Microglia in epilepsy.

Epilepsy is one of most common chronic neurological disorders, and the antiseizure medications developed by targeting neurocentric mechanisms have not effectively reduced the proportion of patients with drug-resistant epilepsy. Further exploration of the cellular or molecular mechanism of epilepsy is expected to provide new options for treatment. Recently, more and more researches focus on brain network components other than neurons, among which microglia have attracted much attention for their diverse biological functions. As the resident immune cells of the central nervous system, microglia have highly plastic transcription, morphology and functional characteristics, which can change dynamically in a context-dependent manner during the progression of epilepsy. In the pathogenesis of epilepsy, highly reactive microglia interact with other components in the epileptogenic network by performing crucial functions such as secretion of soluble factors and phagocytosis, thus continuously reshaping the landscape of the epileptic brain microenvironment. Indeed, microglia appear to be both pro-epileptic and anti-epileptic under the different spatiotemporal contexts of disease, rendering interventions targeting microglia biologically complex and challenging. This comprehensive review critically summarizes the pathophysiological role of microglia in epileptic brain homeostasis alterations and explores potential therapeutic or modulatory targets for epilepsy targeting microglia.

Gene mutations in comorbidity of epilepsy and arrhythmia.

Epilepsy is one of the most common neurological disorders, and sudden unexpected death in epilepsy (SUDEP) is the most severe outcome of refractory epilepsy. Arrhythmia is one of the heterogeneous factors in the pathophysiological mechanism of SUDEP with a high incidence in patients with refractory epilepsy, increasing the risk of premature death. The gene co-expressed in the brain and heart is supposed to be the genetic basis between epilepsy and arrhythmia, among which the gene encoding ion channel contributes to the prevalence of "cardiocerebral channelopathy" theory. Nevertheless, this theory could only explain the molecular mechanism of comorbid arrhythmia in part of patients with epilepsy (PWE). Therefore, we summarized the mutant genes that can induce comorbidity of epilepsy and arrhythmia and the possible corresponding treatments. These variants involved the genes encoding sodium, potassium, calcium and HCN channels, as well as some non-ion channel coding genes such as CHD4, PKP2, FHF1, GNB5, and mitochondrial genes. The relationship between genotype and clinical phenotype was not simple linear. Indeed, genes co-expressed in the brain and heart could independently induce epilepsy and/or arrhythmia. Mutant genes in brain could affect cardiac rhythm through central or peripheral regulation, while in the heart it could also affect cerebral electrical activity by changing the hemodynamics or internal environment. Analysis of mutations in comorbidity of epilepsy and arrhythmia could refine and expand the theory of "cardiocerebral channelopathy" and provide new insights for risk stratification of premature death and corresponding precision therapy in PWE.

[Comparison of amiodarone plus irbesartan regimen versus amiodarone alone on maintaining sinus rhythm in rheumatic heart disease patients with persistent atrial fibrillation post valve replacement and cardioversion].

OBJECTIVE: To compare the efficacy of combined amiodarone and irbesartan use versus amiodarone alone on maintaining sinus rhythm in rheumatic heart disease patients with persistent atrial fibrillation (AF) post valve replacement and cardioversion. METHODS: Patients were randomly divided into amiodarone group (A, n = 31) and amiodarone plus irbesartan group (AI, n = 32) and all patients received Warfarin (INR 2.0 - 3.0). For patients in group A, intravenous amiodarone (600 mg/d) was applied for 10 days and oral amiodarone (200 mg, b.i.d.) was given on the 7th day for 3 days. For patients in group AI, irbesartan (150 mg/d) was added on top of amiodarone at the study begin. Electric cardioversion was performed for patients still with AF on day 10. Amiodarone (200 mg, b.i.d. for 1 week, then 200 mg, q.d. till study end) with or without irbesartan (150 mg/d) was continued thereafter. Patients were followed up for 12 months after sinus rhythm recovery. The primary end points are first recurrence of symptomatic and asymptomatic AF. RESULTS: Twelve months post therapy, number of patients on sinus rhythm was significantly higher (68.7% vs. 41.9%, P<0.05) and left atrium diameter (LAD) was significantly smaller [(48.6 +/- 4.6) mm vs. (51.5 +/- 4.2) mm, P<0.05] in group AI than those in group A. LAD (OR 1.242) and use of irbesartan (OR 0.226) are associated with the AF recurrence. CONCLUSION: Combined amiodarone and irbesartan use is superior to amiodarone alone for maintaining sinus rhythm in rheumatic heart disease patients with persistent AF post valve replacement and cardioversion.