Precise Immobilization Strategy Combined with Rational Design to Improve ß-Agarase Stability.

Recently, the orientational immobilization of enzymes has attracted extensive attention. In this study, we report the development of a strategy combined with rational design to achieve precise site-specific covalent immobilization of ß-agarase. We first rationally screened six surface sites that can be mutated to cysteine by combining molecular dynamics simulation and energy calculation. Site-specific immobilization was successfully achieved by Michael addition reaction of mutant enzymes and maleimide-modified magnetic nanoparticles (MAL-MNPs). The enzyme activity retention rate of R66C-MAL-MNPs and K588C-MAL-MNPs was greater than 96%. The thermal deactivation kinetics study revealed that the site-specific immobilization strategy significantly improved the thermal stability of Aga50D, resulting in a substantial increase in its antidenaturation activity at elevated temperatures, and the highest t1/2 of the immobilized mutant enzymes was increased by an impressive 21.25-fold at 40 °C. The immobilized mutant enzymes also showed significantly enhanced tolerance to metal ions and organic reagents. For instance, all of the immobilized enzymes maintained over 90% of their enzymatic activity in the 50% (v/v) acetone/water solution. The present work may pave the way for the design of precisely immobilized enzymes, which can help promote green manufacturing.

Binding uric acid: a pure chemical solution for the treatment of hyperuricemia.

Hyperuricemia, characterized by elevated uric acid levels and subsequent crystal deposition, contributing to conditions such as gout, cardiovascular events, and kidney injury, poses a significant health threat, particularly in developed countries. Current drug options for treatment are limited, with safety concerns, leading to suboptimal therapeutic outcomes in symptomatic hyperuricemia patients and a lack of pharmaceutical interventions for asymptomatic cases. Distinguishing from the previous drug design strategies, we directly target uric acid, the pathological molecule of hyperuricemia, resulting in a pyrimidine derivative capable of increasing the solubility and excretion of uric acid by forming a complex with it. Its prodrug showed an anti-hyperuricemia activity comparable to benzbromarone and a favorable safety profile in vivo. Our finding provides a strategy purely based on organic chemistry to address the largely unmet therapeutic needs on novel anti-hyperuricemia drugs.

Co-immobilization of ß-agarase and α-agarase for degradation of agarose to prepare bioactive 3,6-anhydro-L-galactose.

Agarose from biomass can be used to synthesize the rare sugar 3,6-anhydro-L-galactose (L-AHG), and the new synthesis route and functional properties of L-AHG have always been the focus of research. Here we developed a novel method to co-immobilize Aga50D and BpGH117 onto streptavidin-coated magnetic nanoparticles and achieved the conversion of agarose to bioactive L-AHG in one pot. Results showed that enzymes were successfully immobilized on the carrier. The activity of co-immobilized enzymes was 2.5-fold higher than that of single immobilized enzymes. Compared with free enzymes, co-immobilized enzymes exhibited enhanced thermal stability. The co-immobilized enzymes retained 79.45 % relative activity at 40 °C for 3 h, while the free enzymes only possessed 21.40 % residual activity. After eight cycles, the co-immobilized enzymes still retained 73.47 % of the initial activity. After silica gel chromatography, the purity of L-AHG obtained by co-immobilized enzymes hydrolysis reached 83.02 %. Furthermore, bioactivity experiments demonstrated that L-AHG displayed better antioxidant and antibacterial effects than neoagarobiose. L-AHG had broad-spectrum antibacterial activity, while neoagarobiose and D-galactose did not show an obvious antibacterial effect. This study provides a feasible method for the production of L-AHG by a co-immobilized multi-enzyme system and confirms that L-AHG plays a key role in the bioactivity of neoagarobiose.

Combined Transcranial Doppler and Melatonin Levels to Predict Delayed Cerebral Ischemia After Subarachnoid Hemorrhage.

