Structural brain assessment of temporal lobe epilepsy based on voxel-based and surface-based morphological features.

AIM OF THE STUDY: This study aimed to assess the cerebral voxel-based and surface-based morphological abnormalities of patients with temporal lobe epilepsy (TLE). MATERIALS AND METHODS: A total of 100 healthy adults and 73 patients with TLE were enrolled in this study, and their 3D T1-weighted MRI data were collected. Voxel-based morphology (VBM) and surface-based morphology (SBM) tools were used to compare the morphological differences between healthy adults and patients with TLE. Receiver-operating characteristic (ROC) curves were used to acquire the boundary values for detecting morphological abnormalities in regions of interest from the corrected VBM and SBM analysis. RESULTS: Our results showed that cortical voxels and decreased thickness areas were located in the widespread cortex and subcortical structures in the TLE group. However, after completing the analysis, we found that the left-TLE lesions were limited to the left temporal pole and left hippocampus, while the right-TLE lesions were located in the bilateral medial temporal lobe, including the right hippocampus and bilateral amygdala. ROC-curve results showed that the volume of the left hippocampus at 4,124.45 mm3 and the thickness of the left temporal pole cortex at 3.50 mm could be used as optimal boundary values based on the curves of the left-TLE group. The right-TLE group curves were poor. CONCLUSIONS: Widespread cerebral morphological TLE abnormalities were represented in this study. However, the lesions may be limited after completing a corrected comparison with clinical information. Boundary values of left-TLE group lesions were also obtained.

The relationship between the interictal epileptiform discharge source connectivity and cortical structural couplings in temporal lobe epilepsy.

Objective: The objective of this study was to explore the relation between interictal epileptiform discharge (IED) source connectivity and cortical structural couplings (SCs) in temporal lobe epilepsy (TLE). Methods: High-resolution 3D-MRI and 32-sensor EEG data from 59 patients with TLE were collected. Principal component analysis was performed on the morphological data on MRI to obtain the cortical SCs. IEDs were labeled from EEG data and averaged. The standard low-resolution electromagnetic tomography analysis was performed to locate the source of the average IEDs. Phase-locked value was used to evaluate the IED source connectivity. Finally, correlation analysis was used to compare the IED source connectivity and the cortical SCs. Results: The features of the cortical morphology in left and right TLE were similar across four cortical SCs, which could be mainly described as the default mode network, limbic regions, connections bilateral medial temporal, and connections through the ipsilateral insula. The IED source connectivity at the regions of interest was negatively correlated with the corresponding cortical SCs. Significance: The cortical SCs were confirmed to be negatively related to IED source connectivity in patients with TLE as detected with MRI and EEG coregistered data. These findings suggest the important role of intervening IEDs in treating TLE.

Characterizing Cerebral Imaging and Electroclinical Features of Five Pseudohypoparathyroidism Cases Presenting with Epileptic Seizures.

Objective: To characterize the cerebral imaging and electroclinical features and investigate their etiological contributions to seizures in pseudoparathyroidism (PHP). Methods: The clinical symptoms, biochemical imaging by magnetic resonance imaging (MRI) and computed tomography (CT) tests, and electroencephalogram (EEG) manifestations of five PHP patients with seizures were retrospectively collected and analyzed. Results: Physical examination showed an average stature in cases 2~4 and short stature in cases 1 and 5. X-ray tests suggested ectopic calcification in four patients. The seizures in four cases were effectively controlled with antiseizure medicines (ASMs). Cerebral CT scans showed extensive brain calcifications in the bilateral basal ganglia (all five cases), cerebellum (cases 1, 3, and 5), thalamus (case 4), and cerebral cortex. Cerebral MRI showed short T1 signals mainly in the basal ganglia. EEG records revealed focal EEG abnormalities, including abnormal slow waves and epileptiform discharges, mainly over the temporal and frontal lobes. The brain areas with focal EEG abnormalities and calcification did not always coincide. Conclusion: The seizures in PHP can be focal to bilateral tonic-clonic. ASMs are effective in epilepsy combined with PHP. Intracranial calcification is not a reliable etiological cause of epilepsy in PHP patients.

Brain structural connectivity sub typing in unilateral temporal lobe epilepsy.

To categorize and clinically characterize subtypes of brain structural connectivity patterns in unilateral temporal lobe epilepsy (TLE). Voxel based morphometry (VBM) and surfaced based morphometry (SBM) analysis were used to detect brain structural alterations associated with TLE from MRI data. Principal component analysis (PCA) was performed to identify subtypes of brain structural connectivity patterns. Correlation analysis was used to explore associations between PC scores and clinical characteristics. A total of 59 patients with TLE and 100 healthy adults were included in this study. Widespread cortical atrophy was shown in both left and right TLE (P < 0.05, FWE corrected). Six principal components (PCs) that explained more than 70% of the variance were extracted for left and right TLE, reflecting patterns of brain structural connectivity. PCs representing perisylvian connectivity were positively correlated with verbal IQ (left TLE: r = 0.696, P < 0.001; right TLE: r = 0.484, P = 0.012) and total IQ (left TLE r = 0.608, P < 0.001) and negatively correlated with disease duration (r = -0.448, P = 0.009). In left TLE, the PC in the ipsilateral mesial temporal region was negatively correlated with age at onset (r = -0.382, P = 0.028). In right TLE, the PC representing the default mode network was negatively correlated with number of antiepileptic drugs (r = -0.407, P = 0.039). This study categorized subtypes of unilateral TLE based on brain structural connectivity patterns. Findings may provide insight into seizure pathways, the pathophysiology of epilepsy, including comorbidities such as cognitive impairment, and help predict treatment outcomes.

