BDNF gene was not significantly different between the refractory epilepsy group, drug-responsive epilepsy group, or the normal control group （P 〉 0.05）. The distribution of TT genotype and T allele frequencies of the MDR1 gene was significantly different in the refractory epilepsy group compared with the drug-responsive epilepsy and normal control groups （P 〈 0.05）. Comparison of haplotype combinations demonstrated that there were no significant differences in combinations of TT＋CC, -FI-＋CT, TC＋CC, and TC＋CT among the three groups （P 〉 0.05）. CONCLUSION： C270T polymorphism of the BDNF gene was not associated with refractory epilepsy in Chinese Han children, but T-129C polymorphism in the MDR1 gene was associated with refractory epilepsy in Chinese Han children. The TT genotype and T allele frequencies could serve as susceptibility loci for refractory epilepsy. Interactions between C270T in BDNF gene and T-129C in MDR1 gene were not observed in refractory epilepsy in Chinese Han children.

A Review of the Surgical Procedures for the Treatment of Drug-Resistant Epilepsy and Their Seizure Control Outcomes

Background: Drug-resistant epilepsy can be defined as the existence of seizures within 6 months, despite adequate therapy regimens with one or more antiepileptic drugs. Epilepsy surgery has been the standard therapy to help those patients who suffer from drug-resistant epilepsy. The goal of this surgery is to halt or reduce the intensity of seizures. This literature review aims to provide an overview of existing surgical procedures for the treatment of drug-resistant epilepsy and the degree of seizure control they provide based on available literature. Methods: Data were collected from medical journal databases, aggregators, and individual publications. The most used databases were PubMed, Medline and NCBI. Some of the keywords used to search these databases include: “drug resistant epilepsy”, “seizure control”, and “neurosurgery”. Results: Epileptic surgery is divided into resective and non-resective procedures. Studies have shown that a full resection of the epileptogenic brain area increases the probability of seizure eradication, however, the risks of postoperative impairments grow as the resection area is extended. On the other hand, patients who are unsuitable for seizure focus removal by resective surgery, such as those with multifocal seizures or overlapping epileptogenic zone with a functional cortex, may benefit from non-resective surgical options such as Vagus Nerve Stimulation and Responsive Neurostimulation. Conclusion: This literature review discusses the comprehensive treatment of epilepsy, especially the surgical treatment of drug-resistant epilepsy. The reviewed studies have shown that epilepsy surgery has promising outcomes in achieving seizure freedom/reducing seizure frequency with minimal adverse effects when performed correctly with the appropriate choice of surgical candidates.

Pharmacokinetic, pharmacodynamic, and neurochemical investigations of lamotrigine-pentylenetetrazole kindled mice to ascertain it as a reliable model for clinical drug-resistant epilepsy

Background:Pentylenetetrazole kindling has long been used for the screening of investigational antiseizure drugs.The presence of lamotrigine,at a very low dose,does not hamper kindling in mice;rather it modifies this epileptogenesis process into drug-resistant epilepsy.The lamotrigine-pentylenetetrazole kindled mice show resistance to lamotrigine,phenytoin,and carbamazepine.It may also be possible that other licensed antiseizure drugs,like the mentioned drugs,remain ineffective in this model;therefore,this was the subject of this study.Methods:Swiss albino mice were kindled with pentylenetetrazole for 35 days in the presence of either methylcellulose vehicle or lamotrigine(subtherapeutic dose,ie,5 mg/kg).Vehicle vs lamotrigine-kindled mice were compared in terms of(a)resistance/response toward nine antiseizure drugs applied as monotherapies and two drug combinations;(b)lamotrigine bioavailability in blood and brain;(c)blood-brain barrier integrity;and(d)amino acids and monoamines in the cerebral cortex and hippocampus.Results:Lamotrigine vs vehicle-kindled mice are similar(or not significantly different P>.05 from each other)in terms of(a)response toward drug combinations;(b)lamotrigine bioavailability;and(c)blood-brain barrier integrity except for,significantly(P<.05)reduced taurine and increased glutamate in the cerebral cortex and hippocampus.Aside from these,lamotrigine-kindled mice show significant(P<.05)resistant to lamotrigine(15 mg/kg),levetiracetam(40 mg/kg);carbamazepine(40 mg/kg),zonisamide(100 mg/kg),gabapentin(224 mg/kg),pregabalin(30 mg/kg),phenytoin(35 mg/kg),and topiramate(300 mg/kg).Conclusion:Lamotrigine-pentylenetetrazole kindling takes longer to develop(~5 weeks)in comparison to lamotrigine-amygdale(~4 weeks)and lamotriginecorneal(~2 weeks)kindling models.However,drug screening through this model may yield superior drugs with novel antiseizure mechanisms.

