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.

Microglia in the context of multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease that commonly results in nontraumatic disability in young adults. The characteristic pathological hallmark of MS is damage to myelin, oligodendrocytes, and axons. Microglia provide continuous surveillance in the CNS microenvironment and initiate defensive mechanisms to protect CNS tissue. Additionally, microglia participate in neurogenesis, synaptic refinement, and myelin pruning through the expression and release of different signaling factors. Continuous activation of microglia has been implicated in neurodegenerative disorders. We first review the lifetime of microglia, including the origin, differentiation, development, and function of microglia. We then discuss microglia participate in the whole processes of remyelination and demyelination, microglial phenotypes in MS, and the NF-κB/PI3K-AKT signaling pathway in microglia. The damage to regulatory signaling pathways may change the homeostasis of microglia, which would accelerate the progression of MS.

Weight Status Is Associated with Blood Pressure, Vital Capacity, Dental Decay, and Visual Acuity among School-Age Children in Chengdu, China.

AIMS: To examine the association of weight status with the prevalence of blood pressure (BP), vital capacity, dental decay, and visual acuity among school-age children in Chengdu, China and to find the potential role of weight status to predict the common and frequently occurring diseases among school-age children. METHODS: A cross-sectional study was conducted among 12,297 children aged 6-18 years from 10 schools in the Jinniu District of Chengdu, China. Body height, weight, waist circumference (WC), and BP were measured. Vital capacity, dental decay, and visual acuity were detected. RESULTS: The overall prevalence of underweight, overweight, obesity, abdominal obesity, high BP, bad vital capacity weight index, dental decay, and low vision were 7.18, 13.47, 7.57, 18.90, 2.78, 21.93, 38.81, and 45.79%, respectively. After controlling for age, gender, and WC, it was found that overweight and obese children had a higher risk of developing high BP than normal weight children ([OR 4.20, p < 0.001] and [OR 8.76, p < 0.001], respectively), And adjusting for age, gender, and chest circumference, the risk of having bad vital capacity weight index among children with overweight and obesity was higher ([OR 2.15, p < 0.001] and [OR 5.40, p < 0.001], respectively), and the risk with underweight was lower (OR 0.35, p < 0.001). After eliminating the influential factors of gender and age, children who were underweight were 1.16 times (OR 1.16, p = 0.048) more likely to have caries than children with normal weight, but obese children were found to have a lower prevalence for dental cavities than children with normal weight (OR 0.79, p = 0.002). Underweight and obese children had a higher prevalence of low vision; the OR of the appearance of low vision was 1.21 (p = 0.016) for underweight children and 1.23 (p = 0.009) for obese children after adjusting the age and gender. CONCLUSIONS: Abnormal weight status among Chengdu urban school-age children was found to be a severe health problem, and it was strongly associated with BP, vital capacity, dental decay, and visual acuity.

Studies on the effect of adenosine on calcium oscillation in hippocampal neurons.

Adenosine (Ade) is an antiepileptic agent. In order to investigate the possible mechanism of action of Ade, its effect on calcium (Ca2+) oscillations in hippocampal neurons of Sprague Dawley (SD) rats was explored. Primary hippocampal neurons were cultured from suckling neonatal SD rats. Cells were cultured for 7-9 days and the Ca2+ oscillations in response to perfusion with Ade were detected using confocal laser scanning microscopy in combination with Fluo-3/AM labeling. This study found that Ade inhibits the spontaneous synchronized Ca2+ oscillation frequency and amplitude in mature hippocampal neurons and such inhibition depends on the Ade dosage level to a certain extent. Ade also had a significant inhibitory effect on high potassium-induced Ca2+ oscillation frequency and amplitude. Ade had a significant inhibitory effect on high-voltage-activated Ca2+ channel-mediated Ca2+ influx and Ca2+ oscillations in neurons. This may be one of the mechanisms for Ade to exert antiepileptic effects as an endogenous substance.

Induction of KLF4 contributes to the neurotoxicity of MPP + in M17 cells: a new implication in Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease in humans. The effect of Krüppel-like factor (KLF) 4 in PD is unknown. In this study, KLF4 was found to be increased in both a time-dependent manner and a dose-dependent manner in response to the incubation with 1-methyl-4-phenylpyridinium (MPP+) in human dopamine neuroblastoma M17 cells, suggesting a potential role in MPP + -induced neurotoxicity. Following experiments showed that overexpression of KLF4 in M17 cells promoted MPP + -induced oxidative stress, embodied by exacerbated reactive oxygen species, 4-hydroxy-2-nonenal, and protein carbonyls. Furthermore, overexpression of KLF4 slowed cell proliferation and promoted lactate dehydrogenase release. Conversely, inhibition of KLF4 in M17 cells attenuated MPP + -induced neurotoxicity. The expression of superoxide dismutase (SOD) 1 in both mRNA and protein levels was found to be decreased by overexpressing KLF4, while increased by knockdown of KLF4. Moreover, promoter luciferase experiments showed that transcriptional activity on SOD1 was inhibited by KLF4. All the results indicated that KLF4 promoted the neurotoxicity of MPP + via inhibiting the transcription of SOD1, suggesting a potential mechanism of increased oxidative stress and cell death in Parkinson's disease.