Objective:To evaluate the clinical efficacy, tolerability and safety of adjunctive perampanel in focal epilepsy patients≥12 years old.Methods:One hundred and nineteen focal epilepsy patients≥12 years old accepted adjunctive perampanel in Department of Neurology, First Affiliated Hospital of Guangxi Medical University from July 2020 to December 2022 were chosen. At 1-3 months, 4-6 months, 7-9 months and 10-12 months after adjunctive perampanel, seizure frequency changes every 28 d, medication retention rate and adverse reactions were recorded to evaluate the clinical efficacy (a reduction in seizure frequency≥50% from baseline was defined as overall valid treatment), tolerability and safety of adjunctive perampanel. According to efficacy results after adjunctive perampanel of 4-6 months (short-term) and 10-12 months (long-term), these patients were divided into valid group and invalid group; and the influencing factors for short-term and long-term efficacy were analyzed.Results:At 1-3, 4-6, 7-9, 10-12 months after adjunctive perampanel, reduction in seizure frequency every 28 d was 66.7% (24.3%, 97.2%), 77.5% (48.6%, 100%), 94.6% (50%, 100%), 100% (70.9%, 100%), enjoying overall valid rate of 60.2% (59/98), 75.0% (7/76), 78.9% (45/57), 86.5% (32/37). The retention rate at 3, 6, 9 and 12 months after adjunctive perampanel was 85.2% (98/115), 67.9% (76/112), 54.3% (57/105), 41.1% (37/90). Adverse reactions were reported in 33 patents (27.7%), mainly with dizziness and secondly with mental symptoms. After short-term and long-term adjunctive perampanel, no significant difference was noted in gender, initial age of adjunctive perampanel, course of disease, etiology, EEG results, imaging results, number and type of combined anti-seizure drugs, or maximum dose of pirampanel between the valid group and invalid group ( P>0.05). Conclusion:Perampanel has good efficacy, tolerability and safety in adolescents and adults≥12 years old with focal epilepsy; no clear influencing factors for pirampanel valid treatment is found so far.

Objective:To investigate the alterations of brain functional network related to disease progression in patients with temporal lobe epilepsy (TLE) and the potential neural mechanism of executive dysfunction.Methods:Nineteen temporal lobe epilepsy patients with a disease course of less than or equal to 5 years (TLE-SD group) and 24 temporal lobe epilepsy patients with a disease course of more than 5 years (TLE-LD group) were recruited from the Epilepsy Clinic of the First Affiliated Hospital of Guangxi Medical University from December 2019 to December 2021. At the same time, 21 healthy control individuals (healthy control group) were recruited from the society and matched with gender, age, and education level. All subjects were evaluated demographic and clinical data, and performed resting state functional magnetic resonance imaging (rs-fMRI) and attention network test (ANT). The topological properties of functional brain network of 3 groups of subjects were calculated using graph theory, and then the hubs were determined. Then the inter-group comparison of hubs properties was carried out, and the correlation analysis with executive control function was performed.Results:The distribution pattern of hub nodes in TLE-SD patients was changed. Compared with the TLE-LD and healthy control groups, the TLE-SD group significantly increased the nodal degree values in brain regions such as the ventrolateral area of the left middle frontal gyrus, the left anterior central gyrus (upper limb area), the cephalic and caudal areas of the left parietal lobule, as well as the inner parietal lobe area, the caudal side of the right parietal lobule, and the right lateral occipital cortex. The nodal values of the brain areas such as the lateral and parietal inner area, the caudal side of the right upper upper lobule, and the right lateral occipital cortex were significantly increased. TLE-SD patients had a significant increase in the middle of the right upper frontal gyrus and the head of the left upper upper lobule. The node efficiency was significantly lower than that of TLE-LD patients, and the node efficiency in the middle of the right upper frontal gyrus was significantly lower than that of the healthy control group. The node network attributes of the left upper lobe were positively correlated with the execution control efficiency, and negatively correlated with the orientation efficiency. No significant difference was detected between TLE-LD patients and healthy controls.Conclusions:In TLE patients, the hubs in the middle of the right superior frontal gyrus were first damaged, and new hubs appeared in the dorsal attention network, the left anterior central gyrus and the right occipital lobe and were overloaded. With the progression of the disease, hubs tended to be redistributed to normality. The left superior parietal lobule may play an important role in the impairment of executive control function in TLE patients.