OBJECTIVE: To investigate the early prediction value of transcranial Doppler ultrasound (TCD) combined with serum melatonin level for delayed cerebral ischemia (DCI) caused by subarachnoid hemorrhage (SAH). METHODS: This paper is a prospective study. A total of 120 patients with SAH treated were included. The patients were divided into the DCI group (40 cases) and non-DCI group (80 cases) according to whether DCI occurred 14 days after SAH (DCI usually occurs 4 to 14 d after bleeding). Baseline data, serum melatonin level, and TCD test results within 24 hours after admission were compared between the 2 groups. Multivariate logistic analysis was used to analyze the factors affecting the occurrence of DCI after SAH. The value of serum melatonin level, middle cerebral artery mean blood flow velocity (MBFV) and their combination in predicting DCI in SAH patients was evaluated. RESULTS: Univariate analysis showed that there were statistically significant differences in the proportion of Fisher grade, Hunt-Hess grade, serum melatonin level, middle cerebral artery systolic blood flow velocity (Vs), MBFV and pulse index (PI) between the 2 groups ( P <0.05). Serum melatonin levels, middle cerebral artery Vs, MBFV, and PI in the DCI group were higher than those in non-DCI group. Logistic regression (LR) analysis showed that serum melatonin level (OR=1.796, 95% CI: 1.575-4.123) and middle cerebral artery MBFV (OR=3.279, 95% CI: 2.112-4.720] were the influencing factors for DCI in SAH patients ( P <0.05). CONCLUSION: Middle cerebral artery MBFV and serum melatonin levels were higher in patients with SAH complicated with DCI, and the combination of the 2 could provide a reference for early clinical prediction of DCI in patients with aneurysmal subarachnoid hemorrhage (aSAH).

Efficacy and safety of Perampanel in the treatment of post stroke epilepsy: A multicenter, real-world study.

Background: Since 2019, Perampanel (PER) has been endorsed in China as an adjunctive treatment for focal seizures, both with and without impaired awareness, and for the transition from focal to bilateral tonic-clonic seizures. Limited research exists regarding the efficacy of PER in treating post-stroke epilepsy (PSE) in China. Empirical studies are essential to guide treatment protocols. We conducted a retrospective study to assess the efficacy and tolerability of PER in 58 PSE patients treated between October 2019 and July 2023. Method: This study encompassed 58 patients with PSE, treated with PER either as monotherapy or as part of adjunctive therapy, and underwent follow-up for a minimum duration of 6 months. The study assessed changes in seizure frequency, adverse events (AEs), drug retention rate, maintenance dose, and adverse reactions following PER treatment. Results: The study included 58 PSE patients, with 60.3% males and 39.7% females, ranging in age from 18 to 89, mostly within the 61-70 age group. Ischemic strokes constituted 58.6% of cases, while hemorrhagic strokes accounted for 41.4%. Focal seizures, either with or without impaired awareness, were noted in 62.1% of patients, and a transition from focal to bilateral tonic-clonic seizures was seen in 32.8%. The retention rates for PER at 3 and 6 months stood at 94.8% and 84.5% respectively, and the most commonly administered maintenance dose was 4 mg/day (41.28%). In the adjunctive therapy group, efficacy rates were 66.7% at 3 months and 78.6% at 6 months, compared to 80.0% at 3 months and 85.7% at 6 months in the monotherapy group. In the efficacy analysis, with a criterion of ≥50% reduction in seizure frequency, the overall efficacy rates at 3 and 6 months were 69.1% and 79.6%, respectively. Adverse reactions occurred in 46.6% of patients, primarily involving irritability and somnolence (both 27.6%), with no marked difference in incidence between the adjunctive and monotherapy groups (P > 0.05). Conclusion: PER exhibits favorable efficacy and tolerability in Chinese PSE patients, possibly at lower doses.

Predictive Value of Quantitative Electroencephalogram Combined with Transcranial Doppler Ultrasound in Delayed Cerebral Ischemia after Subarachnoid Hemorrhage.

