Combined Ex Vivo 9.4T MRI and Quantitative Histopathological Study in Normal and Pathological Neocortical Resections in Focal Epilepsy.
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ABSTRACT:
SUBMITTER: Reeves C
PROVIDER: S-EPMC4950048 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Focal epilepsy is characterised by paroxysmal events, reflecting changes in underlying local brain networks. To capture brain network activity at the maximal temporal resolution of the acquired functional magnetic resonance imaging (fMRI) data, we have previously developed a novel analysis framework called Dynamic Regional Phase Synchrony (DRePS). DRePS measures instantaneous mean phase coherence within neighbourhoods of brain voxels. We use it here to examine how the dynamics of the functional connections of regional brain networks are altered in neocortical focal epilepsy. Using task-free fMRI data from 21 subjects with focal epilepsy and 21 healthy controls, we calculated the power spectral density of DRePS, which is a measure of signal variability in local connectivity estimates. Whole-brain averaged power spectral density of DRePS, or signal variability of local connectivity, was significantly higher in epilepsy subjects compared to healthy controls. Maximal increase in DRePS spectral power was seen in bilateral inferior frontal cortices, ipsilateral mid-cingulate gyrus, superior temporal gyrus, caudate head, and contralateral cerebellum. Our results provide further evidence of common brain abnormalities across people with focal epilepsy. We postulate that dynamic changes in specific cortical brain areas may help maintain brain function in the presence of pathological epileptiform network activity in neocortical focal epilepsy.
| S-EPMC5429237 | biostudies-literature
Project description:ObjectiveIn the present study, we have developed a novel patient-specific rule-based seizure prediction system for focal neocortical epilepsy.MethodsFive univariate measures including correlation dimension, correlation entropy, noise level, Lempel-Ziv complexity, and largest Lyapunov exponent as well as one bivariate measure, nonlinear interdependence, were extracted from non-overlapping 10-s segments of intracranial electroencephalogram (iEEG) data recorded using electrodes implanted deep in the brain and/or placed on the cortical surface. The spatio-temporal information was then integrated by using rules established based on patient-specific changes observed in the period prior to a seizure sample for each patient. The system was tested on 316 h of iEEG data containing 49 seizures recorded in 11 patients with medically intractable focal neocortical epilepsy.ResultsFor seizure occurrence periods of 30 and 50 min our method showed an average sensitivity of 79.9% and 90.2% with an average false prediction rate of 0.17 and 0.11/h, respectively. In terms of sensitivity and false prediction rate, the system showed superiority to random and periodical predictors.ConclusionsThe nonlinear analysis of iEEG in the period prior to seizures revealed patient-specific spatio-temporal changes that were significantly different from those observed within baselines in the majority of the seizures analyzed in this study.SignificanceThe present results suggest that the patient specific rule-based approach may become a potentially useful approach for predicting seizures prior to onset.
| S-EPMC3361618 | biostudies-literature
Project description:Focal cortical dysplasia (FCD) type IIId is a newly proposed type associated with early-life brain insults. Such patients are often considered unsuitable for resective epilepsy surgery, given the usually wide extent of the lesion and the poor correlation of MRI to the epileptogenic pathology. Two patients with intractable epilepsy, early-life ischemic/traumatic injury and MRI findings of extensive unilateral cystic-gliotic and ipsilateral medial temporal sclerotic-malformative lesions were subjected to presurgical evaluation revealing well-localized neocortical ictal onsets. They underwent tailored neocortical resections sparing medial temporal areas and achieved Engel class I postsurgical outcomes. Histopathology was consistent with type IIId focal cortical dysplasia. Successful outcomes with tailored resections may be achieved in cases with this subtype of focal cortical dysplasia, in the presence of converging and well-localized semiological, EEG and functional imaging data, even on a background of complex and extensive MRI abnormalities. Medial temporal pathology, although often present in this setting, is not necessarily the site of ictal onsets, and its resection may not be always mandatory for a favorable outcome.