Objective:To explore the correlation and mechanism between thalamic network abnormality and cognitive decline in patients with temporal lobe epilepsy (TLE).Methods:A total of 53 patients with unilateral TLE were consecutively enrolled through the epilepsy clinic of the First Affiliated Hospital of Guangxi Medical University from December 2018 to February 2020. During the same recruitment interval, 37 health controls(HC) with matching demographic characteristic were recruited. All subjects were received the Montreal cognitive assessment(MoCA) test and multimodal MRI scanning. Voxel-based morphometry method was used to study the changes of thalamic gray matter volume in patients with unilateral TLE. The structural covariance network and functional connectivity network based on seed points were used to analyze the changes of thalamic network in TLE patients. In addition, the correlations among abnormal thalamic structure, thalamic network and cognitive function score were analyzed. SPSS 22.0 software was used for statistical analysis. Independent sample t-test and Mann Whitney U test were used for inter group comparison. In order to explore the relationship between thalamus and thalamic network and cognitive performance in TLE patients, thalamic volume and gray matter volume and functional connection value of brain areas with abnormal synergistic changes were extracted and correlated with MoCA score. Results:The total score of MoCA in TLE patients (27.0(25.0, 29.0)) was significantly decreased compared with HC (29.0(28.0, 30.0))( Z=-4.601, P<0.001). Whole brain gray matter volume analysis showed that compared with HCTLE patients showed significant volume reduction in left cerebellum, right temporal pole, right fusiform gyrus, straight gyrus, bilateral middle temporal gyrus, thalamus, medial and paracingulate gyrus (GRF adjusted, voxel-level P<0.001 and cluster-level P<0.05). The thalamus-associated structural covariance network analysis revealed that compared with healthy controls, TLE patients exhibited decreased connectivity in right fusiform gyrus (MNI: x=28.5, y=-15.0, z=-34.5), left insula (MNI: x=-33.0, y=-18.0, z=-1.5), right middle temporal gyrus (MNI: x=55.5, y=-51.0, z=9.0), left complementary motor area (MNI: x=-10.5, y=1.5, z=57.0) and right posterior central gyrus (MNI: x=31.5, y=-33.0, z=51.0) ( P<0.001, cluster > 100). The thalamus-associated functional connectivity network analysis revealed that TLE patients exhibited decreased connectivity in left insula (MNI: x=-38, y=-7, z=-7), left lingual gyrus (MNI: x=-6, y=-81, z=-12), right lingual gyrus (MNI: x=15, y=-105, z=0) and left triangular inferior frontal gyrus (MNI: x=-39, y=36, z=-6) (GRF correction, voxel-level P<0.001 and cluster-level P<0.05). Volume of left insula which had decreased structural connectivity with thalamus were positively correlated with the MoCA score in TLE patients( r=0.279, P=0.043). Volume of left complementary motor area which had decreased structural connectivity with thalamus was positively correalated with the MoCA score and language score in TLE patients( r=0.323, P=0.018; r=0.334, P=0.015). Volume of left lingual gyrus which had decreased functional connectivity with thalamus was negatively correalated with the memory score in TLE patients ( r=-0.331, P=0.016). Conclusion:Thalamic volume, thalamic structural covariant network and functional connection network are changed in TLE patients. The abnormality of thalamic network is associated with cognitive performance in TLE patients, which may be the neural mechanism of thalamus participating in the cognitive impairment of TLE patients.

