Changes in seizure frequency and anti-seizure medication therapy during pregnancy and one year postpregnancy.

Seizure control in women with epilepsy (WWE) during pregnancy is a vital concern. The aim of this study was to compare changes in seizure frequency and anti-seizure medication (ASM ) therapy in WWE in a real-world setting over three epochs (prepregnancy, pregnancy, and postpregnancy). We screened WWE who were pregnant between 1 January 2010 and 31 December 2020 from the epilepsy follow-up registry database of a tertiary hospital in China. We reviewed and collected follow-up data for the following time periods: 12 months before pregnancy (epoch 1), throughout pregnancy and the first 6 weeks postpartum (epoch 2), and from 6 weeks to 12 months postpartum (epoch 3). Seizures were classified into two categories: tonic‒clonic/focal to bilateral tonic‒clonic seizures and non-tonic‒clonic seizures. The main indicator was the seizure-free rate over the three epochs. Using epoch 1 as a reference, we also compared the percentage of women with an increased seizure frequency, as well as changes in ASM treatment, in epochs 2 and 3. Ultimately, 271 eligible pregnancies in 249 women were included. The seizure-free rates in epoch 1, epoch 2, and epoch 3 were 38.4%, 34.7%, and 43.9%, respectively (P = 0.09). The top three ASMs used in the three epochs were lamotrigine, levetiracetam, and oxcarbazepine. Using epoch 1 as a reference, the percentages of women with increased frequencies of tonic‒clonic/focal to bilateral tonic‒clonic seizures in epoch 2 and epoch 3 were 17.0% and 14.8%, respectively, while the percentages of women with an increased frequency of non-tonic‒clonic seizures in epoch 2 and epoch 3 were 31.0% and 21.8% (P = 0.02). The percentage of women whose ASM dosages were increased in epoch 2 was higher than that in epoch 3 (35.8% vs. 27.3%, P = 0.03). The seizure frequency during pregnancy may not differ significantly from that during prepregnancy and postpregnancy if WWE are treated according to the guidelines.

External validation of the AntiEpileptic Drug Monitoring in PREgnancy (EMPiRE) model for predicting seizures in pregnant women with epilepsy.

BACKGROUND: The AntiEpileptic Drug Monitoring in PREgnancy (EMPiRE) model is the only available tool for predicting seizures in pregnant women with epilepsy (WWE) using anti-seizure medications (ASMs); however, its predictive performance requires validation. This study aimed to evaluate the predictive ability of this model in pregnant Chinese WWE and its potential usefulness in clinical practice. METHODS: Data of the EMPiRE model were derived from the EMPiRE study, a prospective multicenter cohort study that recruited women on ASM monotherapy (lamotrigine, carbamazepine, phenytoin or levetiracetam) or polytherapy (lamotrigine with either carbamazepine, phenytoin or levetiracetam). Based on the applicable population of the EMPiRE model, we evaluated 280 patients registered in the Wenzhou Epilepsy Follow-up Registry Database from January 1, 2010, to December 31, 2020. A total of 158 eligible patients were included in the validation cohort. We collected data on the baseline characteristics of patients, eight predictors of the EMPiRE model and outcome events. The outcome was the occurrence of tonic-clonic or non-tonic-clonic seizures at any time in pregnancy up to 6 weeks postpartum. We used the equation of the EMPiRE model to obtain the predicted probabilities of seizures. The predictive ability of the EMPiRE model was quantified by the C-statistic (scale 0-1, values > 0.5 show discrimination), GiViTI calibration test and decision curve analysis (DCA). RESULTS: Of 158 eligible patients, 96 patients (60.8%, 96/158) experienced one or more seizures at any time between pregnancy and 6 weeks postpartum. The EMPiRE model showed good discrimination with a C-statistic of 0.76 (95% confidence interval [CI] 0.70-0.84). The GiViTI calibration belt showed that the predicted probabilities, which ranged from 16 to 96% (95% CI), were lower than the actual probabilities. DCA indicated that the highest net proportional benefit was obtained for predicted probability thresholds of 15-18% and 54-96%. CONCLUSIONS: The EMPiRE model could discriminate well between WWE with and without seizures during pregnancy and 6 weeks postpartum, but the risk of seizures may be underestimated. The limitations of the model for specific medication regimens may limit its real-world application. If the model is further improved, it will be incredibly valuable.

Eslicarbazepine acetate add-on therapy for drug-resistant focal epilepsy.

