Search

Your search keyword '"Thomas, Rhys H"' showing total 541 results
Start Over Author "Thomas, Rhys H"
541 results on '"Thomas, Rhys H"'

102. Characterising neuropsychiatric disorders in patients with COVID-19 - Authors' reply

Author

Varatharaj, Aravinthan, Pollak, Thomas A, Nicholson, Timothy R, Coles, Jonathan P, Benjamin, Laura A, Carson, Alan, Thomas, Rhys H, Michael, Benedict D, study authors, Coles, Jonathan [0000-0003-4013-679X], and Apollo - University of Cambridge Repository

Subjects
Betacoronavirus, SARS-CoV-2, Mental Disorders, Pneumonia, Viral, COVID-19, Humans, Coronavirus Infections, Pandemics, United Kingdom
Published
2020
Full Text
View/download PDF

104. Semantic Similarity Analysis Reveals Robust Gene-Disease Relationships in Developmental and Epileptic Encephalopathies

Author

Galer, Peter D., Ganesan, Shiva, Lewis-Smith, David, McKeown, Sarah E., Pendziwiat, Manuela, Helbig, Katherine L., Ellis, Colin A., Rademacher, Annika, Smith, Lacey, Poduri, Annapurna, Seiffert, Simone, Spiczak, Sarah Von, Muhle, Hiltrud, Baalen, Andreas Van, Thomas, Rhys H., Krause, Roland, Weber, Yvonne, Helbig, Ingo, Galer, Peter D., Ganesan, Shiva, Lewis-Smith, David, McKeown, Sarah E., Pendziwiat, Manuela, Helbig, Katherine L., Ellis, Colin A., Rademacher, Annika, Smith, Lacey, Poduri, Annapurna, Seiffert, Simone, Spiczak, Sarah Von, Muhle, Hiltrud, Baalen, Andreas Van, Thomas, Rhys H., Krause, Roland, Weber, Yvonne, and Helbig, Ingo

Abstract

Summary 2.1 × 10−5) and “focal clonic seizures” (HP: 0002266; p = 8.9 × 10−6), STXBP1 with “absent speech” (HP: 0001344; p = 1.3 × 10−11), and SLC6A1 with “EEG with generalized slow activity” (HP: 0010845; p = 0.018). Of 41 genes with de novo variants in two or more individuals, 11 genes showed significant phenotypic similarity, including SCN1A (n = 16, p < 0.0001), STXBP1 (n = 14, p = 0.0021), and KCNB1 (n = 6, p = 0.011). Including genetic and phenotypic data of control subjects increased phenotypic similarity for all genetic etiologies, whereas the probability of observing de novo variants decreased, emphasizing the conceptual differences between semantic similarity analysis and approaches based on the expected number of de novo events. We demonstrate that HPO-based phenotype analysis captures unique profiles for distinct genetic etiologies, reflecting the breadth of the phenotypic spectrum in genetic epilepsies. Semantic similarity can be used to generate statistical evidence for disease causation analogous to the traditional approach of primarily defining disease entities through similar clinical features.

Published
2020

105. The ENIGMA-Epilepsy working group: Mapping disease from large data sets.

Author

Sisodiya, Sanjay M, Sisodiya, Sanjay M, Whelan, Christopher D, Hatton, Sean N, Huynh, Khoa, Altmann, Andre, Ryten, Mina, Vezzani, Annamaria, Caligiuri, Maria Eugenia, Labate, Angelo, Gambardella, Antonio, Ives-Deliperi, Victoria, Meletti, Stefano, Munsell, Brent C, Bonilha, Leonardo, Tondelli, Manuela, Rebsamen, Michael, Rummel, Christian, Vaudano, Anna Elisabetta, Wiest, Roland, Balachandra, Akshara R, Bargalló, Núria, Bartolini, Emanuele, Bernasconi, Andrea, Bernasconi, Neda, Bernhardt, Boris, Caldairou, Benoit, Carr, Sarah JA, Cavalleri, Gianpiero L, Cendes, Fernando, Concha, Luis, Desmond, Patricia M, Domin, Martin, Duncan, John S, Focke, Niels K, Guerrini, Renzo, Hamandi, Khalid, Jackson, Graeme D, Jahanshad, Neda, Kälviäinen, Reetta, Keller, Simon S, Kochunov, Peter, Kowalczyk, Magdalena A, Kreilkamp, Barbara AK, Kwan, Patrick, Lariviere, Sara, Lenge, Matteo, Lopez, Seymour M, Martin, Pascal, Mascalchi, Mario, Moreira, José CV, Morita-Sherman, Marcia E, Pardoe, Heath R, Pariente, Jose C, Raviteja, Kotikalapudi, Rocha, Cristiane S, Rodríguez-Cruces, Raúl, Seeck, Margitta, Semmelroch, Mira KHG, Sinclair, Benjamin, Soltanian-Zadeh, Hamid, Stein, Dan J, Striano, Pasquale, Taylor, Peter N, Thomas, Rhys H, Thomopoulos, Sophia I, Velakoulis, Dennis, Vivash, Lucy, Weber, Bernd, Yasuda, Clarissa Lin, Zhang, Junsong, Thompson, Paul M, McDonald, Carrie R, ENIGMA Consortium Epilepsy Working Group, Sisodiya, Sanjay M, Sisodiya, Sanjay M, Whelan, Christopher D, Hatton, Sean N, Huynh, Khoa, Altmann, Andre, Ryten, Mina, Vezzani, Annamaria, Caligiuri, Maria Eugenia, Labate, Angelo, Gambardella, Antonio, Ives-Deliperi, Victoria, Meletti, Stefano, Munsell, Brent C, Bonilha, Leonardo, Tondelli, Manuela, Rebsamen, Michael, Rummel, Christian, Vaudano, Anna Elisabetta, Wiest, Roland, Balachandra, Akshara R, Bargalló, Núria, Bartolini, Emanuele, Bernasconi, Andrea, Bernasconi, Neda, Bernhardt, Boris, Caldairou, Benoit, Carr, Sarah JA, Cavalleri, Gianpiero L, Cendes, Fernando, Concha, Luis, Desmond, Patricia M, Domin, Martin, Duncan, John S, Focke, Niels K, Guerrini, Renzo, Hamandi, Khalid, Jackson, Graeme D, Jahanshad, Neda, Kälviäinen, Reetta, Keller, Simon S, Kochunov, Peter, Kowalczyk, Magdalena A, Kreilkamp, Barbara AK, Kwan, Patrick, Lariviere, Sara, Lenge, Matteo, Lopez, Seymour M, Martin, Pascal, Mascalchi, Mario, Moreira, José CV, Morita-Sherman, Marcia E, Pardoe, Heath R, Pariente, Jose C, Raviteja, Kotikalapudi, Rocha, Cristiane S, Rodríguez-Cruces, Raúl, Seeck, Margitta, Semmelroch, Mira KHG, Sinclair, Benjamin, Soltanian-Zadeh, Hamid, Stein, Dan J, Striano, Pasquale, Taylor, Peter N, Thomas, Rhys H, Thomopoulos, Sophia I, Velakoulis, Dennis, Vivash, Lucy, Weber, Bernd, Yasuda, Clarissa Lin, Zhang, Junsong, Thompson, Paul M, McDonald, Carrie R, and ENIGMA Consortium Epilepsy Working Group

Abstract

Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller-scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well-established by the ENIGMA Consortium, ENIGMA-Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event-based modeling analysis. We explore age of onset- and duration-related features, as well as phenomena-specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA-Epilepsy.

