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.

Aim: To systematically evaluate the safety and tolerability of calcitonin-gene-related peptide binding monoclonal antibodies from the results of randomized controlled trials. Methods: Online databases were searched on calcitonin-gene-related peptide binding monoclonal antibodies for the prevention of episodic migraine. Overall withdrawal, withdrawal due to adverse events, adverse events, serious adverse events and specific adverse events were extracted from the included studies. A meta-analysis was performed with Revman 5.3.0 software. Results: Ten studies that investigated four drugs (galcanezumab, erenumab, fremanezumab and eptinezumab) with 5817 participants were included in this study. Serious adverse events, overall withdrawals, withdrawal due to adverse events and any adverse events were not significantly associated with monoclonal antibody treatment. Injection site pain and erythema were significantly higher in the calcitonin-gene-related peptide binding monoclonal antibodies treatment group than in the placebo group. The rates of serious adverse events were significantly higher in the galcanezumab 120 mg group. Injection site erythema was associated with galcanezumab 120 mg and 240 mg. Injection site pain and nasopharyngitis were associated with galcanezumab 150 mg and 5 mg, respectively. Overall adverse events were significantly higher with erenumab 70 mg and 140 mg. Treatment-related adverse events were significantly higher with fremanezumab 225 mg/month and 675 mg/quarter. Conclusions: This study provides data on the safety and tolerability profiles of calcitonin-gene-related peptide binding monoclonal antibodies and confirms their potential use as preventive treatments for episodic migraine. In addition to the acceptable withdrawal rates, serious adverse events were rare, and the severity of most adverse events was mild to moderate. Injection site reaction may be the major adverse event associated with galcanezumab.

Epilepsy is a collection of neurological disorders characterized by abnormal neuronal discharges, resulting in spontaneous and recurrent unprovoked seizures. Despite the use of over 20 anti-seizure drugs, conventional one-size-fits-all approaches are insufficient to meet the needs of all patients, and about 1/3 patients developed drug-resistant epilepsy. Recently, the establishment of precision medicine-based clinical management for epilepsy may bring new insights, especially omics-based approaches. Single omics approach is limited to addressing questions from a single molecular perspective. Whereas multi-omics approaches enable a comprehensive characterization of multiple molecules, revealing the complex molecular dysregulation networks underlying different epilepsy phenotypes. Furthermore, multi-omics methods have catalyzed a paradigm shift in scientific inquiry, transitioning from traditional hypothesis-driven types to data-driven research architectures. Despite the full potential of multi-omics research yet to be realized, its application in epilepsy holds great promise, from the discovery of epileptic biomarkers to personalized management. In this review, we performed a comprehensive overview of the omics technologies and multi-omics integration strategies, followed by an exploration of their role in enhancing the management of epilepsy treatment and care, hoping to provide new directions for future researches.