BACKGROUND: This is an update of a review first published in 2011, and last updated in 2017. Most people with epilepsy have a good prognosis, but up to 30% of people continue to have seizures despite several regimens of antiepileptic drugs. In this review, we summarized the current evidence regarding eslicarbazepine acetate (ESL) when used as an add-on treatment for drug-resistant focal epilepsy. OBJECTIVES: To evaluate the efficacy and tolerability of ESL when used as an add-on treatment for people with drug-resistant focal epilepsy. SEARCH METHODS: For this update, we searched the following databases on 10 September 2020: Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid). CRS Web includes randomized or quasi-randomized, controlled trials from Specialized Registers of Cochrane Review Groups including Epilepsy, CENTRAL, PubMed, Embase, ClinicalTrials.gov and the WHO ICTRP. There were no language restrictions. We reviewed the reference lists of retrieved studies and contacted the manufacturers of ESL and experts in the field for information about any unpublished or ongoing studies. SELECTION CRITERIA: Randomized placebo-controlled double-blind add-on trials of ESL in people with drug-resistant focal epilepsy. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted data. Outcomes investigated included 50% or greater reduction in seizure frequency, seizure freedom, treatment withdrawal, adverse effects and drug interactions. Primary analyses were by intention to treat (ITT). The dose-response relationship was evaluated in regression models. MAIN RESULTS: We included seven trials (2185 participants, aged 2 to 77 years), which were at low or unclear risk of bias apart from a high risk of attrition bias; all studies were funded by the pharmaceutical company, BIAL. The overall risk ratio (RR) for 50% or greater reduction in seizure frequency was 1.57 (95% confidence interval (CI) 1.34 to 1.83). For adults, the RR was 1.71 (95% CI 1.42 to 2.05; 5 studies, 1799 participants; moderate-certainty evidence); for children aged six to 18 years, the RR was 1.35 (95% CI 0.98 to 1.87; 2 studies, 322 participants; moderate-certainty evidence). Dose regression analysis showed evidence that ESL reduced seizure frequency with an increase in efficacy with increasing doses of ESL. ESL was associated with seizure freedom (RR 3.16, 95% CI 1.73 to 5.78; 6 studies, 1922 participants; moderate-certainty evidence). Participants were more likely to have ESL withdrawn for adverse effects (RR 2.72, 95% CI 1.66 to 4.46; 7 studies, 2185 participants; moderate-certainty evidence), but not for any reason (RR 1.25, 95% CI 0.93 to 1.70; 7 studies, 2185 participants; moderate-certainty evidence). The following adverse effects were associated with ESL: dizziness (RR 2.77, 99% CI 1.85 to 4.15); nausea (RR 2.55, 99% CI 1.39 to 4.67); somnolence (RR 1.75, 99% CI 1.18 to 2.61); diplopia (RR 4.07, 99% CI 1.86 to 8.89); and vomiting (RR 2.37, 99% CI 1.19 to 4.74). Overall, the certainty of the evidence was moderate due to a high discontinuation rate in studies of adults. AUTHORS' CONCLUSIONS: ESL reduces seizure frequency when used as an add-on treatment for adults with drug-resistant focal epilepsy. The trials included in this review were of short-term duration. In addition, this update found that ESL may reduce seizure frequency in children from 6 to 18 years of age; however the results are inconclusive.

External validation and comparison of two prediction models for seizure recurrence after the withdrawal of antiepileptic drugs in adult patients.

OBJECTIVE: The models currently available for predicting the risk of seizure recurrence after antiepileptic drug (AED) withdrawal in adult epilepsy patients include the prediction model developed by Lamberink et al (Lamberink model, 2017) and the Medical Research Council prediction model (MRC model, 1993). However, there was no external validation for the two models. The purpose of this study was to perform an independent external validation and a comparison of the Lamberink model and the MRC model in adult patients. METHODS: The study population was recruited from the Wenzhou Epilepsy Follow-up Registry Database (WEFURD). All the predictors of the Lamberink and MRC models and the occurrence of seizure recurrence in the participants were collected based on the WEFURD. Participants' predicted probabilities of seizure recurrence were obtained by a Web-based tool and the prognostic index formula. The external validation of the Lamberink model and the MRC model were quantified by discrimination, calibration, and decision curve analysis (DCA). RESULTS: Of 212 patients, 126 (59.4%) had seizure recurrence after AED withdrawal. The Lamberink 2-year model, the Lamberink 5-year model, the MRC 1-year model, and the MRC 2-year model had areas under the curve of 0.71 (95% confidence interval [CI] = 0.64-0.78), 0.68 (95% CI = 0.60-0.76), 0.60 (95% CI = 0.50-0.69), and 0.58 (95% CI = 0.50-0.66), respectively. Additionally, the Lamberink 2-year model had a significantly better integrated discrimination improvement than the MRC 2-year model (P < .001). Regarding calibration, the Lamberink 2-year model (P = .121) and the MRC 1-year model (P = .264) were well calibrated, but the Lamberink 5-year model (P = .022) and the MRC 2-year model (P = .008) were not. In the DCA, the Lamberink 2-year model performed well at threshold probabilities of 30%-65%. SIGNIFICANCE: This external validation shows that the Lamberink 2-year model might be more accurate and has greater clinical benefit than others for guiding drug withdrawal in adult epilepsy clinics.