| S-EPMC4150647 | biostudies-literature
Project description:ObjectiveTo characterize seizure and cognitive outcomes of sparing vs removing an magnetic resonance imaging (MRI)-normal hippocampus in patients with temporal lobe epilepsy.MethodsIn this retrospective cohort study, we reviewed clinical, imaging, surgical, and histopathological data on 152 individuals with temporal lobe epilepsy and nonlesional hippocampi categorized into hippocampus-spared (n = 74) or hippocampus-resected (n = 78). Extra-hippocampal lesions were allowed. Pre- and postoperative cognitive data were available on 86 patients. Predictors of seizure and cognitive outcomes were identified using Cox-proportional hazard modeling followed by treatment-specific model reduction according to Akaike information criterion, and built into an online risk calculator.ResultsSeizures recurred in 40% within one postoperative year, and in 63% within six postoperative years. Male gender (P = .03), longer epilepsy duration (P < .01), normal MRI (P = .04), invasive evaluation (P = .02), and acute postoperative seizures (P < .01) were associated with a higher risk of recurrence. We found no significant difference in postoperative seizure freedom rates at 5 years between those whose hippocampus was spared and those whose hippocampus was resected (P = .17). Seizure outcome models built with pre- and postoperative data had bootstrap validated concordance indices of 0.65 and 0.72. The dominant hippocampus-spared group had lower rates of decline in verbal memory (39% vs 70%; P = .03) and naming (41% vs 79%; P = .01) compared to the hippocampus-resected group. Partial hippocampus sparing had the same risk of verbal memory decline as for complete removal.SignificanceSparing or removing an MRI-normal hippocampus yielded similar long-term seizure outcome. A more conservative approach, sparing the hippocampus, only partially shields patients from postoperative cognitive deficits. Risk calculators are provided to facilitate clinical counseling.
| S-EPMC7879196 | biostudies-literature
Project description:ObjectiveThis study investigates high-frequency oscillations (HFOs; 65-600 Hz) as a biomarker of epileptogenic brain and explores three barriers to their clinical translation: (1) Distinguishing pathological HFOs (pathHFO) from physiological HFOs (physHFO). (2) Classifying tissue under individual electrodes as epileptogenic (3) Reproducing results across laboratories.MethodsWe recorded HFOs using intracranial EEG (iEEG) in 90 patients with focal epilepsy and 11 patients without epilepsy. In nine patients with epilepsy putative physHFOs were induced by cognitive or motor tasks. HFOs were identified using validated detectors. A support vector machine (SVM) using HFO features was developed to classify tissue under individual electrodes as normal or epileptogenic.ResultsThere was significant overlap in the amplitude, frequency, and duration distributions for spontaneous physHFO, task induced physHFO, and pathHFO, but the amplitudes of the pathHFO were higher (P < 0.0001). High gamma pathHFO had the strongest association with seizure onset zone (SOZ), and were elevated on SOZ electrodes in 70% of epilepsy patients (P < 0.0001). Failure to resect tissue generating high gamma pathHFO was associated with poor outcomes (P < 0.0001). A SVM classified individual electrodes as epileptogenic with 63.9% sensitivity and 73.7% specificity using SOZ as the target.InterpretationA broader range of interictal pathHFO (65-600 Hz) than previously recognized are biomarkers of epileptogenic brain, and are associated with SOZ and surgical outcome. Classification of HFOs into physiological or pathological remains challenging. Classification of tissue under individual electrodes was demonstrated to be feasible. The open source data and algorithms provide a resource for future studies.
