Systematic Analysis of the Relationship Between Elevated Zinc and Epilepsy.

Previous studies have indicated a potential relationship between zinc and epilepsy. The aim of this study is to investigate the causal relationship between zinc, zinc-dependent carbonic anhydrase, and gray matter volume in brain regions enriched with zinc and epilepsy, as well as explore the possible mechanisms by which zinc contributes to epilepsy. First, this study assessed the risk causality between zinc, carbonic anhydrase, and gray matter volume alterations in zinc-enriched brain regions and various subtypes of epilepsy based on Two-sample Mendelian randomization analysis. And then, this study conducted GO/KEGG analysis based on colocalization analysis, MAGMA analysis, lasso regression, random forest model, and XGBoost model. The results of Mendelian randomization analyses showed a causal relationship between zinc, carbonic anhydrase-4, and generalized epilepsy (p = 0.044 , p = 0.010). Additionally, carbonic anhydrase-1 and gray matter volume of the caudate nucleus were found to be associated with epilepsy and focal epilepsy (p = 0.014, p = 0.003 and p = 0.022, p = 0.009). A colocalization relationship was found between epilepsy and focal epilepsy (PP.H4.abf = 97.7e - 2). Meanwhile, the MAGMA analysis indicated that SNPs associated with epilepsy and focal epilepsy were functionally localized to zinc-finger-protein-related genes (p < 1.0e - 5). The genes associated with focal epilepsy were found to have a molecular function of zinc ion binding (FDR = 2.3e - 6). After the onset of epilepsy, the function of the gene whose expression changed in the rats with focal epilepsy was enriched in the biological process of vascular response (FDR = 4.0e - 5). These results revealed mechanism of the increased risk of epilepsy caused by elevated zinc may be related to the increase of zinc ion-dependent carbonic anhydrase or the increase of the volume of zinc-rich caudate gray matter.

Differences in the distribution of triggers among resting state networks in patients with juvenile myoclonic epilepsy explained by network analysis.

Background: Juvenile myoclonus epilepsy (JME) is an idiopathic generalized epilepsy syndrome. Functional connectivity studies based on graph theory have demonstrated changes in functional connectivity among different brain regions in patients with JME and healthy controls. However, previous studies have not been able to clarify why visual stimulation or increased cognitive load induces epilepsy symptoms in only some patients with JME. Methods: This study constructed a small-world network for the visualization of functional connectivity of brain regions in patients with JME, based on system mapping. We used the node reduction method repeatedly to identify the core nodes of the resting brain network of patients with JME. Thereafter, a functional connectivity network of the core brain regions in patients with JME was established, and it was analyzed manually with white matter tracks restriction to explain the differences in symptom distribution in patients with JME. Results: Patients with JME had 21 different functional connections in their resting state, and no significant differences in their distribution were noted. The thalamus, cerebellum, basal ganglia, supplementary motor area, visual cortex, and prefrontal lobe were the core brain regions that comprised the functional connectivity network in patients with JME during their resting state. The betweenness centrality of the prefrontal lobe and the visual cortex in the core functional connectivity network of patients with JME was lower than that of the other brain regions. Conclusion: The functional connectivity and node importance of brain regions of patients with JME changed dynamically in the resting state. Abnormal discharges originating from the thalamus, cerebellum, basal ganglia, supplementary motor area, visual cortex, and prefrontal cortex are most likely to lead to seizures in patients with JME. Further, the low average value of betweenness centrality of the prefrontal and visual cortices explains why visual stimulation or increased cognitive load can induce epileptic symptoms in only some patients with JME.