BACKGROUND Although few studies have reported hyponatremia due to carbamazepine or oxcarbazepine in patients with epilepsy,no study has investigated cases of carbamazepine-or oxcarbazepine-induced hyponatremia or unst...BACKGROUND Although few studies have reported hyponatremia due to carbamazepine or oxcarbazepine in patients with epilepsy,no study has investigated cases of carbamazepine-or oxcarbazepine-induced hyponatremia or unsteady gait in patients with neuropathic pain.Herein,we report a case of oxcarbazepineinduced lower leg weakness in a patient with trigeminal neuralgia and summarize the diagnosis,treatment,and changes of clinical symptoms.CASE SUMMARY A 78-year-old male with a history of lumbar spinal stenosis was admitted to the hospital after he experienced lancinating pain around his right cheek,eyes,and lip,and was diagnosed with trigeminal neuralgia at the right maxillary and mandibular branch.He was prescribed oxcarbazepine(600 mg/d),milnacipran(25 mg/d),and oxycodone/naloxone(20 mg/10 mg/d)for four years.Four years later,the patient experienced symptoms associated with spinal stenosis,including pain in the lower extremities and unsteady gait.His serum sodium level was 127 mmol/L.Assuming oxcarbazepine to be the cause of the hyponatremia,oxcarbazepine administration was put on hold and the patient was switched to topiramate.At subsequent visit,the patient’s serum sodium level had normalized to 143 mmol/L and his unsteady gait had improved.CONCLUSION Oxcarbazepine-induced hyponatremia may cause lower extremity weakness and unsteady gait,which should be differentiated from those caused by spinal stenosis.展开更多
Objective: To investigate the effects of oxcarbazepine on immune function, thyroid function and related factors in epilepsy patients. Method: 90 patients with epilepsy who visited our hospital from January 2015 to May...Objective: To investigate the effects of oxcarbazepine on immune function, thyroid function and related factors in epilepsy patients. Method: 90 patients with epilepsy who visited our hospital from January 2015 to May 2018 were selected as the observation group and 90 healthy volunteers were selected as control group. All patients in the observation group were treated with oxcarbazepine alone. T lymphocyte subsets, IgA, IgG, IgM, T3, T4, FT3, FT4, TSH, hs-CRP and Hcy in observation group were detected before treatment, 3 months after treatment and 6 months after treatment. The results were compared with those of the control group. Results: The levels of CD3+ and CD4+ in the control group were (65.25±9.51)% and (43.29±6.74)% respectively, which were higher than those in the observation group (P<0.05). The levels of CD8+, IgA and IgG in the control group were (22.40±6.41)%, (2.22±0.51) g/L, (9.99±1.28) g/L respectively, which were lower than those in the observation group (P<0.05). The levels of CD3+ and CD4+ in the observation group after 3 months and 6 months of treatment were significantly higher than those before treatment (P<0.05). The levels of CD8+, IgA and IgG in the observation group after 3 months and 6 months of treatment were significantly lower than those before treatment (P<0.05). There was no significant difference in the level of IgM between the observation group and the control group at each time point (P>0.05). The levels of thyroid hormones in the observation group before treatment and 3 months after treatment were not significantly different from those in the control group (P>0.05). The FT4 of the observation group was (14.98±1.03) pmol/L 6 months after treatment, which was significantly lower than that of the control group before treatment and 3 months after treatment (P<0.05). The levels of T3, T4, FT3 and TSH at each time point in the observation group were not significantly different from those in the control group (P>0.05). Before treatment, there was no significant difference in hs-CRP and Hcy levels between the observation group and the control group (P>0.05). The levels of hs-CRP and Hcy in the observation group were (4.82±0.67) mg/L and (13.36±1.51) umol/L respectively after 3 months of treatment. The levels of hs-CRP and Hcy in the observation group after 3 months of treatment were significantly higher than those before treatment and in the control group, and the difference was statistically significant (P<0.05). The levels of hs-CRP and Hcy in the observation group were (4.99±0.47) mg/L and (16.83±1.94) umol/L respectively after 6 months of treatment. The levels of hs-CRP and Hcy in the observation group were significantly higher than those in the control group after 3 months of treatment and before treatment (P<0.05). Conclusion: Oxcarbazepine can effectively improve the immune function of epilepsy patients, but with the prolongation of medication time, it may have adverse effects on thyroid function, hs-CRP and Hcy.展开更多