Published
2020

107. Artificial intelligence for classification of temporal lobe epilepsy with ROI-level MRI data: A worldwide ENIGMA-Epilepsy study

Author

Gleichgerrcht, Ezequiel, primary, Munsell, Brent C., additional, Alhusaini, Saud, additional, Alvim, Marina K.M., additional, Bargalló, Núria, additional, Bender, Benjamin, additional, Bernasconi, Andrea, additional, Bernasconi, Neda, additional, Bernhardt, Boris, additional, Blackmon, Karen, additional, Caligiuri, Maria Eugenia, additional, Cendes, Fernando, additional, Concha, Luis, additional, Desmond, Patricia M., additional, Devinsky, Orrin, additional, Doherty, Colin P., additional, Domin, Martin, additional, Duncan, John S., additional, Focke, Niels K., additional, Gambardella, Antonio, additional, Gong, Bo, additional, Guerrini, Renzo, additional, Hatton, Sean N., additional, Kälviäinen, Reetta, additional, Keller, Simon S., additional, Kochunov, Peter, additional, Kotikalapudi, Raviteja, additional, Kreilkamp, Barbara A.K., additional, Labate, Angelo, additional, Langner, Soenke, additional, Larivière, Sara, additional, Lenge, Matteo, additional, Lui, Elaine, additional, Martin, Pascal, additional, Mascalchi, Mario, additional, Meletti, Stefano, additional, O'Brien, Terence J., additional, Pardoe, Heath R., additional, Pariente, Jose C., additional, Xian Rao, Jun, additional, Richardson, Mark P., additional, Rodríguez-Cruces, Raúl, additional, Rüber, Theodor, additional, Sinclair, Ben, additional, Soltanian-Zadeh, Hamid, additional, Stein, Dan J., additional, Striano, Pasquale, additional, Taylor, Peter N., additional, Thomas, Rhys H., additional, Elisabetta Vaudano, Anna, additional, Vivash, Lucy, additional, von Podewills, Felix, additional, Vos, Sjoerd B., additional, Weber, Bernd, additional, Yao, Yi, additional, Lin Yasuda, Clarissa, additional, Zhang, Junsong, additional, Thompson, Paul M., additional, Sisodiya, Sanjay M., additional, McDonald, Carrie R., additional, Bonilha, Leonardo, additional, Altmann, Andre, additional, Depondt, Chantal, additional, Galovic, Marian, additional, Thomopoulos, Sophia I., additional, and Wiest, Roland, additional

Published
2021
Full Text
View/download PDF

108. Neurological and Psychiatric Manifestations of COVID-19 in UK Children: A Prospective National Cohort Study

Author

Ray, Stephen T.J., primary, Abdel-Mannan, Omar, additional, Sa, Mario, additional, Fuller, Charlotte, additional, Wood, Greta K., additional, Psyden, Karen, additional, Yoong, Michael, additional, Ramas, S., additional, McCullagh, Helen, additional, Scott, D., additional, McMahon, M., additional, Thomas, Naomi, additional, Taylor, M., additional, Vollmer, Brigitte, additional, Illingworth, Marjorie, additional, McCrea, Nadine, additional, Davies, Victoria, additional, Whitehouse, William, additional, Zuberi, S., additional, Guthrie, Keira, additional, Wassmer, Evangeline, additional, Shah, N., additional, Baker, Mark R., additional, Tiwary, Sangeeta, additional, Petropoulos, Christina, additional, Vlachou, Victoria, additional, Kinali, Maria, additional, Tan, H. Jeen, additional, Varma, Uma, additional, Ram, Dipak, additional, Avula, Shivaram, additional, Breen, Gerome, additional, Enright, Noelle, additional, Hassell, Jane, additional, Ross Russell, Amy L., additional, Kumar, R., additional, Mulholland, Rachel E., additional, Pett, Sarah, additional, Galea, Ian, additional, Thomas, Rhys H., additional, Lim, Ming, additional, Hacohen, Yael, additional, Solomon, T., additional, Griffiths, Michael John, additional, Michael, B.D., additional, Kneen, Rachel, additional, and Group, CoroNerve Studies, additional

Published
2021
Full Text
View/download PDF

109. Spectrum, risk factors and outcomes of neurological and psychiatric complications of COVID-19: a UK-wide cross-sectional surveillance study

Author

Ross Russell, Amy L, primary, Hardwick, Marc, additional, Jeyanantham, Athavan, additional, White, Laura M, additional, Deb, Saumitro, additional, Burnside, Girvan, additional, Joy, Harriet M, additional, Smith, Craig J, additional, Pollak, Thomas A, additional, Nicholson, Timothy R, additional, Davies, Nicholas W S, additional, Manji, Hadi, additional, Easton, Ava, additional, Ray, Stephen, additional, Zandi, Michael S, additional, Coles, Jonathan P, additional, Menon, David K, additional, Varatharaj, Aravinthan, additional, McCausland, Beth, additional, Ellul, Mark A, additional, Thomas, Naomi, additional, Breen, Gerome, additional, Keddie, Stephen, additional, Lunn, Michael P, additional, Burn, John P S, additional, Quattrocchi, Graziella, additional, Dixon, Luke, additional, Rice, Claire M, additional, Pengas, George, additional, Al-Shahi Salman, Rustam, additional, Carson, Alan, additional, Joyce, Eileen M, additional, Turner, Martin R, additional, Benjamin, Laura A, additional, Solomon, Tom, additional, Kneen, Rachel, additional, Pett, Sarah, additional, Thomas, Rhys H, additional, Michael, Benedict D, additional, and Galea, Ian, additional

Published
2021
Full Text
View/download PDF

110. Defining Causality in Neurological &amp; Neuropsychiatric COVID-19 Vaccine Complications: What Have We Learnt from Current and Previous Vaccination Campaigns?

Author

Butler, Matthew, primary, Tamborska, Arina, additional, Wood, Greta, additional, Ellul, Mark, additional, Thomas, Rhys H, additional, Galea, Ian, additional, Pett, Sarah, additional, Solomon, Tom, additional, Pollak, Tom, additional, Michael, Benedict, additional, and Nicholson, Timothy, additional

Published
2021
Full Text
View/download PDF

111. Spectrum, Risk Factors, and Outcomes of Neurological and Psychiatric Complications of COVID-19: A UK-Wide Cross-Sectional Surveillance Study

Author

Ross Russell, Amy, primary, Hardwick, Marc, additional, Jeyanantham, Athavan, additional, White, Laura, additional, Deb, Saumitro, additional, Burnside, Girvan, additional, Joy, Harriet, additional, Smith, Craig, additional, Pollak, Tom, additional, Nicholson, Timothy, additional, Davies, Nicholas WS, additional, Manji, Hadi, additional, Easton, Ava, additional, Ray, Stephen, additional, Zandi, Michael, additional, Coles, Jonathan P, additional, Menon, David, additional, Varatharaj, Aravinthan, additional, McCausland, Beth, additional, Ellul, Mark, additional, Thomas, Naomi, additional, Breen, Gerome, additional, Keddie, Stephen, additional, Lunn, Michael, additional, Al-Shahi Salman, Rustam, additional, Carson, Alan, additional, Joyce, Eileen, additional, Turner, Martin R, additional, Benjamin, Laura, additional, Solomon, Tom, additional, Kneen, Rachel, additional, Pett, Sarah, additional, Thomas, Rhys H, additional, Michael, Benedict, additional, and Galea, Ian, additional

Published
2021
Full Text
View/download PDF

117. GLRB is the third major gene of effect in hyperekplexia

Author

Chung, Seo-Kyung, Bode, Anna, Cushion, Thomas D., Thomas, Rhys H., Hunt, Charlotte, Wood, Sian-Elin, Pickrell, William O., Drew, Cheney J.G., Yamashita, Sumimasa, Shiang, Rita, Leiz, Steffen, Longhardt, Ann-Carolyn, Raile, Vera, Weschke, Bernhard, Puri, Ratna D., Verma, Ishwar C., Harvey, Robert J., Ratnasinghe, Didi D., Parker, Michael, Rittey, Chris, Masri, Amira, Lingappa, Lokesh, Howell, Owain W., Vanbellinghen, Jean-François, Mullins, Jonathan G., Lynch, Joseph W., and Rees, Mark I.