OBJECTIVE: To explore the predictive value of transcranial Doppler ultrasound (TCD) combined with quantitative electroencephalogram (QEEG) in delayed cerebral ischemia (DCI) caused by aneurysmal subarachnoid hemorrhage (aSAH). METHODS: The participants were 105 patients with aSAH treated from June 2020 to December 2022. Patients were divided into DCI group (n = 34) and non-DCI group (n = 71) according to the presence of DCI 14 days after onset. Further comparison was conducted on the baseline data as well as the parameters of QEEG and TCD within 24 hours after admission. Multivariate logistic analysis was performed to investigate risk factors related to DCI within 14 days of admission in aSAH patients. RESULTS: There were significant differences in the comparison of the proportion of Hunt-Hess grading, relative δ power (RDP), relative α power (RAP), relative α/ß power ratio (ADR), as well as peak systolic velocity (Vs), mean blood flow velocity (MBFV) and pulsatility index (PI) of middle cerebral artery between the two groups (P < 0.05). Furthermore, Logistic regression analysis revealed that ADR (odds ratio 1.668, 95% CI 1.369-4.345) and MBFV of middle cerebral artery (odds ratio 3.279, 95% CI 2.332-6.720) were risk factors for the occurrence of DCI in aSAH patients (P < 0.05). In addition, evaluation of the predictive value revealed that combined use of the 2 indicators showed the highest predictive value (area under the curve 0.959, 95% CI 0.896-0.993). CONCLUSIONS: Patients with aSAH complicated by DCI have relatively higher MBFV of middle cerebral artery and ADR. Combined use of the 2 indicators can provide reference for early prediction of DCI in aSAH patients.

Comparative study on different immobilization sites of immobilized ß-agarase based on the biotin/streptavidin system.

ß-Agarase was biotinylated and immobilized onto streptavidin-conjugated magnetic nanoparticles to provide insights into the effect of immobilization sites on ß-agarase immobilization. Results showed that, compared with free enzyme, the stability of prepared immobilized ß-agarases through amino or carboxyl activation were both significantly improved. However, the amino-activated immobilized ß-agarase showed higher thermostability and catalytic efficiency than the carboxyl-activated immobilized ß-agarase. The relative activity of the former was 65.00 % after incubation at 50 °C for 1 h, which was 1.77-fold higher than that of the latter. Additionally, amino-activated immobilization increased the affinity of the enzyme to the substrate, and its maximum reaction rate (0.68 µmol/min) was superior to that of carboxyl-activated immobilization (0.53 µmol/min). The visualization results showed that the catalytic site of ß-agarase after carboxyl-activated immobilization was more susceptible to the immobilization process, and the orientation of the enzyme may also hinder substrate binding and product release. These results suggest that by pre-selecting appropriate activation sites and enzyme orientation, immobilized enzymes with higher catalytic activity and stability can be obtained, making them more suitable for the application of continuous production.

Efficacy and safety of agomelatine in epilepsy patients with sleep and mood disorders: An observational, retrospective cohort study.

OBJECTIVE: To evaluate the therapeutic efficacy and safety of agomelatine for treating the sleep and mood disorders in epilepsy patients. METHODS: Retrospective data were derived from 113 epilepsy patients for at least 8 weeks. All the subjects were divided into two groups, one was treated with agomelatine, the other was treated with escitalopram. Their depression and anxiety states were assessed by Hamilton Depression (HAMD) and Hamilton Anxiety (HAMA) Scales. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). RESULTS: The HAMA, HAMD and PSQI scores in both groups significantly declined after the treatments with agomelatine and escitalopram. However, the agomelatine group exhibited greater improvement in terms of HAMA and PSQI scores compared to the escitalopram group. No severe adverse events were observed in agomelatine group. SIGNIFICANCE: Agomelatine performed better in HAMA and PSQI scores compared to escitalopram, where no significant increase in seizure frequency or side effects were observed. Possibly, agomelatine presents a promising therapeutic option for treating the sleep or mood disorders in epilepsy patients.

Endothelial cell-derived RSPO3 activates Gαi1/3-Erk signaling and protects neurons from ischemia/reperfusion injury.

The current study explores the potential function and the underlying mechanisms of endothelial cell-derived R-spondin 3 (RSPO3) neuroprotection against ischemia/reperfusion-induced neuronal cell injury. In both neuronal cells (Neuro-2a) and primary murine cortical neurons, pretreatment with RSPO3 ameliorated oxygen and glucose deprivation (OGD)/re-oxygenation (OGD/R)-induced neuronal cell death and oxidative injury. In neurons RSPO3 activated the Akt, Erk and ß-Catenin signaling cascade, but only Erk inhibitors reversed RSPO3-induced neuroprotection against OGD/R. In mouse embryonic fibroblasts (MEFs) and neuronal cells, RSPO3-induced LGR4-Gab1-Gαi1/3 association was required for Erk activation, and either silencing or knockout of Gαi1 and Gαi3 abolished RSPO3-induced neuroprotection. In mice, middle cerebral artery occlusion (MCAO) increased RSPO3 expression and Erk activation in ischemic penumbra brain tissues. Endothelial knockdown or knockout of RSPO3 inhibited Erk activation in the ischemic penumbra brain tissues and increased MCAO-induced cerebral ischemic injury in mice. Conversely, endothelial overexpression of RSPO3 ameliorated MCAO-induced cerebral ischemic injury. We conclude that RSPO3 activates Gαi1/3-Erk signaling to protect neuronal cells from ischemia/reperfusion injury.

