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Flavonoids are widely used today in the treatment of ischemic stroke. The therapeutic effects and functions of flavonoids are, therefore, generating more and more interest.
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Objective To investigate the protectve effects and underlying mechanisms of deferroxamine on glutamate-induced injury in cultured hippocampal neurons.Methods Primarily cultured hippocampal neurons from fetal rat were used in a model of glutamate induced neurotoxicity.There were two experimental groups.Neurons were pretreated with deferroxamine before glutamate in the deferroxamine group, and neurons were treated with glutamate only in the control group.The morphological change was examined under microscope.Hoechst 33342 DNA staining method was used to study the ratio of condensed nuclei.The levels of lactate dehydrogenase (LDH), malonaldehyde (MDA) and hydroxyl radical were determined using biochemistry.The change in calcium signal was detected using microfluorescent technique.Results The neurons pretreated by deferroxamine had intact morphology with the ratio of condensed nuclei at 14% ± 6% compared to 58% ± 6% (t= 8.98, P <0.01 ) in the control group.LDH level was (36.42 ± 8.99) U/L in the deferroxamine group and was (68.06 ± 11.26) U/L in the control group ( t =3.25,P<0.05).The respective levels of hydroxyl radical were (34.21 ±4.23) U/L and (47.06 ±8.79) U/L (t = 3.11, P <0.05 ).The respective levels of MDA were (12.26 ± 2.78 ) nmol/mg and (28.86±5.19) nmol/mg(t =4.88,P<0.01).Conclusion Deferroxamine can protect neurons from glutamate induced damage.The mechanisms include an inhibition of Ca2+ overload and reduction in the levels of MDA and hydroxyl radicals.
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Objective To investigate the effects of tissue kallikrein on expressions of bradykinin, bradykinin Bl receptor (B1R) and bradykinin B2 receptor (B2R) in ischemic brain tissue following cerebral ischemia-reperfusion in rats. Methods Fifty-four SD rats were randomly divided into three groups: sham operation, normal saline (NS) (2 ml · kg-1 · d-1, for 3 days), and TK (IK 175 × 10-3 U· kg-1 · d-1,for3 days) groups (n = 18 in each group). After three days,the neurological deficit score and the measurement of cerebral infarct volume were performed,The concentration of bradykinin in the ischemic region was detected by the enzyme- linked imrnunosorbent assay (ELBA).reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the mRNA and protein expressions of BlR, B2R in ischemic brain tissue, respectively. Results Compared with the NS group, the neurological deficit (6.17 ± 1. 17 vs. 8. 17 ± 1.33; t =2.000, P =0- 004) and the cerebral infarct volume (29. 67% ±3. 78% vs. 37. 50% ± 6. 72% ;t =0.078, P =0.005) in the TK group were reduced significantly; the concentration of bradykinin in ischemic brain tissue in the TK group was increased significantly (9.25 ± 1. 13 vs. 15.53 ± 1.68, t =6.283, P =0. 000); the expression of B2R mRNA was up regulated significantly (1. 21 ±0. 17 υs. 2.15 ±0.20; t =0.943,P =0- 000), but the up-regulation of the B2R mRNA expression was not obvious (0.51 ±0.05 υs. 0.57 ±0.06; t =0.058, P =0. 141); the expression of B2R protein in ischemic brain tissue was up-regulated significantly (1. 15 ±0. 16 vs. 1. 88 ± 0.21, t =0. 737, P =0. 000), but the up-regulation of BlR was not obvious (0. 50 ±0.04 vs. 0.53 ±0.05, t = 1.326, P =0. 214). Conclusions TK has protective effect on cerebral ischemia-reperfusion in rats. It may increase the bradykinin concentration in ischemic brain tissue, and up-regulate B2R expression, but it has little effect on Bl R expression.It is speculated that B2R may play a major role in TK protecting ischemic brain tissue.
