Search

Your search keyword '"Balestrini, S.' showing total 286 results
Start Over Author "Balestrini, S.
286 results on '"Balestrini, S.'

2. Whole genome sequencing identifies putative associations between genomic polymorphisms and clinical response to the antiepileptic drug levetiracetam

Author

Vavoulis, DV, Pagnamenta, AT, Knight, SJL, Pentony, MM, Armstrong, M, Galizia, EC, Balestrini, S, Sisodiya, SM, and Taylor, JC

Subjects
Quantitative Biology - Genomics
Abstract

In the context of pharmacogenomics, whole genome sequencing provides a powerful approach for identifying correlations between response variability to specific drugs and genomic polymorphisms in a population, in an unbiased manner. In this study, we employed whole genome sequencing of DNA samples from patients showing extreme response (n=72) and non-response (n=27) to the antiepileptic drug levetiracetam, in order to identify genomic variants that underlie response to the drug. Although no common SNP (MAF>5%) crossed the conventional genome-wide significance threshold of 5e-8, we found common polymorphisms in genes SPNS3, HDC, MDGA2, NSG1 and RASGEF1C, which collectively predict clinical response to levetiracetam in our cohort with ~91% predictive accuracy. Among these genes, HDC, NSG1, MDGA2 and RASGEF1C are potentially implicated in synaptic neurotransmission, while SPNS3 is an atypical solute carrier transporter homologous to SV2A, the known molecular target of levetiracetam. Furthermore, we performed gene- and pathway-based statistical analysis on sets of rare and low-frequency variants (MAF<5%) and we identified associations between the following genes or pathways and response to levetiracetam: a) genes PRKCB and DLG2, which are involved in glutamatergic neurotransmission, a known target of anticonvulsants, including levetiracetam; b) genes FILIP1 and SEMA6D, which are involved in axon guidance and modelling of neural connections; and c) pathways with a role in synaptic neurotransmission, such as WNT5A-dependent internalization of FZD4 and disinhibition of SNARE formation. In summary, our approach to utilise whole genome sequencing on subjects with extreme response phenotypes is a feasible route to generate plausible hypotheses for investigating the genetic factors underlying drug response variability in cases of pharmaco-resistant epilepsy.

Published
2019

3. Dissecting genetics of spectrum of epilepsies with eyelid myoclonia by exome sequencing

Author

Coppola, A, Krithika, S, Iacomino, M, Bobbili, D, Balestrini, S, Bagnasco, I, Bilo, L, Buti, D, Casellato, S, Cuccurullo, C, Ferlazzo, E, Leu, C, Giordano, L, Gobbi, G, Hernandez-Hernandez, L, Lench, N, Martins, H, Meletti, S, Messana, T, Nigro, V, Pinelli, M, Pippucci, T, Bellampalli, R, Salis, B, Sofia, V, Striano, P, Striano, S, Tassi, L, Vignoli, A, Vaudano, AE, Viri, M, Scheffer, IE, May, P, Zara, F, Sisodiya, SM, Coppola, A, Krithika, S, Iacomino, M, Bobbili, D, Balestrini, S, Bagnasco, I, Bilo, L, Buti, D, Casellato, S, Cuccurullo, C, Ferlazzo, E, Leu, C, Giordano, L, Gobbi, G, Hernandez-Hernandez, L, Lench, N, Martins, H, Meletti, S, Messana, T, Nigro, V, Pinelli, M, Pippucci, T, Bellampalli, R, Salis, B, Sofia, V, Striano, P, Striano, S, Tassi, L, Vignoli, A, Vaudano, AE, Viri, M, Scheffer, IE, May, P, Zara, F, and Sisodiya, SM

Abstract

OBJECTIVE: Epilepsy with eyelid myoclonia (EEM) spectrum is a generalized form of epilepsy characterized by eyelid myoclonia with or without absences, eye closure-induced seizures with electroencephalographic paroxysms, and photosensitivity. Based on the specific clinical features, age at onset, and familial occurrence, a genetic cause has been postulated. Pathogenic variants in CHD2, SYNGAP1, NEXMIF, RORB, and GABRA1 have been reported in individuals with photosensitivity and eyelid myoclonia, but whether other genes are also involved, or a single gene is uniquely linked with EEM, or its subtypes, is not yet known. We aimed to dissect the genetic etiology of EEM. METHODS: We studied a cohort of 105 individuals by using whole exome sequencing. Individuals were divided into two groups: EEM- (isolated EEM) and EEM+ (EEM accompanied by intellectual disability [ID] or any other neurodevelopmental/psychiatric disorder). RESULTS: We identified nine variants classified as pathogenic/likely pathogenic in the entire cohort (8.57%); among these, eight (five in CHD2, one in NEXMIF, one in SYNGAP1, and one in TRIM8) were found in the EEM+ subcohort (28.57%). Only one variant (IFIH1) was found in the EEM- subcohort (1.29%); however, because the phenotype of the proband did not fit with published data, additional evidence is needed before considering IFIH1 variants and EEM- an established association. Burden analysis did not identify any single burdened gene or gene set. SIGNIFICANCE: Our results suggest that for EEM, as for many other epilepsies, the identification of a genetic cause is more likely with comorbid ID and/or other neurodevelopmental disorders. Pathogenic variants were mostly found in CHD2, and the association of CHD2 with EEM+ can now be considered a reasonable gene-disease association. We provide further evidence to strengthen the association of EEM+ with NEXMIF and SYNGAP1. Possible new associations between EEM+ and TRIM8, and EEM- and IFIH1, are also reported. A