Modeling critical interaction for metastasis between circulating tumor cells (CTCs) and platelets adhered to the capillary wall.

BACKGROUND AND OBJECTIVE: We used a 2D fluid-solid interaction (FSI) model to investigate the critical conditions for the arrest of the CTCs traveling through the narrowed capillary with a platelet attached to the capillary wall. This computational model allows us to determine the deformations and the progression of the passage of the CTC through different types of microvessels with platelet included. METHODS: The modeling process is obtained using the strong coupling approach following the remeshing procedure. Also, the 1D FE rope element for simulating active ligand-receptor bonds is implemented in our computational tool (described below). RESULTS: A relationship between the CTCs properties (size and stiffness), the platelet size and stiffness, and the ligand-receptor interaction intensity, on one side, and the time in contact between the CTCs and platelet and conditions for the cell arrest, on the other side, are determined. The model is further validated in vitro by using a microfluidic device with metastatic breast tumor cells. CONCLUSIONS: The computational framework that is presented, with accompanying results, can be used as a powerful tool to study biomechanical conditions for CTCs arrest in interaction with platelets, giving a prognosis of disease progression.

Identification of disease-related genes in Plasmodium berghei by network module analysis.

BACKGROUND: Plasmodium berghei has been used as a preferred model for studying human malaria, but only a limited number of disease-associated genes of P. berghei have been reported to date. Identification of new disease-related genes as many as possible will provide a landscape for better understanding the pathogenesis of P. berghei. METHODS: Network module analysis method was developed and applied to identify disease-related genes in P. berghei genome. Sequence feature identification, gene ontology annotation, and T-cell epitope analysis were performed on these genes to illustrate their functions in the pathogenesis of P. berghei. RESULTS: 33,314 genes were classified into 4,693 clusters. 4,127 genes shared by six malaria parasites were identified and are involved in many aspects of biological processes. Most of the known essential genes belong to shared genes. A total of 63 clusters consisting of 405 P. berghei genes were enriched in rodent malaria parasites. These genes participate in various stages of parasites such as liver stage development and immune evasion. Combination of these genes might be responsible for P. berghei infecting mice. Comparing with P. chabaudi, none of the clusters were specific to P. berghei. P. berghei lacks some proteins belonging to P. chabaudi and possesses some specific T-cell epitopes binding by class-I MHC, which might together contribute to the occurrence of experimental cerebral malaria (ECM). CONCLUSIONS: We successfully identified disease-associated P. berghei genes by network module analysis. These results will deepen understanding of the pathogenesis of P. berghei and provide candidate parasite genes for further ECM investigation.

COVID-19 vaccination for patients with epilepsy: A Chinese expert consensus.

Coronavirus disease-2019 (COVID-19) first emerged in late 2019 and has since spread worldwide. More than 600 million people have been diagnosed with COVID-19, and over 6 million have died. Vaccination against COVID-19 is one of the best ways to protect humans. Epilepsy is a common disease, and there are approximately 10 million patients with epilepsy (PWE) in China. However, China has listed "uncontrolled epilepsy" as a contraindication for COVID-19 vaccination, which makes many PWE reluctant to get COVID-19 vaccination, greatly affecting the health of these patients in the COVID-19 epidemic. However, recent clinical practice has shown that although a small percentage of PWE may experience an increased frequency of seizures after COVID-19 vaccination, the benefits of COVID-19 vaccination for PWE far outweigh the risks, suggesting that COVID-19 vaccination is safe and recommended for PWE. Nonetheless, vaccination strategies vary for different PWE, and this consensus provides specific recommendations for PWE to be vaccinated against COVID-19.

Inhibition of TMEM16A improves cisplatin-induced acute kidney injury via preventing DRP1-mediated mitochondrial fission.