Safety and efficacy of a novel responsive neurostimulation system in China for drug-refractory focal epilepsy:The first-in-man study

To the Editor:Recent studies have characterized drugresistant epilepsy(DRE)as essentially a neural network disease.[1]Detection and disconnection of this pathological epileptic connectome or network can greatly improve seizure outcomes.Our team also proposes the development of the newly emerging branch of epileptic networks neurosurgery(ENN).Responsive neurostimulation(RNS)is an ENN-oriented emerging treatment option without the resection of the seizure-onset zone or epileptic focus and aims to control the seizure or other epileptic manifestations by modulating or disrupting the network’s key nodes(epileptic hubs)in a self-responsive way.

Multiple hurdle mechanism and blood-brain barrier in epilepsy:glucocorticoid receptor-heat shock proteins on drug regulation

Epilepsy is a complex neurologic condition which affects over 50 million people worldwide.Pharmacotherapy,primarily involving the use of anti-seizure drugs(ASDs),is an essential part of controlling seizures.However,nearly 30%of patients develop drug-resistant epilepsy,clinically defined as the persistence of seizure following trials of two ASDs(Kwan et al.,2010).Although several hypotheses have been proposed to explain this phenomenon,the mechanism of drug-resistant epilepsy still remains unclear.

Tall gastrodis tuber combined with antiepileptic drugs repairs abnormal perfusion foci in focal epilepsy

One hundred patients with focal epilepsy were recruited for the present study and their seizures controlled with antiepileptic drugs. The patients then orally received a capsule of tall gastrodis tuber powder, a traditional Chinese drug, and underwent single photon emission computed tomography, long-term electroencephalogram, and CT/MRI. Blood drug levels were monitored throughout the study. Before treatment with tall gastrodis tuber, 35 of the 100 cases had abnormal CT/MRI scans; 79 cases had abnormal single photon emission computed tomography images; 86 cases had abnormal electroencephalogram; and a total of 146 abnormal perfusion foci were observed across the 100 subjects. After treatment, the number of patients with normal single photon emission computed tomography images increased by 12; normal electroencephalogram was observed in an additional 27 cases and the number of patients with epileptiform discharge decreased by 29 （34% of 86）; the total number of abnormal perfusion foci decreased by 52 （36%） and changes in abnormal loci were visible in 65 patients. These changes indicate that the administration of tall gastrodis tuber in combination with antiepileptic drugs repairs abnormal perfusion foci in patients with focal epilepsy Our results demonstrate that traditional Chinese drugs can repair abnormal perfusion foci and, as such, are a promising new pathway in the treatment of focal epilepsy.

Brain-derived neurotrophic factor expression is higher in brain tissue from patients with refractory epilepsy than in normal controls

The role of the brain-derived neurotrophic factor in epilepsy remains controversial. The present study utilized light and electron microscopy to investigate pathological and ultrastructural changes in brain tissue obtained from the seizure foci of 24 patients with temporal epilepsy. We found that epileptic tissue showed neuronal degeneration, glial cell proliferation, nuclear vacuolization, and neural cell tropism. Immunoelectron microscopy and immunohistochemistry showed that brain-derived neurotrophic factor was expressed at significantly higher levels in patients with refractory temporal epilepsy compared with normal controls, demonstrating that the pathological changes within seizure foci in patients with refractory epilepsy are associated with brain-derived neurotrophic factor expression alterations.

