Renin-angiotensin inhibitors reduce thrombotic complications in Essential Thrombocythemia and Polycythemia Vera patients with arterial hypertension.

Essential Thrombocythemia (ET) and Polycythemia Vera (PV) are chronic myeloproliferative neoplasms (MPNs) characterized by thrombotic and hemorrhagic complications, leading to a high risk of disability and mortality. Although arterial hypertension was found to be the most significant modifiable cardiovascular (CV) risk factor in the general population, little is known about its role in MPNs as well as a possible role of renin-angiotensin system inhibitors (RASi) in comparison with other anti-hypertensive treatments. We investigated a large cohort of 404 MPN adult patients, 133 diagnosed with PV and 271 with ET. Over half of the patients (53.7%) reported hypertension at MPN diagnosis. The 15-year cumulative incidence of thrombotic-adverse events (TAEs) was significantly higher in patients with hypertension (66.8 ± 10.3% vs 38.5 ± 8.4%; HR = 1.83; 95%CI 1.08-3.1). Multivariate analysis showed that PV diagnosis and hypertension were independently associated with a higher risk of developing TAEs (HR = 3.5; 95%CI 1.928-6.451, p < 0.001 and HR = 1.8; 95%CI 0.983-3.550, p = 0.05, respectively). In multivariate analysis, the diagnosis of PV confirmed a significant predictive role in developing TAEs (HR = 4.4; 95%CI 1.92-10.09, p < 0.01), also considering only MPN patients with hypertension. In addition, we found that the use of RASi showed a protective effect from TAEs both in the whole cohort of MPN with hypertension (HR = 0.46; 95%CI 0.21-0.98, p = 0.04) and in the subgroup of thrombotic high-risk score patients (HR = 0.49; 95%CI 0.24-1.01, p = 0.04). In particular, patients with ET and a high risk of thrombosis seem to benefit most from RASi treatment (HR = 0.27; 95%CI 0.07-1.01, p = 0.03). Hypertension in MPN patients represents a significant risk factor for TAEs and should be adequately treated.

Detection of epileptic activity in presumably normal EEG.

Monitoring epileptic activity in the absence of interictal discharges is a major need given the well-established lack of reliability of patients' reports of their seizures. Up to now, there are no other tools than reviewing the seizure diary; however, seizures may not be remembered or dismissed voluntarily. In the present study, we set out to determine if EEG voltage maps of epileptogenic activity in individual patients can help to identify disease activity, even if their scalp EEG appears normal. Twenty-five patients with pharmacoresistant focal epilepsy were included. For each patient, 6 min of EEG with spikes (yes-spike) and without visually detectable epileptogenic discharges (no-spike) were selected from long-term monitoring recordings (EEG 31-37 channels). For each patient, we identified typical discharges, calculated their average and the corresponding scalp voltage map ('spike-map'). We then fitted the spike-map for each patient on their (i) EEG epochs with visible spikes, (ii) epochs without any visible spike and (iii) EEGs of 48 controls. The global explained variance was used to estimate the presence of the spike-maps. The individual spike-map occurred more often in the spike-free EEGs of patients compared to EEGs of healthy controls (P = 0.001). Not surprisingly, this difference was higher if the EEGs contained spikes (P < 0.001). In patients, spike-maps were more frequent per second (P < 0.001) but with a shorter mean duration (P < 0.001) than in controls, for both no-spike and yes-spike EEGs. The amount of spike-maps was unrelated to clinical variables, like epilepsy severity, drug load or vigilance state. Voltage maps of spike activity are present very frequently in the scalp EEG of patients, even in presumably normal EEG. We conclude that spike-maps are a robust and potentially powerful marker to monitor subtle epileptogenic activity.

Visual analysis of high density EEG: As good as electrical source imaging?