Published
2013
Full Text
View/download PDF

119. Characterising neuropsychiatric disorders in patients with COVID-19 – Authors' reply

Author

Varatharaj, Aravinthan, primary, Pollak, Thomas A, additional, Nicholson, Timothy R, additional, Coles, Jonathan P, additional, Benjamin, Laura A, additional, Carson, Alan, additional, Thomas, Rhys H, additional, Michael, Benedict D, additional, Davies, Nicholas WS, additional, Breen, Gerome, additional, Zandi, Michael, additional, Ellul, Mark A, additional, Thomas, Naomi, additional, Tenorio, Elizabeth L, additional, Sultan, Mustafa, additional, Easton, Ava, additional, Smith, Craig, additional, Kneen, Rachel, additional, Turner, Martin R, additional, Manji, Hadi, additional, Solomon, Tom, additional, Menon, David K, additional, Pett, Sarah L, additional, and Galea, Ian, additional

Published
2020
Full Text
View/download PDF

120. Leukoencephalopathy with calcifications and cysts: Genetic and phenotypic spectrum

Author

Crow, Yanick J, primary, Marshall, Heather, additional, Rice, Gillian I, additional, Seabra, Luis, additional, Jenkinson, Emma M, additional, Baranano, Kristin, additional, Battini, Roberta, additional, Berger, Andrea, additional, Blair, Edward, additional, Blauwblomme, Thomas, additional, Bolduc, Francois, additional, Boddaert, Natalie, additional, Buckard, Johannes, additional, Burnett, Heather, additional, Calvert, Sophie, additional, Caumes, Roseline, additional, Ng, Andy Cheuk‐Him, additional, Chiang, Diana, additional, Clifford, David B, additional, Cordelli, Duccio M, additional, Burca, Anna, additional, Demic, Natasha, additional, Desguerre, Isabelle, additional, De Waele, Liesbeth, additional, Di Fonzo, Alessio, additional, Dunham, S. Richard, additional, Dyack, Sarah, additional, Elmslie, Frances, additional, Ferrand, Mickaël, additional, Fisher, Gemma, additional, Karimiani, Ehsan Ghayoor, additional, Ghoumid, Jamal, additional, Gibbon, Frances, additional, Goel, Himanshu, additional, Hilmarsen, Hilde T, additional, Hughes, Imelda, additional, Jacob, Anu, additional, Jones, Elizabeth A, additional, Kumar, Ram, additional, Leventer, Richard J, additional, MacDonald, Shelley, additional, Maroofian, Reza, additional, Mehta, Sarju G, additional, Metz, Imke, additional, Monfrini, Edoardo, additional, Neumann, Daniela, additional, Noetzel, Michael, additional, O'Driscoll, Mary, additional, Õunap, Katrin, additional, Panzer, Axel, additional, Parikh, Sumit, additional, Prabhakar, Prab, additional, Ramond, Francis, additional, Sandford, Richard, additional, Saneto, Russell, additional, Soh, Calvin, additional, Stutterd, Chloe A, additional, Subramanian, Gopinath M, additional, Talbot, Kevin, additional, Thomas, Rhys H, additional, Toro, Camilo, additional, Touraine, Renaud, additional, Wakeling, Emma, additional, Wassmer, Evangeline, additional, Whitney, Andrea, additional, Livingston, John H, additional, O'Keefe, Raymond T, additional, and Badrock, Andrew P, additional

Published
2020
Full Text
View/download PDF

121. Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study

Author

Varatharaj, Aravinthan, primary, Thomas, Naomi, additional, Ellul, Mark A, additional, Davies, Nicholas W S, additional, Pollak, Thomas A, additional, Tenorio, Elizabeth L, additional, Sultan, Mustafa, additional, Easton, Ava, additional, Breen, Gerome, additional, Zandi, Michael, additional, Coles, Jonathan P, additional, Manji, Hadi, additional, Al-Shahi Salman, Rustam, additional, Menon, David K, additional, Nicholson, Timothy R, additional, Benjamin, Laura A, additional, Carson, Alan, additional, Smith, Craig, additional, Turner, Martin R, additional, Solomon, Tom, additional, Kneen, Rachel, additional, Pett, Sarah L, additional, Galea, Ian, additional, Thomas, Rhys H, additional, Michael, Benedict D, additional, Allen, Claire, additional, Archibald, Neil, additional, Arkell, James, additional, Arthur-Farraj, Peter, additional, Baker, Mark, additional, Ball, Harriet, additional, Bradley-Barker, Verity, additional, Brown, Zoe, additional, Bruno, Stefania, additional, Carey, Lois, additional, Carswell, Christopher, additional, Chakrabarti, Annie, additional, Choulerton, James, additional, Daher, Mazen, additional, Davies, Ruth, additional, Di Marco Barros, Rafael, additional, Dima, Sofia, additional, Dunley, Rachel, additional, Dutta, Dipankar, additional, Ellis, Richard, additional, Everitt, Alex, additional, Fady, Joseph, additional, Fearon, Patricia, additional, Fisniku, Leonora, additional, Gbinigie, Ivie, additional, Gemski, Alan, additional, Gillies, Emma, additional, Gkrania-Klotsas, Effrossyni, additional, Grigg, Julie, additional, Hamdalla, Hisham, additional, Hubbett, Jack, additional, Hunter, Neil, additional, Huys, Anne-Catherine, additional, Ihmoda, Ihmoda, additional, Ispoglou, Sissi, additional, Jha, Ashwani, additional, Joussi, Ramzi, additional, Kalladka, Dheeraj, additional, Khalifeh, Hind, additional, Kooij, Sander, additional, Kumar, Guru, additional, Kyaw, Sandar, additional, Li, Lucia, additional, Littleton, Edward, additional, Macleod, Malcolm, additional, Macleod, Mary Joan, additional, Madigan, Barbara, additional, Mahadasa, Vikram, additional, Manoharan, Manonmani, additional, Marigold, Richard, additional, Marks, Isaac, additional, Matthews, Paul, additional, Mccormick, Michael, additional, Mcinnes, Caroline, additional, Metastasio, Antonio, additional, Milburn-McNulty, Philip, additional, Mitchell, Clinton, additional, Mitchell, Duncan, additional, Morgans, Clare, additional, Morris, Huw, additional, Morrow, Jasper, additional, Mubarak Mohamed, Ahmed, additional, Mulvenna, Paula, additional, Murphy, Louis, additional, Namushi, Robert, additional, Newman, Edward, additional, Phillips, Wendy, additional, Pinto, Ashwin, additional, Price, David Ashley, additional, Proschel, Harald, additional, Quinn, Terry, additional, Ramsey, Deborah, additional, Roffe, Christine, additional, Ross Russell, Amy, additional, Samarasekera, Neshika, additional, Sawcer, Stephen, additional, Sayed, Walee, additional, Sekaran, Lakshmanan, additional, Serra-Mestres, Jordi, additional, Snowdon, Victoria, additional, Strike, Gayle, additional, Sun, James, additional, Tang, Christina, additional, Vrana, Mark, additional, Wade, Ryckie, additional, Wharton, Chris, additional, Wiblin, Lou, additional, Boubriak, Iryna, additional, Herman, Katie, additional, and Plant, Gordon, additional