Published
2024

7. A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Author

Denomme-Pichon A. -S., Bruel A. -L., Duffourd Y., Safraou H., Thauvin-Robinet C., Tran Mau-Them F., Philippe C., Vitobello A., Jean-Marcais N., Moutton S., Thevenon J., Faivre L., Matalonga L., de Boer E., Gilissen C., Hoischen A., Kleefstra T., Pfundt R., de Vries B. B. A., Willemsen M. H., Vissers L. E. L. M., Jackson A., Banka S., Clayton-Smith J., Benetti E., Fallerini C., Renieri A., Ciolfi A., Dallapiccola B., Pizzi S., Radio F. C., Tartaglia M., Ellwanger K., Graessner H., Haack T. B., Zurek B., Havlovicova M., Macek M., Ryba L., Schwarz M., Votypka P., Lopez-Martin E., Posada M., Mencarelli M. A., Rooryck C., Trimouille A., Verloes A., Abbott K. M., Kerstjens M., Martin E. L., Maystadt I., Morleo M., Nigro V., Pinelli M., Riess O., Agathe J. -M. D. S., Santen G. W. E., Thauvin C., Torella A., Vissers L., Zguro K., Boer E. D., Cohen E., Danis D., Gao F., Horvath R., Johari M., Johanson L., Li S., Morsy H., Nelson I., Paramonov I., te Paske I. B. A. W., Robinson P., Savarese M., Steyaert W., Topf A., van der Velde J. K., Vandrovcova J., Ossowski S., Demidov G., Sturm M., Schulze-Hentrich J. M., Schule R., Xu J., Kessler C., Wayand M., Synofzik M., Wilke C., Traschutz A., Schols L., Hengel H., Lerche H., Kegele J., Heutink P., Brunner H., Scheffer H., Hoogerbrugge N., 't Hoen P. A. C., Sablauskas K., de Voer R. M., Kamsteeg E. -J., van de Warrenburg B., van Os N., Paske I. T., Janssen E., Steehouwer M., Yaldiz B., Brookes A. J., Veal C., Gibson S., Maddi V., Mehtarizadeh M., Riaz U., Warren G., Dizjikan F. Y., Shorter T., Straub V., Bettolo C. M., Manera J. D., Hambleton S., Engelhardt K., Alexander E., Peyron C., Pelissier A., Beltran S., Gut I. G., Laurie S., Piscia D., Papakonstantinou A., Bullich G., Corvo A., Fernandez-Callejo M., Hernandez C., Pico D., Lochmuller H., Gumus G., Bros-Facer V., Rath A., Hanauer M., Lagorce D., Hongnat O., Chahdil M., Lebreton E., Stevanin G., Durr A., Davoine C. -S., Guillot-Noel L., Heinzmann A., Coarelli G., Bonne G., Evangelista T., Allamand V., Ben Yaou R., Metay C., Eymard B., Atalaia A., Stojkovic T., Turnovec M., Thomasova D., Kremlikova R. P., Frankova V., Liskova P., Dolezalova P., Parkinson H., Keane T., Freeberg M., Thomas C., Spalding D., Robert G., Costa A., Patch C., Hanna M., Houlden H., Reilly M., Efthymiou S., Cali E., Magrinelli F., Sisodiya S. M., Rohrer J., Muntoni F., Zaharieva I., Sarkozy A., Timmerman V., Baets J., de Vries G., De Winter J., Beijer D., de Jonghe P., Van de Vondel L., De Ridder W., Weckhuysen S., Mutarelli M., Varavallo A., Banfi S., Musacchia F., Piluso G., Ferlini A., Selvatici R., Gualandi F., Bigoni S., Rossi R., Neri M., Aretz S., Spier I., Sommer A. K., Peters S., Oliveira C., Pelaez J. G., Matos A. R., Jose C. S., Ferreira M., Gullo I., Fernandes S., Garrido L., Ferreira P., Carneiro F., Swertz M. A., Johansson L., van der Vries G., Neerincx P. B., Ruvolo D., Kerstjens Frederikse W. S., Zonneveld-Huijssoon E., Roelofs-Prins D., van Gijn M., Kohler S., Metcalfe A., Drunat S., Heron D., Mignot C., Keren B., Lacombe D., Capella G., Valle L., Holinski-Feder E., Laner A., Steinke-Lange V., Cilio M. -R., Carpancea E., Depondt C., Lederer D., Sznajer Y., Duerinckx S., Mary S., Macaya A., Cazurro-Gutierrez A., Perez-Duenas B., Munell F., Jarava C. F., Maso L. B., Marce-Grau A., Colobran R., Hackman P., Udd B., Hemelsoet D., Dermaut B., Schuermans N., Poppe B., Verdin H., Osorio A. N., Depienne C., Roos A., Cordts I., Deschauer M., Striano P., Zara F., Riva A., Iacomino M., Uva P., Scala M., Scudieri P., Basak A. N., Claeys K., Boztug K., Haimel M., W. E G., Ruivenkamp C. A. L., Natera de Benito D., Thompson R., Polavarapu K., Grimbacher B., Zaganas I., Kokosali E., Lambros M., Evangeliou A., Spilioti M., Kapaki E., Bourbouli M., Balicza P., Molnar M. J., De la Paz M. P., Sanchez E. B., Delgado B. M., Alonso Garcia de la Rosa F. J., Schrock E., Rump A., Mei D., Vetro A., Balestrini S., Guerrini R., Chinnery P. F., Ratnaike T., Schon K., Maver A., Peterlin B., Munchau A., Lohmann K., Herzog R., Pauly M., May P., Beeson D., Cossins J., Furini S., Afenjar A., Goldenberg A., Masurel A., Phan A., Dieux-Coeslier A., Fargeot A., Guerrot A. -M., Toutain A., Molin A., Sorlin A., Putoux A., Jouret B., Laudier B., Demeer B., Doray B., Bonniaud B., Isidor B., Gilbert-Dussardier B., Leheup B., Reversade B., Paul C., Vincent-Delorme C., Neiva C., Poirsier C., Quelin C., Chiaverini C., Coubes C., Francannet C., Colson C., Desplantes C., Wells C., Goizet C., Sanlaville D., Amram D., Lehalle D., Genevieve D., Gaillard D., Zivi E., Sarrazin E., Steichen E., Schaefer E., Lacaze E., Jacquemin E., Bongers E., Kilic E., Colin E., Giuliano F., Prieur F., Laffargue F., Morice-Picard F., Petit F., Cartault F., Feillet F., Baujat G., Morin G., Diene G., Journel H., Perthus I., Lespinasse J., Alessandri J. -L., Amiel J., Martinovic J., Delanne J., Albuisson J., Lambert L., Perrin L., Ousager L. B., Van Maldergem L., Pinson L., Ruaud L., Samimi M., Bournez M., Bonnet-Dupeyron M. N., Vincent M., Jacquemont M. -L., Cordier-Alex M. -P., Gerard-Blanluet M., Willems M., Spodenkiewicz M., Doco-Fenzy M., Rossi M., Renaud M., Fradin M., Mathieu M., Holder-Espinasse M. H., Houcinat N., Hanna N., Leperrier N., Chassaing N., Philip N., Boute O., Van Kien P. K., Parent P., Bitoun P., Sarda P., Vabres P., Jouk P. -S., Touraine R., El Chehadeh S., Whalen S., Marlin S., Passemard S., Grotto S., Bellanger S. A., Blesson S., Nambot S., Naudion S., Lyonnet S., Odent S., Attie-Bitach T., Busa T., Drouin-Garraud V., Layet V., Bizaoui V., Cusin V., Capri Y., Alembik Y., Unión Europea. Comisión Europea. H2020, Unión Europea. Comisión Europea. 7 Programa Marco, Instituto de Salud Carlos III, Instituto Nacional de Bioinformatica (España), Ministry of Health (República Checa), Ministry of Education, Youth and Sports (República Checa), Denomme-Pichon, A. -S., Bruel, A. -L., Duffourd, Y., Safraou, H., Thauvin-Robinet, C., Tran Mau-Them, F., Philippe, C., Vitobello, A., Jean-Marcais, N., Moutton, S., Thevenon, J., Faivre, L., Matalonga, L., de Boer, E., Gilissen, C., Hoischen, A., Kleefstra, T., Pfundt, R., de Vries, B. B. A., Willemsen, M. H., Vissers, L. E. L. M., Jackson, A., Banka, S., Clayton-Smith, J., Benetti, E., Fallerini, C., Renieri, A., Ciolfi, A., Dallapiccola, B., Pizzi, S., Radio, F. C., Tartaglia, M., Ellwanger, K., Graessner, H., Haack, T. B., Zurek, B., Havlovicova, M., Macek, M., Ryba, L., Schwarz, M., Votypka, P., Lopez-Martin, E., Posada, M., Mencarelli, M. A., Rooryck, C., Trimouille, A., Verloes, A., Abbott, K. M., Kerstjens, M., Martin, E. L., Maystadt, I., Morleo, M., Nigro, V., Pinelli, M., Riess, O., Agathe, J. -M. D. S., Santen, G. W. E., Thauvin, C., Torella, A., Vissers, L., Zguro, K., Boer, E. D., Cohen, E., Danis, D., Gao, F., Horvath, R., Johari, M., Johanson, L., Li, S., Morsy, H., Nelson, I., Paramonov, I., te Paske, I. B. A. W., Robinson, P., Savarese, M., Steyaert, W., Topf, A., van der Velde, J. K., Vandrovcova, J., Ossowski, S., Demidov, G., Sturm, M., Schulze-Hentrich, J. M., Schule, R., Xu, J., Kessler, C., Wayand, M., Synofzik, M., Wilke, C., Traschutz, A., Schols, L., Hengel, H., Lerche, H., Kegele, J., Heutink, P., Brunner, H., Scheffer, H., Hoogerbrugge, N., 't Hoen, P. A. C., Sablauskas, K., de Voer, R. M., Kamsteeg, E. -J., van de Warrenburg, B., van Os, N., Paske, I. T., Janssen, E., Steehouwer, M., Yaldiz, B., Brookes, A. J., Veal, C., Gibson, S., Maddi, V., Mehtarizadeh, M., Riaz, U., Warren, G., Dizjikan, F. Y., Shorter, T., Straub, V., Bettolo, C. M., Manera, J. D., Hambleton, S., Engelhardt, K., Alexander, E., Peyron, C., Pelissier, A., Beltran, S., Gut, I. G., Laurie, S., Piscia, D., Papakonstantinou, A., Bullich, G., Corvo, A., Fernandez-Callejo, M., Hernandez, C., Pico, D., Lochmuller, H., Gumus, G., Bros-Facer, V., Rath, A., Hanauer, M., Lagorce, D., Hongnat, O., Chahdil, M., Lebreton, E., Stevanin, G., Durr, A., Davoine, C. -S., Guillot-Noel, L., Heinzmann, A., Coarelli, G., Bonne, G., Evangelista, T., Allamand, V., Ben Yaou, R., Metay, C., Eymard, B., Atalaia, A., Stojkovic, T., Turnovec, M., Thomasova, D., Kremlikova, R. P., Frankova, V., Liskova, P., Dolezalova, P., Parkinson, H., Keane, T., Freeberg, M., Thomas, C., Spalding, D., Robert, G., Costa, A., Patch, C., Hanna, M., Houlden, H., Reilly, M., Efthymiou, S., Cali, E., Magrinelli, F., Sisodiya, S. M., Rohrer, J., Muntoni, F., Zaharieva, I., Sarkozy, A., Timmerman, V., Baets, J., de Vries, G., De Winter, J., Beijer, D., de Jonghe, P., Van de Vondel, L., De Ridder, W., Weckhuysen, S., Mutarelli, M., Varavallo, A., Banfi, S., Musacchia, F., Piluso, G., Ferlini, A., Selvatici, R., Gualandi, F., Bigoni, S., Rossi, R., Neri, M., Aretz, S., Spier, I., Sommer, A. K., Peters, S., Oliveira, C., Pelaez, J. G., Matos, A. R., Jose, C. S., Ferreira, M., Gullo, I., Fernandes, S., Garrido, L., Ferreira, P., Carneiro, F., Swertz, M. A., Johansson, L., van der Vries, G., Neerincx, P. B., Ruvolo, D., Kerstjens Frederikse, W. S., Zonneveld-Huijssoon, E., Roelofs-Prins, D., van Gijn, M., Kohler, S., Metcalfe, A., Drunat, S., Heron, D., Mignot, C., Keren, B., Lacombe, D., Capella, G., Valle, L., Holinski-Feder, E., Laner, A., Steinke-Lange, V., Cilio, M. -R., Carpancea, E., Depondt, C., Lederer, D., Sznajer, Y., Duerinckx, S., Mary, S., Macaya, A., Cazurro-Gutierrez, A., Perez-Duenas, B., Munell, F., Jarava, C. F., Maso, L. B., Marce-Grau, A., Colobran, R., Hackman, P., Udd, B., Hemelsoet, D., Dermaut, B., Schuermans, N., Poppe, B., Verdin, H., Osorio, A. N., Depienne, C., Roos, A., Cordts, I., Deschauer, M., Striano, P., Zara, F., Riva, A., Iacomino, M., Uva, P., Scala, M., Scudieri, P., Basak, A. N., Claeys, K., Boztug, K., Haimel, M., W. E, G., Ruivenkamp, C. A. L., Natera de Benito, D., Thompson, R., Polavarapu, K., Grimbacher, B., Zaganas, I., Kokosali, E., Lambros, M., Evangeliou, A., Spilioti, M., Kapaki, E., Bourbouli, M., Balicza, P., Molnar, M. J., De la Paz, M. P., Sanchez, E. B., Delgado, B. M., Alonso Garcia de la Rosa, F. J., Schrock, E., Rump, A., Mei, D., Vetro, A., Balestrini, S., Guerrini, R., Chinnery, P. F., Ratnaike, T., Schon, K., Maver, A., Peterlin, B., Munchau, A., Lohmann, K., Herzog, R., Pauly, M., May, P., Beeson, D., Cossins, J., Furini, S., Afenjar, A., Goldenberg, A., Masurel, A., Phan, A., Dieux-Coeslier, A., Fargeot, A., Guerrot, A. -M., Toutain, A., Molin, A., Sorlin, A., Putoux, A., Jouret, B., Laudier, B., Demeer, B., Doray, B., Bonniaud, B., Isidor, B., Gilbert-Dussardier, B., Leheup, B., Reversade, B., Paul, C., Vincent-Delorme, C., Neiva, C., Poirsier, C., Quelin, C., Chiaverini, C., Coubes, C., Francannet, C., Colson, C., Desplantes, C., Wells, C., Goizet, C., Sanlaville, D., Amram, D., Lehalle, D., Genevieve, D., Gaillard, D., Zivi, E., Sarrazin, E., Steichen, E., Schaefer, E., Lacaze, E., Jacquemin, E., Bongers, E., Kilic, E., Colin, E., Giuliano, F., Prieur, F., Laffargue, F., Morice-Picard, F., Petit, F., Cartault, F., Feillet, F., Baujat, G., Morin, G., Diene, G., Journel, H., Perthus, I., Lespinasse, J., Alessandri, J. -L., Amiel, J., Martinovic, J., Delanne, J., Albuisson, J., Lambert, L., Perrin, L., Ousager, L. B., Van Maldergem, L., Pinson, L., Ruaud, L., Samimi, M., Bournez, M., Bonnet-Dupeyron, M. N., Vincent, M., Jacquemont, M. -L., Cordier-Alex, M. -P., Gerard-Blanluet, M., Willems, M., Spodenkiewicz, M., Doco-Fenzy, M., Rossi, M., Renaud, M., Fradin, M., Mathieu, M., Holder-Espinasse, M. H., Houcinat, N., Hanna, N., Leperrier, N., Chassaing, N., Philip, N., Boute, O., Van Kien, P. K., Parent, P., Bitoun, P., Sarda, P., Vabres, P., Jouk, P. -S., Touraine, R., El Chehadeh, S., Whalen, S., Marlin, S., Passemard, S., Grotto, S., Bellanger, S. A., Blesson, S., Nambot, S., Naudion, S., Lyonnet, S., Odent, S., Attie-Bitach, T., Busa, T., Drouin-Garraud, V., Layet, V., Bizaoui, V., Cusin, V., Capri, Y., Alembik, Y., and Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center]

Subjects
Exome reanalysis, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Multidisciplinaire, généralités & autres [D99] [Sciences de la santé humaine], Developmental disorder, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Biology and Life Sciences, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], ClinVar, Rare diseases, All institutes and research themes of the Radboud University Medical Center, Medicine and Health Sciences, Genetics & genetic processes [F10] [Life sciences], Génétique & processus génétiques [F10] [Sciences du vivant], Multidisciplinary, general & others [D99] [Human health sciences], Exome reanalysi, Genetics (clinical)
Abstract

Purpose: Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the "ClinVar low-hanging fruit" reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods: Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results: We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion: The "ClinVar low-hanging fruit" analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock. The Solve-RD project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement number 779257. Data were analyzed using the RD-Connect Genome-Phenome Analysis Platform, which received funding from the EU projects RD-Connect, Solve-RD, and European Joint Programme on Rare Diseases (grant numbers FP7 305444, H2020 779257, H2020 825575), Instituto de Salud Carlos III (grant numbers PT13/0001/0044, PT17/0009/0019; Instituto Nacional de Bioinformática), and ELIXIR Implementation Studies. The collaborations in this study were facilitated by the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies, one of the 24 European Reference Networks approved by the European Reference Network Board of Member States, cofunded by the European Commission. This project was supported by the Czech Ministry of Health (number 00064203) and by the Czech Ministry of Education, Youth and Sports (number - LM2018132) to M.M. Sí

Published
2023
Full Text
View/download PDF

9. 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

10. Cerebrovascular Compliance Within the Rigid Confines of the Skull

Author

Mair Zamir, M. Erin Moir, Stephen A. Klassen, Christopher S. Balestrini, and J. Kevin Shoemaker

Subjects
cerebral blood flow, cerebrovascular compliance, intracranial compliance, intracranial pressure, pulsatile blood flow, Physiology, QP1-981
Abstract

Pulsatile blood flow is generally mediated by the compliance of blood vessels whereby they distend locally and momentarily to accommodate the passage of the pressure wave. This freedom of the blood vessels to exercise their compliance may be suppressed within the confines of the rigid skull. The effect of this on the mechanics of pulsatile blood flow within the cerebral circulation is not known, and the situation is compounded by experimental access difficulties. We present an approach which we have developed to overcome these difficulties in a study of the mechanics of pulsatile cerebral blood flow. The main finding is that while the innate compliance of cerebral vessels is indeed suppressed within the confines of the skull, this is compensated somewhat by compliance provided by other “extravascular” elements within the skull. The net result is what we have termed “intracranial compliance,” which we argue is more pertinent to the mechanics of pulsatile cerebral blood flow than is intracranial pressure.

Published
2018
Full Text
View/download PDF

13. Comparative effectiveness of antiepileptic drugs in juvenile myoclonic epilepsy

Author

Silvennoinen K., de Lange N., Zagaglia S., Balestrini S., Androsova G., Wassenaar M., Auce P., Avbersek A., Becker F., Berghuis B., Campbell E., Coppola A., Francis B., Wolking S., Cavalleri G. L., Craig J., Delanty N., Johnson M. R., Koeleman B. P. C., Kunz W. S., Lerche H., Marson A. G., O'Brien T. J., Sander J. W., Sills G. J., Striano P., Zara F., van der Palen J., Krause R., Depondt C., Sisodiya S. M., Brodie M. J., Chinthapalli K., de Haan G. -J., Doherty C. P., Heavin S., McCormack M., Petrovski S., Sargsyan N., Slattery L., Willis J., National Institute for Health Research, Silvennoinen, K., de Lange, N., Zagaglia, S., Balestrini, S., Androsova, G., Wassenaar, M., Auce, P., Avbersek, A., Becker, F., Berghuis, B., Campbell, E., Coppola, A., Francis, B., Wolking, S., Cavalleri, G. L., Craig, J., Delanty, N., Johnson, M. R., Koeleman, B. P. C., Kunz, W. S., Lerche, H., Marson, A. G., O'Brien, T. J., Sander, J. W., Sills, G. J., Striano, P., Zara, F., van der Palen, J., Krause, R., Depondt, C., Sisodiya, S. M., Brodie, M. J., Chinthapalli, K., de Haan, G. -J., Doherty, C. P., Heavin, S., Mccormack, M., Petrovski, S., Sargsyan, N., Slattery, L., and Willis, J.

