Search

Your search keyword '"Canafoglia, L."' showing total 351 results
Start Over Author "Canafoglia, L."
351 results on '"Canafoglia, L."'

1. A real-world comparison among third-generation antiseizure medications: Results from the COMPARE study

Author

Roberti, R, Digennaro, G, Anzellotti, F, Arnaldi, D, Belcastro, V, Beretta, S, Boero, G, Bonanni, P, Canafoglia, L, D'Aniello, A, Dainese, F, Decaro, C, Digiacomo, R, Difrancesco, J, Dono, F, Falcicchio, G, Ferlazzo, E, Foschi, N, Franciotta, S, Gambardella, A, Giordano, A, Iannone, L, Labate, A, Laneve, A, Lattanzi, S, Leggio, U, Liguori, C, Maschio, M, Nilo, A, Operto, F, Pascarella, A, Pauletto, G, Renna, R, Strigaro, G, Russo, E, Roberti R., DiGennaro G., Anzellotti F., Arnaldi D., Belcastro V., Beretta S., Boero G., Bonanni P., Canafoglia L., D'Aniello A., Dainese F., DeCaro C., DiGiacomo R., DiFrancesco J. C., Dono F., Falcicchio G., Ferlazzo E., Foschi N., Franciotta S., Gambardella A., Giordano A., Iannone L. F., Labate A., LaNeve A., Lattanzi S., Leggio U., Liguori C., Maschio M., Nilo A., Operto F. F., Pascarella A., Pauletto G., Renna R., Strigaro G., Russo E., Roberti, R, Digennaro, G, Anzellotti, F, Arnaldi, D, Belcastro, V, Beretta, S, Boero, G, Bonanni, P, Canafoglia, L, D'Aniello, A, Dainese, F, Decaro, C, Digiacomo, R, Difrancesco, J, Dono, F, Falcicchio, G, Ferlazzo, E, Foschi, N, Franciotta, S, Gambardella, A, Giordano, A, Iannone, L, Labate, A, Laneve, A, Lattanzi, S, Leggio, U, Liguori, C, Maschio, M, Nilo, A, Operto, F, Pascarella, A, Pauletto, G, Renna, R, Strigaro, G, Russo, E, Roberti R., DiGennaro G., Anzellotti F., Arnaldi D., Belcastro V., Beretta S., Boero G., Bonanni P., Canafoglia L., D'Aniello A., Dainese F., DeCaro C., DiGiacomo R., DiFrancesco J. C., Dono F., Falcicchio G., Ferlazzo E., Foschi N., Franciotta S., Gambardella A., Giordano A., Iannone L. F., Labate A., LaNeve A., Lattanzi S., Leggio U., Liguori C., Maschio M., Nilo A., Operto F. F., Pascarella A., Pauletto G., Renna R., Strigaro G., and Russo E.

Abstract

Objective: There are few comparative data on the third-generation antiseizure medications (ASMs). We aimed to assess and compare the effectiveness of brivaracetam (BRV), eslicarbazepine acetate (ESL), lacosamide (LCM), and perampanel (PER) in people with epilepsy (PWE). Efficacy and tolerability were compared as secondary objectives. Methods: This multicenter, retrospective study collected data from 22 Italian neurology/epilepsy centers. All adult PWE who started add-on treatment with one of the studied ASMs between January 2018 and October 2021 were included. Retention rate was established as effectiveness measure and described using Kaplan–Meier curves and the best fitting survival model. The responder status and the occurrence of adverse events (AEs) were used to evaluate efficacy and safety, respectively. The odds of AEs and drug efficacy were estimated by two multilevel logistic models. Results: A total of 960 patients (52.92% females, median age = 43 years) met the inclusion criteria. They mainly suffered from structural epilepsy (52.29%) with monthly (46.2%) focal seizures (69.58%). Compared with LCM, all the studied ASMs had a higher dropout risk, statistically significant in the BRV levetiracetam (LEV)-naïve (hazard ratio [HR] = 1.97, 95% confidence interval [CI] = 1.17–3.29) and PER groups (HR = 1.64, 95% CI = 1.06–2.55). Women were at higher risk of discontinuing ESL (HR = 5.33, 95% CI = 1.71–16.61), as well as PER-treated patients with unknown epilepsy etiology versus those with structural etiology (HR = 1.74, 95% CI = 1.05–2.88). BRV with prior LEV therapy showed lower odds of efficacy (odds ratio [OR] =.08, 95% CI =.01–.48) versus LCM, whereas a higher efficacy was observed in women treated with BRV and LEV-naïve (OR = 10.32, 95% CI = 1.55–68.78) versus men. PER (OR = 6.93, 95% CI = 3.32–14.44) and BRV in LEV-naïve patients (OR = 6.80, 95% CI = 2.64–17.52) had a higher chance of AEs than LCM. Significance: Comparative evidence from real-world studie

Published
2024

4. GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Author

Stevelink, R, Campbell, C, Chen, S, Abou-Khalil, B, Adesoji, OM, Afawi, Z, Amadori, E, Anderson, A, Anderson, J, Andrade, DM, Annesi, G, Auce, P, Avbersek, A, Bahlo, M, Baker, MD, Balagura, G, Balestrini, S, Barba, C, Barboza, K, Bartolomei, F, Bast, T, Baum, L, Baumgartner, T, Baykan, B, Bebek, N, Becker, AJ, Becker, F, Bennett, CA, Berghuis, B, Berkovic, SF, Beydoun, A, Bianchini, C, Bisulli, F, Blatt, I, Bobbili, DR, Borggraefe, I, Bosselmann, C, Braatz, V, Bradfield, JP, Brockmann, K, Brody, LC, Buono, RJ, Busch, RM, Caglayan, H, Campbell, E, Canafoglia, L, Canavati, C, Cascino, GD, Castellotti, B, Catarino, CB, Cavalleri, GL, Cerrato, F, Chassoux, F, Cherny, SS, Cheung, C-L, Chinthapalli, K, Chou, I-J, Chung, S-K, Churchhouse, C, Clark, PO, Cole, AJ, Compston, A, Coppola, A, Cosico, M, Cossette, P, Craig, JJ, Cusick, C, Daly, MJ, Davis, LK, de Haan, G-J, Delanty, N, Depondt, C, Derambure, P, Devinsky, O, Di Vito, L, Dlugos, DJ, Doccini, V, Doherty, CP, El-Naggar, H, Elger, CE, Ellis, CA, Eriksson, JG, Faucon, A, Feng, Y-CA, Ferguson, L, Ferraro, TN, Ferri, L, Feucht, M, Fitzgerald, M, Fonferko-Shadrach, B, Fortunato, F, Franceschetti, S, Franke, A, French, JA, Freri, E, Gagliardi, M, Gambardella, A, Geller, EB, Giangregorio, T, Gjerstad, L, Glauser, T, Goldberg, E, Goldman, A, Granata, T, Greenberg, DA, Guerrini, R, Gupta, N, Haas, KF, Hakonarson, H, Hallmann, K, Hassanin, E, Hegde, M, Heinzen, EL, Helbig, I, Hengsbach, C, Heyne, HO, Hirose, S, Hirsch, E, Hjalgrim, H, Howrigan, DP, Hucks, D, Hung, P-C, Iacomino, M, Imbach, LL, Inoue, Y, Ishii, A, Jamnadas-Khoda, J, Jehi, L, Johnson, MR, Kalviainen, R, Kamatani, Y, Kanaan, M, Kanai, M, Kantanen, A-M, Kara, B, Kariuki, SM, Kasperaviciute, D, Trenite, DK-N, Kato, M, Kegele, J, Kesim, Y, Khoueiry-Zgheib, N, King, C, Kirsch, HE, Klein, KM, Kluger, G, Knake, S, Knowlton, RC, Koeleman, BPC, Korczyn, AD, Koupparis, A, Kousiappa, I, Krause, R, Krenn, M, Krestel, H, Krey, I, Kunz, WS, Kurki, MI, Kurlemann, G, Kuzniecky, R, Kwan, P, Labate, A, Lacey, A, Lal, D, Landoulsi, Z, Lau, Y-L, Lauxmann, S, Leech, SL, Lehesjoki, A-E, Lemke, JR, Lerche, H, Lesca, G, Leu, C, Lewin, N, Lewis-Smith, D, Li, GH-Y, Li, QS, Licchetta, L, Lin, K-L, Lindhout, D, Linnankivi, T, Lopes-Cendes, I, Lowenstein, DH, Lui, CHT, Madia, F, Magnusson, S, Marson, AG, May, P, McGraw, CM, Mei, D, Mills, JL, Minardi, R, Mirza, N, Moller, RS, Molloy, AM, Montomoli, M, Mostacci, B, Muccioli, L, Muhle, H, Mueller-Schlueter, K, Najm, IM, Nasreddine, W, Neale, BM, Neubauer, B, Newton, CRJC, Noethen, MM, Nothnagel, M, Nuernberg, P, O'Brien, TJ, Okada, Y, Olafsson, E, Oliver, KL, Ozkara, C, Palotie, A, Pangilinan, F, Papacostas, SS, Parrini, E, Pato, CN, Pato, MT, Pendziwiat, M, Petrovski, S, Pickrell, WO, Pinsky, R, Pippucci, T, Poduri, A, Pondrelli, F, Powell, RHW, Privitera, M, Rademacher, A, Radtke, R, Ragona, F, Rau, S, Rees, MI, Regan, BM, Reif, PS, Rhelms, S, Riva, A, Rosenow, F, Ryvlin, P, Saarela, A, Sadleir, LG, Sander, JW, Sander, T, Scala, M, Scattergood, T, Schachter, SC, Schankin, CJ, Scheffer, IE, Schmitz, B, Schoch, S, Schubert-Bast, S, Schulze-Bonhage, A, Scudieri, P, Sham, P, Sheidley, BR, Shih, JJ, Sills, GJ, Sisodiya, SM, Smith, MC, Smith, PE, Sonsma, ACM, Speed, D, Sperling, MR, Stefansson, H, Stefansson, K, Steinhoff, BJ, Stephani, U, Stewart, WC, Stipa, C, Striano, P, Stroink, H, Strzelczyk, A, Surges, R, Suzuki, T, Tan, KM, Taneja, RS, Tanteles, GA, Tauboll, E, Thio, LL, Thomas, GN, Thomas, RH, Timonen, O, Tinuper, P, Todaro, M, Topaloglu, P, Tozzi, R, Tsai, M-H, Tumiene, B, Turkdogan, D, Unnsteinsdottir, U, Utkus, A, Vaidiswaran, P, Valton, L, van Baalen, A, Vetro, A, Vining, EPG, Visscher, F, von Brauchitsch, S, von Wrede, R, Wagner, RG, Weber, YG, Weckhuysen, S, Weisenberg, J, Weller, M, Widdess-Walsh, P, Wolff, M, Wolking, S, Wu, D, Yamakawa, K, Yang, W, Yapici, Z, Yucesan, E, Zagaglia, S, Zahnert, F, Zara, F, Zhou, W, Zimprich, F, Zsurka, G, Ali, QZ, Stevelink, R, Campbell, C, Chen, S, Abou-Khalil, B, Adesoji, OM, Afawi, Z, Amadori, E, Anderson, A, Anderson, J, Andrade, DM, Annesi, G, Auce, P, Avbersek, A, Bahlo, M, Baker, MD, Balagura, G, Balestrini, S, Barba, C, Barboza, K, Bartolomei, F, Bast, T, Baum, L, Baumgartner, T, Baykan, B, Bebek, N, Becker, AJ, Becker, F, Bennett, CA, Berghuis, B, Berkovic, SF, Beydoun, A, Bianchini, C, Bisulli, F, Blatt, I, Bobbili, DR, Borggraefe, I, Bosselmann, C, Braatz, V, Bradfield, JP, Brockmann, K, Brody, LC, Buono, RJ, Busch, RM, Caglayan, H, Campbell, E, Canafoglia, L, Canavati, C, Cascino, GD, Castellotti, B, Catarino, CB, Cavalleri, GL, Cerrato, F, Chassoux, F, Cherny, SS, Cheung, C-L, Chinthapalli, K, Chou, I-J, Chung, S-K, Churchhouse, C, Clark, PO, Cole, AJ, Compston, A, Coppola, A, Cosico, M, Cossette, P, Craig, JJ, Cusick, C, Daly, MJ, Davis, LK, de Haan, G-J, Delanty, N, Depondt, C, Derambure, P, Devinsky, O, Di Vito, L, Dlugos, DJ, Doccini, V, Doherty, CP, El-Naggar, H, Elger, CE, Ellis, CA, Eriksson, JG, Faucon, A, Feng, Y-CA, Ferguson, L, Ferraro, TN, Ferri, L, Feucht, M, Fitzgerald, M, Fonferko-Shadrach, B, Fortunato, F, Franceschetti, S, Franke, A, French, JA, Freri, E, Gagliardi, M, Gambardella, A, Geller, EB, Giangregorio, T, Gjerstad, L, Glauser, T, Goldberg, E, Goldman, A, Granata, T, Greenberg, DA, Guerrini, R, Gupta, N, Haas, KF, Hakonarson, H, Hallmann, K, Hassanin, E, Hegde, M, Heinzen, EL, Helbig, I, Hengsbach, C, Heyne, HO, Hirose, S, Hirsch, E, Hjalgrim, H, Howrigan, DP, Hucks, D, Hung, P-C, Iacomino, M, Imbach, LL, Inoue, Y, Ishii, A, Jamnadas-Khoda, J, Jehi, L, Johnson, MR, Kalviainen, R, Kamatani, Y, Kanaan, M, Kanai, M, Kantanen, A-M, Kara, B, Kariuki, SM, Kasperaviciute, D, Trenite, DK-N, Kato, M, Kegele, J, Kesim, Y, Khoueiry-Zgheib, N, King, C, Kirsch, HE, Klein, KM, Kluger, G, Knake, S, Knowlton, RC, Koeleman, BPC, Korczyn, AD, Koupparis, A, Kousiappa, I, Krause, R, Krenn, M, Krestel, H, Krey, I, Kunz, WS, Kurki, MI, Kurlemann, G, Kuzniecky, R, Kwan, P, Labate, A, Lacey, A, Lal, D, Landoulsi, Z, Lau, Y-L, Lauxmann, S, Leech, SL, Lehesjoki, A-E, Lemke, JR, Lerche, H, Lesca, G, Leu, C, Lewin, N, Lewis-Smith, D, Li, GH-Y, Li, QS, Licchetta, L, Lin, K-L, Lindhout, D, Linnankivi, T, Lopes-Cendes, I, Lowenstein, DH, Lui, CHT, Madia, F, Magnusson, S, Marson, AG, May, P, McGraw, CM, Mei, D, Mills, JL, Minardi, R, Mirza, N, Moller, RS, Molloy, AM, Montomoli, M, Mostacci, B, Muccioli, L, Muhle, H, Mueller-Schlueter, K, Najm, IM, Nasreddine, W, Neale, BM, Neubauer, B, Newton, CRJC, Noethen, MM, Nothnagel, M, Nuernberg, P, O'Brien, TJ, Okada, Y, Olafsson, E, Oliver, KL, Ozkara, C, Palotie, A, Pangilinan, F, Papacostas, SS, Parrini, E, Pato, CN, Pato, MT, Pendziwiat, M, Petrovski, S, Pickrell, WO, Pinsky, R, Pippucci, T, Poduri, A, Pondrelli, F, Powell, RHW, Privitera, M, Rademacher, A, Radtke, R, Ragona, F, Rau, S, Rees, MI, Regan, BM, Reif, PS, Rhelms, S, Riva, A, Rosenow, F, Ryvlin, P, Saarela, A, Sadleir, LG, Sander, JW, Sander, T, Scala, M, Scattergood, T, Schachter, SC, Schankin, CJ, Scheffer, IE, Schmitz, B, Schoch, S, Schubert-Bast, S, Schulze-Bonhage, A, Scudieri, P, Sham, P, Sheidley, BR, Shih, JJ, Sills, GJ, Sisodiya, SM, Smith, MC, Smith, PE, Sonsma, ACM, Speed, D, Sperling, MR, Stefansson, H, Stefansson, K, Steinhoff, BJ, Stephani, U, Stewart, WC, Stipa, C, Striano, P, Stroink, H, Strzelczyk, A, Surges, R, Suzuki, T, Tan, KM, Taneja, RS, Tanteles, GA, Tauboll, E, Thio, LL, Thomas, GN, Thomas, RH, Timonen, O, Tinuper, P, Todaro, M, Topaloglu, P, Tozzi, R, Tsai, M-H, Tumiene, B, Turkdogan, D, Unnsteinsdottir, U, Utkus, A, Vaidiswaran, P, Valton, L, van Baalen, A, Vetro, A, Vining, EPG, Visscher, F, von Brauchitsch, S, von Wrede, R, Wagner, RG, Weber, YG, Weckhuysen, S, Weisenberg, J, Weller, M, Widdess-Walsh, P, Wolff, M, Wolking, S, Wu, D, Yamakawa, K, Yang, W, Yapici, Z, Yucesan, E, Zagaglia, S, Zahnert, F, Zara, F, Zhou, W, Zimprich, F, Zsurka, G, and Ali, QZ

Abstract

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment.

Published
2023

5. A novel KCNC1 gain-of-function variant causing developmental and epileptic encephalopathy: 'Precision medicine' approach with fluoxetine

Author

Ambrosino, P, Ragona, F, Mosca, I, Vannicola, C, Canafoglia, L, Solazzi, R, Rivolta, I, Freri, E, Granata, T, Messina, G, Castellotti, B, Gellera, C, Soldovieri, M, Difrancesco, J, Taglialatela, M, Ambrosino, Paolo, Ragona, Francesca, Mosca, Ilaria, Vannicola, Chiara, Canafoglia, Laura, Solazzi, Roberta, Rivolta, Ilaria, Freri, Elena, Granata, Tiziana, Messina, Giuliana, Castellotti, Barbara, Gellera, Cinzia, Soldovieri, Maria Virginia, DiFrancesco, Jacopo Cosimo, Taglialatela, Maurizio, Ambrosino, P, Ragona, F, Mosca, I, Vannicola, C, Canafoglia, L, Solazzi, R, Rivolta, I, Freri, E, Granata, T, Messina, G, Castellotti, B, Gellera, C, Soldovieri, M, Difrancesco, J, Taglialatela, M, Ambrosino, Paolo, Ragona, Francesca, Mosca, Ilaria, Vannicola, Chiara, Canafoglia, Laura, Solazzi, Roberta, Rivolta, Ilaria, Freri, Elena, Granata, Tiziana, Messina, Giuliana, Castellotti, Barbara, Gellera, Cinzia, Soldovieri, Maria Virginia, DiFrancesco, Jacopo Cosimo, and Taglialatela, Maurizio

Abstract

Variable phenotypes, including developmental encephalopathy with (DEE) or without seizures and myoclonic epilepsy and ataxia due to potassium channel mutation, are caused by pathogenetic variants in KCNC1, encoding for Kv3.1 channel subunits. In vitro, channels carrying most KCNC1 pathogenic variants display loss-of-function features. Here, we describe a child affected by DEE with fever-triggered seizures, caused by a novel de novo heterozygous missense KCNC1 variant (c.1273G>A; V425M). Patch-clamp recordings in transiently transfected CHO cells revealed that, compared to wild-type, Kv3.1 V425M currents (1) were larger, with membrane potentials between −40 and +40 mV; (2) displayed a hyperpolarizing shift in activation gating; (3) failed to inactivate; and (4) had slower activation and deactivation kinetics, consistent with a mixed functional pattern with prevalent gain-of-function effects. Exposure to the antidepressant drug fluoxetine inhibited currents expressed by both wild-type and mutant Kv3.1 channels. Treatment of the proband with fluoxetine led to a rapid and prolonged clinical amelioration, with the disappearance of seizures and an improvement in balance, gross motor skills, and oculomotor coordination. These results suggest that drug repurposing based on the specific genetic defect may provide an effective personalized treatment for KCNC1-related DEEs.

Published
2023

6. IRF2BPL: A new genotype for progressive myoclonus epilepsies

Author

Costa, C, Oliver, KL, Calvello, C, Cameron, JM, Imperatore, V, Tonelli, L, Colavito, D, Franceschetti, S, Canafoglia, L, Berkovic, SF, Prontera, P, Costa, C, Oliver, KL, Calvello, C, Cameron, JM, Imperatore, V, Tonelli, L, Colavito, D, Franceschetti, S, Canafoglia, L, Berkovic, SF, and Prontera, P

Abstract

The progressive myoclonus epilepsies (PMEs) are a heterogeneous group of neurodegenerative disorders, typically presenting in late childhood. An etiologic diagnosis is achieved in about 80% of patients with PME, and genome-wide molecular studies on remaining, well-selected, undiagnosed cases can further dissect the underlying genetic heterogeneity. Through whole-exome sequencing (WES), we identified pathogenic truncating variants in the IRF2BPL gene in two, unrelated patients presenting with PME. IRF2BPL belongs to the transcriptional regulators family and it is expressed in multiple human tissues, including the brain. Recently missense and nonsense mutations in IRF2BPL were found in patients presenting with developmental delay and epileptic encephalopathy, ataxia, and movement disorders, but none with clear PME. We identified 13 other patients in the literature with myoclonic seizures and IRF2BPL variants. There was no clear genotype-phenotype correlation. With the description of these cases, the IRF2BPL gene should be considered in the list of genes to be tested in the presence of PME, in addition to patients with neurodevelopmental or movement disorders.

Published
2023

7. A novel de novo HCN2 loss-of-function variant causing developmental and epileptic encephalopathy treated with a ketogenic diet

Author

Difrancesco, J, Ragona, F, Murano, C, Frosio, A, Melgari, D, Binda, A, Calamaio, S, Prevostini, R, Mauri, M, Canafoglia, L, Castellotti, B, Messina, G, Gellera, C, Previtali, R, Veggiotti, P, Milanesi, R, Barbuti, A, Solazzi, R, Freri, E, Granata, T, Rivolta, I, DiFrancesco, Jacopo C, Ragona, Francesca, Murano, Carmen, Frosio, Anthony, Melgari, Dario, Binda, Anna, Calamaio, Serena, Prevostini, Rachele, Mauri, Mario, Canafoglia, Laura, Castellotti, Barbara, Messina, Giuliana, Gellera, Cinzia, Previtali, Roberto, Veggiotti, Pierangelo, Milanesi, Raffaella, Barbuti, Andrea, Solazzi, Roberta, Freri, Elena, Granata, Tiziana, Rivolta, Ilaria, Difrancesco, J, Ragona, F, Murano, C, Frosio, A, Melgari, D, Binda, A, Calamaio, S, Prevostini, R, Mauri, M, Canafoglia, L, Castellotti, B, Messina, G, Gellera, C, Previtali, R, Veggiotti, P, Milanesi, R, Barbuti, A, Solazzi, R, Freri, E, Granata, T, Rivolta, I, DiFrancesco, Jacopo C, Ragona, Francesca, Murano, Carmen, Frosio, Anthony, Melgari, Dario, Binda, Anna, Calamaio, Serena, Prevostini, Rachele, Mauri, Mario, Canafoglia, Laura, Castellotti, Barbara, Messina, Giuliana, Gellera, Cinzia, Previtali, Roberto, Veggiotti, Pierangelo, Milanesi, Raffaella, Barbuti, Andrea, Solazzi, Roberta, Freri, Elena, Granata, Tiziana, and Rivolta, Ilaria

Abstract

Missense variants of hyperpolarization-activated, cyclic nucleotide-gated (HCN) ion channels cause variable phenotypes, ranging from mild generalized epilepsy to developmental and epileptic encephalopathy (DEE). Although variants of HCN1 are an established cause of DEE, those of HCN2 have been reported in generalized epilepsies. Here we describe the first case of DEE caused by the novel de novo heterozygous missense variant c.1379G>A (p.G460D) of HCN2. Functional characterization in transfected HEK293 cells and neonatal rat cortical neurons revealed that HCN2 p.G460D currents were strongly reduced compared to wild-type, consistent with a dominant negative loss-of-function effect. Immunofluorescence staining showed that mutant channels are retained within the cell and do not reach the membrane. Moreover, mutant HCN2 also affect HCN1 channels, by reducing the Ih current expressed by the HCN1-HCN2 heteromers. Due to the persistence of frequent seizures despite pharmacological polytherapy, the patient was treated with a ketogenic diet, with a significant and long-lasting reduction of episodes. In vitro experiments conducted in a ketogenic environment demonstrated that the clinical improvement observed with this dietary regimen was not mediated by a direct action on HCN2 activity. These results expand the clinical spectrum related to HCN2 channelopathies, further broadening our understanding of the pathogenesis of DEE.

Published
2023

8. Safety of vitamin K antagonist treatment for splanchnic vein thrombosis: a multicenter cohort study

Author

Riva, N., Ageno, W., Poli, D., Testa, S., Rupoli, S., Santoro, R., Lerede, T., Piana, A., Carpenedo, M., Nicolini, A., Ferrini, P.M., Tosetto, A., Paoletti, O., Rancan, E., Federici, I., Canafoglia, L., Maggioni, A., Falanga, A., Martini, G., Mangione, C., Contino, L., Bonfanti, C., Gresele, P., Pedrini, S., Morandini, R., Marigo, L., Nante, G., Sivera, P., Pasca, S., Malcangi, G., Ettorre, C.P., Cavallero, G.B., Falco, P., Ruocco, L., Paparo, C., Bucherini, E., Suriano, L., Crisantemo, R., Ria, L., Toma, A., Insana, A., Zanatta, N., Zammataro, N., Iannone, A.M., Oriana, V., Pezzo, M.P., Isu, G., and Molinatti, M.

Published
2015
Full Text
View/download PDF

9. Brivaracetam as add-on treatment in focal epilepsy: A real-world time-based analysis

Author

Lattanzi, S, De Maria, G, Rosati, E, Didato, G, Chiesa, V, Ranzato, F, Canafoglia, L, Cesnik, E, Anzellotti, F, Meletti, S, Pauletto, G, Nilo, A, Bartolini, E, Marino, D, Tartara, E, Luisi, C, Bonanni, P, Marrelli, A, Stokelj, D, Dainese, F, Foschi, N, Cagnetti, C, Gazzina, S, Contento, M, Biggi, M, Magliani, M, Di Giacomo, R, Pastori, C, Canevini, M, Zambrelli, E, Billo, G, Casazza, M, Fallica, E, Rosa, G, Dono, F, Speranza, R, Cioclu, C, Vaudano, A, Kiferle, L, Galli, R, Guadagni, M, Galimberti, C, Kassabian, B, Ferreri, F, Osanni, E, Ciuffini, R, Badioni, V, Beretta, S, Lattanzi S., De Maria G., Rosati E., Didato G., Chiesa V., Ranzato F., Canafoglia L., Cesnik E., Anzellotti F., Meletti S., Pauletto G., Nilo A., Bartolini E., Marino D., Tartara E., Luisi C., Bonanni P., Marrelli A., Stokelj D., Dainese F., Foschi N., Cagnetti C., Gazzina S., Contento M., Biggi M., Magliani M., Di Giacomo R., Pastori C., Canevini M. P., Zambrelli E., Billo G., Casazza M., Fallica E., Rosa G., Dono F., Speranza R., Cioclu C., Vaudano A. E., Kiferle L., Galli R., Guadagni M., Galimberti C. A., Kassabian B., Ferreri F., Osanni E., Ciuffini R., Badioni V., Beretta S., Lattanzi, S, De Maria, G, Rosati, E, Didato, G, Chiesa, V, Ranzato, F, Canafoglia, L, Cesnik, E, Anzellotti, F, Meletti, S, Pauletto, G, Nilo, A, Bartolini, E, Marino, D, Tartara, E, Luisi, C, Bonanni, P, Marrelli, A, Stokelj, D, Dainese, F, Foschi, N, Cagnetti, C, Gazzina, S, Contento, M, Biggi, M, Magliani, M, Di Giacomo, R, Pastori, C, Canevini, M, Zambrelli, E, Billo, G, Casazza, M, Fallica, E, Rosa, G, Dono, F, Speranza, R, Cioclu, C, Vaudano, A, Kiferle, L, Galli, R, Guadagni, M, Galimberti, C, Kassabian, B, Ferreri, F, Osanni, E, Ciuffini, R, Badioni, V, Beretta, S, Lattanzi S., De Maria G., Rosati E., Didato G., Chiesa V., Ranzato F., Canafoglia L., Cesnik E., Anzellotti F., Meletti S., Pauletto G., Nilo A., Bartolini E., Marino D., Tartara E., Luisi C., Bonanni P., Marrelli A., Stokelj D., Dainese F., Foschi N., Cagnetti C., Gazzina S., Contento M., Biggi M., Magliani M., Di Giacomo R., Pastori C., Canevini M. P., Zambrelli E., Billo G., Casazza M., Fallica E., Rosa G., Dono F., Speranza R., Cioclu C., Vaudano A. E., Kiferle L., Galli R., Guadagni M., Galimberti C. A., Kassabian B., Ferreri F., Osanni E., Ciuffini R., Badioni V., and Beretta S.

Abstract

The study assessed the clinical response to add-on brivaracetam (BRV) in real-world practice by means of time-to-baseline seizure count methodology. Patients with focal epilepsy who were prescribed add-on BRV were identified. Primary endpoint was the time-to-baseline seizure count defined as the number of days until each patient experienced the number of focal seizures that occurred in the 90 days before BRV initiation. Subgroup analysis was performed according to levetiracetam (LEV) status (naive vs prior use). Three-hundred eighty-seven patients were included. The overall median time-to-baseline seizure count was 150 (95% confidence interval [CI] = 130-175) days. The median time-to-baseline seizure count was 198 (lower limit of 95% CI = 168) days for LEV-naive patients, 126 (95% CI = 105-150) days for patients with prior LEV use and withdrawal due to insufficient efficacy, and 170 (95% CI = 128-291) days for patients who discontinued LEV due to adverse events (P =.002). The number of prior antiseizure medications (adjusted hazard ratio [adjHR] = 1.07, 95% CI = 1.02-1.13, P =.009) and baseline monthly seizure frequency (adjHR = 1.004, 95% CI = 1.001-1.008, P =.028) were independently associated with the primary endpoint. Add-on BRV improved seizure control in LEV-naive and LEV-prior patients. The time-to-baseline seizure count represents an informative endpoint alongside traditional study outcomes and designs.

Published
2021

10. Neuro-telehealth for fragile patients in a tertiary referral neurological institute during the COVID-19 pandemic in Milan, Lombardy

Author

Pareyson, D, Pantaleoni, C, Eleopra, R, De Filippis, G, Moroni, I, Freri, E, Zibordi, F, Bulgheroni, S, Pagliano, E, Sarti, D, Silvani, A, Grazzi, L, Tiraboschi, P, Didato, G, Anghileri, E, Bersano, A, Valentini, L, Piacentini, S, Muscio, C, Leonardi, M, Mariotti, C, Eoli, M, Nuzzo, S, Tagliavini, F, Confalonieri, P, De Giorgi, F, Antozzi, C, Ardissone, A, Bersano, E, Boncoraglio, G, Bonvegna, S, Botturi, A, Brambilla, L, Canafoglia, L, Caputi, L, Caroppo, P, Carriero, M, Casali, C, Casazza, M, Catania, A, Ciaccio, C, Cilia, R, Dallabella, E, D'Amico, D, Danti, F, D'Arrigo, S, Decurtis, M, Deleo, F, Devigili, G, Difede, G, Digiacomo, R, Elia, A, Esposito, S, Estienne, M, Fenu, S, Fichera, M, Finocchiaro, G, Frangiamore, R, Gatti, M, Gaviani, P, Giaccone, G, Giani, L, Giovagnoli, A, Andreasi, N, Granata, T, Granocchio, E, Lamperti, C, Lamperti, E, Leone, M, Masson, R, Nanetti, L, Nardocci, N, Pastori, C, Pisciotta, C, Cecchini, A, Ragona, F, Redaelli, V, Saletti, V, Salsano, E, Scelzo, E, Solazzi, R, Tozzo, A, Usai, S, Zorzi, G, Arnoldi, M, Foscan, M, Marchi, A, Pedrinelli, I, Zanin, R, Gazzola, S, Magazu, S, Scopelliti, M, Casalino, T, Desalvatore, M, Mazzanti, S, Taddei, M, Fedeli, A, Sattin, D, Galimberti, L, Zagari, R, Bombonato, M, Fonte, L, Floridia, S, Pareyson D., Pantaleoni C., Eleopra R., De Filippis G., Moroni I., Freri E., Zibordi F., Bulgheroni S., Pagliano E., Sarti D., Silvani A., Grazzi L., Tiraboschi P., Didato G., Anghileri E., Bersano A., Valentini L., Piacentini S., Muscio C., Leonardi M., Mariotti C., Eoli M., Nuzzo S., Tagliavini F., Confalonieri P., De Giorgi F., Antozzi C., Ardissone A., Bersano E., Boncoraglio G., Bonvegna S., Botturi A., Brambilla L., Canafoglia L., Caputi L., Caroppo P., Carriero M. R., Casali C., Casazza M., Catania A., Ciaccio C., Cilia R., DallaBella E., D'Amico D., Danti F. R., D'Arrigo S., DeCurtis M., Deleo F., Devigili G., DiFede G., DiGiacomo R., Elia A., Esposito S., Estienne M., Fenu S., Fichera M., Finocchiaro G., Frangiamore R., Gatti M., Gaviani P., Giaccone G., Giani L., Giovagnoli A. R., Andreasi N. G., Granata T., Granocchio E., Lamperti C., Lamperti E., Leone M., Masson R., Nanetti L., Nardocci N., Pastori C., Pisciotta C., Cecchini A. P., Ragona F., Redaelli V., Saletti V., Salsano E., Scelzo E., Solazzi R., Tozzo A., Usai S., Zorzi G., Arnoldi M. T., Foscan M., Marchi A., Pedrinelli I., Zanin R., Gazzola S., Magazu S., Scopelliti M. R., Casalino T., DeSalvatore M., Mazzanti S., Taddei M., Fedeli A., Sattin D., Galimberti L., Zagari R., Bombonato M., Fonte L., Floridia S., Pareyson, D, Pantaleoni, C, Eleopra, R, De Filippis, G, Moroni, I, Freri, E, Zibordi, F, Bulgheroni, S, Pagliano, E, Sarti, D, Silvani, A, Grazzi, L, Tiraboschi, P, Didato, G, Anghileri, E, Bersano, A, Valentini, L, Piacentini, S, Muscio, C, Leonardi, M, Mariotti, C, Eoli, M, Nuzzo, S, Tagliavini, F, Confalonieri, P, De Giorgi, F, Antozzi, C, Ardissone, A, Bersano, E, Boncoraglio, G, Bonvegna, S, Botturi, A, Brambilla, L, Canafoglia, L, Caputi, L, Caroppo, P, Carriero, M, Casali, C, Casazza, M, Catania, A, Ciaccio, C, Cilia, R, Dallabella, E, D'Amico, D, Danti, F, D'Arrigo, S, Decurtis, M, Deleo, F, Devigili, G, Difede, G, Digiacomo, R, Elia, A, Esposito, S, Estienne, M, Fenu, S, Fichera, M, Finocchiaro, G, Frangiamore, R, Gatti, M, Gaviani, P, Giaccone, G, Giani, L, Giovagnoli, A, Andreasi, N, Granata, T, Granocchio, E, Lamperti, C, Lamperti, E, Leone, M, Masson, R, Nanetti, L, Nardocci, N, Pastori, C, Pisciotta, C, Cecchini, A, Ragona, F, Redaelli, V, Saletti, V, Salsano, E, Scelzo, E, Solazzi, R, Tozzo, A, Usai, S, Zorzi, G, Arnoldi, M, Foscan, M, Marchi, A, Pedrinelli, I, Zanin, R, Gazzola, S, Magazu, S, Scopelliti, M, Casalino, T, Desalvatore, M, Mazzanti, S, Taddei, M, Fedeli, A, Sattin, D, Galimberti, L, Zagari, R, Bombonato, M, Fonte, L, Floridia, S, Pareyson D., Pantaleoni C., Eleopra R., De Filippis G., Moroni I., Freri E., Zibordi F., Bulgheroni S., Pagliano E., Sarti D., Silvani A., Grazzi L., Tiraboschi P., Didato G., Anghileri E., Bersano A., Valentini L., Piacentini S., Muscio C., Leonardi M., Mariotti C., Eoli M., Nuzzo S., Tagliavini F., Confalonieri P., De Giorgi F., Antozzi C., Ardissone A., Bersano E., Boncoraglio G., Bonvegna S., Botturi A., Brambilla L., Canafoglia L., Caputi L., Caroppo P., Carriero M. R., Casali C., Casazza M., Catania A., Ciaccio C., Cilia R., DallaBella E., D'Amico D., Danti F. R., D'Arrigo S., DeCurtis M., Deleo F., Devigili G., DiFede G., DiGiacomo R., Elia A., Esposito S., Estienne M., Fenu S., Fichera M., Finocchiaro G., Frangiamore R., Gatti M., Gaviani P., Giaccone G., Giani L., Giovagnoli A. R., Andreasi N. G., Granata T., Granocchio E., Lamperti C., Lamperti E., Leone M., Masson R., Nanetti L., Nardocci N., Pastori C., Pisciotta C., Cecchini A. P., Ragona F., Redaelli V., Saletti V., Salsano E., Scelzo E., Solazzi R., Tozzo A., Usai S., Zorzi G., Arnoldi M. T., Foscan M., Marchi A., Pedrinelli I., Zanin R., Gazzola S., Magazu S., Scopelliti M. R., Casalino T., DeSalvatore M., Mazzanti S., Taddei M., Fedeli A., Sattin D., Galimberti L., Zagari R., Bombonato M., Fonte L., and Floridia S.