Published
2020
Full Text
View/download PDF

124. Network-based atrophy modelling in the common epilepsies: a worldwide ENIGMA study

Author

Larivière, Sara, primary, Rodríguez-Cruces, Raúl, additional, Royer, Jessica, additional, Caligiuri, Maria Eugenia, additional, Gambardella, Antonio, additional, Concha, Luis, additional, Keller, Simon S., additional, Cendes, Fernando, additional, Yasuda, Clarissa, additional, Bonilha, Leonardo, additional, Gleichgerrcht, Ezequiel, additional, Focke, Niels K., additional, Domin, Martin, additional, Podewills, Felix von, additional, Langner, Soenke, additional, Rummel, Christian, additional, Wiest, Roland, additional, Martin, Pascal, additional, Kotikalapudi, Raviteja, additional, O’Brien, Terence J., additional, Sinclair, Benjamin, additional, Vivash, Lucy, additional, Desmond, Patricia M., additional, Alhusaini, Saud, additional, Doherty, Colin P., additional, Cavalleri, Gianpiero L., additional, Delanty, Norman, additional, Kälviäinen, Reetta, additional, Jackson, Graeme D., additional, Kowalczyk, Magdalena, additional, Mascalchi, Mario, additional, Semmelroch, Mira, additional, Thomas, Rhys H., additional, Soltanian-Zadeh, Hamid, additional, Davoodi-Bojd, Esmaeil, additional, Zhang, Junsong, additional, Lenge, Matteo, additional, Guerrini, Renzo, additional, Bartolini, Emanuele, additional, Hamandi, Khalid, additional, Foley, Sonya, additional, Weber, Bernd, additional, Depondt, Chantal, additional, Absil, Julie, additional, Carr, Sarah J. A., additional, Abela, Eugenio, additional, Richardson, Mark P., additional, Devinsky, Orrin, additional, Severino, Mariasavina, additional, Striano, Pasquale, additional, Tortora, Domenico, additional, Hatton, Sean N., additional, Vos, Sjoerd B., additional, Duncan, John S., additional, Whelan, Christopher D., additional, Thompson, Paul M., additional, Sisodiya, Sanjay M., additional, Bernasconi, Andrea, additional, Labate, Angelo, additional, McDonald, Carrie R., additional, Bernasconi, Neda, additional, and Bernhardt, Boris C., additional

Published
2020
Full Text
View/download PDF

125. Expert opinion: use of valproate in girls and women of childbearing potential with epilepsy: recommendations and alternatives based on a review of the literature and clinical experience—a European perspective

Author

Toledo, Manuel, primary, Mostacci, Barbara, additional, Bosak, Magdalena, additional, Jedrzejzak, Joanna, additional, Thomas, Rhys H., additional, Salas-Puig, Javier, additional, Biraben, Arnaud, additional, and Schmitz, Bettina, additional

Published
2020
Full Text
View/download PDF

131. UK-Wide Surveillance of Neurological and Neuropsychiatric Complications of COVID-19: The First 153 Patients

Author

Varatharaj, Aravinthan, primary, Thomas, Naomi, additional, Ellul, Mark, additional, Davies, Nicholas WS, additional, Pollak, Tom, additional, Tenorio, E.L., additional, Sultan, Mustafa, additional, Easton, Ava, additional, Breen, Gerome, additional, Zandi, Michael, additional, Coles, Jonathan P, additional, Manji, Hadi, additional, Al-Shahi Salman, Rustam, additional, Menon, David, additional, Nicholson, Timothy, additional, Benjamin, Laura, additional, Carson, Alan, additional, Smith, Craig, additional, Turner, Martin R, additional, Solomon, Tom, additional, Kneen, Rachel, additional, Pett, Sarah, additional, Galea, Ian, additional, Thomas, Rhys H, additional, and Michael, Benedict, additional

Published
2020
Full Text
View/download PDF

132. White matter abnormalities across different epilepsy syndromes in adults: an ENIGMA Epilepsy study

Author

Hatton, Sean N, primary, Huynh, Khoa H, additional, Bonilha, Leonardo, additional, Abela, Eugenio, additional, Alhusaini, Saud, additional, Altmann, Andre, additional, Alvim, Marina KM, additional, Balachandra, Akshara R, additional, Bartolini, Emanuele, additional, Bender, Benjamin, additional, Bernasconi, Neda, additional, Bernasconi, Andrea, additional, Bernhardt, Boris, additional, Bargallo, Núria, additional, Caldairou, Benoit, additional, Caligiuri, Maria Eugenia, additional, Carr, Sarah JA, additional, Cavalleri, Gianpiero L, additional, Cendes, Fernando, additional, Concha, Luis, additional, Davoodi-bojd, Esmaeil, additional, Desmond, Patricia M, additional, Devinsky, Orrin, additional, Doherty, Colin P, additional, Domin, Martin, additional, Duncan, John S, additional, Focke, Niels K, additional, Foley, Sonya F, additional, Gambardella, Antonio, additional, Gleichgerrcht, Ezequiel, additional, Guerrini, Renzo, additional, Hamandi, Khalid, additional, Ishikawa, Akaria, additional, Keller, Simon S, additional, Kochunov, Peter V, additional, Kotikalapudi, Raviteja, additional, Kreilkamp, Barbara AK, additional, Kwan, Patrick, additional, Labate, Angelo, additional, Langner, Soenke, additional, Lenge, Matteo, additional, Liu, Min, additional, Lui, Elaine, additional, Martin, Pascal, additional, Mascalchi, Mario, additional, Moreira, José CV, additional, Morita-Sherman, Marcia E, additional, O’Brien, Terence J, additional, Pardoe, Heath R, additional, Pariente, José C, additional, Ribeiro, Letícia F, additional, Richardson, Mark P, additional, Rocha, Cristiane S, additional, Rodríguez-Cruces, Raúl, additional, Rosenow, Felix, additional, Severino, Mariasavina, additional, Sinclair, Benjamin, additional, Soltanian-Zadeh, Hamid, additional, Striano, Pasquale, additional, Taylor, Peter N, additional, Thomas, Rhys H, additional, Tortora, Domenico, additional, Velakoulis, Dennis, additional, Vezzani, Annamaria, additional, Vivash, Lucy, additional, von Podewils, Felix, additional, Vos, Sjoerd B, additional, Weber, Bernd, additional, Winston, Gavin P, additional, Yasuda, Clarissa L, additional, Thompson, Paul M, additional, Jahanshad, Neda, additional, Sisodiya, Sanjay M, additional, and McDonald, Carrie R, additional

Published
2019
Full Text
View/download PDF

135. Forecasting stroke-like episodes and outcomes in mitochondrial disease.

Author

Ng, Yi Shiau, Lax, Nichola Z, Blain, Alasdair P, Erskine, Daniel, Baker, Mark R, Polvikoski, Tuomo, Thomas, Rhys H, Morris, Christopher M, Lai, Ming, Whittaker, Roger G, Gebbels, Alasdair, Winder, Amy, Hall, Julie, Feeney, Catherine, Farrugia, Maria Elena, Hirst, Claire, Roberts, Mark, Lawthom, Charlotte, Chrysostomou, Alexia, and Murphy, Kevin

Subjects
MELAS syndrome, MITOCHONDRIAL DNA, MITOCHONDRIA, SENSORINEURAL hearing loss, CEREBRAL atrophy, GENETIC counseling, RESEARCH, STROKE, GENETIC mutation, DNA, MITOCHONDRIAL pathology, RESEARCH methodology, RETROSPECTIVE studies, EVALUATION research, MITOCHONDRIAL encephalomyopathies, COMPARATIVE studies, RESEARCH funding, DISEASE complications
Abstract