Subjects
Topiramate, Pediatrics, medicine.medical_specialty, Neurology [D14] [Human health sciences], seizure, adverse drug reaction, Clinical Neurology, Lamotrigine, lcsh:RC346-429, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Journal Article, medicine, 030212 general & internal medicine, EpiPGX Consortium, tolerability, lcsh:Neurology. Diseases of the nervous system, seizures, adverse drug reactions, Neurologie [D14] [Sciences de la santé humaine], business.industry, Weight change, Généralités, Carbamazepine, medicine.disease, 3. Good health, valproate, Neurology, Tolerability, Full‐length Original Research, Neurology (clinical), Levetiracetam, Juvenile myoclonic epilepsy, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Objective: To study the effectiveness and tolerability of antiepileptic drugs (AEDs) commonly used in juvenile myoclonic epilepsy (JME). Methods: People with JME were identified from a large database of individuals with epilepsy, which includes detailed retrospective information on AED use. We assessed secular changes in AED use and calculated rates of response (12-month seizure freedom) and adverse drug reactions (ADRs) for the five most common AEDs. Retention was modeled with a Cox proportional hazards model. We compared valproate use between males and females. Results: We included 305 people with 688 AED trials of valproate, lamotrigine, levetiracetam, carbamazepine, and topiramate. Valproate and carbamazepine were most often prescribed as the first AED. The response rate to valproate was highest among the five AEDs (42.7%), and significantly higher than response rates for lamotrigine, carbamazepine, and topiramate; the difference to the response rate to levetiracetam (37.1%) was not significant. The rates of ADRs were highest for topiramate (45.5%) and valproate (37.5%). Commonest ADRs included weight change, lethargy, and tremor. In the Cox proportional hazards model, later start year (1.10 [1.08-1.13], P, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2019

16. Overview of the Canadian Clinician Investigator Trainees’ research presented at the 2019 CSCI-CITAC Joint Meeting

Author

Julieta Lazarte, Joel Neves Briard, Tina Binesh Marvasti, Tianwei E Zhou, Jillian A. Macklin, Sophie Hu, Cory Lefebvre, Mylvaganam Sivakami, Elina K. Cook, Christopher S. Balestrini, Mark Trinder, Heather T Whittaker, Adam Pietrobon, Valera Castanov, and Matthaeus A. Ware

Subjects
Canada, Biomedical Research, Universities, Clinician scientist, media_common.quotation_subject, Library science, Career planning, General Medicine, Research Personnel, Child health, Alberta, Presentation, Clinical investigation, Humans, Early career, Child, Psychology, Societies, Medical, Panel discussion, media_common
Abstract

The 2019 Annual General Meeting and Young Investigators’ Forum of the Canadian Society for Clinical Investigation / Société Canadienne de Recherche Clinique (CSCI/SCRC) and Clinician Investigator Trainee Association of Canada / Association des Cliniciens-Chercheurs en Formation du Canada (CITAC/ACCFC) was held in Banff, Alberta on November 8–10th, 2019. The theme was “Positioning Early Career Investigators for Success: Strategy and Resilience”. Lectures and workshops provided knowledge and tools to facilitate the attendees’ development as clinician investigators. Dr. Jason Berman (President of CSCI/SCRC), Elina Cook (President of CITAC/ACCFC) and Drs. Doreen Rabi and Zelma Kiss (University of Calgary Organizing Co-Chairs) gave opening presentations. The keynote speakers were Dr. William Foulkes (McGill University) (Distinguished Scientist Award winner) and Dr. Andrés Finzi (Université de Montréal) (Joe Doupe Young Investigator Award winner). Dr. Robert Bortolussi (Dalhousie University) received the Distinguished Service Award for his work as the Editor-in-Chief of Clinical and Investigative Medicine and for being instrumental in the development of the Canadian Child Health Clinician Scientist Program. This meeting was the first to host a panel discussion with Drs. Stephen Robbins and Marcello Tonelli from the Canadian Institutes of Health Research. Workshops on communication, career planning and work-life balance were hosted by André Picard and Drs. Todd Anderson, Karen Tang, William Ghali, May Lynn Quan, Alicia Polachek and Shannon Ruzycki. The AGM showcased 90 presentations from clinician investigator trainees from across Canada. Most of the abstracts are summarized in this review. Eight outstanding abstracts were selected for oral presentation at the President’s Forum.

Published
2020
Full Text
View/download PDF

17. Does vascular stiffness predict white matter hyperintensity burden in ischemic heart disease with preserved ejection fraction?

Author

Baraa K. Al-Khazraji, J. Kevin Shoemaker, Christopher S. Balestrini, and Neville Suskin

Subjects
Adult, Male, Middle Cerebral Artery, medicine.medical_specialty, animal structures, Carotid Artery, Common, Physiology, Myocardial Ischemia, Blood Pressure, Disease, 030204 cardiovascular system & hematology, 03 medical and health sciences, Vascular Stiffness, 0302 clinical medicine, Vascular stiffness, Physiology (medical), Internal medicine, medicine.artery, Humans, Medicine, Aged, Ultrasonography, Ejection fraction, business.industry, Stroke Volume, Middle Aged, medicine.disease, Magnetic Resonance Imaging, White Matter, White matter hyperintensity, Middle cerebral artery, Arterial stiffness, Cardiology, Female, Normal blood, Cardiology and Cardiovascular Medicine, business, Ischemic heart, Blood Flow Velocity, 030217 neurology & neurosurgery
Abstract

The survival rate of patients with ischemic heart disease (IHD) is increasing. However, survivors experience increased risk for neurological complications. The mechanisms for this increased risk are unknown. We tested the hypothesis that patients with IHD have greater carotid and cerebrovascular stiffness, and these indexes predict white matter small vessel disease. Fifty participants (age, 40-78 yr), 30 with IHD with preserved ejection fraction and 20 healthy age-matched controls, were studied using ultrasound imaging of the common carotid artery (CCA) and middle cerebral artery (MCA), as well as magnetic resonance imaging (T1, T2-FLAIR), to measure white matter lesion volume (WMLv). Carotid β-stiffness provided the primary measure of peripheral vascular stiffness. Carotid-cerebral pulse wave transit time (ccPWTT) provided a marker of cerebrovascular stiffness. Pulsatility index (PI) and resistive index (RI) of the MCA were calculated as measures of downstream cerebrovascular resistance. When compared with controls, patients with IHD exhibited greater β-stiffness [8.5 ± 3.3 vs. 6.8 ± 2.2 arbitrary units (AU)

Published
2020
Full Text
View/download PDF

18. Methodology for classification and definition of epilepsy syndromes with list of syndromes: Report of the ILAE Task Force on Nosology and Definitions

Author

Wirrell, EC, Nabbout, R, Scheffer, IE, Alsaadi, T, Bogacz, A, French, JA, Hirsch, E, Jain, S, Kaneko, S, Riney, K, Samia, P, Snead, OC, Somerville, E, Specchio, N, Trinka, E, Zuberi, SM, Balestrini, S, Wiebe, S, Cross, JH, Perucca, E, Moshe, SL, Tinuper, P, Wirrell, EC, Nabbout, R, Scheffer, IE, Alsaadi, T, Bogacz, A, French, JA, Hirsch, E, Jain, S, Kaneko, S, Riney, K, Samia, P, Snead, OC, Somerville, E, Specchio, N, Trinka, E, Zuberi, SM, Balestrini, S, Wiebe, S, Cross, JH, Perucca, E, Moshe, SL, and Tinuper, P

Abstract

Epilepsy syndromes have been recognized for >50 years, as distinct electroclinical phenotypes with therapeutic and prognostic implications. Nonetheless, no formally accepted International League Against Epilepsy (ILAE) classification of epilepsy syndromes has existed. The ILAE Task Force on Nosology and Definitions was established to reach consensus regarding which entities fulfilled criteria for an epilepsy syndrome and to provide definitions for each syndrome. We defined an epilepsy syndrome as "a characteristic cluster of clinical and electroencephalographic features, often supported by specific etiological findings (structural, genetic, metabolic, immune, and infectious)." The diagnosis of a syndrome in an individual with epilepsy frequently carries prognostic and treatment implications. Syndromes often have age-dependent presentations and a range of specific comorbidities. This paper describes the guiding principles and process for syndrome identification in both children and adults, and the template of clinical data included for each syndrome. We divided syndromes into typical age at onset, and further characterized them based on seizure and epilepsy types and association with developmental and/or epileptic encephalopathy or progressive neurological deterioration. Definitions for each specific syndrome are contained within the corresponding position papers.

Published
2022

19. Non-Stationary Outcome of Alternating Hemiplegia of Childhood into Adulthood

Author

Perulli, Marco, Poole, J., Di Lazzaro, G., D'Ambrosio, S., Silvennoinen, K., Zagaglia, S., Jimenez-Jimenez, D., Battaglia, Domenica Immacolata, Sisodiya, S. M., Balestrini, S., Perulli M., Battaglia D. (ORCID:0000-0003-0491-4021), Perulli, Marco, Poole, J., Di Lazzaro, G., D'Ambrosio, S., Silvennoinen, K., Zagaglia, S., Jimenez-Jimenez, D., Battaglia, Domenica Immacolata, Sisodiya, S. M., Balestrini, S., Perulli M., and Battaglia D. (ORCID:0000-0003-0491-4021)

Abstract

Background: Although described as non-progressive, alternating hemiplegia of childhood (AHC) can display a sudden deterioration, anecdotally reported mainly in childhood. Outcome in adulthood is uncertain. Objectives: Aim of this study is to describe the long-term follow-up of neurological function in adults with AHC. Methods: Seven adults with AHC were included in this retrospective single-center study. Clinical history and previous investigation data were gathered from the review of medical records. Video-documented neurological examination was performed at the last follow-up visit in four out of the seven reported indivisuals. Results: Over a median follow-up of 16 years, neurological outcome and trajectories were heterogeneous. All individuals showed new neurological signs or symptoms. Three experienced a serious irreversible neurological deterioration after prolonged quadriplegic episodes and/or status epilepticus in their second or third decade. One patient died at age 29. Conclusions: This video-series suggests that AHC in adulthood is not stationary; larger cohorts are needed to identify genotype–phenotype correlations and clinically useful outcome predictors.

Published
2022

20. Endarterectomía carotídea en pacientes sintomáticos y asintomáticos: resultados de morbi-mortalidad desde 1998 hasta 2005 Carotid endarterectomy in symptomatic and asymptomatic patients: morbid-mortality results from 1998 to 2005

Author

Juan G Barrera, Ligia C Mateus, Marisol Carreño, Jorge E Bayter, José F Saaibi, Carlos S Balestrini, Melquisedec Gutiérrez, Jaime Calderón, Víctor R Castillo, Oscar F Calvo, Jimmy G Muñoz, Carlos Santos, Jaime Amarillo, Omar F Gomezese, Freddy López, Camilo Pizarro, Carlos A Luengas, and Ángel M Chávez

Subjects
carótidas, enfermedad carotídea, endarterectomía carotídea, carotid arteries, carotid disease, endarterectomy, ECV, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Antecedentes: el accidente cerebrovascular es la tercera causa de muerte y probablemente la causa más importante de discapacidad a largo plazo. La tasa de mortalidad está entre 15% y 35% con el primer ataque y se eleva a 65% para los accidentes cerebrovasculares subsiguientes. Los resultados a largo y mediano plazo avalan esta técnica quirúrgica para el tratamiento de la enfermedad carotídea, al demostrar altos perfiles de seguridad. Objetivo: determinar los resultados de morbilidad y mortalidad quirúrgica y a 3, 6 y 12 meses de seguimiento, en los pacientes sometidos a endarterectomía carotídea desde 1998 hasta septiembre de 2005. Diseño-método: se evaluaron las historias clínicas de los pacientes sometidos a endarterectomía carotídea, desde 1998 hasta septiembre de 2005. Resultados: se realizaron 42 procedimientos desde 1998 hasta septiembre de 2005; el 57% de los pacientes eran hombres, con edad promedio de 68,8 ± 9,9 años. Los antecedentes de importancia fueron: hipertensión arterial (82%), tabaquismo (61%) y dislipidemia (50%). El 82% de los pacientes mostraban síntomas de enfermedad carotídea. Once pacientes tuvieron lesión de carótida derecha, 16 de carótida izquierda y 15 lesión bilateral, con un promedio de obstrucción de 85 ± 11,4%. La mortalidad fue de 4,7% y no estaba relacionada con el procedimiento quirúrgico. A septiembre de 2005 el 57% de los pacientes egresados estaban libres de síntomas. Conclusiones: la mortalidad para este grupo de pacientes es comparable con los resultados publicados en todo el mundo. La seguridad del procedimiento avala esta técnica quirúrgica como la primera opción en el manejo de la patología carotídea.Antecedents: cerebrovascular disease is the third cause of death and probably the most common cause of significant long term disability. Mortality rate with first stroke is between 15% and 35% and goes up to 65% with subsequent strokes. Results at long and middle term endorse carotid endarterectomy for carotid artery disease treatment by demonstrating high safety profiles. Objective: to determine the surgical morbidity and mortality results at 3, 6 and 12 months of follow-up in patients submitted to carotid endarterectomy from 1998 to 2005. Design-Method: clinical histories of patients submitted to carotid endarterectomy from 1998 to September 2005 were evaluated. Results: 42 procedures were realized since 1998 until September 2005. 57% of the patients were men with mean age 68.8 ± 9.9 years. Important antecedents were arterial hypertension (82%), cigarette smoking (61) and dyslipidemia (50%). 82% showed symptoms of carotid disease. 11 patients had right carotid lesion and in 15 the lesion was bilateral, with mean obstruction of 85 ± 11.4%. Mortality was 4.7% and was not related to the surgical procedure. At September 2005, 57% of the discharged patients were asymptomatic. Conclusions: mortality for this group of patients is comparable to the worldwide published results. Procedure safety guarantees this surgical technique as the first option in this carotid pathology management.