Objective:To study effect of Oxcarbazepine on serum inflammatory factors, intercellular adhesion molecule 1(ICAM-1) and immune function in epileptic.Methods: Selected 95 patients who were diagnosed as epileptic into t...Objective:To study effect of Oxcarbazepine on serum inflammatory factors, intercellular adhesion molecule 1(ICAM-1) and immune function in epileptic.Methods: Selected 95 patients who were diagnosed as epileptic into the observation group and 95 cases of healthy people as the control group;The observation group was given oral oxcarbazepine, continuous treatment for six months;Measured serum inflammatory factors (IL-2, IL-6, TNF-α) level, ICAM-1 and immune-related indexes: change of periphery T lymphocyte subgroup CD3+, CD4+, CD8+and immnuneglublin (IgG, IgA, IgM) level of the observation group before and after treatment, carried out comparative analysis through comparing with the normal control group.Results:Before treatment, compared with the control group, level of IL-2, IL-6, TNF-α, ICAM-1, CD8+, IgA and IgG in observation group were significantly higher than those in control group. CD3+, CD4+ level were significantly decreased when it compared with the control group. Level of IgM in the observation group was higher than that in the control group, but the difference between two groups was not significant. Before treatment, compared inter-class, level of IL-2, IL-6, TNF-α, ICAM-1, CD8+, IgA and IgG in the observation group were significantly lower, but all of these indexes level were still remarkable higher than the control group. It was statistical significant difference;After treatment, the level of CD3+, CD4+ in the observation group were dramatically increased, but both level were still significantly lower than the control group, the difference was statistically significant;Level of IgM after treatment compared with control group and before treatment respectively was no statistical significant difference.Conclusion: The level of inflammatory factors and ICAM-1 always were abnormal in epileptic and they were always with immune dysfunction. Oxcarbazepine was capable of effectively reducing inflammatory factor and ICAM-1 level and positively regulating immune dysfunction.展开更多
As an anticonvulsant,oxcarbazepine(OXC)has attracted considerable attention for its potential threat to aquatic organisms.Density functional theory has been used to study the mechanisms and kinetics of OXC degradation...As an anticonvulsant,oxcarbazepine(OXC)has attracted considerable attention for its potential threat to aquatic organisms.Density functional theory has been used to study the mechanisms and kinetics of OXC degradation initiated by OH radicals in aqueous environment.A total of fourteen OH-addition pathways were investigated,and the addition to the C8 position of the right benzene ringwas themost vulnerable pathway,resulting in the intermediate IM8.The H-abstraction reactions initiated by OH radicalswere also explored,where the extraction site of the methylene group(C14)on the seven-member carbon heterocyclic ring was found to be the optimal path.The calculations show that the total rate constant of OXC with OH radicals is 9.47×10^(9)(mol/L)^(−1)sec^(−1),and the half-life time is 7.32 s at 298 K with the[·OH]of 10^(−11) mol/L.Moreover,the branch ratio values revealed that OH-addition(89.58%)shows more advantageous than H-abstraction(10.42%).To further understand the potential eco-toxicity of OXC and its transformation products to aquatic organisms,acute toxicity and chronic toxicity were evaluated using ECOSAR software.The toxicity assessment revealed that most degradation products such as OXC-2OH,OXC-4OH,OXC-1O-1OOH,and OXC-1OH’are innoxious to fish and daphnia.Conversely,green algae are more sensitive to these compounds.This study can provide an extensive investigation into the degradation of OXC by OH radicals and enrich the understanding of the aquatic oxidation processes of pharmaceuticals and personal care products(PPCPs).展开更多