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Objective To investigate the expression of CD40,CD40L and MMP9 in carotid atherosclerotic plaques and evaluate their roles in carotid atherosclerotic plaque stability.Methods Carotid atherosclerotic plaques were isolated in carotid eversion endarterectomy (GEE) in 37 patients with high-grade stenosis (>70%) including 20 stroke (A group) and 17 non-stroke patients (B group).The control group included samples of normal carotid artery from 11 normal individuals,The RNA expression levels of CD40,CD40 L and MMP9 in all A,B and control groups were quantitatively detected by real-time quantification polymerase chain reaction (PCR) and the protein expression levels were detected by Western blotting analysis.The expression and distribution of CD40,CD40L and MMP9 in carotid atherosclerotic plaques were detected by immunohistochemistry staining.Then correlations between CD40-CD40L and MMP9 were statistically analyzed.Results The relative CD40 mRNA level in high-grade stenosis of A group,B group and normal control were 2.41±0.43,1.03±0.38 and 0.31±0.12,respectively,and MMP9 mRNA 6.88±1.57,1.90±0.44 and 0.39±0.12,respectively.The levels of CD40 and MMP9 mRNA in A group were significantly higher than those in B group (P=0.000),the levels of CD40 and MMP9 in B group were significantly higher than those in controls (P=0.000).There was a linear correlation between CD40 and MMP9 mRNA (r=0.929,P=0.000).However,there were no significantly difference in mRNA levels of CD40L between carotid atherosclerosis and controls.The protein expression levels of CD40,CD40L and MMP9 in A group were significantly higher than those in B group (FCD40=104.100,P=0.000;FCD40L=129.932,P=0.000;FMMP9=13.565,P=0.021) and B group higher than normal controls (FCD40=115.848,P = 0.000;FCD40L= 30.482,P=0.005;FMMP9=35.557,P=0.004).The areas of positive staining of CD40,CD40L and MMP9 in immunochemistry study in A group were significantly higher than those in B group and B group was significantly higher than controls.There were linear correlations between positive staining areas Of CD40 and CD40L,CD40 and MMP9,CD40L and MMP9 (r=0.963,0.959,0.929,P=0.000).Expressions of CD40,CD40L and MMP9 were significantly higher in the shoulder areas of the atherosclerotic plaques than in other areas.Conclusions The CD40-CD40L has an important role in the formation of carotid atherosclerosis and plaque instability,probably by up-regulating MMP9.The expression of CD40L may be regulated by post-transcriptional modification to exert biological effects.
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Objective To investigate the possible effects and underlying mechanisms of desferroxamine (DFO) preconditioning against hypoxia in neurons. Methods Cortical neurons were cultured in DFO under ischemia condition of oxygen-glucose deprivation (OGD). Cell viability was determined by cell counting kit-8 (CCK-8) method; apoptotic cell ratio was examined with Hoechst 33342 staining; the morphological change was observed. Middle cerebral artery was occluded with or without DFO administration to establish the cerebral ischemia rat model. Infarct sizes were examined by TIC staining, and the neurological severity score was evaluated. Meanwhile immunofluorescent staining was employed to detect the protein synthesis of hypoxia inducible factor-1 (HIF-1) and erythropoietin (EPO), RT-PCR was performed to detect the mRNA expression of HIF-1 and EPO as well Results Neuronal viability kept in 49% (OGD group was 25%, t =8. 544, P<0. 05), the rate of apoptosis was 38% (OGD group was 30%, t = 4. 409, P <0.05 ) after administration of DFO (post-DFO) , the morphology of neurons improved. In the model of focal cerebral ischenfia of 30 mg/kg group, neurological severity score was reduced, the percentage of brain infarct decreased 8.5% (t=4.649, P<0.05) 3 days post-DFO(vs control). In the 100 mg/kg group, neurological severity score was 7.44 ±0.39 (t=2.903, P<0.05 ) ,5.60±0.47 (t=10.143, P < 0.01 ) ,6.97 ±0.73 (t=3.142, P<0.05 ), the percentage of brain infarct decreased 12. 0% (t=5.056, P<0.05), 32.3% (t =10.993, P<0.01), 10.6% (t =4.385, P<0.05)2,3 and7 days post-DFO(vs control), respectively. Immunofluorescent staining found synthesis of HIF-1α and EPO in cultured cortex neurons after DFO pretreated; HIF-1α and EPO were upregulated in the neurons of rat brain after DFO pretreated. The mRNA of HIF-1α and EPO upregulated in vivo and in vitro. Conclusion DFO preconditioning can protect the brain against ischemic damage, which is related to the protective effect on neurons. The mechanism of DFO preconditioning may be involved in the expression of HIF-1α and EPO in vivo and in vitro.