Published
2007

21. Experiencia en el manejo endovascular para el tratamiento de la aorta torácica Experience in endovascular management for thoracic aorta treatment

Author

Juan G Barrera, Ligia C Mateus, Marisol Carreño, Jorge E Bayter, José F Saaibi, Carlos S Balestrini, Melquisedec Gutiérrez, Jaime Calderón, Víctor R Castillo, Óscar F Calvo, Jimmy G Muñoz, Carlos Santos, Jaime Amarillo, Ómar F Gomezese, Freddy López, Camilo Pizarro, Carlos A Luengas, and Ángel M Chávez

Subjects
aneurisma de aorta torácica, endoprótesis, tratamiento endovascular, disección de aorta torácica aguda, disección aórtica crónica, thoracic aortic aneurysm, endoprosthesis, endovascular treatment, acute thoracic aortic dissection, chronic aortic dissection, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Antecedentes: el tratamiento endovascular ofrece la posibilidad de cubrir el origen de la disección y evitar que progrese hasta aneurisma de la aorta, y con ello demuestra una reducción en la mortalidad hasta del 16%. Objetivo: evaluar los resultados quirúrgicos en términos de morbi-mortalidad de los pacientes sometidos a manejo endovascular de las lesiones de la aorta torácica en la Fundación Cardiovascular de Colombia desde 2003 hasta 2005. Diseño-método: estudio longitudinal tipo descriptivo retrospectivo, en el que se evaluaron las historias clínicas de todos los pacientes sometidos a manejo endovascular de patología toracoabdominal; en éste sólo se incluyeron los pacientes con procedimientos de la aorta torácica, desde 2003 hasta 2005. El análisis de los datos se realizó en Stata/SE 8,0. Resultados: se realizaron procedimientos de aorta torácica en 16 pacientes. El 75% de los pacientes eran hombres con edad promedio de 55,9 ± 12,6 años. El 87,5% (14 pacientes) presentaban disección aórtica tipo A o B; un paciente transección traumática de la aorta y un paciente aneurisma de aorta torácica descendente. Las disecciones agudas se presentaron en 78,6% (11 pacientes) y las crónicas en 21,4% (3 pacientes). El promedio de endoprótesis usadas fue de 2,8 ± 1. La estancia en la unidad de cuidados intensivos fue de 3 ± 2,7 días. El 81,3% de los pacientes no presentaron complicaciones mayores. La mortalidad fue del 18,7% (3 pacientes). A todos se les realizó control post-operatorio con tomografía axial computarizada, con evolución satisfactoria. Conclusión: de acuerdo con los reportes de la literatura con mayor casuística, se considera que el manejo endovascular para el tratamiento de la disección, aneurisma o trauma aórtico es un procedimiento confiable que disminuye la morbi-mortalidad.Antecedents: endovascular treatment has the possibility of covering the dissection origin and to avoid its progression to aortic aneurysm, showing a 16% mortality reduction. Objective: evaluate surgical results in terms of morbid-mortality in patients submitted to endovascular management of thoracic aortic lesions in the Colombian Cardiovascular Foundation from 2003 to 2005. Design-Method: longitudinal descriptive retrospective study in which clinical histories of all patients submitted to endovascular treatment of thoracico-abdominal aortic lesions were evaluated. Only patients with thoracic aortic procedures between 2003 and 2005 were included. Data analysis was realized in Stata/SE 8,0. Results: thoracic aortic procedures were performed in 16 patients. 75% were male with mean age 55.9 ± 12.6 years. 87.5% (14) had type A or B aortic dissection; one patient had traumatic aortic transection and one had aneurysm of thoracic descendant aorta. Acute dissections were presented in 78.6% (11 patients) and chronic dissections in 21.4% (3 patients). Average of endoprosthesis employed was 2.8 ± 1. Intensive care unit stay was 3 ± 2.7 days. 81.3% had no mayor complications. Mortality was 18.7% (3 patients). All patients had post-operative computerized tomography scan, with satisfactory evolution. Conclusion: according to the largest casuistics literature reports, endovascular management of dissection, aneurysm or aortic trauma is considered a trustworthy procedure that diminishes morbid-mortality.

Published
2007

22. Tratamiento de aorta abdominal e ilíacas con técnica endovascular: Experiencia quirúrgica Treatment of abdominal aorta and iliac arteries with endovascular technique

Author

Juan G Barrera, Ligia C Mateus, Marisol Carreño, Jorge E Bayter, José F Saaibi, Carlos S Balestrini, Melquisedec Gutiérrez, Jaime Calderón, Víctor R Castillo, Oscar F Calvo, Jimmy G Muñoz, Carlos Santos, Omar F Gomezese, Freddy López, Camilo Pizarro, Carlos A Luengas, and Ángel M Chávez

Subjects
aneurisma de aorta abdominal, aneurisma ilíaco, endoprótesis, tratamiento endovascular, abdominal aortic aneurysm, iliac aneurysm, endoprosthesis, endovascular treatment, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Antecedentes: desde 1991 la técnica endovascular se ha aplicado con éxito en el manejo de los aneurismas de aorta infrarrenal, y se ha perfeccionado de manera tal que rápidamente se ha convertido en una alternativa para pacientes de alto riesgo para la cirugía convencional. Objetivo: describir los resultados institucionales en el manejo de las patologías de aorta abdominal e ilíacas mediante técnica endovascular desde 2003 a 2005. Diseño-Método: estudio descriptivo, longitudinal, retrospectivo, en el que se analizaron las historias clínicas de los pacientes sometidos a procedimiento endovascular de aorta abdominal e ilíacas. El análisis se realizó en Stata 8,0 S/E. Resultados: a 9 pacientes se les realizó exclusivamente manejo de lesiones en aorta abdominal e ilíacas. Todos los pacientes del estudio fueron hombres con edad media de 68,9 + 8,1 años. Los diagnósticos fueron aneurisma de aorta infrarrenal en 6 pacientes y aneurismas anastomóticos en los 3 restantes. Se evidenció requerimiento de endoprótesis en promedio de 1,9 + 0,8. Se realizó puente femoro-femoral como procedimiento simultáneo en 4 de los 9 pacientes. El 77,8% de los pacientes no tuvo complicaciones. La mortalidad por el procedimiento alcanzó el 22% (2 pacientes), si bien cabe anotar que las complicaciones se presentaron sólo en esos dos pacientes. Conclusiones: la exclusión de aneurismas de aorta y de ilíacas con endoprótesis modulares, se está implementando ampliamente como una opción válida de tratamiento, con resultados excelentes que evitan los riesgos de la intervención convencional y la morbilidad asociada.Antecedents: since 1991 endovascular technique has been successfully used in the management of infra-renal aortic aneurysms and it has been improved in such a way that it has quickly turned into an alternative for patients considered having high risk for conventional surgery. Objective: describe the institutional results in the management of abdominal aortic pathologies through endovascular technique from 2003 to 2005. Design-Method: descriptive, longitudinal, retrospective study in which clinical histories of patients that underwent an endovascular procedure of abdominal aorta and iliac arteries were analyzed. The analysis was performed in Stata 8,0 S/E. Results: 9 patients received exclusively treatment for abdominal aortic and iliac lesions. All were male individuals with mean age 68.9 ± 8.1 years. 6 patients had diagnosis of infra-renal aortic aneurysm and the other 3 had anastomotic aneurysms. Requirement of endoprosthesis was evidenced in an average of 1.9 ± 0.8. Femoro-femoral bypass surgery was performed as simultaneous procedure in 4 of the 9 patients. 77.8% of patients had no complications. Mortality due to the procedure was 22% (2 patients) and it is important to notice that only these 2 patients had complications. Conclusions: exclusion of aortic and iliac aneurysms with modular endoprosthesis is being widely implemented as a valid treatment option, with excellent results that avoid the risks of conventional surgery and its associated morbidity.

Published
2007

23. Manejo endovascular de la aorta torácica Endovascular treatment of thoracic aorta

Author

Juan G Barrera, Ligia C Mateus, José F Saaibi, Carlos S Balestrini, Jaime Calderón, Marisol Carreño, VíctorR Castillo, Camilo Pizarro, Omar F Gomezese, Freddy López, Ángel M Chaves, Carlos Luengas, Oscar Calvo, Rafael Reyes, Fabio M Aguilera, Jorge E Bayter, Leonardo Salazar, and Jimmy Muñoz

Subjects
aneurisma, aorta torácica, aorta abdominal, endoprótesis, endovascular, aneurysm, thoracic aorta, abdominal aorta, endoprosthesis, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

En comparación con el tratamiento convencional, la terapia endovascular en aneurisma de aorta torácica, presenta los mejores resultados, por lo que se convierte en el tratamiento de elección para la patología de aorta torácica descendente endovascular, por su baja morbimortalidad perioperatoria. El tratamiento quirúrgico por vía retroperitoneal y/o endovascular para aneurisma de aorta abdominal infrarrenal, resulta ser especialmente seguro en pacientes octogenarios o con alta morbilidad. Esta cohorte institucional presenta resultados perioperatorios y en el seguimiento, similares a los reportados en la literatura mundial.Compared with the conventional treatment, endovascular therapy in thoracic aortic aneurysm shows the best results, being the election treatment for the pathology of the descending thoracic aorta, due to its low peri-operative morbid-mortality. Surgical treatment by retro-peritoneal route and/or endovascular for infra-renal abdominal aortic aneurysm is especially safe in octogenarian patients or in those with a high mortality rate. This institutional cohort show peri-operative and follow-up results similar to those reported in the world literature.

Published
2006

24. Arteria carótida y placa 'carótida un órgano' Carotid artery and plaque. 'carotid: an organ'

Author

Juan G Barrera, Ligia C Mateus, José F Saaibi, Carlos S Balestrini, Jaime Calderón, Marisol Carreño, Víctor R Castillo, Camilo Pizarro, Omar F Gomezese, Fredy López, Ángel M Cháves, Carlos A Luengas, Oscar Calvo, Rafael Reyes, Fabio M Aguilera, Jorge E Bayter, Leonardo Salazar, and Jimmy Muñoz

Subjects
enfermedad carotídea, endarterectomía, stent carotídeo, enfermedad cerebrovascular, carotid disease, endarterectomy, carotid stent, cerebrovascular disease, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

En estos momentos es posible hacer recomendaciones sobre las indicaciones de la endarterectomía carotídea, basadas en los ensayos clínicos publicados y en la revisión de grandes series quirúrgicas. Las indicaciones para la cirugía dependerán del grado de estenosis y de la morfología de la placa, así como del estado clínico del paciente y de la morbi-mortalidad del equipo quirúrgico. Este al igual que otros estudios con grandes series de casos, evidencia que la endarterectomía carotídea y/o el manejo endovascular, realizado por equipos expertos, es un procedimiento seguro en pacientes con indicación quirúrgica.It is now possible to recommend indications for aortic endarterectomy, based on published clinical essays and revision of large surgical series. Surgery indications will depend on the stenosis degree and the plaque morphology, as well as on the patient's clinical state and the morbid-mortality in this surgical team. As other studies with large case series, evidences that carotid endarterectomy and/or endovascular management, when realized by expert teams, is a safe procedure in patients with surgical indication.