OBJECTIVE: In this study, we sought to determine whether visual analysis of high density EEG (HD-EEG) would provide similar localizing information comparable to electrical source imaging (ESI). METHODS: HD-EEG (256 electrodes) recordings from 20 patients suffering from unifocal, drug-resistant epilepsy (13 women, mean age 29.1 ±â€¯2.62 years, 11 with temporal lobe epilepsy) were examined. In the visual analysis condition, we identified the 5 contacts with maximal spike amplitude and determined their localization with respect to the underlying cortex. ESI was computed using the LAURA algorithm of the averaged spikes in the patient's individual MRI. We considered the localization "correct" if all 5 contacts were concordant with the resection volume underneath or if ESI was located within the resection as determined by the postoperative MRI. RESULTS: Twelve patients were postoperatively seizure-free (Engel Class IA), while the remaining eight were in class IB to IV. Visual analysis and ESI showed sensitivity of 58% and 75%, specificity of 75% and 87%, and accuracy of 65% and 80%, respectively. In 70% of cases, visual analysis and ESI provided concordant results. CONCLUSIONS: Localization of the electrodes with maximal spike amplitude provides very good estimation of the localization of the underlying source. However, ESI has a higher accuracy and adds 3D information; therefore, it should remain the tool of choice for presurgical evaluation. SIGNIFICANCE: The present study proposes the possibility to analyze HD-EEG visually, in tandem with ESI or alone, if ESI is not accessible.

Localizing non-epileptiform abnormal brain function in children using high density EEG: Electric Source Imaging of focal slowing.

BACKGROUND: Electric Source Imaging (ESI) of interictal epileptiform discharges (IED) is increasingly validated for localizing epileptic activity. In children, IED can be absent or multifocal even in cases of a focal epileptogenic zone and additional electrophysiological markers are needed. Here, we investigated ESI of pathological focal slowing (FS) recorded on EEG as a new localizing marker in children with drug-resistant epilepsy. METHODS: We selected 15 children (median: 12; range: 4-18yrs), with high-density EEG (hdEEG), presurgical evaluation and surgical resection. One patient had a non-lesional MRI. ESI of patient-specific focal slow activity was performed (distributed linear inverse solution and individual head model). The maximal average power in the band of interest was considered as the source of focal slowing (ESI-FS). The Euclidian distance between ESI-FS and the resection (5 mm margin) was compared to the localization of maximal ESI of interictal epileptiform discharges (ESI-IED), interictal FDG-PET and ictal SPECT/SISCOM. RESULTS: In 9/15 patients (60%), ESI of focal slowing (ESI-FS) was inside or ≤5 mm from resection margins. The remaining 6/15 cases had distances ≤15 mm. In 9/15 patients with interictal spikes, the ESI-IED was concordant with the resection. 6/15 patients with concordant ESI-FS showed also interictal concordant ESI of IED; in 3/15 patients, ESI-FS but not ESI-IED was concordant with the resection. In 10/15 patients, ESI-FS was concordant with MRI lesion and for ESI-IED this concordance was on 8/15 patients. Maximal hypometabolism and SISCOM were concordant with the resection for 7/15 and 7/12, respectively. CONCLUSION: These findings suggest that "non-epileptiform" EEG activity, such as focal slowing, could be a complementary useful marker to localize the epileptogenic zone. ESI-FS may notably be applied in young patients without focal interictal spikes or multifocal spikes. This potential new marker of brain dysfunction has potential applications to other neurological disorders associated with slow EEG activity.

L-Dopa Modulation of Brain Connectivity in Parkinson's Disease Patients: A Pilot EEG-fMRI Study.

