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2. Lack of association of first and second-line medication dosing and progression to refractory status epilepticus in children

Author

Barcia Aguilar, Cristina, Amengual-Gual, Marta, Brenton, J. Nicholas, Chapman, Kevin E., Clark, Justice, Gaillard, William D., Goldstein, Joshua L., Goodkin, Howard P., Kahoud, Robert, Lai, Yi-Chen, Mikati, Mohamad A., Morgan, Lindsey A., Payne, Eric T., Press, Craig A., Reece, Latania, Sands, Tristan T., Sannagowdara, Kumar, Sheehan, Theodore, Shellhaas, Renée A., Tasker, Robert C., Wainwright, Mark S., Zhang, Bo, and Loddenkemper, Tobias

Published
2024
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3. Biallelic CRELD1 variants cause a multisystem syndrome, including neurodevelopmental phenotypes, cardiac dysrhythmias, and frequent infections

Author

Borras, Silvia, Clark, Caroline, Dean, John, Miedzybrodzka, Zosia, Ross, Alison, Tennant, Stephen, Dabir, Tabib, Donnelly, Deirdre, Humphreys, Mervyn, Magee, Alex, McConnell, Vivienne, McKee, Shane, McNerlan, Susan, Morrison, Patrick J., Rea, Gillian, Stewart, Fiona, Cole, Trevor, Cooper, Nicola, Cooper-Charles, Lisa, Cox, Helen, Islam, Lily, Jarvis, Joanna, Keelagher, Rebecca, Lim, Derek, McMullan, Dominic, Morton, Jenny, Naik, Swati, O’Driscoll, Mary, Ong, Kai-Ren, Osio, Deborah, Ragge, Nicola, Turton, Sarah, Vogt, Julie, Williams, Denise, Bodek, Simon, Donaldson, Alan, Hills, Alison, Low, Karen, Newbury-Ecob, Ruth, Norman, Andrew M., Roberts, Eileen, Scurr, Ingrid, Smithson, Sarah, Tooley, Madeleine, Abbs, Steve, Armstrong, Ruth, Dunn, Carolyn, Holden, Simon, Park, Soo-Mi, Paterson, Joan, Raymond, Lucy, Reid, Evan, Sandford, Richard, Simonic, Ingrid, Tischkowitz, Marc, Woods, Geoff, Bradley, Lisa, Comerford, Joanne, Green, Andrew, Lynch, Sally, McQuaid, Shirley, Mullaney, Brendan, Berg, Jonathan, Goudie, David, Mavrak, Eleni, McLean, Joanne, McWilliam, Catherine, Reavey, Eleanor, Azam, Tara, Cleary, Elaine, Jackson, Andrew, Lam, Wayne, Lampe, Anne, Moore, David, Porteous, Mary, Baple, Emma, Baptista, Júlia, Brewer, Carole, Castle, Bruce, Kivuva, Emma, Owens, Martina, Rankin, Julia, Shaw-Smith, Charles, Turner, Claire, Turnpenny, Peter, Tysoe, Carolyn, Bradley, Therese, Davidson, Rosemarie, Gardiner, Carol, Joss, Shelagh, Kinning, Esther, Longman, Cheryl, McGowan, Ruth, Murday, Victoria, Pilz, Daniela, Tobias, Edward, Whiteford, Margo, Williams, Nicola, Barnicoat, Angela, Clement, Emma, Faravelli, Francesca, Hurst, Jane, Jenkins, Lucy, Jones, Wendy, Ajith