Published
2006

25. Resúmenes

Author

P. Abad, P. Abreu, N. Acencio, S. Acevedo, V. Acevedo, R. Agohn, L. Albornoz, P. Alvarez, C. Arana, A. Arango, J. J. Arango, A. Arbeláez, L. E. Arbeláez, W. Arboleda, A. Arenas, I. C. Arenas, M. L. Arias, A. Aristizábal, D. Aristizábal, E. Arrieta, M. Arrieta, H. Arroyave, J. A. Arroyo, F. Arteaga, G. Ascione, R. Asenjo, B. Astudillo, L. H. Atehortúa, A. Badel, M. Badiel, S. Balestrini, R. Barragán, C. Barrera, J. C. Barrera, J. G. Barrera, L. M. Benítez, M. J. Bermúdez, O. Bernal, J. Betancourt, G. Blanco, R. Bohórquez, D. Bravo, R. Bresciani, A. Builes, L Buitrago, A. Burgoa, L. P. Báez, J. Cabrales, M. Cabrales, C. Cabrera, A. M. Cadavid, E. Cadavid, R. Cadena, L. C. Caicedo, V. Caicedo, J. Calderón, L. I. Calderón, J. Camacho, P. Camacho, P. A. Camacho, D. M. Camargo, M. T. Campos, G. Campuzano, A. Capasso, H. Cardona, J. Cardona, A. Carreño, M. Carreño, G. Carrillo, G. Casariego, G. Cassalett, H. Castellanos, M. Castillo, V. Castillo, H. Castro, J. Castro, P. Castro, E. Cañas, A. Celis, L. A. Celis, A. Chávez, J. C. Chávez, A. Colorado, E. Contreras, A. Coral, M. Coronado, J. R. Correa, S. Corredor, L. Corzo, O. Corzo, J. M. Cotes, A. Cruz, C. Cubides, F. Cuellar, A. Cuervo, A. Cárdenas, M. Cárdenas, M. E. Cárdenas, P. E. Cárdenas, W. Cárdenas, C. De Viveros, A. Delgadillo, J. Delgado, P. Delgado, B. P. Donado, J. R. Donado, E. Duarte, R. Dueñas, J. G. Duque, M. Duque, L. Durango, A. E. Durán, M. A. Durán, L. M. Dávila, A. Díaz, A. L. Díaz, C. Díaz, G. Díaz, L. Díaz, L. A. Díaz, L. H. Díaz, M. Díaz, S. Díaz, V Díaz, J. Echavarría, D. Echeverri, M. Echeverri, L. Echeverría, R. Echeverría, J. Erdmenger, A. Escobar, C. Escobar, E. Escobar, E. Escorcia, A. Espinosa, R. Espíndola, G. Estrada, J. Estrada, A. M. Estupiñán, C. Eusse, A. Fernández, D. Fernández, H. Fernández, N. Fernández, O. Fernández, R. Fernández, M. Flórez, M. R. Fontanilla, C. A. Fragozo, C. Franco, G. Franco, H. J. Franco, J. Franco, S. Franco, J. Gallo, J. Garcés, E. García, L. García, M. E. Garzón, A. Gaviria, E. Gil, D. Giraldo, J. A. Giraldo, JC. Giraldo, N. Giraldo, O. F. Gomesese, G. González, M. González, R. González, M. Gordillo, R. Guanes, P. Guerra, L. Guerrero, L. Guitérrez, F. Gulh, J. Gutiérrez, M. Gutiérrez, G. Guyatt, L. Guzmán, N. Guzmán, J. Gárces, A. Gómez, C. A. Gómez, F. Gómez, G. Gómez, G. S. Gómez, J. Gómez, J. F. Gómez, M. Gómez, P. F. Gómez, A. Hernández, C. Hernández, E. Hernández, G. Hernández, H. Hernández, L. Hernández, N. Hernández, V. M. Herrera, A. Hoyos, E. F. Hurtado, P. Ibarra, D. Indaburu, A. Iragorri, D. Isaza, F. Jaimes, G. Jaimes, C. Jaramillo, C. J. Jaramillo, G. Jaramillo, J. Jaramillo, J. C. Jaramillo, J. S. Jaramillo, M. Jaramillo, M. H. Jaramillo, N. Jaramillo, R. Jaramillo, M. Jiménes, C. Jiménez, L. Jiménez, L. S. Jiménez, M. Jiménez, A. Jurado, A. F. Jurado, J. Lemus, R. Leyes, J. León, R. Lince, J. Lizarazo, F. Lizcano, A. Llamas, J. F. Llano, B. Lombo, M. Lozano, C. Luengas, L. H. Lugo, F. López, M. López, P. López, I. Malabet, J. Maldonado, E. J. Manrique, F. Manrique, G. Mantilla, E. Manzi, H. Martínez, J. P. Martínez, L. X. Martínez, M. P. Martínez, J. Marín, L. Mateus, N. Matías, A. Mayorga, A. Medina, E. Medina, H. Medina, Mejía, A. Mejía, D. Mejía, I. Mejía, S. Mendoza, A. Merchán, S. Merlano, A. Miranda, C. Molina, J. Montenegro, A. Montero, G. Montero, G. A. Montero, F. Montes, E. Montoya, J. D. Montoya, L. M. Montoya, M. Montoya, E. Moreno, C. Morillo, C. A. Morillo, R. Morris, W. Mosquera, L. Moya, R. Murgueitio, A. Muñoz, J. A. Mármol, A. Márquez, A. Múnera, C. Nader, C. M. Navas, J. J. Navia, A. Negrete, M. E. Niño, C. A. Náder, F. Núñez, J. Ochoa, C. Olaya, L. Olaya, A. Orjuela, H. Orjuela, J. L. Orozco, C. M. Orrego, C. Ortiz, S. D. Ortiz, E. Osorio, C. A. Ospina, M. Oviedo, R. Oñate, L. M. Pabón, G. Palomino, C. Pardo, R. Pardo, G. A. Parra, J. C. Parra, L. E. Parra, T. Parra, M. Patarroyo, L. F. Pava, J. E. Pedraza, O. Pedraza, A. M. Peláz, A. Perafán, P. Perafán, S. Perafán, C. Petro, M. Pineda, J. B. Pinzón, P. S. Pira, C. Pizarro, D. Piñeros, R. Plata, P. Portilla, E. Prada, G. Pradilla, L. G. Pulgarín, G. Páez, L. Páez, C. Pérez, G. E. Pérez, J. Pérez, M. Pérez, K. Quesada, A. Quintero, D. Quintero, M. Quintero, C. Quiroz, M. L. Ramos, A. Ramírez, I. Ramírez, L. Ramírez, M. Ramírez, O. Ramírez, S. Ramírez, G. W. Rangel, J. C. Rendón, A. Restrepo, G. Restrepo, J. A. Restrepo, J. Reynolds, J. D. Rincón, O. S. Rincón, P. Rincón, G. Rivas, L. F. Rivas, F. Riveros, J. L. Roa, N. Roa, A. Rodríguez, D. C. Rodríguez, E. Rodríguez, J. Rodríguez, C. E. Rojas, J. C. Rojas, M. F. Romero, F. Rosas, J. F. Rosas, F. Rosso, C. L. Rueda, M. Rueda, C. F. Rueda-Clausen, A. Ruiz, D. Ruiz, E. J. Ruiz, H. Ruiz, M. Ruiz, M. Ruz, J. F. Saaibi, L. C. Saaibi, C. Salazar, D. Salazar, G. Salazar, C. Saldarriaga, N. Saldoval, C. L. Sanabria, A. G. Sandoval, J. M. Sandoval, N. Sandoval, N. F. Sandoval, H. Santos, J. M. Sarmiento, C. Satizábal, J. M. Senior, D. Serano, N. C. Serrano, F. Silva, F. A. Silva, S. Y. Silva, M. Smieja, E. Solano, J. A. Solano, M. Suárez, L. Sáenz, J. Tello, C. Tenorio, L. F. Tenorio, L. Thabane, C. Tique, N. Toro, A. Torres, G. Torres, P. Torres, Y. Torres, P. Trujillo, M. R. Téllez, J. Umaña, C. E. Uribe, F. Uribe, W. Uribe, M. T. Urrego, M. Vacca, M. Vallejo, D. Vanegas, D. I. Vanegas, E. Vanegas, C. Vargas, R. D. Vargas, J. A. Vega, H. M. Velasco, V. M. Velasco, D. Velásquez, J. Velásquez, J. G. Velásquez, M. Velásquez, O. Velásquez, B. E. Vesga, B.E. Vesga, C. Vidal, L. A. Villa, V. Villa, C. Villa-Roel, J. C. Villalba, C. Villalobos, C. Villamil, C. Villamizar, E. Villamizar, J. C. Villar, A. Villegas, F. Villegas, F. A. Villegas, M. F. Villegas, C. Vázquez, J. F. Vélez, L. A. Vélez, S. Vélez, M. Yabur, J. Zapara, H. Zapata, J. Zapata, J. G. Zarruk, A. Zuluaga, and O. Zuluaga

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Published
2006

26. Utilidad de otras técnicas de imagen en la valoración de la enfermedad coronaria: Ultrasonido intravascular (IVUS)

Author

Carlos S Balestrini, José Federico Saaibi Solano, Tamara Gorgadze, and Libardo Augusto Medina López

Subjects
03 medical and health sciences, 0302 clinical medicine, RC666-701, Diseases of the circulatory (Cardiovascular) system, 030212 general & internal medicine, 030204 cardiovascular system & hematology, Cardiology and Cardiovascular Medicine
Abstract

Resumen: El ultrasonido intravascular en una herramienta de imagen complementaria a la angiografía coronaria para la evaluación de la enfermedad coronaria, que permite una visualización global de la placa aterosclerótica y tiene una aplicación clínica de suma importancia, pues ayuda a definir qué lesiones ameritan o no intervención cuando la angiografía coronaria por sí sola no es clara. De igual manera, permite optimizar las intervenciones coronarias, incluidas intervenciones en tronco, bifurcaciones y oclusiones crónicas, con el fin de disminuir la subexpansión o la malaposición de los stent y de esta manera minimizar eventos clínicos futuros como la trombosis y la restenosis de los stents. De forma adicional, permite realizar un análisis de la composición histológica de la placa aterosclerótica pudiendo identificar características de riesgo para eventos coronarios relacionados con esta. Abstract: Intravascular ultrasound (IVUS) is a complementary imaging tool to coronary angiography for the evaluation of coronary disease. It provides an overview of the atherosclerotic plaque and has a clinical application of considerable importance, as it helps to define whether or not lesions merit an intervention when coronary angiography on its own is not clear. Similarly, it helps to optimise coronary interventions, including those in the trunk, bifurcations, and chronic occlusions, with aim of decreasing the sub-expansion or poor positioning of the stent, and thus minimises future clinical events like thrombosis and the restenosis of the stents. Additionally, it helps to perform an analysis of the histological composition of the atherosclerotic plaque, on being able to identify risk characteristics for coronary events associated with the plaque. Palabras clave: Angiografía, Enfermedad coronaria, Imagen, Ecografía intravascular, Angioplastia coronaria, Keywords: Angiography, Coronary disease, Image, Intravascular ultrasound, Coronary angioplasty

Published
2019
Full Text
View/download PDF

27. Autonomic Dysregulation in Adolescent Concussion Is Sex- and Posture-Dependent

Author

Kolten C. Abbott, Christopher S. Balestrini, Lisa Fischer, Stephen A. Klassen, Douglas D. Fraser, Marcy Erin Moir, and Joel Kevin Shoemaker

Subjects
sex differences, Male, medicine.medical_specialty, Mean arterial pressure, adolescent concussion, Supine position, Adolescent, Adolescent concussion, Posture, Poison control, Physical Therapy, Sports Therapy and Rehabilitation, Sitting, 03 medical and health sciences, 0302 clinical medicine, Sex Factors, Heart Rate, Internal medicine, Heart rate, Concussion, Sex differences, medicine, Sport-related concussion, Heart rate variability, Humans, Autonomic nervous system, Orthopedics and Sports Medicine, 030212 general & internal medicine, Child, Brain Concussion, Original Research, business.industry, sport-related concussion, autonomic nervous system, heart rate variability, blood pressure, 030229 sport sciences, medicine.disease, Blood pressure, Case-Control Studies, Cardiology, Female, business
Abstract

Objective: To study autonomic responses to postural changes in concussed adolescents. The influence of sex was also studied. Design: Longitudinal cohort observational study. Participants: Concussed adolescents (CONC; n = 65; 26 male adolescents; age 15 ± 1 years, range = 12-18 years) and a control (CTRL) group of nonconcussed adolescents of similar age and sport (CTRL; n = 54; 29 male adolescents; age 14 ± 1 years, range = 12-18 years). Interventions: Concussed participants were monitored through 6 weekly visits throughout usual physician care. Control participants underwent 2 visits separated by at least 1 week to account for intrapersonal variation in testing measures. Main Outcome Measures: Heart rate variability as the root mean square of successive differences in R–R intervals (RMSSD), heart rate (HR), and blood pressure [mean arterial pressure (MAP) and diastolic blood pressure (DBP)] were measured in supine, sitting, and standing postures. Results: A mixed analysis of variance revealed a group × sex × posture interaction (P = 0.04) where seated values of RMSSD were less in concussed female participants versus control female participants (42 ± 4 vs 61 ± 7 ms; P = 0.01; Mann–Whitney rank test). Compared with CTRL, CONC exhibited increased pretesting seated DBP (69 ± 1 vs 74 ± 1 mm Hg; P < 0.01), MAP (83 ± 1 vs 86 ± 1 mm Hg; P = 0.02), and baseline seated HR (72 ± 1 vs 77 ± 2 bpm; P = 0.03). Values of DBP (P = 0.03) and MAP (P < 0.01) improved at clinical discharge, whereas the RMSSD in female participants did not (P > 0.5). Data are mean ± SEM. Conclusions: A modest reduction in female cardiac autonomic regulation was observed during seated postures. Alterations in seated concussed DBP and MAP, but not RMSSD, resolved at clinical discharge (median = 37 days). The results indicate that, in adolescents, concussion may impair cardiovagal function in a sex- and posture-dependent manner. The findings also suggest that BP metrics, but not RMSSD, are associated with clinical concussion recovery.