Abstract

Background: Lombardy was severely hit by the COVID-19 pandemic since February 2020 and the Health System underwent rapid reorganization. Outpatient clinics were stopped for non-urgent patients: it became a priority to manage hundreds of fragile neurological patients who suddenly had less reference points. In Italy, before the pandemic, Televisits were neither recognized nor priced. Methods: At the Fondazione IRCCS Istituto Neurologico C. Besta, we reorganized outpatient clinics to deliver Neuro-telemedicine services, including Televisits and Teleneurorehabilitation, since March 2020. A dedicated Working Group prepared the procedure, tested the system, and designed satisfaction questionnaires for adults and children. Results: After a pilot phase, we prepared a procedure for Telemedicine outpatient clinics which was approved by hospital directions. It included prescription, booking, consenting, privacy and data protection, secure connection with patients (Teams Microsoft 365), electronic report preparation and delivery, reporting, and accountability of the services. During the March–September 2020 period, we delivered 3167 Telemedicine services, including 1618 Televisits, to 1694 patients (972 adults, 722 children) with a wide range of chronic neurological disorders. We successfully administered different clinical assessment and scales. Satisfaction among patients and caregivers was very high. Conclusions: During the dramatic emergency, we were able to take care of more than 1600 patients by organizing Neuro-telehealth in a few weeks, lessening the impact of the pandemic on fragile patients with chronic neurological disorders; this strategy is now stably embedded in our care pathways. In Italy, Telehealth is at present recognized and priced and is becoming a stable pillar of the health system.

Published
2021

13. Brivaracetam as Early Add-On Treatment in Patients with Focal Seizures: A Retrospective, Multicenter, RealWorld Study

Author

Lattanzi, S., Canafoglia, L., Canevini, M. P., Casciato, S., Cerulli Irelli, E., Chiesa, V., Dainese, F., De Maria, G., Didato, G., Di Gennaro, G., Falcicchio, G., Fanella, M., Ferlazzo, E., Gangitano, M., La Neve, A., Mecarelli, O., Montalenti, E., Morano, A., Piazza, F., Pizzanelli, C., Pulitano, P., Ranzato, F., Rosati, E., Tassi, L., Di Bonaventura, C., Alicino, A., Ascoli, M., Assenza, G., Avorio, F., Badioni, V., Banfi, P., Bartolini, E., Basili, L. M., Belcastro, V., Beretta, S., Berto, I., Biggi, M., Billo, G., Boero, G., Bonanni, P., Bongorno, J., Brigo, F., Caggia, E., Cagnetti, C., Calvello, C., Cesnik, E., Chianale, G., Ciampanelli, D., Ciuffini, R., Cocito, D., Colella, D., Contento, M., Costa, C., Cumbo, E., D'Aniello, A., Deleo, F., Difrancesco, J. C., Di Giacomo, R., Di Liberto, A., Domina, E., Dono, F., Durante, V., Elia, M., Estraneo, A., Evangelista, G., Faedda, M. T., Failli, Y., Fallica, E., Fattouch, J., Ferrari, A., Ferreri, F., Fisco, G., Fonti, D., Fortunato, F., Foschi, N., Francavilla, T., Galli, R., Gazzina, S., Giallonardo, A. T., Giorgi, F. S., Giuliano, L., Habetswallner, F., Izzi, F., Kassabian, B., Labate, A., Luisi, C., Magliani, M., Maira, G., Mari, L., Marino, D., Mascia, A., Mazzeo, A., Meletti, S., Milano, C., Nilo, A., Orlando, B., Paladin, F., Pascarella, M. G., Pastori, C., Pauletto, G., Peretti, A., Perri, G., Pezzella, M., Piccioli, M., Pignatta, P., Pilolli, N., Pisani, F., Pisani, L. R., Placidi, F., Pollicino, P., Porcella, V., Pradella, S., Puligheddu, M., Quadri, S., Quarato, P. P., Quintas, R., Renna, R., Rizzo, G. R., Rum, A., Salamone, E. M., Savastano, E., Sessa, M., Stokelj, D., Tartara, E., Tombini, M., Tumminelli, G., Vaudano, A. E., Ventura, M., Vigano, I., Viglietta, E., Vignoli, A., Villani, F., Zambrelli, E., Zummo, L., Lattanzi, Simona, Canafoglia, Laura, Canevini, Maria Paola, Casciato, Sara, Cerulli Irelli, Emanuele, Chiesa, Valentina, Dainese, Filippo, De Maria, Giovanni, Didato, Giuseppe, Di Gennaro, Giancarlo, Falcicchio, Giovanni, Fanella, Martina, Ferlazzo, Edoardo, Gangitano, Massimo, La Neve, Angela, Mecarelli, Oriano, Montalenti, Elisa, Morano, Alessandra, Piazza, Federico, Pizzanelli, Chiara, Pulitano, Patrizia, Ranzato, Federica, Rosati, Eleonora, Tassi, Laura, and Di Bonaventura, Carlo

Subjects
Antiseizure medication, Focal seizures, Brivaracetam, Epilepsy, Neurology, Settore MED/26 - Neurologia, Neurology (clinical), Settore MED/26, Settore MED/39 - Neuropsichiatria Infantile
Abstract

Introduction: In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Most real-world research on BRV has focused on refractory epilepsy. The aim of this analysis was to assess the 12-month effectiveness and tolerability of adjunctive BRV when used as early or late adjunctive treatment in patients included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). Methods: BRIVAFIRST was a 12-month retrospective, multicenter study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of sustained seizure response, sustained seizure freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs. Data were compared for patients treated with add-on BRV after 1-2 (early add-on) and ≥ 3 (late add-on) prior antiseizure medications. Results: A total of 1029 patients with focal epilepsy were included in the study, of whom 176 (17.1%) received BRV as early add-on treatment. The median daily dose of BRV at 12months was 125 (100-200) mg in the early add-on group and 200 (100-200) in the late add-on group (p

Published
2022

14. Neuro-telehealth for fragile patients in a tertiary referral neurological institute during the COVID-19 pandemic in Milan, Lombardy

Author

Pareyson D., Pantaleoni C., Eleopra R., De Filippis G., Moroni I., Freri E., Zibordi F., Bulgheroni S., Pagliano E., Sarti D., Silvani A., Grazzi L., Tiraboschi P., Didato G., Anghileri E., Bersano A., Valentini L., Piacentini S., Muscio C., Leonardi M., Mariotti C., Eoli M., Nuzzo S., Tagliavini F., Confalonieri P., De Giorgi F., Antozzi C., Ardissone A., Bersano E., Boncoraglio G., Bonvegna S., Botturi A., Brambilla L., Canafoglia L., Caputi L., Caroppo P., Carriero M. R., Casali C., Casazza M., Catania A., Ciaccio C., Cilia R., DallaBella E., D'Amico D., Danti F. R., D'Arrigo S., DeCurtis M., Deleo F., Devigili G., DiFede G., DiGiacomo R., Elia A., Esposito S., Estienne M., Fenu S., Fichera M., Finocchiaro G., Frangiamore R., Gatti M., Gaviani P., Giaccone G., Giani L., Giovagnoli A. R., Andreasi N. G., Granata T., Granocchio E., Lamperti C., Lamperti E., Leone M., Masson R., Nanetti L., Nardocci N., Pastori C., Pisciotta C., Cecchini A. P., Ragona F., Redaelli V., Saletti V., Salsano E., Scelzo E., Solazzi R., Tozzo A., Usai S., Zorzi G., Arnoldi M. T., Foscan M., Marchi A., Pedrinelli I., Zanin R., Gazzola S., Magazu S., Scopelliti M. R., Casalino T., DeSalvatore M., Mazzanti S., Taddei M., Fedeli A., Sattin D., Galimberti L., Zagari R., Bombonato M., Fonte L., Floridia S., Pareyson, D, Pantaleoni, C, Eleopra, R, De Filippis, G, Moroni, I, Freri, E, Zibordi, F, Bulgheroni, S, Pagliano, E, Sarti, D, Silvani, A, Grazzi, L, Tiraboschi, P, Didato, G, Anghileri, E, Bersano, A, Valentini, L, Piacentini, S, Muscio, C, Leonardi, M, Mariotti, C, Eoli, M, Nuzzo, S, Tagliavini, F, Confalonieri, P, De Giorgi, F, Antozzi, C, Ardissone, A, Bersano, E, Boncoraglio, G, Bonvegna, S, Botturi, A, Brambilla, L, Canafoglia, L, Caputi, L, Caroppo, P, Carriero, M, Casali, C, Casazza, M, Catania, A, Ciaccio, C, Cilia, R, Dallabella, E, D'Amico, D, Danti, F, D'Arrigo, S, Decurtis, M, Deleo, F, Devigili, G, Difede, G, Digiacomo, R, Elia, A, Esposito, S, Estienne, M, Fenu, S, Fichera, M, Finocchiaro, G, Frangiamore, R, Gatti, M, Gaviani, P, Giaccone, G, Giani, L, Giovagnoli, A, Andreasi, N, Granata, T, Granocchio, E, Lamperti, C, Lamperti, E, Leone, M, Masson, R, Nanetti, L, Nardocci, N, Pastori, C, Pisciotta, C, Cecchini, A, Ragona, F, Redaelli, V, Saletti, V, Salsano, E, Scelzo, E, Solazzi, R, Tozzo, A, Usai, S, Zorzi, G, Arnoldi, M, Foscan, M, Marchi, A, Pedrinelli, I, Zanin, R, Gazzola, S, Magazu, S, Scopelliti, M, Casalino, T, Desalvatore, M, Mazzanti, S, Taddei, M, Fedeli, A, Sattin, D, Galimberti, L, Zagari, R, Bombonato, M, Fonte, L, and Floridia, S

Subjects
Adult, medicine.medical_specialty, Telemedicine, Neurology, Referral, Dermatology, Telehealth, 03 medical and health sciences, 0302 clinical medicine, Pandemic, medicine, Humans, Outpatient clinic, 030212 general & internal medicine, Medical prescription, Child, Pandemics, Referral and Consultation, SARS-CoV-2, business.industry, Teleneurorehabilitation, COVID-19, General Medicine, medicine.disease, Televisit, Psychiatry and Mental health, Italy, Neuro-telehealth, Neurology (clinical), Neurosurgery, Medical emergency, business, 030217 neurology & neurosurgery
Abstract

Background: Lombardy was severely hit by the COVID-19 pandemic since February 2020 and the Health System underwent rapid reorganization. Outpatient clinics were stopped for non-urgent patients: it became a priority to manage hundreds of fragile neurological patients who suddenly had less reference points. In Italy, before the pandemic, Televisits were neither recognized nor priced. Methods: At the Fondazione IRCCS Istituto Neurologico C. Besta, we reorganized outpatient clinics to deliver Neuro-telemedicine services, including Televisits and Teleneurorehabilitation, since March 2020. A dedicated Working Group prepared the procedure, tested the system, and designed satisfaction questionnaires for adults and children. Results: After a pilot phase, we prepared a procedure for Telemedicine outpatient clinics which was approved by hospital directions. It included prescription, booking, consenting, privacy and data protection, secure connection with patients (Teams Microsoft 365), electronic report preparation and delivery, reporting, and accountability of the services. During the March–September 2020 period, we delivered 3167 Telemedicine services, including 1618 Televisits, to 1694 patients (972 adults, 722 children) with a wide range of chronic neurological disorders. We successfully administered different clinical assessment and scales. Satisfaction among patients and caregivers was very high. Conclusions: During the dramatic emergency, we were able to take care of more than 1600 patients by organizing Neuro-telehealth in a few weeks, lessening the impact of the pandemic on fragile patients with chronic neurological disorders; this strategy is now stably embedded in our care pathways. In Italy, Telehealth is at present recognized and priced and is becoming a stable pillar of the health system.

Published
2021

15. Adjunctive Brivaracetam in Focal Epilepsy: Real-World Evidence from the BRIVAracetam add-on First Italian netwoRk STudy (BRIVAFIRST)

Author

Lattanzi, S., Canafoglia, L., Canevini, M. P., Casciato, S., Chiesa, V., Dainese, F., De Maria, G., Didato, G., Falcicchio, G., Fanella, M., Ferlazzo, E., Fisco, G., Gangitano, M., Giallonardo, A. T., Giorgi, F. S., La Neve, A., Mecarelli, O., Montalenti, E., Piazza, F., Pulitano, P., Quarato, P. P., Ranzato, F., Rosati, E., Tassi, L., Di Bonaventura, C., Alicino, A., Ascoli, M., Assenza, G., Avorio, F., Badioni, V., Banfi, P., Bartolini, E., Basili, L. M., Belcastro, V., Beretta, S., Berto, I., Biggi, M., Billo, G., Boero, G., Bonanni, P., Bongorno, J., Brigo, F., Caggia, E., Cagnetti, C., Calvello, C., Irelli, E. C., Cesnik, E., Chianale, G., Ciampanelli, D., Ciuffini, R., Cocito, D., Colella, D., Contento, M., Costa, C., Cumbo, E., D'Aniello, A., Deleo, F., Difrancesco, J. C., Di Gennaro, G., Di Giacomo, R., Di Liberto, A., Domina, E., Donato, F., Dono, F., Durante, V., Elia, M., Estraneo, A., Evangelista, G., Faedda, M. T., Failli, Y., Fallica, E., Fattouch, J., Ferrari, A., Ferreri, F., Fonti, D., Fortunato, F., Foschi, N., Francavilla, T., Galli, R., Gazzina, S., Giuliano, L., Habetswallner, F., Izzi, F., Kassabian, B., Labate, A., Luisi, C., Magliani, M., Maira, G., Mari, L., Marino, D., Mascia, A., Mazzeo, A., Meletti, S., Morano, A., Nilo, A., Orlando, B., Paladin, F., Pascarella, M. G., Pastori, C., Pauletto, G., Peretti, A., Perri, G., Pezzella, M., Piccioli, M., Pignatta, P., Pilolli, N., Pisani, F., Pisani, L. R., Placidi, F., Pollicino, P., Porcella, V., Pradella, S., Puligheddu, M., Quadri, S., Quintas, R., Renna, R., Rossi, J., Rum, A., Salamone, E. M., Savastano, E., Sessa, M., Stokelj, D., Tartara, E., Tombini, M., Tumminelli, G., Ventura, M., Vigano, I., Viglietta, E., Vignoli, A., Villani, F., Zambrelli, E., Zummo, L., Lattanzi S., Canafoglia L., Canevini M.P., Casciato S., Chiesa V., Dainese F., De Maria G., Didato G., Falcicchio G., Fanella M., Ferlazzo E., Fisco G., Gangitano M., Giallonardo A.T., Giorgi F.S., La Neve A., Mecarelli O., Montalenti E., Piazza F., Pulitano P., Quarato P.P., Ranzato F., Rosati E., Tassi L., and Di Bonaventura C.

Subjects
medicine.medical_specialty, business.industry, Context (language use), Brivaracetam, medicine.disease, Discontinuation, law.invention, Psychiatry and Mental health, Epilepsy, Randomized controlled trial, Tolerability, focal epilepsy, add-on therapy, seizure, law, Concomitant, Internal medicine, Medicine, Pharmacology (medical), Neurology (clinical), Levetiracetam, Original Research Article, business, medicine.drug
Abstract

Background: In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. Objective: This multicentre study assessed the effectiveness and tolerability of adjunctive BRV in a large population of patients with focal epilepsy in the context of real-world clinical practice. Methods: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a retrospective, multicentre study including adult patients prescribed adjunctive BRV. Patients with focal epilepsy and 12-month follow-up were considered. Main outcomes included the rates of seizure‐freedom, seizure response (≥50% reduction in baseline seizure frequency), and treatment discontinuation. The incidence of adverse events (AEs) was also considered. Analyses by levetiracetam (LEV) status and concomitant use of strong enzyme-inducing antiseizure medications (EiASMs) and sodium channel blockers (SCBs) were performed. Results: A total of 1029 patients with a median age of 45years (33–56) was included. At 12 months, 169 (16.4%) patients were seizure-free and 383 (37.2%) were seizure responders. The rate of seizure freedom was 22.3% in LEV-naive patients, 7.1% in patients with prior LEV use and discontinuation due to insufficient efficacy, and 31.2% in patients with prior LEV use and discontinuation due to AEs (p&nbsp

Published
2021

16. Progressive epileptic encephalopathy associated with a novel HCN2 mutation

Author

Binda, A, Murano, C, DI FRANCESCO, J, Castellotti, B, Milanesi, R, Ragona, F, Freri, E, Canafoglia, L, Franceschetti, S, Solazzi, R, Granata, T, Gellera, C, Rivolta, I, Binda A, MURANO, CARMEN, Di Francesco JC, Castellotti B, Milanesi R, Ragona F, Freri E, Canafoglia L, Franceschetti S, Solazzi R, Granata T, Gellera C, Rivolta I, Binda, A, Murano, C, DI FRANCESCO, J, Castellotti, B, Milanesi, R, Ragona, F, Freri, E, Canafoglia, L, Franceschetti, S, Solazzi, R, Granata, T, Gellera, C, Rivolta, I, Binda A, MURANO, CARMEN, Di Francesco JC, Castellotti B, Milanesi R, Ragona F, Freri E, Canafoglia L, Franceschetti S, Solazzi R, Granata T, Gellera C, and Rivolta I

Abstract

So far mutations in HCN2 gene, encoding for the hyperpolarization-activated cyclic nucleotide-gated channel 2, have been related to mild epileptic clinical phenotypes. In this study, a novel HCN2 mutation was found in a proband, now aged 7 years old, with a congenital encephalopathy characterized by drug resistant epilepsy, severe developmental delay, ataxia, dystonia and cerebral visual impairment. A convulsive status epilepticus at 5 months of age marked the onset of epilepsy. The HCN2 mutation affects an aminoacid located in the S6 transmembrane helix (p.Gly460Asp) and is carried in heterozygosis. To describe the functional consequences of the mutant channel, whole-cell patch-clamp experiments were performed in HEK293 cells expressing HCN2 wild type (WT) or p.Gly460Asp channel. A coexpression of the same amount of plasmid encoding for the wt or the mutant form of the channel mimed the heterozygous condition. A complete abolishment of the current was observed considering the mutant compared to the WT channel (-9.9±1.2 pA/pF, n=20 vs -31.2±8.4 pA/pF, n=44 respectively; p<0.05) and the heterozygous condition led to a significant reduction of the current density (-20.1±5.1 pA/pF n=35; p<0.05). WT and heterozygotic channels shared overlapping activation curves (V1/2 and k -92.9±0.3 mV and 5.6±0.3, n=29 vs -91.6±0.2 mV and 5.6±0.2, n=16 respectively) and no significant differences were present in their kinetics of both activation and deactivation. In conclusion, this is the first study linking HCN2 to progressive epileptic encephalopathy. The Gly460Asp mutation seems to act as a loss-of-function that could potentially affect the control of neuronal excitability and therefore explain the proband pathological condition.

Published
2019

17. Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3

Author

Florian R. T., Kraft F., Leitao E., Kaya S., Klebe S., Magnin E., van Rootselaar A. -F., Buratti J., Kuhnel T., Schroder C., Giesselmann S., Tschernoster N., Altmueller J., Lamiral A., Keren B., Nava C., Bouteiller D., Forlani S., Jornea L., Kubica R., Ye T., Plassard D., Jost B., Meyer V., Deleuze J. -F., Delpu Y., Avarello M. D. M., Vijfhuizen L. S., Rudolf G., Hirsch E., Kroes T., Reif P. S., Rosenow F., Ganos C., Vidailhet M., Thivard L., Mathieu A., Bourgeron T., Kurth I., Rafehi H., Steenpass L., Horsthemke B., Berkovic S. F., Bisulli F., Brancati F., Canafoglia L., Casari G., Guerrini R., Ishiura H., Licchetta L., Mei D., Pippucci T., Sadleir L., Scheffer I. E., Striano P., Tinuper P., Tsuji S., Zara F., LeGuern E., Klein K. M., Labauge P., Bennett M. F., Bahlo M., Gecz J., Corbett M. A., Tijssen M. A. J., van den Maagdenberg A. M. J. M., Depienne C., Florian, R. T., Kraft, F., Leitao, E., Kaya, S., Klebe, S., Magnin, E., van Rootselaar, A. -F., Buratti, J., Kuhnel, T., Schroder, C., Giesselmann, S., Tschernoster, N., Altmueller, J., Lamiral, A., Keren, B., Nava, C., Bouteiller, D., Forlani, S., Jornea, L., Kubica, R., Ye, T., Plassard, D., Jost, B., Meyer, V., Deleuze, J. -F., Delpu, Y., Avarello, M. D. M., Vijfhuizen, L. S., Rudolf, G., Hirsch, E., Kroes, T., Reif, P. S., Rosenow, F., Ganos, C., Vidailhet, M., Thivard, L., Mathieu, A., Bourgeron, T., Kurth, I., Rafehi, H., Steenpass, L., Horsthemke, B., Berkovic, S. F., Bisulli, F., Brancati, F., Canafoglia, L., Casari, G., Guerrini, R., Ishiura, H., Licchetta, L., Mei, D., Pippucci, T., Sadleir, L., Scheffer, I. E., Striano, P., Tinuper, P., Tsuji, S., Zara, F., Leguern, E., Klein, K. M., Labauge, P., Bennett, M. F., Bahlo, M., Gecz, J., Corbett, M. A., Tijssen, M. A. J., van den Maagdenberg, A. M. J. M., Depienne, C., Institute of Human Genetics - Institut für Humangenetik [Essen], Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen)-Universitat Duisberg-Essen, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Amsterdam Neuroscience [Pays-Bas], Vrije Universiteit Amsterdam [Amsterdam] (VU)-University of Amsterdam [Amsterdam] (UvA)-VU University Medical Center [Amsterdam], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre for Molecular Medicine Cologne [Cologne] (CMMC), University Hospital of Cologne [Cologne], Cologne Center for Genomics [Cologne] (CCG), University of Cologne, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), genomic vision, Leiden University Medical Center (LUMC), Universiteit Leiden, Centre de référence des épilepsies rares [CHRU Strasbourg] (CRéER), Centre Hospitalier Régional Universitaire de Strasbourg (CHRU de Strasbourg), Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, School of Biological Sciences [Adelaïde], University of Adelaide, Goethe-University Frankfurt am Main, Philipps Universität Marburg = Philipps University of Marburg, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), The Walter and Eliza Hall Institute of Medical Research (WEHI), University of Melbourne, Epilepsy Research Centre, University of Calgary, Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), South Australian Health and Medical Research Institute [ Adelaide] (SAHMRI), University Medical Center Groningen [Groningen] (UMCG), This study has been financially supported by three different grants from the Fondation Maladies rares to C.D. (2009, 2010, 2016), Assistance Publique des Hôpitaux de Paris (APHP), INSERM, the 'Investissements d’Avenir' programme ANR-10-IAIHU-06 (IHU-A-ICM), University Duisburg-Essen and University Hospital Essen. M.B. was supported by an Australian National Health and Medical Research Council (NHMRC) Program Grant (GNT1054618) and an NHMRC Senior Research Fellowship (GNT1102971). This work was also supported by the Victorian Government’s Operational Infrastructure Support Program and the NHMRC Independent Research Institute Infrastructure Support Scheme (IRIISS). Laura Canafoglia: Member of the European Reference Network on Rare and Complex epilepsies, ERN EpiCARE., We thank the families for their participation in this study, Agnès Rastetter (ICM, Paris, France) for RNA extraction, and Emmanuelle Apartis (Hôpital Saint-Antoine, Paris, France) for electrophysiological assessment of Family 1. DNA extraction and cell culture of lymphoblasts have been performed at the DNA and cell bank of ICM (Paris, France). RNA-seq has been performed on the GenomEast platform of IGBMC, Illkirch, France. WGS has been performed by the Centre National de Recherche en Génomique Humaine (CNRGH) Institut de Biologie François Jacob, Evry, France. We thank Jean-Louis Mandel and Nicolas Charlet-Berguerand (IGBMC, Strasbourg, France), Cécile Cazeneuve (Hôpital Pitié-Salpêtrière, Paris, France), Charles Marcaillou (Integragen, Evry, France) and Isabel Silveira (Porto, Portugal) for valuable discussions., FAME consortium : Berkovic SF, Bisulli F, Brancati F, Canafoglia L, Casari G, Guerrini R, Ishiura H, Licchetta L, Mei D, Pippucci T, Sadleir L, Scheffer IE, Striano P, Tinuper P, Tsuji S, Zara F., Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre National de Recherche en Génomique Humaine (CNRGH), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), RWTH Aachen University, Universität Duisburg-Essen [Essen], Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Philipps University of Marburg, Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Université de Paris (UP), Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Rahel T. Florian, Florian Kraft, Elsa Leitão, Sabine Kaya, Stephan Klebe, Eloi Magnin, Anne-Fleur van Rootselaar, Julien Buratti, Theresa Kühnel, Christopher Schröder, Sebastian Giesselmann, Nikolai Tschernoster, Janine Altmueller, Anaide Lamiral, Boris Keren, Caroline Nava, Delphine Bouteiller, Sylvie Forlani, Ludmila Jornea, Regina Kubica, Tao Ye, Damien Plassard, Bernard Jost, Vincent Meyer, Jean-François Deleuze, Yannick Delpu, Mario D.M. Avarello, Lisanne S. Vijfhuizen, Gabrielle Rudolf, Edouard Hirsch, Thessa Kroes, Philipp S. Reif, Felix Rosenow, Christos Ganos, Marie Vidailhet, Lionel Thivard, Alexandre Mathieu, Thomas Bourgeron, Ingo Kurth, Haloom Rafehi, Laura Steenpass, Bernhard Horsthemke, FAME consortium, Eric LeGuern, Karl Martin Klein, Pierre Labauge, Mark F. Bennett, Melanie Bahlo, Jozef Gecz, Mark A. Corbett, Marina A.J. Tijssen, Arn M.J.M. van den Maagdenberg, Christel Depienne, Francesca Bisulli, Laura Licchetta, Paolo Tinuper, MATHIEU, Alexandre, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)

Subjects
Male, MESH: Introns, [SDV]Life Sciences [q-bio], Medizin, MESH: DNA Repeat Expansion, Epilepsies, Myoclonic, [SDV.GEN] Life Sciences [q-bio]/Genetics, MARCH6, expansion, MESH: Ubiquitin-Protein Ligases/genetics, MESH: Aged, MESH: Middle Aged, DNA Repeat Expansion, Neurodegenerative diseases, MESH: Epilepsies, Myoclonic, Chromosome Mapping, Middle Aged, MESH: Epilepsies, Myoclonic/genetics, Pedigree, MESH: Young Adult, Female, ddc:500, MESH: Membrane Proteins, Technology Platforms, Genomic instability, Adult, Adolescent, MESH: Pedigree, Ubiquitin-Protein Ligases, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Familial Adult Myoclonic Epilepsy type 3, Article, Young Adult, Humans, Aged, MESH: Adolescent, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, Epilepsy, Membrane Proteins, MESH: Adult, MESH: Membrane Proteins/genetics, MESH: Ubiquitin-Protein Ligases, MESH: Male, Introns, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, MESH: Chromosome Mapping, MESH: Female, Neurological disorders
Abstract

Familial Adult Myoclonic Epilepsy (FAME) is a genetically heterogeneous disorder characterized by cortical tremor and seizures. Intronic TTTTA/TTTCA repeat expansions in SAMD12 (FAME1) are the main cause of FAME in Asia. Using genome sequencing and repeat-primed PCR, we identify another site of this repeat expansion, in MARCH6 (FAME3) in four European families. Analysis of single DNA molecules with nanopore sequencing and molecular combing show that expansions range from 3.3 to 14 kb on average. However, we observe considerable variability in expansion length and structure, supporting the existence of multiple expansion configurations in blood cells and fibroblasts of the same individual. Moreover, the largest expansions are associated with micro-rearrangements occurring near the expansion in 20% of cells. This study provides further evidence that FAME is caused by intronic TTTTA/TTTCA expansions in distinct genes and reveals that expansions exhibit an unexpectedly high somatic instability that can ultimately result in genomic rearrangements., Familial cortical myoclonic tremor with epilepsy (FAME) is a slowly progressing cortical tremor mapping to various genomic loci, including intronic expansions in SAMD12 for FAME1. Here, Florian et al. describe mixed intronic TTTTA/TTTCA expansions of various lengths in the first intron of MARCH6 as a cause of FAME3.

Published
2019

18. Correction to: Adjunctive Brivaracetam in Focal Epilepsy: Real‑World Evidence from the BRIVAracetam add‑on First Italian netwoRk Study (BRIVAFIRST) (CNS Drugs, (2021), 35, 12, (1289-1301), 10.1007/s40263-021-00856-3)

Author

Lattanzi, S., Canafoglia, L., Canevini, M. P., Casciato, S., Chiesa, V., Dainese, F., De Maria, G., Didato, G., Falcicchio, G., Fanella, M., Ferlazzo, E., Fisco, G., Gangitano, M., Giallonardo, A. T., Giorgi, F. S., La Neve, A., Mecarelli, O., Montalenti, E., Piazza, F., Pulitano, P., Quarato, P. P., Ranzato, F., Rosati, E., Tassi, L., Di Bonaventura, C., Alicino, A., Ascoli, M., Assenza, G., Avorio, F., Badioni, V., Banfi, P., Bartolini, E., Basili, L. M., Belcastro, V., Beretta, S., Berto, I., Biggi, M., Billo, G., Boero, G., Bonanni, P., Bongorno, J., Brigo, F., Caggia, E., Cagnetti, C., Calvello, C., Irelli, E. C., Cesnik, E., Chianale, G., Ciampanelli, D., Ciuffini, R., Cocito, D., Colella, D., Contento, M., Costa, C., Cumbo, E., D'Aniello, A., Deleo, F., Difrancesco, J. C., Gennaro, G., Di Giacomo, R., Di Liberto, A., Domina, E., Donato, F., Dono, F., Durante, V., Elia, M., Estraneo, A., Evangelista, G., Faedda, M. T., Failli, Y., Fallica, E., Fattouch, J., Ferrari, A., Ferreri, F., Fonti, D., Fortunato, F., Foschi, N., Francavilla, T., Galli, R., Gazzina, S., Giuliano, L., Habetswallner, F., Izzi, F., Kassabian, B., Labate, A., Luisi, C., Magliani, M., Maira, G., Mari, L., Marino, D., Mascia, A., Mazzeo, A., Meletti, S., Morano, A., Nilo, A., Orlando, B., Paladin, F., Pascarella, M. G., Pastori, C., Pauletto, G., Peretti, A., Perri, G., Pezzella, M., Piccioli, M., Pignatta, P., Pilolli, N., Pisani, F., Pisani, L. R., Placidi, F., Pollicino, P., Porcella, V., Pradella, S., Puligheddu, M., Quadri, S., Quintas, R., Renna, R., Rossi, J., Rum, A., Salamone, E. M., Savastano, E., Sessa, M., Stokelj, D., Tartara, E., Tombini, M., Tumminelli, G., Ventura, M., Vigano, I., Viglietta, E., Vignoli, A., Villani, F., Zambrelli, E., and Zummo, L.