Kumar, V.K., Lees, Melissa, Loughlin, Sam, Male, Alison, Morrogh, Deborah, Rosser, Elisabeth, Scott, Richard, Wilson, Louise, Beleza, Ana, Deshpande, Charu, Flinter, Frances, Holder, Muriel, Irving, Melita, Izatt, Louise, Josifova, Dragana, Mohammed, Shehla, Molenda, Aneta, Robert, Leema, Roworth, Wendy, Ruddy, Deborah, Ryten, Mina, Yau, Shu, Bennett, Christopher, Blyth, Moira, Campbell, Jennifer, Coates, Andrea, Dobbie, Angus, Hewitt, Sarah, Hobson, Emma, Jackson, Eilidh, Jewell, Rosalyn, Kraus, Alison, Prescott, Katrina, Sheridan, Eamonn, Thomson, Jenny, Bradshaw, Kirsty, Dixit, Abhijit, Eason, Jacqueline, Haines, Rebecca, Harrison, Rachel, Mutch, Stacey, Sarkar, Ajoy, Searle, Claire, Shannon, Nora, Sharif, Abid, Suri, Mohnish, Vasudevan, Pradeep, Canham, Natalie, Ellis, Ian, Greenhalgh, Lynn, Howard, Emma, Stinton, Victoria, Swale, Andrew, Weber, Astrid, Banka, Siddharth, Breen, Catherine, Briggs, Tracy, Burkitt-Wright, Emma, Chandler, Kate, Clayton-Smith, Jill, Donnai, Dian, Douzgou, Sofia, Gaunt, Lorraine, Jones, Elizabeth, Kerr, Bronwyn, Langley, Claire, Metcalfe, Kay, Smith, Audrey, Wright, Ronnie, Bourn, David, Burn, John, Fisher, Richard, Hellens, Steve, Henderson, Alex, Montgomery, Tara, Splitt, Miranda, Straub, Volker, Wright, Michael, Zwolinski, Simon, Allen, Zoe, Bernhard, Birgitta, Brady, Angela, Brooks, Claire, Busby, Louise, Clowes, Virginia, Ghali, Neeti, Holder, Susan, Ibitoye, Rita, Wakeling, Emma, Blair, Edward, Carmichael, Jenny, Cilliers, Deirdre, Clasper, Susan, Gibbons, Richard, Kini, Usha, Lester, Tracy, Nemeth, Andrea, Poulton, Joanna, Price, Sue, Shears, Debbie, Stewart, Helen, Wilkie, Andrew, Albaba, Shadi, Baker, Duncan, Balasubramanian, Meena, Johnson, Diana, Parker, Michael, Quarrell, Oliver, Stewart, Alison, Willoughby, Josh, Crosby, Charlene, Elmslie, Frances, Homfray, Tessa, Jin, Huilin, Lahiri, Nayana, Mansour, Sahar, Marks, Karen, McEntagart, Meriel, Saggar, Anand, Tatton-Brown, Kate, Butler, Rachel, Clarke, Angus, Corrin, Sian, Fry, Andrew, Kamath, Arveen, McCann, Emma, Mugalaasi, Hood, Pottinger, Caroline, Procter, Annie, Sampson, Julian, Sansbury, Francis, Varghese, Vinod, Baralle, Diana, Callaway, Alison, Cassidy, Emma J., Daniels, Stacey, Douglas, Andrew, Foulds, Nicola, Hunt, David, Kharbanda, Mira, Lachlan, Katherine, Mercer, Catherine, Side, Lucy, Temple, I. Karen, Wellesley, Diana, Ambrose, J.C., Arumugam, P., Baple, E.L., Bleda, M., Boardman-Pretty, F., Boissiere, J.M., Boustred, C.R., Caulfield, M.J., Chan, G.C., Craig, C.E.H., Daugherty, L.C., de