Comparison of the performance of two depression rating scales in patients with epilepsy in southern China.

OBJECTIVE: The aim of this study was to evaluate and compare the performance of the Chinese version of the Neurological Disorder Depression Inventory for Epilepsy (CNDDI-E) with that of the depression subscale of the Hospital Anxiety and Depression Scale (C-HADS-D) as screening tools for depression in the same patients with epilepsy (PWE). METHODS: A total of 213 consecutive PWE were evaluated. Receiver operating characteristic (ROC) analysis was performed using the C-NDDI-E and C-HADS-D as predictors and the Chinese version of the Mini International Neuropsychiatric Interview (C-MINI) as the gold standard. RESULTS: The area under the curve (AUC) for the C-NDDI-E was 0.870, and the optimal cutoff score was >11 (sensitivity 85.71%, specificity 79.78%); for the C-HADS-D, the AUC was 0.804, and the optimal cutoff score was >5 (sensitivity 85.71%, specificity 62.36%). The AUC for the C-NDDI-E was larger than the AUC for the C-HADS-D, but the comparison of the AUCs revealed no significant differences (P = 0.1444). CONCLUSION: Our findings indicate that the C-NDDI-E and C-HADS-D have high validity and support the use of these screening tools for depression in PWE. Moreover, the C-NDDI-E is a better screening scale for diagnosing depression than the C-HADS-D according to the results of this study.

Comparison of the performance of suicide ideation scales in adult patients with epilepsy in China.

OBJECTIVE: The aims of this study were to evaluate and compare the performance of the Chinese version of the Suicide Ideation Scale-Current (SSI-C) and the Suicide Ideation Scale-Worst (SSI-W) as suicide ideation screening tools in patients with epilepsy (PWE). METHODS: A consecutive sample of Chinese adult PWE recruited from a tertiary hospital completed the SSI-C and SSI-W and the suicidality module of the Chinese version of the Mini International Neuropsychiatric Interview (MINI) Plus 5.0.0. RESULTS: A total of 260 consecutive PWE were recruited. The area under the curve (AUC) for the SSI-C was 0.831, and the optimal cutoff score was >1 (sensitivity 73%, specificity 91%); for the SSI-W, the AUC was 0.958, and the optimal cutoff score was >2 (sensitivity 94.6%, specificity 87.4%). The AUC for the SSI-W was larger than that for the SSI-C, and the two-factor structure was considered significant. CONCLUSION: Our results showed that the SSI-C and SSI-W had good validity as suicidal ideation screening tools in PWE in southern China and can be recommended for clinical suicidal ideation screening. The SSI-W is a better suicidal ideation screening tool than the SSI-C according to the results of our study.

Risk factors for suicidal tendency in adult patients with epilepsy in China.

OBJECTIVE: The major cause of premature mortality in people with epilepsy (PWE) is suicide. Actual data on the risk of suicidal tendency in adult PWE in China are scarce. In our study, associations between possible risk factors and suicidal tendency in adult PWE in China were investigated. METHODS: People with epilepsy (n = 251) were recruited, and their demographic and clinical characteristics were evaluated. Suicide risk was examined using the suicidality module (SM) of the Mini International Neuropsychiatric Interview (MINI) Plus Chinese Version 5.0.0. RESULTS: Suicidal tendency was present in 36 (14.3%) of the 251 PWE. On the basis of the results of univariate analyses, family relationship (P < 0.001), age at epilepsy onset (P = 0.037), seizure-free period (P = 0.041), seizures/month (P = 0.015), depressive disorders (P < 0.001), and number of antiepileptic drugs (AEDs) (P = 0.017) were associated with suicidal tendency. Multivariate analysis revealed that moderate or poor family relationships (odds ratio (OR): 6.468, 95% confidence interval (CI): 2.418-17.300) and depressive disorders (OR: 3.548, 95% CI: 1.575-7.995) were associated with high odds of suicidal tendency. CONCLUSION: Suicidal tendency is common among adult PWE. This study reveals that family relationships and depressive disorders are independent risk factors for suicidal tendency among adult PWE. Therefore, while maintaining treatment of epilepsy, more attention should be directed to the social support and mental state of PWE to prevent suicide.