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Objective To investigate the efficacy of hyperbaric oxygen combined with donepezil in the treat-ment of patients with vascular dementia(VD). Methods Sixty-four patients with VD were randomly divided into a control group(donepezil group,n=32)and a treatment group(hyperbaric oxygen combined with donepezil,n=32).The course of treatment was 12 weeks.All patients were tested using the Mini-Mental State Examination(MMSE)and Hasegawa's dementia scale(HDS)before and after treatment. Results After 12 weeks of treatment,the MMSE scores and HDS scores of patients increased significantly in both the control and treatment groups.There were signifi-cant differences between the control and treatment groups in terms of MMSE and HDS scores.Conclusion Hyperbar-ic oxygen combined with donepezil could significantly improve cognition in VD patients.
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The article describes the molecular structure and biological characteristics of thrombin and thrombin receptor.It manly discusses thrombin caused the mechanisms of cerebral edema formation after intracerebral hemorrhage by prormoting cell inflammtory reaction,neuron apoptosis and injurying blood-brain barrier.
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Objective To explore contents of amino acid neurotransmitters and expression of GABAAreceptor subunits'mRNA in subareas of basal ganglia in unilateral rat model of Parkinson's disease (PD).Methods The rat model of PD was established through right unilateral intranigral microinjection of 6-hydroxydopamine(6-OHDA)in this study.Thawed samples were taken form neostriatum(Str).globus pallidus internus(Gpi),globus pallidus externum(Gpe)and subthalamic nucleus(STN).then contents of amino acid neurotransmitters were analyzed by established high performance liquid chromatography (HPLC)-electrochemical detection methods.The subunits α1,α2,β2/3 and γ2 of GABAA receptor in Str,Gpi,Gpe and STN wre examined with Northern Enzyme linked immunosorbent assay(ELISA).Results The content of GABA in Str,Gpi,Gpe and STN of diseased side were significantly increased as compared with undiseasedside.The level of glutamic acid(Glu)in Str,Gpe and STN and contents of aspartic acid (Asp)and glycine(Gly)in STN of the diseased side were significantly increased.In Str.there was a significant decrease of mRNA expression either in the subunit α1(105.3±24.5)or in the subunit β2/3(113.7 ±15.3)of GABAA receptor in the diseased side as compared with the undiseased 8ide(186.7 ±37.2,157.4±32.4,t=5.16,3.45;P<0.01).In Gpi,there was a significant increase of mRNA expression in the subunit α1(P<0.05)and α2,β2/3(P<0.01)of GABAA receptor in lesion side.In Gpe,there was a significant decrease of mRNA expression in the subunit α2(179.1±26.8)andβ2/3(154.7 ±37.8)of GABAA receptor in the diseased side(219.3.±19.7,231.1±55.8,t=3.42,3.21:P<0.01).In STN of right unilateral 6-0HDA lesion rat.there was a significant decrease of mRNA expression both in the subunitα1,α2 and β2/3(P<0.01)of GABAA receptor and in the subunit γ2(P<0.05)of GABAA receptor in the diseased side.Conclusions Changes of amino acid neurotransmitter contents and GABAA receptor subunits'mRNA expressional level in subareas of basal ganglia may be involved in PD.
