Exploring ASL perfusion MRI as a substitutive modality for 18F-FDG PET in determining the laterality of mesial temporal lobe epilepsy.

OBJECTIVE: The aim of this investigation was to determine whether a correlation could be discerned between perfusion acquired through ASL MRI and metabolic data acquired via 18F-fluorodeoxyglucose (18F-FDG) PET in mesial temporal lobe epilepsy (mTLE). METHODS: ASL MRI and 18F-FDG PET data were gathered from 22 mTLE patients. Relative cerebral blood flow (rCBF) asymmetry index (AIs) were measured using ASL MRI, and standardized uptake value ratio (SUVr) maps were obtained from 18F-FDG PET, focusing on bilateral vascular territories and key bitemporal lobe structures (amygdala, hippocampus, and parahippocampus). Intra-group comparisons were carried out to detect hypoperfusion and hypometabolism between the left and right brain hemispheres for both rCBF and SUVr in right and left mTLE. Correlations between the two AIs computed for each modality were examined. RESULTS: Significant correlations were observed between rCBF and SUVr AIs in the middle temporal gyrus, superior temporal gyrus, and hippocampus. Significant correlations were also found in vascular territories of the distal posterior, intermediate anterior, intermediate middle, proximal anterior, and proximal middle cerebral arteries. Intra-group comparisons unveiled significant differences in rCBF and SUVr between the left and right brain hemispheres for right mTLE, while hypoperfusion and hypometabolism were infrequently observed in any intracranial region for left mTLE. CONCLUSION: The study's findings suggest promising concordance between hypometabolism estimated by 18F-FDG PET and hypoperfusion determined by ASL perfusion MRI. This raises the possibility that, with prospective technical enhancements, ASL perfusion MRI could be considered an alternative modality to 18F-FDG PET in the future.

Dynamic Functional Connectivity Analysis Using Network-Based Brain State Identification, Application on Temporal Lobe Epilepsy.

Epilepsy is a brain network disorder caused by discharges of interconnected groups of neurons and resulting brain dysfunction. The brain network can be characterized by intra- and inter-regional functional connectivity (FC). However, since the BOLD signal is inherently non-stationary, the FC is evidenced to be varying over time. Considering the dynamic characteristics of the functional network, we aimed to obtain dynamic brain states and their properties using network-based analyses for the comparison of healthy control and temporal lobe epilepsy (TLE) groups and also lateralization of TLE patients. We used dwelling time, transition time, and brain network connection in each state as the dynamic features for this purpose. Results showed a significant difference in dwelling time and transition time between the healthy control group and both left TLE and right TLE groups and also a significant difference in brain network connections between the left and right TLE groups.

Dynamic causal modeling of reorganization of memory and language networks in temporal lobe epilepsy.

OBJECTIVE: To evaluate the alterations of language and memory functions using dynamic causal modeling, in order to identify the epileptogenic hemisphere in temporal lobe epilepsy (TLE). METHODS: Twenty-two patients with left TLE and 13 patients with right TLE underwent functional magnetic resonance imaging (fMRI) during four memory and four language mapping tasks. Dynamic causal modeling (DCM) was employed on fMRI data to examine effective directional connectivity in memory and language networks and the alterations in people with TLE compared to healthy individuals. RESULTS: DCM analysis suggested that TLE can influence the memory network more widely compared to the language network. For memory mapping, it demonstrated overall hyperconnectivity from the left hemisphere to the other cranial regions in the picture encoding, and from the right hemisphere to the other cranial regions in the word encoding tasks. On the contrary, overall hypoconnectivity was seen from the brain hemisphere contralateral to the seizure onset in the retrieval tasks. DCM analysis further manifested hypoconnectivity between the brain's hemispheres in the language network in patients with TLE compared to controls. The CANTAB® neuropsychological test revealed a negative correlation for the left TLE and a positive correlation for the right TLE cohorts for the connections extracted by DCM that were significantly different between the left and right TLE cohorts. INTERPRETATION: In this study, dynamic causal modeling evidenced the reorganization of language and memory networks in TLE that can be used for a better understanding of the effects of TLE on the brain's cognitive functions.

Alteration of intracranial blood perfusion in temporal lobe epilepsy, an arterial spin labeling study.