Comparisons of drug efficacy and time-effect among magnesium valproate,sustained-release magnesium valproate tablet and depakine chrono for epilepsy An experiment of determining cortical convulsive threshold in rats undergoing electrical stimulation

BACKGROUND： Scholars have investigated the differences in drug metabolism and pharmacodynamics between valproate and its sustained-release tablets only from the angle of pharmaceutical sciences or clinical practice. Whether the fact that differences in drug efficacy and time-effect of different doses of valproate and different types of sustained-release valproate tablets at the same concentration can be quantitatively reflected by determining the changes in convulsive threshold pre- and post-administration in rat models of determining the convulsive threshold developed by direct cortical electrical stimulation remains unclear. OBJECTIVE： This study aimed to compare the drug efficacy and time-effect among magnesium valproate, sustained-release magnesium valproate tablet and depakine chrono in the treatment of epilepsy by determining the convulsive threshold of rat models created by direct cortical electrical stimulation, and human serum drug concentration before and after administration. DESIGN： A controlled observational experiment. SETTING： Research Institute of Epilepsy, Shanxi Medical University. MATERIALS： Adult health male SD rats of clean grade, weighing 200 - 220 g, provided by the Laboratory Animal Center of Shanxi Medical University. The protocol was carried out in accordance with requests from Animal Ethics Committees for guidance. Magnesium valproate （Lot No. 041004） and sustained-release magnesium valproate tablet （Lot No. 050501） were produced in Hunan Xiangzhong Pharmaceutical Co., Ltd. METHODS： This study was carried out in the Laboratory for Epilepsy, Shanxi Medical University between June and August 2005. （1）All the SD rats were created into models for determining cortical convulsive threshold. They were randomly divided into 4 groups with 20 rats in each： magnesium valproate tablet group, sustained-release magnesium valproate tablet group, depakine chrono group and control group. After being modeled, the rats in the first 3 groups were intragastrically administrated with magnesium valproate, sustained-release magnesium valproate tablet and depakine chrono, respectively, while the control group were intragastrically administrated with the same volume of normal saline. （2）Convulsive threshold of each fasting rat was determined 0.5 hour before, and 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14 and 24 hours after single administration, separately. （3） Convulsive threshold was determined repeatedly 2 weeks after single administration. Each rat was administrated two times daily successively. Convulsive threshold was determined 0.5 hour before, and 0.5, 2.5, 7 and 12 hours after administration, separately. （4）Hepatic and renal tissues were harvested for pathological examination after 1 month of administration. （5）Nine healthy voluntary medical stuffs were recruited in this study. Written informed consents of experiment were obtained each involved subject. The study was given an approval by the Ethics Committee of Shanxi Medical University. According to the scheme, the 9 volunteers were randomly assigned into 3 groups, in which, volunteers were asked to take magnesium valproate 500 g, sustained-release magnesium valproate tablet 500 g and depakine chrono 500 g, respectively, in the morning under the condition of fasting. Serum drug concentration of each drug was determined by fluorescence polarization immunoassay at different time points. MAIN OUTCOME MEASURES： （2） Rat convulsive threshold after single and repeated administrations. （2）Hepatic and renal pathological examination results. （3） Serum drug concentration in vivo. RESULTS：（4）Rat convulsive threshold after single and repeated administrations： Drug efficacy in the magnesium valproate tablet group reached to a peak level 1 to 2 hours after single administration, and was obviously higher than that in the other groups 1 hour after administration （P 〈 0.05）. Drug efficacy in the sustained-release magnesium valproate tablet group and depakine chrono group both reached to a peak level 7 hours after administration, and was significantly higher than that in the control group （P 〈 0.05）. After repeated administrations, the average peak valley deviation of the convulsive threshold in the magnesium valproate tablet group was 120- 150 μ A, which was 2 and 2.5 times as that in the sustained-release magnesium valproate tablet group and depakine chrono group, respectively. After repeated administrations for 10 times, convulsive threshold was increased by 440 μ A in the sustained-release magnesium valproate tablet group, and by 230 μ A in the depakine chrono group in comparison with before administration. （2） Hepatic and renal pathological examination results： No obvious differences in hepatic and renal impairment were found among the 4 groups after I month of administration successively. （3） Serum drug concentration in vivo： Serum-drug concentration of magnesium valproate was increased fast and reached to a peak level 0.5 - 2 hours after administration, remained at a relatively stable level 2 - 4 hours after administration, and then was slowly decreased. The drug efficacy of sustained-release magnesium valproate tablet and depakine chrono was slowly released 1 - 6 hours after administration, reached to a peak level at about 7 hours, and could last for about 16 hours. CONCLUSION： Magnesium valproate has a rapid onset and offset of action. Sustained-release magnesium valproate tablet has a slow onset but long duration of drug efficacy. Depakine chrono can be easier to be absorbed than sustained-release magnesium valproate tablet, but its long-term effect on improving the convulsive threshold is inferior to sustained-release magnesium valproate tablet.