Validation of the Chinese version of the Scale for Suicide Ideation-Worst in adult patients with epilepsy.

OBJECTIVE: The aim of this study was to validate the Chinese version of the Scale for Suicide Ideation-Worst (SSI-W) for screening suicide ideation in Chinese adult patients with epilepsy (PWE). METHOD: A consecutive sample of Chinese adult PWE from a tertiary hospital completed the SSI-W and the suicidality module of the Chinese version of the Mini International Neuropsychiatric Interview (MINI) Plus 5.0.0. RESULTS: A total of 269 PWE completed the scales. According to the MINI, 59 patients (21.9%) had suicidal ideation. The Cronbach's α coefficient for the SSI-W was 0.96. Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) for the SSI-W was 0.957 (95% confidence interval [CI] = 0.935-0.980). With a cutoff score of 2 points, the SSI-W demonstrated the best psychometric properties: a sensitivity of 95.8%, a specificity of 87.3%, a positive predictive value (PPV) of 56.7%, and a negative predictive value (NPV) of 99.0%. The scores for items 11 (Reason for attempt) and 18 (Final acts) were not significantly different (p > 0.05) in patients with suicidal ideation, while the scores for the other items were significantly different between these groups of patients. CONCLUSION: The Chinese version of the SSI-W proved to be a reliable and effective assessment tool for screening suicidal ideation in Chinese adult PWE.

Reliability and validity of the Chinese version of the Patient Health Questionnaire 9 (C-PHQ-9) in patients with epilepsy.

OBJECTIVE: The aim of this study was to evaluate the clinical reliability and validity of the Chinese version of the Patient Health Questionnaire 9 (C-PHQ-9) in patients with epilepsy. METHODS: A total of 213 consecutive adult patients with epilepsy were evaluated. Receiver operating characteristic (ROC) analysis was performed using C-PHQ-9 and Chinese version of Patient Health Questionnaire 2 (C-PHQ-2) as predictors and the Mini International Neuropsychiatric Interview Plus Version 5.0.0 as the gold standard. RESULTS: The C-PHQ-9 was easily understood and quickly finished by the patients. According to the gold standard, the prevalence of current major depressive disorder in this population was 16.4%. Cronbach's α coefficient for the C-PHQ-9 was 0.860. The ROC analysis showed an area under the curve (AUC) of 0.888 (95% confidence interval [CI] = 0.838-0.927). At a cutoff score of >6, the C-PHQ-9 had a sensitivity of 82.86%, a specificity of 84.27%, a positive predictive value of 50.9%, and a negative predictive value of 96.2%. The C-PHQ-2 at a cutoff score of >1 resulted in the greatest balance of sensitivity and specificity (77.14% and 75.28%, respectively). CONCLUSION: Our findings support a high reliability and validity for the C-PHQ-9 as a screening tool for the detection of current major depression in Chinese patients with epilepsy.

Investigation of microstructural abnormalities in white and gray matter around hippocampus with diffusion tensor imaging (DTI) in temporal lobe epilepsy (TLE).

OBJECTIVE: The objective of this study was to apply diffusion tensor imaging (DTI) to investigate microstructural abnormalities in temporal lobe epilepsy (TLE) with and without hippocampal sclerosis (HS). MATERIALS: Totally, 19 patients with TLE with HS and 23 patients with TLE without HS were included. Fiber tracking fibers focused on the parahippocampal cingulum (PHC), cingulate gyrus (CG), and fornix (FORX). Fractional anisotropy (FA) and mean diffusivity (MD) values were obtained, and hippocampal volumes were measured. RESULTS: Compared with the contralateral side, for the HS group, FA values of ipsilateral CG and FORX were significantly decreased, and MD value of ipsilateral hippocampus was significantly higher, with significantly declined ipsilateral hippocampal volume. For the MRI-Neg group, FA values of ipsilateral CG, FORX, and hippocampus were significantly decreased, while MD values of ipsilateral FORX and hippocampus were significantly higher. Moreover, for the MRI-Neg group, the FA value of contralateral PHC was significantly decreased. Fractional anisotropy values of ipsilateral CG for both groups were significantly decreased, and FA value of ipsilateral FORX for the HS group was significantly decreased. Furthermore, MD value of ipsilateral hippocampus for the HS group was significantly higher, and FA value of ipsilateral hippocampus for the MRI-Neg group was significantly decreased. In addition, ipsilateral hippocampal volumes for both groups were significantly decreased. Fractional anisotropy value of ipsilateral CG and FORX had a correlation with the seizure frequency. CONCLUSION: Diffusion tensor imaging can detect microstructural abnormalities in brain from patients with TLE, which might be hard to find with routine Magnetic Resonance Imaging (MRI) sequence.