Burca, A., Devereau, A., Elgar, G., Foulger, R.E., Fowler, T., FurióTarí, P., Hackett, J.M., Halai, D., Hamblin, A., Henderson, S., Holman, J.E., Hubbard, T.J.P., Ibáñez, K., Jackson, R., Jones, L.J., Kasperaviciute, D., Kayikci, M., Lahnstein, L., Lawson, K., Leigh, S.E.A., Leong, I.U.S., Lopez, F.J., MaleadyCrowe, F., Mason, J., McDonagh, E.M., Moutsianas, L., Mueller, M., Murugaesu, N., Need, A.C., Odhams, C.A., Patch, C., Perez-Gil, D., Polychronopoulos, D., Pullinger, J., Rahim, T., Rendon, A., Riesgo-Ferreiro, P., Rogers, T., Ryten, M., Savage, K., Sawant, K., Scott, R.H., Siddiq, A., Sieghart, A., Smedley, D., Smith, K.R., Sosinsky, A., Spooner, W., Stevens, H.E., Stuckey, A., Sultana, R., Thomas, E.R.A., Thompson, S.R., Tucci, A., Walsh, E., Watters, S.A., Welland, M.J., Williams, E., Witkowska, K., Acosta, Maria T., Adam, Margaret, Adams, David R., Agrawal, Pankaj B., Alejandro, Mercedes E., Alvey, Justin, Amendola, Laura, Andrews, Ashley, Ashley, Euan A., Azamian, Mahshid S., Bacino, Carlos A., Bademci, Guney, Baker, Eva, Balasubramanyam, Ashok, Baldridge, Dustin, Bale, Jim, Bamshad, Michael, Barbouth, Deborah, Bayrak-Toydemir, Pinar, Beck, Anita, Beggs, Alan H., Behrens, Edward, Bejerano, Gill, Bennet, Jimmy, Berg-Rood, Beverly, Bernstein, Jonathan A., Berry, Gerard T., Bican, Anna, Bivona, Stephanie, Blue, Elizabeth, Bohnsack, John, Bonnenmann, Carsten, Bonner, Devon, Botto, Lorenzo, Boyd, Brenna, Briere, Lauren C., Brokamp, Elly, Brown, Gabrielle, Burke, Elizabeth A., Burrage, Lindsay C., Butte, Manish J., Byers, Peter, Byrd, William E., Carey, John, Carrasquillo, Olveen, Peter Chang, Ta Chen, Chanprasert, Sirisak, Chao, Hsiao-Tuan, Clark, Gary D., Coakley, Terra R., Cobban, Laurel A., Cogan, Joy D., Coggins, Matthew, Cole, F. Sessions, Colley, Heather A., Cooper, Cynthia M., Craigen, William J., Crouse, Andrew B., Cunningham, Michael, D'Souza, Precilla, Dai, Hongzheng, Dasari, Surendra, Davids, Mariska, Dayal, Jyoti G., Deardorff, Matthew, Dell'Angelica, Esteban C., Dhar, Shweta U., Dipple, Katrina, Doherty, Daniel, Dorrani, Naghmeh, Douine, Emilie D., Draper, David D., Duncan, Laura, Earl, Dawn, Eckstein, David J., Emrick, Lisa T., Eng, Christine M., Esteves, Cecilia, Estwick, Tyra, Falk, Marni, Fernandez, Liliana, Ferreira, Carlos, Fieg, Elizabeth L., Findley, Laurie C., Fisher, Paul G., Fogel, Brent L., Forghani, Irman, Fresard, Laure, Gahl, William A., Glass, Ian, Godfrey, Rena A., Golden-Grant, Katie, Goldman, Alica M., Goldstein, David B., Grajewski, Alana, Groden, Catherine A., Gropman, Andrea L., Gutierrez, Irma, Hahn, Sihoun, Hamid, Rizwan, Hanchard, Neil A., Hassey, Kelly, Hayes, Nichole, High, Frances, Hing, Anne, Hisama, Fuki M., Holm, Ingrid A., Hom, Jason, Horike-Pyne, Martha, Huang, Alden, Huang, Yong, Isasi, Rosario, Jamal, Fariha, Jarvik, Gail P., Jarvik, Jeffrey, Jayadev, Suman, Johnston, Jean M., Karaviti, Lefkothea, Kelley, Emily G., Kennedy, Jennifer, Kiley, Dana, Kohane, Isaac S., Kohler, Jennefer N., Krakow, Deborah, Krasnewich, Donna