Published
2021

29. Vascular Stiffening and the Brain: Direct Measures of Cerebrovascular Stiffness in Aging and Vasodilation

Author

Balestrini, Christopher S.

Subjects
cerebrovascular, cerebrovascular impedance, pulse wave velocity, cardiovascular system, cardiovascular diseases, Circulatory and Respiratory Physiology, Arterial stiffness, white matter, phase contrast magnetic resonance imaging, circulatory and respiratory physiology
Abstract

Dampening of pulsatile pressure waves within blood vessels is an essential feature of the arterial system. Vascular stiffening increases the speed and the pulsatile energy of the pressure wave, leaving low resistance organs like the brain vulnerable to microvascular mechanical damage. Due to access limitations, the effect of cerebrovascular stiffening on brain structure and neurological outcomes remains unknown. The purpose of this thesis was to assess the influence of vascular stiffening in peripheral arteries on white matter integrity (WMLv) (Chapter 2), obtain direct measures of cerebrovascular stiffness via phase contrast magnetic resonance imaging (PCMRI) (Chapter 3), and examine the impact of acute vasodilation on cerebrovascular stiffness (Chapter 4). We found that ischemic heart disease patients (IHD) had greater vascular stiffness compared with controls. However, IHD status did not influence WMLv. Regardless of vascular pathology, common carotid stiffness and ultrasound-based carotid-cerebral pulse wave transit times were associated with WMLv independently. Therefore, we applied PCMRI to the cerebral vessels to acquire direct measures of cerebrovascular stiffness in the internal carotid (ICA) and middle cerebral (MCA) arteries. Using cardiac-gated PCRMI, we collected blood flow velocity data at multiple segments of the ICA (icaPWV) and M1-M2 segment of the MCA (mcaPWV) to construct time–intensity curves and calculate PWV at temporal resolutions up to 25ms. We demonstrated that mcaPWV can detect vascular stiffening in a cross-section of young and older healthy individuals. Additionally, PWV increases from extracranial to intracranial segments, and this acceleration is amplified with age. We then measured peripheral and intracranial vascular stiffness in response to vasodilation using hypercapnia (HC; 6% CO2, 21% O2, balanced N2) and nitroglycerin (NTG; 0.4mg, sublingual) in healthy young adults. Vasodilation in the MCA increased PWV and characteristic impedance. Additionally, the preferential effect of HC on conduit and downstream vascular properties of cerebral vessels versus non-specific conduit vasodilation of NTG suggests that multiple mechanisms may contribute to cerebrovascular stiffening. This thesis provides a method to obtain direct measures of intracranial PWV and demonstrates the capacity for acute modification of cerebrovasculature stiffness. This work may advance future understanding of cerebrovascular changes, damage, and therapeutics in vulnerable populations.

Published
2020

30. Concussion Symptoms Predictive of Adolescent Sport-Related Concussion Injury

Author

Lisa Fischer, David Humphreys, Mark Daley, Christopher S. Balestrini, Marci Erin Moir, Emilie Woehrle, Kolten C. Abbott, Alexandra Harriss, Douglas D. Fraser, and Joel Kevin Shoemaker

Subjects
Male, medicine.medical_specialty, Adolescent, media_common.quotation_subject, Post-concussion symptom scale, Poison control, Physical Therapy, Sports Therapy and Rehabilitation, Anxiety, Irritability, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Sleep Initiation and Maintenance Disorders, Outcome Assessment, Health Care, Sadness, Concussion, Injury prevention, medicine, Medicine and Health Sciences, Psychology, Humans, Orthopedics and Sports Medicine, Affective Symptoms, 030212 general & internal medicine, Child, Retrospective Studies, media_common, Post-Concussion Syndrome, business.industry, Decision Trees, Youth Sports, Neurosciences, Retrospective cohort study, 030229 sport sciences, Rivermead post-concussion symptoms questionnaire, medicine.disease, Concussion symptoms, Irritable Mood, Predictive value of tests, Athletic Injuries, Physical therapy, Female, Self Report, Symptom Assessment, medicine.symptom, business
Abstract

Objective To assess the predictive capability of the postconcussion symptom scale (PCSS) of the sport concussion assessment tool (SCAT) III to differentiate concussed and nonconcussed adolescents. Design Retrospective. Setting Tertiary. Participants Sixty-nine concussed (15.2 ± 1.6 years old) and 55 control (14.4 ± 1.7 years old) adolescents. Independent variables Postconcussion symptom scale. Main outcome measure Two-proportion z-test determined differences in symptom endorsement between groups. To assess the predictive power of the PCSS, we trained an ensemble classifier composed of a forest of 1000 decision trees to classify subjects as concussed, or not concussed, based on PCSS responses. The initial classifier was trained on all 22-concussion symptoms addressed in the PCSS, whereas the second classifier removed concussion symptoms that were not statistically significant between groups. Results Concussion symptoms common between groups were trouble falling asleep, more emotional, irritability, sadness, and anxious. After removal, analysis of the second classifier indicated that the 5 leading feature rankings of symptoms were headache, head pressure, light sensitivity, noise sensitivity, and "don't feel right," which accounted for 52% of the variance between groups. Conclusions Collectively, self-reported symptoms through the PCSS can differentiate concussed and nonconcussed adolescents. However, predictability for adolescent patients may be improved by removing emotional and sleep domain symptoms.

Published
2020

31. Physician-Scientist trainees: A 'call to action' to confront future career challenges

Author

Christopher S. Balestrini

Subjects
Canada, Biomedical Research, 020208 electrical & electronic engineering, Perspective (graphical), Translational research, 02 engineering and technology, General Medicine, Future career, Medical research, 01 natural sciences, Call to action, 010309 optics, Physicians, 0103 physical sciences, 0202 electrical engineering, electronic engineering, information engineering, Humans, Engineering ethics, Sociology, Students, PATH (variable)
Abstract

Throughout their careers, physician-scientists must adapt to the dynamic landscape of the medical research environment. As such, current physicianscientist trainees must overcome unique obstacles on the path to productive research careers. In the paper by Levit et al. in this month’s Clinical and Investigative Medicine issue, Canadian research leaders describe the challenges and opportunities for the next generation of physician-scientists [1]. They paint a cautiously optimistic picture. The current article is an outlook and concurrent “call to action” for how ongoing physician-scientist concerns can be conquered from the perspective of a current Canadian MD-PhD student.

Published
2020

32. Commentaries on Viewpoint: Physiology and fast marathons

Author

Andrew N. Bosch, José Manuel González-Yáñez, Wouter Hoogkamer, Daniel Boullosa, João Paulo Vilas-Boas, Ricardo J. Fernandes, Mikaela C. Gabler, Beat Knechtle, Robert F. Chapman, Daniel H. Craighead, Richard C. Blagrove, Jonathon W. Senefeld, Grégoire P. Millet, Anton Ušaj, Shane A. Bielko, Stephen J. Ives, Dieter Böning, Rodrigo Ramirez-Campillo, Daniel Muniz-Pumares, Billy Sperlich, Margaret A. Leist, Rasmus Kopp Hansen, Rodrigo Del Rio, Borja Muniz-Pardos, Fergus M. Guppy, Laura Hottenrott, Pedro L. Valenzuela, Peter G. Weyand, Kuno Hottenrott, Arthur H. Dewolf, Juan Del Coso, Paul J. Stapley, Jeferson Macedo Vianna, David C. Andrade, Stefanos Volianitis, Flávio de Oliveira Pires, Thiago Ribeiro Lopes, Hunter L. Paris, Alicia S. Oumsang, Konstantinos Angeloudis, Jordan Santos-Concejero, Ana Lilia Rayas-Gómez, Felix Proessl, Julien Louis, Hans-Christer Holmberg, Cayque Brietzke, Pantelis Theo Nikolaidis, Shalaya Kipp, Erin C. Sinai, Stéphane Perrey, Yuri de Almeida Costa Campos, Tadej Debevec, Brandon A. Yates, William Malysa, Philip R. Hayes, Tony Meireles dos Santos, Alain Riveros-Rivera, Curtis S. Goss, Shaun Sutehall, Christoph Zinner, José Manuel González-Rayas, Paulo Henrique Silva Marques de Azevedo, Ben Hunter, Bastien Bontemps, Fernando González-Mohíno, Thomas Gronwald, Christopher S. Balestrini, Albaro Escalera, Paulo Estevão Franco-Alvarenga, Rodger Kram, Sandro Fernandes da Silva, Mast T. Lige, Gwenael Layec, José María González-Ravé, Miller P. Guimarães, Bruno M. Silva, Niels H. Secher, Lindsay Bottoms, Romuald Lepers, Davide Malatesta, and Yannis P. Pitsiladis

Subjects
Cognitive science, FISIOLOGIA DO EXERCÍCIO, Physiology, Physiology (medical), Psychology, Running
Published
2020
Full Text
View/download PDF

33. The aetiologies of epilepsy

Author

Balestrini, S, Arzimanoglou, A, Bluemcke, I, Scheffer, IE, Wiebe, S, Zelano, J, Walker, MC, Balestrini, S, Arzimanoglou, A, Bluemcke, I, Scheffer, IE, Wiebe, S, Zelano, J, and Walker, MC

Abstract

The identification of the aetiology of a patient's epilepsy is instrumental in the diagnosis, prognostic counselling and management of the epilepsies. Indeed, the aetiology can be important for determining the recurrence risk of single seizures and so for making a diagnosis of epilepsy. Here, we divide the aetiologies into six categories: structural, genetic, infectious, metabolic, immune (all of which are part of the International League Against Epilepsy [ILAE] classification system) and neurodegenerative (which we have considered separately because of its growing importance in epilepsy). These are not mutually exclusive categories and many aetiologies fall into more than one category. Indeed, genetic factors probably play a role, to varying degrees, in the risk of seizures in all people with epilepsy. In each of the categories, we discuss what we regard as the most important aetiologies; importance being determined not only by prevalence but also by clinical significance. The introduction contains information suitable for level 1 competency (entry level), whilst the subsequent sections contain information aimed at level 2 competency (proficiency level) as part of the new ILAE competency-based curriculum. As we move towards precision medicine and targeted therapies, so aetiologies will play an even greater role in the management of epilepsy.