In this retrospective, multicentre, observational cohort study, we sought to determine the clinical, radiological, EEG, genetics and neuropathological characteristics of mitochondrial stroke-like episodes and to identify associated risk predictors. Between January 1998 and June 2018, we identified 111 patients with genetically determined mitochondrial disease who developed stroke-like episodes. Post-mortem cases of mitochondrial disease (n = 26) were identified from Newcastle Brain Tissue Resource. The primary outcome was to interrogate the clinico-radiopathological correlates and prognostic indicators of stroke-like episode in patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome (MELAS). The secondary objective was to develop a multivariable prediction model to forecast stroke-like episode risk. The most common genetic cause of stroke-like episodes was the m.3243A>G variant in MT-TL1 (n = 66), followed by recessive pathogenic POLG variants (n = 22), and 11 other rarer pathogenic mitochondrial DNA variants (n = 23). The age of first stroke-like episode was available for 105 patients [mean (SD) age: 31.8 (16.1)]; a total of 35 patients (32%) presented with their first stroke-like episode ≥40 years of age. The median interval (interquartile range) between first and second stroke-like episodes was 1.33 (2.86) years; 43% of patients developed recurrent stroke-like episodes within 12 months. Clinico-radiological, electrophysiological and neuropathological findings of stroke-like episodes were consistent with the hallmarks of medically refractory epilepsy. Patients with POLG-related stroke-like episodes demonstrated more fulminant disease trajectories than cases of m.3243A>G and other mitochondrial DNA pathogenic variants, in terms of the frequency of refractory status epilepticus, rapidity of progression and overall mortality. In multivariate analysis, baseline factors of body mass index, age-adjusted blood m.3243A>G heteroplasmy, sensorineural hearing loss and serum lactate were significantly associated with risk of stroke-like episodes in patients with the m.3243A>G variant. These factors informed the development of a prediction model to assess the risk of developing stroke-like episodes that demonstrated good overall discrimination (area under the curve = 0.87, 95% CI 0.82-0.93; c-statistic = 0.89). Significant radiological and pathological features of neurodegeneration were more evident in patients harbouring pathogenic mtDNA variants compared with POLG: brain atrophy on cranial MRI (90% versus 44%, P < 0.001) and reduced mean brain weight (SD) [1044 g (148) versus 1304 g (142), P = 0.005]. Our findings highlight the often idiosyncratic clinical, radiological and EEG characteristics of mitochondrial stroke-like episodes. Early recognition of seizures and aggressive instigation of treatment may help circumvent or slow neuronal loss and abate increasing disease burden. The risk-prediction model for the m.3243A>G variant can help inform more tailored genetic counselling and prognostication in routine clinical practice. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

136. Epilepsy and seizures in young people with 22q11.2 deletion syndrome:Prevalence and links with other neurodevelopmental disorders

Author

Eaton, Christopher B., Thomas, Rhys H., Hamandi, Khalid, Payne, Gareth C., Kerr, Michael P., Linden, David E. J., Owen, Michael J., Cunningham, Adam C., Bartsch, Ulrich, Struik, Siske S., van den Bree, Marianne B. M., RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, RS: MHeNs - R2 - Mental Health, School for Mental Health & Neuroscience, and RS: MHeNs - R3 - Neuroscience

Subjects
ILAE, CHILDHOOD, PSYCHOPATHOLOGY, CHILDREN, INTERNATIONAL-LEAGUE, seizure semiology, CLASSIFICATION, psychiatric disorder, unprovoked seizure, SYNAPTIC PLASTICITY, SCHIZOPHRENIA, ADOLESCENTS, RELIABILITY, Full‐length Original Research, febrile seizure, electroencephalography
Abstract

Objective: The true prevalence of epileptic seizures and epilepsy in 22q11.2 deletion syndrome (22q11.2DS) is unknown, because previous studies have relied on historical medical record review. Associations of epilepsy with other neurodevelopmental manifestations (eg, specific psychiatric diagnoses) remain unexplored. Methods: The primary caregivers of 108 deletion carriers (mean age 13.6 years) and 60 control siblings (mean age 13.1 years) completed a validated epilepsy screening questionnaire. A subsample (n = 44) underwent a second assessment with interview, prolonged electroencephalography (EEG), and medical record and epileptologist review. Intelligence quotient (IQ), psychopathology, and other neurodevelopmental problems were examined using neurocognitive assessment and questionnaire/interview. Results: Eleven percent (12/108) of deletion carriers had an epilepsy diagnosis (controls 0%, P = 0.004). Fifty-seven of the remaining 96 deletion carriers (59.4%) had seizures or seizurelike symptoms (controls 13.3%, 8/60, P

Published
2019

137. Clinical spectrum of -related epileptic disorders

Author

Wolking, Stefan, May, Patrick, Mei, Davide, Møller, Rikke S, Balestrini, Simona, Helbig, Katherine L, Altuzarra, Cecilia Desmettre, Chatron, Nicolas, Kaiwar, Charu, Stöhr, Katharina, Widdess-Walsh, Peter, Mendelsohn, Bryce A, Numis, Adam, Cilio, Maria-Roberta, Van Paesschen, Wim, Svendsen, Lene L, Oates, Stephanie, Hughes, Elaine, Goyal, Sushma, Brown, Kathleen, Sifuentes Saenz, Margarita, Dorn, Thomas, Muhle, Hiltrud, Pagnamenta, Alistair T, Vavoulis, Dimitris V, Knight, Samantha J L, Taylor, Jenny C, Canevini, Maria Paola, Darra, Francesca, Gavrilova, Ralitza H, Powis, Zöe, Tang, Shan, Marquetand, Justus, Armstrong, Martin, McHale, Duncan, Klee, Eric W, Kluger, Gerhard J, Lowenstein, Daniel H, Weckhuysen, Sarah, Pal, Deb K, Helbig, Ingo, Guerrini, Renzo, Thomas, Rhys H, Rees, Mark I, Lesca, Gaetan, Sisodiya, Sanjay M, Weber, Yvonne G, Lal, Dennis, Marini, Carla, Lerche, Holger, Schubert, Julian, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, and UCL - (SLuc) Service de neurologie pédiatrique

Subjects
Male, Drug Resistant Epilepsy, Adolescent, Learning Disabilities, Developmental Disabilities, Infant, Newborn, Mutation, Missense, High-Throughput Nucleotide Sequencing, Infant, Syntaxin 1, Electroencephalography, Sequence Analysis, DNA, Seizures, Febrile, Young Adult, Phenotype, Loss of Function Mutation, Child, Preschool, Humans, Anticonvulsants, Female, Epilepsies, Partial, Child, Epileptic Syndromes
Abstract

OBJECTIVE: The aim of this study was to expand the spectrum of epilepsy syndromes related to STX1B, encoding the presynaptic protein syntaxin-1B, and establish genotype-phenotype correlations by identifying further disease-related variants. METHODS: We used next-generation sequencing in the framework of research projects and diagnostic testing. Clinical data and EEGs were reviewed, including already published cases. To estimate the pathogenicity of the variants, we used established and newly developed in silico prediction tools. RESULTS: We describe 17 new variants in STX1B, which are distributed across the whole gene. We discerned 4 different phenotypic groups across the newly identified and previously published patients (49 patients in 23 families): (1) 6 sporadic patients or families (31 affected individuals) with febrile and afebrile seizures with a benign course, generally good drug response, normal development, and without permanent neurologic deficits; (2) 2 patients with genetic generalized epilepsy without febrile seizures and cognitive deficits; (3) 13 patients or families with intractable seizures, developmental regression after seizure onset and additional neuropsychiatric symptoms; (4) 2 patients with focal epilepsy. More often, we found loss-of-function mutations in benign syndromes, whereas missense variants in the SNARE motif of syntaxin-1B were associated with more severe phenotypes. CONCLUSION: These data expand the genetic and phenotypic spectrum of STX1B-related epilepsies to a diverse range of epilepsies that span the International League Against Epilepsy classification. Variants in STX1B are protean and contribute to many different epilepsy phenotypes, similar to SCN1A, the most important gene associated with fever-associated epilepsies.