Long-Term Impact in the Quality of Life of Patients with Drug-Resistant Epilepsy That Use Cannabidiol

Introduction: Epilepsy is considered a chronic neurological condition that manifests itself with seizures, where 30% - 40% of patients do not achieve control of their seizures despite proper management. Seizures represent a significant limitation in the patient’s daily activities and are often accompanied by emotional and relational difficulties that have a great impact on the quality of life of the patient and their families. Cannabidiol (CBD) has been found to be effective in controlling seizures and may also improve cognitive and behavioral abilities. Material and Methods: The Quality of Life of the Patient with Epilepsy (CAVE) scale was applied to patients with refractory epilepsies who use Cannabidiol (CBD) added to their base therapy, before the use of CBD and after 12 months of follow-up. The presentation of collateral effects was also evaluated. Results: Out of 34 patients, 26 (76.5%) increased their CAVE value at the end of the study and only 1 (2.9%) decreased. 19 (55.9%) improved in learning and behavior, 55.8% in the frequency of seizures and 79.4% reported a decrease in the intensity of seizures. There were other positive side effects such as improvement in alertness, language, sleep and behavior. The main side effects were mild and transitory, including drowsiness, and constipation. There was a correlation between the global perception of improvement and seizure control. Conclusions: This study shows that in the long term CBD improves the quality of life of patients with refractory epilepsies, through the control of seizures and the improvement of cognitive and behavioral functions.

Treatment of epilepsy in China Formal or informal?

Antiepileptic drugs are the preferred treatment approach for epileptic patients. However, informal treatment is important for intractable epilepsy. In this study, 500 epileptic patients were recruited from the General Hospital of Beijing Military Area Command of Chinese PLA during the period of October 2009 to January 2012. These involved patients that had been medically treated for at least 1 year. Information on the initial treatment and changes to treatment regimens for each patient was collected through questionnaires. The survey results showed that 52.3% of the epileptic patients searched for treatment after the first seizure, and the mean numbers of seizures was 12.8; 59.8% of the epileptic patients were diagnosed at the first visit, and the mean onset time was 17 months after the first seizure. After diagnosis, patients were treated for an average of 20 days, and the median time was 1 day. Formal anti-epileptic drugs were selected as the first treatment regimen by 67.8% of patients, and 77.5% of these drugs were monotherapies. The mean and median numbers of seizure were respectively 36.9 and 3.0 times before the first regimen was changed. The regimen was changed within the first 6 months by 46.6% of patients, and after the first and second years of treatment, the proportions increased to 54.0% and 71.8%, respectively. In total, 78.5% of the regi- mens were changed to informal treatments. The informal treatment of epilepsy in China is common, being initiated by either patients or physicians. Enhancing epileptic treatment services in hospital, improving physicians＇ professional quality, and strengthening health propaganda may promote the normalization of drug treatment of epilepsy in China.

