A novel locus for generalized epilepsy with febrile seizures plus in French families.

International audienceBACKGROUND: Generalized epilepsy with febrile seizures plus (GEFS(+)) is a familial autosomal dominant entity characterized by the association of febrile and afebrile seizures. Mutations in 3 genes--the sodium channel alpha1 subunit gene (SCN1A), the sodium channel beta1 subunit gene (SCN1B), and the gamma2 GABA receptor subunit gene (GABRG2)--and linkage to 2 other loci on 2p24 and 21q22 have been identified in families with GEFS(+), indicating genetic heterogeneity. OBJECTIVES: To localize by means of linkage analysis a new gene for GEFS(+) in a large family with 11 affected members and to test the new locus in 4 additional families with GEFS(+). DESIGN: Family-based linkage analysis. SETTING: University hospital. PATIENTS: Five French families with GEFS(+) and at least 7 available affected members with autosomal dominant transmission. All the patients had febrile seizures and/or afebrile generalized tonic-clonic seizures or absence epilepsy. MAIN OUTCOME MEASURES: We analyzed 380 microsatellite markers and conducted linkage analysis. RESULTS: In the largest family, a 10-cM-density genomewide scan revealed linkage to a 13-Mb (megabase) interval on chromosome 8p23-p21 with a maximum pairwise logarithm of odds (LOD) score of 3.00 (at Theta = 0) for markers D8S351 and D8S550 and a multipoint LOD score of 3.23. A second family with GEFS(+) was also possibly linked to chromosome 8p23-p21 and the region was narrowed to a 7.3-Mb candidate interval, flanked by markers D8S1706 and D8S549. We have not, so far, identified mutations in the coding exons of 6 candidate genes (MTMR9, MTMR7, CTSB, SGCZ, SG223, and ATP6V1B2) located in the genetic interval. CONCLUSIONS: We report a sixth locus for GEFS(+) on chromosome 8p23-p21. Because no ion channel genes are located in this interval, identification of the responsible gene will probably uncover a new mechanism of pathogenesis for GEFS(+)

The written declaration on epilepsy : an important achievement for Europe and beyond

On 15th September 2011, the European Written Declaration on Epilepsy was passed by the European Union (EU) Parliament. This was a significant moment for all people who have been fighting over the years for a just recognition of the importance of epilepsy in the European political agenda. The whole process described below included several months of concerted effort by Members of the European Parliament (MEPs) and by Epilepsy Advocacy Europe (EAE), a joint task force of the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). ILAE and IBE member associations in Europe and many individuals also contributed greatly to the success of this initiative.peer-reviewe

An intracranial EEG study of the neural dynamics of musical valence processing

The processing of valence is known to recruit the amygdala, orbitofrontal cortex and relevant sensory areas. However, how these regions interact remains unclear. We recorded cortical electrical activity from 7 epileptic patients implanted with depth electrodes for presurgical evaluation while they listened to positively and negatively valenced musical chords. Time frequency analysis suggested a specific role of the orbitofrontal cortex in the processing of positively valenced stimuli while, most importantly, Granger causality analysis revealed that the amygdala tends to drive both the orbitofrontal cortex and the auditory cortex in theta and alpha frequency bands, during the processing of valenced stimuli. Results from the current study show the amygdala to be a critical hub in the emotion processing network: specifically one that influences not only the higher order areas involved in the evaluation of the stimulus’s emotional value but also the sensory cortical areas involved in the processing of its low level acoustic features

Human Gamma Oscillations during Slow Wave Sleep

Neocortical local field potentials have shown that gamma oscillations occur spontaneously during slow-wave sleep (SWS). At the macroscopic EEG level in the human brain, no evidences were reported so far. In this study, by using simultaneous scalp and intracranial EEG recordings in 20 epileptic subjects, we examined gamma oscillations in cerebral cortex during SWS. We report that gamma oscillations in low (30–50 Hz) and high (60–120 Hz) frequency bands recurrently emerged in all investigated regions and their amplitudes coincided with specific phases of the cortical slow wave. In most of the cases, multiple oscillatory bursts in different frequency bands from 30 to 120 Hz were correlated with positive peaks of scalp slow waves (“IN-phase” pattern), confirming previous animal findings. In addition, we report another gamma pattern that appears preferentially during the negative phase of the slow wave (“ANTI-phase” pattern). This new pattern presented dominant peaks in the high gamma range and was preferentially expressed in the temporal cortex. Finally, we found that the spatial coherence between cortical sites exhibiting gamma activities was local and fell off quickly when computed between distant sites. Overall, these results provide the first human evidences that gamma oscillations can be observed in macroscopic EEG recordings during sleep. They support the concept that these high-frequency activities might be associated with phasic increases of neural activity during slow oscillations. Such patterned activity in the sleeping brain could play a role in off-line processing of cortical networks

