MRI and ~1H-MRS detects volumetric and metabolic abnormalities of hippocampal sclerosis in temporal lobe epilepsy

Objective：To further investigate the ability of MRI and ^1H-MRS techniques for presurgical evaluation of hippocampal sclerosis. Methods：MRI and ^1H-MRS were performed on 30 healthy subjects to determine the confidence levels. Eight patients who were pathologically confirmed hippocampal sclerosis were then studied using the same protocols. The difference of hippocampal formation （DHF） was used to determine atrophy of hippocampus. Areas under the peak of N-acetylaspartate（NAA） ,Creatine（Cr） and Choline （Cho） were measured, and the ratios of NAA/Cr, Cho/Cr, and NAA/Cr＋Cho were calculated. NAA/Cr＋Cho value was applied to localize the seizure focus. Results：Two patients showed hippocampal atrophy according to DHF value. NAA/Cr ratio decreased significantly in ipsilateral hippocampus compared to that in contralateral hippocampus and control subjects（P 〈 0.01）. Cho/Cr value increased in both ipsi- and contralateral hippocampus in comparison with that in control subjects（P〈 0.01）. NAA/Cr＋Cho ratio, however, significantly reduced in both ipsi-and contralateral hippocampus（P〈 0.01） with lowest NAA/Cr＋Cho ratio in seizure foci. Six patients could be lateralized by reduced and/or asymmetric NAA/Cr＋Cho value. Conclusion：^1H-MRS should be a promising diagnostic tool to detect neuron abnormality, ^1H-MRS and MRI complement each other in presurgical lateralization of epileptogenic lesion in epilepsy patients.

Effects of febrile seizures in mesial temporal lobe epilepsy with hippocampal sclerosis on gene expression using bioinformatical analysis

Background:To investigate the effect of long-term febrile convulsions on gene expression in mesial temporal lobe epilepsy with hippocampal sclerosis(MTLE-HS)and explore the molecular mechanism of MTLE-HS.Methods:Microarray data of MTLE-HS were obtained from the Gene Expression Omnibus database.Differentially expressed genes(DEGs)between MTLE-HS with and without febrile seizure history were screened by the GEO2R software.Pathway enrichment and gene ontology of the DEGs were analyzed using the DAVID online database and FunRich software.Protein–protein interaction(PPI)networks among DEGs were constructed using the STRING database and analyzed by Cytoscape.Results:A total of 515 DEGs were identified in MTLE-HS samples with a febrile seizure history compared to MTLEHS samples without febrile seizure,including 25 down-regulated and 490 up-regulated genes.These DEGs were expressed mostly in plasma membrane and synaptic vesicles.The major molecular functions of those genes were voltage-gated ion channel activity,extracellular ligand-gated ion channel activity and calcium ion binding.The DEGs were mainly involved in biological pathways of cell communication signal transduction and transport.Five genes(SNAP25,SLC32A1,SYN1,GRIN1,and GRIA1)were significantly expressed in the MTLE-HS with prolonged febrile seizures.Conclusion:The pathogenesis of MTLE-HS involves multiple genes,and prolonged febrile seizures could cause differential expression of genes.Thus,investigations of those genes may provide a new perspective into the mechanism of MTLE-HS.

Activation of medial septum cholinergic neurons restores cognitive function in temporal lobe epilepsy

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.

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.

Research on Medial Temporal Lobe Epilepsy by Combining Structural and Functional MRI

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.

Study on hippocampal volume with quantitative 3T magnetic resonance imaging in Chinese patients with epilepsy

Background It was still rare for the quantitative magnetic resonance imaging （MRI） research of regional changes in hippocampus sclerosis （HS） in Chinese patients with epilepsy. This study aimed to study the hippocampal volumes （HVs） with quantitative MRI measurement in Chinese patients with epilepsy. Methods Forty-six Chinese patients with epilepsy （intractable epilepsy （IE）, n=21; non-intractable epilepsy （NIE）, n=25） and 25 normal controls were collected between July 2007 and March 2008. All of the subjects underwent a 3T high-resolution MRI with oblique coronal thin sections oriented perpendicular to the hippocampal long axis. Hippocampal structures were assessed by visual detection, and HVs were quantitatively studied with a Picture Archiving and Communication System （PACS）. Results Our study suggested that there was no significant difference in gender （P 〉0.05） while the right hippocampal head volume （HHV）, hippocampal body volume （HBV）, and the whole hippocampal volume （HCV） were greater than the left one （P 〈0.05）, but no significant difference was found in bilateral hippocampal tail volume （HTV） （P 〉0.05） in normal controls. That unilateral/diffuse （64%/21%） and bilateral/focal （86%/20%） hippocampal atrophy （HA） were significant in IE and NIE patients, respectively. Anterior hippocampus, especially HHV （26% in IE and 20% in NIE） and HBV （29% in IE and 12% in NIE）, had more significant atrophy than the HTV （5% in IE and 0% in NIE） in patients with epilepsy.

Independent temporal lobe epilepsy in patients with tuberous sclerosis complex

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.

Brain MRI of hippocampal volumetry in patients with refractory temporal lobe epilepsy

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

An Autopsy Case of Suspected Anti‑N‑Methyl‑D‑Aspartate Receptor Encephalitis

N-methyl-D-aspartate receptor(NMDAR)encephalitis is a rare type of autoimmune limbic encephalitis.Herein,we report an autopsy case of highly suspected anti‑NMDAR encephalitis,based on the patient’s past psychiatric history and autopsy findings of bilateral hippocampal sclerosis and ovarian teratoma.We found that it can be difficult to accurately diagnose autoimmune encephalitis at postmortem forensic autopsy without a case history and background information.