Clinical Observation on 930 Child Epilepsy Cases Treated with Anti-epilepsy Capsules

1090 cases of child epilepsy were divided randomly into two groups: the treatment group (930 cases treated with anti-epilepsy capsules) and the control group (160 cases treated with luminal). The results showed that in the treatment group, 534 cases were markedly effective, 241 effective, 96 improved, 46 ineffective, and 13 aggravated, with a total effective rate of 83.33%; while in the control group, 64 cases were markedly effective, 19 effective, 38 improved, 29 ineffective, and 10 aggravated, with a total effective rate of 51.88%. The treatment group showed an obviously higher total effective rate than that in the control group (P<0.01). After treatment, cases in the two groups all had lower frequency of epilepsy attacks and shorter duration of each attack as compared with that before treatment (P<0.01), but the situation was obviously better in the treatment group. The anti-epilepsy capsules had very good effect on various types of epilepsy, especially on autonomic epilepsy and on epilepsies due to wind, phlegm, or terror as differentiated in TCM. After treatment, the recovery rate shown by EEG examination was 54.3% in the treatment group, while 38.4% in the control group, the former being obviously higher than the latter (P<0.01).

Clinical Characteristics and Current Medical Practice in a Group of Sudanese Patients with Epilepsy: A Cross Sectional Hospital Based-Study

Introduction: The epilepsy classification in under developed countries faces many difficulties in reporting, work-up and management strategies. Exploring local practice in general hospitals will positively add to the welfare of patients with epilepsy. The objectives of this study were to assess the current medical practice in epilepsy work up and to study the selection of AEDs as per ILAE guidelines. Methods: This was a cross sectional-retrospective hospital based study, conducted between April and September 2016 in Omdurman Teaching Hospital, Khartoum, Sudan. Patients aged 18 years old and above were enrolled. Epilepsy was defined as having at least two non-provoked seizures in the least 6 months in a patient who was assessed by clinical review and electroencephalogram (EEG). Epilepsy was classified as generalized, focal or unclassified. Medications refer to all internationally licensed antiepileptic medications (AEDs) in 2016. Results: One hundred adult Sudanese patients were enrolled for this study. The most common event described during the ictal phase was tongue biting in 50% of participants followed by body stiffness in 46%. Epilepsy was classified as generalized in 84%, focal in 11% and unclassified in 5% patients. In generalized epilepsy, the MRI detected 23.3% abnormal findings higher than the CT which detected 14.8% (4/27), p value = 0.032. In focal epilepsy, the CT detected 75% abnormal findings higher than the MRI which detected 33.3%, p value = 0.02. The AEDs used were as follows: Carbamazepine (CBZ) 48%, Na valproate (VP) 33%, Lamotrigine (LMT) 2%, Levetricetan (LVT) 1%, CBZ + VP 14% and CBZ + Oxcarbazepine (OXC) 2%. Conclusion: The current medical practice in Omdurman teaching hospital should be modified to match the international league against epilepsy (ILAE) guidelines in workup, management, AEDs selection and classification of epilepsy.

The influence of immunomodulator on the immunoglobulin and T cell subsets in children with intractable epilepsy

Objective:To observe the influence of immunomodulator on the immunoglobulin and T cell subsets in children with intractable epilepsy.Method:A total of 82 children with intractable epilepsy in our hospital were selected and randomly divided into 2 groups: the control group (41 cases) and the observation group (41 cases). Routine antiepileptic drugs were given to the control group. Medication regimen was that more than 2 kinds of anti epileptic drugs were be combined used. But the immunomodulator wasn't used. Treatment of immune globulin was given to the control group on the basis of observation group. By taking the 400 mg/kg/d as the standard of dosage, for 5 d every course of treatment. One course of treatment was carried out every month, 3 months in total. The changes of IgA, IgG, IgM and CD3+, CD4+, CD8+, CD4+/CD8+ were compared in 2 groups before and after treatment.Result: The comparison of IgA, IgG, IgM in the two groups before treatment was not statistically significant. After treatment, IgA, IgG in observation group were significantly higher than that before treatment and the difference was statistically significant. However, there was no significant difference on the IgM. There was no significant difference on the IgA, IgG, IgM in the control group compared with that before treatment. IgA, IgG in observation group was significant higher than that in the control group. The comparison of IgM between 2 groups was not statistically significant. The comparison of CD3+, CD4+, CD8+, CD4+/CD8+ in the two groups before treatment was not statistically significant. After treatment, CD3+, CD4+, CD4+/CD8+ in observation group were significantly higher than that before treatment;CD8+ in observation group was significantly lower than that before treatment. The difference was statistically significant. There was no significant difference on the CD3+, CD4+, CD8+, CD4+/CD8+ in the control group compared with that before treatment. CD3+, CD4+, CD4+/CD8+ in observation group was significant higher than that in the control group. CD8+ in observation group was significant lower than that in the control group. The difference was statistically significant.Conclusion:Compared with using routine antiepileptic drugs , application of immune globulin as an immunomodulator combined with conventional antiepileptic drug in children with refractory epilepsy can effectively improve the expression of IgA, IgG, IgM and T cell subsets, which has a positive effect on the immune function of the children.