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Objective The study is designed to evaluate the difference in identification for depression and clinical effectiveness of its treatment between psychiatrists and non-psychiatric Dhysieians at out-patient departments of general hospitals and to analyze its related factors.Methods Totally,680 patients who visited psychiatric clinics in nine general hospitals of Shanghai at first time were screened by psychiatrists using Composite International Diagnostic Interview(CIDI)for depression and the screening resuhs were compared to the diagnosis made by non-psychiatric physicians as goal-keepers there.Altogether 297 patients with depression were recruited and assessed using Hamilton Depression Rating Scale(HAMD)and Hamilton Anxiety Rating Scale(HAMA).A self-made questionnaire for basic information was used to assess the ability for identification of depression in non-psychiatric physicians of general hospitals.Results Psychiatrists identified depression correctly in 337 of 680 patients who visited psychiatric clinics in general hospitals at their first visit,but non-psychiatric physicians only identified 216 patients,with statistically significant difference(χ2=30.73,P=0.000).A consistent agreement on depression diagnosis between the findings by psychiatrists and by CIDI was reached with Kappa of 0.774,but Kappa for that between the findings by non-psychiatric physicians and CIDI was 0.439.Effectiveness of treatment for depression by psychiatrists was better than that by non-psychiatric physicians,with higher total score and scores for each item of HAMD four,eight and 12 weeks after treatment,respectively(P<0.05 or P<0.01).Length of professional work of non-psychiatric physicians and annual time for professional training in management of mental disorders associated with their ability of identification for depression(P<0.05).Conclusion Ability of non-psychiatric physicians to identify alQd cope with depression in the psychiatric department of general hospitals was insufficient,suggesting that more importance should be attached to the management of service quality at psychiatric department of general hospitals.
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@#Objective To investigate the difference of endothelial cell (EC) in ultrastructure,markers and permeability between blood-brain barrier (BBB) and blood-nerve barrier (BNB).MethodsThe rat brain cortex and sciatic nerve were removed.Ultrastructure of endothelial cell was observed with electron microscopy.Employing immunohistochemical (IHC)staining,the relative distribution was determined for the OX-26,endothelial barrier antigen (EBA)and extravasated fibrinogen around microvessels.ResultsMicrovessels both in BBB and in BNB did share the same tight junctions.However,BNB had a significantly larger number of vesicles than that of BBB.Microvessels in BNB did not express the OX-26 and EBA,but staining weakly positive for fibrinogen,while microvessels in BBB showed strong positive for OX-26 and EBA,perivascular staining of fibrinogen had not been seen.ConclusionTight junctions were present in both BBB and BNB endothelial cell,but there was a significant difference between them in the number of the pinocytotic vesicles,markers expression and permeability.
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<p><b>OBJECTIVE</b>To observe trinucleotide repeat number, (CTG)n in the 3'-untranslated region of the myotonic protein kinase (MTPK) gene in a clinically suspected woman with myotonic dystrophy (DM) family history and her abortus, in order to confirm the necessity of exerting antenatal examination in patients or suspected individuals with DM family history.</p><p><b>METHODS</b>Long Expand Template polymerase chain reaction (PCR) system was used to analyze CTG trinucleotide repeat numbers located in the 3' untranslated region of MTPK on chromosome 19q13.2-3 in both peripheral white cells and muscles of the suspected mother and the other two DM patients in the family. The tissues of her abortus and blood of a health woman were detected, too.</p><p><b>RESULTS</b>CTG repeats in both peripheral white cells and muscles of the suspected mother and the tissue of abortus were higher than normal range of CTG repeat number. There is no significant difference between blood and muscle samples. High CTG repeats were detected in blood and muscles of the typical DM members in the family, but in the blood sample of control, CTG repeats is normal.</p><p><b>CONCLUSION</b>CTG trinucleotide analyses and antenatal examination should be done in pregnant with a DM family history, in order to reduce the birth rate of DM offspring.</p>
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Adulto , Feminino , Humanos , DNA , Feto , Metabolismo , Distrofia Miotônica , Diagnóstico , Genética , Diagnóstico Pré-Natal , Repetições de TrinucleotídeosRESUMO
AIM: To investigate the clinical effect and side-effects of paroxetine in the treatment of generalized anxiety (GA). METHODS: Ninety patients who met Chinese classification and diagnostic criteria of mental disorders, 2nd Rev Ed (CCMD-2-R) criteria for GA were randomly divided into paroxetine group of 30 patients (M 12, F 18; age 40 a±s 13 a) which was treated with paroxetine 20-40 mg, po, qd or bid, benzodiazepines group of 30 patients (M 13, F 17; age 37 a±13 a) among them, 16 patients were treated with alprazolam 0.4-0.8 mg, po, bid or tid, 14 patients were treated with clonazepam 1-2 mg, po, bid or tid and placebo group of 30 patients (M 11, F 19; age 37 a±13 a) which was treated with placebo 1 tablet, tid for 12 wk. Effects were evaluated with Hamailton anxiety scale (HAMA), self-rating anxiety scale (SAS), clinical global impression scales (CGI) and treatment emergent symptoms scale (TESS), before and after the wk 2,4,8,12 of treatment. RESULTS: The excellent response rates of paroxetine group and benzodiazepines group were 90 % and 50 % (P<0.01). The side-effects of paroxetine group were dry mouth, constipation, nausea, but those were less than that of benzodiazepines group. CONCLUSION: The study suggests that paroxetine is an effective drug for the long treatment of GA and the side-effect is less.
