Using network dynamic fMRI for detection of epileptogenic foci

Abstract\ud \ud Background\ud Epilepsy is one of the most prevalent neurological disorders. It remains medically intractable for about one-third of patients with focal epilepsy, for whom precise localization of the epileptogenic zone responsible for seizure initiation may be critical for successful surgery. Existing fMRI literature points to widespread network disturbances in functional connectivity. Per previous scalp and intracranial EEG studies and consistent with excessive local synchronization during interictal discharges, we hypothesized that, relative to same regions in healthy controls, epileptogenic foci would exhibit less chaotic dynamics, identifiable via entropic analyses of resting state fMRI time series.\ud \ud \ud Methods\ud In order to first validate this hypothesis on a cohort of patients with known ground truth, here we test individuals with well-defined epileptogenic foci (left mesial temporal lobe epilepsy). We analyzed voxel-wise resting-state fMRI time-series using the autocorrelation function (ACF), an entropic measure of regulation and feedback, and performed follow-up seed-to-voxel functional connectivity analysis. Disruptions in connectivity of the region exhibiting abnormal dynamics were examined in relation to duration of epilepsy and patients’ cognitive performance using a delayed verbal memory recall task.\ud \ud \ud Results\ud ACF analysis revealed constrained (less chaotic) functional dynamics in left temporal lobe epilepsy patients, primarily localized to ipsilateral temporal pole, proximal to presumed focal points. Autocorrelation decay rates differentiated, with 100 % accuracy, between patients and healthy controls on a subject-by-subject basis within a leave-one-subject out classification framework. Regions identified via ACF analysis formed a less efficient network in patients, as compared to controls. Constrained dynamics were linked with locally increased and long-range decreased connectivity that, in turn, correlated significantly with impaired memory (local left temporal connectivity) and epilepsy duration (left temporal – posterior cingulate cortex connectivity).\ud \ud \ud Conclusions\ud Our current results suggest that data driven functional MRI methods that target network dynamics hold promise in providing clinically valuable tools for identification of epileptic regions.This research was supported by the National Science Foundation (CBET\ud 1264440; LRMP) and the Sao Paulo Research Foundation (Young\ud Investigators Awards FAPESP 11/08573-4; JSI)

Níveis diferentes de MT-I/II entre pacientes com MTLE com ou sem crise generalizada: os níveis hipocampais de MT-I/II afetam o alastramento das crises, ou o alastramento das crises promove expressão diferencial de MT-I/II?

In the central nervous system, zinc is released along with glutamate during neurotransmission and, in excess, can promote neuronal death. Experimental studies have shown that metallothioneins I/II (MT-I/II), which chelate free zinc, can affect seizures and reduce neuronal death after status epilepticus. Our aim was to evaluate the expression of MT-I/II in the hippocampus of patients with temporal lobe epilepsy (TLE). Hippocampi from patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE) were evaluated for expression of MT-I/II and for neuronal, astroglial, and microglial populations. Compared to control cases, MTLE group displayed widespread increase in MT-I/II expression, astrogliosis and reduced neuronal population. MT-I/II levels did not correlate with any clinical variables, but patients with secondary generalized seizures (SGS) had less MT-I/II than patients without SGS. In conclusion, MT-I/II expression was increased in hippocampi from MTLE patients and our data suggest that it may be associated with different seizure spread patterns

Validation of the Subjective Handicap of Epilepsy (SHE) in Brazilian patients with epilepsy

The objectives of the study were to translate and adapt the Subjective Handicap of Epilepsy (SHE) instrument to Brazilian Portuguese and to determine its psychometric properties for the evaluation of quality of life in patients with epilepsy. A sample of 448 adult patients with epilepsy with different clinical profiles (investigation, preoperative period, postoperative period, and drug treatment follow-up) was evaluated with the SHE and the Epilepsy Surgery Inventory (ESI-55). Exploratory factorial analysis demonstrated that four factors explained 60.47% of the variance and were sensitive to discriminate the different clinical groups, with the preoperative group having the poorest quality of life. Internal consistency ranged from 0.92 to 0.96, and concurrent validity with the ESI-55 was moderate/strong (0.32-0.70). Test-retest reliability was confirmed, with an ICC value of 0.54 (2 days), 0.91 (7 days), and 0.97 (30 days). The SHE had satisfactory psychometric qualities for use in the Brazilian population, similar to those of the original version. The instrument seems to be more adequate in psychometric terms for the postoperative and drug treatment follow-up groups, and its use should be encouraged. (c) 2012 Elsevier Inc. All rights reserved