Published
2021

19. Correction to: Adjunctive Brivaracetam in Focal Epilepsy: Real‑World Evidence from the BRIVAracetam add‑on First Italian netwoRk Study (BRIVAFIRST) (CNS Drugs, (2021), 10.1007/s40263-021-00856-3)

Author

Lattanzi, S., Canafoglia, L., Canevini, M. P., Casciato, S., Chiesa, V., Dainese, F., De Maria, G., Didato, G., Falcicchio, G., Fanella, M., Ferlazzo, E., Fisco, G., Gangitano, M., Giallonardo, A. T., Giorgi, F. S., La Neve, A., Mecarelli, O., Montalenti, E., Piazza, F., Pulitano, P., Quarato, P. P., Ranzato, F., Rosati, E., Tassi, L., Di Bonaventura, C., Alicino, A., Ascoli, M., Assenza, G., Avorio, F., Badioni, V., Banfi, P., Bartolini, E., Basili, L. M., Belcastro, V., Beretta, S., Berto, I., Biggi, M., Billo, G., Boero, G., Bonanni, P., Bongorno, J., Brigo, F., Caggia, E., Cagnetti, C., Calvello, C., Irelli, E. C., Cesnik, E., Chianale, G., Ciampanelli, D., Ciuffini, R., Cocito, D., Colella, D., Contento, M., Costa, C., Cumbo, E., D'Aniello, A., Deleo, F., Difrancesco, J. C., Gennaro, G., Di Giacomo, R., Di Liberto, A., Domina, E., Donato, F., Dono, F., Durante, V., Elia, M., Estraneo, A., Evangelista, G., Faedda, M. T., Failli, Y., Fallica, E., Fattouch, J., Ferrari, A., Ferreri, F., Fonti, D., Fortunato, F., Foschi, N., Francavilla, T., Galli, R., Gazzina, S., Giuliano, L., Habetswallner, F., Izzi, F., Kassabian, B., Labate, A., Luisi, C., Magliani, M., Maira, G., Mari, L., Marino, D., Mascia, A., Mazzeo, A., Meletti, S., Morano, A., Nilo, A., Orlando, B., Paladin, F., Pascarella, M. G., Pastori, C., Pauletto, G., Peretti, A., Perri, G., Pezzella, M., Piccioli, M., Pignatta, P., Pilolli, N., Pisani, F., Pisani, L. R., Placidi, F., Pollicino, P., Porcella, V., Pradella, S., Puligheddu, M., Quadri, S., Quintas, R., Renna, R., Rossi, J., Rum, A., Salamone, E. M., Savastano, E., Sessa, M., Stokelj, D., Tartara, E., Tombini, M., Tumminelli, G., Ventura, M., Vigano, I., Viglietta, E., Vignoli, A., Villani, F., Zambrelli, E., and Zummo, L.

Published
2021

20. Progressive Myoclonus Epilepsies Diagnostic Yield With Next-Generation Sequencing in Previously Unsolved Cases

Author

Canafoglia, L, Franceschetti, S, Gambardella, A, Striano, P, Giallonardo, AT, Tinuper, P, Di Bonaventura, C, Michelucci, R, Ferlazzo, E, Granata, T, Magaudda, A, Licchetta, L, Filla, A, La Neve, A, Riguzzi, P, Cantisani, TA, Fanella, M, Castellotti, B, Gellera, C, Bahlo, M, Zara, F, Courage, C, Lehesjoki, A-E, Oliver, KL, Berkovic, SF, Canafoglia, L, Franceschetti, S, Gambardella, A, Striano, P, Giallonardo, AT, Tinuper, P, Di Bonaventura, C, Michelucci, R, Ferlazzo, E, Granata, T, Magaudda, A, Licchetta, L, Filla, A, La Neve, A, Riguzzi, P, Cantisani, TA, Fanella, M, Castellotti, B, Gellera, C, Bahlo, M, Zara, F, Courage, C, Lehesjoki, A-E, Oliver, KL, and Berkovic, SF

Abstract

BACKGROUND AND OBJECTIVES: To assess the current diagnostic yield of genetic testing for the progressive myoclonus epilepsies (PMEs) of an Italian series described in 2014 where Unverricht-Lundborg and Lafora diseases accounted for ∼50% of the cohort. METHODS: Of 47/165 unrelated patients with PME of indeterminate genetic origin, 38 underwent new molecular evaluations. Various next-generation sequencing (NGS) techniques were applied including gene panel analysis (n = 7) and/or whole-exome sequencing (WES) (WES singleton n = 29, WES trio n = 7, and WES sibling n = 4). In 1 family, homozygosity mapping was followed by targeted NGS. Clinically, the patients were grouped in 4 phenotypic categories: "Unverricht-Lundborg disease-like PME," "late-onset PME," "PME plus developmental delay," and "PME plus dementia." RESULTS: Sixteen of 38 (42%) unrelated patients reached a positive diagnosis, increasing the overall proportion of solved families in the total series from 72% to 82%. Likely pathogenic variants were identified in NEU1 (2 families), CERS1 (1 family), and in 13 nonfamilial patients in KCNC1 (3), DHDDS (3), SACS, CACNA2D2, STUB1, AFG3L2, CLN6, NAXE, and CHD2. Across the different phenotypic categories, the diagnostic rate was similar, and the same gene could be found in different phenotypic categories. DISCUSSION: The application of NGS technology to unsolved patients with PME has revealed a collection of very rare genetic causes. Pathogenic variants were detected in both established PME genes and in genes not previously associated with PME, but with progressive ataxia or with developmental encephalopathies. With a diagnostic yield >80%, PME is one of the best genetically defined epilepsy syndromes.

Published
2021

21. Sub-genic intolerance, ClinVar, and the epilepsies: A whole-exome sequencing study of 29,165 individuals

Author

Motelow, JE, Povysil, G, Dhindsa, RS, Stanley, KE, Allen, AS, Feng, Y-CA, Howrigan, DP, Abbott, LE, Tashman, K, Cerrato, F, Cusick, C, Singh, T, Heyne, H, Byrnes, AE, Churchhouse, C, Watts, N, Solomonson, M, Lal, D, Gupta, N, Neale, BM, Cavalleri, GL, Cossette, P, Cotsapas, C, De Jonghe, P, Dixon-Salazar, T, Guerrini, R, Hakonarson, H, Heinzen, EL, Helbig, I, Kwan, P, Marson, AG, Petrovski, S, Kamalakaran, S, Sisodiya, SM, Stewart, R, Weckhuysen, S, Depondt, C, Dlugos, DJ, Scheffer, IE, Striano, P, Freyer, C, Krause, R, May, P, McKenna, K, Regan, BM, Bennett, CA, Leu, C, Leech, SL, O'Brien, TJ, Todaro, M, Stamberger, H, Andrade, DM, Ali, QZ, Sadoway, TR, Krestel, H, Schaller, A, Papacostas, SS, Kousiappa, I, Tanteles, GA, Christou, Y, Sterbova, K, Vlckova, M, Sedlackova, L, Lassuthova, P, Klein, KM, Rosenow, F, Reif, PS, Knake, S, Neubauer, BA, Zimprich, F, Feucht, M, Reinthaler, EM, Kunz, WS, Zsurka, G, Surges, R, Baumgartner, T, von Wrede, R, Pendziwiat, M, Muhle, H, Rademacher, A, van Baalen, A, von Spiczak, S, Stephani, U, Afawi, Z, Korczyn, AD, Kanaan, M, Canavati, C, Kurlemann, G, Muller-Schluter, K, Kluger, G, Haeusler, M, Blatt, I, Lemke, JR, Krey, I, Weber, YG, Wolking, S, Becker, F, Lauxmann, S, Bosselmann, C, Kegele, J, Hengsbach, C, Rau, S, Steinhoff, BJ, Schulze-Bonhage, A, Borggraefe, I, Schankin, CJ, Schubert-Bast, S, Schreiber, H, Mayer, T, Korinthenberg, R, Brockmann, K, Wolff, M, Dennig, D, Madeleyn, R, Kalviainen, R, Saarela, A, Timonen, O, Linnankivi, T, Lehesjoki, A-E, Rheims, S, Lesca, G, Ryvlin, P, Maillard, L, Valton, L, Derambure, P, Bartolomei, F, Hirsch, E, Michel, V, Chassoux, F, Rees, M, Chung, S-K, Pickrell, WO, Powell, R, Baker, MD, Fonferko-Shadrach, B, Lawthom, C, Anderson, J, Schneider, N, Balestrini, S, Zagaglia, S, Braatz, V, Johnson, MR, Auce, P, Sills, GJ, Baum, LW, Sham, PC, Cherny, SS, Lui, CHT, Delanty, N, Doherty, CP, Shukralla, A, El-Naggar, H, Widdess-Walsh, P, Barisi, N, Canafoglia, L, Franceschetti, S, Castellotti, B, Granata, T, Ragona, F, Zara, F, Iacomino, M, Riva, A, Madia, F, Vari, MS, Salpietro, V, Scala, M, Mancardi, MM, Nobili, L, Amadori, E, Giacomini, T, Bisulli, F, Pippucci, T, Licchetta, L, Minardi, R, Tinuper, P, Muccioli, L, Mostacci, B, Gambardella, A, Labate, A, Annesi, G, Manna, L, Gagliardi, M, Parrini, E, Mei, D, Vetro, A, Bianchini, C, Montomoli, M, Doccini, V, Barba, C, Hirose, S, Ishii, A, Suzuki, T, Inoue, Y, Yamakawa, K, Beydoun, A, Nasreddine, W, Zgheib, NK, Tumiene, B, Utkus, A, Sadleir, LG, King, C, Caglayan, SH, Arslan, M, Yapici, Z, Topaloglu, P, Kara, B, Yis, U, Turkdogan, D, Gundogdu-Eken, A, Bebek, N, Tsai, M-H, Ho, C-J, Lin, C-H, Lin, K-L, Chou, I-J, Poduri, A, Shiedley, BR, Shain, C, Noebels, JL, Goldman, A, Busch, RM, Jehi, L, Najm, IM, Ferguson, L, Khoury, J, Glauser, TA, Clark, PO, Buono, RJ, Ferraro, TN, Sperling, MR, Lo, W, Privitera, M, French, JA, Schachter, S, Kuzniecky, R, Devinsky, O, Hegde, M, Greenberg, DA, Ellis, CA, Goldberg, E, Helbig, KL, Cosico, M, Vaidiswaran, P, Fitch, E, Berkovic, SF, Lerche, H, Lowenstein, DH, Goldstein, DB, Motelow, JE, Povysil, G, Dhindsa, RS, Stanley, KE, Allen, AS, Feng, Y-CA, Howrigan, DP, Abbott, LE, Tashman, K, Cerrato, F, Cusick, C, Singh, T, Heyne, H, Byrnes, AE, Churchhouse, C, Watts, N, Solomonson, M, Lal, D, Gupta, N, Neale, BM, Cavalleri, GL, Cossette, P, Cotsapas, C, De Jonghe, P, Dixon-Salazar, T, Guerrini, R, Hakonarson, H, Heinzen, EL, Helbig, I, Kwan, P, Marson, AG, Petrovski, S, Kamalakaran, S, Sisodiya, SM, Stewart, R, Weckhuysen, S, Depondt, C, Dlugos, DJ, Scheffer, IE, Striano, P, Freyer, C, Krause, R, May, P, McKenna, K, Regan, BM, Bennett, CA, Leu, C, Leech, SL, O'Brien, TJ, Todaro, M, Stamberger, H, Andrade, DM, Ali, QZ, Sadoway, TR, Krestel, H, Schaller, A, Papacostas, SS, Kousiappa, I, Tanteles, GA, Christou, Y, Sterbova, K, Vlckova, M, Sedlackova, L, Lassuthova, P, Klein, KM, Rosenow, F, Reif, PS, Knake, S, Neubauer, BA, Zimprich, F, Feucht, M, Reinthaler, EM, Kunz, WS, Zsurka, G, Surges, R, Baumgartner, T, von Wrede, R, Pendziwiat, M, Muhle, H, Rademacher, A, van Baalen, A, von Spiczak, S, Stephani, U, Afawi, Z, Korczyn, AD, Kanaan, M, Canavati, C, Kurlemann, G, Muller-Schluter, K, Kluger, G, Haeusler, M, Blatt, I, Lemke, JR, Krey, I, Weber, YG, Wolking, S, Becker, F, Lauxmann, S, Bosselmann, C, Kegele, J, Hengsbach, C, Rau, S, Steinhoff, BJ, Schulze-Bonhage, A, Borggraefe, I, Schankin, CJ, Schubert-Bast, S, Schreiber, H, Mayer, T, Korinthenberg, R, Brockmann, K, Wolff, M, Dennig, D, Madeleyn, R, Kalviainen, R, Saarela, A, Timonen, O, Linnankivi, T, Lehesjoki, A-E, Rheims, S, Lesca, G, Ryvlin, P, Maillard, L, Valton, L, Derambure, P, Bartolomei, F, Hirsch, E, Michel, V, Chassoux, F, Rees, M, Chung, S-K, Pickrell, WO, Powell, R, Baker, MD, Fonferko-Shadrach, B, Lawthom, C, Anderson, J, Schneider, N, Balestrini, S, Zagaglia, S, Braatz, V, Johnson, MR, Auce, P, Sills, GJ, Baum, LW, Sham, PC, Cherny, SS, Lui, CHT, Delanty, N, Doherty, CP, Shukralla, A, El-Naggar, H, Widdess-Walsh, P, Barisi, N, Canafoglia, L, Franceschetti, S, Castellotti, B, Granata, T, Ragona, F, Zara, F, Iacomino, M, Riva, A, Madia, F, Vari, MS, Salpietro, V, Scala, M, Mancardi, MM, Nobili, L, Amadori, E, Giacomini, T, Bisulli, F, Pippucci, T, Licchetta, L, Minardi, R, Tinuper, P, Muccioli, L, Mostacci, B, Gambardella, A, Labate, A, Annesi, G, Manna, L, Gagliardi, M, Parrini, E, Mei, D, Vetro, A, Bianchini, C, Montomoli, M, Doccini, V, Barba, C, Hirose, S, Ishii, A, Suzuki, T, Inoue, Y, Yamakawa, K, Beydoun, A, Nasreddine, W, Zgheib, NK, Tumiene, B, Utkus, A, Sadleir, LG, King, C, Caglayan, SH, Arslan, M, Yapici, Z, Topaloglu, P, Kara, B, Yis, U, Turkdogan, D, Gundogdu-Eken, A, Bebek, N, Tsai, M-H, Ho, C-J, Lin, C-H, Lin, K-L, Chou, I-J, Poduri, A, Shiedley, BR, Shain, C, Noebels, JL, Goldman, A, Busch, RM, Jehi, L, Najm, IM, Ferguson, L, Khoury, J, Glauser, TA, Clark, PO, Buono, RJ, Ferraro, TN, Sperling, MR, Lo, W, Privitera, M, French, JA, Schachter, S, Kuzniecky, R, Devinsky, O, Hegde, M, Greenberg, DA, Ellis, CA, Goldberg, E, Helbig, KL, Cosico, M, Vaidiswaran, P, Fitch, E, Berkovic, SF, Lerche, H, Lowenstein, DH, and Goldstein, DB

Abstract

Both mild and severe epilepsies are influenced by variants in the same genes, yet an explanation for the resulting phenotypic variation is unknown. As part of the ongoing Epi25 Collaboration, we performed a whole-exome sequencing analysis of 13,487 epilepsy-affected individuals and 15,678 control individuals. While prior Epi25 studies focused on gene-based collapsing analyses, we asked how the pattern of variation within genes differs by epilepsy type. Specifically, we compared the genetic architectures of severe developmental and epileptic encephalopathies (DEEs) and two generally less severe epilepsies, genetic generalized epilepsy and non-acquired focal epilepsy (NAFE). Our gene-based rare variant collapsing analysis used geographic ancestry-based clustering that included broader ancestries than previously possible and revealed novel associations. Using the missense intolerance ratio (MTR), we found that variants in DEE-affected individuals are in significantly more intolerant genic sub-regions than those in NAFE-affected individuals. Only previously reported pathogenic variants absent in available genomic datasets showed a significant burden in epilepsy-affected individuals compared with control individuals, and the ultra-rare pathogenic variants associated with DEE were located in more intolerant genic sub-regions than variants associated with non-DEE epilepsies. MTR filtering improved the yield of ultra-rare pathogenic variants in affected individuals compared with control individuals. Finally, analysis of variants in genes without a disease association revealed a significant burden of loss-of-function variants in the genes most intolerant to such variation, indicating additional epilepsy-risk genes yet to be discovered. Taken together, our study suggests that genic and sub-genic intolerance are critical characteristics for interpreting the effects of variation in genes that influence epilepsy.

Published
2021

23. Polygenic burden in focal and generalized epilepsies

Author

Leu C., Stevelink R., Smith A. W., Goleva S. B., Kanai M., Ferguson L., Campbell C., Kamatani Y., Okada Y., Sisodiya S. M., Cavalleri G. L., Koeleman B. P. C., Lerche H., Jehi L., Davis L. K., Najm I. M., Palotie A., Daly M. J., Busch R. M., Lal D., Feng Y. -C. A., Howrigan D. P., Abbott L. E., Tashman K., Cerrato F., Churchhouse C., Gupta N., Neale B. M., Berkovic S. F., Goldstein D. B., Lowenstein D. H., Cossette P., Cotsapas C., De Jonghe P., Dixon-Salazar T., Guerrini R., Hakonarson H., Heinzen E. L., Helbig I., Kwan P., Marson A. G., Petrovski S., Kamalakaran S., Stewart R., Weckhuysen S., Depondt C., Dlugos D. J., Scheffer I. E., Striano P., Freyer C., Krause R., May P., McKenna K., Regan B. M., Bellows S. T., Bennett C. A., Johns E. M. C., Macdonald A., Shilling H., Burgess R., Weckhuysen D., Bahlo M., O'Brien T. J., Todaro M., Stamberger H., Andrade D. M., Sadoway T. R., Mo K., Krestel H., Gallati S., Papacostas S. S., Kousiappa I., Tanteles G. A., Sterbova K., Vlckova M., Sedlackova L., Lassuthova P., Klein K. M., Rosenow F., Reif P. S., Knake S., Kunz W. S., Zsurka G., Elger C. E., Bauer J., Rademacher M., Pendziwiat M., Muhle H., Rademacher A., Van Baalen A., Von Spiczak S., Stephani U., Afawi Z., Korczyn A. D., Kanaan M., Canavati C., Kurlemann G., Muller-Schluter K., Kluger G., Hausler M., Blatt I., Lemke J. R., Krey I., Weber Y. G., Wolking S., Becker F., Hengsbach C., Rau S., Maisch A. F., Steinhoff B. J., Schulze-Bonhage A., Schubert-Bast S., Schreiber H., Borggrafe I., Schankin C. J., Mayer T., Korinthenberg R., Brockmann K., Dennig D., Madeleyn R., Kalviainen R., Auvinen P., Saarela A., Linnankivi T., Lehesjoki A. -E., Rees M. I., Chung S. -K., Pickrell W. O., Powell R., Schneider N., Balestrini S., Zagaglia S., Braatz V., Johnson M. R., Auce P., Sills G. J., Baum L. W., Sham P. C., Cherny S. S., Lui C. H. T., Barisic N., Delanty N., Doherty C. P., Shukralla A., McCormack M., El-Naggar H., Canafoglia L., Franceschetti S., Castellotti B., Granata T., Zara F., Iacomino M., Madia F., Vari M. S., Mancardi M. M., Salpietro V., Bisulli F., Tinuper P., Licchetta L., Pippucci T., Stipa C., Muccioli L., Minardi R., Gambardella A., Labate A., Annesi G., Manna L., Gagliardi M., Parrini E., Mei D., Vetro A., Bianchini C., Montomoli M., Doccini V., Marini C., Suzuki T., Inoue Y., Yamakawa K., Birute T., Ruta M., Algirdas U., Ruta P., Jurgita G., Ruta S., Sadleir L. G., King C., Mountier E., Caglayan S. H., Arslan M., Yapici Z., Yis U., Topaloglu P., Kara B., Turkdogan D., Gundogdu-Eken A., Bebek N., Ugur-Iseri S., Baykan B., Salman B., Haryanyan G., Yucesan E., Kesim Y., Ozkara C., Sheidley B. R., Shain C., Poduri A., Buono R. J., Ferraro T. N., Sperling M. R., Lo W., Privitera M., French J. A., Schachter S., Kuzniecky R. I., Devinsky O., Hegde M., Khankhanian P., Helbig K. L., Ellis C. A., Spalletta G., Piras F., Gili T., Ciullo V., Leu C., Stevelink R., Smith A.W., Goleva S.B., Kanai M., Ferguson L., Campbell C., Kamatani Y., Okada Y., Sisodiya S.M., Cavalleri G.L., Koeleman B.P.C., Lerche H., Jehi L., Davis L.K., Najm I.M., Palotie A., Daly M.J., Busch R.M., Lal D., Feng Y.-C.A., Howrigan D.P., Abbott L.E., Tashman K., Cerrato F., Churchhouse C., Gupta N., Neale B.M., Berkovic S.F., Goldstein D.B., Lowenstein D.H., Cossette P., Cotsapas C., De Jonghe P., Dixon-Salazar T., Guerrini R., Hakonarson H., Heinzen E.L., Helbig I., Kwan P., Marson A.G., Petrovski S., Kamalakaran S., Stewart R., Weckhuysen S., Depondt C., Dlugos D.J., Scheffer I.E., Striano P., Freyer C., Krause R., May P., McKenna K., Regan B.M., Bellows S.T., Bennett C.A., Johns E.M.C., Macdonald A., Shilling H., Burgess R., Weckhuysen D., Bahlo M., O'Brien T.J., Todaro M., Stamberger H., Andrade D.M., Sadoway T.R., Mo K., Krestel H., Gallati S., Papacostas S.S., Kousiappa I., Tanteles G.A., Sterbova K., Vlckova M., Sedlackova L., Lassuthova P., Klein K.M., Rosenow F., Reif P.S., Knake S., Kunz W.S., Zsurka G., Elger C.E., Bauer J., Rademacher M., Pendziwiat M., Muhle H., Rademacher A., Van Baalen A., Von Spiczak S., Stephani U., Afawi Z., Korczyn A.D., Kanaan M., Canavati C., Kurlemann G., Muller-Schluter K., Kluger G., Hausler M., Blatt I., Lemke J.R., Krey I., Weber Y.G., Wolking S., Becker F., Hengsbach C., Rau S., Maisch A.F., Steinhoff B.J., Schulze-Bonhage A., Schubert-Bast S., Schreiber H., Borggrafe I., Schankin C.J., Mayer T., Korinthenberg R., Brockmann K., Dennig D., Madeleyn R., Kalviainen R., Auvinen P., Saarela A., Linnankivi T., Lehesjoki A.-E., Rees M.I., Chung S.-K., Pickrell W.O., Powell R., Schneider N., Balestrini S., Zagaglia S., Braatz V., Johnson M.R., Auce P., Sills G.J., Baum L.W., Sham P.C., Cherny S.S., Lui C.H.T., Barisic N., Delanty N., Doherty C.P., Shukralla A., McCormack M., El-Naggar H., Canafoglia L., Franceschetti S., Castellotti B., Granata T., Zara F., Iacomino M., Madia F., Vari M.S., Mancardi M.M., Salpietro V., Bisulli F., Tinuper P., Licchetta L., Pippucci T., Stipa C., Muccioli L., Minardi R., Gambardella A., Labate A., Annesi G., Manna L., Gagliardi M., Parrini E., Mei D., Vetro A., Bianchini C., Montomoli M., Doccini V., Marini C., Suzuki T., Inoue Y., Yamakawa K., Birute T., Ruta M., Algirdas U., Ruta P., Jurgita G., Ruta S., Sadleir L.G., King C., Mountier E., Caglayan S.H., Arslan M., Yapici Z., Yis U., Topaloglu P., Kara B., Turkdogan D., Gundogdu-Eken A., Bebek N., Ugur-Iseri S., Baykan B., Salman B., Haryanyan G., Yucesan E., Kesim Y., Ozkara C., Sheidley B.R., Shain C., Poduri A., Buono R.J., Ferraro T.N., Sperling M.R., Lo W., Privitera M., French J.A., Schachter S., Kuzniecky R.I., Devinsky O., Hegde M., Khankhanian P., Helbig K.L., Ellis C.A., Spalletta G., Piras F., Gili T., Ciullo V., Commission of the European Communities, Medical Research Council (MRC), Tumienė, Birutė, Mameniškienė, Rūta, Utkus, Algirdas, Praninskienė, Rūta, Grikinienė, Jurgita, Samaitienė-Aleknienė, Rūta, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, University of Helsinki, Helsinki Institute of Life Science HiLIFE, and Department of Medical and Clinical Genetics

Subjects
0301 basic medicine, Male, Multifactorial Inheritance, Epi25 Consortium, Databases, Factual, FEATURES, Genome-wide association study, Epilepsies, 3124 Neurology and psychiatry, Cohort Studies, Epilepsy, 0302 clinical medicine, Cost of Illness, 1ST SEIZURE, HISTORY, genetics, POPULATION, 11 Medical and Health Sciences, education.field_of_study, medicine.diagnostic_test, SCORES, Single Nucleotide, Biobank, 3. Good health, 17 Psychology and Cognitive Sciences, Genetic generalized epilepsy, Epilepsy, Generalized, Female, Partial, Cohort study, Human, medicine.medical_specialty, Population, European Continental Ancestry Group, Clinical Neurology, BIOBANK, Polymorphism, Single Nucleotide, epilepsy, genetic generalized epilepsy, common variant risk, Databases, 03 medical and health sciences, Genetic, Internal medicine, medicine, Journal Article, Genetics, Humans, Genetic Predisposition to Disease, Polymorphism, GENOME-WIDE ASSOCIATION, Generalized epilepsy, education, SEIZURE RECURRENCE, Factual, METAANALYSIS, Genetic testing, Neurology & Neurosurgery, RISK PREDICTION, Generalized, business.industry, 3112 Neurosciences, Common variant risk, Genetic Variation, Original Articles, medicine.disease, Comorbidity, Cost of Illne, Epilepsies, Partial, Genome-Wide Association Study, 030104 developmental biology, Neurology (clinical), Cohort Studie, business, 030217 neurology & neurosurgery
Abstract

See Hansen and Møller (doi:10.1093/brain/awz318) for a scientific commentary on this article. Using polygenic risk scores from a genome-wide association study in generalized and focal epilepsy, Leu et al. reveal a significantly higher genetic burden for epilepsy in multiple cohorts of people with epilepsy compared to population controls. Quantification of common variant burden may be valuable for epilepsy prognosis and treatment., Rare genetic variants can cause epilepsy, and genetic testing has been widely adopted for severe, paediatric-onset epilepsies. The phenotypic consequences of common genetic risk burden for epilepsies and their potential future clinical applications have not yet been determined. Using polygenic risk scores (PRS) from a European-ancestry genome-wide association study in generalized and focal epilepsy, we quantified common genetic burden in patients with generalized epilepsy (GE-PRS) or focal epilepsy (FE-PRS) from two independent non-Finnish European cohorts (Epi25 Consortium, n = 5705; Cleveland Clinic Epilepsy Center, n = 620; both compared to 20 435 controls). One Finnish-ancestry population isolate (Finnish-ancestry Epi25, n = 449; compared to 1559 controls), two European-ancestry biobanks (UK Biobank, n = 383 656; Vanderbilt biorepository, n = 49 494), and one Japanese-ancestry biobank (BioBank Japan, n = 168 680) were used for additional replications. Across 8386 patients with epilepsy and 622 212 population controls, we found and replicated significantly higher GE-PRS in patients with generalized epilepsy of European-ancestry compared to patients with focal epilepsy (Epi25: P = 1.64×10−15; Cleveland: P = 2.85×10−4; Finnish-ancestry Epi25: P = 1.80×10−4) or population controls (Epi25: P = 2.35×10−70; Cleveland: P = 1.43×10−7; Finnish-ancestry Epi25: P = 3.11×10−4; UK Biobank and Vanderbilt biorepository meta-analysis: P = 7.99×10−4). FE-PRS were significantly higher in patients with focal epilepsy compared to controls in the non-Finnish, non-biobank cohorts (Epi25: P = 5.74×10−19; Cleveland: P = 1.69×10−6). European ancestry-derived PRS did not predict generalized epilepsy or focal epilepsy in Japanese-ancestry individuals. Finally, we observed a significant 4.6-fold and a 4.5-fold enrichment of patients with generalized epilepsy compared to controls in the top 0.5% highest GE-PRS of the two non-Finnish European cohorts (Epi25: P = 2.60×10−15; Cleveland: P = 1.39×10−2). We conclude that common variant risk associated with epilepsy is significantly enriched in multiple cohorts of patients with epilepsy compared to controls—in particular for generalized epilepsy. As sample sizes and PRS accuracy continue to increase with further common variant discovery, PRS could complement established clinical biomarkers and augment genetic testing for patient classification, comorbidity research, and potentially targeted treatment.

Published
2019

24. Gabapentin treatment in a patient with KCNQ2 developmental epileptic encephalopathy

Author

Soldovieri, M, Freri, E, Ambrosino, P, Rivolta, I, Mosca, I, Binda, A, Murano, C, Ragona, F, Canafoglia, L, Vannicola, C, Solazzi, R, Granata, T, Castellotti, B, Messina, G, Gellera, C, Labalme, A, Lesca, G, Difrancesco, J, Taglialatela, M, Soldovieri, Maria Virginia, Freri, Elena, Ambrosino, Paolo, Rivolta, Ilaria, Mosca, Ilaria, Binda, Anna, Murano, Carmen, Ragona, Francesca, Canafoglia, Laura, Vannicola, Chiara, Solazzi, Roberta, Granata, Tiziana, Castellotti, Barbara, Messina, Giuliana, Gellera, Cinzia, Labalme, Audrey, Lesca, Gaetan, DiFrancesco, Jacopo C., Taglialatela, Maurizio, Soldovieri, M, Freri, E, Ambrosino, P, Rivolta, I, Mosca, I, Binda, A, Murano, C, Ragona, F, Canafoglia, L, Vannicola, C, Solazzi, R, Granata, T, Castellotti, B, Messina, G, Gellera, C, Labalme, A, Lesca, G, Difrancesco, J, Taglialatela, M, Soldovieri, Maria Virginia, Freri, Elena, Ambrosino, Paolo, Rivolta, Ilaria, Mosca, Ilaria, Binda, Anna, Murano, Carmen, Ragona, Francesca, Canafoglia, Laura, Vannicola, Chiara, Solazzi, Roberta, Granata, Tiziana, Castellotti, Barbara, Messina, Giuliana, Gellera, Cinzia, Labalme, Audrey, Lesca, Gaetan, DiFrancesco, Jacopo C., and Taglialatela, Maurizio

Abstract

De novo variants in KCNQ2 encoding for Kv7.2 voltage-dependent neuronal potassium (K+) channel subunits are associated with developmental epileptic encephalopathy (DEE). We herein describe a the clinical and electroencephalographic (EEG) features of a child with early-onset DEE caused by the novel KCNQ2 p.G310S variant. In vitro experiments demonstrated that the mutation induces loss-of-function effects on the currents produced by channels incorporating mutant subunits; these effects were counteracted by the selective Kv7 opener retigabine and by gabapentin, a recently described Kv7 activator. Given these data, the patient started treatment with gabapentin, showing a rapid and sustained clinical and EEG improvement over the following months. Overall, these results suggest that gabapentin can be regarded as a precision therapy for DEEs due to KCNQ2 loss-of-function mutations.

Published
2020

26. DISTRIBUTION OF PROGRESSIVE MYOCLONUS EPILEPSIES IN ITALY; POSITIVELY DIAGNOSED AND UNCLASSIFIED PATIENTS: p827

Author

Canafoglia, L., Franceschetti, S., Michelucci, R., Magaudda, A., Rubboli, G., Tinuper, P., Striano, P., Striano, S., Gambardella, A., Neve, La A., Francavilla, T., Ferlazzo, E., Italiano, D., Gobbi, G., Villani, F., Nardocci, N., Granata, T., Veggiotti, P., Pareyson, D., Coppola, G., Uziel, G., Belcastro, V., Bisulli, F., Spreafico, R., Guerrini, R., Viri, M., Zucca, C., Capovilla, G., Giovagnoli, A. R., Canevini, M. P., Binelli, S., Casazza, M., Cantisani, A. T., Filla, A., Pezzella, M., Santucci, M., Parmeggiani, A., Posar, A., De Maria, G., Marini, C., Bianchi, A., Ragona, F., Freri, E., Mariotti, C., and Costa, P.

Published
2012

28. Serum and tissue CTACK/CCL27 chemokine levels in early mycosis fungoides may be correlated with disease-free survival following treatment with interferon alfa and psoralen plus ultraviolet A therapy

Author

Goteri, G., Rupoli, S., Campanati, A., Zizzi, A., Picardi, P., Cardelli, M., Giantomassi, F., Canafoglia, L., Marchegiani, F., Mozzicafreddo, G., Brandozzi, G., Stramazzotti, D., Ganzetti, G., Lisa, R., Simonetti, O., Offidani, A., Federici, I., Filosa, G., and Leoni, P.