Published
2019

139. Clinical spectrum of STX1B-related epileptic disorders

Author

Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Wolking, Stefan, May, Patrick, Mei, Davide, Møller, Rikke S., Balestrini, Simona, Helbig, Katherine L., Altuzurra, Cecilia D., Chatron, Nicolas, Kaiwar, Charu, Stöhr, Katharina, Widdess-Walsh, Peter, Mendelsohn, Bryce A., Numis, Adam, Cilio, Maria R., Van Paesschen, Wim, Svendsen, Lene L., Oates, Stephanie, Hughes, Elaine, Goyal, Sushma, Brown, Kathleen, Sifuentes Saenz, Dorn, Thomas, Muhle, Hiltrud, Pagnamenta, Alistair T., Vavoulis, Dimitris V., Knight, Samantha J.L., Taylor, Jenny C., Canevini, Maria P., Darra, Franchesca, Gavrilova, Ralitza H., Powis, Zöe, Tang, Shan, Marquetand, Justus, Armstrong, Martin, McHale, Duncan, Klee, Ernst W., Kluger, Gerhard J., Lowenstein, Daniel H., Weckhuysen, Sarah, Pal, Deb K., Helbig, Ingo, Guerrini, Renzo, Thomas, Rhys H., Rees, Mark I., Lesca, Gaetan, Sisodiya, Sanjay M., Weber, Yvonne G., Lal, Dennis, Marini, Carla, Lerche, Holger, Schubert, Julian, Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Wolking, Stefan, May, Patrick, Mei, Davide, Møller, Rikke S., Balestrini, Simona, Helbig, Katherine L., Altuzurra, Cecilia D., Chatron, Nicolas, Kaiwar, Charu, Stöhr, Katharina, Widdess-Walsh, Peter, Mendelsohn, Bryce A., Numis, Adam, Cilio, Maria R., Van Paesschen, Wim, Svendsen, Lene L., Oates, Stephanie, Hughes, Elaine, Goyal, Sushma, Brown, Kathleen, Sifuentes Saenz, Dorn, Thomas, Muhle, Hiltrud, Pagnamenta, Alistair T., Vavoulis, Dimitris V., Knight, Samantha J.L., Taylor, Jenny C., Canevini, Maria P., Darra, Franchesca, Gavrilova, Ralitza H., Powis, Zöe, Tang, Shan, Marquetand, Justus, Armstrong, Martin, McHale, Duncan, Klee, Ernst W., Kluger, Gerhard J., Lowenstein, Daniel H., Weckhuysen, Sarah, Pal, Deb K., Helbig, Ingo, Guerrini, Renzo, Thomas, Rhys H., Rees, Mark I., Lesca, Gaetan, Sisodiya, Sanjay M., Weber, Yvonne G., Lal, Dennis, Marini, Carla, Lerche, Holger, and Schubert, Julian

Abstract

Objective: The aim of this study was to expand the spectrum of epilepsy syndromes related to STX1B, encoding the presynaptic protein syntaxin-1B, and to establish genotype-phenotype correlations by identifying further disease-related variants. Methods: We used next generation sequencing in the framework of research projects and diagnostic testing. Clinical data and EEGs were reviewed, including already published cases. To estimate the pathogenicity of the variants, we used established and newly developed in silico prediction tools. Results: We describe fifteen new variants in STX1B which are distributed across the whole gene. We discerned four different phenotypic groups across the newly identified and previously published patients (49 in 23 families): 1) Six sporadic patients or families (31 affected individuals) with febrile and afebrile seizures with a benign course, generally good drug response, normal development and without permanent neurological deficits; 2) two patients of genetic generalized epilepsy without febrile seizures and cognitive deficits; 3) thirteen patients or families with intractable seizures, developmental regression after seizure onset and additional neuropsychiatric symptoms; 4) two patients with focal epilepsy. Nonsense mutations were found more often in benign syndromes, whereas missense variants in the SNARE motif of syntaxin-1B were associated with more severe phenotypes. Conclusion: These data expand the genetic and phenotypic spectrum of STX1B-related epilepsies to a diverse range of epilepsies that span the ILAE classification. Variants in STX1B are protean, and able to contribute to many different epilepsy phenotypes, similar to SCN1A, the most important gene associated with fever-associated epilepsies.

Published
2019

140. White matter abnormalities across different epilepsy syndromes in adults: an ENIGMA Epilepsy study

Author

Hatton, Sean N., Huynh, Khoa H., Bonilha, Leonardo, Abela, Eugenio Cecilio, Alhusaini, Saud, Altmann, André, Alvim, Marina K. M., Balachandra, Akshara R., Bartolini, Emanuele, Bender, Benjamin, Bernasconi, Neda, Bernasconi, Andrea, Bernhardt, Boris, Bargallo, Núria, Caldairou, Benoit, Caligiuri, Maria Eugenia, Carr, Sarah J. A., Cavalleri, Gianpiero L., Cendes, Fernando, Concha, Luis, Davoodi-Bojd, Esmaeil, Desmond, Patricia M., Devinsky, Orrin, Doherty, Colin P., Domin, Martin, Duncan, John S., Focke, Niels K., Foley, Sonya F., Gambardella, Antonio, Gleichgerrcht, Ezequiel, Guerrini, Renzo, Hamandi, Khalid, Ishikawa, Akari, Keller, Simon S., Kochunov, Peter V., Kotikalapudi, Raviteja, Kreilkamp, Barbara A. K., Kwan, Patrick, Labate, Angelo, Langner, Sönke, Lenge, Matteo, Liu, Min, Lui, Elaine, Martin, Pascal, Mascalchi, Mario, Moreira, José Carlos Vasques, Morita-Sherman, Marcia Elisabete, O’Brien, Terence J., Pardoe, Heath R., Pariente Zorrilla, José Carlos, Ribeiro, Letı́cia F., Richardson, Mark Philip, Rocha, Cristiane S., Rodrı́guez-Cruces, Raúl, Rosenow, Felix, Severino, Mariasavina, Sinclair, Benjamin, Soltanian-Zadeh, Hamid, Striano, Pasquale, Taylor, Peter N., Thomas, Rhys H., Tortora, Domenico, Velakoulis, Dennis, Vezzani, Annamaria, Vivash, Lucy, Podewils, Felix von, Vos, Sjoerd B., Weber, Bernd, Winston, Gavin P., Yasuda, Clarissa L., Thompson, Paul M., Jahanshad, Neda, Sisodiya, Sanjay M., McDonald, Carrie R., Hatton, Sean N., Huynh, Khoa H., Bonilha, Leonardo, Abela, Eugenio Cecilio, Alhusaini, Saud, Altmann, André, Alvim, Marina K. M., Balachandra, Akshara R., Bartolini, Emanuele, Bender, Benjamin, Bernasconi, Neda, Bernasconi, Andrea, Bernhardt, Boris, Bargallo, Núria, Caldairou, Benoit, Caligiuri, Maria Eugenia, Carr, Sarah J. A., Cavalleri, Gianpiero L., Cendes, Fernando, Concha, Luis, Davoodi-Bojd, Esmaeil, Desmond, Patricia M., Devinsky, Orrin, Doherty, Colin P., Domin, Martin, Duncan, John S., Focke, Niels K., Foley, Sonya F., Gambardella, Antonio, Gleichgerrcht, Ezequiel, Guerrini, Renzo, Hamandi, Khalid, Ishikawa, Akari, Keller, Simon S., Kochunov, Peter V., Kotikalapudi, Raviteja, Kreilkamp, Barbara A. K., Kwan, Patrick, Labate, Angelo, Langner, Sönke, Lenge, Matteo, Liu, Min, Lui, Elaine, Martin, Pascal, Mascalchi, Mario, Moreira, José Carlos Vasques, Morita-Sherman, Marcia Elisabete, O’Brien, Terence J., Pardoe, Heath R., Pariente Zorrilla, José Carlos, Ribeiro, Letı́cia F., Richardson, Mark Philip, Rocha, Cristiane S., Rodrı́guez-Cruces, Raúl, Rosenow, Felix, Severino, Mariasavina, Sinclair, Benjamin, Soltanian-Zadeh, Hamid, Striano, Pasquale, Taylor, Peter N., Thomas, Rhys H., Tortora, Domenico, Velakoulis, Dennis, Vezzani, Annamaria, Vivash, Lucy, Podewils, Felix von, Vos, Sjoerd B., Weber, Bernd, Winston, Gavin P., Yasuda, Clarissa L., Thompson, Paul M., Jahanshad, Neda, Sisodiya, Sanjay M., and McDonald, Carrie R.