Validation of the Chinese version of the Hamilton Rating Scale for Depression in adults with epilepsy.

OBJECTIVE: This study aimed to validate the Chinese version of the 17-item Hamilton Rating Scale for Depression (C-HRSD-17) for use in adult patients with epilepsy (PWE). METHODS: A consecutive sample of Chinese adult PWE from a tertiary hospital was examined using the C-HRSD-17 and the Mini International Neuropsychiatric Interview (MINI) Plus Chinese Version 5.0.0. RESULTS: A total of 191 PWE completed the assessment of depression. According to the MINI, thirty patients (15.7%) had current major depressive disorder (MDD). The Cronbach's α coefficient for the C-HRSD-17 was 0.832. Receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.983 (95% CI = 0.968-0.998). With a cutoff score of 9, the C-HRSD-17 demonstrated the best psychometric properties, with a sensitivity of 96.7%, a specificity of 93.8%, a positive predictive value (PPV) of 74.4%, and a negative predictive value (NPV) of 99.3%. CONCLUSION: The C-HRSD-17 proved to be a valid and reliable assessment tool, with a cutoff score of 9 for screening of current MDD in Chinese adult PWE.

Eslicarbazepine acetate add-on for drug-resistant partial epilepsy.

BACKGROUND: This is an updated version of the Cochrane Review published in the Cochrane Library 2011, Issue 12.The majority of people with epilepsy have a good prognosis, but up to 30% of people continue to have seizures despite several regimens of antiepileptic drugs. In this review, we summarized the current evidence regarding eslicarbazepine acetate (ESL) when used as an add-on treatment for drug-resistant partial epilepsy. OBJECTIVES: To evaluate the efficacy and tolerability of ESL when used as an add-on treatment for people with drug-resistant partial epilepsy. SEARCH METHODS: The searches for the original review were run in November 2011. Subsequently, we searched the Cochrane Epilepsy Group Specialized Register (6 December 2016), the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 11) and MEDLINE (1946 to 6 December 2016). There were no language restrictions. We reviewed the reference lists of retrieved studies to search for additional reports of relevant studies. We also contacted the manufacturers of ESL and experts in the field for information about any unpublished or ongoing studies. SELECTION CRITERIA: Randomized placebo controlled double-blind add-on trials of ESL in people with drug-resistant partial epilepsy. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted data. Outcomes investigated included 50% or greater reduction in seizure frequency, seizure freedom, treatment withdrawal, adverse effects, and drug interactions. Primary analyses were by intention to treat (ITT). The dose-response relationship was evaluated in regression models. MAIN RESULTS: We included five trials (1799 participants) rated at low risk of bias; all studies were funded by BIAL. The overall risk ratio (RR) with 95% confidence interval (CI) for 50% or greater reduction in seizure frequency was 1.71 (95% CI 1.42 to 2.05). Dose regression analysis showed evidence that ESL reduced seizure frequency with an increase in efficacy with increasing doses of ESL. ESL was significantly associated with seizure freedom (RR 2.90, 95% CI 1.49 to 5.68). Participants were more likely to have ESL withdrawn for adverse effects (RR 2.66, 95% CI 1.42 to 4.96) but not for any reason (RR 1.19, 95% CI 0.86 to 1.64). The following adverse effects were significantly associated with ESL: dizziness (RR 2.81, 99% CI 1.86 to 4.27); nausea (RR 2.61, 99% CI 1.36 to 5.01); diplopia (RR 4.14, 99% CI 1.74 to 9.84); somnolence (RR 1.71, 99% CI 1.11 to 2.63) and vomiting (RR 3.30, 99% CI 1.34 to 8.13). Overall the quality of the evidence was rated as moderate to high. AUTHORS' CONCLUSIONS: ESL reduces seizure frequency when used as an add-on treatment for people with drug-resistant partial epilepsy. The trials included in this review were of short-term duration and focused on adults. One new trial has been included in this update, but the conclusions are unchanged.