Published
2012
Full Text
View/download PDF

30. HCN1 novel mutations in familiar generalized epilepsy

Author

Binda, A, Murano, C, Granata, T, Ragona, F, Freri, E, Franceschetti, S, Canafoglia, L, Castellotti, B, Gellere, C, Milanesi, r, DiFrancesco, JC, Rivolta, I, Binda, A, Murano, C, Granata, T, Ragona, F, Freri, E, Franceschetti, S, Canafoglia, L, Castellotti, B, Gellere, C, Milanesi, R, Difrancesco, J, and Rivolta, I

Subjects
Epilepsy, HCN1, patch-clamp
Published
2018

32. Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3

Author

Florian, R.T., Kraft, F., Leitao, E., Kaya, S., Klebe, S., Magnin, E., Rootselaar, A.F. van, Buratti, J., Kuhnel, T., Schroder, C., Giesselmann, S., Tschernoster, N., Altmueller, J., Lamiral, A., Keren, B., Nava, C., Bouteiller, D., Forlani, S., Jornea, L., Kubica, R., Ye, T., Plassard, D., Jost, B., Meyer, V., Deleuze, J.F., Delpu, Y., Avarello, M.D.M., Vijfhuizen, L.S., Rudolf, G., Hirsch, E., Kroes, T., Reif, P.S., Rosenow, F., Ganos, C., Vidailhet, M., Thivard, L., Mathieu, A., Bourgeron, T., Kurth, I., Rafehi, H., Steenpass, L., Horsthemke, B., Berkovic, S.F., Bisulli, F., Brancati, F., Canafoglia, L., Casari, G., Guerrini, R., Ishiura, H., Licchetta, L., Mei, D., Pippucci, T., Sadleir, L., Scheffer, I.E., Striano, P., Tinuper, P., Tsuji, S., Zara, F., LeGuern, E., Klein, K.M., Labauge, P., Bennett, M.F., Bahlo, M., Gecz, J., Corbett, M.A., Tijssen, M.A.J., Maagdenberg, A.M.J.M. van den, Depienne, C., and FAME Consortium

Abstract

Familial Adult Myoclonic Epilepsy (FAME) is a genetically heterogeneous disorder characterized by cortical tremor and seizures. Intronic TTTTA/TTTCA repeat expansions in SAMD12 (FAME1) are the main cause of FAME in Asia. Using genome sequencing and repeat-primed PCR, we identify another site of this repeat expansion, in MARCH6 (FAME3) in four European families. Analysis of single DNA molecules with nanopore sequencing and molecular combing show that expansions range from 3.3 to 14 kb on average. However, we observe considerable variability in expansion length and structure, supporting the existence of multiple expansion configurations in blood cells and fibroblasts of the same individual. Moreover, the largest expansions are associated with micro-rearrangements occurring near the expansion in 20% of cells. This study provides further evidence that FAME is caused by intronic TTTTA/TTTCA expansions in distinct genes and reveals that expansions exhibit an unexpectedly high somatic instability that can ultimately result in genomic rearrangements.

Published
2019

34. Fourth meeting of the European Neurological Society 25–29 June 1994 Barcelona, Spain: Abstracts of Symposia and free communications