Studies of functional neurosurgery and electroencephalography in Parkinson's disease have demonstrated abnormally synchronous activity between basal ganglia and motor cortex. Functional neuroimaging studies investigated brain dysfunction during motor task or resting state and primarily have shown altered patterns of activation and connectivity for motor areas. L-dopa administration relatively normalized these functional alterations. The aim of this pilot study was to examine the effects of L-dopa administration on functional connectivity in early-stage PD, as revealed by simultaneous recording of functional magnetic resonance imaging (fMRI) and electroencephalographic (EEG) data. Six patients with diagnosis of probable PD underwent EEG-fMRI acquisitions (1.5 T MR scanner and 64-channel cap) before and immediately after the intake of L-dopa. Regions of interest in the primary motor and sensorimotor regions were used for resting state fMRI analysis. From the EEG data, weighted partial directed coherence was computed in the inverse space after the removal of gradient and cardioballistic artifacts. fMRI results showed that the intake of L-dopa increased functional connectivity within the sensorimotor network, and between motor areas and both attention and default mode networks. EEG connectivity among regions of the motor network did not change significantly, while regions of the default mode network showed a strong tendency to increase their outflow toward the rest of the brain. This pilot study provided a first insight into the potentiality of simultaneous EEG-fMRI acquisitions in PD patients, showing for both techniques the analogous direction of increased connectivity after L-dopa intake, mainly involving motor, dorsal attention and default mode networks.

The predictive value of hypometabolism in focal epilepsy: a prospective study in surgical candidates.

PURPOSE: FDG PET is an established tool in presurgical epilepsy evaluation, but it is most often used selectively in patients with discordant MRI and EEG results. Interpretation is complicated by the presence of remote or multiple areas of hypometabolism, which leads to doubt as to the true location of the seizure onset zone (SOZ) and might have implications for predicting the surgical outcome. In the current study, we determined the sensitivity and specificity of PET localization prospectively in a consecutive unselected cohort of patients with focal epilepsy undergoing in-depth presurgical evaluation. METHODS: A total of 130 patients who underwent PET imaging between 2006 and 2015 matched our inclusion criteria, and of these, 86 were operated on (72% with a favourable surgical outcome, Engel class I). Areas of focal hypometabolism were identified using statistical parametric mapping and concordance with MRI, EEG and intracranial EEG was evaluated. In the surgically treated patients, postsurgical outcome was used as the gold standard for correctness of localization (minimum follow-up 12 months). RESULTS: PET sensitivity and specificity were both 95% in 86 patients with temporal lobe epilepsy (TLE) and 80% and 95%, respectively, in 44 patients with extratemporal epilepsy (ETLE). Significant extratemporal hypometabolism was observed in 17 TLE patients (20%). Temporal hypometabolism was observed in eight ETLE patients (18%). Among the 86 surgically treated patients, 26 (30%) had hypometabolism extending beyond the SOZ. The presence of unilobar hypometabolism, included in the resection, was predictive of complete seizure control (p = 0.007), with an odds ratio of 5.4. CONCLUSION: Additional hypometabolic areas were found in one of five of this group of nonselected patients with focal epilepsy, including patients with "simple" lesional epilepsy, and this finding should prompt further in-depth evaluation of the correlation between EEG findings, semiology and PET. Hypometabolism confined to the epileptogenic zone as defined by EEG and MRI is associated with a favourable postoperative outcome in both TLE and ETLE patients.

Nicotine increases sleep spindle activity.

Studies have shown that both nicotine and sleep spindles are associated with enhanced memorisation. Further, a few recent studies have shown how cholinergic input through nicotinic and muscarinic receptors can trigger or modulate sleep processes in general, and sleep spindles in particular. To better understand the interaction between nicotine and sleep spindles, we compared in a single blind randomised study the characteristics of sleep spindles in 10 healthy participants recorded for 2 nights, one with a nicotine patch and one with a sham patch. We investigated differences in sleep spindle duration, amplitude, intra-spindle oscillation frequency and density (i.e. spindles per min). We found that under nicotine, spindles are more numerous (average increase: 0.057 spindles per min; 95% confidence interval: [0.025-0.089]; p = .0004), have higher amplitude (average amplification: 0.260 µV; confidence interval: [0.119-0.402]; p = .0032) and last longer (average lengthening: 0.025 s; confidence interval: [0.017-0.032]; p = 2.7e-11). These results suggest that nicotine can increase spindle activity by acting on nicotinic acetylcholine receptors, and offer an attractive hypothesis for common mechanisms that may support memorisation improvements previously reported to be associated with nicotine and sleep spindles.