Risks of suicidality in adult patients with epilepsy

AIM: To determine the prevalence and risks of suicidality in a group of patients with epilepsy. METHODS: Included were 200 adult patients and 100 matched healthy subjects. The clinical interview using The Diagnostic and Statistical Manual of Mental Disorders(4th edition), Beck Depression Inventory(2nd edition)(BDI-Ⅱ), Hamilton Anxiety Rating Scale(HAM-A), Yale-Brown Obsessive Compulsive Scale(Y-BOCS) and Eysenck Personality Questionnaire-Revised Rating Scale testings were used for diagnosis and assessment of severity of psychiatric symptoms. Blood concentrations of serotonin, catecholamines and dopamine were also measured.RESULTS: Suicidality was reported in 35%(compared to 9% for controls), of them 80%, 72.86%, 55.71% and 52.9% had depression, anxiety, obsession and aggression respectively. Patients with suicidality had higher scores of BDI-Ⅱ(P = 0.0001), HAM-A(P = 0.0001), and Y-BOCS(P = 0.037) and lower scores of psychotic(P = 0.0001) and extroversion(P = 0.025) personality traits. Regardless the presence or absence of suicidality, patients with epilepsy had low serotonin(P = 0.006), noradrenaline(P = 0.019) and adrenaline(P = 0.0001) levels. With suicidality, significant correlations were identified between:(1) age and scores of BDI-Ⅱ(r = 0.235, P = 0.0001) and HAM-A(r = 0.241, P = 0.046);(2) age at onset and concentrations of noradrenaline(r =-0.502, P = 0.024);(3) duration of illness and scores of BDI-Ⅱ(r = 0.247, P = 0.041), Y-BOCS(r = 0.270, P = 0.025) and neurotic personality trait(r =-0.284, P = 0.018); and(4) doses of antiepileptic drugs and scores of psychotic personality traits(r =-0.495, P = 0.006 for carbamazepine; r =-0.508, P = 0.0001 for valproate).CONCLUSION: This is the first study which systematically estimated the prevalence and risks of suicidality in a homogenous group of patients with epilepsy. This study emphasizes the importance of epilepsy itself as a risk for suicidality and not its treatment.

Epilepsy Properties and Seizure Suppression in a Severe Motor and Intellectual Disabilities

Purpose: In hospitalized patients with severe motor and intellectual disabilities (SMID), we analyzed the association of the SMID class to factors such as the prevalence of epilepsy, frequency of seizures and number of concomitantly used anti-epileptic drugs (AEDs), and evaluated the usefulness of addition of the new AEDs (gabapentin, topiramate, lamotrigine and levetiracetam) to the treatment regimen. Results: The prevalence of epilepsy in the study population was about 60%. There were 39.5% who were free of epileptic seizures during the 6-year survey period and remained well-controlled with medication. As the SMID increased in severity, the frequency of seizures increased, the number of concomitantly used AEDs increased, and the tendency towards addition of new AEDs became more marked. About the use situation of new AED and old AED, this comparison revealed a tendency towards addition of a new AED when the seizures were poorly controlled in response to concomitant use of multiple old AEDs. The frequency of seizures and the number of concomitantly used AEDs were higher in patients with SMID of high severity than in those with SMID of low severity. Analysis of the time-course of the frequency of seizures before and after the addition of new AEDs revealed a significant reduction in the frequency of seizures following the addition of the new AEDs (P > 0.001). Conclusions: These results suggest that the new AEDs are useful in the management of SMID-associated epilepsy, because of their effect of reducing the frequency of SMID-associated seizures and their high tolerability.