Background: A critical necessity before surgical resection in mesial temporal lobe epilepsy (mTLE) is lateralizing the seizure focus in the temporal lobe. This study aimed to investigate the differences in perfusion pattern changes in right and left mTLE. Methods: 42 mTLE patients (22 left and 20 right mTLE) and 14 controls were surveyed with pulsed arterial spin labeling at 3.0 T. The mean cerebral blood flow (CBF) and asymmetry index (AI) were calculated in the bilateral temporal lobe, amygdala, hippocampus, parahippocampus, and nine bilateral vascular territories ROIs. The alterations in whole-brain CBF were identified using statistical parametric mapping (SPM). Results: CBF decreased in ipsilateral sides in both epilepsy subcohorts, with right mTLE showing a significant difference in most ROIs while left mTLE exhibiting no significant change. CBF comparison of left mTLE and controls showed a significant drop in ROI analysis in left middle temporal and left intermediate posterior cerebral artery and in AI analysis in parahippocampus, distal anterior cerebral artery, distal middle cerebral artery, and intermediate anterior cerebral artery. CBF hypoperfusion was seen in ROI analysis in the left intermediate anterior cerebral artery, left middle temporal, right middle temporal, left superior temporal in the right mTLE compared to controls. Left mTLE CBF differed significantly from right mTLE CBF in right distal middle cerebral artery ROI and AI of proximal middle cerebral artery. Conclusion: Our result revealed that mTLE affects extratemporal regions and both mTLE subcohorts with different perfusion patterns, which may enhance the performance of preoperative MRI assessment in lateralization procedures.

Outcome of epilepsy surgery in lesional epilepsy: Experiences from a developing country.

BACKGROUND: Our aim was to report the postoperative seizure outcome and associated factors in patients with lesional epilepsy, in a low-income setting. METHODS: This longitudinal prospective study included patients who underwent epilepsy surgery at Kashani Comprehensive Epilepsy Center between 2014 and 2019. Post-surgical outcomes were reported according to the Engel score, and patients were classified into two groups of seizure free (SF) and not-seizure free (NSF). RESULTS: A total of 148 adult patients, with a mean age of 30.45 ±â€¯9.23 years were included. The SF outcome was reported in 86.5% of patients and antiepileptic drugs (AEDs) were reduced or discontinued in 45.9%. The mean follow-up duration was 26.7 ±â€¯14.9 months. Temporal lobe lesions (76.3%) and mesial temporal sclerosis (MTS) (56.7%) were the most frequent etiologies. Temporal lesion (Incidence relative risk (IRR): 1.76, 95% CI [1.08-2.87], p = 0.023), prior history of CNS infection (IRR:1.18, 95% CI [1.03-1.35], p = 0.019), use of intra-operative ECoG (IRR:1.73, 95% CI [1.06-2.81], p = 0.028), and absence of IEDs in postoperative EEG (IRR: 1.41, 95% CI [1.18-1.70], p < 0.001) were positive predictors for a favorable outcome. CONCLUSION: Many patients with drug-resistant lesional epilepsy showed a favorable response to surgery. We believe that resective epilepsy surgery in low-income settings is a major treatment option. The high frequency of patients with drug-resistant epilepsy in developing countries is associated with high rates of morbidity and mortality. Hence, strategies to increase access to epilepsy surgery in these settings are urgently needed.

Temporal and extratemporal atrophic manifestation of temporal lobe epilepsy using voxel-based morphometry and corticometry: clinical application in lateralization of epileptogenic zone.

BACKGROUND: Advances in MRI acquisition and data processing have become important for revealing brain structural changes. Previous studies have reported widespread structural brain abnormalities and cortical thinning in patients with temporal lobe epilepsy (TLE), as the most common form of focal epilepsy. METHODS: In this research, healthy control cases (n = 20) and patients with left TLE (n = 19) and right TLE (n = 14) were recruited, all underwent 3.0 T MRI with magnetization-prepared rapid gradient echo sequence to acquire T1-weighted images. Morphometric alterations in gray matter were identified using voxel-based morphometry (VBM). Volumetric alterations in subcortical structures and cortical thinning were also determined. RESULTS: Patients with left TLE demonstrated more prevailing and widespread changes in subcortical volumes and cortical thickness than right TLE, mainly in the left hemisphere, compared to the healthy group. Both VBM analysis and subcortical volumetry detected significant hippocampal atrophy in ipsilateral compared to contralateral side in TLE group. In addition to hippocampus, subcortical volumetry found the thalamus and pallidum bilaterally vulnerable to the TLE. Furthermore, the TLE patients underwent cortical thinning beyond the temporal lobe, affecting gray matter cortices in frontal, parietal, and occipital lobes in the majority of patients, more prevalently for left TLE cases. Exploiting volume changes in individual patients in the hippocampus alone led to 63.6% sensitivity and 100% specificity for lateralization of TLE. CONCLUSION: Alteration of gray matter volumes in subcortical regions and neocortical temporal structures and also cortical gray matter thickness were evidenced as common effects of epileptogenicity, as manifested by the majority of cases in this study.