Author

Harms, L., Bock, A., JÄnisch, W., Valdueza, J., Weber, J., Link, I., De Keyser, J., Goossens, A., Wilczak, N., Vedeler, C., Bjorge, L., Uvestad, E., Conti, G., Williams, K., Ginsberg, L., Rafique, S., Rapoport, S. I., Gershfeld, N. L., De La Meilleure, G., Crevits, L., Faiss, J. H., Heye, N., Blanke, J., Sackmann, A., Kastrup, O., Doornbos, R., van der Worp, H. B., Kappelle, L. J., Bar, P. R., Davie, C. A., Barker, G. J., Brenton, D., Miller, D. H., Thompson, A. J., Block, F., Schwarz, M., Delodovici, L., Baruzzi, F., Bonaldi, G., Dario, A., Marra, A., Mercuri, A., Dworzak, F., Cavallari, P., Confalonieri, P., Zuffi, M., Antozzi, C., Cornelio, F., Baldissera, F., Chassande, B., Ameri, A., Eymard, B., Poisson, M., Vérier, A., Brunet, P., Congia, S., Murgia, P. L., Cannas, A., Borghero, G., Uselli, S., Mellino, G., Ferrai, R., Lampis, R., Massa, R., Muzzetto, B., Giannini, F., Rossi, S., Cioni, R., d'Aniello, C., Guarneri, A., Battistini, N., Ceriani, F., Del Santo, A., Poloni, M., Campo, J. F., Iglesias, F., Guitera, M. V., Farinas, C., Pascual, J., Leno, C., Berciano, J., Thorpe, I. W., Kendall, B. E., McDonald, W. I., Moulignier, A., Dromer, F., Baudrimont, M., Dupont, B., Gozlan, J., El Amrani, M., Petit, J. C., Roullet, E., Sterzi, R., Causaran, R., Protti, A., Riva, M., Erminio, F., Arena, O., Villa, F., Maccagnano, E., Miletta, M., Spinelli, F., Ben-Hur, T., Weidenfeldl, J., Rao, N. S., Chari, C. C., Laforet, P., Matheron, S., Adams, D., Chemouilli, Ph., Desi, M., Said, G., Davous, P., Lionnet, F., Pulik, M., Genet, P., Rozenberg, F., Cartier, L. M., Castillo, J. L., Cea, J. G., Villagra, R., de Saint Martin, L., Mahieux, F., Manifacier, M. J., Mattos, K., Queiros, C., Publio, L., Vinhas, V., PeÇanha-Martins, A. C., Melo, A., Liska, U., Zifko, U., Budka, H., Drlicek, M., Grisold, W., Kaufmann, R., Kaiser, R., Czygan, M., Gomes, I., Jones, N., Cunha, S., EmbiruÇu, E. Katiane, Vieira, V., Araujo, I., Alexandra, M., Ferreira, A., Goes, J., Chemouilli, P., Israel-Biet, Masson, H., Lacroix, C., Gasnault, J., Hildebrandt-Müller, B., Oschmann, P., Krack, P., Willems, W. R., Dorndorf, W., Freitas, V., Bittencourt, A., Fernandes, D., Nascimento, M. H., Severo, M., Moraes, D., Muller, M., Hasert, K., Merkelbach, S., Schimrigk, K., van Oosten, B. W., Lai, M., Polman, C. H., Bertelsmann, F. W., Hodgkinson, S., Cabre, P. H., Volpe, L., Smadja, D., Vernant, J. P., Villaroya, H., Violleau, K., Younes-Chennoufi, A. Ben, Baumann, N., Villanueva-Hemandez, P., Ballabriga, J., Basart, E., Arbizu, T. X., Perez-Serra, J., Vinuels, F., Giron, J. M., Castilla, J. M., Redondo, L., Izquierdo, G., Lauer, K., Henneberg, A., Bittmann, N., Link, D., Wollinsky, K. H., Mobner, R., Fassbender, K., Kuhnen, J., Schwartz, A., Hennerici, M., Miller, A., Lider, O., Abramsky, O., Weiner, H. L., Offner, H., Vanderbark, A. A., Paoino, E., Fainardi, E., Addonizio, M. C., Ruppi, P., Tola, M. R., Granieri, E., Carreras, M., Sazdovitch, V., Joutel, A., Verdier-taillefer, M. H., Heinzlef, O., Radder, C., Tournier-Lasserve, E., Brenner, R. E., Munro, P. M. G., Williams, S. C. R., Bell, J. D., Hawkins, C. P., Filippi, M., Campi, A., Dousset, V., Canal, N., Comi, G., Zhu, J., Weber, F., Retska, R., List, J., Zhang, L., Brock, M., Taphoorn, M. J. B., Heimans, J. J., van der Veen, E. A., Karim, A. B. M. F., Sarazin, M., Argentino, N., Delattre, J. Y., Derkinderen, P., Buchwald, B., Schroter, G., Serve, G., Franke, C. H., Conrad, B., Kitchen, N. D., Thomas, D. G. T., Forman, A. D., Ang, Kie- Kian, Price, R., Stephens, C., Salmaggi, A., Nermni, R., Silvani, A., Forno, M. G., Luksch, R., Boiardi, A., Grzelec, H., Fryze, C., Nowacki, P., Zdziarska, B., Sanson, M., Merel, P., Richard, S., Rouleau, G., Thomas, G., Olsen, N. K., Pfeiffer, P., Egund, N., Bentzen, S. M., Johannesen, L., Mondrup, K., Rose, C., Zyluk, B., Wondrusch, E., Berger, O., Fast, N., Jellinger, K., Lindner, K., Urman, A., Thibault, J. L., Duyckaerts, Ch., Strik, H., Muller, B., Richter, E., Krauseneck, P., Steinbrecher, A., Schabet, M., Hess, C., Bamberg, M., Dichgans, J., Counsell, C. E., McLeod, M., Grant, R., Creel, G. B., Claus, D., Sieber, E., Engelhardt, A., Rechlin, T., Thierauf, P., Neubauer, U., Peresson, M., Di Giovacchino, G., Romani, G. L., Di Silverio, F., Danek, A., Kuffner, M., Hoermann, R., Schopohl, J., Laska, M., Heye, B., Zangaladze, A. T., Valls-SoIè, J., Cammarota, A., Alvarez, R., Tolosa, E., Hallett, M., Ulbricht, D., Ganslandt, O., Kober, H., Vieth, J., Grummich, P., Pongratz, H., Brigel, C., Fahlbusch, R., Serra, F. P., Palma, V., Nolfe, G., Buscaino, G. A., Rothstein, T. L., Gibson J. M., Morrison P. M., Collins A. D., Eiselt, M., Wagnur, H., Zwiener, U., Schindler, T., Efendi, H., Ertekin, C., Erfas, M., Larsson, L. E., Sirin, H., AraÇ, N., Toygar, A., Demir, Y., Seddigh, S., Vogt, T. H., Hundemer, H., Visbeck, A., Pastena, L., Faralli, F., Mainardi, G., Gagliardi, R., Linden, D., Berlit, P., Lopez, O. L., Becker, J. T., Jungreis, C., Brenner, R., Rezek, D., Dekesky, S. T., Estol, C., Boller, F., Fernandez, J. M., Mederer, S., Batlle, J., Turon, A., Codina, A., Hitzenberger, P., Vila, N., Valls-SolÇ, J., Chamorro, A., Pouget, J., Schmied, A., Morin, D., Azulay, J. Ph., Vedel, J. P., Montalt, J., Escudero, J., Barona, R., Campos, A., Varli, K., Ertem, E., Uludag, B., Yagiz, A., Privorkin, Z., Steinvil, Y., Kott, E., Combarros, O., Sanchez-Pernaute, R., Orizaola, P., Mokrusch, Th., Kutluaye, E., Selcuki, D., Ertikin, C., Zettl, U., Gold, R., Harvey, G. K., Hartung, H. P., Toyka, K. V., Wokke, J. H. J., Oey, P. L., Ippel, P. F., Jansen, G. H., Franssen, H., Toyooka, K., Fujimura, H., Ueno, S., Yoshikawa, H., Yorifuji, S., Yanagihara, T., Talamon, C., Tzourio, C., Kiefer, R., Jung, S., Toyka, K., Ruolt, I., Tranchant, C., Mohr, M., Warter, J. M., Younger, D. S., Rosoklija, G., Hays, A. P., Kurita, R., Hasegawa, O., Matsumto, M., Komiyama, A., Nara, Y., Oueslati, S., Belal, S., Turki, I., Ben Hamida, C., Hentati, F., Ben Hamida, M., Kwiecinski, H., Krolicki, L., Domzal-Stryga, A., Dellemijn, P. L. I., van Deventer, P., van Moll, B., Drogendijk, T., Vecht, Ch. J., Nemni S., Amadio, Fazio, R., Galardin, G., Delodovici, M. L., Peghi, E., Monticelli, M. L., Sessa, A., Viguera, M. L., Palomar, M., Gamez, J., Cervera, C., Navarro, C., Serena, J., Duran, I., Fernandez, A. L., Comabella, M., Nos, C., Rio, J., Montalban, J., Navarro, X., Verdu, E., Darbra, S., Buti, M., Mrabet, A., Fredj, M., Gouider, R., Tounsi, H., Khalfallah, N., Haddad, A., Dbaiss, T., Ghnassia, R., Rouillet, E., Chedru, F., Porsche, H., Strenge, H., Li, S. W., Young, Y. P., Garcia, A. A., Baron, P., Scarpini, E., Bianchi, R., Conti, A., Livraghi, S., Rees, J. H., Gregson, N. A., Hughes, R. A. C., Sedano, M. J., Calleja, J., Canga, E., Bahou, Y., Biary, N., Al Deeb, S. M., Guern, E. L. E., Gugenheim, M., Tardieu, S., Aisonobe, T. M., Agid, Y., Bouche, P., Brice, A., Rautenstrauss, B., Nelis, E., Grehl, H., Van Broeckhoven, C., Pfeiffer, R. A., Liehr, T., Ganzmann, E., Gehring, C., Neundörfer, B., Geremia, L., Doronzo, R., Sacilotto, G., Sergi, P., Pastorino, G. C., Scarlato, G., Planté-Bordeneuve, V., Mantel, A., Baas, F., Moser, H., Antonini, A., Psylla, M., Günther, I., Vontobell, P., Beer, H. F., Leenders, K. L., Chaudhuri, K. Ray, Parker, J., Pye, I. F., Millac, P. A. H., Abbott, R. J., Sutter, M., Albani, C., de Rijk, M. C., Breteler, M. M. B., Graveland, G. A., van der Mechè, F. G. A., Hofman, A., Keipes, M., Hilger, Ch., Diederich, N., Metz, H., Hentges, F., Pollak, P., Benabid, A. L., Limousin, P., Hoffmann, D., Benazzouz, A., Perret, J., Laihinen, A., Rinne, J. O., Ruottinen, H., Nagren, K., Lehikoinen, P., Oikonen, V., Ruotsalainen, U., Rinne, U. K., Cocozza, S., Pizzuti, A., Cavalcanti, F., Monticelli, A., Pianese, L., Redolfi, E., Paiau, F., Di Donato, S., Pandolfo, M., Palau, F., Monros, E., De Michele, G., Smeyers, P., Lopez-ArLandis, J., Uilchez, J., Filla, A., Genis, D., Matilla, T., Volpini, V., Blanchs, M. I., Davalos, A., Molins, A., Rosell, J., Estivill, X., De Jonghe, P., Smeyers, G., Krols, L., Mercelis, R., Hazan, J., Weissenbach, J., Martin, J. J., Warner, T. A. T., Williams, L., Orb, A. S., Harding, A. E., Giunti, P., Sweeney, M. G., Spadaro, M., Jodice, C., Novelletto, A., Malaspina, P., Frontali, M., Salmon, E., Gregoire, Del Fiore, Comar, Franck, G., Scheltens, P. H., Siegfried, K., Dartigues, E., De Deyn, P., Horn, R., Nelson, I., Hanna, M. G., Morgan-Hughes, J. A., Collinge, J., Palmer, M. S., Campbell, T., Mahal, S., Sidle, K., Humphreys, C., Tavitian, B., Pappata, S., Jobert, A., Crouzel, A. M., DiGiamberardino, L., Steimetz, G., Barbanti, P., Fabbrini, G., Salvatore, M., Buzzi, M. G., Di Piero, V., Petraroli, R., Sbriccoli, A., Pocchiari, M., Macchi, G., Lenzi, G. L., Spiegel, R., Maguire, P., Schmid, W., Ott, A., Bots, M. L., Grobbe, D. E., Hofman, A., Howard, R. S., Russell, S., Losseff, N., Hirsch, N. P., Couderc, R., Bailleul, S., Nargeot, M. C., Touchon, J., Picot, M. C., Rizzo, M., Watson, G., McGehee, D., Dingus, T., Kappos, L., Radü, E. W., Haas, J., Hartard, C. H., Spuler, S., Yousry, T., Voltz, R., Scheller, A., Holler, E., Hohlfeld, R., Scolding, N. J., Sussman, J., Kolar, O. J., Farlow, M. R., Rice, P. H., Zipp, F., Sotgiu, S., Weiss, E. H., Wekerle, H., Chalmers, R., Robertson, N., Compston, D. A. S., Martino, G., Clementi, E., Brambilla, E., Moiola, L., Martinelli, V., Colombo, B., Poggi, A., Rovaris, M., Grimaldi, L. M. E., Roth, M. P., Descoins, P., Ballivet, S., Ruidavets, J. B., Waubant, E., Nogueira, L., Cambon-Thomsen, A., Clanet, M., Leppert, D., Hauser, S., Lugaresi, A., Tartaro, A., D'aurelio, P., Befalo, L. L. O., Thomas, A., Malatesta, G., Gambi, D., Benedikz, J. E. G., Magnusson, H., Poser, C. M., Guomundsson, G., Bates, T. E., Davies, S. E. C., Clark, J. B., Landon, D. N., ùther, J. R., Rautenberg, W., Overgaard, K., Sereghy, T., Pedersen, H., Boysen, G., Diez-Tejedor, E., Carceller, F., Gutierrez, M., Lopez-Pajares, R., Roda, J. M., Chandra, B., Ricart, W., Gonzalez-Huix, F., Molina, A., Rundek, T., Demarin, V., De Reuck, J., Boon, P., Decoq, D., Strijckmans, K., Goethals, P., Lemahieu, I., Nibbio, A., Chabriat, H., Vahedi, K., Nagy, T., Verin, M., Mas, J. L., Julien, J., Ducrocq, X., Iba-Zizen, M. T., Cabanis, E. A., Bousser, M. G., Rolland, Y., Landgraf, F., Bompais, B., Lemaitre, M. H., Edan, G., Vorstrup, S., Knudsen, L., Olsen, K. Skovgaard, Videbaek, C., Schroeder, T., van Gijn, J., Jansen, H. M. L., Pruim, J., Paans, A. M. J., Willemsen, A. T. M., Hew, J. M., vd Vliet, A. M., Haaxma, R., Vaalburg, W., Minderhoud, J. M., Korf, J., Soudain, S. E., Ho, T. W., Mishu, B., Li, C. Y., Nachainkin, I., Gao, C. Y., Cornblath, D. R., Griffin, J. W., Asbury, A. K., Blaser, M. J., McKhann, G. M., Ho, T., Macko, C., Xue, P., Stadlan, E. M., Ramos-Alvarez, M., Valenciano, L., Visser, L. H., van der Meché, F. G. A., van Darn, P. A., Meulstee, J., Schmitz, P. I. M., Jacobs, B., Oomes, P. G., Kleyweg, R. P., Jacobs, B. C., Endtz, H. P., van Doorn, P. A., van der Mech, F. G. A., Van den Berg, L. H., Mollee, I., Logtenberg, T., Thomas, P. K., Plant, G., Baxter, P. J., Luis, R. Santiago, Matsumoto, M., Notermans, N. C., Wokke, J. H. J., Lokhorst, H. M., van der Graaf, Y., Jennekens, F. G. I., Azulay, J. P., Bille-Turg, F., Valentin, P., Farnarier, G. G., Pellissier, J. F., Serratrice, G., Quasthoff, S., Schneider, U., Grafe, P., Hilkens, P. H. E., Moll, J. W. B., van der Burg, M. E. L., Planting, A. S. T., van Putten, W. L. J., van den Bent, M. J., Birklein, F., Spitzer, A., Lang, E., Neundorfer, B., Diehl, R. R., Lücke, D., Smith, G. D. P., Mathias, C. J., Serra, J., Campera, M., Ochoa, J. L., Ray Chaudhuri, K., Pavitt, D., Alam, M., Handwerker, H. O., Bleasdale-Barr, K., Smith, G., Murray, N. M. F., Hawkins, P., Pepys, M., Gellera, C., DiDonato, S., Taroni, F., Uncini, A., Di Muzio, A., Servidei, S., Silvestri, G., Lodi, R., Iotti, S., Barbiroli, B., Morrissey, S. P., Borruat, F. X., Francis, D., Mosely, I., Hansen, H. C., Helmke, K., Kunze, K., Sadzot, B., Maquet, P., Lemaire, Plenevaux, Damhaut, Sommer, C., Myers, R. R., Berta, E., Mantegazza, R., Argov, Z., Shapira, Y., Wirguin, I., Beuuer, J., Franke, C., Roberts, M., Willison, H., Vincent, A., Newsom-Davis, J., Morrison, K. E., Damels, R., Francis, M., Campbell, L., Davies, K. E., Kohler, W., Bucka, C., Hertel, G., Kanovsky, P., Auer, D., Ackermann, H., Klose, U., Naegele, Th., Bien, S., Voigt, K., Fink, G. R., Stephan, K. M., Wise, R. J. S., Mullatti, N., Hewer, L., Frackowiak, R. S. J., Weiller, C. S., Rijnites, M., Jueptner, M., Bauermann, T., Krams, M., Diener, H. C., van Walderveen, M. A. A., Barkhof, F., Hommes, O. R., Valk, J., Willmer, J. P., Guzman, D. A., Passingham, R. E., Silbersweig, D., Ceballos-Baumann, A., Frith, C. D., Frackowiak, R., Lucas, C. H., Goullard, L., Marchau, M. J., Godefroy, O., Rondepierre, P. H., Chamas, E., Mounier-Vehier, F., Leys, D., Renato, J., Verdugo, M. S. C., Campero, M., Jose, L., Ochoa, D. S. C., Vivancos, F., Tejedor, E. Diez, Martinez, N., Roda, J., Frank, A., Barreiro, P., Satoh, Y., Nagata, K., Maeda, T., Hirata, Y., YalÇinerner, B., Ozkara, C., Ozer, F., Ozer, S., Hanoglu, L., Zunker, P., Pozo, J. L., Oberwittler, C., Schick, A., Buschmann, H. -Ch., Ringelstein, E. Bernd, Lara, M., Anzola, G. P., Magoni, M., Volta, G. Dalla, Tarasov, A., Feigin, V., Beaudry, M. G., Carrier, S., Chicoutimi, Henriques, I. L., Bogoussslavsky, J., van Melle, G., Mathieu, J., Perusse, L., Allard, P., Prevost, C., Cantin, L., Bouchard, J. M., De Braekeleer, M., Agbo, C., Neau, J. P., Tantot, A. M., Dary-Auriol, M., Ingrand, P., Gil, R., Baltadjiev, D., Zekin, D., Sabey, K., Gennaula, C. P., Pope, B. A., Caparros-Lefebvre, D., Girard-Buttaz, I., Pruvo, J. P., Petit, H., Hipola, D., Martin, M., Giménez-Roldan, S., Ivanez, V., Japaridze, G., Carrasco, J. L., Picomell, I., Herranz, J. L., Macias, J. A., Nieto, M., Noya, M., Oller, L., Kiteva-Trencevska, G., Delgado, M. R., Liu, H., Luengo, A., Parra, J., Colas, J., Fernandez, M. J., Manzanares, R., Kornhuber, M. E., Malashkhia, V., Orkodashili, G., Martinez, M., Bonaventura, I., Porta, G., Martinez, I., Fernandez, A., Aguilar, M., Masnou, P., Drouet, A., Dreyfus, M., Cartron, J., Morel-Kopp, M. C., Tchernia, G., Kaplan, C., Lammers, M. W., Hekster, Y. A., Keyser, A., Meinardi, H., Renier, W. O., Boon, P. A. J. M., Have, M. D., Kint, B., Cruz, P., Cadilha, A., Almeida, R., Goncalves, M., Pimenta, M., Ramos, L. M. P., Polder, T. W., Broere, C. A., Polman, L., Rother, I., Rother, M., Schlaug, G., Arnold, S., Holthausen, H., Wunderlich, G., Ebner, A., Luders, H., Witte, O. W., Seitz, R. J., Serra, L. L., Gallicchio, B., Rotondi, F., Wieshmann, U., Meierkord, H., Sabev, K., Di Carlo, V., Gueguen, B., Derouesné, Ch., Ancri, D., Bourdel, M. C., Guillou, S., Aliaga, R., Chornet, M. A., Rodrigo, A., Pascual, A. Pascual -Leone, Catala, M. D., Pascual-Leone, A., Benbadis, S. R., Dinner, D. S., Chelune, G. J., Lüders, H. O., Piedmonte, M. R., Blanco, T., Lopez, M. P., Romero, B., Deltoro, A., Pascual, A., Pascual, Leone, Bolgert, F., Josse, M. O., Tassan, P., Touze, E., Laplane, D., Godenberg, F., Brizioli, E., Del Gobbo, M., Pelliccioni, G., Scarpino, O., Durak, H., Damlacik, G., Tunca, Z., Fidaner, H., Yurekli, Y., Yemez, B., Kaygisiz, A., Anllo, E. A., Esperet, E., Giovagnoli, A. R., Casazza, M., Spreafico, R., Avanzini, G., Mascheroni, S., Vecchio, I., Tornali, C., Antonuzzo, A., Grasso, A. A., Bella, R., Pennisi, G., Raffaele, R., Broeckx, J., Schildermans, F., Hospers, W., Deberdt, W., Carney, J. M., Aksenova, M., Chen, M. S., Juncadella, M., Busquets, N., De la Fuente, I., Rodriguez, A., Rubio, F., Soler, R., Khati, C., Pillon, B., Deweer, B., Malapani, C., Malichard, N., Dubois, B., Rancurel, G., Lopez, D. L., Jungreia, G., DeKosky, S. T., Boiler, F., Weiller, C., Rijntjes, M., Mueller, S. P., Maguire, E. A., Burke, E. T., Staunton, H., Phillips, J., Rousseaux, M., Pena, J., Bertran, I., Santacruz, P., Lopez, R., Catafau, A., Lomena, F., Blesa, R., Rampello, L., Nicoletti, A., Cabaret, M., Lesoin, F., Steinling, M., Tournev, I., Maier-Hauff, K., Schroeder, M., Wolf, A., Cochin, J. P., Noel, I., Augustin, P., Auzou, P., Hannequin, D., Maria, V., Lopez-Bresnahan, Danielle, D. M., Antin-Ozerkis B. A., Bartels, E., Rodiek, S. O., Flugel, K. A., Campos, D. M., Salas-Puig, J., Del Rio, J. Sanhez, Vidal, J. A., Lahoz, C. H., Eraksoy, M., Barlas, O., Barlas, M., Bayindir, C., Ozcan, H., Birbamer, G., Gerstenbrand, F., Felber, S., Luz, G., Aichner, F., Seidel, G., Kaps, M., Hutzelmann, A., Gerriets, T., Kruggel, F., Martin, P. J., Gaunt, M. E., Abbot, R. J., Naylor, A. R., Meary, E., Dilouya, A., Meder, J. F., De Recondo, J., Lebtahi, R., Neff, K. W., Meairs, S., Viola, S., Matta, E., Aquilone, L., Rise, I. R., Authier, F. J., Kondo, H., Ghnassia, R. T., Degos, J. D., Gherardi, R. K., Bardoni A., Ciafaloni E., Comi G. P., Bresolin N., Robotti M., Moggio M., Rigoletto C., Roses A., Scarlato G., Castelli, E., Turconi, A., Bresolin, N., Perani, D., Felisari, G., Chariot, P., de Pinieux, G., Astier, A., Jacotot, B., Gherardi, R., Fischer-Gagnepain, V., Louboutin, J. P., Crespo, F., Florea-Strat, A., Fromont, G., Sabourin, J. -C., Gonano, E. -F., Moroni, I., Prelle, A., Iannaccone, S., Quattrini, A., deRino, F., Sessa, M., Golzi, V., Smirne, S., Nemni, R., Turpin, J. C., Lucotte, G., Jacobs, S. C. J. M., Willems, P. W. A., Bootsma, A. L., Lasa, A., Calaf, M., Baiget, M., Gallano, B., Fichter-Gagnepain, V., Mazzucchelli, F., D'Angelo, M. G., Velicogna, M., Bet, L., Comi, G. P., Bordoni, A., Gonano, E. F., Bazzi, P., Rapuzzi, S., Moggio, M., Fagiolari, G., Ciscato, P., Messina, A., Battistel, A., Ryniewicz, B., Sangla, I., Desnuelle, C., Paquis, V., Cozzone, P. J., Bendahan, D., Sturenburg, H. J., Kohncke, G., Castellli, E., Linssen, W., Stegeman, D., Binkhorst, R., Notermans, S., Jaspert, A., Fahsold, R., de Munain, A. Lopez, Cobo, A., Martorell, L., Poza, J. J., Navarrete Palau, D., Emparanza, J. I., Sanchez-Roy, R., Vilchez, J. J., Hernandez, M., Tena, J. Garcia, Perla, C., Koutroumanidis, M., Papathanasopoulos, P., Papadimitriou, A., Papapetropoulos, T. H., Divari, R., Hadjigeorgiou, G. M., Anastasopoulos, I., Sansone, V., Rotondo, G., Meola, G., Rigoletto, C., Messina, S., Szwabowska-Orzeszko, E., Jozwiak, S., Michalowicz, R., Szaplyko, W., Petrella, M. A., Della Marca, G., Masullo, G., Mennuni, G. F., Kompf, D., Wascher, E., Verleger, R., Kaido, M., Soga, F., Toyooka, H., Bayon, C., Rubio, J., Carlomagno, S., Parlato, V., Santoro, A., Lavarone, A., Bonavita, V., Pentore, R., Venneri, A., Pasquier, F., Lebert, F., Grymonprez, L., Lefebvre, C., Van der Linden, M., Derouesné, C., Renault, B., Lacomblez, L., Homeyer, P., Ouss, L., Neuman, E., Malbezin, M., Barrandon, S., Guez, D., Stevens, M., van Swieten, J. C., Franke, C. L., Sanchez, A., Castellvirel, S., Mila, M., Jimenez, D., Pallesta, F., Ruiz, P. J. Garcia, Barrio, A., Barroso, T., Benitez, J., de Yebenes, J. Garcia, Manubens, J. M., Martinez-Lage, J. M., Larumbe, R., Muruzabal, J., Lacruz, F., Quesada, Pedro, Gallego, J., Ferini-Strambi, L., Marcone, A., Garancini, P., Tedesi, B., Jacob, B., Rozewicz, L., Langdon, D., Davie, C., Ron, M., Thompson, A., Koepp, M. J., Hansen, M. L., Guldin, B., Pressler, R. M., Ried, S., Scholz, C., Monaco, F., Gianelli, M., Schiavalla, M. P., Naldi, P., Cantello, R., Torta, R., Verze, L., Mutani, R., Knott, H., Ferbert, A., Schulze-Bonhage, A., Aust, W., Di Mascio, R., Marchioli, R., Vitullo, F., Di Pasquale, A., Sciulli, L., Kramer, V., Tognoni, G., Santacruz, P., Lopez, R., Marti, M. J., Charques, I., Catafau, A., Lomeila, F., Peila, J., Bertran, I., Blesa, R., Krendel, D. A., Costiga, D. A., Koeppen, S., Korn, W. M., Brugge, S., Schmitz, D., Scheulen, M. E., King, R. H. M., Robertson, A. M., Thomas, P. K., Kerkhofs, A., Vermersch, P., Dereeper, O., Daems Monpeun, C., Parent, M., Deplanque, D., Petit, H., Campero, M., Serra, J., Ochoa, J. L., Martinez-Matos, J. A., Montero, J., Olivé, M., Rene, R., Vidaller, A., Gugenheim, M., Gouider, R., Le Guern, E., Brice, A., Agid, Y., Bouche, P., Grisold, W., Ziflo, U., Drlicek, M., Budka, H., Jellinger, K., Zielinski, C. H., Ginsberg, L., King, R. H. M., Workman, J., Platts, A. D., Thomas, P. K., Gherardi, R. K., Florea-Strat, A., Poron, F., Sabourin, J. -C., Fazio, R., Nemni, R., Franceschi, M., Lorenzetti, I., Rinaldi, L., Canal, N., Weilbach, F. X., Sennlaub, A., Jung, S., Gold, R., Toyka, K. V., Hartung, H. P., Giegerich, G., Ellie, E., Vital, A., Steck, A. J., Vital, C., Julien, J., Doneda, P., Pizzul, S., Scarpini, E., Chiodi, P., Ramacci, M. T., Livraghi, S., Maimone, D., Annunziata, P., Salvadori, C., Guazzi, G. C., Arne-Bes, M. C., Delisle, M. B., Fabre, N., Hurtevent, J. F., Bes, A., Baudoin-Martin, D., Laborde, E., Viallet, F., Creisson, C., Crespi, V., Bogliun, G., Marzorati, L., Zincone, A., D'Angelo, L., Liberani, A., Merlini, M., Rivolta, R., Creange, A., Sabourin, J. -C., Theodorou, I., Gherardi, R. K., Conti, A. M., Malosio, M. L., Baron, P. L., Scarlato, G., Chorao, R., Rosas, M. J., Leite, I., Callea, L., Donati, E., Bargnani, C., Bud, M., Verdu, E., Navarro, X., Braun, S., Einius, S., Poindron, P., Warier, J. M., Bradley, J., Bekkelund, S. I., Torbergsen, T., Mellgren, S. I., Carlomagno, S., Parlato, V., Santoro, A., Lavarone, A., Boller, F., Bonavita, V., Engelhardt, A., Lörler, H., Robeck, S., Kluglein, C., Comi, G., Avoledo, V., Locatelli, T., Leocani, L., Galardi, G., Magnani, G., Medaglini, S., Chkhikvishvili, T. S., Zangaladze, A., Bratoeva, M., Kovachev, P., Chavdarov, D., Artemis, N., Karacostas, D., Milonas, I., Arpa, J., Lopez-Pajares, R., Cruz-Matinez, A., Sarria, J., Palomo, F., Alonso, M., Rodriguez-Al-barino, A., Lacasa, T., Nos, J., Barreiro, P., Martinez, A. Cruz, Villoslada, C., Alons, M., Taghavy, A., Hamer, H., Kratzer, A., Dethy, S., Pauwels, T., Monclus, M., Luxen, A., Goldman, S., Ziegler, M., Crambes, O., Ragueneau, I., Arnaud, F., Zappia, M., Montesanti, R., Colao, R., Palmieri, A., Branca, D., Nicoletti, G., Rizzo, M., Parlato, G., Quattrone, A., Vanacore, N., Zuchegna, P., Bonifati, V., Meco, G., Scholz, J., Friedrich, H. -J., Rohl, A., Ulm, G., Vieregge, P., Savettieri, G., Rocca, W. A., Meneghini, F., Grigoletto, F., Morgante, L., Reggio, A., Salemi, G., Di Pierri, R., OzckmekÇi, S., Ertan, S., Yeni, N., Apaydin, H., Erkol, G., Kiziltan, G., Denktas, F., Ranoux, D., de Recondo, J., Ostergaard, L., Werdelin, L., Odin, P., Lindvall, O., Dupont, E., Christensen, P. B., Boisen, E., Jensen, N. B., Schmiegelow, M., Ingwersen, S. H., Matias-Guiu, J., Canet, T., Falip, R., Martin, R., Galiano, L., Voloshin, M. Y., Burchinskaya, L. F., Cabrera-Valdivia, F., Jimenez-Jimenez, F. J., Molina, J. A., Fernandez-Calle, P., Vazquez, A., Canizares-Liebana, F., Larumbe-Lobalde, S., Ayuso-Peralta, L., Rabasa, M., Codoceo, R., Arrieta, F. J., Aguilar, M. V., Jorge-Santamaria, A., Martinez-Para, M. C., Alarcon, J., Mateo, D., Gimenez-Roldan, S., Gencheva, E., Tzonev, T. z., Georgiev, G., Petkova, P., Gasparini, M., Vanacore, N., Meco, N. G., de la Sierra, G., Aguado, F., Revilla, M., Varela, L., Rico, H., Feve, A., N'Guyen, J. P., Bathien, N., Fenelon, G., Veroust, J., Cesaro, P., Egersbach, G., Hattig, H., Schelosky, L., Wissel, J., Poewe, W., Durif, F., Albuisson, E., Debilly, B., Tournilhac, M., Magnani, C., Mocellini, C., Soffietti, R., Schiffer, D., Cardozo, A., Cruz-Sanchez, F. F., Falip, L., Potagas, G., Ziegler, M., Rondot, P., Bonifati, V., Fabrizio, E., Meco, G., Bostantjopoulou, S., Katsarou, Z., Kyriazis, G., Baas, H., Demisch, L., Esser, A., Zoeller, F., Burklin, F., Harder, S., Fischer, P. A., Arcusa, M. J., Hermandez, S., Claramonte, F. J., Pascual, A. Pascual- Leone, Alonso, M. D., Catata, M. D., Alessandri, A., Giustini, P., Dufour, A., Ciusani, E., Nespolo, A., Roelcke U., Radu E. W., von Ammon K., Maguire R. P., Leenders K. L., Radionova, M., Chavdarov, D., Bratoeva, M., Tzekov, Ch., Pietrangeli, A., Bove, L., Pace, A., Falqui, L., Jandolo, B., Potemkowski, A., Muller B., Reinhard I., Krone A., Warmuth M., Brocker E. M., Krauseneck P., Meyding-Lamadé, U., Krieger, D., Sartor, K., Hacke, W., Maugard-Louboutin, C., Fayet, G., Sagan, C., Martin, S., Ménégalli, D., Lajat, Y., Resche, F., Koriech, O. M., Al Moutaery, K., Yaqub, B., Jochens, R., Wolters, A., Venz, S., Cordes, M., Hecht, B. K., Chatel, M., Gaudray, P., Turc-Carel, C., Gioanni, J., Ayraud, N., Hecht, F., Rumbach, L., Racadot, E., Bataillard, M., Billot, M., Pariset, J., Wijdenes, J., Montalban, Rio J., Tintoré, M., Galan, I., Acarin, N., Rapaport, S., Huberman, M., Shechtcr, D., Karabudak, R., Kilinc, M., Boyacigil, S., Cila, A., Polo, J. M., Setien, S., Sanchez, R., Figols, J., Zubimendi, A., Nadareishvili, Z. G., Massot, R., Marés, R., Gallecho, F., Richart, C., Hernandez, M. A., Garcia, M. R., Lorenzo, J. N., Leon, C., Muros, M., Togores, J., Kutluk, K., Damlacik, G. A., Tekinsoy, B., Obuz, O., Baklan, B., Idiman, E., Genc, K., Zielasek, J., Schmidt, B., Liew, F. Y., Gulay, Z., Yulug, N., Wong, K. S., Wong, T. W., Yu, T. S., Kay, R., Poupon, R., Giral, P., Roberti, C., Zanette, E. M., Chiarotti, F., Brusa, L., Cerbo, R., Prusinski, A., Pondal, M., Canton, R., Dominigo, Erodriguez J., Pereira Monteino J. M., Pereira Monteino X., Pardo, J., Carroacedo, A., Barros, F., Lema, M., Castillo, J., Melchor, A., Montiel, I., Guiu, J. Matias, Kloss, T. M., Keidel, M., Jacob, M., Idiman, F., Idman, E., Ozturk, V., Metin, E., Yilmaz, M., Gerard, J. M., Bouton, R., Decamps, D., Herbaut, A. G., Delecluse, F., Cavenaile, M., Divano, L., Chazot, G., Boureau, F., Emile, J., Bertin, L., d'Allens, H., Ferro, J. M., Costa, I., Carletto, F., Catarci, T., Padovani, A., Iandolo, B., Bartoli, M., Bonamini, M., Pulcinelli, F., Pignatelli, P., Russo, M., Gazzaniga, P. P., Barros, J., Pinheiro, J., Correia, A. P., Monteiro, J. M. Pereira, Alvarez-Cermeno, J. C., Avello, G., Sastre, J. L., Vecino, A., Cesar, J. M., Leone, M., Stankov, B., D'Amico, D., Maltempo, C., Moschian, F., Fraschini, F., Bussone, G., Molto, J. M., Fernandez, E., Fernandez, A. Morento, Barreiro, A., Siclia, J., Castejon, P., Mihout, B., Malberin, M., Salzman, V., Bogousslavsky, J., Meneghetti, G., Baracchini, C., Bozzato, G., Marini, B., Mendel, T., Czlonkowska, A., Pasierski, T., Szwed, H., Marta-Moreno, J., Lopez-Delval, J., Mostacero, E., Morales, F., Mahagne, M. H., Rogopoulos, A., Bertrand, F., Bedoucha, P., Lanteri-Minet, M., Riva, D., Zorzi, C., Milani, N., Vajsar, J., Ronen, G., Macgregor, D., Becker, L., Susseve, J., Seidl, Z., Faber, J., Obenberger, J., Springer, R., Bax, R. T., Eckardt, T., Czettritz, G. V., Emmrich, P., Vlaski-Jekic, S., Petrova, V., Cherninkova, S., Gudeva, T., Tzekov, C., Devoti, M., Franceschetti, S., Mientus, S., Vienna, P., Vashtang, Y., Tazir, M., Assami, S., Oulbani, D., Kaci Ahmed, M. Ait, Andersen, G., Vestergaard, K., Riis, J. O., Chavdarov, D., Corbo, M., Previtali, S., Allen, R. R., McKay, W. C., Rowbotham, M. C., Castellvi-Pel, S., Banchs, I., Kruyer, H., Corral, J., Saugeir-Veber, P., Munnich, A., Bonneau, D., Rozet, J. M., Le Merrer, M., Boespflug-Tanguy, O., Gokyigit, A., Oktem, O., Demir, G., Caliskan, A., Gardiner, R. M., Shorvon, Simon, Wieser, Heinz -Gregor, Hossmann, K. A., Steinberg, A., van Crevel, H., Ducros, A., Labauge, P., Pinsard, N., Ponsot, G., Gouttiere, F., Gastaut, J. L., Delrieu, O., BesanÇon, V., Klopstock, T., May, A., Seibel, P., Papagiannuli, E., Reichmann, H., Gurses, C., Aykut, C., Aktan, S., De Vuono, G., Fiacco, F., Gazzaniga Pozzill, P. P., Assuerus, V., Jacomet, C., Picard, O., Rozenbaum, W., Nueckel, M., Osschmann, P., Horning, C. R., Caldarelli-Stefano, R., Omodeo-Zorini, E., Rivolta, G. E., Maserati, R., Cagni, A., Ferrante, P., Lamadé, W., Heb, Th., Gosztonyl, G., Daral, G., Fresquet, C., Storch-Hagenlocher, B., Wildemann, B., Jager, G., Fuhry, L., Van Paesschen, W., Grunewald, R. A., Duncan, J. S., Connelly, A., Jackson, G. D., Sisodiya, S., Raymond, A. A., Shorvon, S. D., Fish, D. R., Stevens, J. M., Savic, I., Pauli, S., Thorell, J. O., Browne, R. H., Kornhuber, J., Retz, W., Riederer, P., Boon, F., Calliauw, L., Hoksergen, I., Thiery, E., Caemert, J., Decoo, D., Desomer, A., Chevalier, Y., Grinspan, A., Hirsch, E., Moszkowski, J., Marescaux, C., Yaqub, B. A., Valdueza, J. M., Puchner, M. J. A., Dammann, O., Vortmeyer, A., Herrmann, H. -D., Peterson, W., Prevett, M. C., Cunningham, V., Brooks, D. J., Pomes, A., Sunol, C., Durwen, H. F., Confavreux, Ch., Grimaud, J., Saddier, P., Moreau, T., Cortinovis-Tourniaire, P., Aimard, G., Adeleine, P., Paty, D. W., Wiles, C. M., Midgard, R., Riise, T., Kvale, G., Nyland, H., Stodal, H., Haase, A., Lassmann, H., Deeb, S. M. Al., Bruyn, G. W., Semana, G., Teisserenc, H., Alizadeh, M., Loiseau, P., Birebent, B., Yaouanq, J., Genetet, B., Sabouraud, O., Charron, D. J., Shaw, C. E., Stelmasiak, C., Solski, J., Nowicki, J., Jakubowska, B., Ryba, M., Grieb, P., Garcia-Merino, A., Usuku, K., Yunis, E., Alper, C., Hauser, S. L., Betuel, H., Gebuhrer, L., Salier, J. P., Kellar-Wood, H., Govan, G. G., Bromberg, J. E. C., Rinkel, G. J. E., Algra, A., Moulin, T., Stojkovic, T., Chavrot, D., Klotzsch, C., Kaiser-Rub, K., Nahser, H. C., Klijn, C. J. M., Tulleken, C. A. F., Rappelle, L. J., Daffertshofer, M., Kother, J., Hornig, C. R., Rust, D. S., Busse, O., Laun, A., Corabianu, O., Berbinschi, A., Chastang, C., Cophignon, J., Haguenau, M., Ketelslegers, J. M., Jander, S., Kramer, M., Schröter, M., Witte, O. W., Stoll, G., Möbner, R., Barak, V., Sarova-Ponchas, I., Holon, Le Coz, P., Woimant, F., George, B., Merland, J. J., Chleide, E., Casademont, J., Barrientos, A., Cardellach, F., Cervantes, F., Grau, J. M., Montoya, J., Rozman, C., Urbano-Marquez, A., Nunes, V., Lane, R. J. M., Archard, L. C., Schapira, A. H. V., Cooper, J. M., Barnes, P. R. J., Kemp, G. J., Taylor, D. J., Toscano, A., Garavaglia, B., Vita, G., Rodolico, C., Aguennouz, M., Messina, C., Mariottu, C., Uziel, G., Carrara, F., Mora, M., Zeviani, M., Mahe, B., Milpied, N., Bernasconi, P., Torchiana, E., Simoncini, O., Dalakas, M. C., Goebels, N., Michaelis, D., HÄcker, G., Ptacek, L., Gonzalez, A., Sevilla, T., Diaz, C., Baggi, F., Andreetta, F., Bielicki, G., Tanguy, A., Zanca, M., Renou, J. P., De Deyn, P. P., Marescau, B., Pickut, B. A., Cobo, A. M., Emparanza, J. L., Munain, A. Lopez de, Marti-Masso J. F., Ciafalon, E., Bardoni, A., Fortunato, F., Garghentino, R., Roses, A., Metz-Lutz, M. N., Coquerel, A., Pfaff, F., Dussallant, M., Gaudriault, G., Zsurger, N., Le Cam-Duchez, V., Berod, A., Vincent, J. P., Tayot, J., Rostene, W., Giraud, G., Minault, C., Vallée, J., Cailloux, F., Law, L., Paulson, O. B., Britton, T. C., Dones, I., Servello, D., Molteni, F., Mariani, G., Broggi, G., Hassan, S. M., Jennekens, F. G. I., Wieneke, G., Veldman, H., Fritz, C., Braune, H. -J., Sullivan, E. P. O., Jenkins, I. H., Henderson, L., Kennard, C., Brunholzl, Ch., Calvet, J. Pascual, Insa, Jm. Soler, Serradell, A. Pou, Coria, F., Rubio, I., Garcia, M. A., Duarte, J., Sempere, A. P., Claveria, L. E., Blanco, I., Ferrarini, M., Testa, D., Cazzaniga, C., Farinotti, M., Filippini, G., Hawkes, C. H., Graham, A., McDonald, A., Chroni, E., Heatley, F. W., Spencer, G. T., Moulard, B., Camu, W., Dhib, M., Diaye, M. N., Malafosse, A., Meininger, V., Billiard, M., Baldy-Moulinier, M., Léger, J. M., Harpin, M. L., Willison, H. J., Veitch, J., Herron, B., AlMemar, A., Reiners, K., Michels, M., Hughes, R. A. G., Heidenreich, F., Archelos, J. J., Uchuya, M., Graus, F., Feltri, L., Scherer, S. S., Wrabetz, L., van Schaik, I. N., Vermeulen, M., Brand, A., Tekin, S., Afsar, N., Sarropoulos, A., (née Schönbeck), S. Spuler, Schönhuber, R., Espadaler, J. M., Fardeau, M., Pino, I. M., Diez Tejedor, E., Rio, F. Garcia, Prados, C., Gomez, L., Munoz, J., Bouchard, C., Barrett, M. J., Coulton, G. R., Casadevall, J., Sala, R. Alvarez, Garcia, J. M. Pino, Dupuis, M. J. M., Mezt, R., Jean, D., Maes, E., Smits, R. C. F., Emmen, H. H., Kulig, B. M., van Loenen, A. C., de Waal, R., van Diemen, H. A. M., Koetsier, J. C., Ince, D., Ferri, R., Durelli, L., Bangioanni, M. R., Ferrero, B., Riva, A., Bergaasco, B., Stenager, E., Stenager, E. N., Jensen, K., De Andres, C., Anaya, F., Dimova, V., Hansen, A. W., Norby, S., Edal, A. L., Rosenberg, T., Thorpe, J. W., Filippi, M., Horsfleld, M. A., Reganati, P., Baratti, C., Bressi, S., Ozurk, V., Yeil, S., Rodegher, M., Sirabian, G., Alberoni, M., Eoli, M., La Mantia, L., Manetti, E., Zaffaroni, M., Milanese, C., Corsini, E., de Castro, P., Carreno, M., Iriarte, J., Heide, W., Barado, J., Echaniz, P., Cuadrado, E., Baykan-Kurt, B., Oktem-Tanor, O., Bahar, S., Konyalioglu, R., Tumac, A., Gok, S., Gurvit, H., Gursoy, G., Henderson, C. E., Westarp, M. E., Perron, H., Hoff-Jörgensen, R., Rasmussen, H., Schraff, S., Kornhuber, H. H., Moseley, I. F., Colangelo, A. M., Fetoni, V., Parati, E., Austoni, L., DiGiovanni, A., Meucci, N., Nobile-Orazio, E., Scarlato, G., Goi, G., Lombardo, A., Bairati, C., Aversa, E., Caputo, D., Ferrarese, C., Canafoglia, L., Frigo, M., Pecora, N., Riva, R., Frattola, L., Carpo, M., Gamba, M., Meussi, N., Barbieri, S., Ostermeyer, B., Patten, B. M., Abeta, S., Inoue, N., Matsui, H., Yoshino, Y., Pizzi, C. Delli, Ragno, M., Losseff, N. A., Fletcher, N. A., Thorpe, J., Droogan, A. G., Harper, R., Hawkins, S. A., Patterson, V. H., Bell, P., Soeterboek, A. A. J., Koehler, P. J., Urtasun, M., Vilchez, J., Castel-lvi-Rel, S., Gine, R., Villa, M., Koehler, W., Kumar, A. J., Edwin, D., Moser, H. W., Guidetti, D., Ferlini, A., Motti, L., Bondavalli, M., Patrosso, M. C., Ghidoni, E., Alfaro, A., Giros, M. L., Barcelo, A., Piqueras, A., Martinez, V., Rango, M., Bamonti, F., Greco, F., Spagnoli, D., Tomei, G., Zetta, L., Honczarenko, K., Jezewski, T., Kojder, I., Verlooy, J., Reempts, Jos V., Deuren, B. V., Borgers, M., Gajda, J. U., Ley-Pozo, J., Louwen, P., Happe, S., Buschmann, H. C., Ringelstein, E. B., Yamawaki, T., Takao, M., Suzuki, N., WeilBenborn, K., Schellong, S., Ehrenheim, C., Wollenhaupt, J., Goetz, C., Lubach, D., Vion-Dury, J., Nicoli, F., Confort-Gouny, S. O., Dhiver, C. O., Lamoureux, S., Salvan, A. M., Gastaut, J. -A., Gastaut, J. -L., Cozzone, P., Ribalta, T., Santamaria, J., Drewes, A. M., Taagholt, S. J., van den Berg, J. S. P., Limburg, M., Valldeoriola, F., Valls-Solé, J., Marti, M. J., Trenkwalder, C., Stiasny, K., Collado-Scidel, V., Wetter, T., Kazenwadel, J., Kohnen, R., Ramm, S., Oertel, W. H., Thajeb, P., Starck, M., Albrecht, H., Pollmann, W., Konic, N., Split, W., Sulkowski, W., Kowalska, S., Sawradewicz-Rybak, M., Musior, M., Scaioli, V., Brock, S., Ciano, C., Palazzini, E., Servan, J., Aoba, S., Yamaguchi, S., Johkura, K., Rosin, L., Solimena, M., De Camilli, P., Meinck, H. -M., Roquer, J., Marti, N., Cano, A., Pou-Serradell, A., Robeck, S., Enqelhardt, A., Kalden, J. R., Dhaenens, G., Tyrdal, S., Broere, C. A. J., Polman, L. J., Gomez, R., Alberdi, M., Delgado, J. M., Kansu, E., Saribas, O., Zileli, T., Proust, F., Freger, P., Creissard, P., Proano, J., Patrignani, J., Castro, J., Ugarte, A., Giros, Ma. L., Pampols, Ta., Sabev, C., Gikova, S., Antonova, N., Georgieva, L., Stanev, V., Popova, G., Kostadinova, S., Pepeliarska, M., Pierre-Jerome, C., Bekkelund, S. I., Husby, G., Mellgren, S. I., Attaccalite, A., Guidi, M., Passero, S., Caruso, V., HÄgele, J., Lohmeyer, J., Heilmann, M., Ohly, A., Ceballos-Baumann, A. O., Joussen, K., Sonka, K., Chave, B., Confort-Gouny, S., Houallah, T., Neundoerfer, B., Tex, S., Seeber, C., Mokrusch, T., Urdiain, T. X. Arbizu, Yelamos, S. M., Villanueva, P., Serra, J. Peres, Braghi, S., Bonifacio, E., Natali-Sora, M. G., Debbink, Y. N., Marra, T. R., Mossman, S., Timmings, P., Seitz-Dertinger, S., Solbach, W., Mainz, A., Manfredini, E., Calabrese, E., Allaria, S., Mariani, C., Sinaki, M., Lynn, S., Westerlind, K., Ossege, L. M., Voss, B., Wiethege, Th., Sindern, E., Malin, J. p., Le Doze, F., Chapon, F., de la Sayette, V., Schaeffer, S., Dary, M., Lechevalier, B., Viader, F., de Pommery, J., Weill-Fulazza, J., Menetrey, M., Lazzarino, L. G., Nicolai, A., Nappo, A., Blin, J., Mazetti, P., Mazoyer, B., Ayed, S. Ben, Rivaud, S., Vidailhet, M., Pierrot-Deseilligny, C., Chase, T., Jordan, K. G., Gergaud, J. M., Breux, J. P., Roblot, P., Grollier, G., Giraudon, B. Becq, Dobato, J. L., Gilabert, Y. Perez, Blanco, J. L. Munoz, de Kruijk, J., Twijnstra, A., Wilmink, J., Leffers, P., Iniguez, C., Jimenez-Escrig, A., Nocito, M., Villar, M. L., Gonzalez-Porque, P., Gobernado, J. M., Chandler, H. C., Crockard, H. A., Henderson, F., Rossi, T., Maidani, M., Pujol, A., Rimola, A., Beltran, J., Garcia-Valdecasas, J. C., Navasa, M., Grande, L., Galofre, J., Visa, J., Rodes, J., Ruiz, M., Pampols, T., Bruce, L., Tanner, M. J. A., Lefaucheur, J. P., Verroust, J., Taghavy, A., Hamer, H., Benomar, A., Cancel, G., Stevanin, G., Durr, A., Labaune, C., Desnizza, V., Widjaja-Cramer, B., Schulze-Bonhage, A., Kott, H., Ferbert, A., Sanz-Sebastian, C., Pascual, L. F., Alegria, F. Abad, Kushnir, M., Groozman, G. B., Korczyn, A. D., Drory, Ve., Korczyn, A., Guggenheim, H., Baykouchev, St., Struppler, A., Tchalucova, N., Jotova, J., Mokri, B., Parisi, J. E., Scheithauer, B. W., Piepgras, D. G., Miller, M., Kornhuber, A. W., Köhler, A., Hülser, P. J., Kriebel, J., Alonso-Villaverde, C., Castro, A., Masana, L., Urda, A. Martin, Fernandez, J., Mares, R., Torre, L., Mayayo, E., Lossos, A., Gomori, M., Libson, E., Goldfarb, A., Seigal, T., de Louw, A., Praamstra, P., Horstink, M., Cools, A., Tarrats, E. Basart, Calopa, M., Martinez, S., Ballabrina, J., Taussig, D., Marion, M. -H., Mallecourt, J., Ranoux, D., Gasser, T., Kabus, C., Ozelius, L., Wenzel, R., Breakefield, X. O., Boot, H., Poublon, R. M. L., Bogaard, J. M., GinaÏ, A. Z., Cabezas, C., Scholz, J., Nitschke, N., Vieregge, P., Wirk, B., Hochberg, F. H., Hefter, H., Kessler, K., Wirrwar, A., Stocklin, G., Tournier-Lasserves, E., Agundez, J. Garcia, Ruiz, E., Li, X. P., Hedlund, P. B., Fuxe, K., Kulisevsky, J., Avila, A., Berthier, M. L., Gerard, J. -M., Cambier, J., Caucheteur, C., Deuschl, G., Köster, B., Scheidt, C., Lücking, C. H., Mena, M. A., Chedru, F., Oubary, P., Rondot, P., Anagnostou, C. N., Panagopoulos, C. P., Ziogas, D. E., Vermersch, P., Robitaille, Y., Gauvreau, D., Destée, A., Delacourte, A., Ficola, U., Marozzi, P., Piccoli, F., Janelidze, M., Shakarishvili, R., Gagoshidze, T., Vashadze, T., Tsiskaridze, A., Djannelidze, M., Trullen, J. M. Perez, Pardo, P. J. Modrego, Vazquez-Andre, M. L., Bail, L., Naccache, L., Gauvrit, J. L., Panisset, M., Boller, A. F., Giannini, M., Zanette, E., Di Cesare, S., Altieri, M., Maloteaux, J. M., Delwaide, C., Sciaky, M., Newman, S. K., Kennedy, A. M., Frackowiack, R. S. J., Warrington, E. K., Rossor, M. N., Martinez-Lage, Pablo, Martinez Lage, J. Manuel, Manubens, JosÇ M., Lacruz, Francisco, Larumbe, Rosa, Muruzabal, Javier, Locatelli, T., Cursi, M., Mauri, M., Liberati, D., Fornada, C., Iriarte, L. M., Lopez, M., Grilo, A., Repeto, M., Brasic, J. R., Barnett, J. Y., Sheitman, B. B., Young, J. G., Shalit, F., Brodie, C., Sredni, B., Engelien, A., Stern, E., Huber, W., Frith, C., Miralles, F., Albadalejo, M. D., Antem, M., Pastor, I., Estelies, M. A., Del Ser, T., Ochoa, H. Severo, Munoz, D., Hachinski, V., Cucinotta, D., Senin, U., Girardello, R., Crepaldi, G., Croria, F., Schens, D. B., Vigo-Pelfrey, C., SempereE, A. P., Ortega, M. P., Bava, L., Magni, E., Aronovich, B. D., Treves, T. A., Bornstein, N. M., Van Blercom, N., Blecic, S., Violon, Ph., Hildebrand, J., Zamboni, M., Ambrosoli, L., Poli, A., Kuehnen, J., Tilgner, C., Raltzig, M., Moering, B., Faiss, J., Deeb, S. M. Al, Daif, A., Sharif, H., Tatay, J., Caroeller, F., Avendano, C., Vinogradova, T., Pinto, A. N., Canhao, P., Neau, J. -Ph., Pacquereau, J., Meurice, J. -C., Schwab, M., Bauer, R., Deeb, M. AL, Tjan, T. J., Aabed, M., Berges, S., Crepin-Leblond, T., Chavot, D., Cattin, F., Snidaro, M. H., Chopard, J. L., Ley, C. Oliveras, Alameda, F., Alfonso, S., Podobnik-Sarkanji, S., Pniewski, J., Torbicki, A., Mieszkowski, J., Plaza, I., Petrunjashev, V., Velcheva, I., Hadjiev, D., Yancheva, S., Petrov, L., Karakaneva, S., Petkov, A., Nikolov, E., Niehaus, L., Sacchetti, M. L., Toni, D., Fiorelli, M., Gori, C., Argentino, C., Lyrer, Ph., Radu, E. W., Gratzl, O., Rondepierre, Ph., Leclerc, X., Marchau, Jr, M., Scheltens, Ph., Hamon, M., Janssens, E., Henon, H., Lucas, C., KuÇukoglu, H., Baybas, S., Dervis, A., YalÇiner, B., Yilmaz, N., Ozturk, M., Arpaci, B., Navarro, J. A., Arenas, J., Perez-Sempere, A., Egido, J. A., Soriano-Soriano, C., Beau, P., Gergaud, J. -M., Coudero, C., Dierckx, R. A., Dobbeleir, A., Timmermans, E., Vandevivere, J., Lucas, C. H., Gomez, M., Aguirre, J., Berenguer, A., Duran, C., Parrilla, J., Gonzalez, F., Gironell, A., Rey, A., Marti-Vilalta, J. L., de Lecinana, M. Alonso, Federico, F., Conte, C., Simone, I. L., Giannini, P., Liguori, M., Lucivero, V., Picciola, E., Tortorella, C., Drislane, F., Wang, A. Ming, Di Mascio, R., Marchioli, R., Vitullo, F., Di Pasquale, A., Sciulli, L., Kramer, V., Tognoni, G., Levivier, M., del Olmo, A., Caballero, E., Degaey, I., de Bruijn, S. F. T. M., Tchaoussoglou, I., Bastianello, S., Pozzilli, C., Cervello, A., Catala, N., Koskas, F., Kieffer, E., Botia, E., Vivancos, J., Leon, T., Segura, T., Ramo, C., Lopez, F., Karepov, V. G., Gur, A. J., Berlanga, B., Gracia, V., Fiol, C., Kurtel, H., Ozkutlu, U., Yegen, B., Grau, A. J., Buggle, F., Heindle, S., Steichen-Wiehn, C., Banerjee, T., Maiwald, M., Becher, H., Villafana, W., Medina, F., Fernandez-Real, J. M., Soler, S., Planas, E., Iceman, E., Doganer, I., Badlan, G., Genc, B., Yulug, K., Ideman, E., Dural, H., Kutlul, K., Damalik, G., Baklan, Y., Metin, B., Tekinsoy, E., Iriarte, I., Subira, M. L., Crockar, A. D., Treacy, M., McNell, T. A., Grazzi, L., Ediboglu, N., Bilgin, H., Ertas, S., Goument, J. -P., Basset, C., Campos, Y., Garcia-Silva, T., Cabello, A., Bussaglia, E., Tizzano, E., Colomer, J., Gimbergues, P., Campagne, D., Bommelaer, C., Delaguillaume, B., Ramtami, H., Ait-Kaci-Ahmed, M., Pascual L. F., Fernandez T., Hortells M., Sanz C., Morales F., Lauritzen, L., Picard, F., Sellal, F., Collard, M., Avramidis, T., Alexiou, E., Anastopoulos, T., Frongillo, D., Delfino, F. A., Cannata, M., Calo, L., Vichi, R., Antonini, G., Fragola, V., Cannata, D., Salas, M., Ruiz, C., Angelard, B., Lacau, J., Guily, St., Sendtner, M., Goadsby, Peter J., Quin, N. P., Gadian, D. G., Roland, P. E., Seitz, Rudiger J., Frackowiak, Richard S. J., Becker, G., Krone, A., Schmidt, K., Hofmann, E., Bogdahn, U., Rosenfeld, M. R., Meneses, P., Kaplitt, M. G., Dalmau, J., Posner, J., Cordon-Cardon, C., Hoang-Xuan, K., Vega, F., Nishisho, I., Moisan, J. P., Theillet, C., Delattre, O., Zhu, Jiahong, Walther, W., Posner, J. B., Roelcke, U., von Ammon, K., Pellikka, R., Lucking, C. H., Walon, C., Boucquey, D., -Van Rijckevorsel, K. Harmant, Lannoy, N., Verellen-Dunoulin, Ch., Liszka, U., Cavaletti, G., Casati, B., Kolig, C., Bogliun, G., Marzorati, L., Johannsen, L., Chio, A., Ruda, R., Vigliani, M. C., Sciolla, R., Seliak, D., Hoang-Xuang, K., Villanueva, J. A., Montalban, X., Arboix, A., Colosimo, C., Albanese, A., Hughes, A. J., de Bruin, V., Lees, A. J., Kowalski, J. W., Banfi, S., Santoro, L., Perretti, A., Castaldo, I., Barbieri, F., Campanella, G., Bhatia, K. P., Mardsen, C. D., de Bruin, V. S., Machedo, C., Ceballos-Baumann, D., Marsden, C. D., Brooks, D. B. J., Wennlng, G. K., Quinn, N., McDonald, W. l., Warner, T. T., Bain, P. C., Davis, M. B., Conway, D., Shaunak, S., O'Sullivan, E., Crawford, T., Lawden, M., Blunt, S., Rapoport, A., Sarova-Pinchas, I., de Beyl, D. Zegers, Mavroudakis, N., Blanc, S., Godinot, C., Lenoir, G., Barkhof, M. S. F., Tas, M. W., Baron, P. L., Constantin, C., Cassatella, M. A., Langdon, D. W., Webb, S., Gasparini, P., Zeviani, A., Kidd, D., Mammi, S., Cahalon, L., Hershkoviz, R., Lahat, N., Wallach, D., Annunziata, P., Martino, T., Maimone, D., Guazzi, G. C., Porrini, A. M., Dell'Arciprete, L., Rothwell, P. M., Stewart, R. R. C., Cull, R. E., Willmes, K., Poeck, K., Russell, D., Braekken, S. K., Brucher, R., Svennevig, J., Hermesl, M., Bruckmann, H., Biraben, A., Sliwka, U., Meyer, B., Schondube, F., Noth, J., Lavenu, I., Lammers, C., Waldecker, B., Haberbosch, W., Stam, J., Schneider, R., Gautier, J. C., Berlit, T. P., Fauser, B., Kuhne, D., Geraud, G., Danielli, A., Larrue, V., Bes, A., Timmerman, E., Bono, F., Bruni, A. C., Valalentino, P., Montesi, M. P., Talerico, G., Zappia, M., Sabatelli, M., Quattrone, A., Pareyson, D., Lorenzetti, D., Sghirlanzoni, A., Castellotti, B., Lupski, J. R., Archidiacono, N., Antonacci, R., Marzella, R., Rocchi, M., Samuel, D., Goulon-Goeau, C., Costa, P. P., Bismuth, H., Said, G., De Jongh P., Lofgren A., Timmerman V., Vance J. M., Van Broeckhoven C., Martin J. -J., Martinez, A. Cruz, Bort, S., Arpa, J., Misra, P., King, R. H. M., Badhia, K., Anderson, M., Caballo, A., Vichez, J., Gabriel, J. M., Erne, B., Miescher, G. C., Ulrich, J., Vital, A., Vital, C., Steck, A., Petry, K., Labatut, I., Hilmi, S., Ellie, E., Ferrini-Strambi, L., Zucconl, M., Marchettini, P., Palazzi, S., Oehlschlager, M., Pepinsky, R. B., Gemignani, F., Marbini, A., Pavesi, G., Di Vittorio, S., Manganelli, P., Mancia, D., Vermersh, P., Roche, J., Durocher, A. M., Dewailly, Ph., Dettmers, C., Fink, G., Lemon, R., Stephan, K., Passingham, D., Weder, B., Knorr, U., Huang, Y., Butterfield, D. A., Peris, M. L., Peiro, C., Pascual, A. Pascual-Leone, Bottini, G., Folnegovic-Smalc, V., Knezevic, S., Bokonjic, R., Ersmark, B., Torres, M. Gonzalez, Guiraud-Chaumeil, B., Haugaard, K., Jovicic, A., Chr, Lang, Levic, Z., Parra, C. Martinez, Ochoa, J. Patrignani, Titlbach, O., Wikkelso, C., Caparros-Lefevre, D., Debachy, B., Verier, A., Cantinho, G., Santos, A. I., Godinho, F., Bagunya, J., Roig, T., Ensenyat, A., Santiag, O., Trabucchi, H., De Leo, D., Koch, Ch., Zeumer, H., Matkovic, Z., Morris, P., Donaghy, M., Köhler, W., Kammer, T., Röther, J., Navon, R., Fontaine, B., Wu, Y., Capdevila, A., Guardiola, M. J., van Dijk, G. W., Notermans, N. C., Kruize, A. A., Kater, L., Bertelt, C., Hesse, S., Friedrich, H., Mauritz, K. -H., Giron, L. T., Watanabe, I. S., Ewing, D., Koepp, M., Lempert, T., Sander, B., Kauerz, U., Mehdorn, H. M., Hezel, J., Eickhoff, W., Kryst, T., Timsit, S., Gardeur, D., Reis, Mitermayer Galvao dos, Secor, E., Filho, A. Andrade, Silva, M. Cardoso, Santos, S. R. Silveira, Vasilaski, G., Reis, E. A. dos, Velupillai, P., Harn, D. A., Tigera, J. Garcia, Dreke, R. Martinez, Crespo, R. Piedra, Besses, C., Acin, P., Massons, J., Florensa, L., Oliveres, M., Sans-Sabrafen, J., Wicklein, E. M., Pleiffer, G., Kunre, K., Dieterich, M., Brandt, Th., Guarino, M., Stracciari, A., Pazzaglia, P., D'Alessandro, R., Santilli, I., Donato, M., The European Velnacrine Study Group, The Dutch Guillain-Barré study group, The COP-1 Multicenter Clinical and Research Group Study, and European Study Group

Published
1994
Full Text
View/download PDF

35. Intronic ATTTC repeat expansions in STARD7 in familial adult myoclonic epilepsy linked to chromosome 2

Author

Corbett, MA, Kroes, T, Veneziano, L, Bennett, MF, Florian, R, Schneider, AL, Coppola, A, Licchetta, L, Franceschetti, S, Suppa, A, Wenger, A, Mei, D, Pendziwiat, M, Kaya, S, Delledonne, M, Straussberg, R, Xumerle, L, Regan, B, Crompton, D, van Rootselaar, A-F, Correll, A, Catford, R, Bisulli, F, Chakraborty, S, Baldassari, S, Tinuper, P, Barton, K, Carswell, S, Smith, M, Berardelli, A, Carroll, R, Gardner, A, Friend, KL, Blatt, I, Iacomino, M, Di Bonaventura, C, Striano, S, Buratti, J, Keren, B, Nava, C, Forlani, S, Rudolf, G, Hirsch, E, Leguern, E, Labauge, P, Balestrini, S, Sander, JW, Afawi, Z, Helbig, I, Ishiura, H, Tsuji, S, Sisodiya, SM, Casari, G, Sadleir, LG, van Coller, R, Tijssen, MAJ, Klein, KM, van den Maagdenberg, AMJM, Zara, F, Guerrini, R, Berkovic, SF, Pippucci, T, Canafoglia, L, Bahlo, M, Striano, P, Scheffer, IE, Brancati, F, Depienne, C, Gecz, J, Corbett, MA, Kroes, T, Veneziano, L, Bennett, MF, Florian, R, Schneider, AL, Coppola, A, Licchetta, L, Franceschetti, S, Suppa, A, Wenger, A, Mei, D, Pendziwiat, M, Kaya, S, Delledonne, M, Straussberg, R, Xumerle, L, Regan, B, Crompton, D, van Rootselaar, A-F, Correll, A, Catford, R, Bisulli, F, Chakraborty, S, Baldassari, S, Tinuper, P, Barton, K, Carswell, S, Smith, M, Berardelli, A, Carroll, R, Gardner, A, Friend, KL, Blatt, I, Iacomino, M, Di Bonaventura, C, Striano, S, Buratti, J, Keren, B, Nava, C, Forlani, S, Rudolf, G, Hirsch, E, Leguern, E, Labauge, P, Balestrini, S, Sander, JW, Afawi, Z, Helbig, I, Ishiura, H, Tsuji, S, Sisodiya, SM, Casari, G, Sadleir, LG, van Coller, R, Tijssen, MAJ, Klein, KM, van den Maagdenberg, AMJM, Zara, F, Guerrini, R, Berkovic, SF, Pippucci, T, Canafoglia, L, Bahlo, M, Striano, P, Scheffer, IE, Brancati, F, Depienne, C, and Gecz, J

Abstract

Familial Adult Myoclonic Epilepsy (FAME) is characterised by cortical myoclonic tremor usually from the second decade of life and overt myoclonic or generalised tonic-clonic seizures. Four independent loci have been implicated in FAME on chromosomes (chr) 2, 3, 5 and 8. Using whole genome sequencing and repeat primed PCR, we provide evidence that chr2-linked FAME (FAME2) is caused by an expansion of an ATTTC pentamer within the first intron of STARD7. The ATTTC expansions segregate in 158/158 individuals typically affected by FAME from 22 pedigrees including 16 previously reported families recruited worldwide. RNA sequencing from patient derived fibroblasts shows no accumulation of the AUUUU or AUUUC repeat sequences and STARD7 gene expression is not affected. These data, in combination with other genes bearing similar mutations that have been implicated in FAME, suggest ATTTC expansions may cause this disorder, irrespective of the genomic locus involved.