Manual Hippocampal Subfield Segmentation Using High-Field MRI: Impact of Different Subfields in Hippocampal Volume Loss of Temporal Lobe Epilepsy Patients

In patients with temporal lobe epilepsy (TLE), presurgical magnetic resonance imaging (MRI) often reveals hippocampal atrophy, while neuropathological assessment indicates the different types of hippocampal sclerosis (HS). Different HS types are not discriminated in MRI so far. We aimed to define the volume of each hippocampal subfield on MRI manually and to compare automatic and manual segmentations for the discrimination of HS types. The T2-weighted images from 14 formalin-fixed age-matched control hippocampi were obtained with 4.7T MRI to evaluate the volume of each subfield at the anatomical level of the hippocampal head, body, and tail. Formalin-fixed coronal sections at the level of the body of 14 control cases, as well as tissue samples from 24 TLE patients, were imaged with a similar high-resolution sequence at 3T. Presurgical three-dimensional (3D) T1-weighted images from TLE went through a FreeSurfer 6.0 hippocampal subfield automatic assessment. The manual delineation with the 4.7T MRI was identified using Luxol Fast Blue stained 10-μm-thin microscopy slides, collected at every millimeter. An additional section at the level of the body from controls and TLE cases was submitted to NeuN immunohistochemistry for neuronal density estimation. All TLE cases were classified according to the International League Against Epilepsy's (ILAE's) HS classification. Manual volumetry in controls revealed that the dentate gyrus (DG)+CA4 region, CA1, and subiculum accounted for almost 90% of the hippocampal volume. The manual 3T volumetry showed that all TLE patients with type 1 HS (TLE-HS1) had lower volumes for DG+CA4, CA2, and CA1, whereas those TLE patients with HS type 2 (TLE-HS2) had lower volumes only in CA1 (p ≤ 0.038). Neuronal cell densities always decreased in CA4, CA3, CA2, and CA1 of TLE-HS1 but only in CA1 of TLE-HS2 (p ≤ 0.003). In addition, TLE-HS2 had a higher volume (p = 0.016) and higher neuronal density (p < 0.001) than the TLE-HS1 in DG + CA4. Automatic segmentation failed to match the manual or histological findings and was unable to differentiate TLE-HS1 from TLE-HS2. Total hippocampal volume correlated with DG+CA4 and CA1 volumes and neuronal density. For the first time, we also identified subfield-specific pathology patterns in the manual evaluation of volumetric MRI scans, showing the importance of manual segmentation to assess subfield-specific pathology patterns

Towards motion insensitive EEG-fMRI:Correcting motion-induced voltages and gradient artefact instability in EEG using an fMRI prospective motion correction (PMC) system

The simultaneous acquisition of electroencephalography and functional magnetic resonance imaging (EEG-fMRI) is a multimodal technique extensively applied for mapping the human brain. However, the quality of EEG data obtained within the MRI environment is strongly affected by subject motion due to the induction of voltages in addition to artefacts caused by the scanning gradients and the heartbeat. This has limited its application in populations such as paediatric patients or to study epileptic seizure onset. Recent work has used a Moiré-phase grating and a MR-compatible camera to prospectively update image acquisition and improve fMRI quality (prospective motion correction: PMC). In this study, we use this technology to retrospectively reduce the spurious voltages induced by motion in the EEG data acquired inside the MRI scanner, with and without fMRI acquisitions. This was achieved by modelling induced voltages from the tracking system motion parameters; position and angles, their first derivative (velocities) and the velocity squared. This model was used to remove the voltages related to the detected motion via a linear regression. Since EEG quality during fMRI relies on a temporally stable gradient artefact (GA) template (calculated from averaging EEG epochs matched to scan volume or slice acquisition), this was evaluated in sessions both with and without motion contamination, and with and without PMC. We demonstrate that our approach is capable of significantly reducing motion-related artefact with a magnitude of up to 10mm of translation, 6° of rotation and velocities of 50mm/s, while preserving physiological information. We also demonstrate that the EEG-GA variance is not increased by the gradient direction changes associated with PMC. Provided a scan slice-based GA template is used (rather than a scan volume GA template) we demonstrate that EEG variance during motion can be supressed towards levels found when subjects are still. In summary, we show that PMC can be used to dramatically improve EEG quality during large amplitude movements, while benefiting from previously reported improvements in fMRI quality, and does not affect EEG data quality in the absence of large amplitude movements