The Epilepsy of Infancy With Migrating Focal Seizures: Identification of de novo Mutations of the KCNT2 Gene That Exert Inhibitory Effects on the Corresponding Heteromeric KNa1.1/KNa1.2 Potassium Channel.

The epilepsy of infancy with migrating focal seizures (EIMFS; previously called Malignant migrating partial seizures of infancy) are early-onset epileptic encephalopathies (EOEE) that associate multifocal ictal discharges and profound psychomotor retardation. EIMFS have a genetic origin and are mostly caused by de novo mutations in the KCNT1 gene, and much more rarely in the KCNT2 gene. KCNT1 and KCNT2 respectively encode the KNa1.1 (Slack) and KNa1.2 (Slick) subunits of the sodium-dependent voltage-gated potassium channel KNa. Functional analyses of the corresponding mutant homomeric channels in vitro suggested gain-of-function effects. Here, we report two novel, de novo truncating mutations of KCNT2: one mutation is frameshift (p.L48Qfs43), is situated in the N-terminal domain, and was found in a patient with EOEE (possibly EIMFS); the other mutation is nonsense (p.K564*), is located in the C-terminal region, and was found in a typical EIMFS patient. Using whole-cell patch-clamp recordings, we have analyzed the functional consequences of those two novel KCNT2 mutations on reconstituted KNa1.2 homomeric and KNa1.1/KNa1.2 heteromeric channels in transfected chinese hamster ovary (CHO) cells. We report that both mutations significantly impacted on KNa function; notably, they decreased the global current density of heteromeric channels by ~25% (p.K564*) and ~55% (p.L48Qfs43). Overall our data emphasize the involvement of KCNT2 in EOEE and provide novel insights into the role of heteromeric KNa channel in the severe KCNT2-related epileptic phenotypes. This may have important implications regarding the elaboration of future treatment.

Mangiferin prevents corticosterone-induced behavioural deficits via alleviation of oxido-nitrosative stress and down-regulation of indoleamine 2,3-dioxygenase (IDO) activity.

BACKGROUND: In recent years, a substantial amount of experimental studies have demonstrated that exogenous administration of corticosterone causes anxiety and depressive-like behaviour in rodents which involves hypothalamic-pituitary-adrenal axis dysregulation. Our present study aimed to explore the neuroprotective potential of mangiferin against corticosterone-induced anxiety and depressive-like behaviour. METHODS: Corticosterone (40 mg/kg; subcutaneously) was administered once daily in swiss albino mice for 21 days. Mice were treated simultaneously with mangiferin (40 mg/kg; p.o.), 30 min prior to the corticosterone injection. RESULTS: Chronic administration of corticosterone caused anxiety and depressive-like behaviour in mice which was significantly alleviated by mangiferin treatment. Biochemical analysis revealed that mangiferin treatment significantly attenuated corticosterone-induced oxido-nitrosative stress and neuroinflammation in the hippocampus region. Furthermore, concomitant treatment with mangiferin significantly enhanced the hippocampal brain-derived neurotrophic factor (BDNF) level and decreased the serum corticosterone level in the corticosterone-treated animals. Western blotting analysis revealed that corticosterone administration significantly up-regulated the indoleamine 2,3-dioxygenase (IDO) protein expression level in the hippocampus which was significantly reduced by mangiferin treatment. CONCLUSION: Taken together, our results suggest that mangiferin exerts anti-anxiety and antidepressant effect in corticosterone-treated rats, which is probably mediated through up-regulation of BDNF level along with inhibition of oxido-nitrosative stress, neuroinflammation and IDO up-regulation in the hippocampus region.

A Point Mutation in SCN1A 5' Genomic Region Decreases the Promoter Activity and Is Associated with Mild Epilepsy and Seizure Aggravation Induced by Antiepileptic Drug.

The SCN1A gene with 1274 point mutations in the coding regions or genomic rearrangements is the most clinically relevant epilepsy gene. Recent studies have demonstrated that variations in the noncoding regions are potentially associated with epilepsies, but no distinct mutation has been reported. We sequenced the 5' upstream region of SCN1A in 166 patients with epilepsy and febrile seizures who were negative for point mutations in the coding regions or genomic rearrangements. A heterozygous mutation h1u-1962 T > G was identified in a patient with partial epilepsy and febrile seizures, which was aggravated by oxcarbazepine. This mutation was transmitted from the patient's asymptomatic mother and not found in the 110 normal controls. h1u-1962 T > G was located upstream the most frequently used noncoding exon and within the promoter sequences. Further experiments showed that this mutation decreased the promoter activity by 42.1 % compared with that of the paired haplotype (P < 0.001). In contrast to the null expression that results in haploinsufficiency and severe phenotype, this mutation caused relatively less impairment, explaining the mild epilepsy with incomplete penetrance. The antiepileptic drug-induced seizure aggravation in this patient suggests clinical attention for mutations or variations in noncoding regions that may affect SCN1A expression.