Published
2019

36. Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3

Author

Florian, RT, Kraft, F, Leitao, E, Kaya, S, Klebe, S, Magnin, E, van Rootselaar, A-F, Buratti, J, Kuehnel, T, Schroeder, C, Giesselmann, S, Tschernoster, N, Altmueller, J, lamiral, A, Keren, B, Nava, C, Bouteiller, D, Forlani, S, Jornea, L, Kubica, R, Ye, T, Plassard, D, Jost, B, Meyer, V, Deleuze, J-F, Delpu, Y, Avarello, MDM, Vijfhuizen, LS, Rudolf, G, Hirsch, E, Kroes, T, Reif, PS, Rosenow, F, Ganos, C, Vidailhet, M, Thivard, L, Mathieu, A, Bourgeron, T, Kurth, I, Rafehi, H, Steenpass, L, Horsthemke, B, Berkovic, SF, Bisulli, F, Brancati, F, Canafoglia, L, Casari, G, Guerrini, R, Ishiura, H, Licchetta, L, Mei, D, Pippucci, T, Sadleir, L, Scheffer, IE, Striano, P, Tinuper, P, Tsuji, S, Zara, F, LeGuern, E, Klein, KM, Labauge, P, Bennett, MF, Bahlo, M, Gecz, J, Corbett, MA, Tijssen, MAJ, van den Maagdenberg, AMJM, Depienne, C, Florian, RT, Kraft, F, Leitao, E, Kaya, S, Klebe, S, Magnin, E, van Rootselaar, A-F, Buratti, J, Kuehnel, T, Schroeder, C, Giesselmann, S, Tschernoster, N, Altmueller, J, lamiral, A, Keren, B, Nava, C, Bouteiller, D, Forlani, S, Jornea, L, Kubica, R, Ye, T, Plassard, D, Jost, B, Meyer, V, Deleuze, J-F, Delpu, Y, Avarello, MDM, Vijfhuizen, LS, Rudolf, G, Hirsch, E, Kroes, T, Reif, PS, Rosenow, F, Ganos, C, Vidailhet, M, Thivard, L, Mathieu, A, Bourgeron, T, Kurth, I, Rafehi, H, Steenpass, L, Horsthemke, B, Berkovic, SF, Bisulli, F, Brancati, F, Canafoglia, L, Casari, G, Guerrini, R, Ishiura, H, Licchetta, L, Mei, D, Pippucci, T, Sadleir, L, Scheffer, IE, Striano, P, Tinuper, P, Tsuji, S, Zara, F, LeGuern, E, Klein, KM, Labauge, P, Bennett, MF, Bahlo, M, Gecz, J, Corbett, MA, Tijssen, MAJ, van den Maagdenberg, AMJM, and Depienne, C

Abstract

Familial Adult Myoclonic Epilepsy (FAME) is a genetically heterogeneous disorder characterized by cortical tremor and seizures. Intronic TTTTA/TTTCA repeat expansions in SAMD12 (FAME1) are the main cause of FAME in Asia. Using genome sequencing and repeat-primed PCR, we identify another site of this repeat expansion, in MARCH6 (FAME3) in four European families. Analysis of single DNA molecules with nanopore sequencing and molecular combing show that expansions range from 3.3 to 14 kb on average. However, we observe considerable variability in expansion length and structure, supporting the existence of multiple expansion configurations in blood cells and fibroblasts of the same individual. Moreover, the largest expansions are associated with micro-rearrangements occurring near the expansion in 20% of cells. This study provides further evidence that FAME is caused by intronic TTTTA/TTTCA expansions in distinct genes and reveals that expansions exhibit an unexpectedly high somatic instability that can ultimately result in genomic rearrangements.

Published
2019

37. HCN ion channels and accessory proteins in epilepsy: genetic analysis of a large cohort of patients and review of the literature

Author

Difrancesco, J, Castellotti, B, Milanesi, R, Ragona, F, Freri, E, Canafoglia, L, Franceschetti, S, Ferrarese, C, Magri, S, Taroni, F, Costa, C, Labate, A, Gambardella, A, Solazzi, R, Binda, A, Rivolta, I, Di Gennaro, G, Casciato, S, D'Incerti, L, Barbuti, A, Difrancesco, D, Granata, T, Gellera, C, DiFrancesco, Jacopo C., Castellotti, Barbara, Milanesi, Raffaella, Ragona, Francesca, Freri, Elena, Canafoglia, Laura, Franceschetti, Silvana, Ferrarese, Carlo, Magri, Stefania, Taroni, Franco, Costa, Cinzia, Labate, Angelo, Gambardella, Antonio, Solazzi, Roberta, Binda, Anna, Rivolta, Ilaria, Di Gennaro, Giancarlo, Casciato, Sara, D'Incerti, Ludovico, Barbuti, Andrea, DiFrancesco, Dario, Granata, Tiziana, Gellera, Cinzia, Difrancesco, J, Castellotti, B, Milanesi, R, Ragona, F, Freri, E, Canafoglia, L, Franceschetti, S, Ferrarese, C, Magri, S, Taroni, F, Costa, C, Labate, A, Gambardella, A, Solazzi, R, Binda, A, Rivolta, I, Di Gennaro, G, Casciato, S, D'Incerti, L, Barbuti, A, Difrancesco, D, Granata, T, Gellera, C, DiFrancesco, Jacopo C., Castellotti, Barbara, Milanesi, Raffaella, Ragona, Francesca, Freri, Elena, Canafoglia, Laura, Franceschetti, Silvana, Ferrarese, Carlo, Magri, Stefania, Taroni, Franco, Costa, Cinzia, Labate, Angelo, Gambardella, Antonio, Solazzi, Roberta, Binda, Anna, Rivolta, Ilaria, Di Gennaro, Giancarlo, Casciato, Sara, D'Incerti, Ludovico, Barbuti, Andrea, DiFrancesco, Dario, Granata, Tiziana, and Gellera, Cinzia

Abstract

The Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels are highly expressed in the Central Nervous Systems, where they are responsible for the I h current. Together with specific accessory proteins, these channels finely regulate neuronal excitability and discharge activity. In the last few years, a substantial body of evidence has been gathered showing that modifications of I h can play an important role in the pathogenesis of epilepsy. However, the extent to which HCN dysfunction is spread among the epileptic population is still unknown. The aim of this work is to evaluate the impact of genetic mutations potentially affecting the HCN channels’ activity, using a NGS approach. We screened a large cohort of patients with epilepsy of unknown etiology for mutations in HCN1, HCN2 and HCN4 and in genes coding for accessory proteins (MiRP1, Filamin A, Caveolin-3, TRIP8b, Tamalin, S-SCAM and Mint2). We confirmed the presence of specific mutations of HCN genes affecting channel function and predisposing to the development of the disease. We also found several previously unreported additional genetic variants, whose contribution to the phenotype remains to be clarified. According to these results and data from literature, alteration of HCN1 channel function seems to play a major role in epilepsy, but also dysfunctional HCN2 and HCN4 channels can predispose to the development of the disease. Our findings suggest that inclusion of the genetic screening of HCN channels in diagnostic procedures of epileptic patients should be recommended. This would help pave the way for a better understanding of the role played by I h dysfunction in the pathogenesis of epilepsy.

Published
2019

38. Screening of SLC2A1 in a large cohort of patients suspected for Glut1 deficiency syndrome: identification of novel variants and associated phenotypes

Author

Castellotti, B, Ragona, F, Freri, E, Solazzi, R, Ciardullo, S, Tricomi, G, Venerando, A, Salis, B, Canafoglia, L, Villani, F, Franceschetti, S, Nardocci, N, Gellera, C, Difrancesco, J, Granata, T, Castellotti, Barbara, Ragona, Francesca, Freri, Elena, Solazzi, Roberta, CIARDULLO, STEFANO, Tricomi, Giovanni, Venerando, Anna, Salis, Barbara, Canafoglia, Laura, Villani, Flavio, Franceschetti, Silvana, Nardocci, Nardo, Gellera, Cinzia, DiFrancesco, Jacopo C., Granata, Tiziana, Castellotti, B, Ragona, F, Freri, E, Solazzi, R, Ciardullo, S, Tricomi, G, Venerando, A, Salis, B, Canafoglia, L, Villani, F, Franceschetti, S, Nardocci, N, Gellera, C, Difrancesco, J, Granata, T, Castellotti, Barbara, Ragona, Francesca, Freri, Elena, Solazzi, Roberta, CIARDULLO, STEFANO, Tricomi, Giovanni, Venerando, Anna, Salis, Barbara, Canafoglia, Laura, Villani, Flavio, Franceschetti, Silvana, Nardocci, Nardo, Gellera, Cinzia, DiFrancesco, Jacopo C., and Granata, Tiziana

Abstract

Glucose transporter type 1 deficiency syndrome (Glut1 DS) is a rare neurological disorder caused by impaired glucose delivery to the brain. The clinical spectrum of Glut1 DS mainly includes epilepsy, paroxysmal dyskinesia (PD), developmental delay and microcephaly. Glut1 DS diagnosis is based on the identification of hypoglycorrhachia and pathogenic mutations of the SLC2A1 gene. Here, we report the molecular screening of SLC2A1 in 354 patients clinically suspected for Glut1 DS. From this cohort, we selected 245 patients for whom comprehensive clinical and laboratory data were available. Among them, we identified 19 patients carrying nucleotide variants of pathological significance, 5 of which were novel. The symptoms of onset, which varied from neonatal to adult age, included epilepsy, PD or non-epileptic paroxysmal manifestations. The comparison of the clinical features between the 19 SLC2A1 mutated and the 226 non-mutated patients revealed that the onset of epilepsy within the first year of life (when associated with developmental delay or other neurological manifestations), the association of epilepsy with PD and acquired microcephaly are more common in mutated subjects. Taken together, these data confirm the variability of expression of the phenotypes associated with mutation of SLC2A1 and provide useful clinical tools for the early identification of subjects highly suspected for the disease

Published
2019

40. The management of acute venous thromboembolism in clinical practice - study rationale and protocol of the European PREFER in VTE Registry

Author

Agnelli, G., Gitt, A. K., Bauersachs, R., Fronk, E. -M., Laeis, P., Mismetti, P., Monreal, M., Willich, S. N., Wolf, W. -P., Cohen, A. T., Brodmann, M., Rief, P., Eischer, L., Stoshikj, S., Hirschl, M., Weinmann, S., Marschang, P., Abbadie, F., Achkar, A., Addala, A., Adnet, F., Alexandra, J. -F., Aquilanti, S., Belhassane, A., Benaroya, A., Berremili, T., Grenot, M. C., Birr, V., Holtea, D., Bonnin, C., Bosler, F., Durand, M. -G. B., Brisot, D., Brousse, C., De La Fuente, T., Cayman, R., Cazaubon, M., Champion, O., Chanut, M., Chevalet, P., Connault, J., Durant, C., Constans, J., Cordeanu, M., Couturaud, F., Lacut, K., De Dedker, L., Decoulx, E., Derrien, B., Diamand, J. -M., Diard, A., Douadi, Y., Dupas, S., Remond, S. S. M., Sevestre, M. -A., Edhery, S., Falvo, N., Taralunga, C. F., Ferrari, E., Gaillard, C., Garrigues, D., Gillet, J. L., Giordana, P., Grange, C., Vital-Durand, D., Grare, F., Henni, A. H., Heuser, S., Schmidt, J., Hidden-Henic, V., Hottin, D., Imbert, B., Pernod, G., Jakob, D., Jacquinandi, V., Jurus, C., Lacoste, A., Laroche, J. -P., Martin, M., Mazollier, C., Mersel, T., Miserey, G., Nedey, C., Nou, M., Quere, I., Ouvry, P., Peuch, B., Pichot, O., Poulain, V., Ray, P., Rifai, A., Roy, P. -M., Saby, J. -C., Simon, F., Simonot-Lalandec, E., Stephan, D., Tissot, A., Vodoungnon, H., Adamczyk, A., Schnabl, S., Ahmad, W. A., Weber, H., Axthelm, C., Bergmann, K., Beschorner, U., Knittel, M., Binias, K. -H., Pasligh, M., Boral, M., Friederike, G., Bratsch, H., Brauer, G., Burghard, S., Demann, C., Rennebaum, C., Demmig, A., Eberlein, U., Enger, F., Eschenburg, J., Forkmann, L., Frank, J., Freischmidt, H., Gassauer, M., Fritsche, I., Kubicek-Hofmann, C., Goebels, M. -C., Guggenbichler, S., Hartel, D., Hartmann, K., Heilberger, P., Heinsius, A., Held, M., Schnupp, S., Herman, G., Herold, J., Hertrich, F., Hommel, H., Hutte, G., Kalka, C., Jungandreas, K., Ramthor, M., Karcher, J., Werner, N., Karl-Wollweber, S., Keilhau, D. -A., Kittel, K., Knolinski, T., Kohler, C., Werth, S., Kopplin, U., Korner, I., Wittig, K., Kroger, K., Moysidis, T., Kroschel, U., Leschke, M., zur Nieden, T., Lubbert, G., Lutz, A., Wucherpfennig, P., Marencke, G. -H., Mortensen, K., Reppel, M., Nelles, H., Nestler, K., Neumeister, A., Schlosser, A., Oettler, W., Ott, I., Otto, A., Pertermann, A., Pfister, R., Pindur, L., Pourhassan, S., Predel, D., Pudollek, T., Reimer, D., Richter, C., Rieker, E., Rothenbucher, G., Rothhagen, B., Rudolff, S., Stucker, M., Schafer, A., Sonnenschein, K., Schafnitzl, W., Schellong, S., Voigts, B., Schiller, M., Schmeink, T., Schneider, H., Schon, N., Schulze, M., Sechtem, U., Sedl, S., Werno, H. S., Stachowitz, J., Thieme, M., Tiefenbacher, C., Tsantilas, D., Vieth, P., vom Dahl, J., Grun-Himmelmann, K., von Bilderling, P., von Maltik, T., Weinrich, K., Weyer, M., Koln, E. K., Wirtz, P., Wittig, I., Zierock, P., Ageno, W., Caprioli, M., Rancan, E., Guercini, F., Mommi, V., Amitrano, M., Cannavacciuolo, F., Amore, M., D'Antoni, S., Angelini, E., Forgia, S. L., Antignani, P. L., Calandra, G., Arone, A., Perticone, F., Sciacqua, A., Asaro, G., Bellisi, M., Attanzio, M. T., Pinto, A., Attinasi, V., Cillari, E., Sorvillo, S., Balbarini, A., Santini, C., Violo, C., Banfi, E., Lodigiani, C., Barcellona, D., Delpin, S., Marongiu, S., Barillari, G., Pasca, S, Bartolini, C., Verdecchia, P., Bartone, M., Mancuso, G., Bellanuova, I., Felis, S., Bellizzi, A., Masotti, L., Bianchi, M., Carugati, A., Bianchini, G., Guarnera, G., Boari, B., Gallerani, M., Pasin, M., Bortoluzzi, C., Parisi, R., Brucoli, C., Palasciano, G., Camporese, G., Tonello, C., Canafoglia, L., Rupoli, S., Cancellieri, E., Paoletti, O., Testa, S., Carlizza, A., Carnovali, M., Sada, S., Samaden, A., Casarsa, C., Mearelli, F., Pivetti, G., Catalini, R., Zingaretti, O., Vascolare, M., Cavazza, S., Cosmi, B., Cenci, C., Prisco, D., Silvestri, E., Ceresa, F., Patane, F., Ciampa, A., Siniscalchi, V., Ciarambino, T., De Bartolomeo, G., Clemente, M., Conti, F., Paiella, L., D'Avino, M., D'Alessandro, A., Placentino, M., Sollazzo, V., D'Angelo, A., Vigano, S., De Campora, P., Sangiuolo, R., De Franciscis, S., Serra, R., De Gaudenzi, E., De Santis, F., Piccinni, G. C., De Tommaso, I. D., Di Francesco, L., Vincentelli, G. M., Di Maggio, R., Saccullo, G., Siragusa, S., Di Micco, P., Fontanella, A., Di Michele, D., Di Minno, G., Tufano, A., Di Nisio, M., Porreca, E., Donadio, F., Imberti, D., Enea, I., Fabbian, F., Manfredini, R., Pala, M., Falanga, A., Milesi, V., Fiore, V., Franco, E., Giudice, G., Frausini, G., Rovinelli, M., Fuorlo, M., Landolfi, R., Morretti, T., Gamberini, S., Salmi, R., Ghirarduzzi, A., Veropalumbo, M. R., Ghizzi, M., Pepe, C., Gianniello, F., Martinelli, I., Iosub, D. I., Piovella, F., Iozzi, E., Talerico, A., Regina, M. L., Orlandini, F., Marconi, L., Palla, A., Marcucci, R., Poli, D., Margheriti, R., Sala, G., Marra, A., Marrocco, F., Montagna, E. S., Silvestris, F., Vallarelli, S., Mos, L., Rossetto, V., Mugno, F., Di Salvo, M., Nitti, C., Pennacchioni, M., Salvi, A., Olivieri, O., Tosi, F., Zorzi, F., Onesta, M., Pagliara, V., Villalta, S., Paolucci, G., Severino, S., Pierri, F., Russo, V., Pizzini, A. M., Quintavalla, R., Rubino, P., Ria, L., Schenone, A., Strafino, C., Tropeano, P., Vetrano, A., Zanatta, N., Cansino, M. D. A., Gutierrez, J. A., de las Revillas, F. A., Fernandez, C. A., Mijares, N. C., Blanco-Molina, M. A., Garcia, M. A., Seijo, D. J., Blazquez, R. A., Lopez-Saez, J. -B., Rodrigo, E. A., Blanch, J. V., Arxe, A. A., Dalmau, F. G. -B., Quincoces, A. B., Loizaga, A. G., Perez, J. L. B., Diaz, P. B., Loaiza, A. Q., Castellote, M. C., Alcantara, I. C., Padierna, M. L., Exposito, M. C., Mas, A. C., Castro, F. C., Sanz, R. C., de Saracho, J. O., de la Fuente, E. C., de Ancos Aracil, C., Ruiz, J. R., de Daborenea Gonzalez, M. D., Iglesias, A. F., de la Fuente Aguado, J., Gonzalez, L. G., del Carmen Fernandez-Capitan, M., Hernandez, A. L., del Toro Cervera, J., Rus, G. P., Bregel, J. L. D., Fernandez, F. D., Teresa Elias Hernandez, Palomares, L. J., Bataler, R. F., Rodriguez, J. A. N., Garcia, J. M. G., Porras, J. R. G., Garcia, M. G., Lopez, E. H., Lazaro, A. R., Jaras, M. J., Castro, D. J., Madridejos, R. J. -R., Navas, J. M. P., Lecumberri, R., Martinez, N., Castellanos, G. T. L., Espinosa, L. M., Jimenez, L. L., Cobo, O. M., Saiz, C. M., Pizarro, Y. R., Yglesias, P. J. M., Martin del Pozo, M., Melibovsky, L., Altarriba, E. S., Bosch, M. M., Secades, R. M., Lujan, J. M. M., Mestre, A. R., Moral, P. M., Parra, J. A. T., Flores, A. M., Munoz-Torrero, J. F. S., Rodriguez, F. J. M., Fernandez, M. J. N., Sibajas, E. O., de Sedas, M. V., Caballero, P. P., del Campo, I. P. M., Sanchez, J. P., Gallego, A. R., Alvarez, I. V., Beltran, E. M. R., Fuentes, D. S., Schilling, V. R., Alvarez, J. S., Lopez, G. T., Caralt, J. M. S., Miranda, R. T., de Antonio, E. U., Banyai, M., Frank, U., Gian Reto Jorg, Jeanneret, C., Staub, D., Ackroyd, S., Agarwal, G., Mearns, B., Alikhan, R., Allameddine, A., Al-Refaie, F., Arden, C., Austin, A., Bakhai, A., Barton, T., Ewad, H., Body, R., Thachil, J., Chacko, J., Chandra, D., Charters, F., Church, A., Mcgrane, F., Clements, J., Clifford, P., Cox, D., Crouch, M., Crowther, M., Davies, E., Davies, M., Dimitri, S., Drebes, A., Franklin, S., George, J., Irvine, N., Gerofke, H., Gibbs, C., Goh, T., Gupta, S., Holmes, J., Jackson-Voyzey, E., Jones, N., Kallat, A., Kerr, P., Kesteven, P., Lench, T., Lester, W., Lowe, G., Lewis, M., Mccormack, T., Mccoye, A., Moriarty, A., Morris, W., Myers, B., Narayanan, M., Oo, N., Reed, M., Rose, P., Saja, K., Sivakumaran, M., Sohal, M., Solomons, G., Sultanzadeh, S. J., Venton, T., Wakeling, J., Walby, C., Waldron, M., Watt, S., Willcock, W., Agnelli, G., Gitt, A. K., Bauersachs, R., Fronk, E. -M., Laeis, P., Mismetti, P., Monreal, M., Willich, S. N., Wolf, W. -P., Cohen, A. T., Brodmann, M., Rief, P., Eischer, L., Stoshikj, S., Hirschl, M., Weinmann, S., Marschang, P., Abbadie, F., Achkar, A., Addala, A., Adnet, F., Alexandra, J. -F., Aquilanti, S., Belhassane, A., Benaroya, A., Berremili, T., Grenot, M. C., Birr, V., Holtea, D., Bonnin, C., Bosler, F., Durand, M. -G. B., Brisot, D., Brousse, C., De La Fuente, T., Cayman, R., Cazaubon, M., Champion, O., Chanut, M., Chevalet, P., Connault, J., Durant, C., Constans, J., Cordeanu, M., Couturaud, F., Lacut, K., De Dedker, L., Decoulx, E., Derrien, B., Diamand, J. -M., Diard, A., Douadi, Y., Dupas, S., Remond, S. S. M., Sevestre, M. -A., Edhery, S., Falvo, N., Taralunga, C. F., Ferrari, E., Gaillard, C., Garrigues, D., Gillet, J. L., Giordana, P., Grange, C., Vital-Durand, D., Grare, F., Henni, A. H., Heuser, S., Schmidt, J., Hidden-Henic, V., Hottin, D., Imbert, B., Pernod, G., Jakob, D., Jacquinandi, V., Jurus, C., Lacoste, A., Laroche, J. -P., Martin, M., Mazollier, C., Mersel, T., Miserey, G., Nedey, C., Nou, M., Quere, I., Ouvry, P., Peuch, B., Pichot, O., Poulain, V., Ray, P., Rifai, A., Roy, P. -M., Saby, J. -C., Simon, F., Simonot-Lalandec, E., Stephan, D., Tissot, A., Vodoungnon, H., Adamczyk, A., Schnabl, S., Ahmad, W. A., Weber, H., Axthelm, C., Bergmann, K., Beschorner, U., Knittel, M., Binias, K. -H., Pasligh, M., Boral, M., Friederike, G., Bratsch, H., Brauer, G., Burghard, S., Demann, C., Rennebaum, C., Demmig, A., Eberlein, U., Enger, F., Eschenburg, J., Forkmann, L., Frank, J., Freischmidt, H., Gassauer, M., Fritsche, I., Kubicek-Hofmann, C., Goebels, M. -C., Guggenbichler, S., Hartel, D., Hartmann, K., Heilberger, P., Heinsius, A., Held, M., Schnupp, S., Herman, G., Herold, J., Hertrich, F., Hommel, H., Hutte, G., Kalka, C., Jungandreas, K., Ramthor, M., Karcher, J., Werner, N., Karl-Wollweber, S., Keilhau, D. -A., Kittel, K., Knolinski, T., Kohler, C., Werth, S., Kopplin, U., Korner, I., Wittig, K., Kroger, K., Moysidis, T., Kroschel, U., Leschke, M., zur Nieden, T., Lubbert, G., Lutz, A., Wucherpfennig, P., Marencke, G. -H., Mortensen, K., Reppel, M., Nelles, H., Nestler, K., Neumeister, A., Schlosser, A., Oettler, W., Ott, I., Otto, A., Pertermann, A., Pfister, R., Pindur, L., Pourhassan, S., Predel, D., Pudollek, T., Reimer, D., Richter, C., Rieker, E., Rothenbucher, G., Rothhagen, B., Rudolff, S., Stucker, M., Schafer, A., Sonnenschein, K., Schafnitzl, W., Schellong, S., Voigts, B., Schiller, M., Schmeink, T., Schneider, H., Schon, N., Schulze, M., Sechtem, U., Sedl, S., Werno, H. S., Stachowitz, J., Thieme, M., Tiefenbacher, C., Tsantilas, D., Vieth, P., vom Dahl, J., Grun-Himmelmann, K., von Bilderling, P., von Maltik, T., Weinrich, K., Weyer, M., Koln, E. K., Wirtz, P., Wittig, I., Zierock, P., Ageno, W., Caprioli, M., Rancan, E., Guercini, F., Mommi, V., Amitrano, M., Cannavacciuolo, F., Amore, M., D'Antoni, S., Angelini, E., Forgia, S. L., Antignani, P. L., Calandra, G., Arone, A., Perticone, F., Sciacqua, A., Asaro, G., Bellisi, M., Attanzio, M. T., Pinto, A., Attinasi, V., Cillari, E., Sorvillo, S., Balbarini, A., Santini, C., Violo, C., Banfi, E., Lodigiani, C., Barcellona, D., Delpin, S., Marongiu, S., Barillari, G., Pasca, S., Bartolini, C., Verdecchia, P., Bartone, M., Mancuso, G., Bellanuova, I., Felis, S., Bellizzi, A., Masotti, L., Bianchi, M., Carugati, A., Bianchini, G., Guarnera, G., Boari, B., Gallerani, M., Pasin, M., Bortoluzzi, C., Parisi, R., Brucoli, C., Palasciano, G., Camporese, G., Tonello, C., Canafoglia, L., Rupoli, S., Cancellieri, E., Paoletti, O., Testa, S., Carlizza, A., Carnovali, M., Sada, S., Samaden, A., Casarsa, C., Mearelli, F., Pivetti, G., Catalini, R., Zingaretti, O., Vascolare, M., Cavazza, S., Cosmi, B., Cenci, C., Prisco, D., Silvestri, E., Ceresa, F., Patane, F., Ciampa, A., Siniscalchi, V., Ciarambino, T., De Bartolomeo, G., Clemente, M., Conti, F., Paiella, L., D'Avino, M., D'Alessandro, A., Placentino, M., Sollazzo, V., D'Angelo, A., Vigano, S., De Campora, P., Sangiuolo, R., De Franciscis, S., Serra, R., De Gaudenzi, E., De Santis, F., Piccinni, G. C., De Tommaso, I. D., Di Francesco, L., Vincentelli, G. M., Di Maggio, R., Saccullo, G., Siragusa, S., Di Micco, P., Fontanella, A., Di Michele, D., Di Minno, G., Tufano, A., Di Nisio, M., Porreca, E., Donadio, F., Imberti, D., Enea, I., Fabbian, F., Manfredini, R., Pala, M., Falanga, A., Milesi, V., Fiore, V., Franco, E., Giudice, G., Frausini, G., Rovinelli, M., Fuorlo, M., Landolfi, R., Morretti, T., Gamberini, S., Salmi, R., Ghirarduzzi, A., Veropalumbo, M. R., Ghizzi, M., Pepe, C., Gianniello, F., Martinelli, I., Iosub, D. I., Piovella, F., Iozzi, E., Talerico, A., Regina, M. L., Orlandini, F., Marconi, L., Palla, A., Marcucci, R., Poli, D., Margheriti, R., Sala, G., Marra, A., Marrocco, F., Montagna, E. S., Silvestris, F., Vallarelli, S., Mos, L., Rossetto, V., Mugno, F., Di Salvo, M., Nitti, C., Pennacchioni, M., Salvi, A., Olivieri, O., Tosi, F., Zorzi, F., Onesta, M., Pagliara, V., Villalta, S., Paolucci, G., Severino, S., Pierri, F., Russo, V., Pizzini, A. M., Quintavalla, R., Rubino, P., Ria, L., Schenone, A., Strafino, C., Tropeano, P., Vetrano, A., Zanatta, N., Cansino, M. D. A., Gutierrez, J. A., de las Revillas, F. A., Fernandez, C. A., Mijares, N. C., Blanco-Molina, M. A., Garcia, M. A., Seijo, D. J., Blazquez, R. A., Lopez-Saez, J. -B., Rodrigo, E. A., Blanch, J. V., Arxe, A. A., Dalmau, F. G. -B., Quincoces, A. B., Loizaga, A. G., Perez, J. L. B., Diaz, P. B., Loaiza, A. Q., Castellote, M. C., Alcantara, I. C., Padierna, M. L., Exposito, M. C., Mas, A. C., Castro, F. C., Sanz, R. C., de Saracho, J. O., de la Fuente, E. C., de Ancos Aracil, C., Ruiz, J. R., de Daborenea Gonzalez, M. D., Iglesias, A. F., de la Fuente Aguado, J., Gonzalez, L. G., del Carmen Fernandez-Capitan, M., Hernandez, A. L., del Toro Cervera, J., Rus, G. P., Bregel, J. L. D., Fernandez, F. D., Teresa Elias, Hernandez, Palomares, L. J., Bataler, R. F., Rodriguez, J. A. N., Garcia, J. M. G., Porras, J. R. G., Garcia, M. G., Lopez, E. H., Lazaro, A. R., Jaras, M. J., Castro, D. J., Madridejos, R. J. -R., Navas, J. M. P., Lecumberri, R., Martinez, N., Castellanos, G. T. L., Espinosa, L. M., Jimenez, L. L., Cobo, O. M., Saiz, C. M., Pizarro, Y. R., Yglesias, P. J. M., Martin del Pozo, M., Melibovsky, L., Altarriba, E. S., Bosch, M. M., Secades, R. M., Lujan, J. M. M., Mestre, A. R., Moral, P. M., Parra, J. A. T., Flores, A. M., Munoz-Torrero, J. F. S., Rodriguez, F. J. M., Fernandez, M. J. N., Sibajas, E. O., de Sedas, M. V., Caballero, P. P., del Campo, I. P. M., Sanchez, J. P., Gallego, A. R., Alvarez, I. V., Beltran, E. M. R., Fuentes, D. S., Schilling, V. R., Alvarez, J. S., Lopez, G. T., Caralt, J. M. S., Miranda, R. T., de Antonio, E. U., Banyai, M., Frank, U., Gian Reto, Jorg, Jeanneret, C., Staub, D., Ackroyd, S., Agarwal, G., Mearns, B., Alikhan, R., Allameddine, A., Al-Refaie, F., Arden, C., Austin, A., Bakhai, A., Barton, T., Ewad, H., Body, R., Thachil, J., Chacko, J., Chandra, D., Charters, F., Church, A., Mcgrane, F., Clements, J., Clifford, P., Cox, D., Crouch, M., Crowther, M., Davies, E., Davies, M., Dimitri, S., Drebes, A., Franklin, S., George, J., Irvine, N., Gerofke, H., Gibbs, C., Goh, T., Gupta, S., Holmes, J., Jackson-Voyzey, E., Jones, N., Kallat, A., Kerr, P., Kesteven, P., Lench, T., Lester, W., Lowe, G., Lewis, M., Mccormack, T., Mccoye, A., Moriarty, A., Morris, W., Myers, B., Narayanan, M., Oo, N., Reed, M., Rose, P., Saja, K., Sivakumaran, M., Sohal, M., Solomons, G., Sultanzadeh, S. J., Venton, T., Wakeling, J., Walby, C., Waldron, M., Watt, S., Willcock, W., Zafar, A., Agnelli, G, Gitt, A, Bauersachs, R, Fronk, E, Laeis, P, Mismetti, P, Monreal, M, Willich, S, Wolf, W, Cohen, A, Brodmann, M, Rief, P, Eischer, L, Stoshikj, S, Hirschl, M, Weinmann, S, Marschang, P, Abbadie, F, Achkar, A, Addala, A, Adnet, F, Alexandra, J, Aquilanti, S, Belhassane, A, Benaroya, A, Berremili, T, Grenot, M, Birr, V, Holtea, D, Bonnin, C, Bosler, F, Durand, M, Brisot, D, Brousse, C, De La Fuente, T, Cayman, R, Cazaubon, M, Champion, O, Chanut, M, Chevalet, P, Connault, J, Durant, C, Constans, J, Cordeanu, M, Couturaud, F, Lacut, K, De Dedker, L, Decoulx, E, Derrien, B, Diamand, J, Diard, A, Douadi, Y, Dupas, S, Remond, S, Sevestre, M, Edhery, S, Falvo, N, Taralunga, C, Ferrari, E, Gaillard, C, Garrigues, D, Gillet, J, Giordana, P, Grange, C, Vital-Durand, D, Grare, F, Henni, A, Heuser, S, Schmidt, J, Hidden-Henic, V, Hottin, D, Imbert, B, Pernod, G, Jakob, D, Jacquinandi, V, Jurus, C, Lacoste, A, Laroche, J, Martin, M, Mazollier, C, Mersel, T, Miserey, G, Nedey, C, Nou, M, Quere, I, Ouvry, P, Peuch, B, Pichot, O, Poulain, V, Ray, P, Rifai, A, Roy, P, Saby, J, Simon, F, Simonot-Lalandec, E, Stephan, D, Tissot, A, Vodoungnon, H, Adamczyk, A, Schnabl, S, Ahmad, W, Weber, H, Axthelm, C, Bergmann, K, Beschorner, U, Knittel, M, Binias, K, Pasligh, M, Boral, M, Friederike, G, Bratsch, H, Brauer, G, Burghard, S, Demann, C, Rennebaum, C, Demmig, A, Eberlein, U, Enger, F, Eschenburg, J, Forkmann, L, Frank, J, Freischmidt, H, Gassauer, M, Fritsche, I, Kubicek-Hofmann, C, Goebels, M, Guggenbichler, S, Hartel, D, Hartmann, K, Heilberger, P, Heinsius, A, Held, M, Schnupp, S, Herman, G, Herold, J, Hertrich, F, Hommel, H, Hutte, G, Kalka, C, Jungandreas, K, Ramthor, M, Karcher, J, Werner, N, Karl-Wollweber, S, Keilhau, D, Kittel, K, Knolinski, T, Kohler, C, Werth, S, Kopplin, U, Korner, I, Wittig, K, Kroger, K, Moysidis, T, Kroschel, U, Leschke, M, zur Nieden, T, Lubbert, G, Lutz, A, Wucherpfennig, P, Marencke, G, Mortensen, K, Reppel, M, Nelles, H, Nestler, K, Neumeister, A, Schlosser, A, Oettler, W, Ott, I, Otto, A, Pertermann, A, Pfister, R, Pindur, L, Pourhassan, S, Predel, D, Pudollek, T, Reimer, D, Richter, C, Rieker, E, Rothenbucher, G, Rothhagen, B, Rudolff, S, Stucker, M, Schafer, A, Sonnenschein, K, Schafnitzl, W, Schellong, S, Voigts, B, Schiller, M, Schmeink, T, Schneider, H, Schon, N, Schulze, M, Sechtem, U, Sedl, S, Werno, H, Stachowitz, J, Thieme, M, Tiefenbacher, C, Tsantilas, D, Vieth, P, vom Dahl, J, Grun-Himmelmann, K, von Bilderling, P, von Maltik, T, Weinrich, K, Weyer, M, Koln, E, Wirtz, P, Wittig, I, Zierock, P, Ageno, W, Caprioli, M, Rancan, E, Guercini, F, Mommi, V, Amitrano, M, Cannavacciuolo, F, Amore, M, D'Antoni, S, Angelini, E, Forgia, S, Antignani, P, Calandra, G, Arone, A, Perticone, F, Sciacqua, A, Asaro, G, Bellisi, M, Attanzio, M, Pinto, A, Attinasi, V, Cillari, E, Sorvillo, S, Balbarini, A, Santini, C, Violo, C, Banfi, E, Lodigiani, C, Barcellona, D, Delpin, S, Marongiu, S, Barillari, G, Pasca, S, Bartolini, C, Verdecchia, P, Bartone, M, Mancuso, G, Bellanuova, I, Felis, S, Bellizzi, A, Masotti, L, Bianchi, M, Carugati, A, Bianchini, G, Guarnera, G, Boari, B, Gallerani, M, Pasin, M, Bortoluzzi, C, Parisi, R, Brucoli, C, Palasciano, G, Camporese, G, Tonello, C, Canafoglia, L, Rupoli, S, Cancellieri, E, Paoletti, O, Testa, S, Carlizza, A, Carnovali, M, Sada, S, Samaden, A, Casarsa, C, Mearelli, F, Pivetti, G, Catalini, R, Zingaretti, O, Vascolare, M, Cavazza, S, Cosmi, B, Cenci, C, Prisco, D, Silvestri, E, Ceresa, F, Patane, F, Ciampa, A, Siniscalchi, V, Ciarambino, T, De Bartolomeo, G, Clemente, M, Conti, F, Paiella, L, D'Avino, M, D'Alessandro, A, Placentino, M, Sollazzo, V, D'Angelo, A, Vigano, S, De Campora, P, Sangiuolo, R, De Franciscis, S, Serra, R, De Gaudenzi, E, De Santis, F, Piccinni, G, De Tommaso, I, Di Francesco, L, Vincentelli, G, Di Maggio, R, Saccullo, G, Siragusa, S, Di Micco, P, Fontanella, A, Di Michele, D, Di Minno, G, Tufano, A, Di Nisio, M, Porreca, E, Donadio, F, Imberti, D, Enea, I, Fabbian, F, Manfredini, R, Pala, M, Falanga, A, Milesi, V, Fiore, V, Franco, E, Giudice, G, Frausini, G, Rovinelli, M, Fuorlo, M, Landolfi, R, Morretti, T, Gamberini, S, Salmi, R, Ghirarduzzi, A, Veropalumbo, M, Ghizzi, M, Pepe, C, Gianniello, F, Martinelli, I, Iosub, D, Piovella, F, Iozzi, E, Talerico, A, Regina, M, Orlandini, F, Marconi, L, Palla, A, Marcucci, R, Poli, D, Margheriti, R, Sala, G, Marra, A, Marrocco, F, Montagna, E, Silvestris, F, Vallarelli, S, Mos, L, Rossetto, V, Mugno, F, Di Salvo, M, Nitti, C, Pennacchioni, M, Salvi, A, Olivieri, O, Tosi, F, Zorzi, F, Onesta, M, Pagliara, V, Villalta, S, Paolucci, G, Severino, S, Pierri, F, Russo, V, Pizzini, A, Quintavalla, R, Rubino, P, Ria, L, Schenone, A, Strafino, C, Tropeano, P, Vetrano, A, Zanatta, N, Cansino, M, Gutierrez, J, de las Revillas, F, Fernandez, C, Mijares, N, Blanco-Molina, M, Garcia, M, Seijo, D, Blazquez, R, Lopez-Saez, J, Rodrigo, E, Blanch, J, Arxe, A, Dalmau, F, Quincoces, A, Loizaga, A, Perez, J, Diaz, P, Loaiza, A, Castellote, M, Alcantara, I, Padierna, M, Exposito, M, Mas, A, Castro, F, Sanz, R, de Saracho, J, de la Fuente, E, de Ancos Aracil, C, Ruiz, J, de Daborenea Gonzalez, M, Iglesias, A, de la Fuente Aguado, J, Gonzalez, L, del Carmen Fernandez-Capitan, M, Hernandez, A, del Toro Cervera, J, Rus, G, Bregel, J, Fernandez, F, Teresa Elias, H, Palomares, L, Bataler, R, Rodriguez, J, Garcia, J, Porras, J, Lopez, E, Lazaro, A, Jaras, M, Castro, D, Madridejos, R, Navas, J, Lecumberri, R, Martinez, N, Castellanos, G, Espinosa, L, Jimenez, L, Cobo, O, Saiz, C, Pizarro, Y, Yglesias, P, Martin del Pozo, M, Melibovsky, L, Altarriba, E, Bosch, M, Secades, R, Lujan, J, Mestre, A, Moral, P, Parra, J, Flores, A, Munoz-Torrero, J, Rodriguez, F, Fernandez, M, Sibajas, E, de Sedas, M, Caballero, P, del Campo, I, Sanchez, J, Gallego, A, Alvarez, I, Beltran, E, Fuentes, D, Schilling, V, Alvarez, J, Lopez, G, Caralt, J, Miranda, R, de Antonio, E, Banyai, M, Frank, U, Gian Reto, J, Jeanneret, C, Staub, D, Ackroyd, S, Agarwal, G, Mearns, B, Alikhan, R, Allameddine, A, Al-Refaie, F, Arden, C, Austin, A, Bakhai, A, Barton, T, Ewad, H, Body, R, Thachil, J, Chacko, J, Chandra, D, Charters, F, Church, A, Mcgrane, F, Clements, J, Clifford, P, Cox, D, Crouch, M, Crowther, M, Davies, E, Davies, M, Dimitri, S, Drebes, A, Franklin, S, George, J, Irvine, N, Gerofke, H, Gibbs, C, Goh, T, Gupta, S, Holmes, J, Jackson-Voyzey, E, Jones, N, Kallat, A, Kerr, P, Kesteven, P, Lench, T, Lester, W, Lowe, G, Lewis, M, Mccormack, T, Mccoye, A, Moriarty, A, Morris, W, Myers, B, Narayanan, M, Oo, N, Reed, M, Rose, P, Saja, K, Sivakumaran, M, Sohal, M, Solomons, G, Sultanzadeh, S, Venton, T, Wakeling, J, Walby, C, Waldron, M, Watt, S, Willcock, W, and Zafar, A