| S-EPMC6144446 | biostudies-literature
Project description:Neocortical epilepsy is frequently drug-resistant. Surgery to remove the epileptogenic zone is only feasible in a minority of cases, leaving many patients without an effective treatment. We report the potential efficacy of gene therapy in focal neocortical epilepsy using a rodent model in which epilepsy is induced by tetanus toxin injection in the motor cortex. By applying several complementary methods that use continuous wireless electroencephalographic monitoring to quantify epileptic activity, we observed increases in high frequency activity and in the occurrence of epileptiform events. Pyramidal neurons in the epileptic focus showed enhanced intrinsic excitability consistent with seizure generation. Optogenetic inhibition of a subset of principal neurons transduced with halorhodopsin targeted to the epileptic focus by lentiviral delivery was sufficient to attenuate electroencephalographic seizures. Local lentiviral overexpression of the potassium channel Kv1.1 reduced the intrinsic excitability of transduced pyramidal neurons. Coinjection of this Kv1.1 lentivirus with tetanus toxin fully prevented the occurrence of electroencephalographic seizures. Finally, administration of the Kv1.1 lentivirus to an established epileptic focus progressively suppressed epileptic activity over several weeks without detectable behavioral side effects. Thus, gene therapy in a rodent model can be used to suppress seizures acutely, prevent their occurrence after an epileptogenic stimulus, and successfully treat established focal epilepsy.
| S-EPMC3605784 | biostudies-other
Project description:The aim of this study is to determine whether the use of 7 tesla (T) MRI in clinical practice leads to higher detection rates of focal cortical dysplasias in possible candidates for epilepsy surgery.In our center patients are referred for 7 T MRI if lesional focal epilepsy is suspected, but no abnormalities are detected at one or more previous, sufficient-quality lower-field MRI scans, acquired with a dedicated epilepsy protocol, or when concealed pathology is suspected in combination with MR-visible mesiotemporal sclerosis-dual pathology. We assessed 40 epilepsy patients who underwent 7 T MRI for presurgical evaluation and whose scans (both 7 T and lower field) were discussed during multidisciplinary epilepsy surgery meetings that included a dedicated epilepsy neuroradiologist. We compared the conclusions of the multidisciplinary visual assessments of 7 T and lower-field MRI scans.In our series of 40 patients, multidisciplinary evaluation of 7 T MRI identified additional lesions not seen on lower-field MRI in 9 patients (23%). These findings were guiding in surgical planning. So far, 6 patients underwent surgery, with histological confirmation of focal cortical dysplasia or mild malformation of cortical development.Seven T MRI improves detection of subtle focal cortical dysplasia and mild malformations of cortical development in patients with intractable epilepsy and may therefore contribute to identification of surgical candidates and complete resection of the epileptogenic lesion, and thus to postoperative seizure freedom.
| S-EPMC5719847 | biostudies-other
Project description:One third of patients with medically refractory focal epilepsy have normal-appearing MRI scans. This poses a problem as identification of the epileptogenic region is required for surgical treatment. This study performs a multimodal voxel-based analysis (VBA) to identify brain abnormalities in MRI-negative focal epilepsy. Data was collected from 69 focal epilepsy patients (42 with discrete lesions on MRI scans, 27 with no visible findings on scans), and 62 healthy controls. MR images comprised T1-weighted, fluid-attenuated inversion recovery (FLAIR), fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging, and neurite density index (NDI) from neurite orientation dispersion and density imaging. These multimodal images were coregistered to T1-weighted scans, normalized to a standard space, and smoothed with 8 mm FWHM. Initial analysis performed voxel-wise one-tailed t-tests separately on grey matter concentration (GMC), FLAIR, FA, MD, and NDI, comparing patients with epilepsy to controls. A multimodal non-parametric combination (NPC) analysis was also performed simultaneously on FLAIR, FA, MD, and NDI. Resulting p-maps were family-wise error rate corrected, threshold-free cluster enhanced, and thresholded at p < 0.05. Sensitivity was established through visual comparison of results to manually drawn lesion masks or seizure onset zone (SOZ) from stereoelectroencephalography. A leave-one-out cross-validation with the same analysis protocols was performed on controls to determine specificity. NDI was the best performing individual modality, detecting focal abnormalities in 38% of patients with normal MRI and conclusive SOZ. GMC demonstrated the lowest sensitivity at 19%. NPC provided superior performance to univariate analyses with 50% sensitivity. Specificity in controls ranged between 96 and 100% for all analyses. This study demonstrated the utility of a multimodal VBA utilizing NPC for detecting epileptogenic lesions in MRI-negative focal epilepsy. Future work will apply this approach to datasets from other centres and will experiment with different combinations of MR sequences.
