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.

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.

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.

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.

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.

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.

All-in-one interictal presurgical imaging in patients with epilepsy: single-session EEG/PET/(f)MRI.

PURPOSE: In patients with pharmacoresistant focal epilepsy, resection of the epileptic focus can lead to freedom from seizures or significant improvement in well-selected candidates. Localization of the epileptic focus with multimodal concordance is crucial for a good postoperative outcome. Beyond the detection of epileptogenic lesions on structural MRI and focal hypometabolism on FDG PET, EEG-based Electric Source Imaging (ESI) and simultaneous EEG and functional MRI (EEG-fMRI) are increasingly applied for mapping epileptic activity. We here report presurgical multimodal interictal imaging using a hybrid PET/MR scanner for single-session FDG PET, MRI, EEG-fMRI and ESI. METHODS: This quadrimodal imaging procedure was performed in a single session in 12 patients using a high-density (256 electrodes) MR-compatible EEG system and a hybrid PET/MR scanner. EEG was used to exclude subclinical seizures during uptake of the PET tracer, to compute ESI on interictal epileptiform discharges and to guide fMRI analysis for mapping haemodynamic changes correlated with interictal epileptiform activity. RESULTS: The whole multimodal recording was performed in less than 2 hours with good patient comfort and data quality. Clinically contributory examinations with at least two modalities were obtained in nine patients and with all modalities in five patients. CONCLUSION: This single-session quadrimodal imaging procedure provided reliable and contributory interictal clinical data. This procedure avoids multiple scanning sessions and is associated with less radiation exposure than PET-CT. Moreover, it guarantees the same medication level and medical condition for all modalities. The procedure improves workflow and could reduce the duration and cost of presurgical epilepsy evaluations.

Pulse artifact detection in simultaneous EEG-fMRI recording based on EEG map topography.

One of the major artifact corrupting electroencephalogram (EEG) acquired during functional magnetic resonance imaging (fMRI) is the pulse artifact (PA). It is mainly due to the motion of the head and attached electrodes and wires in the magnetic field occurring after each heartbeat. In this study we propose a novel method to improve PA detection by considering the strong gradient and inversed polarity between left and right EEG electrodes. We acquired high-density EEG-fMRI (256 electrodes) with simultaneous electrocardiogram (ECG) at 3 T. PA was estimated as the voltage difference between right and left signals from the electrodes showing the strongest artifact (facial and temporal). Peaks were detected on this estimated signal and compared to the peaks in the ECG recording. We analyzed data from eleven healthy subjects, two epileptic patients and four healthy subjects with an insulating layer between electrodes and scalp. The accuracy of the two methods was assessed with three criteria: (i) standard deviation, (ii) kurtosis and (iii) confinement into the physiological range of the inter-peak intervals. We also checked whether the new method has an influence on the identification of epileptic spikes. Results show that estimated PA improved artifact detection in 15/17 cases, when compared to the ECG method. Moreover, epileptic spike identification was not altered by the correction. The proposed method improves the detection of pulse-related artifacts, particularly crucial when the ECG is of poor quality or cannot be recorded. It will contribute to enhance the quality of the EEG increasing the reliability of EEG-informed fMRI analysis.

Negative BOLD response to interictal epileptic discharges in focal epilepsy.

In EEG-fMRI studies, BOLD responses related to interictal epileptic discharges (IEDs) are most often the expected positive response (activation) but sometimes a surprising negative response (deactivation). The significance of deactivation in the region of IED generation is uncertain. The aim of this study was to determine if BOLD deactivation was caused by specific IED characteristics. Among focal epilepsy patients who underwent 3T EEG-fMRI from 2006 to 2011, those with negative BOLD having a maximum t-value in the IED generating region were selected. As controls, subjects with maximum activation in the IED generating region were selected. We established the relationship between the type of response (activation/deactivation) and (1) presence of slow wave in the IEDs, (2) lobe of epileptic focus, (3) occurrence as isolated events or bursts, (4) spatial extent of the EEG discharge. Fifteen patients with deactivation and 15 with activation were included. The IEDs were accompanied by a slow wave in 87 % of patients whose primary BOLD was a deactivation and only in 33 % of patients with activation. In the deactivation group, the epileptic focus was more frequently in the posterior quadrant and involved larger cortical areas, whereas in the activation group it was more frequently temporal. IEDs were more frequently of long duration in the deactivation group. The main factor responsible for focal deactivations is the presence of a slow wave, which is the likely electrographic correlate of prolonged inhibition. This adds a link to the relationship between electrophysiological and BOLD activities.