Objective:To investigate longitudinal alterations of brain functional complex network by rest-stage functional magnetic resonance imaging (rs-fMRI) and graph theory in patients with temporal lobe epilepsy (TLE).Methods:A total of 13 TLE patients (TLE baseline group) and 13 healthy controls (healthy control group) were enrolled to observe alterations in complex functional network. The subjects were recruited in the Epilepsy Clinic of the First Affiliated Hospital of Guangxi Medical University from January 2015 to April 2018. For longitudinal analysis, TLE patients were followed-up for three years (TLE follow-up group). All participants underwent rs-fMRI and attention network test (ANT). Finally, a cross-sectional study was conducted by comparing the area under the curve (AUC) between the TLE baseline group and the healthy control group, and a longitudinal analysis was conducted by comparing the AUC between the TLE baseline group and the TLE follow-up group.Results:Cross-sectional analysis showed that the alerting function of the TLE baseline group was declined [The tonic alertness reaction time, phasic alertness reaction time and alertness were (727.00±126.07) ms, (692.85±132.37) ms, and (34.15±23.50) ms, respectively in the TLE baseline group, which were (639.87±81.41) ms, (589.50±80.59) ms, and (50.37±14.71) ms, respectively in the healthy control group, with statistically significant differences between the two groups ( t=-2.09, P=0.047; t=-2.41, P=0.024; t=2.11, P=0.045)]; the TLE baseline group demonstrated decreased clustering coefficient in left supplementary motor area (SMA.L)(AUC was 0.162±0.044, 0.189±0.021, respectively; t=-4.14, P=4.67E-04) and left inferior parietal supramarginal angular gyri (AUC was 0.178±0.021, 0.202±0.026, respectively; t=-2.42, P=0.024), and decreased nodal local efficiency in SMA.L (AUC was 0.239±0.045, 0.260±0.022, respectively; t=-4.13, P=4.77E-04) and left inferior temporal gyrus (AUC was 0.233±0.036, 0.253±0.027, respectively; t=-3.03, P=0.006) compared with the healthy control group, and both SMA.L clustering coefficient and nodal local efficiency were positively correlated with TLE patients′ duration ( r=0.652, P<0.05; r=0.611, P<0.05). Longitudinal analysis showed that the global network efficiency of the TLE follow-up group decreased (The AUC of the TLE baseline group was 0.182±0.008, and the AUC of the TLE follow-up group was 0.169±0.015, t=2.73, P=0.017), which was negatively correlated with alertness ( r=-0.617, P<0.05). Conclusions:TLE patients show impairment of topological properties of brain functional network. SMA.L is a significant node in network. Alterations of brain functional network associate with duration. The decline in global network efficiency may be a characteristic of progressive deficit to TLE.

Objectives To investigate the alterations of homotopic connectivity in unilateral temporal lobe epilepsy (TLE). Methods Resting-state functional MR imaging data were acquired from patients with unilateral temporal lobe epi?lepsy (n=43) [21 left temporal lobe epilepsy(LTLE) and 22 right temporal lobe epilepsy(RTLE)] and normal controls (NC) (n=20). The functional connectivity between any pair of symmetric interhemispheric voxels (i.e., functional homotopy) was measured by voxel-mirrored homotopic connectivity (VMHC). Results Compared with NC group, the LTLE patients showed decreased functional connectivity in the bilateral supplementary motor areas(t=-3.35), middle temporal gyri (t=-3.50), medial frontal gyri(t=-3.20)and inferior parietal lobules(t=-3.66), and increased interhemispheric func?tional connectivity in the bilateral angular gyri(t= 3.03), occipital gyri(t= 4.25) and superior parietal gyri(t= 3.62). Compared with control subjects, RTLE patients exhibited decreased functional connectivity in the bilateral middle tempo?ral gyri(t=-4.26), precentral gyri(t=-3.29), as well as increased interhemispheric functional connectivity between bi?lateral inferior occipital gyri(t=3.22),parahippocampa gyri(t=3.32), cerebellum(t=3.50). Conclusions There are al?terations of the functional synchronization and coordination in the two hemispheres in unilateral TLE patients.