Distinct patterns of hippocampal subfield volume loss in left and right mesial temporal lobe epilepsy.

OBJECTIVE: To investigate the pattern and severity of hippocampal subfield volume loss in patients with left and right mesial temporal lobe epilepsy (mTLE) using quantitative MRI volumetric analysis. METHODS: A total of 21 left and 14 right mTLE subjects, as well as 15 healthy controls, were enrolled in this cross-sectional study. A publically available magnetic resonance imaging (MRI) brain volumetry system (volBrain) was used for volumetric analysis of hippocampal subfields. The T1-weighted images were processed with a HIPS pipeline. RESULTS: A distinct pattern of hippocampal subfield atrophy was found between left and right mTLE patients when compared with controls. Patients with left mTLE exhibited ipsilateral hippocampal atrophy and segmental volume depletion of the Cornu Ammonis (CA) 2/CA3, CA4/dentate gyrus (DG), and strata radiatum-lacunosum-moleculare (SR-SL-SM). Those with right mTLE exhibited similar ipsilateral hippocampal atrophy but with additional segmental CA1 volume depletion. More extensive bilateral subfield volume loss was apparent with right mTLE patients. CONCLUSION: We demonstrate that left and right mTLE patients show a dissimilar pattern of hippocampal subfield atrophy, suggesting the pathophysiology of epileptogenesis in left and right mTLE to be different.

Dynamic functional connectivity in temporal lobe epilepsy: a graph theoretical and machine learning approach.

PURPOSE: Functional magnetic resonance imaging (fMRI) in resting state can be used to evaluate the functional organization of the human brain in the absence of any task or stimulus. The functional connectivity (FC) has non-stationary nature and consented to be varying over time. By considering the dynamic characteristics of the FC and using graph theoretical analysis and a machine learning approach, we aim to identify the laterality in cases of temporal lobe epilepsy (TLE). METHODS: Six global graph measures are extracted from static and dynamic functional connectivity matrices using fMRI data of 35 unilateral TLE subjects. Alterations in the time trend of the graph measures are quantified. The random forest (RF) method is used for the determination of feature importance and selection of dynamic graph features including mean, variance, skewness, kurtosis, and Shannon entropy. The selected features are used in the support vector machine (SVM) classifier to identify the left and right epileptogenic sides in patients with TLE. RESULTS: Our results for the performance of SVM demonstrate that the utility of dynamic features improves the classification outcome in terms of accuracy (88.5% for dynamic features compared with 82% for static features). Selecting the best dynamic features also elevates the accuracy to 91.5%. CONCLUSION: Accounting for the non-stationary characteristics of functional connectivity, dynamic connectivity analysis of graph measures along with machine learning approach can identify the temporal trend of some specific network features. These network features may be used as potential imaging markers in determining the epileptogenic hemisphere in patients with TLE.

Graph theory application with functional connectivity to distinguish left from right temporal lobe epilepsy.

OBJECTIVE: To investigate the application of graph theory with functional connectivity to distinguish left from right temporal lobe epilepsy (TLE). METHODS: Alterations in functional connectivity within several brain networks - default mode (DMN), attention (AN), limbic (LN), sensorimotor (SMN) and visual (VN) - were examined using resting-state functional MRI (rs-fMRI). The study accrued 21 left and 14 right TLE as well as 17 nonepileptic control subjects. The local nodal degree, a feature of graph theory, was calculated foreach of the brain networks. Multivariate logistic regression analysis was performed to determine the accuracy of identifying seizure laterality based on significant differences in local nodal degree in the selected networks. RESULTS: Left and right TLE patients showed dissimilar patterns of alteration in functional connectivity when compared to control subjects. Compared with right TLE, patients with left TLE exhibited greater nodal degree' (i.e. hyperconnectivity) with right superomedial frontal gyrus (in DMN), inferior frontal gyrus pars triangularis (in AN), right caudate and left superior temporal gyrus (in LN) and left paracentral lobule (in SMN), while showing lesser nodal degree (i.e. hypoconnectivity) with left temporal pole (in DMN), right insula (in LN), left supplementary motor area (in SMN), and left fusiform gyrus (in VN). The LN showed the highest accuracy of 82.9% among all considered networks in determining laterality of the TLE. By combinations of local degree attributes in the DMN, AN, LN, and VN, logistic regression analysis demonstrated an accuracy of 94.3% by comparison. CONCLUSION: Our study demonstrates the utility of graph theory application to brain network analysis as a potential biomarker to assist in the determination of TLE laterality and improve the confidence in presurgical decision-making in cases of TLE.