Tobacco habits in nocturnal frontal lobe epilepsy.

The beneficial effect of nicotine has been reported in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) patients, but not tested in sporadic cases. Recently, a nicotine defect in the arousal pathway has been hypothesized even in sporadic NFLE patients and their relatives. This case-control family study was designed to test whether NFLE subjects were more likely to use tobacco than controls, as an indirect marker of cholinergic arousal system dysregulation. At least four relatives were included for each NFLE proband and control. Each subject was questioned about tobacco habits; 434 individuals were recruited. Moreover, we compared NFLE patients with age- and sex-matched controls to determine whether they are more likely to use tobacco. We found a slightly higher trend of tobacco use in NFLE probands compared to that in control subjects; we did not find any significant difference in the distribution of tobacco use among NFLE group compared to that in the control group.

Patterns of altered functional connectivity in mesial temporal lobe epilepsy.

PURPOSE: In mesial temporal lobe epilepsy (MTLE) the epileptogenic area is confined to the mesial temporal lobe, but other cortical and subcortical areas are also affected and cognitive and psychiatric impairments are usually documented. Functional connectivity methods are based on the correlation of the blood oxygen level dependent (BOLD) signal between brain regions, which exhibit consistent and reproducible functional networks from resting state data. The aim of this study is to compare functional connectivity of patients with MTLE during the interictal period with healthy subjects. We hypothesize that patients show reduced functional connectivity compared to controls, the interest being to determine which regions show this reduction. METHODS: We selected electroencephalography-functional magnetic resonance imaging (EEG-fMRI) resting state data without EEG spikes from 16 patients with right and 7 patients with left MTLE. EEG-fMRI resting state data of 23 healthy subjects matched for age, sex, and manual preference were selected as controls. Four volumes of interest in the left and right amygdalae and hippocampi (LA, RA, LH, and RH) were manually segmented in the anatomic MRI of each subject. The averaged BOLD time course within each volume of interest was used to detect brain regions with BOLD signal correlated with it. Group differences between patients and controls were estimated. KEY FINDINGS: In patients with right MTLE, group difference functional connectivity maps (RMTLE - controls) showed for RA and RH decreased connectivity with the brain areas of the default mode network (DMN), the ventromesial limbic prefrontal regions, and contralateral mesial temporal structures; and for LA and LH, decreased connectivity with DMN and contralateral hippocampus. Additional decreased connectivity was found between LA and pons and between LH and ventromesial limbic prefrontal structures. In patients with left MTLE, functional connectivity maps (LMTLE - controls) showed for LA and LH decreased connectivity with DMN, contralateral hippocampus, and bilateral ventromesial limbic prefrontal regions; no change in connectivity was detected for RA; and for RH, there was decreased connectivity with DMN, bilateral ventromesial limbic prefrontal regions, and contralateral amygdala and hippocampus. SIGNIFICANCE: In unilateral MTLE, amygdala and hippocampus on the affected and to a lesser extent on the healthy side are less connected, and are also less connected with the dopaminergic mesolimbic and the DMNs. Changes in functional connectivity between mesial temporal lobe structures and these structures may explain cognitive and psychiatric impairments often found in patients with MTLE.

Widespread epileptic networks in focal epilepsies: EEG-fMRI study.

