Features of animal models of complex partial epilepsy established through unilateral,bilateral and alternate-side kindling at hippocampus of rats

BACKGROUND： Electrical stimulation kindling model, having epilepsy-inducing and spontaneous seizure and other advantages, is a very ideal experimental animal model. But the kindling effect might be different at different sites. OBJECTIVE： To compare the features of animal models of complex partial epilepsy established through unilateral, bilateral and alternate-side kindling at hippocampus and successful rate of modeling among these 3 different ways. DESIGN： A randomized and controlled animal experiment SETTING： Department of Neurology, Qilu Hospital, Shandong University MATERIALS： Totally 60 healthy adult Wistar rats, weighing 200 to 300 g, of either gender, were used in this experiment. BL-410 biological functional experimental system （Taimeng Science and Technology Co. Ltd, Chengdu） and SE-7102 type electronic stimulator （Guangdian Company, Japan） were used in the experiment. METHODS： This experiment was carried out in the Experimental Animal Center of Shandong University from April to June 2004. After rats were anesthetized, electrode was implanted into the hippocampus. From the first day of measurement of afterdischarge threshold value, rats were given two-square-wave suprathreshold stimulation once per day with 400 μA intensity, 1ms wave length, 60 Hz frequency for 1 s duration. Left hippocampus was stimulated in unilateral kindling group, bilateral hippocampi were stimulated in bilateral kindling group, and left and right hippocampi were stimulated alternately every day in the alternate-side kindling group. Seizure intensity was scored： grade 0： normal, 1： wet dog-like shivering, facial spasm, such as, winking, touching the beard, rhythmic chewing and so on; 2： rhythmic nodding; 3： forelimb spasm;4： standing accompanied by bilateral forelimb spasm;5： tumbling, losing balance, four limbs spasm. Modeling was successful when seizure intensity reached grade 5. t test was used for the comparison of mean value between two samples. MAIN OUTCOME MEASURES： Comparison of the successful rate of modeling, the times of stimulation to reach intensity of grade 5, the lasting time of seizure of grade 3 of rats in each group. RESULTS： Four rats of alternate-side kindling group dropped out due to infection-induced electrode loss, and 56 rats were involved in the result analysis. The successful rate of unilateral kindling group, bilateral kin- dling group and alternate-side kindling group was 55%（11/20）,100%（16/16）and 100%（20/20）, respective- ly. The stimuli to reach the grade 5 spasm were significantly more in the bilateral kindling group than in the unilateral kindling group [（30.63±3.48）, （19.36±3.47）times, t=8.268, P 〈 0.01], and those were significantly fewer in the alternate-side kindling group than in the unilateral kindling group [（ 10.85±1.98）times, t=-8.744, P 〈 0.01]. The duration of grade 3 spasm was significantly longer in the bilateral kindling group than in the unilateral kindling group [（9.75±2.59）, （3.21 ±1.58）days,t=-8.183,P 〈 0.01], Among 20 successful rats of al- ternate-side kindling group, grade 5 spasm was found in the left hippocampi of 11 rats, but grade 3 spasm in their right hippocampi; Grade 5 spasm was found in the right hippocampi of the other 9 rats, grade 4 spasm in the left hippocampus of 1 rat and grade 3 of 8 rats. CONCLUSION ： The speed of establishing epilepsy seizure model by alternate-side kindling is faster than that by unilateral kindling, while that by bilateral kindling is slower than that by unilateral kindling. The successful rate is very high to establish complex partial epilepsy with alternate-side or bilateral kindling. Epilepsy seizure established by alternate-side kindling has antagonistic effect of kindling and the seizure duration of grade 3 spasm is prolonged.

A follow-up study on newer anti-epileptic drugs as add-on and monotherapy for partial epilepsy in China

Background Recently,new anti-epileptic drugs （AEDs） have been more frequently selected to treat epilepsy.In the present study,we evaluated the dynamic changes of efficacy and safety of three newer AEDs for treating partial epilepsy in China.Methods Patients were collected sequentially and were divided into three groups which accepted oxcarbazepine （OXC）,lamotrigine （LTG） or topiramate （TPM） therapy.Each group included monotherapy and add-on therapy subgroups.We followed all patients for one year and recorded the indexes of efficacy and safety in detail.Results A total of 909 patients finished the follow-up observation.No significant difference was found in proportion of patients with 〉 or =50% reduction,〉 or =75% reduction and 100% seizure reduction in the LTG and OXC groups between the first and the second six months.In the TPM group there was a statistical difference between the first and the second six months in proportion of patients with 〉 or =50% reduction （P=-0.002）,〉 or =75% reduction （P 〈0.0001） and 100% seizure reduction （P=0.009） in the monotherapy subgroup,and about 〉 or =75% reduction and 100% seizure reduction in the add-on therapy subgroup （P 〈0.0001）.The efficacy between the add-on and monotherapy subgroups showed a statistical difference.The safety of the three newer AEDs was good.Conclusions The three newer AEDs all showed good efficacy and tolerability for partial epilepsy.And the efficacy can be maintained for at least one year.