| S-EPMC8503566 | biostudies-literature
Project description:Background and purposeVoxel-based morphometry is widely used for detecting gray matter abnormalities in epilepsy. However, its performance with changing parameters, smoothing and statistical threshold, is debatable. More important, the potential yield of combining multiple MR imaging contrasts (multispectral voxel-based morphometry) is still unclear. Our aim was to objectify smoothing and statistical cutoffs and systematically compare the performance of multispectral voxel-based morphometry with existing T1 voxel-based morphometry in patients with focal epilepsy and previously negative MRI.Materials and methods3D T1-, T2-, and T2-weighted FLAIR scans were acquired for 62 healthy volunteers and 13 patients with MR imaging negative for focal epilepsy on a Magnetom Skyra 3T scanner with an isotropic resolution of 0.9 mm3. We systematically optimized the main voxel-based morphometry parameters, smoothing level and statistical cutoff, with T1 voxel-based morphometry as a reference. As a next step, the performance of multispectral voxel-based morphometry models, T1+T2, T1+FLAIR, and T1+T2+FLAIR, was compared with that of T1 voxel-based morphometry using gray matter concentration and gray matter volume analysis.ResultsWe found the best performance of T1 at 12 mm and a T-threshold (statistical cutoff) of 3.7 for gray matter concentration analysis. When we incorporated these parameters, after expert visual interpretation of concordant and discordant findings, we identified T1+FLAIR as the best model with a concordant rate of 46.2% and a concordant rate/discordant rate of 1.20 compared with T1 with 30.8% and 0.67, respectively. Visual interpretation of voxel-based morphometry findings decreased concordant rates from 38.5%-46.2% to 15.4%-46.2% and discordant rates from 53.8%-84.6% to 30.8%-46.2% and increased specificity across models from 33.9%-40.3% to 46.8%-54.8%.ConclusionsMultispectral voxel-based morphometry, especially T1+FLAIR, can yield superior results over single-channel T1 in focal epilepsy patients with a negative conventional MR imaging.
| S-EPMC7655351 | biostudies-literature
Project description:BackgroundWe aimed to evaluate the diagnostic yield of seven-tesla (7T) magnetic resonance imaging (MRI) with post-processing of three-dimensional (3D) T1-weighted (T1W) images by the morphometric analysis program (MAP) in epilepsy surgical candidates whose 3T MRI results were inconclusive or negative.MethodsWe recruited 35 patients with pharmacoresistant focal epilepsy. A multidisciplinary team including an experienced neuroradiologist evaluated their seizure semiology, video-electroencephalography data, 3T MRI and post-processing results, and co-registered FDG-PET. Eleven patients had suspicious lesions on 3T MRI and the other 24 patients were strictly MRI-negative. 7T MRI evaluation was then performed to aid clinical decision. Among patients with pathologically proven focal cortical dysplasia (FCD) type II, signs of FCD were retrospectively evaluated in each MRI sequence (T1W, T2W, and FLAIR), and positive rates were analyzed in each MAP feature map (junction, extension, and thickness).Results7T MRI evaluation confirmed the lesion in nine of the 11 (81.8%) patients with suspicious lesions on 3T MRI. It also revealed new lesions in four of the 24 (16.7%) strictly MRI-negative patients. Histopathology showed FCD type II in 11 of the 13 (84.6%) 7T MRI-positive cases. Unexpectedly, three of the four newly identified FCD lesions were located in the posterior quadrant. Blurred gray-white boundary was the most frequently observed sign of FCD, appearing on 7T T1W image in all cases and on T2W and FLAIR images in only about half cases. The 7T junction map successfully detected FCD (10/11) in more cases than the extension (1/11) and thickness (0/11) maps. The 3D T1W images at 7T exhibited superior cerebral gray-white matter contrast, more obviously blurred gray-white boundary of FCD, and larger and brighter positive zones in post-processing than 3T T1W images.Conclusion7T MRI with post-processing can enhance the detection of subtle epileptogenic lesions for MRI-negative epilepsy and may optimize surgical strategies for patients with focal epilepsy.
| S-EPMC8191069 | biostudies-literature