Risk of seizure relapse after antiepileptic drug withdrawal in adult patients with focal epilepsy.

OBJECTIVE: The objective of this study was to estimate the risk of a seizure relapse and the high-risk period of recurrence after antiepileptic drug (AED) withdrawal and to determine the predictive factors for a seizure relapse in adult patients with focal epilepsy who were seizure-free for more than 2years. METHODS: Using the Wenzhou Epilepsy Follow-Up Registry Database, 200 adult patients with focal epilepsy were recruited, who were undergoing follow-up, met the inclusion criteria of this study, were seizure-free for more than 2years, began withdrawing between June 2003 and June 2014, and were followed up prospectively for at least 1year or until a seizure relapse. The risk of recurrence and the time to seizure relapse were analyzed by the Kaplan-Meier method, and the predictive factors were identified by the Cox proportional hazard regression model. RESULT: A total of 99 patients had an unprovoked relapse during the follow-up period. The relapse rate was 49.5%, and each year, the recurrence probability of 12, 24, 36, 48, 60, 72, and 84months after AED withdrawal was 24.0%, 20.4%, 8.3%, 2.7%, 4.6%, 0.97%, and 0.98%, respectively. The two independent risk factors for recurrence after withdrawal in adult patients with focal epilepsy were a longer duration of active epilepsy and a shorter seizure-free period before withdrawal. CONCLUSION: The high-risk period of a seizure relapse in adult patients with focal epilepsy is the first 2years after withdrawal, and beyond 5years after withdrawal, seizures rarely relapse (relapse rate<1%). A seizure-free period for less than 4years before withdrawal is a predictive factor of risk for seizure recurrence after AED withdrawal in adult patients with focal epilepsy.

Effects of white matter microstructure lesions on language and memory function in magnetic resonance imaging-negative temporal lobe epilepsy determined by diffusion tensor imaging.

OBJECTIVES: This study was conducted to investigate the associations between white matter lesions and language and memory dysfunctions in patients with magnetic resonance imaging (MRI)-negative temporal lobe epilepsy. MATERIALS AND METHODS: This study included 26 patients with temporal lobe epilepsy, who did not have significant findings on conventional MRI scanning, and 17 healthy subjects as control. Diffusion tensor imaging data was obtained with a 3Tesla (T) MRI scanner. Neuropsychological scores of language and memory functions were measured. One-way analysis of variance was used to analyze abnormal fractional anisotropy and mean diffusivity values. Correlations were performed to evaluate the relationship between fractional anisotropy/mean diffusivity of each fiber tract and neuropsychological measures. Regression analysis was performed to determine the contribution of each fiber tract to cognitive performance. RESULTS: Our data showed significantly decreased neuropsychological scores in the left and right temporal lobe epilepsy groups compared with control; it however, failed to show a statistical difference between the two groups. For the left temporal lobe epilepsy group, the mean diffusivity of the left parahippocampal and cingulate cortex, right arcuate fasciculus, and left fornix were significantly higher than control. Fractional anisotropy of the right fornix and mean diffusivity of the left uncinate fasciculus were significantly related to confrontational naming scores. There were significant correlations between the fractional anisotropy of the left fornix and verbal delayed memory scores and between the fractional anisotropy of the left fornix and nonverbal delayed memory scores. The mean diffusivity of left fractional anisotropy and the fractional anisotropy of the left uncinate fasciculus were significantly related to confrontational naming and verbal fluency scores, and seizure frequency was significantly related to nonverbal delayed memory scores. CONCLUSIONS: Language and memory function impairment was correlated with white matter structural integrity.

Brain protection conferred by long-term administration of 2-(2-benzofuranyl)-2-imidazoline against experimental autoimmune encephalomyelitis.

