Correlation between thalamic network abnormity and cognitive function in patients with temporal lobe epilepsy / 中华行为医学与脑科学杂志

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.

Alterations of brain functional complex network in temporal lobe epilepsy patients: a functional magnetic resonance imaging study / 中华神经科杂志

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.

Interhemispheric Functional and Structural Alterations in Unilateral Temporal Lobe Epilepsy / 中国医学影像学杂志

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.

Interhemispheric functional alterations in unilateral temporal lobe epilepsy / 中国神经精神疾病杂志

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.

Correlation between white matter microstructural lesions by diffusion tensor imaging and clinical profiles in patients with temporal lobe epilepsy and hippocampal sclerosis / 实用放射学杂志

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.

The efficiency of expressing human neprilysin by using lentiviral vector transduction in neural stem cells / 中华神经科杂志

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.

Diffusion tensor imaging of the bilateral uncinate fasciculus in patients with temporal lobe epilepsy / 南方医科大学学报

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>Thirty 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.</p><p><b>RESULTS</b>In 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.</p><p><b>CONCLUSIONS</b>FA 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.</p>

Efficacy assessment of sodium valproate in treating 607 patients with epilepsy in rural China / 中华神经科杂志

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.

The attentional networks in patients with temporal lobe epilepsy / 中国神经精神疾病杂志

Objective To investigate the attentional network in patients with temporal lobe epilepsy(TLE) and the disease-related factors. Methods Fity-four patients with TLE and 40 controls were enrolled in our hospital from January 2007 to December 2008.The computerized ANT software was used for evaluating the attentional network efficiency and the clinical date of the patients with TLE were recorded. Logistic regression was used to identify the risk factors of attentional network efficiency. Results The mean reaction time(TLE:688.2±138.1 ms;Control:625.1±100.1 ms, t=2.06, P <0.05)and executive control network efficiency (TLE:155.7±57.0 ms;Control:108.0±33.8 ms, t=4.62, P <0.01) of the TLE group were lower than the healthy control group. The efficiency of alerting network and orienting network between the two groups were no significant difference. Logistic regression analysis showed that the positive epileptiform activity was an independent risk factor of the attentional impairment(95% CI : 1.03～42.33, OR =6.603, P =0.043). Conclusions The ANT demonstrate that patients with TLE may accompany with attentional executive control network efficiency impairment. Epileptiform discharge may cause attentional executive network efficiency impairment.

Diffusion changes in substantia nigra following striatum infarction with diffusion tensor imaging / 中华神经科杂志

Objective To investigate the diffusion changes in ipsilateral substantia nigra after a chronic striatum infarction with diffusion tensor imaging ( DTI ) and its connotation for clinical lecture.Methods Participators underwent a DTI scan and were divided into three groups. The striatum infarction (SI) group consisted of twenty patients with chronic basal ganglia infarction with striatum involved, while the non striatum infarction (NSI) group consisted of another twenty patients with chronic basal ganglia infarctions without striatum involved. The control group consisted of twenty healthy volunteers. Before the DTI scan all patients underwent a clinical evaluation with Modified Rankin Scale (mRS) and Barthol Index,and the four patients of SI group with symptoms like Parkinson disease underwent an additional evaluation with the third subscale of Unified Parkinson' s Disease Rating Scale ( UPDRS Ⅲ ). Results Compared with NSI and control groups, the infarct side substantia nigra MD of SI group increased by 30. 86 percent (t =40.07,P=0.000) and 31.42 percent (t =42. 64,P =0.000). The FA values from the three groups were not different. There were four patients with some symptoms like Parkinson disease in SI group. Compared with those patients without symptom like Parkinson disease in SI group, the infarct side substantia nigra MD of these four patients increased by 22 percent(t = 18.03, P =0. 01 ). Moreover, the infarct side substantia nigra MD of these four patients was correlated with their UPDRS Ⅲ positively ( r = 0. 97, P = 0. 03 ).Conclusions The secondary degeneration in the ipsilateral side substantia nigra after striatum infarction could be detested quantitatively with diffusion tensor imaging. The secondary degeneration in substantia nigra may be responsible for the symptoms like Parkinson disease in striatum infarction patients.

Clinical significance of cerebrospinal fluid neuropeptide Y in epileptic patients with intelligence disturbance / 中国综合临床

Objective To explore the clinical significance of cerebrospinal fluid neuropeptide Y in epileptic patients with intelligence disturbance.Methods The Full Intelligence Quotient (FIQ) of 78 cases of epileptic patients were assessed by WAIS-RC.The subjects were divided into intelligence disturbance group and non-intelligence disturbance group.Their cerebrospinal fluid neuropeptide Y Was tested by using radio immunoassay.Results The content of neuropeptide Y in intelligence disturbance group Was obviously higher than that in non-intelligence disturbance group (P<0.01).Conclusion Intelligence disturbance in epileptic patients is related to the increased Neuropeptide Y.Neuropeptide Y may reflect the intelligence condition in epileptic patients.

Clinical and pathological features of Churge-Strauss syndrome combined leukocytoclastic vasculitis(report of 1 case) / 临床神经病学杂志

Objective To investigate the clinical and pathological features of Churge-Strauss syndrome(CSS) combined leukocytoclastic vasculitis.Methods The clinical data of 1 patient with CSS combined leukocytoclastic vasculitis was analyzed retrospectively.Results The main symptoms of the case were peripheral nerve damage,violation of the skin lesions,gastrointestinal tract,lung,and central nervous system;peripheral blood eosinophil count was high.The pathological examine showed vessel wall and skin organizations had a large number of eosinophils infiltration,small vessel walls,as well as granuloma formation around multiple segmental fibrinoid necrotizing vasculitis.Eventually died of multiple organ failure.Conclusion The clinical manifestations of CSS combined leukocytoclastic vasculitis have vasculitis and peripheral neuropathy mainly;the pathological features are that vessel wall and skin organizations have a large number of inflammatory cells infiltration;the late multi-system are involved,and the prognosis is poor.