Stochastic fluctuations of permittivity coupling regulate seizure dynamics in partial epilepsy

Partial epilepsy is characterized by recurrent seizures that arise from a localized pathological brain region. During the onset of partial epilepsy, the seizure evolution commonly exhibits typical timescale separation phenomenon. This timescale separation behavior can be mimicked by a paradigmatic model termed as Epileptor, which consists of coupled fast-slow neural populations via a permittivity variable. By incorporating permittivity noise into the Epileptor model, we show here that stochastic fluctuations of permittivity coupling participate in the modulation of seizure dynamics in partial epilepsy. In particular, introducing a certain level of permittivity noise can make the model produce more comparable seizure-like events that capture the temporal variability in realistic partial seizures. Furthermore, we observe that with the help of permittivity noise our stochastic Epileptor model can trigger the seizure dynamics even when it operates in the theoretical nonepileptogenic regime. These findings establish a deep mechanistic understanding on how stochastic fluctuations of permittivity coupling shape the seizure dynamics in partial epilepsy,and provide insightful biological implications.

Neural matrix and its role in preoperative evaluation of partial epilepsy

The network characteristic of the central neural system has been widely accepted as a basic fabric form. However,the matrix characteristics of neural network are still not fully understood. If we ignore the matrix characteristics of the neural networks and just pay close attention to its connection mode,we are likely to fall into the theory of mechanical reductionism. This can lead to a problem in representing consciousness in a disadvantageous situation. It can also be a barrier to further improving the global workspace theory. Incomplete elucidation of the mechanisms of consciousness representation can also affect the assessment of the surgical outcome of partial epilepsy with conscious injury. Therefore,this paper reviews the epistemological development of neuroscience. We will initially describe the matrix characteristics of the neural system and their significance to the information processing mechanism,and further explore the role of neural matrix in identifying cases of partial epilepsy with little effect on the resection of the lesion.

Prospective research on the efficacy and safety of oxcarbazepine as monotherapy and add-on therapy for partial epilepsy

The purpose of our research was to evaluate the efficacy,tolerance,and safety of oxcarbazepine(OXC)as monotherapy and add-on therapy for partial epilepsy.We carried out a prospective clinical follow-up trial at the Epilepsy Center of Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology.Sixty-seven patients with partial epilepsy received OXC therapy.The patients were randomly divided into a monotherapy group and an add-on therapy group.We observed the efficacy and safety in thefirst three months and the following three months respectively,and compared them with each other.There was a significant difference in the decrease of seizure frequency between the two groups(P=0.002).There was a significant difference in the percentage of seizure-free between the monotherapy and the add-on therapy groups in thefirst three months(P=0.02),and there were also statistical differences in the 50%response rate(P=0.017)and the percentage of seizure-free in the following three months(P=0.019).No difference was found in the 50%response rate,the 75%response rate,and the percentage of seizure-free between thefirst three months and the following three months in the whole group and the two subgroups(P>0.05).The incidence rate of side effects due to the therapy was 19.40%(13 of 67).The side effects were mainly found in thefirst three months.It is concluded that OXC is thefirst-line anti-epileptic drug(AED)for partial seizures,and could be used as the monotherapy and add-on therapy for newly diagnosed patients and patients that failed to tolerate or benefit from other AEDs.

Long-term Effectiveness of Antiepileptic Drug Monotherapy in Partial Epileptic Patients： A 7-year Study in an Epilepsy Center in China

Background： It is important to choose an appropriate antiepileptic drug （AED） to manage partial epilepsy. Traditional AEDs, such as carbamazepine （CBZ） and valproate （VPA）, have been proven to have good therapeutic effects. However, in recent years, a variety of new AEDs have increasingly been used as first-line treatments for partial epilepsy. As the studies regarding the effectiveness of new drugs and comparisons between new AEDs and traditional AEDs are few, it is determined that these are areas in need of further research. Accordingly, this study investigated the long-term effectiveness of six AEDs used as monotherapy in patients with partial epilepsy. Methods： This is a retrospective, long-term observational study. Patients with partial epilepsy who received monotherapy with one of six AEDs, namely, CBZ, VPA, topiramate （TPM）, oxcarbazepine （OXC）, lamotrigine （LTG）, or levetiracetam （LEV）, were identified and followed up from May 2007 to October 2014, and time to first seizure after treatment, 12-month remission rate, retention rate, reasons for treatment discontinuation, and adverse effects were evaluated. Results： A total of 789 patients were enrolled. The median time of follow-up was 56.95 months. CBZ exhibited the best time to first seizure, with a median time to first seizure of 36.06 months （95% confidential interval： 30.64~4.07）. CBZ exhibited the highest 12-month remission rate （85.55%）, which was significantly higher than those of TPM （69.38%, P = 0.006）, LTG （70.79%, P= 0.001）, LEV （72.54%, P = 0.005）, and VPA （73.33%, P = 0.002）. CBZ, OXC, and LEV had the best retention rate, followed by LTG, TPM, and VPA. Overall, adverse effects occurred in 45.87% of patients, and the most common adverse effects were memory problems （8.09%）, rashes （7.76%）, abnormal hepatic function （6.24%）, and drowsiness （6.24%）. Conclusion： This study demonstrated that CBZ, OXC, and LEV are relatively effective in managing tbcal epilepsy as measured by time to first seizure, 12-month remission rate, and retention rate.

Hemodynamic consideration of intracranial aneurysm

We reviewed basic considerations in fluid dynamics of cerebral aneurysms and applied these in surgery on the three most common types: internal carotid-posterior communicating artery,middle cerebral artery,and anterior communicating artery. It was found that aneurysmal initiation and growth do not occur at symmetric bifurcations. As blood flow always obeys the law of inertia,jet flow into the aneurysm will disperse along the wall; assuming the aneurysmal wall strength is even,the shape of the aneurysm becomes round or oval. When neurosurgeons encounter an aneurysm that is not round or oval,the wall may be fragile and requires great care during surgical manipulation.