Purpose To investigate the alterations of homotopic functional connectivity and interhemispheric structural connectivity in patients with unilateral temporal lobe epilepsy (unilateral TLE).Materials and Methods Resting-state functional MR imaging data were acquired from patients in the first affliated hospital of Guang Zhou Medical University who were enrolled from Oct.2013 to Oct.2015 with unilateral temporal lobe epilepsy (n=43) [21 left TLE(LTLE) and 22 right TLE(RTLE)] and normal controls (NC) (n=24).We mainly concerned about the functional connectivity between any pair of symmetric interhemispheric voxels which were measured by voxel-mirrored homotopic connectivity (VMHC).Structural magnetic resonance images were acquired in 10 LTLE patients,16 RTLE patients and 20 NCs.Homotopic regions showing abnormal functional connectivity in patients were adopted as regions of interest for DTI.The FA values were compared between groups.Two-sample t test were used.Results Compared with NC group,the LTLE patients showed increased interhemispheric functional connectivity among the bilateral angular gyri,occipital gyri and superior parietal gyri,and decreased functional connectivity between the bilateral supplementary motor areas,middle temporal gyri,medial frontal gyri and inferior parietal lobules.Compared with control subjects,RTLE patients exhibited increased interhemispheric functional connectivity among bilateral inferior occipital gyri,parahippocampa gyri,cerebellum,as well as decreased functional connectivity among the bilateral middle temporal gyri,precentral gyri and inferi or frontalgyri.Statistical results indicated that the FA value of the commissural fiber bundles connecting the bilateral hippocampal gyri was smaller in RTLE patients than NC patients (t=10.55,P＜0.01).The FA value of the association fibers connecting the bilateral hippocampal gyrus had no significant difference between the LTLE group and NC group.Conclusion The increase or decrease of VMHC value in some brain regions in TLE suggested that there were changes in the functional synchronization and coordination in the two hemispheres in patients with unilateral TLE.In the RTLE patients,some brain regions which had abnormal interhemispheric functional connectivity also had structural damage.

Objective Diffusion tensor imaging(DTI)was used to explore the characteristics of white matter (WM)microstruc-ture lesion in patients with temporal lobe epilepsy(TLE)and hippocampal sclerosis(HS).Then we investigated the influence of the age of epilepsy onset and the course on WM changes.Methods DTI data were obtained in 30 TLE patients with HS and 23 age and sex-matched healthy controls.Thirteen patients had left HS (LHS)and seventeen had right HS (RHS).Between-group compari-sons of fractional anisotropy (FA)were carried out by using track-based spatial statistics (TBSS).In addition,FA in regions of in-terest (ROI)where white matter lesions had statistically significant difference was correlated with the age of onset and the course. Results Subjects in the LHS group,as compared to healthy controls,demonstrated these clusters of reduced FA:bilateral corona radiata,the left genu of corpus callosum,the right body and splenium of corpus callosum,the right posterior thalamic radiation,ex-ternal capsule and superior longitudinal fasciculus.White the subjects in the RHS group,the clusters of reduced FA are involving bi-lateral corpus callosum,corona radiata,posterior thalamic radiation,cingulum,superior longitudinal fasciculus,and the right ante-rior limb of internal capsule,the right retrolenticular part of internal capsule and external capsule.In LHS group,the FA of the left genu of corpus callosum was negatively correlated with the course,and the FA of the right anterior corona radiata was positively cor-related with the age of onset.In RHS group,the FA of the bilateral superior corona radiata was positively correlated with the course.Conclusion DTI detects extensive changes in TLE with HS that are not confined to temporal lobe.The age of epilepsy onset in LHS was correlated with the changes of anterior corona radiata,while the course and the WM change were not definitely linked to each other.