Acute kidney injury (AKI) is associated with high morbidity and mortality. Our previous study has demonstrated that TMEM16A, a Ca2+-activated chloride channel, contributes to renal fibrosis progression in chronic kidney disease. However, whether TMEM16A is involved in AKI is still unknown. In this study, we established cisplatin AKI mice model and found that TMEM16A expression was upregulated in the injured kidney. In vivo knockdown of TMEM16A effectively prevented cisplatin-induced tubular cell apoptosis, inflammation and kidney function loss. Western blot and transmission electron microscopy (TEM) revealed that TMEM16A knockdown inhibited Drp1 translocation from the cytoplasm to mitochondria and prevented mitochondrial fission in tubular cells. Consistently, in cultured HK2 cells, knockdown or inhibition of TMEM16A by shRNA or its specific inhibitor suppressed cisplatin-induced mitochondrial fission and its associated energy dysfunction, ROS accumulation, and cell apoptosis via inhibiting Drp1 activation. Further investigation showed that genetic knockdown or pharmacological inhibition of TMEM16A inhibited cisplatin-induced Drp1 Ser-616 site phosphorylation through ERK1/2 signaling pathway, whereas overexpression of TMEM16A promoted this effect. Treatment with Drp1 or ERK1/2 inhibitor could efficiently prevent cisplatin-induced mitochondrial fission. Collectively, our data suggest that TMEM16A inhibition alleviated cisplatin-induced AKI by preventing tubular cell mitochondrial fission through the ERK1/2 / Drp1 pathway. Inhibition of TMEM16A may be a novel therapeutic strategy for AKI.

Interaction between COVID-19 and epilepsy during the omicron surge: A cross-sectional survey conducted in China tertiary hospital.

Objective: It is unclear whether patients with epilepsy are more susceptible to SARS-CoV-2 infection, whether they experience more severe manifestations of COVID-19, and whether seizures worsen after SARS-CoV-2 infection. Our study aims to explore these points and provide comprehensive and practical guidance for patients with epilepsy. Methods: We designed a questionnaire to collect variables from epilepsy patients. We used the Chi-square test, Fisher's exact test, or Mann-Whitney U test to analyze differences between the two groups. Multiple logistic regressions were employed to determine the risk factors for relevant outcome variables. Results: We identified a total of 181 patients, with 74% (n = 134) reporting COVID-19. The patients' educational level was found to be a risk factor for COVID-19 (OR = 0.33, 95% CI 0.14-0.80, P = 0.013). When comparing seizure frequency changes between epilepsy patients with and without COVID-19, no statistically significant difference was observed (P > 0.05). However, an increase in seizure frequency was significantly associated with higher levels of anxiety (P < 0.001) and depression (P < 0.005). Conclusion: The risk of COVID-19 infection may be increased in patients with epilepsy. COVID-19 infection does not seem to worsen seizures in epilepsy patients. Patients with epilepsy rarely develop more severe clinical manifestations of COVID-19 after SARS-CoV-2 infection. During the COVID-19 pandemic, patients with epilepsy who also suffer from anxiety and depression may experience an increase in the frequency of their seizures.

The relationship between the number of CAG repeats and clinical manifestations: a survey of Chinese DRPLA family.

OBJECTIVE: To describe the clinical, radiological, and genetic characteristics of a Chinese family with dentatorubropallidoluysian atrophy (DRPLA). Explore the distribution of CAG repeat size to the clinical features of patients. METHODS: We collected the clinical symptoms and DNA analysis for the DRPLA gene was performed on the family members. DRPLA patients reported in the literature were reviewed to analyze the association between CAG repeat size and clinical features. RESULTS: Six family members were confirmed by genetic analysis. The number of CAG repeat in the proband, her sister, her grandmother, her father, her uncle, and her cousin, was determined respectively as 63, 75, 50, 50, 50, 54. In our family, the sister of the proband had the earliest onset age and the most severe clinical symptoms, followed by the proband, and other family members showed no obvious clinical symptoms. Consistent with the conclusion of previous studies, the more repeats CAG, the earlier the age of onset and the severer phenotypes are. CONCLUSION: We found six family members have CAG repeat expansion in the DRPLA gene on chromosome 12p13. Even in the same family, patients have different clinical presentations. The size of CAG repeats is negatively correlated with the age of onset and positively correlated with symptom severity. When the number of repeats is ≥ 63, the age at onset is < 21 years old, and obvious clinical symptoms generally appear. It seems to say the more repeats CAG, the earlier the age of onset and the severer phenotypes are. LIMITATIONS: With a small number of cases in our family, the conclusion that the more CAG repeats, the earlier the onset and the more severe the clinical symptoms cannot be fully proved.