Diagnostic Biomarkers of Epilepsy.

BACKGROUND: Diagnostic biomarkers of epilepsy are objectively measurable variables associated with the development of epilepsy or the propensity to generate seizures. Identification of biomarkers could be helpful for differential diagnosis and for tailored therapeutic approaches. OBJECTIVE: This review focuses on diagnostic biomarkers of epilepsy, including genetic, serological, neuroimaging and electrophysiological variables. METHODS: References were mainly identified through PubMed search until December 2017 and backtracking of references in pertinent studies. RESULTS: Several promising diagnostic biomarkers of epilepsy exist, with causative value or predicting liability to develop seizures after acquired brain injuries. Short non-coding RNAs are deregulated in serum and cerebral tissue of epilepsy subjects: these molecules are promising diagnostic biomarkers, being easy to assess and reproducible. Advanced imaging techniques may allow identification of subtle epileptogenic lesions, often with prognostic value. Novel electrophysiological biomarkers of epilepsy include perturbed cortical connectivity and excitability induced by transcranial magnetic stimulation, as well as high-frequency oscillations detected by intracranial and scalp electroencephalographic recordings. Finally, serological biomarkers may support the differential diagnosis between epileptic seizures and non-epileptic events. CONCLUSION: Ongoing research on diagnostic biomarkers of epilepsy is promising and future preclinical and clinical studies are warranted.

European trends in epilepsy surgery.

OBJECTIVE: Resective surgery is effective in treating drug-resistant focal epilepsy, but it remains unclear whether improved diagnostics influence postsurgical outcomes. Here, we compared practice and outcomes over 2 periods 15 years apart. METHODS: Sixteen European centers retrospectively identified 2 cohorts of children and adults who underwent epilepsy surgery in the period of 1997 to 1998 (n = 562) or 2012 to 2013 (n = 736). Data collected included patient (sex, age) and disease (duration, localization and diagnosis) characteristics, type of surgery, histopathology, Engel postsurgical outcome, and complications, as well as imaging and electrophysiologic tests performed for each case. Postsurgical outcome predictors were included in a multivariate logistic regression to assess the strength of date of surgery as an independent predictor. RESULTS: Over time, the number of operated cases per center increased from a median of 31 to 50 per 2-year period (p = 0.02). Mean disease duration at surgery decreased by 5.2 years (p < 0.001). Overall seizure freedom (Engel class 1) increased from 66.7% to 70.9% (adjusted p = 0.04), despite an increase in complex surgeries (extratemporal and/or MRI negative). Surgeries performed during the later period were 1.34 times (adjusted odds ratio; 95% confidence interval 1.02-1.77) more likely to yield a favorable outcome (Engel class I) than earlier surgeries, and improvement was more marked in extratemporal and MRI-negative temporal epilepsy. The rate of persistent neurologic complications remained stable (4.6%-5.3%, p = 0.7). CONCLUSION: Improvements in European epilepsy surgery over time are modest but significant, including higher surgical volume, shorter disease duration, and improved postsurgical seizure outcomes. Early referral for evaluation is required to continue on this encouraging trend.

MP2RAGE and Susceptibility-Weighted Imaging in Lesional Epilepsy at 7T.