Converging Intracranial Markers of Conscious Access

We compared conscious and nonconscious processing of briefly flashed words using a visual masking procedure while recording intracranial electroencephalogram (iEEG) in ten patients. Nonconscious processing of masked words was observed in multiple cortical areas, mostly within an early time window (<300 ms), accompanied by induced gamma-band activity, but without coherent long-distance neural activity, suggesting a quickly dissipating feedforward wave. In contrast, conscious processing of unmasked words was characterized by the convergence of four distinct neurophysiological markers: sustained voltage changes, particularly in prefrontal cortex, large increases in spectral power in the gamma band, increases in long-distance phase synchrony in the beta range, and increases in long-range Granger causality. We argue that all of those measures provide distinct windows into the same distributed state of conscious processing. These results have a direct impact on current theoretical discussions concerning the neural correlates of conscious access

Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32

Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% and account for 20-30% of all epilepsies. Despite their high heritability of 80%, the genetic factors predisposing to GGEs remain elusive. To identify susceptibility variants shared across common GGE syndromes, we carried out a two-stage genome-wide association study (GWAS) including 3020 patients with GGEs and 3954 controls of European ancestry. To dissect out syndrome-related variants, we also explored two distinct GGE subgroups comprising 1434 patients with genetic absence epilepsies (GAEs) and 1134 patients with juvenile myoclonic epilepsy (JME). Joint Stage-1 and 2 analyses revealed genome-wide significant associations for GGEs at 2p16.1 (rs13026414, Pmeta = 2.5 × 10−9, OR[T] = 0.81) and 17q21.32 (rs72823592, Pmeta = 9.3 × 10−9, OR[A] = 0.77). The search for syndrome-related susceptibility alleles identified significant associations for GAEs at 2q22.3 (rs10496964, Pmeta = 9.1 × 10−9, OR[T] = 0.68) and at 1q43 for JME (rs12059546, Pmeta = 4.1 × 10−8, OR[G] = 1.42). Suggestive evidence for an association with GGEs was found in the region 2q24.3 (rs11890028, Pmeta = 4.0 × 10−6) nearby the SCN1A gene, which is currently the gene with the largest number of known epilepsy-related mutations. The associated regions harbor high-ranking candidate genes: CHRM3 at 1q43, VRK2 at 2p16.1, ZEB2 at 2q22.3, SCN1A at 2q24.3 and PNPO at 17q21.32. Further replication efforts are necessary to elucidate whether these positional candidate genes contribute to the heritability of the common GGE syndrome

Seizure anticipation : are neurophenomenological approaches able to detect preictal symptoms ?

International audienceAnalysis of electroencephalographic signals and several brain imaging studies suggest that a preictal state precedes the onset of seizures. In this study, we used phenomenological strategies to detect modifications in patients experience before their seizures. We observed that patients with partial epilepsy feeling an aura (n = 9) frequently experienced prodromes (n = 6). Prodromes were subtle preictal symptoms, varying among patients and having common negative features. They were generally continuous before seizures and could last hours, whereas auras were sudden and intermittent. All patients were able to recognize facilitating factors. We also found that patients spontaneously develop cognitive countermeasures to avoid facilitating factors (n = 6), to prevent a seizure (n = 1) or to interrupt a seizure (n = 5). Prodromes are not specific enough for clinical use, but could refine the behavioral strategies used in the treatment of epilepsy and the pathophysiology of the preictal state

Seizure anticipation: Are neuro-phenomenological approaches able to detect preictal symptoms? Epilepsy and Behavior 2006; 9:298-306 Petitmengin C. Towards the source of thoughts. The gestural and transmodal dimension of lived experience. Journal of Consci

Abstract Analysis of electroencephalographic signals and several brain imaging studies suggest that a preictal state precedes the onset of seizures. In this study, we used phenomenological strategies to detect modifications in patients&apos; experience before their seizures. We observed that patients with partial epilepsy feeling an aura (n = 9) frequently experienced prodromes (n = 6). Prodromes were subtle preictal symptoms, varying among patients and having common negative features. They were generally continuous before seizures and could last hours, whereas auras were sudden and intermittent. All patients were able to recognize facilitating factors. We also found that patients spontaneously develop cognitive countermeasures to avoid facilitating factors (n = 6), to prevent a seizure (n = 1) or to interrupt a seizure (n = 5). Prodromes are not specific enough for clinical use, but could refine the behavioral strategies used in the treatment of epilepsy and the pathophysiology of the preictal state

Perception temporelle dans la négligence spatiale unilatérale

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