Independent predictors and a prognostic model for surgical outcome in refractory frontal lobe epilepsy

Purpose: Refractory frontal lobe epilepsy (FLE) remains one of the most challenging surgically remediable epilepsy syndromes. Nevertheless, definition of independent predictors and predictive models of postsurgical seizure outcome remains poorly explored in FLE. Methods: We retrospectively analyzed data from 70 consecutive patients with refractory FLE submitted to surgical treatment at our center from July 1994 to December 2006. Univariate results were submitted to logistic regression models and Cox proportional hazards regression to identify isolated risk factors for poor surgical results and to construct predictive models for surgical outcome in FLE. Results: From 70 patients submitted to surgery, 45 patients (64%) had favorable outcome and 37 (47%) became seizure free. Isolated risk factors for poor surgical outcome are expressed in hazard ratio (H.R.) and were time of epilepsy (H.R.=4.2; 95% C.I.=.1.5-11.7; p=0.006), ictal EEG recruiting rhythm (H.R. = 2.9; 95% C.I. = 1.1-7.7; p=0.033); normal MRI (H.R. = 4.8; 95% C.I. = 1.4-16.6; p = 0.012), and MRI with lesion involving eloquent cortex (H.R. = 3.8; 95% C.I. = 1.2-12.0; p = 0.021). Based on these variables and using a logistic regression model we constructed a model that correctly predicted long-term surgical outcome in up to 80% of patients. Conclusion: Among independent risk factors for postsurgical seizure outcome, epilepsy duration is a potentially modifiable factor that could impact surgical outcome in FLE. Early diagnosis, presence of an MRI lesion not involving eloquent cortex, and ictal EEG without recruited rhythm independently predicted favorable outcome in this series. (C) 2011 Elsevier B.V. All rights reserved.FAPESP/CINAPCE [04/14004-9]FAPESP/CINAPCECNPqCNPqCNPq [306644/2010-0]CNPqBrazilian research governmental grantsBrazilian research governmental grant

Psychiatric comorbidity in refractory focal epilepsy: A study of 490 patients

We studied the prevalence and associated factors of psychiatric comorbidities in 490 patients with refractory focal epilepsy. Of these, 198 (40.4%) patients had psychiatric comorbidity. An Axis I diagnosis was made in 154 patients (31.4%) and an Axis II diagnosis (personality disorder) in another 44 (8.97%) patients. After logistic regression, positive family history of psychiatric comorbidities (O.R.=1.98; 95% CI=1.10-3.58; p=0.023), the presence of Axis II psychiatric comorbidities (O.R.=3.25; 95% CI=1.70-6.22; p<0.0001), and the epileptogenic zone located in mesial temporal lobe structures (O.R.=1.94; 95% CI=1.25-3.03; p=0.003) remained associated with Axis I psychiatric comorbidities. We concluded that a combination of clinical variables and selected structural abnormalities of the central nervous system contributes to the development of psychiatric comorbidities in patients with focal epilepsy. (C) 2012 Published by Elsevier Inc.Brazilian Government agenciesBrazilian Government agenciesFAPESP/CINAPCE [04/14004-9]FAPESP/CINAPCECNPq [306644/2010-0, 483108/2010-3]CNPqFAPERGS/PRONEMFAPERGS/PRONE