Anti-NMDA Receptor Encephalitis Presenting with Status Epilepticus: Brucellosis as a Possible Triggering Factor: A Case Report.

Brucellosis is a common zoonotic infection caused by bacterial genus Brucella, a Gram-negative bacterium, and continued to be a health problem in endemic areas. Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an autoimmune disease which can lead to status epilepticus. A 19-year-old male patient was referred to our hospital with status epilepticus. The diagnosis of brucellosis was confirmed about 2 weeks before. The brain magnetic resonance imaging was normal. Lumbar puncture was performed, and cerebral spinal fluid (CSF) was in normal limits. The patient was treated with antiepileptic, anti-brucellosis agents. Two weeks after discharge, the patient readmitted to hospital with status epilepticus again. Extensive workup was negative except that NMDAR antibodies were detected in serum and CSF. The diagnosis of anti-NMDAR encephalitis was established. Brucellosis as a triggering factor for NMDAR encephalitis should be considered.

Evolution of Graph Theory in Dynamic Functional Connectivity for Lateralization of Temporal Lobe Epilepsy.

Resting-state functional magnetic resonance imaging (rsfMRI) has described the functional architecture of the human brain in the absence of any task or stimulus. Since the functional connectivity (FC), has non-stationary nature, it is evidenced to be varying over time. Using dynamic functional connectivity, six graph theoretical characteristics were measured and compared between left and right temporal lobe epilepsy (TLE). We also obtain a trend for each characteristic in the time course of experiments. The results demonstrated that the static connectivity analysis failed to fully separate the left and right TLE patients for some characteristics, whereby the dynamic analysis has been shown capable of identifying the laterality. Furthermore, the results suggest that the temporal trend of some graph theoretical characteristics can be exploited as a novel marker for TLE laterality.

Cardiac arrest associated with epileptic seizures: A case report with simultaneous EEG and ECG.

Ictal asystole is a rare, probably underestimated manifestation of epileptic seizures whose pathophysiology is still debated. This report describes two patients who had cardiac asystole at the end of their seizure. The first patient was a 13-year-old boy with complex partial seizures.. His MRI showed symmetrical signal abnormality in the bilateral parietooccipital lobe accompanied by mild gliosis and volume loss. During a 3-day long-term video-EEG monitoring, he had cardiac arrest at the end of one of his seizures that was secondarily generalized. The second one was a 42-year-old veteran with penetrating head trauma in the left frontal lobe due to shell injury. During long-term video-EEG monitoring, he had one generalized tonic-clonic seizure accompanied by bradycardia and cardiac asystole. Asystoles could have a role in the incidence of sudden unexpected death in epilepsy (SUDEP), meaning that the presence of ictal bradycardia is a risk factor for SUDEP. In cases of epileptic cardiac dysrhythmia, prolonged simultaneous EEG/ECG monitoring may be required. Cardiological investigation should be included in epilepsy management.

Bumetanide reduces seizure frequency in patients with temporal lobe epilepsy.

Alterations in the balance of K-Na-2Cl cotransporter (NKCC1) and Na-Cl cotransporter (KCC2) activity may cause depolarizing effect of γ-aminobutyric Acid (GABA), and contribute to epileptogenesis in human temporal lobe epilepsy. NKCC1 facilitates accumulation of chloride inside neurons and favors depolarizing responses to GABA. In the current pilot study we provide the first documented look at efficacy of bumetanide, a specific NKCC1 antagonist, on reduction of seizure frequency in adult patients with temporal lobe epilepsy. According to our results, seizure frequency was reduced considerably in these patients. Furthermore, epileptiform discharges decreased in two of our patients. If the efficacy of bumetanide is proven in large scale studies, it can be used as a supplemental therapy in temporal lobe epilepsy.