Background:To assess efficacy and safety of oxcarbazepine (OXC) oral suspension in pediatric patients aged 2-16 years with partial seizures (PS) and/or generalized tonic-clonic seizures (GTCS) in real-world clinical p...Background:To assess efficacy and safety of oxcarbazepine (OXC) oral suspension in pediatric patients aged 2-16 years with partial seizures (PS) and/or generalized tonic-clonic seizures (GTCS) in real-world clinical practice in China.Methods:This 26-week,single arm,multicenter and observational study recruited patients aged 2-16 years with PS or GTCS suitable for OXC oral suspension treatment.Enrolled patients received OXC oral suspension treatment for 26 weeks.Primary endpoints included mean seizure frequency at the end of the treatment and mean seizure frequency reduction at the end of the treatment vs.baseline.Secondary efficacy-related endpoints and safety parameters were also assessed.Results:Nine hundred and eighty-seven pediatric patients were enrolled and 912 (92.4%) completed the study.The mean seizure frequencies at baseline and the end of week 26 were 13.40±64.92 and 1.62±19.47 times/month,respectively.The mean seizure frequency reduction was 10.03±63.67 times/month and the mean seizure frequency reduction percentage was 90.02%±5127.0% (P<0.0001).After 26 weeks of treatment,82.36%,7.24% and 3.86% of the patients became controlled,significantly improved and improved,respectively.Adverse events (AEs) were reported in 74 (7.65%) patients.Rash was the most common AE.The efficacy of OXC was not affected by seizure types,age or gender.Conclusion:This study confirms the efficacy and good safety profile of OXC oral suspension in Chinese pediatric patients aged 2-16 years with PS and/or GTCS.展开更多
Background This study aimed to assess efficacy and safety of oxcarbazepine (OXC) oral suspension in pediatric patients aged 2-5 years with partial seizures (PS) and/or generalized tonic-clonic seizures (GTCS) in real-...Background This study aimed to assess efficacy and safety of oxcarbazepine (OXC) oral suspension in pediatric patients aged 2-5 years with partial seizures (PS) and/or generalized tonic-clonic seizures (GTCS) in real-world clinical practice in China. Methods This 26-week, prospective, single-arm, multicenter, observational study recruited pediatric patients aged 2-5 years with PS or GTCS suitable for OXC oral suspension treatment based on physicians' judgments from 11 medical centers in China. Enrolled subjects started OXC oral suspension treatment as monotherapy or in combination with other antiepileptic drugs. Primary efficacy outcome was the percentage of pediatric subjects achieving ≥ 50% seizure frequency reduction at the end of the 26-week treatment. Secondary efficacy-related parameters and safety parameters such as adverse events (AEs) and serious AEs (SAEs) were also monitored during the 26-week treatment period. Results Six hundred and six pediatric patients were enrolled and 531 (87.6%) completed the study. After 26 weeks of treat-ment, 93.3% subjects achieved ≥ 50% seizure frequency reduction, and 81.8% achieved 100% seizure frequency reduction compared to baseline. Among diff erent seizure types, OXC was eff ective in all subjects with simple PS and in > 90% of subject with other type of seizure present in the study. AEs were observed in 49 (8.1%) subjects. Only three subjects expe-rienced SAE. Rash (n = 18, 2.97%) was the most common AE. Only 17 subjects discontinued due to AEs. Conclusion This study, reporting the real-world data, further confi rms the efficacy and good safety profi le of OXC oral suspension in Chinese pediatric patients aged 2-5 years with PS and/or GTCS.展开更多
Genetic mutants of voltage-gated sodium channels(VGSCs)are considered to be responsible for the increasing number of epilepsy syndromes.Previous research has indicated that mutations of one of the VGSC genes,SCN9A(Nav...Genetic mutants of voltage-gated sodium channels(VGSCs)are considered to be responsible for the increasing number of epilepsy syndromes.Previous research has indicated that mutations of one of the VGSC genes,SCN9A(Navl.7),result in febrile seizures and Dravet syndrome in humans.Despite these recent efforts,the electrophysiological basis of SCN9A mutations remains unclear.Here,we performed a genetic screen of patients with febrile seizures and identified a novel missense mutation of SCN9A(W1150R).Electrophysiological characterization of different SCN9A mutants in HEK293T cells,the previously-reported N641Y and K655R variants,as well as the newly-found W1150R variant,revealed that the current density of the W1150R and N641Y variants was significantly larger than that of the wild-type(WT)channel.The time constants of recovery from fast inactivation of the N641Y and K655R variants were markedly lower than in the WT channel.The W1150R variant caused a negative shift of the G-V curve in the voltage dependence of steady-state activation.All mutants displayed persistent currents larger than the WT channel.In addition,we found that oxcarbazepine(OXC),one of the antiepileptic drugs targeting VGSCs,caused a significant shift to more negative potential for the activation and inactivation in WT and mutant channels.OXC-induced inhibition of currents was weaker in the W1150R variant than in the WT.Furthermore,with administering OXC the time constant of the N641Y variant was longer than those of the other two SCN9A mutants.In all,our results indicated that the point mutation W1150R resulted in a novel gain-of-function variant.These findings indicated that SCN9A mutants contribute to an increase in seizure,and show distinct sensitivity to OXC.展开更多