BACKGROUND AND PURPOSE: Surgery is the first choice therapeutic approach in case of drug-resistant epilepsy. Unfortunately, up to 43% of patients referred for presurgical assessment do not have a lesion detectable by routine 3T magnetic resonance imaging (MRI) (MRI-negative), although most of them likely have an underlying epileptogenic lesion. Thus, new MRI modalities with increased sensibility for epileptogenic lesions are required. This paper describes the magnetization-prepared two rapid acquisition gradient echoes (MP2RAGE) and susceptibility-weighted imaging (SWI) findings at 7T in a series of patients with drug-resistant epilepsy of different etiologies. METHODS: Prospective pilot study of 7 patients with drug-resistant lesional epilepsy and absence of contraindications for MRI underwent a research 7T head-only scanner. Qualitative analysis of the high-resolution MP2RAGE and SWI sequences is given for each case. This study was approved by the local ethics committee. Written informed consent was obtained from each participant. RESULTS: This study shows that such sequences at ultra-high field are new and valuable approaches to unravel and characterize epileptogenic lesions. Particularly, MP2RAGE shows a better delineation of lesions due to high gray-white matter contrast and structural resolution, and SWI reveals new imaging signs related to improved magnitude and phase contrast imaging. CONCLUSION: MRI at ultra-high field is very promising for the detection of inconspicuous epileptogenic lesions and may facilitate epilepsy surgery of a great number of to-date MRI-negative patients.

Automated diagnosis of temporal lobe epilepsy in the absence of interictal spikes.

Objective: To diagnose and lateralise temporal lobe epilepsy (TLE) by building a classification system that uses directed functional connectivity patterns estimated during EEG periods without visible pathological activity. Methods: Resting-state high-density EEG recording data from 20 left TLE patients, 20 right TLE patients and 35 healthy controls was used. Epochs without interictal spikes were selected. The cortical source activity was obtained for 82 regions of interest and whole-brain directed functional connectivity was estimated in the theta, alpha and beta frequency bands. These connectivity values were then used to build a classification system based on two two-class Random Forests classifiers: TLE vs healthy controls and left vs right TLE. Feature selection and classifier training were done in a leave-one-out procedure to compute the mean classification accuracy. Results: The diagnosis and lateralization classifiers achieved a high accuracy (90.7% and 90.0% respectively), sensitivity (95.0% and 90.0% respectively) and specificity (85.7% and 90.0% respectively). The most important features for diagnosis were the outflows from left and right medial temporal lobe, and for lateralization the right anterior cingulate cortex. The interaction between features was important to achieve correct classification. Significance: This is the first study to automatically diagnose and lateralise TLE based on EEG. The high accuracy achieved demonstrates the potential of directed functional connectivity estimated from EEG periods without visible pathological activity for helping in the diagnosis and lateralization of TLE.

Clinical Neuroimaging Using 7 T MRI: Challenges and Prospects.

The aim of this article is to illustrate the principal challenges, from the medical and technical point of view, associated with the use of ultrahigh field (UHF) scanners in the clinical setting and to present available solutions to circumvent these limitations. We would like to show the differences between UHF scanners and those used routinely in clinical practice, the principal advantages, and disadvantages, the different UHFs that are ready be applied to routine clinical practice such as susceptibility-weighted imaging, fluid-attenuated inversion recovery, 3-dimensional time of flight, magnetization-prepared rapid acquisition gradient echo, magnetization-prepared 2 rapid acquisition gradient echo, and diffusion-weighted imaging, the technical principles of these sequences, and the particularities of advanced techniques such as diffusion tensor imaging, spectroscopy, and functional imaging at 7TMR. Finally, the main clinical applications in the field of the neuroradiology are discussed and the side effects are reported.

EEG source connectivity to localize the seizure onset zone in patients with drug resistant epilepsy.