Published
2021

34. Climate change and epilepsy: Insights from clinical and basic science studies

Author

Gulcebi, M, Bartolini, E, Lee, O, Lisgaras, CP, Onat, F, Mifsud, J, Striano, P, Vezzani, A, Hildebrand, MS, Jimenez-Jimenez, D, Junck, L, Lewis-Smith, D, Scheffer, IE, Thijs, RD, Zuberi, SM, Blenkinsop, S, Fowler, HJ, Foley, A, Sisodiya, SM, Balestrini, S, Berkovic, S, Cavalleri, G, Correa, DJ, Custodio, HM, Galovic, M, Guerrini, R, Henshall, D, Howard, O, Hughes, K, Katsarou, A, Koeleman, BPC, Krause, R, Lowenstein, D, Mandelenaki, D, Marini, C, O'Brien, TJ, Pace, A, De Palma, L, Perucca, P, Pitkanen, A, Quinn, F, Selmer, KK, Steward, CA, Swanborough, N, Thijs, R, Tittensor, P, Trivisano, M, Weckhuysen, S, Zara, F, Gulcebi, M, Bartolini, E, Lee, O, Lisgaras, CP, Onat, F, Mifsud, J, Striano, P, Vezzani, A, Hildebrand, MS, Jimenez-Jimenez, D, Junck, L, Lewis-Smith, D, Scheffer, IE, Thijs, RD, Zuberi, SM, Blenkinsop, S, Fowler, HJ, Foley, A, Sisodiya, SM, Balestrini, S, Berkovic, S, Cavalleri, G, Correa, DJ, Custodio, HM, Galovic, M, Guerrini, R, Henshall, D, Howard, O, Hughes, K, Katsarou, A, Koeleman, BPC, Krause, R, Lowenstein, D, Mandelenaki, D, Marini, C, O'Brien, TJ, Pace, A, De Palma, L, Perucca, P, Pitkanen, A, Quinn, F, Selmer, KK, Steward, CA, Swanborough, N, Thijs, R, Tittensor, P, Trivisano, M, Weckhuysen, S, and Zara, F

Abstract

Climate change is with us. As professionals who place value on evidence-based practice, climate change is something we cannot ignore. The current pandemic of the novel coronavirus, SARS-CoV-2, has demonstrated how global crises can arise suddenly and have a significant impact on public health. Global warming, a chronic process punctuated by acute episodes of extreme weather events, is an insidious global health crisis needing at least as much attention. Many neurological diseases are complex chronic conditions influenced at many levels by changes in the environment. This review aimed to collate and evaluate reports from clinical and basic science about the relationship between climate change and epilepsy. The keywords climate change, seasonal variation, temperature, humidity, thermoregulation, biorhythm, gene, circadian rhythm, heat, and weather were used to search the published evidence. A number of climatic variables are associated with increased seizure frequency in people with epilepsy. Climate change-induced increase in seizure precipitants such as fevers, stress, and sleep deprivation (e.g. as a result of more frequent extreme weather events) or vector-borne infections may trigger or exacerbate seizures, lead to deterioration of seizure control, and affect neurological, cerebrovascular, or cardiovascular comorbidities and risk of sudden unexpected death in epilepsy. Risks are likely to be modified by many factors, ranging from individual genetic variation and temperature-dependent channel function, to housing quality and global supply chains. According to the results of the limited number of experimental studies with animal models of seizures or epilepsy, different seizure types appear to have distinct susceptibility to seasonal influences. Increased body temperature, whether in the context of fever or not, has a critical role in seizure threshold and seizure-related brain damage. Links between climate change and epilepsy are likely to be multifactorial, compl

Published
2021

35. Postictal Psychosis in Epilepsy: A Clinicogenetic Study

Author

Braatz, V, Custodio, HM, Leu, C, Agro, L, Wang, B, Calafato, S, Rayner, G, Doyle, MG, Hengsbach, C, Bisulli, F, Weber, YG, Gambardella, A, Delanty, N, Cavalleri, G, Foong, J, Scheffer, IE, Berkovic, SF, Bramon, E, Balestrini, S, Sisodiya, SM, Braatz, V, Custodio, HM, Leu, C, Agro, L, Wang, B, Calafato, S, Rayner, G, Doyle, MG, Hengsbach, C, Bisulli, F, Weber, YG, Gambardella, A, Delanty, N, Cavalleri, G, Foong, J, Scheffer, IE, Berkovic, SF, Bramon, E, Balestrini, S, and Sisodiya, SM

Abstract

OBJECTIVE: Psychoses affecting people with epilepsy increase disease burden and diminish quality of life. We characterized postictal psychosis, which comprises about one quarter of epilepsy-related psychoses, and has unknown causation. METHODS: We conducted a case-control cohort study including patients diagnosed with postictal psychosis, confirmed by psychiatric assessment, with available data regarding epilepsy, treatment, psychiatric history, psychosis profile, and outcomes. After screening 3,288 epilepsy patients, we identified 83 with psychosis; 49 had postictal psychosis. Controls were 98 adults, matched by age and epilepsy type, with no history of psychosis. Logistic regression was used to investigate clinical factors associated with postictal psychosis; univariate associations with a p value < 0.20 were used to build a multivariate model. Polygenic risk scores for schizophrenia were calculated. RESULTS: Cases were more likely to have seizure clustering (odds ratio [OR] = 7.59, p < 0.001), seizures with a recollected aura (OR = 2.49, p = 0.013), and a family history of psychiatric disease (OR = 5.17, p = 0.022). Cases showed predominance of right temporal epileptiform discharges (OR = 4.87, p = 0.007). There was no difference in epilepsy duration, neuroimaging findings, or antiseizure treatment between cases and controls. Polygenic risk scores for schizophrenia in an extended cohort of postictal psychosis cases (n = 58) were significantly higher than in 1,366 epilepsy controls (R2 = 3%, p = 6 × 10-3 ), but not significantly different from 945 independent patients with schizophrenia (R2 = 0.1%, p = 0.775). INTERPRETATION: Postictal psychosis occurs under particular circumstances in people with epilepsy with a heightened genetic predisposition to schizophrenia, illustrating how disease biology (seizures) and trait susceptibility (schizophrenia) may interact to produce particular outcomes (postictal psychosis) in a common disease. ANN NEUROL 2021;90:464-476.

Published
2021

36. 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

37. An Investigation of Dynamic Cerebral Autoregulation in Adolescent Concussion

Author

J. Kevin Shoemaker, Douglas D. Fraser, Lisa Fischer, Christopher S. Balestrini, Kolten C. Abbott, Stephen A. Klassen, and M. Erin Moir

Subjects
Male, Middle Cerebral Artery, medicine.medical_specialty, Adolescent, Brachial Artery, medicine.medical_treatment, Blood Pressure, Physical Therapy, Sports Therapy and Rehabilitation, Anxiety, 030204 cardiovascular system & hematology, Pediatrics, Cerebral autoregulation, Electrocardiography, 03 medical and health sciences, 0302 clinical medicine, Respiratory Rate, Initial visit, Internal medicine, Concussion, Homeostasis, Humans, Medicine, Orthopedics and Sports Medicine, Cardiac Output, Brain Concussion, Rehabilitation, Vasomotor, business.industry, Hemodynamics, Stroke Volume, Ultrasonography, Doppler, medicine.disease, Blood pressure, Cerebral blood flow, Cerebrovascular Circulation, Athletic Injuries, Cardiology, Brachial artery Blood pressure, Female, business, Blood Flow Velocity, 030217 neurology & neurosurgery
Abstract

Purpose Although cerebrovascular impairments are believed to contribute to concussion symptoms, little information exists regarding brain vasomotor control in adolescent concussion, particularly autoregulatory control that forms a fundamental response mechanism during changes in blood pressure. This research tested the hypothesis that adolescent concussion is marked by impaired dynamic cerebral autoregulation. Methods Nineteen concussed adolescents (15 ± 2 yr, 13 females) and 18 healthy controls (15 ± 2 yr, 9 females) completed two sit-to-stand trials. Brachial artery blood pressure and cerebral blood flow velocity in the right middle cerebral artery were measured continuously. Dynamic rate of regulation was calculated as the rate of change in cerebrovascular resistance relative to the change in arterial blood pressure. The concussed adolescents were followed through their rehabilitation for up to 12 wk. Results At the first visit, the concussed adolescents demonstrated reduced rate of regulation compared with the healthy controls (0.12 ± 0.04 vs 0.19 ± 0.06 s, P ≤ 0.001). At the concussed adolescents final visit, after symptom resolution, the rate of regulation improved to levels that were not different from the healthy controls (n = 9; 0.15 ± 0.08 vs 0.19 ± 0.06 s, P= 0.06). Two distinct groups were observed at the final visit with some individuals experiencing recovery of dynamic cerebral autoregulation and others showing no marked change from the initial visit. Conclusion Adolescents demonstrate an impairment in dynamic cerebral autoregulation after concussion that improves along with clinical symptoms in some individuals and remains impaired in others despite symptom resolution.

Published
2018
Full Text
View/download PDF

39. Evaluation of a 3-Dimensional-Printed Head Simulation Technique for Teaching Flexible Nasopharyngoscopy to Radiation Oncology Residents

Author

Goodman, Christopher D., primary, Pautler, Justin D., additional, Balestrini, Christopher S., additional, Cobos, Santiago, additional, D'Souza, Leah, additional, Eansor, Paige, additional, Jaswal, Jasbir, additional, Nichols, Anthony, additional, Norris, Madeleine, additional, Sharma, Manas, additional, Willmore, Katherine, additional, Warner, Andrew, additional, Murrell, Donna H., additional, and Palma, David A., additional

Published
2021
Full Text
View/download PDF

40. Overview of the Canadian Clinician Investigator Trainees’ research presented at the 2019 CSCI-CITAC Joint Meeting

Author

Castanov, Valera, primary, Zhou, Tianwei E., additional, Balestrini, Christopher S., additional, Lefebvre, Cory, additional, Cook, Elina K., additional, Whittaker, Heather T., additional, Macklin, Jillian, additional, Briard, Joel N., additional, Lazarte, Julieta, additional, Trinder, Mark, additional, Ware, Matthaeus A., additional, Hu, Sophie, additional, Pietrobon, Adam, additional, and Marvasti, Tina B., additional

Published
2020
Full Text
View/download PDF

42. 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
Full Text
View/download PDF

44. Evaluation of a 3D-Printed-Head Simulation Technique for Teaching Flexible Nasopharyngoscopy to Radiation Oncology Residents

Author

Santiago Cobos, Madeleine E. Norris, Paige Eansor, David A. Palma, Anthony C. Nichols, Leah A. D'Souza, Donna H. Murrell, Katherine E. Willmore, Manas Sharma, Justin D. Pautler, Christopher D. Goodman, Andrew Warner, Christopher S. Balestrini, and Jasbir Jaswal

Subjects
Models, Anatomic, medicine.medical_specialty, Cancer Research, Wilcoxon signed-rank test, media_common.quotation_subject, Teaching method, Fidelity, Nasopharyngoscopy, Nose, Article, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Radiation oncology, Medicine and Health Sciences, Medicine, Humans, Medical physics, Radiology, Nuclear Medicine and imaging, Head and neck, Simulation Training, media_common, Radiation, business.industry, Internship and Residency, Rubric, Endoscopy, Test (assessment), Oncology, 030220 oncology & carcinogenesis, Printing, Three-Dimensional, Radiation Oncology, Pharynx, business, Head
Abstract

© 2020 Elsevier Inc. Purpose: Simulation-based medical education is an effective tool for medical teaching, but simulation-based medical education deployment in radiation oncology (RO) is limited. Flexible nasopharyngoscopy (FNP), an essential skill for RO residents, requires practice that typically occurs on volunteer patients, introducing the potential for stress and discomfort. We sought to develop a high-fidelity simulator and intervention that provides RO residents the opportunity to develop FNP skills in a low-pressure environment. Methods and Materials: Computed tomography images were used to create an anatomically accurate 3-dimensional–printed model of the head and neck region. An intervention incorporating didactic instruction, multimedia content, and FNP practice on the model was designed and administered to RO residents attending the Anatomy and Radiology Contouring Bootcamp. Participants completed pre- and postintervention evaluations of the training session and model fidelity, and self-assessments of FNP skill and confidence performing FNP. Participants were video recorded performing FNP pre- and postintervention. Videos were scored by a blinded observer on a predefined rubric. Changes in scores were evaluated using the Wilcoxon signed-rank test. Results: Twenty-four participants from 17 institutions and 4 countries completed the intervention, 50% were women, and most were senior residents. Postintervention, FNP confidence and FNP performance improved significantly (mean ± standard deviation on a 10-point scale: 1.8 ± 1.8, P < .001; 2.2 ± 2.0, P < .001, respectively). Participants felt the model was helpful (mean ± standard deviation on a 5-point scale: 4.2 ± 0.6), anatomically correct (4.1 ± 0.9), and aided in spatial comprehension (4.3 ± 0.8). Overall satisfaction for the intervention was high (4.3 ± 0.8). Participants strongly agreed the intervention should be integrated into RO training programs (4.3 ± 0.8). Conclusions: A 3-dimensional–printed model and associated intervention were effective at improving FNP performance and the teaching method was rated highly by participants. RO residents may benefit from broader dissemination of this technique to improve trainee performance.