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 Epi...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.展开更多
文摘BACKGROUND Although few studies have reported hyponatremia due to carbamazepine or oxcarbazepine in patients with epilepsy,no study has investigated cases of carbamazepine-or oxcarbazepine-induced hyponatremia or unsteady gait in patients with neuropathic pain.Herein,we report a case of oxcarbazepineinduced lower leg weakness in a patient with trigeminal neuralgia and summarize the diagnosis,treatment,and changes of clinical symptoms.CASE SUMMARY A 78-year-old male with a history of lumbar spinal stenosis was admitted to the hospital after he experienced lancinating pain around his right cheek,eyes,and lip,and was diagnosed with trigeminal neuralgia at the right maxillary and mandibular branch.He was prescribed oxcarbazepine(600 mg/d),milnacipran(25 mg/d),and oxycodone/naloxone(20 mg/10 mg/d)for four years.Four years later,the patient experienced symptoms associated with spinal stenosis,including pain in the lower extremities and unsteady gait.His serum sodium level was 127 mmol/L.Assuming oxcarbazepine to be the cause of the hyponatremia,oxcarbazepine administration was put on hold and the patient was switched to topiramate.At subsequent visit,the patient’s serum sodium level had normalized to 143 mmol/L and his unsteady gait had improved.CONCLUSION Oxcarbazepine-induced hyponatremia may cause lower extremity weakness and unsteady gait,which should be differentiated from those caused by spinal stenosis.
文摘Objective: To investigate the effects of oxcarbazepine on immune function, thyroid function and related factors in epilepsy patients. Method: 90 patients with epilepsy who visited our hospital from January 2015 to May 2018 were selected as the observation group and 90 healthy volunteers were selected as control group. All patients in the observation group were treated with oxcarbazepine alone. T lymphocyte subsets, IgA, IgG, IgM, T3, T4, FT3, FT4, TSH, hs-CRP and Hcy in observation group were detected before treatment, 3 months after treatment and 6 months after treatment. The results were compared with those of the control group. Results: The levels of CD3+ and CD4+ in the control group were (65.25±9.51)% and (43.29±6.74)% respectively, which were higher than those in the observation group (P<0.05). The levels of CD8+, IgA and IgG in the control group were (22.40±6.41)%, (2.22±0.51) g/L, (9.99±1.28) g/L respectively, which were lower than those in the observation group (P<0.05). The levels of CD3+ and CD4+ in the observation group after 3 months and 6 months of treatment were significantly higher than those before treatment (P<0.05). The levels of CD8+, IgA and IgG in the observation group after 3 months and 6 months of treatment were significantly lower than those before treatment (P<0.05). There was no significant difference in the level of IgM between the observation group and the control group at each time point (P>0.05). The levels of thyroid hormones in the observation group before treatment and 3 months after treatment were not significantly different from those in the control group (P>0.05). The FT4 of the observation group was (14.98±1.03) pmol/L 6 months after treatment, which was significantly lower than that of the control group before treatment and 3 months after treatment (P<0.05). The levels of T3, T4, FT3 and TSH at each time point in the observation group were not significantly different from those in the control group (P>0.05). Before treatment, there was no significant difference in hs-CRP and Hcy levels between the observation group and the control group (P>0.05). The levels of hs-CRP and Hcy in the observation group were (4.82±0.67) mg/L and (13.36±1.51) umol/L respectively after 3 months of treatment. The levels of hs-CRP and Hcy in the observation group after 3 months of treatment were significantly higher than those before treatment and in the control group, and the difference was statistically significant (P<0.05). The levels of hs-CRP and Hcy in the observation group were (4.99±0.47) mg/L and (16.83±1.94) umol/L respectively after 6 months of treatment. The levels of hs-CRP and Hcy in the observation group were significantly higher than those in the control group after 3 months of treatment and before treatment (P<0.05). Conclusion: Oxcarbazepine can effectively improve the immune function of epilepsy patients, but with the prolongation of medication time, it may have adverse effects on thyroid function, hs-CRP and Hcy.
