MicroRNAs as potential biomarkers in temporal lobe epilepsy and mesial temporal lobe epilepsy

Temporal lobe epilepsy is the most common form of focal epilepsy in adults,accounting for one third of all diagnosed epileptic patients,with seizures originating from or involving mesial temporal structures such as the hippocampus,and many of these patients being refractory to treatment with anti-epileptic drugs.Temporal lobe epilepsy is the most common childhood neurological disorder and,compared with adults,the symptoms are greatly affected by age and brain development.Diagnosis of temporal lobe epilepsy relies on clinical examination,patient history,electroencephalographic recordings,and brain imaging.Misdiagnosis or delay in diagnosis is common.A molecular biomarker that could distinguish epilepsy from healthy subjects and other neurological conditions would allow for an earlier and more accurate diagnosis and appropriate treatment to be initiated.Among possible biomarkers of pathological changes as well as potential therapeutic targets in the epileptic brain are micro RNAs.Most of the recent studies had performed micro RNA profiling in body fluids such as blood plasma and blood serum and brain tissues such as temporal cortex tissue and hippocampal tissue.A large number of micro RNAs were dysregulated when compared to healthy controls and with some overlap between individual studies that could serve as potential biomarkers.For example,in adults with temporal lobe epilepsy,possible biomarkers are miR-199a-3p in blood plasma and miR-142-5p in blood plasma and blood serum.In adults with mesial temporal lobe epilepsy,possible biomarkers are miR-153 in blood plasma and miR-145-3p in blood serum.However,in many of the studies involving patients who receive one or several anti-epileptic drugs,the influence of these on micro RNA expression in body fluids and brain tissues is largely unknown.Further studies are warranted with children with temporal lobe epilepsy and consideration should be given to utilizing mouse or rat and non-human primate models of temporal lobe epilepsy.The animal models could be used to confirm micro RNA findings in human patients and to test the effects of targeting specific micro RNAs on disease progression and behavior.

Anomalous expression of chloride transporters in the sclerosed hippocampus of mesial temporal lobe epilepsy patients

The Na＋-K＋-CI- cotransporter 1 and K＋-CI- cotransporter 2 regulate the levels of intracellular chloride in hippocampal cells. Impaired chloride transport by these proteins is thought to be involved in the pathophysiological mechanisms of mesial temporal lobe epilepsy. Imbalance in the relative expression of these two proteins can lead to a collapse of CI- homeostasis, resulting in a loss of gamma-aminobutyric acid-ergic inhibition and even epileptiform discharges. In this study, we investigated the expression of Na＋-K＋-CI- cotransporter 1 and K＋-CI- cotransporter 2 in the sclerosed hippocampus of patients with mesial temporal lobe epilepsy, using western blot analysis and immunohistochemistry. Compared with the histologically normal hippocampus, the sclerosed hippocampus showed increased Na＋-K＋-Cl- cotransporter 1 expression and decreased K＋-CI- cotransporter 2 expression, especially in CA2 and the dentate gyrus. The change was more prominent for the Na＋-K＋-CI- cotransporter 1 than for the K＋-CI- cotransporter 2. These experimental findings indicate that the balance between intracellular and extracellular chloride may be disturbed in hippocampal sclerosis, contributing to the hyperexcitability underlying epileptic seizures. Changes in Na＋-K＋-CI-cotransporter 1 expression seems to be the main contributor. Our study may shed new light on possible therapies for patients with mesial temporal lobe epilepsy with hippocampal sclerosis.