PURPOSE: To assess the extent of brain involvement during focal epileptic activity, we studied patterns of cortical and subcortical metabolic changes coinciding with interictal epileptic discharges (IEDs) using group analysis of simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) scans in patients with focal epilepsy. METHODS: We selected patients with temporal lobe epilepsy (TLE, n = 32), frontal lobe epilepsy (FLE, n = 14), and posterior quadrant epilepsy (PQE, n = 20) from our 3 Tesla EEG-fMRI database. We applied group analysis upon the blood oxygen-level dependent (BOLD) response associated with focal IEDs. KEY FINDINGS: Patients with TLE and FLE showed activations and deactivations, whereas in PQE only deactivations occurred. In TLE and FLE, the largest activation was in the mid-cingulate gyri bilaterally. In FLE, activations were also found in the ipsilateral frontal operculum, thalamus, and internal capsule, and in the contralateral cerebellum, whereas in TLE, we found additional activations in the ipsilateral mesial and neocortical temporal regions, insula, and cerebellar cortex. All three groups showed deactivations in default mode network regions, the most widespread being in the TLE group, and less in PQE and FLE. SIGNIFICANCE: These results indicate that different epileptic syndromes result in unique and widespread networks related to focal IEDs. Default mode regions are deactivated in response to focal discharges in all three groups with syndrome specific pattern. We conclude that focal IEDs are associated with specific networks of widespread metabolic changes that may cause more substantial disturbance to brain function than might be appreciated from the focal nature of the scalp EEG discharges.

Combining EEG and fMRI in the study of epileptic discharges.

The combining of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) is a unique noninvasive method for investigating the brain regions involved at the time of epileptic discharges. The neuronal discharges taking place during an interictal spike or spike-wave burst result in an increase in metabolism and blood flow, which is reflected in the blood oxygen-level dependent (BOLD) signal measured by fMRI. This increase is most intense in the region generating the discharge but is also present in regions affected by the discharge. On occasion, epileptic discharges result in decreased metabolism, the origin of which is only partially understood. EEG-fMRI applied to focal epilepsy results in maxima of the BOLD signal most often concordant with other methods of localization and has been shown to help in localizing epileptic foci in nonlesional frontal lobe epilepsy. It has also demonstrated the involvement of the thalamus in generalized epileptic discharges. In patients with new-onset epilepsy it could be used to evaluate the source and extent of the brain structures involved during discharges and their evolution as the disease progresses.

Reproducibility of interictal EEG-fMRI results in patients with epilepsy.

PURPOSE: Combined electroencephalography (EEG) and functional MRI (EEG-fMRI) can be useful in the evaluation of epilepsy patients. The reproducibility of EEG-fMRI findings needs to be established to consider it as a clinically valuable method. We addressed the intrasubject reproducibility of EEG-fMRI and the possible superiority of higher magnetic field strength in patients who were scanned twice. METHODS: Fifteen patients were studied: Seven had one 1.5T and one 3T scan and eight had two 3T EEG-fMRI studies. Equal numbers of events of the same interictal epileptic discharge (IED) were included, and IED-related blood oxygenation level dependent (BOLD) results were compared. KEY FINDINGS: In 1.5T-3T comparisons, five patients had BOLD responses in both studies, but in four there was a better response (higher maximum t-score and larger cluster) in 3T studies. One patient had a BOLD response in the 3T study only. The remaining patient had no BOLD response in either study. In 3T-3T comparisons, results were reproducible in five of eight patients, and one patient had no response in both studies. The two remaining patients had previous extensive surgery and extremely frequent IEDs. Some of the reproduced patterns in other patients, however, differed in terms of maximum t-score and cluster size. SIGNIFICANCE: EEG-fMRI appears to provide reasonable reproducibility, although repeated studies may show differences. The absence of BOLD response seems to be reproducible as well. EEG-fMRI results tend to benefit from higher field scanners (3T over 1.5T). Further studies are needed to determine if reproducibility depends on specific clinical, electrographic, or anatomic findings.

Changes preceding interictal epileptic EEG abnormalities: comparison between EEG/fMRI and intracerebral EEG.