文摘Objective:To study effect of Oxcarbazepine on serum inflammatory factors, intercellular adhesion molecule 1(ICAM-1) and immune function in epileptic.Methods: Selected 95 patients who were diagnosed as epileptic into the observation group and 95 cases of healthy people as the control group;The observation group was given oral oxcarbazepine, continuous treatment for six months;Measured serum inflammatory factors (IL-2, IL-6, TNF-α) level, ICAM-1 and immune-related indexes: change of periphery T lymphocyte subgroup CD3+, CD4+, CD8+and immnuneglublin (IgG, IgA, IgM) level of the observation group before and after treatment, carried out comparative analysis through comparing with the normal control group.Results:Before treatment, compared with the control group, level of IL-2, IL-6, TNF-α, ICAM-1, CD8+, IgA and IgG in observation group were significantly higher than those in control group. CD3+, CD4+ level were significantly decreased when it compared with the control group. Level of IgM in the observation group was higher than that in the control group, but the difference between two groups was not significant. Before treatment, compared inter-class, level of IL-2, IL-6, TNF-α, ICAM-1, CD8+, IgA and IgG in the observation group were significantly lower, but all of these indexes level were still remarkable higher than the control group. It was statistical significant difference;After treatment, the level of CD3+, CD4+ in the observation group were dramatically increased, but both level were still significantly lower than the control group, the difference was statistically significant;Level of IgM after treatment compared with control group and before treatment respectively was no statistical significant difference.Conclusion: The level of inflammatory factors and ICAM-1 always were abnormal in epileptic and they were always with immune dysfunction. Oxcarbazepine was capable of effectively reducing inflammatory factor and ICAM-1 level and positively regulating immune dysfunction.
基金This work was supported by the Shandong Provincial Natural Science Foundation of China(No.ZR2021MB039)the National Natural Science Foundation of China(No.21607089)the Shandong Provincial Key Research and Development Program(Major Scientific and Technological Innovation Project)(No.2020CXGC011402).
文摘As an anticonvulsant,oxcarbazepine(OXC)has attracted considerable attention for its potential threat to aquatic organisms.Density functional theory has been used to study the mechanisms and kinetics of OXC degradation initiated by OH radicals in aqueous environment.A total of fourteen OH-addition pathways were investigated,and the addition to the C8 position of the right benzene ringwas themost vulnerable pathway,resulting in the intermediate IM8.The H-abstraction reactions initiated by OH radicalswere also explored,where the extraction site of the methylene group(C14)on the seven-member carbon heterocyclic ring was found to be the optimal path.The calculations show that the total rate constant of OXC with OH radicals is 9.47×10^(9)(mol/L)^(−1)sec^(−1),and the half-life time is 7.32 s at 298 K with the[·OH]of 10^(−11) mol/L.Moreover,the branch ratio values revealed that OH-addition(89.58%)shows more advantageous than H-abstraction(10.42%).To further understand the potential eco-toxicity of OXC and its transformation products to aquatic organisms,acute toxicity and chronic toxicity were evaluated using ECOSAR software.The toxicity assessment revealed that most degradation products such as OXC-2OH,OXC-4OH,OXC-1O-1OOH,and OXC-1OH’are innoxious to fish and daphnia.Conversely,green algae are more sensitive to these compounds.This study can provide an extensive investigation into the degradation of OXC by OH radicals and enrich the understanding of the aquatic oxidation processes of pharmaceuticals and personal care products(PPCPs).
