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 th...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.展开更多
Cognitive impairment is the most common complication in patients with temporal lobe epilepsy with hippocampal scle rosis.There is no effective treatment for cognitive impairment.Medial septum cholinergic neurons have ...Cognitive impairment is the most common complication in patients with temporal lobe epilepsy with hippocampal scle rosis.There is no effective treatment for cognitive impairment.Medial septum cholinergic neurons have been reported to be a potential target for controlling epileptic seizures in tempo ral lobe epile psy.However,their role in the cognitive impairment of temporal lobe epilepsy remains unclear.In this study,we found that patients with temporal lobe epile psy with hippocampal sclerosis had a low memory quotient and severe impairment in verbal memory,but had no impairment in nonverbal memory.The cognitive impairment was slightly correlated with reduced medial septum volume and medial septum-hippocampus tra cts measured by diffusion tensor imaging.In a mouse model of chronic temporal lobe epilepsy induced by kainic acid,the number of medial septum choline rgic neurons was reduced and acetylcholine release was reduced in the hippocampus.Furthermore,selective apoptosis of medial septum cholinergic neurons mimicked the cognitive deficits in epileptic mice,and activation of medial septum cholinergic neurons enhanced hippocampal acetylcholine release and restored cognitive function in both kainic acid-and kindling-induced epile psy models.These res ults suggest that activation of medial septum cholinergic neurons reduces cognitive deficits in temporal lobe epilepsy by increasing acetylcholine release via projections to the hippocampus.展开更多
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 pathophys...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.展开更多
Epilepsy is a common neurological disorder, and its electrophysiology characteristic is abnormally high excitability and synchronization of the neural activity. This paper focuses on the study of medial temporal lobe ...Epilepsy is a common neurological disorder, and its electrophysiology characteristic is abnormally high excitability and synchronization of the neural activity. This paper focuses on the study of medial temporal lobe epilepsy with hippocampal sclerosis. The hippocampus plays an important role in short-term memory. However, little is known about the connectivity between hippocampal structures and adjacent brain regions. The functional and structural connectivity between patients and controls was investigated by using the techniques of functional magnetic resonance imaging and diffusion tensor imaging in the paper. Three pairs of ROIs related to working memory from BOLD-fMRI data were chosen. These ROIs were registrated from MNI space to individual space and the fiber bundle between two ROIs were traced in the DTI images. The results show that the number of fiber bundle of patients reduce among these ROIs, such as left hippocampus and right hippocampus, left hippocampus and left thalamus, left hippocampus and left frontal lobe and so on. And the number of fiber bundle of patients increase among these ROIs, such as left thalamus and right thalamus, right hippocampus and right thalamus. And the FA values of the fiber bundles of patients in some regions related to left hippocampus decrease. The cause of abnormal functional and structural connections due to the damage of hippocampus in medial temporal lobe epilepsy is studied from a new perspective.展开更多
Objective To detect for hippocampal sclerosis presurgically in a group of patients with refractory temporal lobe epilepsy Methods Eighty four consecutive patients with refractory temporal lobe epilepsy were subjec...Objective To detect for hippocampal sclerosis presurgically in a group of patients with refractory temporal lobe epilepsy Methods Eighty four consecutive patients with refractory temporal lobe epilepsy were subjected to brain MRI of hippocampal volumetry A ratio of smaller to larger hippocampal volume was determined and unilateral hippocampal atrophy (HA) was diagnosed if the ratio is less than 0 91 Results Unilateral HA was diagnosed in 42 patients (50%) and bilateral HA in 1 patient Other MRI abnormalities were detected in 18 patients with or without coexisting HA Conclusions Hippocampal sclerosis can be detected presurgically in many patients by brain MRI Additional abnormalities not detected by brain CT can also be demonstrated展开更多
Tuberous sclerosis complex(TSC)is a rare disease that involves multiple organs,including the brain;approximately 80%-90%of TSC patients exhibit TSC-associated epilepsy.Independent temporal lobe epilepsy(TLE),TSC-unrel...Tuberous sclerosis complex(TSC)is a rare disease that involves multiple organs,including the brain;approximately 80%-90%of TSC patients exhibit TSC-associated epilepsy.Independent temporal lobe epilepsy(TLE),TSC-unrelated epilepsy,is particularly rare in patients with TSC.Here,we describe three patients with TSC with independent TLEs that were confirmed by stereo-electroencephalography(EEG),postoperative pathological findings,and seizure outcome at follow-up.The patients were retrospectively enrolled at two centers;their ictal epileptiform discharge onsets were determined using electrode contacts in the hippocampus during stereo-EEG.The three patients underwent anterior temporal lobectomies and remained seizure-free at 1-5 years after surgery.Postoperative pathological examinations confirmed hippocampal sclerosis in all three patients.Furthermore,postoperative intelligence quotient improvement was evident in one patient,while the quality of life was improved in two patients at 12 months after surgery.展开更多
文摘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.