Electrical source imaging (ESI) from interictal scalp EEG is increasingly validated and used as a valuable tool in the presurgical evaluation of epilepsy as a reflection of the irritative zone. ESI of ictal scalp EEG to localize the seizure onset zone (SOZ) remains challenging. We investigated the value of an approach for ictal imaging using ESI and functional connectivity analysis (FC). Ictal scalp EEG from 111 seizures in 27 patients who had Engel class I outcome at least 1 year following resective surgery was analyzed. For every seizure, an artifact-free epoch close to the seizure onset was selected and ESI using LORETA was applied. In addition, the reconstructed sources underwent FC using the spectrum-weighted Adaptive Directed Transfer Function. This resulted in the estimation of the SOZ in two ways: (i) the source with maximal power after ESI, (ii) the source with the strongest outgoing connections after combined ESI and FC. Next, we calculated the distance between the estimated SOZ and the border of the resected zone (RZ) for both approaches and called this the localization error ((i) LEpow and (ii) LEconn respectively). By comparing LEpow and LEconn, we assessed the added value of FC. The source with maximal power after ESI was inside the RZ (LEpow = 0 mm) in 31% of the seizures and estimated within 10 mm from the border of the RZ (LEpow ≤ 10 mm) in 42%. Using ESI and FC, these numbers increased to 72% for LEconn = 0 mm and 94% for LEconn ≤ 10 mm. FC provided a significant added value to ESI alone (p < 0.001). ESI combined with subsequent FC is able to localize the SOZ in a non-invasive way with high accuracy. Therefore it could be a valuable tool in the presurgical evaluation of epilepsy.

Source localization of ictal epileptic activity based on high-density scalp EEG data.

OBJECTIVE: Electrical source imaging (ESI) is a well-established approach to localizing the epileptic focus in drug-resistant focal epilepsy. So far, ESI has been used primarily on interictal events. Emerging evidence suggests that ictal ESI is also feasible and potentially useful. We aimed to investigate the diagnostic accuracy of ESI on ictal events using high-density electroencephalography (EEG). METHODS: We performed ictal ESI on 14 patients (9 with temporal lobe epilepsy) admitted for presurgical evaluation who presented seizures during a long-term (≥18 h) high-density EEG recording (13 with 256 electrodes and one with 128 electrodes), and subsequently 8 of them underwent epilepsy surgery (postoperative follow-up >1 year). Artifact-free EEG epochs at ictal οnset were selected for further analysis. The predominant ictal rhythm was identified and filtered (±1 Hz around the main frequency). ESI was computed for each time point using an individual head model and a distributed linear inverse solution, and the average across source localizations was localized. For validation, results were compared with the resection area and postoperative outcome. RESULTS: Ictal ESI correctly localized the epileptic seizure-onset zone in the resection area in five of six postoperatively seizure-free patients. Interictal and ictal ESI were concordant in 9 of 14 patients and partially concordant in additional 4 of 14 patients (93%). Divergent solutions were found in only one of the 14 patients (7%). SIGNIFICANCE: Ictal ESI is a promising localization technique in focal epilepsy.

Contributions of EEG-fMRI to Assessing the Epileptogenicity of Focal Cortical Dysplasia.

Purpose: To examine the ability of the BOLD response to EEG spikes to assess the epileptogenicity of the lesion in patients with focal cortical dysplasia (FCD). Method: Patients with focal epilepsy and FCD who underwent 3T EEG-fMRI from 2006 to 2010 were included. Diagnosis of FCD was based on neuroradiology (MRI+), or histopathology in MRI-negative cases (MRI-). Patients underwent 120 min EEG-fMRI recording session. Spikes similar to those recorded outside the scanner were marked in the filtered EEG. The lesion (in MRI+) or the removed cortex (in MRI-) was marked on the anatomical T1 sequence, blindly to the BOLD response, after reviewing the FLAIR images. For each BOLD response we assessed the concordance with the spike field and with the lesion in MRI+ or the removed cortex in MRI-. BOLD responses were considered "concordant" if the maximal t-value was inside the marking. Follow-up after resection was used as gold-standard. Results: Twenty patients were included (13 MRI+, 7 MRI-), but in seven the EEG was not active or there were artifacts during acquisition. In all 13 studied patients, at least one BOLD response was concordant with the spike field; in 9/13 (69%) at least one BOLD response was concordant with the lesion: in 6/7 (86%) MRI+ and in 3/6 (50%) MRI- patients. Conclusions: Our study shows a high level of concordance between FCD and BOLD response. This data could provide useful information especially for MRI negative patients. Moreover, it shows in almost all FCD patients, a metabolic involvement of remote cortical or subcortical structures, corroborating the concept of epileptic network.