文摘Background:To assess efficacy and safety of oxcarbazepine (OXC) oral suspension in pediatric patients aged 2-16 years with partial seizures (PS) and/or generalized tonic-clonic seizures (GTCS) in real-world clinical practice in China.Methods:This 26-week,single arm,multicenter and observational study recruited patients aged 2-16 years with PS or GTCS suitable for OXC oral suspension treatment.Enrolled patients received OXC oral suspension treatment for 26 weeks.Primary endpoints included mean seizure frequency at the end of the treatment and mean seizure frequency reduction at the end of the treatment vs.baseline.Secondary efficacy-related endpoints and safety parameters were also assessed.Results:Nine hundred and eighty-seven pediatric patients were enrolled and 912 (92.4%) completed the study.The mean seizure frequencies at baseline and the end of week 26 were 13.40±64.92 and 1.62±19.47 times/month,respectively.The mean seizure frequency reduction was 10.03±63.67 times/month and the mean seizure frequency reduction percentage was 90.02%±5127.0% (P<0.0001).After 26 weeks of treatment,82.36%,7.24% and 3.86% of the patients became controlled,significantly improved and improved,respectively.Adverse events (AEs) were reported in 74 (7.65%) patients.Rash was the most common AE.The efficacy of OXC was not affected by seizure types,age or gender.Conclusion:This study confirms the efficacy and good safety profile of OXC oral suspension in Chinese pediatric patients aged 2-16 years with PS and/or GTCS.
文摘Background This study aimed to assess efficacy and safety of oxcarbazepine (OXC) oral suspension in pediatric patients aged 2-5 years with partial seizures (PS) and/or generalized tonic-clonic seizures (GTCS) in real-world clinical practice in China. Methods This 26-week, prospective, single-arm, multicenter, observational study recruited pediatric patients aged 2-5 years with PS or GTCS suitable for OXC oral suspension treatment based on physicians' judgments from 11 medical centers in China. Enrolled subjects started OXC oral suspension treatment as monotherapy or in combination with other antiepileptic drugs. Primary efficacy outcome was the percentage of pediatric subjects achieving ≥ 50% seizure frequency reduction at the end of the 26-week treatment. Secondary efficacy-related parameters and safety parameters such as adverse events (AEs) and serious AEs (SAEs) were also monitored during the 26-week treatment period. Results Six hundred and six pediatric patients were enrolled and 531 (87.6%) completed the study. After 26 weeks of treat-ment, 93.3% subjects achieved ≥ 50% seizure frequency reduction, and 81.8% achieved 100% seizure frequency reduction compared to baseline. Among diff erent seizure types, OXC was eff ective in all subjects with simple PS and in > 90% of subject with other type of seizure present in the study. AEs were observed in 49 (8.1%) subjects. Only three subjects expe-rienced SAE. Rash (n = 18, 2.97%) was the most common AE. Only 17 subjects discontinued due to AEs. Conclusion This study, reporting the real-world data, further confi rms the efficacy and good safety profi le of OXC oral suspension in Chinese pediatric patients aged 2-5 years with PS and/or GTCS.
基金We are grateful to Prof.Ren Lai and Shilong Yang(Kunming Institute of Zoology,Chinese Academy of Sciences)for providing the pEZ-Lv206-hNav 1.7 plasmid.This work was supported by the National Natural Science Foundation of China(81603410,31571032,and 31771191)the Shanghai Municipal Commission of Health and Family Planning Foundation(20184Y0086)+2 种基金Innovation Program of Shanghai Municipal Education Commission(15ZZ063)the Research Project of Putuo Hospital,Shanghai University of Traditional Chinese Medicine(2016102A and 2016208A)a Project for Capacity Promotion of Putuo District Clinical Special Disease.