Published
2020
Full Text
View/download PDF

45. The landscape of epilepsy-related GATOR1 variants (vol 21, pg 398, 2019)

Author

Baldassari, S., Picard, F., Verbeek, N.E., Kempen, M. van, Brilstra, E.H., Lesca, G., Conti, V., Guerrini, R., Bisulli, F., Licchetta, L., Pippucci, T., Tinuper, P., Hirsch, E., Saint Martin, A. de, Chelly, J., Rudolf, G., Chipaux, M., Ferrand-Sorbets, S., Dorfmuller, G., Sisodiya, S., Balestrini, S., Schoeler, N., Hernandez-Hernandez, L., Krithika, S., Oegema, R., Hagebeuk, E., Gunning, B., Deckers, C., Berghuis, B., Wegner, I., Niks, E.H., Jansen, F.E., Braun, K., Jong, D. de, Rubboli, G., Talvik, I., Sander, V., Uldall, P., Jacquemont, M.L., Nava, C., Leguern, E., Julia, S., Gambardella, A., d'Orsi, G., Crichiutti, G., Faivre, L., Darmency, V., Benova, B., Krsek, P., Biraben, A., Lebre, A.S., Jennesson, M., Sattar, S., Marchal, C., Nordli, D.R., Lindstrom, K., Striano, P., Lomax, L.B., Kiss, C., Bartolomei, F., Lepine, A.F., Schoonjans, A.S., Stouffs, K., Jansen, A., Panagiotakaki, E., Ricard-Mousnier, B., Thevenon, J., Bellescize, J. de, Catenoix, H., Dorn, T., Zenker, M., Muller-Schluter, K., Brandt, C., Krey, I., Polster, T., Wolff, M., Balci, M., Rostasy, K., Achaz, G., Zacher, P., Becher, T., Cloppenborg, T., Yuskaitis, C.J., Weckhuysen, S., Poduri, A., Lemke, J.R., Moller, R.S., and Baulac, S.

Published
2019

46. Cardiac phenotype in ATP1A3-related syndromes A multicenter cohort study

Author

Balestrini, S, Mikati, MA, Alvarez-Garcia-Roves, R, Carboni, M, Hunanyan, AS, Kherallah, B, McLean, M, Prange, L, De Grandis, E, Gagliardi, A, Pisciotta, L, Stagnaro, M, Veneselli, E, Campistol, J, Fons, C, Pias-Peleteiro, L, Brashear, A, Miller, C, Samoes, R, Brankovic, V, Padiath, QS, Potic, A, Pilch, J, Vezyroglou, A, Bye, AME, Davis, AM, Ryan, MM, Semsarian, C, Hollingsworth, G, Scheffer, IE, Granata, T, Nardocci, N, Ragona, F, Arzimanoglou, A, Panagiotakaki, E, Carrilho, I, Zucca, C, Novy, J, Parowicz, M, Weckhuysen, S, Pons, R, Groppa, S, Sinden, DS, Pitt, GS, Tinker, A, Ashworth, M, Michalak, Z, Thom, M, Cross, JH, Vavassori, R, Kaski, JP, Sisodiya, SM, Dzieiyc, K, Mazurkiewicz-Beldzinska, M, Balestrini, S, Mikati, MA, Alvarez-Garcia-Roves, R, Carboni, M, Hunanyan, AS, Kherallah, B, McLean, M, Prange, L, De Grandis, E, Gagliardi, A, Pisciotta, L, Stagnaro, M, Veneselli, E, Campistol, J, Fons, C, Pias-Peleteiro, L, Brashear, A, Miller, C, Samoes, R, Brankovic, V, Padiath, QS, Potic, A, Pilch, J, Vezyroglou, A, Bye, AME, Davis, AM, Ryan, MM, Semsarian, C, Hollingsworth, G, Scheffer, IE, Granata, T, Nardocci, N, Ragona, F, Arzimanoglou, A, Panagiotakaki, E, Carrilho, I, Zucca, C, Novy, J, Parowicz, M, Weckhuysen, S, Pons, R, Groppa, S, Sinden, DS, Pitt, GS, Tinker, A, Ashworth, M, Michalak, Z, Thom, M, Cross, JH, Vavassori, R, Kaski, JP, Sisodiya, SM, Dzieiyc, K, and Mazurkiewicz-Beldzinska, M

Abstract

OBJECTIVE: To define the risks and consequences of cardiac abnormalities in ATP1A3-related syndromes. METHODS: Patients meeting clinical diagnostic criteria for rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) with ATP1A3 genetic analysis and at least 1 cardiac assessment were included. We evaluated the cardiac phenotype in an Atp1a3 knock-in mouse (Mashl+/-) to determine the sequence of events in seizure-related cardiac death. RESULTS: Ninety-eight patients with AHC, 9 with RDP, and 3 with CAPOS (63 female, mean age 17 years) were included. Resting ECG abnormalities were found in 52 of 87 (60%) with AHC, 2 of 3 (67%) with CAPOS, and 6 of 9 (67%) with RDP. Serial ECGs showed dynamic changes in 10 of 18 patients with AHC. The first Holter ECG was abnormal in 24 of 65 (37%) cases with AHC and RDP with either repolarization or conduction abnormalities. Echocardiography was normal. Cardiac intervention was required in 3 of 98 (≈3%) patients with AHC. In the mouse model, resting ECGs showed intracardiac conduction delay; during induced seizures, heart block or complete sinus arrest led to death. CONCLUSIONS: We found increased prevalence of ECG dynamic abnormalities in all ATP1A3-related syndromes, with a risk of life-threatening cardiac rhythm abnormalities equivalent to that in established cardiac channelopathies (≈3%). Sudden cardiac death due to conduction abnormality emerged as a seizure-related outcome in murine Atp1a3-related disease. ATP1A3-related syndromes are cardiac diseases and neurologic diseases. We provide guidance to identify patients potentially at higher risk of sudden cardiac death who may benefit from insertion of a pacemaker or implantable cardioverter-defibrillator.

Published
2020

47. Overview of the Canadian Clinician Investigator Trainees’ research presented at the 2019 CSCI-CITAC Joint Meeting

Author

Castanov, Valera, Zhou, Tianwei E., Balestrini, Christopher S., Lefebvre, Cory, Cook, Elina K., Whittaker, Heather T., Macklin, Jillian, Briard, Joel N., Lazarte, Julieta, Trinder, Mark, Ware, Matthaeus A., Mylvaganam, Sivakami, Hu, Sophie, Pietrobon, Adam, Marvasti, Tina B., Castanov, Valera, Zhou, Tianwei E., Balestrini, Christopher S., Lefebvre, Cory, Cook, Elina K., Whittaker, Heather T., Macklin, Jillian, Briard, Joel N., Lazarte, Julieta, Trinder, Mark, Ware, Matthaeus A., Mylvaganam, Sivakami, Hu, Sophie, Pietrobon, Adam, and Marvasti, Tina B.

Abstract

The 2019 Annual General Meeting and Young Investigators’ Forum of the Canadian Society for Clinical Investigation / Société Canadienne de Recherche Clinique (CSCI/SCRC) and Clinician Investigator Trainee Association of Canada / Association des Cliniciens-Chercheurs en Formation du Canada (CITAC/ACCFC) was held in Banff, Alberta on November 8–10th, 2019. The theme was “Positioning Early Career Investigators for Success: Strategy and Resilience”. Lectures and workshops provided knowledge and tools to facilitate the attendees’ development as clinician investigators. Dr. Jason Berman (President of CSCI/SCRC), Elina Cook (President of CITAC/ACCFC) and Drs. Doreen Rabi and Zelma Kiss (University of Calgary Organizing Co-Chairs) gave opening presentations. The keynote speakers were Dr. William Foulkes (McGill University) (Distinguished Scientist Award winner) and Dr. Andrés Finzi (Université de Montréal) (Joe Doupe Young Investigator Award winner). Dr. Robert Bortolussi (Dalhousie University) received the Distinguished Service Award for his work as the Editor-in-Chief of Clinical and Investigative Medicine and for being instrumental in the development of the Canadian Child Health Clinician Scientist Program. This meeting was the first to host a panel discussion with Drs. Stephen Robbins and Marcello Tonelli from the Canadian Institutes of Health Research. Workshops on communication, career planning and work-life balance were hosted by André Picard and Drs. Todd Anderson, Karen Tang, William Ghali, May Lynn Quan, Alicia Polachek and Shannon Ruzycki. The AGM showcased 90 presentations from clinician investigator trainees from across Canada. Most of the abstracts are summarized in this review. Eight outstanding abstracts were selected for oral presentation at the President’s Forum.

Published
2020

48. Physician-Scientist trainees: A “call to action” to confront future career challenges

Author

Balestrini, Christopher S. and Balestrini, Christopher S.

Abstract

Throughout their careers, physician-scientists must adapt to the dynamic landscape of the medical research environment. As such, current physicianscientist trainees must overcome unique obstacles on the path to productive research careers. In the paper by Levit et al. in this month’s Clinical and Investigative Medicine issue, Canadian research leaders describe the challenges and opportunities for the next generation of physician-scientists [1]. They paint a cautiously optimistic picture. The current article is an outlook and concurrent “call to action” for how ongoing physician-scientist concerns can be conquered from the perspective of a current Canadian MD-PhD student.

Published
2020

49. Commentaries on Viewpoint : Physiology and fast marathons

Author

Santos-Concejero, J., González-Mohíno, F., González-Ravé, J. M., Perrey, S., Dewolf, A. H., Yates, B. A., Anton, U., Tadej, D., González-Rayas, J. M., Rayas-Gómez, A. L., González-Yáñez, J. M., Lepers, R., Stapley, P., Louis, J., Proessl, F., Nikolaidis, P. T., Knechtle, B., Muniz-Pumares, D., Hunter, B., Bottoms, L., Bontemps, B., Valenzuela, P. L., Boullosa, D., Del Coso, J., Blagrove, R. C., Hayes, P. R., Millet, G. P., Malatesta, D., de Almeida Costa Campos, Y., Pereira Guimarães, M., Macedo Vianna, J., Fernandes da Silva, S., Silva Marques de Azevedo, P. H., Paris, H. L., Leist, M. A., Lige, M. T., Malysa, W., Oumsang, A. S., Sinai, E. C., Hansen, R. K., Secher, N. H., Volianitis, S., Hottenrott, L., Hottenrott, K., Gronwald, T., Senefeld, J. W., Fernandes, R. J., Vilas-Boas, J. P., Riveros-Rivera, A., Böning, D., Craighead, D. H., Kipp, S., Kram, R., Zinner, C., Sperlich, B., Holmberg, Hans-Christer, Muniz-Pardos, B., Sutehall, S., Angeloudis, K., Guppy, F. M., Bosch, A., Pitsiladis, Y., Andrade, D. C., Del Rio, R., Ramirez-Campillo, R., Lopes, T. R., Silva, B. M., Ives, S. J., Weyand, P. G., Brietzke, C., Franco-Alvarenga, P. E., Meireles dos Santos, T., Pires, F. O., Layec, G., Hoogkamer, W., Balestrini, C. S., Goss, C. S., Gabler, M. C., Escalera, A., Bielko, S. A., Chapman, R. F., Santos-Concejero, J., González-Mohíno, F., González-Ravé, J. M., Perrey, S., Dewolf, A. H., Yates, B. A., Anton, U., Tadej, D., González-Rayas, J. M., Rayas-Gómez, A. L., González-Yáñez, J. M., Lepers, R., Stapley, P., Louis, J., Proessl, F., Nikolaidis, P. T., Knechtle, B., Muniz-Pumares, D., Hunter, B., Bottoms, L., Bontemps, B., Valenzuela, P. L., Boullosa, D., Del Coso, J., Blagrove, R. C., Hayes, P. R., Millet, G. P., Malatesta, D., de Almeida Costa Campos, Y., Pereira Guimarães, M., Macedo Vianna, J., Fernandes da Silva, S., Silva Marques de Azevedo, P. H., Paris, H. L., Leist, M. A., Lige, M. T., Malysa, W., Oumsang, A. S., Sinai, E. C., Hansen, R. K., Secher, N. H., Volianitis, S., Hottenrott, L., Hottenrott, K., Gronwald, T., Senefeld, J. W., Fernandes, R. J., Vilas-Boas, J. P., Riveros-Rivera, A., Böning, D., Craighead, D. H., Kipp, S., Kram, R., Zinner, C., Sperlich, B., Holmberg, Hans-Christer, Muniz-Pardos, B., Sutehall, S., Angeloudis, K., Guppy, F. M., Bosch, A., Pitsiladis, Y., Andrade, D. C., Del Rio, R., Ramirez-Campillo, R., Lopes, T. R., Silva, B. M., Ives, S. J., Weyand, P. G., Brietzke, C., Franco-Alvarenga, P. E., Meireles dos Santos, T., Pires, F. O., Layec, G., Hoogkamer, W., Balestrini, C. S., Goss, C. S., Gabler, M. C., Escalera, A., Bielko, S. A., and Chapman, R. F.

Published
2020
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results