Abstract

The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analyzed from 1,069 non-epileptic controls and 1,249 patients: temporal lobe epilepsy with hippocampal sclerosis (N=599), temporal lobe epilepsy with normal MRI (N=275), genetic generalized epilepsy (N=182) and nonlesional extratemporal epilepsy (N=193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fiber tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at p<0.001). Across “all epilepsies” lower fractional anisotropy was observed in most fiber tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. Less robust effects were seen with mean diffusivity. Syndrome-specific fractional anisotropy and mean diffusivity differences were most pronounced in patients with hippocampal sclerosis in the ipsilateral parahippocampal cingulum and external capsule, with smaller effects across most other tracts. Those with temporal lobe epilepsy and normal MRI showed a similar pattern of greater ipsilateral than contralateral abnormalities, but less marked than those in patients with hip

Published
2019

141. ANKLE ARTHRITIS

Author

THOMAS, RHYS H. and DANIELS, TIMOTHY R.

Published
2003

142. Neurologic phenotypes associated with COL4A1 / 2 mutations

Author

Zagaglia, Sara, Selch, Christina, Radić Nišević, Jelena, Mei, Davide, Michalak, Zuzanna, Hernandez-Hernandez, Laura, Krithika, S., Vezyroglou, Katharina, Varadkar, Sophia M., Pepler, Alexander, Biskup, Saskia, Leão, Miguel, Gärtner, Jutta, Merkenschlager, Andreas, Jaksch, Michaela, Møller, Rikke S., Gardella, Elena, Kristiansen, Britta Schlott, Hansen, Lars Kjærsgaard, Vari, Maria Stella, Helbig, Katherine L., Desai, Sonal, Smith-Hicks, Constance L., Hino-Fukuyo, Naomi, Talvik, Tiina, Laugesaar, Rael, Ilves, Pilvi, Õunap, Katrin, Körber, Ingrid, Hartlieb, Till, Kudernatsch, Manfred, Winkler, Peter, Schimmel, Mareike, Hasse, Anette, Knuf, Markus, Heinemeyer, Jan, Makowski, Christine, Ghedia, Sondhya, Subramanian, Gopinath M., Striano, Pasquale, Thomas, Rhys H., Micallef, Caroline, Thom, Maria, Werring, David J., Kluger, Gerhard Josef, Cross, J. Helen, Guerrini, Renzo, Balestrini, Simona, and Sisodiya, Sanjay M.

Subjects
Adult, Collagen Type IV, Male, Epilepsy, Adolescent, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Neurologija, Young Adult, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Neurology, Child, Preschool, Mutation, Humans, Female, Nervous System Diseases, Child, Genetic Association Studies
Abstract

Objective To characterize the neurologic phenotypes associated with COL4A1/2 mutations and to seek genotype–phenotype correlation. Methods We analyzed clinical, EEG, and neuroimaging data of 44 new and 55 previously reported patients with COL4A1/COL4A2 mutations. Results Childhood-onset focal seizures, frequently complicated by status epilepticus and resistance to antiepileptic drugs, was the most common phenotype. EEG typically showed focal epileptiform discharges in the context of other abnormalities, including generalized sharp waves or slowing. In 46.4% of new patients with focal seizures, porencephalic cysts on brain MRI colocalized with the area of the focal epileptiform discharges. In patients with porencephalic cysts, brain MRI frequently also showed extensive white matter abnormalities, consistent with the finding of diffuse cerebral disturbance on EEG. Notably, we also identified a subgroup of patients with epilepsy as their main clinical feature, in which brain MRI showed nonspecific findings, in particular periventricular leukoencephalopathy and ventricular asymmetry. Analysis of 15 pedigrees suggested a worsening of the severity of clinical phenotype in succeeding generations, particularly when maternally inherited. Mutations associated with epilepsy were spread across COL4A1 and a clear genotype–phenotype correlation did not emerge. Conclusion COL4A1/COL4A2 mutations typically cause a severe neurologic condition and a broader spectrum of milder phenotypes, in which epilepsy is the predominant feature. Early identification of patients carrying COL4A1/COL4A2 mutations may have important clinical consequences, while for research efforts, omission from large-scale epilepsy sequencing studies of individuals with abnormalities on brain MRI may generate misleading estimates of the genetic contribution to the epilepsies overall.

Published
2018

143. Neurologic phenotypes associated with COL4A1/2 mutations

Author

Zagaglia, Sara, Selch, Christina, Nisevic, Jelena R., Mei, Davide, Michalak, Zuzanna, Hernandez-Hernandez, Laura, Krithika, S., Vezyroglou, Katharina, Varadkar, Sophia M., Pepler, Alexander, Biskup, Saskia, Leão, Miguel, Gärtner, Jutta, Merkenschlager, Andreas, Jaksch, Michaela, Møller, Rikke S., Gardella, Elena, Kristiansen, Britta S., Hansen, Lars K., Vari, Maria S., Helbig, Katherine L., Desai, Sonal, Smith-Hicks, Constance L., Hino-Fukuyo, Naomi, Talvik, Tiina, Laugesaar, Rael, Ilves, Pilvi, Õunap, Katrin, Körber, Ingrid, Hartlieb, Till, Kudernatsch, Manfred, Winkler, Peter, Schimmel, Mareike, Hasse, Anette, Knuf, Markus, Heinemeyer, Jan, Makowski, Christine, Ghedia, Sondhya, Subramanian, Gopinath M., Striano, Pasquale, Thomas, Rhys H., Micallef, Caroline, Thom, Maria, Werring, David J., Kluger, Gerhard J., Cross, J. Helen, Guerrini, Renzo, Balestrini, Simona, and Sisodiya, Sanjay M.

Subjects
COL4A2 protein, human, White Matter, Porencephaly, Article
Abstract

Objective: To characterize the neurologic phenotypes associated with COL4A1/2 mutations and to seek genotype–phenotype correlation.\ud \ud Methods: We analyzed clinical, EEG, and neuroimaging data of 44 new and 55 previously reported patients with COL4A1/COL4A2 mutations.\ud \ud Results: Childhood-onset focal seizures, frequently complicated by status epilepticus and resistance to antiepileptic drugs, was the most common phenotype. EEG typically showed focal epileptiform discharges in the context of other abnormalities, including generalized sharp waves or slowing. In 46.4% of new patients with focal seizures, porencephalic cysts on brain MRI colocalized with the area of the focal epileptiform discharges. In patients with porencephalic cysts, brain MRI frequently also showed extensive white matter abnormalities, consistent with the finding of diffuse cerebral disturbance on EEG. Notably, we also identified a subgroup of patients with epilepsy as their main clinical feature, in which brain MRI showed nonspecific findings, in particular periventricular leukoencephalopathy and ventricular asymmetry. Analysis of 15 pedigrees suggested a worsening of the severity of clinical phenotype in succeeding generations, particularly when maternally inherited. Mutations associated with epilepsy were spread across COL4A1 and a clear genotype–phenotype correlation did not emerge.\ud \ud Conclusion: COL4A1/COL4A2 mutations typically cause a severe neurologic condition and a broader spectrum of milder phenotypes, in which epilepsy is the predominant feature. Early identification of patients carrying COL4A1/COL4A2 mutations may have important clinical consequences, while for research efforts, omission from large-scale epilepsy sequencing studies of individuals with abnormalities on brain MRI may generate misleading estimates of the genetic contribution to the epilepsies overall.