Targeted metabolomics reveals serum changes of amino acids in mild to moderate ischemic stroke and stroke mimics.

Background: The pathophysiological processes linked to an acute ischemic stroke (IS) can be reflected in the circulating metabolome. Amino acids (AAs) have been demonstrated to be one of the most significant metabolites that can undergo significant alteration after a stroke. Methods: We sought to identify the potential biomarkers for the early detection of IS using an extensive targeted technique for reliable quantification of 27 different AAs based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). A cohort with 216 participants was enrolled, including 70 mild to moderate ischemic stroke patients (National Institutes of Health Stroke Scale < 15, MB group), 76 stroke mimics (MM group) and 70 healthy controls (NC group). Results: It was found that upon comparing MB and MM to control patients, AAs shifts were detected via partial least squares discrimination analysis (PLS-DA) and pathway analysis. Interestingly, MB and MM exhibited similar AAs pattern. Moreover, ornithine, asparagine, valine, citrulline, and cysteine were identified for inclusion in a biomarker panel for early-stage stroke detection based upon an AUC of 0.968 (95% CI 0.924-0.998). Levels of ornithine were positively associated with infract volume, 3 months mRS score, and National Institutes of Health Stroke Scale (NIHSS) score in MB. In addition, a metabolites biomarker panel, including ornithine, taurine, phenylalanine, citrulline, cysteine, yielded an AUC of 0.99 (95% CI 0.966-1) which can be employed to effectively discriminate MM patients from control. Conclusion: Overall, alternations in serum AAs are characteristic metabolic features of MB and MM. AAs could serve as promising biomarkers for the early diagnosis of MB patients since mild to moderate IS patients were enrolled in the study. The metabolism of AAs can be considered as a key indicator for both the prevention and treatment of IS.

Plasma lipid profiles and homocysteine levels in anti-N-methyl-D-aspartate receptor encephalitis.

Introduction: We aimed to investigate whether lipid profiles and homocysteine levels in patients with anti-N-methyl-D-aspartate receptor encephalitis are related to clinical presentation and prognosis, which may contribute to further research on the pathogenesis and treatment of this disease. Methods: This study included a total of 43 patients with anti-N-methyl-D-aspartate receptor encephalitis and 43 sex-age-matched healthy controls. Baseline demography, clinical data, patient outcomes, and ancillary examination results were recorded. Patients were followed up every 2-3 months during the first year. The modified Rankin Scale score was used to evaluate the therapeutic effect and clinical outcome. Results: Among the 43 patients included in this study, 55.81% were male, the mean age of onset was 27 years old, and the median modified Rankin Scale score on admission was 3.0. Apolipoprotein A-1 was significantly lower in patients with anti-N-methyl-D-aspartate receptor encephalitis compared with healthy controls (p = 0.004). Compared with healthy controls, homocysteine (p = 0.002), apolipoprotein B (p = 0.004), Lpa (p = 0.045), and apolipoprotein B/apolipoprotein A-1 (p = 0.001) were significantly increased in patients with anti-N-methyl-D-aspartate receptor encephalitis. According to the modified Rankin Scale scores, 6 months after discharge, 72.09% of patients had a good prognosis and 27.91% had a poor prognosis. In the good prognosis group, age (p = 0.031), lipoprotein a (p = 0.023), apolipoprotein A-1 (p = 0.027) at baseline, and the modified Rankin Scale score on admission (p = 0.019) were significantly higher than those in the poor prognosis group. Conclusion: This study suggests the possibility that serum lipid profile and homocysteine play an important role in the pathogenesis of anti-N-methyl-D-aspartate receptor encephalitis, providing support for lipid-lowering treatment of anti-N-methyl-D-aspartate receptor encephalitis patients.

Efficacy and tolerability of lacosamide as adjunctive therapy in patients with focal-onset seizures: an observational, prospective study.