Subjects
Drug Utilization, Pediatrics, medicine.medical_specialty, Novel Oral Anticoagulants, Registry, Deep vein, Alternative medicine, Anticoagulation, Patient satisfaction, Quality of life, Health care, medicine, Anticoagulation, Novel Oral Anticoagulants, Prevention, Registry, Venous Thromboembolism, Vitamin K antagonists, cardiovascular diseases, business.industry, Prevention, Venous Thromboembolism, Vitamin K antagonists, Hematology, Novel Oral Anticoagulant, medicine.disease, equipment and supplies, Pulmonary embolism, medicine.anatomical_structure, Emergency medicine, Original Clinical Investigation, Observational study, business
Abstract

Background: Venous thromboembolism (VTE) is a major health problem, with over one million events every year in Europe. However, there is a paucity of data on the current management in real life, including factors influencing treatment pathways, patient satisfaction, quality of life (QoL), and utilization of health care resources and the corresponding costs. The PREFER in VTE registry has been designed to address this and to understand medical care and needs as well as potential gaps for improvement. Methods/design: The PREFER in VTE registry was a prospective, observational, multicenter study conducted in seven European countries including Austria, France Germany, Italy, Spain, Switzerland, and the UK to assess the characteristics and the management of patients with VTE, the use of health care resources, and to provide data to estimate the costs for 12 months treatment following a first-time and/or recurrent VTE diagnosed in hospitals or specialized or primary care centers. In addition, existing anticoagulant treatment patterns, patient pathways, clinical outcomes, treatment satisfaction, and health related QoL were documented. The centers were chosen to reflect the care environment in which patients with VTE are managed in each of the participating countries. Patients were eligible to be enrolled into the registry if they were at least 18 years old, had a symptomatic, objectively confirmed first time or recurrent acute VTE defined as either distal or proximal deep vein thrombosis, pulmonary embolism or both. After the baseline visit at the time of the acute VTE event, further follow-up documentations occurred at 1, 3, 6 and 12 months. Follow-up data was collected by either routinely scheduled visits or by telephone calls. Results: Overall, 381 centers participated, which enrolled 3,545 patients during an observational period of 1 year. Conclusion: The PREFER in VTE registry will provide valuable insights into the characteristics of patients with VTE and their acute and mid-term management, as well as into drug utilization and the use of health care resources in acute first-time and/or recurrent VTE across Europe in clinical practice. Trial registration: Registered in DRKS register, ID number: DRKS00004795

Published
2015

46. A loss-of-function HCN4 mutation associated with familial benign myoclonic epilepsy in infancy causes increased neuronal excitability

Author

Campostrini, G, Difrancesco, J, Castellotti, B, Milanesi, R, Gnecchi-Ruscone, T, Bonzanni, M, Bucchi, A, Baruscotti, M, Ferrarese, C, Franceschetti, S, Canafoglia, L, Ragona, F, Freri, E, Labate, A, Gambardella, A, Costa, C, Gellera, C, Granata, T, Barbuti, A, Difrancesco, D, Difrancesco, JC, Freri, Elena, Labate, Angelo, Campostrini, G, Difrancesco, J, Castellotti, B, Milanesi, R, Gnecchi-Ruscone, T, Bonzanni, M, Bucchi, A, Baruscotti, M, Ferrarese, C, Franceschetti, S, Canafoglia, L, Ragona, F, Freri, E, Labate, A, Gambardella, A, Costa, C, Gellera, C, Granata, T, Barbuti, A, Difrancesco, D, Difrancesco, JC, Freri, Elena, and Labate, Angelo

Abstract

HCN channels are highly expressed and functionally relevant in neurons and increasing evidence demonstrates their involvement in the etiology of human epilepsies. Among HCN isoforms, HCN4 is important in cardiac tissue, where it underlies pacemaker activity. Despite being expressed also in deep structures of the brain, mutations of this channel functionally shown to be associated with epilepsy have not been reported yet. Using Next Generation Sequencing for the screening of patients with idiopathic epilepsy, we identified the p.Arg550Cys (c.1648C>T) heterozygous mutation on HCN4 in two brothers affected by benign myoclonic epilepsy of infancy. Functional characterization in heterologous expression system and in neurons showed that the mutation determines a loss of function of HCN4 contribution to activity and an increase of neuronal discharge, potentially predisposing to epilepsy. Expressed in cardiomyocytes, mutant channels activate at slightly more negative voltages than wild-type (WT), in accordance with borderline bradycardia. While HCN4 variants have been frequently associated with cardiac arrhythmias, these data represent the first experimental evidence that functional alteration of HCN4 can also be involved in human epilepsy through a loss-of-function effect and associated increased neuronal excitability. Since HCN4 appears to be highly expressed in deep brain structures only early during development, our data provide a potential explanation for a link between dysfunctional HCN4 and infantile epilepsy. These findings suggest that it may be useful to include HCN4 screening to extend the knowledge of the genetic causes of infantile epilepsies, potentially paving the way for the identification of innovative therapeutic strategies.

Published
2018

47. HCN1 mutation spectrum: From neonatal epileptic encephalopathy to benign generalized epilepsy and beyond

Author

Marini, C, Porro, A, Rastetter, A, Dalle, C, Rivolta, I, Bauer, D, Oegema, R, Nava, C, Parrini, E, Mei, D, Mercer, C, Dhamija, R, Chambers, C, Coubes, C, Thévenon, J, Kuentz, P, Julia, S, Pasquier, L, Dubourg, C, Carré, W, Rosati, A, Melani, F, Pisano, T, Giardino, M, Innes, A, Alembik, Y, Scheidecker, S, Santos, M, Figueiroa, S, Garrido, C, Fusco, C, Frattini, D, Spagnoli, C, Binda, A, Granata, T, Ragona, F, Freri, E, Franceschetti, S, Canafoglia, L, Castellotti, B, Gellera, C, Milanesi, R, Mancardi, M, Clark, D, Kok, F, Helbig, K, Ichikawa, S, Sadler, L, Neupauerová, J, Laššuthova, P, Šterbová, K, Laridon, A, Brilstra, E, Koeleman, B, Lemke, J, Zara, F, Striano, P, Soblet, J, Smits, G, Deconinck, N, Barbuti, A, Difrancesco, D, Leguern, E, Guerrini, R, Santoro, B, Hamacher, K, Thiel, G, Moroni, A, Di Francesco, J, Depienne, C, Innes, AM, Mancardi, MM, Clark, DR, Helbig, KL, Lemke, JR, DiFrancesco, D, LeGuern, E, Di Francesco, JC, Marini, C, Porro, A, Rastetter, A, Dalle, C, Rivolta, I, Bauer, D, Oegema, R, Nava, C, Parrini, E, Mei, D, Mercer, C, Dhamija, R, Chambers, C, Coubes, C, Thévenon, J, Kuentz, P, Julia, S, Pasquier, L, Dubourg, C, Carré, W, Rosati, A, Melani, F, Pisano, T, Giardino, M, Innes, A, Alembik, Y, Scheidecker, S, Santos, M, Figueiroa, S, Garrido, C, Fusco, C, Frattini, D, Spagnoli, C, Binda, A, Granata, T, Ragona, F, Freri, E, Franceschetti, S, Canafoglia, L, Castellotti, B, Gellera, C, Milanesi, R, Mancardi, M, Clark, D, Kok, F, Helbig, K, Ichikawa, S, Sadler, L, Neupauerová, J, Laššuthova, P, Šterbová, K, Laridon, A, Brilstra, E, Koeleman, B, Lemke, J, Zara, F, Striano, P, Soblet, J, Smits, G, Deconinck, N, Barbuti, A, Difrancesco, D, Leguern, E, Guerrini, R, Santoro, B, Hamacher, K, Thiel, G, Moroni, A, Di Francesco, J, Depienne, C, Innes, AM, Mancardi, MM, Clark, DR, Helbig, KL, Lemke, JR, DiFrancesco, D, LeGuern, E, and Di Francesco, JC

Abstract

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels control neuronal excitability and their dysfunction has been linked to epileptogenesis but few individuals with neurological disorders related to variants altering HCN channels have been reported so far. In 2014, we described five individuals with epileptic encephalopathy due to de novo HCN1 variants. To delineate HCN1-related disorders and investigate genotype-phenotype correlations further, we assembled a cohort of 33 unpublished patients with novel pathogenic or likely pathogenic variants: 19 probands carrying 14 different de novo mutations and four families with dominantly inherited variants segregating with epilepsy in 14 individuals, but not penetrant in six additional individuals. Sporadic patients had epilepsy with median onset at age 7 months and in 36% the first seizure occurred during a febrile illness. Overall, considering familial and sporadic patients, the predominant phenotypes were mild, including genetic generalized epilepsies and genetic epilepsy with febrile seizures plus (GEFS+) spectrum. About 20% manifested neonatal/infantile onset otherwise unclassified epileptic encephalopathy. The study also included eight patients with variants of unknown significance: One adopted patient had two HCN1 variants, four probands had intellectual disability without seizures, and three individuals had missense variants inherited from an asymptomatic parent. Of the 18 novel pathogenic missense variants identified, 12 were associated with severe phenotypes and clustered within or close to transmembrane domains, while variants segregating with milder phenotypes were located outside transmembrane domains, in the intracellular N- and C-terminal parts of the channel. Five recurrent variants were associated with similar phenotypes. Using whole-cell patch-clamp, we showed that the impact of 12 selected variants ranged from complete loss-of-function to significant shifts in activation kinetics and/or volta

Published
2018

48. A novel de novo HCN1 loss-of-function mutation in genetic generalized epilepsy causing increased neuronal excitability

Author

Bonzanni, M, Difrancesco, J, Milanesi, R, Campostrini, G, Castellotti, B, Bucchi, A, Baruscotti, M, Ferrarese, C, Franceschetti, S, Canafoglia, L, Ragona, F, Freri, E, Labate, A, Gambardella, A, Costa, C, Rivolta, I, Gellera, C, Granata, T, Barbuti, A, Difrancesco, D, Bonzanni, Mattia, DiFrancesco, Jacopo C., Milanesi, Raffaella, Campostrini, Giulia, Castellotti, Barbara, Bucchi, Annalisa, Baruscotti, Mirko, Ferrarese, Carlo, Franceschetti, Silvana, Canafoglia, Laura, Ragona, Francesca, Freri, Elena, Labate, Angelo, Gambardella, Antonio, Costa, Cinzia, RIVOLTA, ILARIA, Gellera, Cinzia, Granata, Tiziana, Barbuti, Andrea, DiFrancesco, Dario, Bonzanni, M, Difrancesco, J, Milanesi, R, Campostrini, G, Castellotti, B, Bucchi, A, Baruscotti, M, Ferrarese, C, Franceschetti, S, Canafoglia, L, Ragona, F, Freri, E, Labate, A, Gambardella, A, Costa, C, Rivolta, I, Gellera, C, Granata, T, Barbuti, A, Difrancesco, D, Bonzanni, Mattia, DiFrancesco, Jacopo C., Milanesi, Raffaella, Campostrini, Giulia, Castellotti, Barbara, Bucchi, Annalisa, Baruscotti, Mirko, Ferrarese, Carlo, Franceschetti, Silvana, Canafoglia, Laura, Ragona, Francesca, Freri, Elena, Labate, Angelo, Gambardella, Antonio, Costa, Cinzia, RIVOLTA, ILARIA, Gellera, Cinzia, Granata, Tiziana, Barbuti, Andrea, and DiFrancesco, Dario

Abstract

The causes of genetic epilepsies are unknown in the majority of patients. HCN ion channels have a widespread expression in neurons and increasing evidence demonstrates their functional involvement in human epilepsies. Among the four known isoforms, HCN1 is the most expressed in the neocortex and hippocampus and de novo HCN1 point mutations have been recently associated with early infantile epileptic encephalopathy. So far, HCN1 mutations have not been reported in patients with idiopathic epilepsy. Using a Next Generation Sequencing approach, we identified the de novo heterozygous p.Leu157Val (c.469C > G) novel mutation in HCN1 in an adult male patient affected by genetic generalized epilepsy (GGE), with normal cognitive development. Electrophysiological analysis in heterologous expression model (CHO cells) and in neurons revealed that L157V is a loss-of-function, dominant negative mutation causing reduced HCN1 contribution to net inward current and responsible for an increased neuronal firing rate and excitability, potentially predisposing to epilepsy. These data represent the first evidence that autosomal dominant missense mutations of HCN1 can also be involved in GGE, without the characteristics of epileptic encephalopathy reported previously. It will be important to include HCN1 screening in patients with GGE, in order to extend the knowledge of the genetic causes of idiopathic epilepsies, thus paving the way for the identification of innovative therapeutic strategies.

Published
2018

49. The management of acute venous thromboembolism in clinical practice - study rationale and protocol of the European PREFER in VTE Registry