Epileptic spasms in epilepsy with myoclonic-atonic seizures (Doose syndrome).

AIM: To describe the occurrence of epileptic spasms in epilepsy with myoclonic-atonic seizures (EMAS) or Doose syndrome. METHODS: Case descriptions of patients with EMAS and epileptic spasms. Diagnosis of EMAS was performed according to the following criteria: (1) onset of myoclonic, myoclonic-atonic, or atonic seizures at between 7 months and 6 years of age; (2) normal development before onset of epilepsy; (3) absence of structural cerebral abnormalities on MRI; (4) presence of generalized spike-waves or polyspike-waves on EEG; and (5) exclusion of other myoclonic epilepsies. RESULTS: Four patients with EMAS were included. For each of them, epileptic spasms were documented by video interpretation, or video-EEG when available. CONCLUSIONS: Our description of epileptic spasms in four patients with EMAS enlarges the spectrum of seizures that may be observed in this syndrome, as well as the number of epilepsy syndromes which may involve epileptic spasms. This evidence suggests that the presence of epileptic spasms is consistent with a diagnosis of EMAS; epileptic spasms should therefore not be considered a seizure type that excludes diagnosis of this epilepsy syndrome. The prognostic significance of epileptic spasms associated with EMAS remains unknown.

Epileptic networks are strongly connected with and without the effects of interictal discharges.

OBJECTIVE: Epilepsy is increasingly considered as the dysfunction of a pathologic neuronal network (epileptic network) rather than a single focal source. We aimed to assess the interactions between the regions that comprise the epileptic network and to investigate their dependence on the occurrence of interictal epileptiform discharges (IEDs). METHODS: We analyzed resting state simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) recordings in 10 patients with drug-resistant focal epilepsy with multifocal IED-related blood oxygen level-dependent (BOLD) responses and a maximum t-value in the IED field. We computed functional connectivity (FC) maps of the epileptic network using two types of seed: (1) a 10-mm diameter sphere centered in the global maximum of IED-related BOLD map, and (2) the independent component with highest correlation to the IED-related BOLD map, named epileptic component. For both approaches, we compared FC maps before and after regressing out the effect of IEDs in terms of maximum and mean t-values and percentage of map overlap. RESULTS: Maximum and mean FC maps t-values were significantly lower after regressing out IEDs at the group level (p < 0.01). Overlap extent was 85% ± 12% and 87% ± 12% when the seed was the 10-mm diameter sphere and the epileptic component, respectively. SIGNIFICANCE: Regions involved in a specific epileptic network show coherent BOLD fluctuations independent of scalp EEG IEDs. FC topography and strength is largely preserved by removing the IED effect. This could represent a signature of a sustained pathologic network with contribution from epileptic activity invisible to the scalp EEG.

Presurgical brain mapping in epilepsy using simultaneous EEG and functional MRI at ultra-high field: feasibility and first results.