PURPOSE: To evaluate the efficacy and tolerability of adjunctive lacosamide (LCM) in patients with focal-onset seizures, with or without combined secondarily generalized seizures. METHODS: 106 patients aged ≥ 16 years were recruited consecutively in this single-center prospective observational study. All patients received LCM as an add-on treatment on the basis of clinical judgement. Seizure frequency, adverse events (AEs) and retention rates were obtained at 3 and 6 months after LCM introduction. RESULT: The overall response rates were 53.3 and 70.4% after 3 and 6 months, respectively, and the freedom of seizures at the same points was reached at 19 and 26.5%. The retention rates were 99.1% at the 3-month follow-up and 93.3% at the 6-month follow-up. The overall incidence of adverse events was 35.8%. The leading AEs were dizziness (16.98%) and sedation (6.6%). CONCLUSIONS: Our study confirmed the efficacy and tolerability of adjunctive LCM in Chinese patients in real-life conditions. Based on our treatment experience, a universal maintenance dose of LCM would be needed in Chinese patients.

Predictive role of blood-based indicators in neuromyelitis optica spectrum disorders.

Introduction: This study aimed to assess the predictive role of blood markers in neuromyelitis optica spectrum disorders (NMOSD). Methods: Data from patients with NMOSD, multiple sclerosis (MS), and healthy individuals were retrospectively collected in a 1:1:1 ratio. The expanded disability status scale (EDSS) score was used to assess the severity of the NMOSD upon admission. Receiver operating characteristic (ROC) curve analysis was used to distinguish NMOSD patients from healthy individuals, and active NMOSD from remitting NMOSD patients. Binary logistic regression analysis was used to evaluate risk factors that could be used to predict disease recurrence. Finally, Wilcoxon signed-rank test or matched-sample t-test was used to analyze the differences between the indicators in the remission and active phases in the same NMOSD patient. Results: Among the 54 NMOSD patients, neutrophil count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) (platelet × NLR) were significantly higher than those of MS patients and healthy individuals and positively correlated with the EDSS score of NMOSD patients at admission. PLR can be used to simultaneously distinguish between NMOSD patients in the active and remission phase. Eleven (20.4%) of the 54 patients had recurrence within 12 months. We found that monocyte-to-lymphocyte ratio (MLR) (AUC = 0.76, cut-off value = 0.34) could effectively predict NMOSD recurrence. Binary logistic regression analysis showed that a higher MLR at first admission was the only risk factor for recurrence (p = 0.027; OR = 1.173; 95% CI = 1.018-1.351). In patients in the relapsing phase, no significant changes in monocyte and lymphocyte count was observed from the first admission, whereas patients in remission had significantly higher levels than when they were first admitted. Conclusion: High PLR is a characteristic marker of active NMOSD, while high MLR is a risk factor for disease recurrence. These inexpensive indicators should be widely used in the diagnosis, prognosis, and judgment of treatment efficacy in NMOSD.

Efficacy, tolerability and safety of perampanel in children and adolescents with epilepsy: Systematic review and meta-analysis.

OBJECTIVE: Perampanel (PER) is a novel antiepileptic drug. The efficacy, tolerability and safety of PER in children and adolescents with epilepsy are still unclear. We aimed to study the efficacy and safety of PER in children and adolescents with epilepsy. METHODS: We searched PubMed, Embase and Cochrane Library for relevant literature up to November 2022. Then we extracted the relevant data from eligible literature for systematic review and meta-analysis. RESULT: Twenty-one studies involving 1968 children and adolescent patients were included. A reduction in seizure frequency of at least 50 percent occurred in 51.5% (95% confidence interval [CI] [47.1%, 55.9%]) of patients. Complete seizure cessation occurred in 20.6% (95%CI [16.7%, 25.4%]). The incidence of adverse events was 40.8% (95%CI [33.8%, 48.2%]). The most common adverse events were drowsiness 15.3% (95% CI [13.7%, 16.9%]), irritability 9.3% (95%CI [8.0%, 10.6%]), dizziness 8.4% (95% CI [7.2%, 9.7%]). The incidence of drug discontinuation due to adverse events was 9.2% (95% CI [7.0%, 11.5%]). CONCLUSION: PER is generally well tolerated and effective in the treatment of epilepsy in children and adolescents. Larger studies are still needed to explore the application of PER in children and adolescents. RISK OF BIAS AND LIMITATION: The funnel plot suggests that there may be publication bias in our meta-analysis, and most of the included studies were Asian, so there may be some racial differences.