Oxcarbazepine for trigeminal neuralgia may induce lower extremity weakness: A case report

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.

Effect of Oxcarbazepine on serum inflammatory factors, intercellular adhesion molecule 1 and immune function in epileptic

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.

Effect of oxcarbazepine on immune function, thyroid function and related factors in epilepsy patients

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.

Oxcarbazepine oral suspension in pediatric patients with partial seizures and/or generalized tonic-clonic seizures: a multi-center, single arm, observational study in China

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.

SCN9A Epileptic Encephalopathy Mutations Display a Gain-offunction Phenotype and Distinct Sensitivity to Oxcarbazepine

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.

Oxcarbazepine oral suspension in young pediatric patients with partial seizures and/or generalized tonic-clonic seizures in routine clinical practice in China: a prospective observational study

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.

Theoretical insights into the degradation mechanisms, kinetics and eco-toxicity of oxcarbazepine initiated by OH radicals in aqueous environments

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).

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

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

Expert consensus of the Chinese Association for the Study of Pain on ion channel drugs for neuropathic pain

Neuropathic pain(NPP)is a kind of pain caused by disease or damage impacting the somatosensory system.Ion channel drugs are the main treatment for NPP;however,their irregular usage leads to unsatisfactory pain relief.To regulate the treatment of NPP with ion channel drugs in clinical practice,the Chinese Association for the Study of Pain organized first-line pain management experts from China to write an expert consensus as the reference for the use of ion channels drugs.Here,we reviewed the mechanism and characteristics of sodium and calcium channel drugs,and developed recommendations for the therapeutic principles and clinical practice for carbamazepine,oxcarbazepine,lidocaine,bulleyaconitine A,pregabalin,and gabapentin.We hope this guideline provides guidance to clinicians and patients on the use of ion channel drugs for the management of NPP.

Effect of voltage-gated sodium channels blockers on motility and viability of human spermin vitro

Objective:To test the effect of voltage-gated sodium channels (VGSCs) blockers on the motility and viability of human spermin-vitro and to evaluate the tested compounds as potential contact spermicidal.Methods: Sperm samples were obtained from healthy non-smoking volunteers of age 25-30 years who had not taken any drug 3 months before and during the course of the study. The effect of VGSCs blockers evaluated from two pharmacological classes including antiarrhythmic (amiodarone, procainamide and disopyramide) and antiepileptic (carbamazepine, oxcarbazepine, phenytoin, and lamotrigine) drugs. They were tested on thein-vitro motility and viability of human sperm using Computer Assisted Semen Analyzer.Results:All tested drugs except oxcarbazepine showed dose dependent inhibition of total motility with significant reduction (P<0.05) at the maximum concentration of 200 μM when compared with the control. The concentrations of drugs that reduced total sperm motility to 50% of control (half maximal inhibitory concentration) were 2.76, 14.16 and 20.29 μM for phenytoin, lamotrigine and carbamazepine, respectively;and 2.53, 5.32 and 0.37 μM for amiodarone, procainamide and disopyramide, respectively. The anti-motility effects were reversible to various degrees. There was statistically insignificant difference in the inhibition of sperm viability among amiodarone, procainamide and disopyramide. Phenytoin demonstrated the most potent spermicidal action.Conclusions:VGSCs blockers have significant adverse effects onin-vitro motility of human spermatozoa. Soin-vivo studies are required to determine their potential toxicological effects on human semen quality, which is an important factor regarding fertility. Moreover, these drugs have the potential to be developed into contact spermicidal.