文摘Genetic mutants of voltage-gated sodium channels(VGSCs)are considered to be responsible for the increasing number of epilepsy syndromes.Previous research has indicated that mutations of one of the VGSC genes,SCN9A(Navl.7),result in febrile seizures and Dravet syndrome in humans.Despite these recent efforts,the electrophysiological basis of SCN9A mutations remains unclear.Here,we performed a genetic screen of patients with febrile seizures and identified a novel missense mutation of SCN9A(W1150R).Electrophysiological characterization of different SCN9A mutants in HEK293T cells,the previously-reported N641Y and K655R variants,as well as the newly-found W1150R variant,revealed that the current density of the W1150R and N641Y variants was significantly larger than that of the wild-type(WT)channel.The time constants of recovery from fast inactivation of the N641Y and K655R variants were markedly lower than in the WT channel.The W1150R variant caused a negative shift of the G-V curve in the voltage dependence of steady-state activation.All mutants displayed persistent currents larger than the WT channel.In addition,we found that oxcarbazepine(OXC),one of the antiepileptic drugs targeting VGSCs,caused a significant shift to more negative potential for the activation and inactivation in WT and mutant channels.OXC-induced inhibition of currents was weaker in the W1150R variant than in the WT.Furthermore,with administering OXC the time constant of the N641Y variant was longer than those of the other two SCN9A mutants.In all,our results indicated that the point mutation W1150R resulted in a novel gain-of-function variant.These findings indicated that SCN9A mutants contribute to an increase in seizure,and show distinct sensitivity to OXC.
基金supported by the National Natural Science Foundation of China(Grant No.30770752).
文摘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.
文摘目的探讨定痫方加减联合奥卡西平治疗血液透析相关性癫痫(Hemodialysis-associated seizure,HAS)肾虚痰瘀证的临床疗效。方法选取2019年1月—2021年12月期间石家庄市中医院收治的HAS患者34例,按随机数字表法分为对照组和观察组,每组各17例。对照组口服奥卡西平片,观察组在对照组基础上加服定痫方加减治疗。治疗3个月后,观察比较两组患者临床疗效,治疗前后中医证候积分、血清神经元特异性烯醇化酶(Neuron-specific enolase,NSE)、胶质纤维酸性蛋白(Glial fibrillary acidic protein,GFAP)、S100钙结合蛋白B(S100 calcium-binding protein B,S100B)及炎性因子[肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、白介素-1β(Interleukin-1β,IL-1β)、环氧化酶-2(Cyclooxygenase-2,COX-2)及高迁移率族蛋白B1(High mobility group protein B1,HMGB1)]水平,记录两组患者治疗前后癫痫发作持续时间和发作频次。结果治疗后观察组总有效率94.12%(16/17)高于对照组82.35%(14/17),差异有统计学意义(P<0.05)。治疗后两组患者各项证候积分和总积分均较治疗前降低,差异有统计学意义(P<0.05);且观察组各项证候积分和总积分均低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者癫痫发作持续时间和发作频次均较治疗前降低,差异有统计学意义(P<0.05);且观察组癫痫发作持续时间和发作频次低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者血清NSE、GFAP和S100B水平均较治疗前降低,差异有统计学意义(P<0.05);且观察组NSE、GFAP和S100B水平均低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者血清TNF-α、IL-1β、COX-2及HMGB1水平均较治疗前降低,差异有统计学意义(P<0.05);且观察组TNF-α、IL-1β、COX-2及HMGB1水平均低于对照组,差异有统计学意义(P<0.05)。治疗期间两组患者均未见明显的药物不良反应。结论定痫方加减联合奥卡西平治疗HAS肾虚痰瘀证的临床疗效显著且安全,可减轻血脑屏障破坏和神经元损伤程度,改善患者癫痫症状,其机制可能与抑制脑内炎症反应有关。