PURPOSE: In simultaneous scalp electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), blood oxygen level dependent (BOLD) changes occurring before the spike have been sometimes described but could not be explained. To characterize the origin of this prespike BOLD signal change, we looked for electrographic changes in stereo-EEG (SEEG) possibly preceding the scalp spike in patients that showed early BOLD response in EEG/fMRI. METHODS: We studied four patients with drug-resistant focal epilepsy who underwent EEG/fMRI, showed a prespike BOLD response, and were then studied with depth electrodes for presurgical localization of the epileptic generator. Early BOLD responses in the region of the spike field were analyzed using models with hemodynamic response functions (HRFs) peaking from -9 to +9 s around the spike. SEEG recordings in the period and location corresponding to the early HRF responses were analyzed to detect if electrographic changes were present in the SEEG before the scalp abnormality. KEY FINDINGS: One of the four patients presented a SEEG interictal discharge in the period corresponding to the early BOLD response. In the other three, no electrographic changes were detected in the SEEG in the period corresponding to early BOLD changes. SIGNIFICANCE: Although the early BOLD activity may sometimes be explained by a synchronized neural discharge detectable with SEEG but not visible on the scalp EEG, in most cases the early BOLD response reflects a metabolic phenomenon that does not appear to result from a synchronized neuronal discharge. Prespike metabolic responses can result from synchronized or nonsynchronized neuronal activity, or from nonneuronal mechanisms including glia.

Functional connectivity in patients with idiopathic generalized epilepsy.

PURPOSE: Idiopathic generalized epilepsy (IGE) is characterized by electroencephalography (EEG) recordings with generalized spike wave discharges (GSWDs) arising from normal background activity. Although GSWDs are the result of highly synchronized activity in the thalamocortical network, EEG without GSWDs is believed to represent normal brain activity. The aim of this study was to investigate whether thalamocortical interactions are altered even during GSWD-free EEG periods in patients with IGE. METHODS: A GSWD-related group analysis was performed in 12 IGE patients to define seeds in areas involved during GSWDs. EEG-functional magnetic resonance imaging (fMRI) datasets from 22 IGE patients without GSWDs during the investigation and 30 age-matched healthy controls were then selected to investigate functional connectivity in GSWD-related areas. Blood oxygen level dependent (BOLD) signal changes were extracted from seeds defined by the GSWD-related group analysis. The averaged time course within each seed was used to detect brain regions with BOLD signal correlated with the seed. Group differences between patients and controls were estimated. KEY FINDINGS: The GSWD-related group analysis showed BOLD activation in the thalamus, the frontomesial cortex, and the cerebellum and BOLD deactivation in default mode areas. For the connectivity analysis, eight seeds were placed bilaterally in the thalamus, mesial frontal cortex, precuneus, and cerebellum. The functional connectivity analysis of these seeds did not show clearly altered functional connectivity for patients versus controls. SIGNIFICANCE: The results underscore the paroxysmal nature of GSWDs: Although GSWDs are characterized by highly synchronized activity in the thalamocortical network, the functional connectivity in areas involved during GSWDs does not demonstrate abnormality in GSWD-free periods.

Postictal hyperfamiliarity for unknown faces.

Hyperfamiliarity for unknown faces (HFUF) is a rare disorder in which unfamiliar people or faces appear familiar. Three young adults were admitted for acute symptomatic secondarily generalized tonic-clonic seizures (two) and psychomotor status (one). During the days following the seizures the patients continuously experienced a strong familiarity for unknown people, including other patients, visitors, and hospital staff. This disorder disappeared gradually, lasting a mean of 13 days. Brain MRI showed left amygdalohippocampal lesions, suggesting the etiology of encephalitis in two patients and multiple "active" demyelinating lesions in one patient. Interictal and ictal EEG findings showed left temporal epileptiform abnormalities. Two patients had a transitory defect of verbal memory. HFUF is a newly defined postictal symptom, more likely to arise from left temporal epileptic discharges. In our cases it was associated with acute lesions of the temporal areas, suggesting that its occurrence may also imply a structural etiology of epilepsy.

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.