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AIM: To compare the effects between topiramate and slow-release sodium valproate in treating refractory epilepsy. METHODS: Topiramate group of 39 patients (M 21, F 18; age 28 a± s 20 a) was compared with sodium valproate group of 41 patients (M 22, F 19; age 27 a±17 a) in antiepileptic effect of refractory epilepsy. Adult's and children's dosages of topiramate were increased gradually about 200 mg*d-1 and 4 mg*kg*d-1 respectively during about 2 mo, po, bid, for 6 mo as a course. Adult's dosage of slow-release sodium valproate was 0.5-1 g*d-1, and children's was increased gradually to total dosage: 15-30 mg*kg*d-1, po, qd or bid (morning or morning and noon), for 6 mo as a course. Effects were analysed between these two drugs after treatment 4 and 6 mo. RESULTS: Simple and complex partial seizures with or without secondary generalized seizure, in topiramate group were much more improved than these in sodium valproate group 6 mo after treatment. Four patients of topiramate group appeared temporary adverse reactions of central nervous system, such as tiredness, sleepiness and distraction, but one patient of sodium valproate group had severer decreased function of bone marrow. CONCLUSION: Topiramate is one of effective antiepileptic drugs and superior to slow-release sodium valproate. There are the apparent absence of any effects of topiramate on the bone marrow and on indexes of liver and kidney.
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0.05). Conclusion In our samples, this two polymorphisms in A2M might play similar roles in the susceptibilities to PD and AD.
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Objective:To study the effect of Mg 2+ on glutamate and energy metabolites during focal cerebral ischemia and reperfusion in rats. Methods: Twelve male Wistar rats were divided into 2 groups(n=6):magnesium sulfate(100 mg/kg, i.p.) group and saline group.Cerebral ischemia was produced by occlusion of middle cerebral artery with a nylon thread for 60 min and followed by 60 min reperfusion.Microdialysis probes were stereotaxically implanted into the cortex; dialysates were collected every 15 min to determine the concentrations of glucose, lactic acid and glutamate. Results: There was a dynamic decrease of glucose and an increase of lactic acid and glutamate during ischemia and reperfusion in saline group.Glucose decreased slightly in magnesium sulfate group during ischemia and recovered to normal rapidly during reperfusion. The lactic acid levels in magnesium sulfate group were lower than that in saline group during early stage of ischemia(0-15 min) and reperfusion.There were significant attenuation in the elevation of glutamate during ischemia and reperfusion when magnesium sulfate was administered and recovered to normal after 30 min of reperfusion. Conclusion: The preservation of cellular energy metabolism,the decrease of lactacidosis and attenuation of glutamate level during ischemia and reperfusion may contribute to the neuroprotective effects of Mg 2+ .