Our previous studies showed that 2-(2-benzofuranyl)-2-imidazoline (2-BFI), a ligand to type 2 imidazoline receptor, was protective against brain and spinal cord injury caused by experimental autoimmune encephalomyelitis (EAE). In the present study, we investigated the effect of long-term administration of 2-BFI and the dose-dependent response relationship of long-term administration of 2-BFI with neuroprotection. Treatment with 2-BFI at doses of 5, 10, and 20 mg/kg for 14 days significantly reduced hind limb paralysis and the severity of EAE compared with the EAE control group. Long-term use of 2-BFI was not only safe to mice, but also dose-dependently reduced the expression of inflammatory cytokines, including TNF-α, Interferon-γ and Interleukin-17A, compared with the EAE control group. Expressions of neuronal injury markers, including cytochrome c, AIF and ß-APP, were also reduced significantly in response to long-term 2-BFI treatment. Together, these results provided new evidence to demonstrate that 2-BFI is a safe and effective candidate for further development as a therapeutic drug for treatment of multiple sclerosis.

Effects of adding adjuvants to propofol on the post-anesthesia cognitive function in patients undergoing gastroscopy/colonoscopy: a systematic review and meta-analysis.

OBJECTIVES: This study aimed to elucidate the effects of propofol plus adjuvants on postoperative cognitive dysfunction (POCD) and patient satisfaction. METHODS: Studies published up to September 2023 on the Chinese National Knowledge Infrastructure (CNKI), Wanfang Data, Sinomed, PubMed, Embase, Cochrane Library, Web of Science, and Clinictrials.gov websites were searched. Binary summary of results was used for meta-analyses. RESULTS: We included 18 studies (2691 patients). The combined sedation did not affect the processing speed (ES = 0.02, 95%CI: -0.01, 0.04; I2 = 79.3%, p < 0.001), attention (ES = 0.02, 95%CI: -0.02, 0.05; I2 = 95.0%, p < 0.001), nor working memory (ES = 0.02, 95%CI: -0.03, 0.06; I2 = 94.4%, p < 0.001) in CogState brief battery tool. A significant effect of combined sedation was observed in the domain of visual learning in CogState tool (ES = -0.03, 95%CI: -0.04, -0.02; I2 = 15.8%, p = 0.306). The TDT (ES = 4.96, 95%CI: 2.92, 7.00) indicates that combined sedation would increase error rates in the tests of cognitive function. The DSST (ES = 0.16, 95% CI: -0.44, 0.75) shown that combined sedation does not affect cognitive function. In addition, an insignificant difference in patient satisfaction between combined sedation and propofol alone was observed (ES = -0.03, 95%CI: -0.09, 0.02). CONCLUSION: The available evidence suggests that propofol combined with adjuvants may affect POCD but not patient satisfaction. REGISTRATION NUMBER: INPLASY2023110092.

Genetic inactivation of the adenosine A(2A) receptor exacerbates brain damage in mice with experimental autoimmune encephalomyelitis.

Studies with multiple sclerosis patients and animal models of experimental autoimmune encephalomyelitis (EAE) implicate adenosine and adenosine receptors in modulation of neuroinflammation and brain injury. Although the involvement of the A(1) receptor has been recently demonstrated, the role of the adenosine A(2A) receptor (A(2A)R) in development of EAE pathology is largely unknown. Using mice with genetic inactivation of the A(2A) receptor, we provide direct evidence that loss of the A(2A)R exacerbates EAE pathology in mice. Compared with wild-type mice, A(2A)R knockout mice injected with myelin oligodendroglia glycoprotein peptide had a higher incidence of EAE and exhibited higher neurological deficit scores and greater decrease in body weight. A(2A)R knockout mice displayed increased inflammatory cell infiltration and enhanced microglial cell activation in cortex, brainstem, and spinal cord. In addition, demyelination and axonal damage in brainstem were exacerbated, levels of Th1 cytokines increased, and Th2 cytokines decreased. Collectively, these findings suggest that extracellular adenosine acting at A(2A)Rs triggers an important neuroprotective mechanism. Thus, the A(2A) receptor is a potential target for therapeutic approaches to multiple sclerosis.

Neurovascular protection conferred by 2-BFI treatment during rat cerebral ischemia.

Stroke is caused by vascular dysfunction and currently there are no effective therapeutics to stroke induced brain damage. In contrast to an intense emphasis on neuroprotection, relatively few studies have addressed means of vascular protection in cerebral ischemia. Here we discovered that the ligand to immidazolin receptor, 2-BFI, not only provided potent neuroprotection during middle cerebral artery occlusion in rat, which confirmed our previous reports, but also protected the integrity of the cerebral vasculature. Treatment with 2-BFI twice daily after the occlusion of the middle cerebral artery for 14 d significantly improved the neurological deficits, reduced brain infarction, and importantly, protected the cerebral vasculature as evidenced by the increased expression of an endothelial marker, von Willebrand factor, and better preservation of the cerebral vasculature, as viewed under a confocal microscope on rat brain perfused with FITC-labeled dextran. These results indicated that 2-BFI contributes to protection of neurovasculature. Understanding the molecular mechanisms could eventually lead to development of more effective therapies for stroke.