Objective To study the transduction efficiency of expressing human neprilysin by using a lentiviral vector (Lenti-NEP) in mouse embryonic neural stem cells (NSC) in vitro.Methods Primary NSC were harvested from C57BL/6J pregnant mouse at embryonic day 11.5 and transducted with LentiNEP.Immunofluorescent stainingand Western blot were performed to detect NEP protein expression in NSC.Degradation of amyloid beta 1-40 (Aβ1-40) by NEP protein transduced with Lenti-NEP in NSC was analyzed using ELISA and HPLC.Results Over 90％ NSC were successfully transduced with Lenti-NEP via observation of fused protein green fluorescent protein under the microscopy.Expressions of NEP transduced with Lenti-NEP in NSC and of the markers of NSC (nestin) and neuron (MAP2).The enzyme activity of 2.5 μg (21.00 ± 2.51) and 1.0 μg (15.00 ± 0.54) NEP on degrading Aβ1-40 was shown to improve significantly compared to 0.5 μg NEP(8.00 ±0.81,t =40.4 and 12.7,respectively,both P ＜0.01).The activity of NEP was inhibited in the presence of 50 μmol/L phosphoramidon (0.5 pg:0.08 ±0.01 ;1.0 μg:0.04 ±0.01 ;2.5 μg:0.05 ±0.01,t =17.2,51.3 and 14.1,respectively,all P ＜0.01).The hydrolytic cleavage on degrading Aβ1-40 by NEP was 11.4％,28.4％ and 93.7％ with incubation for 1 h,4 h and 12 h,respectively.Conclusions Lentiviral vector successfully delivers NEP gene to NSC in vitro.Targeting on NEP and NSC may provide potential therapeutic tool for Alzheimer' s disease.

OBJECTIVETo study the structural integrity and continuity of the bilateral uncinate fasciculus (UF) in patients with temporal lobe epilepsy (TLE) using magnetic resonance diffusion tensor imaging (DTI) and evaluate the impact of structural damage of the UF on the executive function of the patients.

METHODSThirty patients with TLE (14 left, 16 right) and 15 healthy control subjects underwent DTI scanning between January, 2007 and July, 2011, and the left and right UF were analyzed for fractional anisotropy (FA) and fiber mean length.

RESULTSIn the control subjects, the average FA was significantly higher in the left than in the right UF (P<0.01). In patients with left TLE, the average FA of the left UF was significantly lower than that of the control subjects (P<0.01), but the FA of the right UF was comparable with that of the control group (P>0.05). In patients with right TLE, the average FA of the left and right UF was significantly lower than that of the control group (P<0.05 and P<0.01). In patients with unilateral TLE, the FA of their bilateral UF was similar. No significant difference was found in the mean length of UF fiber between these 3 groups.

CONCLUSIONSFA is normally higher in the left UF than in the right UF, but inpatients with TLE, the left FA tends to have a lowered UF regardless of which hemisphere is involved, suggesting an early pathology in the microstructure of the left UF. This finding may help in the investigation of possible reasons for executive function damage in TLE patients.

Objective To observe the efficacy and the side-effects of sodium valproate (VPA) in patients with epilepsy in rural China. Methods Epilepsy patients were selected from rural areas of Tianmen in Hubei province and Tiandong county in Guangxi province according to the inclusion and exclusion criteria.Efficacy evaluation standard depending on the change of seizure frequency compared with the situation prior to entering the treatment group. Among the treated patients, no seizures, seizure reduced ＞ 75%, seizure reduced 50%-75% sums for the total effective rate. Results All 607 patients with epilepsy were treated and followed up, the male were 395 (65. 1% ) female 212 (34. 9% ), and 579 patients were treated for 12 months. Patients with generalized tonic-clonic seizures were 517 (85.2%), absence seizures 20 (3. 3% )and the other types of seizures 70 (11.5% ) including simple partial seizures, tonic, clonic, myoclonic or atonic seizures etc. The completed control of seizures ( without any seizures) during the period after taking 3 months, 6 months, 12 months were 270 (45.5%), 249 (42. 3% ) and 238 (41.1%) respectively. The total effective rates in the three periods were 65.2% , 75.4% and 85.5% respectively. The 58 patients in the total group showed side-effects during the follow-up period, mainly including drowsiness, lethargy,fatigue, dizziness, headache and tremor. Nineteen patients (3. 1% ) quitted the treatment group.Conclusions The VPA is an effective antiepileptic drug and no more severe side-effects. It is the same as Phenobarbital and suitable to be used in rural areas of China.