OBJECTIVES: The aim of this study was to demonstrate that eloquent cortex and epileptic-related hemodynamic changes can be safely and reliably detected using simultaneous electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) recordings at ultra-high field (UHF) for clinical evaluation of patients with epilepsy. MATERIALS AND METHODS: Simultaneous EEG-fMRI was acquired at 7 T using an optimized setup in nine patients with lesional epilepsy. According to the localization of the lesion, mapping of eloquent cortex (language and motor) was also performed in two patients. RESULTS: Despite strong artifacts, efficient correction of intra-MRI EEG could be achieved with optimized artifact removal algorithms, allowing robust identification of interictal epileptiform discharges. Noise-sensitive topography-related analyses and electrical source localization were also performed successfully. Localization of epilepsy-related hemodynamic changes compatible with the lesion were detected in three patients and concordant with findings obtained at 3 T. Local loss of signal in specific regions, essentially due to B 1 inhomogeneities were found to depend on the geometric arrangement of EEG leads over the cap. CONCLUSION: These results demonstrate that presurgical mapping of epileptic networks and eloquent cortex is both safe and feasible at UHF, with the benefits of greater spatial resolution and higher blood-oxygenation-level-dependent sensitivity compared with the more traditional field strength of 3 T.

Altered directed functional connectivity in temporal lobe epilepsy in the absence of interictal spikes: A high density EEG study.

OBJECTIVE: In patients with epilepsy, seizure relapse and behavioral impairments can be observed despite the absence of interictal epileptiform discharges (IEDs). Therefore, the characterization of pathologic networks when IEDs are not present could have an important clinical value. Using Granger-causal modeling, we investigated whether directed functional connectivity was altered in electroencephalography (EEG) epochs free of IED in left and right temporal lobe epilepsy (LTLE and RTLE) compared to healthy controls. METHODS: Twenty LTLE, 20 RTLE, and 20 healthy controls underwent a resting-state high-density EEG recording. Source activity was obtained for 82 regions of interest (ROIs) using an individual head model and a distributed linear inverse solution. Granger-causal modeling was applied to the source signals of all ROIs. The directed functional connectivity results were compared between groups and correlated with clinical parameters (duration of the disease, age of onset, age, and learning and mood impairments). RESULTS: We found that: (1) patients had significantly reduced connectivity from regions concordant with the default-mode network; (2) there was a different network pattern in patients versus controls: the strongest connections arose from the ipsilateral hippocampus in patients and from the posterior cingulate cortex in controls; (3) longer disease duration was associated with lower driving from contralateral and ipsilateral mediolimbic regions in RTLE; (4) aging was associated with a lower driving from regions in or close to the piriform cortex only in patients; and (5) outflow from the anterior cingulate cortex was lower in patients with learning deficits or depression compared to patients without impairments and to controls. SIGNIFICANCE: Resting-state network reorganization in the absence of IEDs strengthens the view of chronic and progressive network changes in TLE. These resting-state connectivity alterations could constitute an important biomarker of TLE, and hold promise for using EEG recordings without IEDs for diagnosis or prognosis of this disorder.

Functional brain networks in epilepsy: recent advances in noninvasive mapping.

PURPOSE OF REVIEW: Epilepsy is one of the most frequent chronic neurological disorders. Recent evidences strongly suggest that epilepsy is due to a dysfunction within an epileptic network, rather than due to the pathological activity of single sources. The aim of this article is to review the recent advances on functional connectivity revealed by noninvasive neuroimaging techniques. RECENT FINDINGS: Functional connectivity detected through hemodynamic [functional MRI (fMRI)] and electro-magnetic techniques (EEG/MEG) in patients with epilepsy gives an insight into the physiopathogenesis of epileptic network underlying focal epilepsies and specific epileptic syndromes. An increasing number of studies suggest a relevance for surgical cases, both for localizing the focus and for predicting postsurgical cognitive impairment, based on the interactions between pathological and physiological networks. SUMMARY: fMRI and EEG/MEG functional connectivity are complementary techniques and help in identifying the interactions between epileptic activity and physiological networks at different scales. Neuropsychological and neuropsychiatric impairment can be explained by such interactions. fMRI and EEG/MEG functional connectivity help in localizing important drivers of epileptic activity and can also help in predicting postsurgical outcome. Given the large number of methods applied, strict validation, mostly obtained in surgical series, is of utmost importance to understand the benefits and limitations of each technique.