Author

Agnelli, G, Gitt, A, Bauersachs, R, Fronk, E, Laeis, P, Mismetti, P, Monreal, M, Willich, S, Wolf, W, Cohen, A, Brodmann, M, Rief, P, Eischer, L, Stoshikj, S, Hirschl, M, Weinmann, S, Marschang, P, Abbadie, F, Achkar, A, Addala, A, Adnet, F, Alexandra, J, Aquilanti, S, Belhassane, A, Benaroya, A, Berremili, T, Grenot, M, Birr, V, Holtea, D, Bonnin, C, Bosler, F, Durand, M, Brisot, D, Brousse, C, De La Fuente, T, Cayman, R, Cazaubon, M, Champion, O, Chanut, M, Chevalet, P, Connault, J, Durant, C, Constans, J, Cordeanu, M, Couturaud, F, Lacut, K, De Dedker, L, Decoulx, E, Derrien, B, Diamand, J, Diard, A, Douadi, Y, Dupas, S, Remond, S, Sevestre, M, Edhery, S, Falvo, N, Taralunga, C, Ferrari, E, Gaillard, C, Garrigues, D, Gillet, J, Giordana, P, Grange, C, Vital-Durand, D, Grare, F, Henni, A, Heuser, S, Schmidt, J, Hidden-Henic, V, Hottin, D, Imbert, B, Pernod, G, Jakob, D, Jacquinandi, V, Jurus, C, Lacoste, A, Laroche, J, Martin, M, Mazollier, C, Mersel, T, Miserey, G, Nedey, C, Nou, M, Quere, I, Ouvry, P, Peuch, B, Pichot, O, Poulain, V, Ray, P, Rifai, A, Roy, P, Saby, J, Simon, F, Simonot-Lalandec, E, Stephan, D, Tissot, A, Vodoungnon, H, Adamczyk, A, Schnabl, S, Ahmad, W, Weber, H, Axthelm, C, Bergmann, K, Beschorner, U, Knittel, M, Binias, K, Pasligh, M, Boral, M, Friederike, G, Bratsch, H, Brauer, G, Burghard, S, Demann, C, Rennebaum, C, Demmig, A, Eberlein, U, Enger, F, Eschenburg, J, Forkmann, L, Frank, J, Freischmidt, H, Gassauer, M, Fritsche, I, Kubicek-Hofmann, C, Goebels, M, Guggenbichler, S, Hartel, D, Hartmann, K, Heilberger, P, Heinsius, A, Held, M, Schnupp, S, Herman, G, Herold, J, Hertrich, F, Hommel, H, Hutte, G, Kalka, C, Jungandreas, K, Ramthor, M, Karcher, J, Werner, N, Karl-Wollweber, S, Keilhau, D, Kittel, K, Knolinski, T, Kohler, C, Werth, S, Kopplin, U, Korner, I, Wittig, K, Kroger, K, Moysidis, T, Kroschel, U, Leschke, M, zur Nieden, T, Lubbert, G, Lutz, A, Wucherpfennig, P, Marencke, G, Mortensen, K, Reppel, M, Nelles, H, Nestler, K, Neumeister, A, Schlosser, A, Oettler, W, Ott, I, Otto, A, Pertermann, A, Pfister, R, Pindur, L, Pourhassan, S, Predel, D, Pudollek, T, Reimer, D, Richter, C, Rieker, E, Rothenbucher, G, Rothhagen, B, Rudolff, S, Stucker, M, Schafer, A, Sonnenschein, K, Schafnitzl, W, Schellong, S, Voigts, B, Schiller, M, Schmeink, T, Schneider, H, Schon, N, Schulze, M, Sechtem, U, Sedl, S, Werno, H, Stachowitz, J, Thieme, M, Tiefenbacher, C, Tsantilas, D, Vieth, P, vom Dahl, J, Grun-Himmelmann, K, von Bilderling, P, von Maltik, T, Weinrich, K, Weyer, M, Koln, E, Wirtz, P, Wittig, I, Zierock, P, Ageno, W, Caprioli, M, Rancan, E, Guercini, F, Mommi, V, Amitrano, M, Cannavacciuolo, F, Amore, M, D'Antoni, S, Angelini, E, Forgia, S, Antignani, P, Calandra, G, Arone, A, Perticone, F, Sciacqua, A, Asaro, G, Bellisi, M, Attanzio, M, Pinto, A, Attinasi, V, Cillari, E, Sorvillo, S, Balbarini, A, Santini, C, Violo, C, Banfi, E, Lodigiani, C, Barcellona, D, Delpin, S, Marongiu, S, Barillari, G, Pasca, S, Bartolini, C, Verdecchia, P, Bartone, M, Mancuso, G, Bellanuova, I, Felis, S, Bellizzi, A, Masotti, L, Bianchi, M, Carugati, A, Bianchini, G, Guarnera, G, Boari, B, Gallerani, M, Pasin, M, Bortoluzzi, C, Parisi, R, Brucoli, C, Palasciano, G, Camporese, G, Tonello, C, Canafoglia, L, Rupoli, S, Cancellieri, E, Paoletti, O, Testa, S, Carlizza, A, Carnovali, M, Sada, S, Samaden, A, Casarsa, C, Mearelli, F, Pivetti, G, Catalini, R, Zingaretti, O, Vascolare, M, Cavazza, S, Cosmi, B, Cenci, C, Prisco, D, Silvestri, E, Ceresa, F, Patane, F, Ciampa, A, Siniscalchi, V, Ciarambino, T, De Bartolomeo, G, Clemente, M, Conti, F, Paiella, L, D'Avino, M, D'Alessandro, A, Placentino, M, Sollazzo, V, D'Angelo, A, Vigano, S, De Campora, P, Sangiuolo, R, De Franciscis, S, Serra, R, De Gaudenzi, E, De Santis, F, Piccinni, G, De Tommaso, I, Di Francesco, L, Vincentelli, G, Di Maggio, R, Saccullo, G, Siragusa, S, Di Micco, P, Fontanella, A, Di Michele, D, Di Minno, G, Tufano, A, Di Nisio, M, Porreca, E, Donadio, F, Imberti, D, Enea, I, Fabbian, F, Manfredini, R, Pala, M, Falanga, A, Milesi, V, Fiore, V, Franco, E, Giudice, G, Frausini, G, Rovinelli, M, Fuorlo, M, Landolfi, R, Morretti, T, Gamberini, S, Salmi, R, Ghirarduzzi, A, Veropalumbo, M, Ghizzi, M, Pepe, C, Gianniello, F, Martinelli, I, Iosub, D, Piovella, F, Iozzi, E, Talerico, A, Regina, M, Orlandini, F, Marconi, L, Palla, A, Marcucci, R, Poli, D, Margheriti, R, Sala, G, Marra, A, Marrocco, F, Montagna, E, Silvestris, F, Vallarelli, S, Mos, L, Rossetto, V, Mugno, F, Di Salvo, M, Nitti, C, Pennacchioni, M, Salvi, A, Olivieri, O, Tosi, F, Zorzi, F, Onesta, M, Pagliara, V, Villalta, S, Paolucci, G, Severino, S, Pierri, F, Russo, V, Pizzini, A, Quintavalla, R, Rubino, P, Ria, L, Schenone, A, Strafino, C, Tropeano, P, Vetrano, A, Zanatta, N, Cansino, M, Gutierrez, J, de las Revillas, F, Fernandez, C, Mijares, N, Blanco-Molina, M, Garcia, M, Seijo, D, Blazquez, R, Lopez-Saez, J, Rodrigo, E, Blanch, J, Arxe, A, Dalmau, F, Quincoces, A, Loizaga, A, Perez, J, Diaz, P, Loaiza, A, Castellote, M, Alcantara, I, Padierna, M, Exposito, M, Mas, A, Castro, F, Sanz, R, de Saracho, J, de la Fuente, E, de Ancos Aracil, C, Ruiz, J, de Daborenea Gonzalez, M, Iglesias, A, de la Fuente Aguado, J, Gonzalez, L, del Carmen Fernandez-Capitan, M, Hernandez, A, del Toro Cervera, J, Rus, G, Bregel, J, Fernandez, F, Teresa Elias, H, Palomares, L, Bataler, R, Rodriguez, J, Garcia, J, Porras, J, Lopez, E, Lazaro, A, Jaras, M, Castro, D, Madridejos, R, Navas, J, Lecumberri, R, Martinez, N, Castellanos, G, Espinosa, L, Jimenez, L, Cobo, O, Saiz, C, Pizarro, Y, Yglesias, P, Martin del Pozo, M, Melibovsky, L, Altarriba, E, Bosch, M, Secades, R, Lujan, J, Mestre, A, Moral, P, Parra, J, Flores, A, Munoz-Torrero, J, Rodriguez, F, Fernandez, M, Sibajas, E, de Sedas, M, Caballero, P, del Campo, I, Sanchez, J, Gallego, A, Alvarez, I, Beltran, E, Fuentes, D, Schilling, V, Alvarez, J, Lopez, G, Caralt, J, Miranda, R, de Antonio, E, Banyai, M, Frank, U, Gian Reto, J, Jeanneret, C, Staub, D, Ackroyd, S, Agarwal, G, Mearns, B, Alikhan, R, Allameddine, A, Al-Refaie, F, Arden, C, Austin, A, Bakhai, A, Barton, T, Ewad, H, Body, R, Thachil, J, Chacko, J, Chandra, D, Charters, F, Church, A, Mcgrane, F, Clements, J, Clifford, P, Cox, D, Crouch, M, Crowther, M, Davies, E, Davies, M, Dimitri, S, Drebes, A, Franklin, S, George, J, Irvine, N, Gerofke, H, Gibbs, C, Goh, T, Gupta, S, Holmes, J, Jackson-Voyzey, E, Jones, N, Kallat, A, Kerr, P, Kesteven, P, Lench, T, Lester, W, Lowe, G, Lewis, M, Mccormack, T, Mccoye, A, Moriarty, A, Morris, W, Myers, B, Narayanan, M, Oo, N, Reed, M, Rose, P, Saja, K, Sivakumaran, M, Sohal, M, Solomons, G, Sultanzadeh, S, Venton, T, Wakeling, J, Walby, C, Waldron, M, Watt, S, Willcock, W, Zafar, A, Agnelli G., Gitt A. K., Bauersachs R., Fronk E. -M., Laeis P., Mismetti P., Monreal M., Willich S. N., Wolf W. -P., Cohen A. T., Brodmann M., Rief P., Eischer L., Stoshikj S., Hirschl M., Weinmann S., Marschang P., Abbadie F., Achkar A., Addala A., Adnet F., Alexandra J. -F., Aquilanti S., Belhassane A., Benaroya A., Berremili T., Grenot M. C., Birr V., Holtea D., Bonnin C., Bosler F., Durand M. -G. B., Brisot D., Brousse C., De La Fuente T., Cayman R., Cazaubon M., Champion O., Chanut M., Chevalet P., Connault J., Durant C., Constans J., Cordeanu M., Couturaud F., Lacut K., De Dedker L., Decoulx E., Derrien B., Diamand J. -M., Diard A., Douadi Y., Dupas S., Remond S. S. M., Sevestre M. -A., Edhery S., Falvo N., Taralunga C. F., Ferrari E., Gaillard C., Garrigues D., Gillet J. L., Giordana P., Grange C., Vital-Durand D., Grare F., Henni A. H., Heuser S., Schmidt J., Hidden-Henic V., Hottin D., Imbert B., Pernod G., Jakob D., Jacquinandi V., Jurus C., Lacoste A., Laroche J. -P., Martin M., Mazollier C., Mersel T., Miserey G., Nedey C., Nou M., Quere I., Ouvry P., Peuch B., Pichot O., Poulain V., Ray P., Rifai A., Roy P. -M., Saby J. -C., Simon F., Simonot-Lalandec E., Stephan D., Tissot A., Vodoungnon H., Adamczyk A., Schnabl S., Ahmad W. A., Weber H., Axthelm C., Bergmann K., Beschorner U., Knittel M., Binias K. -H., Pasligh M., Boral M., Friederike G., Bratsch H., Brauer G., Burghard S., Demann C., Rennebaum C., Demmig A., Eberlein U., Enger F., Eschenburg J., Forkmann L., Frank J., Freischmidt H., Gassauer M., Fritsche I., Kubicek-Hofmann C., Goebels M. -C., Guggenbichler S., Hartel D., Hartmann K., Heilberger P., Heinsius A., Held M., Schnupp S., Herman G., Herold J., Hertrich F., Hommel H., Hutte G., Kalka C., Jungandreas K., Ramthor M., Karcher J., Werner N., Karl-Wollweber S., Keilhau D. -A., Kittel K., Knolinski T., Kohler C., Werth S., Kopplin U., Korner I., Wittig K., Kroger K., Moysidis T., Kroschel U., Leschke M., zur Nieden T., Lubbert G., Lutz A., Wucherpfennig P., Marencke G. -H., Mortensen K., Reppel M., Nelles H., Nestler K., Neumeister A., Schlosser A., Oettler W., Ott I., Otto A., Pertermann A., Pfister R., Pindur L., Pourhassan S., Predel D., Pudollek T., Reimer D., Richter C., Rieker E., Rothenbucher G., Rothhagen B., Rudolff S., Stucker M., Schafer A., Sonnenschein K., Schafnitzl W., Schellong S., Voigts B., Schiller M., Schmeink T., Schneider H., Schon N., Schulze M., Sechtem U., Sedl S., Werno H. S., Stachowitz J., Thieme M., Tiefenbacher C., Tsantilas D., Vieth P., vom Dahl J., Grun-Himmelmann K., von Bilderling P., von Maltik T., Weinrich K., Weyer M., Koln E. K., Wirtz P., Wittig I., Zierock P., Ageno W., Caprioli M., Rancan E., Guercini F., Mommi V., Amitrano M., Cannavacciuolo F., Amore M., D'Antoni S., Angelini E., Forgia S. L., Antignani P. L., Calandra G., Arone A., Perticone F., Sciacqua A., Asaro G., Bellisi M., Attanzio M. T., Pinto A., Attinasi V., Cillari E., Sorvillo S., Balbarini A., Santini C., Violo C., Banfi E., Lodigiani C., Barcellona D., Delpin S., Marongiu S., Barillari G., Pasca S., Bartolini C., Verdecchia P., Bartone M., Mancuso G., Bellanuova I., Felis S., Bellizzi A., Masotti L., Bianchi M., Carugati A., Bianchini G., Guarnera G., Boari B., Gallerani M., Pasin M., Bortoluzzi C., Parisi R., Brucoli C., Palasciano G., Camporese G., Tonello C., Canafoglia L., Rupoli S., Cancellieri E., Paoletti O., Testa S., Carlizza A., Carnovali M., Sada S., Samaden A., Casarsa C., Mearelli F., Pivetti G., Catalini R., Zingaretti O., Vascolare M., Cavazza S., Cosmi B., Cenci C., Prisco D., Silvestri E., Ceresa F., Patane F., Ciampa A., Siniscalchi V., Ciarambino T., De Bartolomeo G., Clemente M., Conti F., Paiella L., D'Avino M., D'Alessandro A., Placentino M., Sollazzo V., D'Angelo A., Vigano S., De Campora P., Sangiuolo R., De Franciscis S., Serra R., De Gaudenzi E., De Santis F., Piccinni G. C., De Tommaso I. D., Di Francesco L., Vincentelli G. M., Di Maggio R., Saccullo G., Siragusa S., Di Micco P., Fontanella A., Di Michele D., Di Minno G., Tufano A., Di Nisio M., Porreca E., Donadio F., Imberti D., Enea I., Fabbian F., Manfredini R., Pala M., Falanga A., Milesi V., Fiore V., Franco E., Giudice G., Frausini G., Rovinelli M., Fuorlo M., Landolfi R., Morretti T., Gamberini S., Salmi R., Ghirarduzzi A., Veropalumbo M. R., Ghizzi M., Pepe C., Gianniello F., Martinelli I., Iosub D. I., Piovella F., Iozzi E., Talerico A., Regina M. L., Orlandini F., Marconi L., Palla A., Marcucci R., Poli D., Margheriti R., Sala G., Marra A., Marrocco F., Montagna E. S., Silvestris F., Vallarelli S., Mos L., Rossetto V., Mugno F., Di Salvo M., Nitti C., Pennacchioni M., Salvi A., Olivieri O., Tosi F., Zorzi F., Onesta M., Pagliara V., Villalta S., Paolucci G., Severino S., Pierri F., Russo V., Pizzini A. M., Quintavalla R., Rubino P., Ria L., Schenone A., Strafino C., Tropeano P., Vetrano A., Zanatta N., Cansino M. D. A., Gutierrez J. A., de las Revillas F. A., Fernandez C. A., Mijares N. C., Blanco-Molina M. A., Garcia M. A., Seijo D. J., Blazquez R. A., Lopez-Saez J. -B., Rodrigo E. A., Blanch J. V., Arxe A. A., Dalmau F. G. -B., Quincoces A. B., Loizaga A. G., Perez J. L. B., Diaz P. B., Loaiza A. Q., Castellote M. C., Alcantara I. C., Padierna M. L., Exposito M. C., Mas A. C., Castro F. C., Sanz R. C., de Saracho J. O., de la Fuente E. C., de Ancos Aracil C., Ruiz J. R., de Daborenea Gonzalez M. D., Iglesias A. F., de la Fuente Aguado J., Gonzalez L. G., del Carmen Fernandez-Capitan M., Hernandez A. L., del Toro Cervera J., Rus G. P., Bregel J. L. D., Fernandez F. D., Teresa Elias Hernandez, Palomares L. J., Bataler R. F., Rodriguez J. A. N., Garcia J. M. G., Porras J. R. G., Garcia M. G., Lopez E. H., Lazaro A. R., Jaras M. J., Castro D. J., Madridejos R. J. -R., Navas J. M. P., Lecumberri R., Martinez N., Castellanos G. T. L., Espinosa L. M., Jimenez L. L., Cobo O. M., Saiz C. M., Pizarro Y. R., Yglesias P. J. M., Martin del Pozo M., Melibovsky L., Altarriba E. S., Bosch M. M., Secades R. M., Lujan J. M. M., Mestre A. R., Moral P. M., Parra J. A. T., Flores A. M., Munoz-Torrero J. F. S., Rodriguez F. J. M., Fernandez M. J. N., Sibajas E. O., de Sedas M. V., Caballero P. P., del Campo I. P. M., Sanchez J. P., Gallego A. R., alvarez I. V., Beltran E. M. R., Fuentes D. S., Schilling V. R., alvarez J. S., Lopez G. T., Caralt J. M. S., Miranda R. T., de Antonio E. U., Banyai M., Frank U., Gian Reto Jorg, Jeanneret C., Staub D., Ackroyd S., Agarwal G., Mearns B., Alikhan R., Allameddine A., Al-Refaie F., Arden C., Austin A., Bakhai A., Barton T., Ewad H., Body R., Thachil J., Chacko J., Chandra D., Charters F., Church A., McGrane F., Clements J., Clifford P., Cox D., Crouch M., Crowther M., Davies E., Davies M., Dimitri S., Drebes A., Franklin S., George J., Irvine N., Gerofke H., Gibbs C., Goh T., Gupta S., Holmes J., Jackson-Voyzey E., Jones N., Kallat A., Kerr P., Kesteven P., Lench T., Lester W., Lowe G., Lewis M., McCormack T., McCoye A., Moriarty A., Morris W., Myers B., Narayanan M., Oo N., Reed M., Rose P., Saja K., Sivakumaran M., Sohal M., Solomons G., Sultanzadeh S. J., Venton T., Wakeling J., Walby C., Waldron M., Watt S., Willcock W., Zafar A., Agnelli, G, Gitt, A, Bauersachs, R, Fronk, E, Laeis, P, Mismetti, P, Monreal, M, Willich, S, Wolf, W, Cohen, A, Brodmann, M, Rief, P, Eischer, L, Stoshikj, S, Hirschl, M, Weinmann, S, Marschang, P, Abbadie, F, Achkar, A, Addala, A, Adnet, F, Alexandra, J, Aquilanti, S, Belhassane, A, Benaroya, A, Berremili, T, Grenot, M, Birr, V, Holtea, D, Bonnin, C, Bosler, F, Durand, M, Brisot, D, Brousse, C, De La Fuente, T, Cayman, R, Cazaubon, M, Champion, O, Chanut, M, Chevalet, P, Connault, J, Durant, C, Constans, J, Cordeanu, M, Couturaud, F, Lacut, K, De Dedker, L, Decoulx, E, Derrien, B, Diamand, J, Diard, A, Douadi, Y, Dupas, S, Remond, S, Sevestre, M, Edhery, S, Falvo, N, Taralunga, C, Ferrari, E, Gaillard, C, Garrigues, D, Gillet, J, Giordana, P, Grange, C, Vital-Durand, D, Grare, F, Henni, A, Heuser, S, Schmidt, J, Hidden-Henic, V, Hottin, D, Imbert, B, Pernod, G, Jakob, D, Jacquinandi, V, Jurus, C, Lacoste, A, Laroche, J, Martin, M, Mazollier, C, Mersel, T, Miserey, G, Nedey, C, Nou, M, Quere, I, Ouvry, P, Peuch, B, Pichot, O, Poulain, V, Ray, P, Rifai, A, Roy, P, Saby, J, Simon, F, Simonot-Lalandec, E, Stephan, D, Tissot, A, Vodoungnon, H, Adamczyk, A, Schnabl, S, Ahmad, W, Weber, H, Axthelm, C, Bergmann, K, Beschorner, U, Knittel, M, Binias, K, Pasligh, M, Boral, M, Friederike, G, Bratsch, H, Brauer, G, Burghard, S, Demann, C, Rennebaum, C, Demmig, A, Eberlein, U, Enger, F, Eschenburg, J, Forkmann, L, Frank, J, Freischmidt, H, Gassauer, M, Fritsche, I, Kubicek-Hofmann, C, Goebels, M, Guggenbichler, S, Hartel, D, Hartmann, K, Heilberger, P, Heinsius, A, Held, M, Schnupp, S, Herman, G, Herold, J, Hertrich, F, Hommel, H, Hutte, G, Kalka, C, Jungandreas, K, Ramthor, M, Karcher, J, Werner, N, Karl-Wollweber, S, Keilhau, D, Kittel, K, Knolinski, T, Kohler, C, Werth, S, Kopplin, U, Korner, I, Wittig, K, Kroger, K, Moysidis, T, Kroschel, U, Leschke, M, zur Nieden, T, Lubbert, G, Lutz, A, Wucherpfennig, P, Marencke, G, Mortensen, K, Reppel, M, Nelles, H, Nestler, K, Neumeister, A, Schlosser, A, Oettler, W, Ott, I, Otto, A, Pertermann, A, Pfister, R, Pindur, L, Pourhassan, S, Predel, D, Pudollek, T, Reimer, D, Richter, C, Rieker, E, Rothenbucher, G, Rothhagen, B, Rudolff, S, Stucker, M, Schafer, A, Sonnenschein, K, Schafnitzl, W, Schellong, S, Voigts, B, Schiller, M, Schmeink, T, Schneider, H, Schon, N, Schulze, M, Sechtem, U, Sedl, S, Werno, H, Stachowitz, J, Thieme, M, Tiefenbacher, C, Tsantilas, D, Vieth, P, vom Dahl, J, Grun-Himmelmann, K, von Bilderling, P, von Maltik, T, Weinrich, K, Weyer, M, Koln, E, Wirtz, P, Wittig, I, Zierock, P, Ageno, W, Caprioli, M, Rancan, E, Guercini, F, Mommi, V, Amitrano, M, Cannavacciuolo, F, Amore, M, D'Antoni, S, Angelini, E, Forgia, S, Antignani, P, Calandra, G, Arone, A, Perticone, F, Sciacqua, A, Asaro, G, Bellisi, M, Attanzio, M, Pinto, A, Attinasi, V, Cillari, E, Sorvillo, S, Balbarini, A, Santini, C, Violo, C, Banfi, E, Lodigiani, C, Barcellona, D, Delpin, S, Marongiu, S, Barillari, G, Pasca, S, Bartolini, C, Verdecchia, P, Bartone, M, Mancuso, G, Bellanuova, I, Felis, S, Bellizzi, A, Masotti, L, Bianchi, M, Carugati, A, Bianchini, G, Guarnera, G, Boari, B, Gallerani, M, Pasin, M, Bortoluzzi, C, Parisi, R, Brucoli, C, Palasciano, G, Camporese, G, Tonello, C, Canafoglia, L, Rupoli, S, Cancellieri, E, Paoletti, O, Testa, S, Carlizza, A, Carnovali, M, Sada, S, Samaden, A, Casarsa, C, Mearelli, F, Pivetti, G, Catalini, R, Zingaretti, O, Vascolare, M, Cavazza, S, Cosmi, B, Cenci, C, Prisco, D, Silvestri, E, Ceresa, F, Patane, F, Ciampa, A, Siniscalchi, V, Ciarambino, T, De Bartolomeo, G, Clemente, M, Conti, F, Paiella, L, D'Avino, M, D'Alessandro, A, Placentino, M, Sollazzo, V, D'Angelo, A, Vigano, S, De Campora, P, Sangiuolo, R, De Franciscis, S, Serra, R, De Gaudenzi, E, De Santis, F, Piccinni, G, De Tommaso, I, Di Francesco, L, Vincentelli, G, Di Maggio, R, Saccullo, G, Siragusa, S, Di Micco, P, Fontanella, A, Di Michele, D, Di Minno, G, Tufano, A, Di Nisio, M, Porreca, E, Donadio, F, Imberti, D, Enea, I, Fabbian, F, Manfredini, R, Pala, M, Falanga, A, Milesi, V, Fiore, V, Franco, E, Giudice, G, Frausini, G, Rovinelli, M, Fuorlo, M, Landolfi, R, Morretti, T, Gamberini, S, Salmi, R, Ghirarduzzi, A, Veropalumbo, M, Ghizzi, M, Pepe, C, Gianniello, F, Martinelli, I, Iosub, D, Piovella, F, Iozzi, E, Talerico, A, Regina, M, Orlandini, F, Marconi, L, Palla, A, Marcucci, R, Poli, D, Margheriti, R, Sala, G, Marra, A, Marrocco, F, Montagna, E, Silvestris, F, Vallarelli, S, Mos, L, Rossetto, V, Mugno, F, Di Salvo, M, Nitti, C, Pennacchioni, M, Salvi, A, Olivieri, O, Tosi, F, Zorzi, F, Onesta, M, Pagliara, V, Villalta, S, Paolucci, G, Severino, S, Pierri, F, Russo, V, Pizzini, A, Quintavalla, R, Rubino, P, Ria, L, Schenone, A, Strafino, C, Tropeano, P, Vetrano, A, Zanatta, N, Cansino, M, Gutierrez, J, de las Revillas, F, Fernandez, C, Mijares, N, Blanco-Molina, M, Garcia, M, Seijo, D, Blazquez, R, Lopez-Saez, J, Rodrigo, E, Blanch, J, Arxe, A, Dalmau, F, Quincoces, A, Loizaga, A, Perez, J, Diaz, P, Loaiza, A, Castellote, M, Alcantara, I, Padierna, M, Exposito, M, Mas, A, Castro, F, Sanz, R, de Saracho, J, de la Fuente, E, de Ancos Aracil, C, Ruiz, J, de Daborenea Gonzalez, M, Iglesias, A, de la Fuente Aguado, J, Gonzalez, L, del Carmen Fernandez-Capitan, M, Hernandez, A, del Toro Cervera, J, Rus, G, Bregel, J, Fernandez, F, Teresa Elias, H, Palomares, L, Bataler, R, Rodriguez, J, Garcia, J, Porras, J, Lopez, E, Lazaro, A, Jaras, M, Castro, D, Madridejos, R, Navas, J, Lecumberri, R, Martinez, N, Castellanos, G, Espinosa, L, Jimenez, L, Cobo, O, Saiz, C, Pizarro, Y, Yglesias, P, Martin del Pozo, M, Melibovsky, L, Altarriba, E, Bosch, M, Secades, R, Lujan, J, Mestre, A, Moral, P, Parra, J, Flores, A, Munoz-Torrero, J, Rodriguez, F, Fernandez, M, Sibajas, E, de Sedas, M, Caballero, P, del Campo, I, Sanchez, J, Gallego, A, Alvarez, I, Beltran, E, Fuentes, D, Schilling, V, Alvarez, J, Lopez, G, Caralt, J, Miranda, R, de Antonio, E, Banyai, M, Frank, U, Gian Reto, J, Jeanneret, C, Staub, D, Ackroyd, S, Agarwal, G, Mearns, B, Alikhan, R, Allameddine, A, Al-Refaie, F, Arden, C, Austin, A, Bakhai, A, Barton, T, Ewad, H, Body, R, Thachil, J, Chacko, J, Chandra, D, Charters, F, Church, A, Mcgrane, F, Clements, J, Clifford, P, Cox, D, Crouch, M, Crowther, M, Davies, E, Davies, M, Dimitri, S, Drebes, A, Franklin, S, George, J, Irvine, N, Gerofke, H, Gibbs, C, Goh, T, Gupta, S, Holmes, J, Jackson-Voyzey, E, Jones, N, Kallat, A, Kerr, P, Kesteven, P, Lench, T, Lester, W, Lowe, G, Lewis, M, Mccormack, T, Mccoye, A, Moriarty, A, Morris, W, Myers, B, Narayanan, M, Oo, N, Reed, M, Rose, P, Saja, K, Sivakumaran, M, Sohal, M, Solomons, G, Sultanzadeh, S, Venton, T, Wakeling, J, Walby, C, Waldron, M, Watt, S, Willcock, W, Zafar, A, Agnelli G., Gitt A. K., Bauersachs R., Fronk E. -M., Laeis P., Mismetti P., Monreal M., Willich S. N., Wolf W. -P., Cohen A. T., Brodmann M., Rief P., Eischer L., Stoshikj S., Hirschl M., Weinmann S., Marschang P., Abbadie F., Achkar A., Addala A., Adnet F., Alexandra J. -F., Aquilanti S., Belhassane A., Benaroya A., Berremili T., Grenot M. C., Birr V., Holtea D., Bonnin C., Bosler F., Durand M. -G. B., Brisot D., Brousse C., De La Fuente T., Cayman R., Cazaubon M., Champion O., Chanut M., Chevalet P., Connault J., Durant C., Constans J., Cordeanu M., Couturaud F., Lacut K., De Dedker L., Decoulx E., Derrien B., Diamand J. -M., Diard A., Douadi Y., Dupas S., Remond S. S. M., Sevestre M. -A., Edhery S., Falvo N., Taralunga C. F., Ferrari E., Gaillard C., Garrigues D., Gillet J. L., Giordana P., Grange C., Vital-Durand D., Grare F., Henni A. H., Heuser S., Schmidt J., Hidden-Henic V., Hottin D., Imbert B., Pernod G., Jakob D., Jacquinandi V., Jurus C., Lacoste A., Laroche J. -P., Martin M., Mazollier C., Mersel T., Miserey G., Nedey C., Nou M., Quere I., Ouvry P., Peuch B., Pichot O., Poulain V., Ray P., Rifai A., Roy P. -M., Saby J. -C., Simon F., Simonot-Lalandec E., Stephan D., Tissot A., Vodoungnon H., Adamczyk A., Schnabl S., Ahmad W. A., Weber H., Axthelm C., Bergmann K., Beschorner U., Knittel M., Binias K. -H., Pasligh M., Boral M., Friederike G., Bratsch H., Brauer G., Burghard S., Demann C., Rennebaum C., Demmig A., Eberlein U., Enger F., Eschenburg J., Forkmann L., Frank J., Freischmidt H., Gassauer M., Fritsche I., Kubicek-Hofmann C., Goebels M. -C., Guggenbichler S., Hartel D., Hartmann K., Heilberger P., Heinsius A., Held M., Schnupp S., Herman G., Herold J., Hertrich F., Hommel H., Hutte G., Kalka C., Jungandreas K., Ramthor M., Karcher J., Werner N., Karl-Wollweber S., Keilhau D. -A., Kittel K., Knolinski T., Kohler C., Werth S., Kopplin U., Korner I., Wittig K., Kroger K., Moysidis T., Kroschel U., Leschke M., zur Nieden T., Lubbert G., Lutz A., Wucherpfennig P., Marencke G. -H., Mortensen K., Reppel M., Nelles H., Nestler K., Neumeister A., Schlosser A., Oettler W., Ott I., Otto A., Pertermann A., Pfister R., Pindur L., Pourhassan S., Predel D., Pudollek T., Reimer D., Richter C., Rieker E., Rothenbucher G., Rothhagen B., Rudolff S., Stucker M., Schafer A., Sonnenschein K., Schafnitzl W., Schellong S., Voigts B., Schiller M., Schmeink T., Schneider H., Schon N., Schulze M., Sechtem U., Sedl S., Werno H. S., Stachowitz J., Thieme M., Tiefenbacher C., Tsantilas D., Vieth P., vom Dahl J., Grun-Himmelmann K., von Bilderling P., von Maltik T., Weinrich K., Weyer M., Koln E. K., Wirtz P., Wittig I., Zierock P., Ageno W., Caprioli M., Rancan E., Guercini F., Mommi V., Amitrano M., Cannavacciuolo F., Amore M., D'Antoni S., Angelini E., Forgia S. L., Antignani P. L., Calandra G., Arone A., Perticone F., Sciacqua A., Asaro G., Bellisi M., Attanzio M. T., Pinto A., Attinasi V., Cillari E., Sorvillo S., Balbarini A., Santini C., Violo C., Banfi E., Lodigiani C., Barcellona D., Delpin S., Marongiu S., Barillari G., Pasca S., Bartolini C., Verdecchia P., Bartone M., Mancuso G., Bellanuova I., Felis S., Bellizzi A., Masotti L., Bianchi M., Carugati A., Bianchini G., Guarnera G., Boari B., Gallerani M., Pasin M., Bortoluzzi C., Parisi R., Brucoli C., Palasciano G., Camporese G., Tonello C., Canafoglia L., Rupoli S., Cancellieri E., Paoletti O., Testa S., Carlizza A., Carnovali M., Sada S., Samaden A., Casarsa C., Mearelli F., Pivetti G., Catalini R., Zingaretti O., Vascolare M., Cavazza S., Cosmi B., Cenci C., Prisco D., Silvestri E., Ceresa F., Patane F., Ciampa A., Siniscalchi V., Ciarambino T., De Bartolomeo G., Clemente M., Conti F., Paiella L., D'Avino M., D'Alessandro A., Placentino M., Sollazzo V., D'Angelo A., Vigano S., De Campora P., Sangiuolo R., De Franciscis S., Serra R., De Gaudenzi E., De Santis F., Piccinni G. C., De Tommaso I. D., Di Francesco L., Vincentelli G. M., Di Maggio R., Saccullo G., Siragusa S., Di Micco P., Fontanella A., Di Michele D., Di Minno G., Tufano A., Di Nisio M., Porreca E., Donadio F., Imberti D., Enea I., Fabbian F., Manfredini R., Pala M., Falanga A., Milesi V., Fiore V., Franco E., Giudice G., Frausini G., Rovinelli M., Fuorlo M., Landolfi R., Morretti T., Gamberini S., Salmi R., Ghirarduzzi A., Veropalumbo M. R., Ghizzi M., Pepe C., Gianniello F., Martinelli I., Iosub D. I., Piovella F., Iozzi E., Talerico A., Regina M. L., Orlandini F., Marconi L., Palla A., Marcucci R., Poli D., Margheriti R., Sala G., Marra A., Marrocco F., Montagna E. S., Silvestris F., Vallarelli S., Mos L., Rossetto V., Mugno F., Di Salvo M., Nitti C., Pennacchioni M., Salvi A., Olivieri O., Tosi F., Zorzi F., Onesta M., Pagliara V., Villalta S., Paolucci G., Severino S., Pierri F., Russo V., Pizzini A. M., Quintavalla R., Rubino P., Ria L., Schenone A., Strafino C., Tropeano P., Vetrano A., Zanatta N., Cansino M. D. A., Gutierrez J. A., de las Revillas F. A., Fernandez C. A., Mijares N. C., Blanco-Molina M. A., Garcia M. A., Seijo D. J., Blazquez R. A., Lopez-Saez J. -B., Rodrigo E. A., Blanch J. V., Arxe A. A., Dalmau F. G. -B., Quincoces A. B., Loizaga A. G., Perez J. L. B., Diaz P. B., Loaiza A. Q., Castellote M. C., Alcantara I. C., Padierna M. L., Exposito M. C., Mas A. C., Castro F. C., Sanz R. C., de Saracho J. O., de la Fuente E. C., de Ancos Aracil C., Ruiz J. R., de Daborenea Gonzalez M. D., Iglesias A. F., de la Fuente Aguado J., Gonzalez L. G., del Carmen Fernandez-Capitan M., Hernandez A. L., del Toro Cervera J., Rus G. P., Bregel J. L. D., Fernandez F. D., Teresa Elias Hernandez, Palomares L. J., Bataler R. F., Rodriguez J. A. N., Garcia J. M. G., Porras J. R. G., Garcia M. G., Lopez E. H., Lazaro A. R., Jaras M. J., Castro D. J., Madridejos R. J. -R., Navas J. M. P., Lecumberri R., Martinez N., Castellanos G. T. L., Espinosa L. M., Jimenez L. L., Cobo O. M., Saiz C. M., Pizarro Y. R., Yglesias P. J. M., Martin del Pozo M., Melibovsky L., Altarriba E. S., Bosch M. M., Secades R. M., Lujan J. M. M., Mestre A. R., Moral P. M., Parra J. A. T., Flores A. M., Munoz-Torrero J. F. S., Rodriguez F. J. M., Fernandez M. J. N., Sibajas E. O., de Sedas M. V., Caballero P. P., del Campo I. P. M., Sanchez J. P., Gallego A. R., alvarez I. V., Beltran E. M. R., Fuentes D. S., Schilling V. R., alvarez J. S., Lopez G. T., Caralt J. M. S., Miranda R. T., de Antonio E. U., Banyai M., Frank U., Gian Reto Jorg, Jeanneret C., Staub D., Ackroyd S., Agarwal G., Mearns B., Alikhan R., Allameddine A., Al-Refaie F., Arden C., Austin A., Bakhai A., Barton T., Ewad H., Body R., Thachil J., Chacko J., Chandra D., Charters F., Church A., McGrane F., Clements J., Clifford P., Cox D., Crouch M., Crowther M., Davies E., Davies M., Dimitri S., Drebes A., Franklin S., George J., Irvine N., Gerofke H., Gibbs C., Goh T., Gupta S., Holmes J., Jackson-Voyzey E., Jones N., Kallat A., Kerr P., Kesteven P., Lench T., Lester W., Lowe G., Lewis M., McCormack T., McCoye A., Moriarty A., Morris W., Myers B., Narayanan M., Oo N., Reed M., Rose P., Saja K., Sivakumaran M., Sohal M., Solomons G., Sultanzadeh S. J., Venton T., Wakeling J., Walby C., Waldron M., Watt S., Willcock W., and Zafar A.

Abstract

Background: Venous thromboembolism (VTE) is a major health problem, with over one million events every year in Europe. However, there is a paucity of data on the current management in real life, including factors influencing treatment pathways, patient satisfaction, quality of life (QoL), and utilization of health care resources and the corresponding costs. The PREFER in VTE registry has been designed to address this and to understand medical care and needs as well as potential gaps for improvement. Methods/design: The PREFER in VTE registry was a prospective, observational, multicenter study conducted in seven European countries including Austria, France Germany, Italy, Spain, Switzerland, and the UK to assess the characteristics and the management of patients with VTE, the use of health care resources, and to provide data to estimate the costs for 12 months treatment following a first-time and/or recurrent VTE diagnosed in hospitals or specialized or primary care centers. In addition, existing anticoagulant treatment patterns, patient pathways, clinical outcomes, treatment satisfaction, and health related QoL were documented. The centers were chosen to reflect the care environment in which patients with VTE are managed in each of the participating countries. Patients were eligible to be enrolled into the registry if they were at least 18 years old, had a symptomatic, objectively confirmed first time or recurrent acute VTE defined as either distal or proximal deep vein thrombosis, pulmonary embolism or both. After the baseline visit at the time of the acute VTE event, further follow-up documentations occurred at 1, 3, 6 and 12 months. Follow-up data was collected by either routinely scheduled visits or by telephone calls. Results: Overall, 381 centers participated, which enrolled 3,545 patients during an observational period of 1 year. Conclusion: The PREFER in VTE registry will provide valuable insights into the characteristics of patients with VTE and their acute

Published
2015

50. Safety of vitamin K antagonist treatment for splanchnic vein thrombosis: a multicenter cohort study

Author

Riva, N, Ageno, W, Poli, D, Testa, S, Rupoli, S, Santoro, R, Lerede, T, Piana, A, Carpenedo, M, Nicolini, A, Ferrini, P, Tosetto, A, Paoletti, O, Rancan, E, Federici, I, Canafoglia, L, Lancisi, G, Salesi, G, Maggioni, A, Falanga, A, Martini, G, Mangione, C, Contino, L, Bonfanti, C, Gresele, P, Marigo, L, Nante, G, Sivera, P, Pasca, S, Malcangi, G, Ettorre, C, Cavallero, B, Falco, P, Ruocco, L, Paparo, C, Bucherini, E, Suriano, L, Crisantemo, R, Toma, A, Insana, A, Zanatta, N, Iannone, A, Oriana, V, Pezzo, M, Isu, G, Molinatti, M, Riva N, Ageno W, Poli D, Testa S, Rupoli S, Santoro R, Lerede T, Piana A, Carpenedo M, Nicolini A, Ferrini PM, Tosetto A, Paoletti O, Rancan E, Federici I, Canafoglia L, Lancisi GM, Salesi G, Maggioni A, Falanga A, Martini G, Mangione C, Contino L, Bonfanti C, Gresele P, Marigo L, Nante G, Sivera P, Pasca S, Malcangi G, Ettorre CP, Cavallero B, Falco P, Ruocco L, Paparo C, Bucherini E, Suriano L, Crisantemo R, Toma A, Insana A, Zanatta N, Iannone AM, Oriana V, Pezzo MP, Isu G, Molinatti M, Riva, N, Ageno, W, Poli, D, Testa, S, Rupoli, S, Santoro, R, Lerede, T, Piana, A, Carpenedo, M, Nicolini, A, Ferrini, P, Tosetto, A, Paoletti, O, Rancan, E, Federici, I, Canafoglia, L, Lancisi, G, Salesi, G, Maggioni, A, Falanga, A, Martini, G, Mangione, C, Contino, L, Bonfanti, C, Gresele, P, Marigo, L, Nante, G, Sivera, P, Pasca, S, Malcangi, G, Ettorre, C, Cavallero, B, Falco, P, Ruocco, L, Paparo, C, Bucherini, E, Suriano, L, Crisantemo, R, Toma, A, Insana, A, Zanatta, N, Iannone, A, Oriana, V, Pezzo, M, Isu, G, Molinatti, M, Riva N, Ageno W, Poli D, Testa S, Rupoli S, Santoro R, Lerede T, Piana A, Carpenedo M, Nicolini A, Ferrini PM, Tosetto A, Paoletti O, Rancan E, Federici I, Canafoglia L, Lancisi GM, Salesi G, Maggioni A, Falanga A, Martini G, Mangione C, Contino L, Bonfanti C, Gresele P, Marigo L, Nante G, Sivera P, Pasca S, Malcangi G, Ettorre CP, Cavallero B, Falco P, Ruocco L, Paparo C, Bucherini E, Suriano L, Crisantemo R, Toma A, Insana A, Zanatta N, Iannone AM, Oriana V, Pezzo MP, Isu G, and Molinatti M

Abstract

Background: The treatment of splanchnic vein thrombosis (SVT) is challenging, due to the increased risk of bleeding and potentially life-threatening complications. Current recommendations are based on evidence from the treatment of venous thrombosis in usual sites, but small observational studies in SVT population suggest that the bleeding risk may offset the benefit of anticoagulant treatment in this setting. The aim of this study was to evaluate the safety of vitamin K antagonists (VKAs) in SVT patients. Methods: We retrospectively included SVT patients treated with VKAs followed by 37 Italian anticoagulation clinics, until June 2013. The primary outcome was the incidence of major bleeding (MB), according to the ISTH definition, during VKA treatment. Vascular events, including both arterial and venous thrombosis, and mortality were also documented. Results: Three hundred and seventy-five patients were included (median age 53 years; 54.7% males). During a median VKA treatment duration of 1.98 years, 15 MB events occurred, corresponding to an incidence rate of 1.24 (95% confidence interval [CI], 0.75-2.06) per 100 patient-years. Gastrointestinal bleeding represented 40% of all MB events. At multivariate analysis, the presence of esophageal varices emerged as independent predictor of MB (hazard ratio 5.4; 95% CI, 1.4-21.1). The incidence rate of vascular events on treatment was 1.37 (95% CI, 0.84-2.23) per 100 patient-years and the mortality rate was 0.83 (95% CI, 0.44-1.54) per 100 patient-years. Conclusions: Selected SVT patients followed by anticoagulation clinics for the management of VKA treatment show a low rate of major bleeding and vascular events.

Published
2015

Catalog

Books, media, physical & digital resources
See catalog results