Microscopic Anterior Callosotomy for Management of Intractable Epilepsy (Al-Azhar Experience)

Background: Anterior Corpus Callosotomy is a palliative treatment for drug-resistant generalized or multifocal epilepsy patients where focus excision is not an option for management. Callosotomy prevents propagation of epileptic discharge from one cerebral hemisphere to the other. Objective: To describe Al-Azhar University Hospitals experience and clinical outcome of Anterior Corpus Callosotomy for management of drug-resistant generalized epilepsy patients as an inexpensive palliative method. Patients and Methods: In this study, there are 15 patients admitted to Neurosurgery Department in Al-Azhar University Hospitals with drug-resistant generalized epilepsy. These patients were not candidates for lesionectomy. They were managed by anterior two thirds Corpus Callosotomy between February 2017 and December 2019. They were followed at outpatient clinic for at least 14 months. Clinical outcome regarding seizure control was assessed using Engel classification. Results: All 15 patients in this study underwent anterior two thirds corpus callosotomy and followed for at least 14 months. The post-operative improvement of seizure frequency has been evaluated using Engel outcome scale with 12 patients (80%) of the patients becoming Engel class II and 3 patients (20%) becoming Engel class III. Only 3 patients (20%) had minor transient postoperative complications;one patient (6.67%) had contra-lateral lower limb heaviness Grade 4 which was transient, one patient (6.67%) had contra-lateral lower limb Jacksonian focal fits and one patient (6.67%) had behavioral changes for one month. Conclusion: Corpus callosotomy is a palliative procedure and inexpensive method for management of patients with intractable focal with generalization and generalized drug-resistant epilepsy who are not suitable for resective surgery and with good outcome.

Prevalence of epilepsy in the onchocerciasis endemic middle belt of Ghana after 27 years of mass drug administration with ivermectin

BackgroundIn onchocerciasis-endemic areas with high ongoing Onchocerca volvulus transmission,a high prevalence of epilepsy has been reported.This study aimed to determine the prevalence and clinical characteristics of epilepsy in the Bono Region of Ghana following 27 years of implementation of ivermectin mass drug administration(MDA).MethodsBetween October 2020 and August 2021,cross-sectional surveys were conducted in nine communities in the Tain District and Wenchi Municipality of the Bono Region of Ghana.In the first stage,a random door-to-door approach was used to screen the population for epilepsy using a pre-tested questionnaire.Persons suspected of having epilepsy were invited for a second-stage neurological examination for case verification.Community O.volvulus microfilarial infection status and Ov16 seropositivity were also determined.Ninety-five confidence intervals(95%CI)for prevalence values were calculated using the Wilson Score Interval.ResultsOf the 971 participants,500(51.5%)were females,and the median age(interquartile range)was 26(15‒43)years.Fourteen participants(1.4%,95%CI:1.0‒2.0)were diagnosed as having epilepsy with generalized seizures being the most frequent seizure type(85.7%,12/14).The overall microfilarial prevalence of O.volvulus was 10.3%(November 2020)and 9.9%(August 2021);the Ov16 seroprevalence was 22.2%(June 2021).Only 63.2%took ivermectin in the last round of MDA distribution in March 2021.ConclusionsThe 1.4%prevalence of epilepsy in the Bono region is similar to the median epilepsy prevalence in sub-Saharan Africa.However,the persistent microfilarial prevalence and low ivermectin study coverage call for the Ghana Onchocerciasis Elimination Programme to step up its efforts to ensure that the gains achieved are consolidated and improved to achieve the elimination of onchocerciasis by 2030.