2-BFI attenuates experimental autoimmune encephalomyelitis-induced spinal cord injury with enhanced B-CK, CaATPase, but reduced calpain activity.

The lack of disease-modifying pharmacological agents for effective treatment of multiple sclerosis (MS) still represents a large and urgent unmet medical need. Our previous studies showed that ligands to type 2 imidazoline receptors (I(2)R) were effective in protecting spinal cord injury caused by experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. In this study, we further examined the protective property of a very selective ligand of I(2)R, 2-(2-benzofuranyl) 2-imidazoline (2-BFI) against EAE. Importantly, a mechanism of 2-BFI-mediated protection was investigated which possibly involves an I(2)R binding protein, brain-creatine kinase (B-CK), as well as CaATPase and calpain. The enzymatic activity of B-CK and CaATPase was significantly reduced in EAE injured spinal cord. Reduction of B-CK activity in EAE spinal cord may lead to energy reduction and dysfunction in cellular calcium homeostasis. Increased intracellular calcium evokes elevation of calpain activity occurring in EAE spinal cord which causes further tissue damage. Indeed, EAE injured spinal cord showed significant reduction in CaATPase and increase calpain activities. Remarkably, spinal cord tissue from mice treated daily with 2-BFI during the progression of EAE significantly restored B-CK and CaATPase enzymatic activities and showed no induction in calpain activity. Moreover, EAE spinal cord from 2-BFI treated mice also demonstrated better preservation of myelin; reduced axonal injury, as evidenced by the lower level of ß-APP expression, and above all, highly improved neurobehavioral scores (p<0.01; n=10). These findings suggest that 2-BFI can be further developed as a therapeutic drug for MS treatment.

Eslicarbazepine acetate add-on for drug-resistant partial epilepsy.

BACKGROUND: The majority of people with epilepsy will have a good prognosis, but up to 30% of patients will continue to have seizures despite several regimens of antiepileptic drugs. In this review we summarized the current evidence regarding eslicarbazepine acetate (ESL) when used as an add-on treatment for drug-resistant partial epilepsy. OBJECTIVES: To evaluate the efficacy and tolerability of ESL when used as an add-on treatment for people with drug-resistant partial epilepsy. SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialized Register (3 November 2011), The Cochrane Central Register of Controlled Trials (CENTRAL issue 4 of 4, The Cochrane Library 2011), and MEDLINE (1948 to October week 4, 2011). There were no language restrictions. We reviewed the reference lists of retrieved studies to search for additional reports of relevant studies. We also contacted the manufacturers of ESL and experts in the field for information about any unpublished or ongoing studies. SELECTION CRITERIA: Randomized placebo controlled double-blind add-on trials of ESL in people with drug-resistant partial epilepsy. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted data. Outcomes investigated included 50% or greater reduction in seizure frequency; seizure freedom; treatment withdrawal; adverse effects; and drug interactions. Primary analyses were by intention to treat. The dose response relationship was evaluated in regression models. MAIN RESULTS: Four trials (1146 participants) were included; all studies were funded by BIAL. The overall relative risk (RR) with 95% confidence interval (CIs) for 50% or greater reduction in seizure frequency outcome was 1.86 (95% CI 1.46 to 2.36). Dose regression analysis showed evidence that ESL reduced seizure frequency with an increase in efficacy with increasing doses of ESL. ESL was significantly associated with seizure freedom (RR 3.04, 95% CI 1.44 to 6.42). Participants seemed more likely (albeit not significantly) to have ESL withdrawn for adverse effects (RR 2.26, 95% CI 0.98 to 5.21) but not for any reason (RR 1.07, 95% CI 0.73 to 1.57). The following adverse effects were significantly associated with ESL: dizziness (RR 3.09, 99% CI 1.76 to 5.43); nausea (RR 3.06, 99% CI 1.07 to 8.74); and diplopia (RR 3.73, 99% CI 1.19 to 11.64). AUTHORS' CONCLUSIONS: Eslicarbazepine acetate reduces seizure frequency when used as an add-on treatment for people with drug-resistant partial epilepsy. The trials included in this review were of short-term duration and focused on adults.