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Objective To study the clinical features of hyperkalemic periodic paralysis (hyperKPP) and the relationship with SCN4A gene in a Chinese family Methods The clinical features of 7 patients in a Chinese family with hyperKPP were summarized All 24 exons of SCN4A gene were screened with denaturing high performance liquid chromatography (DHPLC) technology, and then sequence analysis was performed on those with abnormal elution peak Results This family showed typical clinical features of hyperKPP but without myotonia Three mutations were found in exon 13, 23 and 24 respectively Linkage analysis and direct sequencing showed the mutation in exon 24 was a synonymous mutation The mutation in exon 23 was a missense mutation, but proved to be a benign polimophism; the mutation in exon 13 was proved leading to the best known amino acid exchange Thr704Met Conclusion SCN4A gene should be related to hyperKPP, and Thr704Met be responsible for hyperKPP in this Chinese family
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Objective To study the risk factors of type 2 diabetes mellitus patients complicated with cerebral infarction.Methods 32 type 2 diabetes mellitus patients complicated with cerebral infarction(group A) and 30 type 2 diabetes mellitus patients (group B) were enrolled in the study. The living habit, history, blood lipids, blood glucose, body mass index and height were investigated, also common carotid artery intimal thickness (CCA-IMT) and plaque incidence rate were measured by two-dimensional color Doppler ultrasound, and the relationship between them was evaluated.Results There were significant differences between two groups in age, duration of smoking, course of diabetes, high density lipoprotein (HDL) and fasting blood glucose (FBG) (all P
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AIM: To study the difference in glucose and lactate levels between brain extracellular fluid (ECF) and plasma in rabbits in the different blood glucose levels. METHODS: Using intracerebral microdialysis technology, brain ECF levels of glucose and lactate were measured in every 10 min under basal conditions and during a hyperglycemia-hypoglycemia clamp study. RESULTS: Under basal condition, brain ECF glucose levels were markedly lower than ambient plasma levels (30% of plasma), whereas ECF lactate levels were substantially higher (165% of plasma). During the hyperglycemia-hypoglycemia clamps, the relationship between plasma and ECF levels of glucose remained similar, but changes in ECF glucose lagged about 30 min. There were no substantially changes in ECF levels of lactate during dynamical study. CONCLUSION: There are striking differences in glucose and lactate levels between brain ECF and plasma. Lactate may involve in the metabolic process of central nervous system.
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Objective To study the effectiveness of Huperzine A,Nimodipine and the combinative utilization to age associated memory impairment(AAMI) and the influence of those to the plasma total antioxidant capacity(TAC) and calcium of platelet.Methods 140 patients with AAMI were randomly divided into 4 groups(35 cases in each group).Huperzine group administrated with Huperzine A 100 ?g thrice a day;Nimodipine group administrated with Nimodipine 30 mg thrice a day;combined group administrated with Huperzine A 100 ?g twice a day and Nimodipine 30 mg thrice a day;control group administrated with Vitamin B6 10 mg thrice a day.All the cases were treated for 6 weeks.Before and after treatment,the memory function were tested by WMS.The levels of plasma TAC and calcium of platelet were also measured at the same time.Results After treatment,the scores of WMS,the levels of plasma TAC and calcium of platelet in Huperzine A group,Nimodipine group and combined group were higher than before treatment and those in control group(all P
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Objective: To study the clinical characteristics of antiepileptic drug discontinuation after seizure remission in patients with tuberous sclerosis (TS)-induced epilepsy. Methods: Of 98 epilepsy patients with TS,15 with seizure remission and subsequent antiepileptic drug discontinuation were followed up. The relapse rates of seizures and the retreatments were observed. The causes of seizure relapse were analyzed. Results :Ten(66. 7%) patients had sustained seizure remissions and 5 (33. 3%) had relapses in 15 patients after a mean follow-up of 5 years. Antiepileptic drugs was restarted in the 5 relapsed cases and were successful in a girl, leaving a total sustained remission rate of 73. 3% (11/15) and an absolute relapse rate of 26. 7% (4/15). The relapse was associated with abnormal electroencephalogram, multiple cerebral lesions and biological changes of puberty. Conclusion:The relapse rate of TS epilepsy is similar to the relapse rate of other epilepsies. Reasonable discontinuation of antiepileptic drugs should be considered in the patients who attained seizure remission.