基金National Natural Science Foundation of China,Nos.82003 729 (to Ying W),82022071 (to YiW)Natural Science Foundation of Shandong Province of China,No.ZR2020QH357 (to Ying W)Public Welfare Technology Research Program of Zhejiang Province,No.LGF20H09001 1 (to JF)。
文摘Cognitive impairment is the most common complication in patients with temporal lobe epilepsy with hippocampal scle rosis.There is no effective treatment for cognitive impairment.Medial septum cholinergic neurons have been reported to be a potential target for controlling epileptic seizures in tempo ral lobe epile psy.However,their role in the cognitive impairment of temporal lobe epilepsy remains unclear.In this study,we found that patients with temporal lobe epile psy with hippocampal sclerosis had a low memory quotient and severe impairment in verbal memory,but had no impairment in nonverbal memory.The cognitive impairment was slightly correlated with reduced medial septum volume and medial septum-hippocampus tra cts measured by diffusion tensor imaging.In a mouse model of chronic temporal lobe epilepsy induced by kainic acid,the number of medial septum choline rgic neurons was reduced and acetylcholine release was reduced in the hippocampus.Furthermore,selective apoptosis of medial septum cholinergic neurons mimicked the cognitive deficits in epileptic mice,and activation of medial septum cholinergic neurons enhanced hippocampal acetylcholine release and restored cognitive function in both kainic acid-and kindling-induced epile psy models.These res ults suggest that activation of medial septum cholinergic neurons reduces cognitive deficits in temporal lobe epilepsy by increasing acetylcholine release via projections to the hippocampus.
基金supported by the Science and Technology Foundation of Guangdong Province,No.2008B060600063the National Natural Science Foundation of China,No. 81071050the Natural Science Foundation of Guangdong Province,No. S2011020005483
文摘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.
基金National Natural Science Foundation of Chinagrant number: 6075107
文摘Epilepsy is a common neurological disorder, and its electrophysiology characteristic is abnormally high excitability and synchronization of the neural activity. This paper focuses on the study of medial temporal lobe epilepsy with hippocampal sclerosis. The hippocampus plays an important role in short-term memory. However, little is known about the connectivity between hippocampal structures and adjacent brain regions. The functional and structural connectivity between patients and controls was investigated by using the techniques of functional magnetic resonance imaging and diffusion tensor imaging in the paper. Three pairs of ROIs related to working memory from BOLD-fMRI data were chosen. These ROIs were registrated from MNI space to individual space and the fiber bundle between two ROIs were traced in the DTI images. The results show that the number of fiber bundle of patients reduce among these ROIs, such as left hippocampus and right hippocampus, left hippocampus and left thalamus, left hippocampus and left frontal lobe and so on. And the number of fiber bundle of patients increase among these ROIs, such as left thalamus and right thalamus, right hippocampus and right thalamus. And the FA values of the fiber bundles of patients in some regions related to left hippocampus decrease. The cause of abnormal functional and structural connections due to the damage of hippocampus in medial temporal lobe epilepsy is studied from a new perspective.
文摘Objective To detect for hippocampal sclerosis presurgically in a group of patients with refractory temporal lobe epilepsy Methods Eighty four consecutive patients with refractory temporal lobe epilepsy were subjected to brain MRI of hippocampal volumetry A ratio of smaller to larger hippocampal volume was determined and unilateral hippocampal atrophy (HA) was diagnosed if the ratio is less than 0 91 Results Unilateral HA was diagnosed in 42 patients (50%) and bilateral HA in 1 patient Other MRI abnormalities were detected in 18 patients with or without coexisting HA Conclusions Hippocampal sclerosis can be detected presurgically in many patients by brain MRI Additional abnormalities not detected by brain CT can also be demonstrated
基金Beijing Natural Science Foundation of China,Grant/Award Number:7202045National Nature Science Foundation of China,Grant/Award Number:82071488。
文摘Tuberous sclerosis complex(TSC)is a rare disease that involves multiple organs,including the brain;approximately 80%-90%of TSC patients exhibit TSC-associated epilepsy.Independent temporal lobe epilepsy(TLE),TSC-unrelated epilepsy,is particularly rare in patients with TSC.Here,we describe three patients with TSC with independent TLEs that were confirmed by stereo-electroencephalography(EEG),postoperative pathological findings,and seizure outcome at follow-up.The patients were retrospectively enrolled at two centers;their ictal epileptiform discharge onsets were determined using electrode contacts in the hippocampus during stereo-EEG.The three patients underwent anterior temporal lobectomies and remained seizure-free at 1-5 years after surgery.Postoperative pathological examinations confirmed hippocampal sclerosis in all three patients.Furthermore,postoperative intelligence quotient improvement was evident in one patient,while the quality of life was improved in two patients at 12 months after surgery.