Anterior temporal lobectomy improved mood status and quality of life in Chinese patients with mesial temporal lobe epilepsy:a single-arm cohort study

Background: Many studies have emphasized that selective resection of epileptic lesions in temoral lobe is associated with better preservation of cognition function;whether this applies to patients with refractory mesial temporal lobe epilepsy (MTLE) remains unknown. The objective of this study was to evaluate changes in cognitive functions, mood status, and quality of life after anterior temporal lobectomy in patients with refractory MTLE. Methods: This single-arm cohort study assessed cognitive function, mood status, and quality of life, as well as electroencephalography findings, in patients with refractory MTLE who underwent anterior temporal lobectomy at Xuanwu Hospital from January 2018 to March 2019. Pre- and post-operative characteristics were compared to evaluate the effects of surgery. Results: Anterior temporal lobectomy significantly reduced the frequencies of epileptiform discharges. The overall success rate of surgery was acceptable. Anterior temporal lobectomy did not result in significant changes in overall cognitive functions (P > 0.05), although changes in certain domains, including visuospatial ability, executive ability, and abstract thinking, were detected. Anterior temporal lobectomy resulted in improvements in anxiety and depression symptoms and quality of life. Conclusions: Anterior temporal lobectomy reduced epileptiform discharges and incidence of post-operative seizures as well as resulted in improved mood status and quality of life without causing significant changes in cognitive function.

Machine learning for detecting mesial temporal lobe epilepsy by structural and functional neuroimaging

Mesial temporal lobe epilepsy(mTLE),the most common type of focal epilepsy,is associated with functional and structural brain alterations.Machine learning(ML)techniques have been successfully used in discriminating mTLE from healthy controls.However,either functional or structural neuroimaging data are mostly used separately as input,and the opportunity to combine both has not been exploited yet.We conducted a multimodal ML study based on functional and structural neuroimaging measures.We enrolled 37 patients with left mTLE,37 patients with right mTLE,and 74 healthy controls and trained a support vector ML model to distinguish them by using each measure and the combinations of the measures.For each single measure,we obtained a mean accuracy of 74%and 69%for discriminating left mTLE and right mTLE from controls,respectively,and 64%when all patients were combined.We achieved an accuracy of 78%by integrating functional data and 79%by integrating structural data for left mTLE,and the highest accuracy of 84%was obtained when all functional and structural measures were combined.These findings suggest that combining multimodal measures within a single model is a promising direction for improving the classification of individual patients with mTLE.

Lateralizing value of ictal face wiping in patients with mesial temporal lobe epilepsy

Objective To investigate the lateralizing value of ictal face wiping(FW)in patients with refractory mesial temporal lobe epilepsy(MTLE).Methods Presurgical video types were retrospectively reviewed among 96 patients who were seizure-free for at least 3 years after temporal lobectomy between 1997 and 2012.Attention

Temporal lobe epilepsy associated with human herpes virus 6

Human herpes virus 6(HHV-6)is a ubiquitous and most common pathogen that affects humans.Human herpes virus 6B(HHV-6B)is a wide spread human herpesvirus that infects most people when they are children,establishes latent infections in the central nervous system(CNS),especially in the hippocampus and amygdala,and induces neurologic diseases.HHV-6 can establish a latent infection and be reactivated by various stimuli.Recently,viral genomic DNA of HHV-6B has been detected in surgically removed brain tissues of intractable epilepsy patients,suggesting the involvement of HHV-6B in the pathogenesis of epilepsy.Temporal lobe epilepsy(TLE)has been shown to be closely related with HHV-6B.TLE patients with HHV-6B in their brains suffer from reiterative attacks of febrile seizures and hippocampal sclerosis.However,the mechanisms underlying the contribution of this virus to the development of TLE remains unknown.The direct damage and immune activation caused by the virus are involved in the process of neuron damage,abnormal neural circuit formation and glial cell proliferation.In addition,some cytokines like interleukin-17A(IL-17A),nuclear factor-kappa B(NF-κb),transforming growth factor-β(TGF-β),mitogen-activated protein kinase(MAPK)and phospholipase A2 are up-regulated and involved in the pathological process of TLE.More studies are needed to clarify the mechanisms underlying the link between HHV-6B and epilepsy,and identify biomarkers to recognize different patient groups for anti-inflammatory or immunomodulatory therapies.