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(+)

Loss of memory for auditory-spatial associations following unilateral medial temporal-lobe damage

The goal of the present experiment was to determine the role of medial temporal-lobe structures in episodic memory of auditory-spatial associations. By using a two-alternative forced choice paradigm in which an association between eight different sounds and their spatial location must be recognized, learning abilities over 10 learning sessions were tested in 19 patients who had undergone a right or a left medial temporal-lobe resection for the relief of intractable seizures as well as in nine normal control participants. The data demonstrated that significant learning took place over the successive sessions for all the participants. In addition, the results showed that patients with left but not right medial temporal-lobe lesion were impaired in this learning task as compared to normal participants, suggesting the predominant implication of left medial temporal-lobe structures in auditory-spatial associative learning. The predominant role of left hemisphere structures in this memory task could be explained by a spatial categorical coding, which was enhanced by the use of eight loud-speakers. This result also suggests that the ability to store an episodic event associated with a rich spatial (or temporal) context depends on the left medial temporal-lobe structures. Thus, this finding provides an interesting parallel with data obtained in the visual modality by documenting for the first time the role of the left medial temporal-lobe in episodic learning of auditory-spatial associations

The effects of railway noise on sleep medication intake: results from the ALPNAP-study

In the 1980s/90s, a number of socio-acoustic surveys and laboratory studies on railway noise effects have observed less reported disturbance/interference with sleep at the same exposure level compared with other modes of transportation. This lower grade of disturbance has received the label "railway bonus", was implemented in noise legislation in a number of European countries and was applied in planning and environmental impact assessments. However, majority of the studies investigating physiological outcomes did not find the bespoke difference. In a telephone survey (N=1643) we investigated the relationship between railway noise and sleep medication intake and the impact of railway noise events on motility parameters during night was assessed with contact-free high resolution actimetry devices. Multiple logistic regression analysis with cubic splines was applied to assess the probability of sleep medication use based on railway sound level and nine covariates. The non-linear exposure-response curve showed a statistically significant leveling off around 60 dB (A), Lden. Age, health status and trauma history were the most important covariates. The results were supported also by a similar analysis based on the indicator "night time noise annoyance". No railway bonus could be observed above 55 dB(A), Lden. In the actimetry study, the slope of rise of train noise events proved to be almost as important a predictor for motility reactions as was the maximum sound pressure level - an observation which confirms similar findings from laboratory experiments and field studies on aircraft noise and sleep disturbance. Legislation using a railway bonus will underestimate the noise impact by about 10 dB (A), Lden under the conditions comparable with those in the survey study. The choice of the noise calculation method may influence the threshold for guideline setting

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

Outdoor sound propagation: comparisons between calculations performed with atmos, a pe-based model, and wind tunnel experiments

Noise impact of road and railway infrastructures are more and more severely regulated by national laws: acceptable thresholds and reception levels are decreasing. It becomes necessary to predict more and more finely meteorology and its interactions with boundaries effects in current sound prediction models. ATMOS (Advanced Theoretical Models for Outdoor Sound propagation), a PE (Parabolic Equation) based calculation code dedicated to complex outdoor situations, has been developed to fulfil this need. In order to validate it, a measurement campaign has been performed in the wind tunnel of CSTB, Nantes (France). Such measurements present many advantages compared to outdoor experimentations. The main one is the possibility to control precisely many parameters such as temperature, wind speed profile and wind direction. Aerodynamic measurements as well as computational fluid dynamic simulations with FLUENT have also been undertaken in parallel to acoustical studies. Their results have been used to perform excess attenuation calculations with ATMOS. Comparisons between measurements and numerical simulations for realistic complex traffic noise configurations are presented here for a few cases (flat ground, impedance jump, noise barrier, embankment)

Epilepsy priorities in Europe: A report of the ILAE-IBE Epilepsy Advocacy Europe Task Force.

The European Forum on Epilepsy Research (ERF2013), which took place in Dublin, Ireland, on May 26-29, 2013, was designed to appraise epilepsy research priorities in Europe through consultation with clinical and basic scientists as well as representatives of lay organizations and health care providers. The ultimate goal was to provide a platform to improve the lives of persons with epilepsy by influencing the political agenda of the EU. The Forum highlighted the epidemiologic, medical, and social importance of epilepsy in Europe, and addressed three separate but closely related concepts. First, possibilities were explored as to how the stigma and social burden associated with epilepsy could be reduced through targeted initiatives at EU national and regional levels. Second, ways to ensure optimal standards of care throughout Europe were specifically discussed. Finally, a need for further funding in epilepsy research within the European Horizon 2020 funding programme was communicated to politicians and policymakers participating to the forum. Research topics discussed specifically included (1) epilepsy in the developing brain; (2) novel targets for innovative diagnostics and treatment of epilepsy; (3) what is required for prevention and cure of epilepsy; and (4) epilepsy and comorbidities, with a special focus on aging and mental health. This report provides a summary of recommendations that emerged at ERF2013 about how to (1) strengthen epilepsy research, (2) reduce the treatment gap, and (3) reduce the burden and stigma associated with epilepsy. Half of the 6 million European citizens with epilepsy feel stigmatized and experience social exclusion, stressing the need for funding trans-European awareness campaigns and monitoring their impact on stigma, in line with the global commitment of the European Commission and with the recommendations made in the 2011 Written Declaration on Epilepsy. Epilepsy care has high rates of misdiagnosis and considerable variability in organization and quality across European countries, translating into huge societal cost (0.2% GDP) and stressing the need for cost-effective programs of harmonization and optimization of epilepsy care throughout Europe. There is currently no cure or prevention for epilepsy, and 30% of affected persons are not controlled by current treatments, stressing the need for pursuing research efforts in the field within Horizon 2020. Priorities should include (1) development of innovative biomarkers and therapeutic targets and strategies, from gene and cell-based therapies to technologically advanced surgical treatment; (2) addressing issues raised by pediatric and aging populations, as well as by specific etiologies and comorbidities such as traumatic brain injury (TBI) and cognitive dysfunction, toward more personalized medicine and prevention; and (3) translational studies and clinical trials built upon well-established European consortia

Effect of unilateral temporal lobe resection on short-term memory for auditory object and sound location

To investigate auditory spatial and nonspatial short-term memory, a sound location discrimination task and an auditory object discrimination task were used in patients with medial temporal lobe resection. The results showed a double dissociation between the side of the medial temporal lobe lesion and the nature of the auditory discrimination deficits, suggesting that right and left temporal lobe structures are differently involved in auditory spatial and nonspatial short-term memory