Published
2018

144. Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study

Author

Whelan, Christopher D., Altmann, Andre, Botía, Juan A., Jahanshad, Neda, Hibar, Derrek P., Absil, Julie, Alhusaini, Saud, Alvim, Marina K.M., Auvinen, Pia, Bartolini, Emanuele, Bergo, Felipe P.G., Bernardes, Tauana, Blackmon, Karen, Braga, Barbara, Caligiuri, Maria Eugenia, Calvo, Anna, Carr, Sarah J., Chen, Jian, Chen, Shuai, Cherubini, Andrea, David, Philippe, Domin, Martin, Foley, Sonya, França, Wendy, Haaker, Gerrit, Isaev, Dmitry, Keller, Simon S., Kotikalapudi, Raviteja, Kowalczyk, Magdalena A., Kuzniecky, Ruben, Langner, Soenke, Lenge, Matteo, Leyden, Kelly M., Liu, Min, Loi, Richard Q., Martin, Pascal, Mascalchi, Mario, Morita, Marcia E., Pariente, Jose C., Rodríguez-Cruces, Raul, Rummel, Christian, Saavalainen, Taavi, Semmelroch, Mira K., Severino, Mariasavina, Thomas, Rhys H., Tondelli, Manuela, Tortora, Domenico, Vaudano, Anna Elisabetta, Vivash, Lucy, Von Podewils, Felix, Wagner, Jan, Weber, Bernd, Yao, Yi, Yasuda, Clarissa L., Zhang, Guohao, Bargalló, Nuria, Bender, Benjamin, Bernasconi, Neda, Bernasconi, Andrea, Bernhardt, Boris C., Blümcke, Ingmar, Carlson, Chad, Cavalleri, Gianpiero L., Cendes, Fernando, Concha, Luis, Delanty, Norman, Depondt, Chantal, Devinsky, Orrin, Doherty, Colin P., Focke, Niels K., Gambardella, Antonio, Guerrini, Renzo, and Hamandi, Khalid

Subjects
thalamus, epilepsy, MRI, precentral gyrus
Abstract

Progressive functional decline in the epilepsies is largely unexplained. We formed the ENIGMA-Epilepsy consortium to understand factors that influence brain measures in epilepsy, pooling data from 24 research centres in 14 countries across Europe, North and South America, Asia, and Australia. Structural brain measures were extracted from MRI brain scans across 2149 individuals with epilepsy, divided into four epilepsy subgroups including idiopathic generalized epilepsies (n =367), mesial temporal lobe epilepsies with hippocampal sclerosis (MTLE; left, n = 415; right, n = 339), and all other epilepsies in aggregate (n = 1026), and compared to 1727 matched healthy controls. We ranked brain structures in order of greatest differences between patients and controls, by meta-Analysing effect sizes across 16 subcortical and 68 cortical brain regions. We also tested effects of duration of disease, age at onset, and age-by-diagnosis interactions on structural measures. We observed widespread patterns of altered subcortical volume and reduced cortical grey matter thickness. Compared to controls, all epilepsy groups showed lower volume in the right thalamus (Cohen's d = â '0.24 to â '0.73; P < 1.49 × 10 â '4), and lower thickness in the precentral gyri bilaterally (d = â '0.34 to â '0.52; P < 4.31 × 10 â '6). Both MTLE subgroups showed profound volume reduction in the ipsilateral hippocampus (d = â '1.73 to â '1.91, P < 1.4 × 10 â '19), and lower thickness in extrahippocampal cortical regions, including the precentral and paracentral gyri, compared to controls (d = â '0.36 to â '0.52; P < 1.49 × 10 â '4). Thickness differences of the ipsilateral temporopolar, parahippocampal, entorhinal, and fusiform gyri, contralateral pars triangularis, and bilateral precuneus, superior frontal and caudal middle frontal gyri were observed in left, but not right, MTLE (d = â '0.29 to â '0.54; P < 1.49 × 10 â '4). Contrastingly, thickness differences of the ipsilateral pars opercularis, and contralateral transverse temporal gyrus, were observed in right, but not left, MTLE (d = â '0.27 to â '0.51; P < 1.49 × 10 â '4). Lower subcortical volume and cortical thickness associated with a longer duration of epilepsy in the all-epilepsies, all-other-epilepsies, and right MTLE groups (beta, b < â '0.0018; P < 1.49 × 10 â '4). In the largest neuroimaging study of epilepsy to date, we provide information on the common epilepsies that could not be realistically acquired in any other way. Our study provides a robust ranking of brain measures that can be further targeted for study in genetic and neuropathological studies. This worldwide initiative identifies patterns of shared grey matter reduction across epilepsy syndromes, and distinctive abnormalities between epilepsy syndromes, which inform our understanding of epilepsy as a network disorder, and indicate that certain epilepsy syndromes involve more widespread structural compromise than previously assumed.

Published
2018

145. Epilepsy and seizures in young people with 22q11.2 deletion syndrome: Prevalence and links with other neurodevelopmental disorders

Author

Eaton, Christopher B., primary, Thomas, Rhys H., additional, Hamandi, Khalid, additional, Payne, Gareth C., additional, Kerr, Michael P., additional, Linden, David E. J., additional, Owen, Michael J., additional, Cunningham, Adam C., additional, Bartsch, Ullrich, additional, Struik, Siske S., additional, and Bree, Marianne B. M., additional

Published
2019
Full Text
View/download PDF

147. Paediatric sudden unexpected death in epilepsy: A parental report cohort.

Author

Craig, Donald P., Choi, Yun Young, Hughes, Elaine, Osland, Karen, Hanna, Jane, Kerr, Mike P., and Thomas, Rhys H.

Subjects
PARENTAL death, SUDDEN death, CHILDREN with epilepsy, CHILDHOOD epilepsy, CHILD death, VAGUS nerve, EPILEPSY
Abstract

Background: Sudden unexpected death in epilepsy (SUDEP) accounts for a large percentage of deaths in children with epilepsy. Contributing factors to paediatric SUDEP are incompletely understood. Aims of Study: The Epilepsy Deaths Register (EDR) is an anonymized register that compiles information on deaths related to epilepsy, across all ages and epilepsy classifications. Using the EDR, we sought to identify key risk factors for SUDEP in children to assist the development of preventive measures. Methods: All registrations between the ages of 1 and 16 years were reviewed to identify definite or probable SUDEP. These cases were analysed to identify common demographics, comorbidities, monitoring, treatments and circumstances near to the deaths. Results: We identified forty‐six cases (27 males) of definite or probable SUDEP. Paediatric SUDEP is more common in a 12‐ to 16‐year age group and in those with neuro‐disability. Most paediatric SUDEP occurs during apparent sleep. There were four cases with a vagus nerve stimulator. SUDEP can occur early after the onset of seizures. Conclusions: This is the largest single cohort of SUDEP reported in children. Reports from caregivers can augment population data. Surveillance in sleep is a priority area of development. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

150. Complement system biomarkers in epilepsy

Author

Kopczynska, Maja, primary, Zelek, Wioleta M., additional, Vespa, Simone, additional, Touchard, Samuel, additional, Wardle, Mark, additional, Loveless, Samantha, additional, Thomas, Rhys H., additional, Hamandi, Khalid, additional, and Morgan, B. Paul, additional

Published
2018
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results