M., Kravets, Elijah, Korrick, Susan, Koziura, Mary, Krier, Joel B., Lalani, Seema R., Lam, Byron, Lam, Christina, Lanpher, Brendan C., Lanza, Ian R., Lau, C. Christopher, LeBlanc, Kimberly, Lee, Brendan H., Lee, Hane, Levitt, Roy, Lewis, Richard A., Lincoln, Sharyn A., Liu, Pengfei, Liu, Xue Zhong, Longo, Nicola, Loo, Sandra K., Loscalzo, Joseph, Maas, Richard L., Macnamara, Ellen F., MacRae, Calum A., Maduro, Valerie V., Majcherska, Marta M., Mak, Bryan, Malicdan, May Christine V., Mamounas, Laura A., Manolio, Teri A., Mao, Rong, Maravilla, Kenneth, Markello, Thomas C., Marom, Ronit, Marth, Gabor, Martin, Beth A., Martin, Martin G., Martínez-Agosto, Julian A., Marwaha, Shruti, McCauley, Jacob, McCormack, Colleen E., McCray, Alexa T., McGee, Elisabeth, Mefford, Heather, Merritt, J. Lawrence, Might, Matthew, Mirzaa, Ghayda, Morava, Eva, Moretti, Paolo M., Morimoto, Marie, Mulvihill, John J., Murdock, David R., Nakano-Okuno, Mariko, Nath, Avi, Nelson, Stan F., Newman, John H., Nicholas, Sarah K., Nickerson, Deborah, Nieves-Rodriguez, Shirley, Novacic, Donna, Oglesbee, Devin, Orengo, James P., Pace, Laura, Pak, Stephen, Pallais, J. Carl, Papp, Jeanette C., Parker, Neil H., Phillips, John A., Posey, Jennifer E., Potocki, Lorraine, Pusey, Barbara N., Quinlan, Aaron, Raskind, Wendy, Raja, Archana N., Rao, Deepak A., Renteria, Genecee, Reuter, Chloe M., Rives, Lynette, Robertson, Amy K., Rodan, Lance H., Rosenfeld, Jill A., Rosenwasser, Natalie, Ruzhnikov, Maura, Sacco, Ralph, Sampson, Jacinda B., Samson, Susan L., Saporta, Mario, Scott, C. Ron, Schaechter, Judy, Schedl, Timothy, Scott, Daryl A., Sharma, Prashant, Shin, Jimann, Signer, Rebecca, Sillari, Catherine H., Silverman, Edwin K., Sinsheimer, Janet S., Sisco, Kathy, Smith, Edward C., Smith, Kevin S., Solem, Emily, Solnica-Krezel, Lilianna, Stoler, Joan M., Stong, Nicholas, Sullivan, Jennifer A., Sun, Angela, Sutton, Shirley, Sweetser, David A., Sybert, Virginia, Tabor, Holly K., Tamburro, Cecelia P., Tekin, Mustafa, Telischi, Fred, Thorson, Willa, Tifft, Cynthia J., Toro, Camilo, Tran, Alyssa A., Tucker, Brianna M., Urv, Tiina K., Vanderver, Adeline, Velinder, Matt, Viskochil, Dave, Vogel, Tiphanie P., Wahl, Colleen E., Wallace, Stephanie, Walley, Nicole M., Walsh, Chris A., Walker, Melissa, Wambach, Jennifer, Wan, Jijun, Wang, Lee-Kai, Wangler, Michael F., Ward, Patricia A., Wegner, Daniel, Wener, Mark, Wenger, Tara, Perry, Katherine Wesseling, Westerfield, Monte, Wheeler, Matthew T., Whitlock, Jordan, Wolfe, Lynne A., Woods, Jeremy D., Yamamoto, Shinya, Yang, John, Yu, Guoyun, Zastrow, Diane B., Zhao, Chunli, Zuchner, Stephan, Jeffries, Lauren, Mis, Emily K., McWalter, Kirsty, Donkervoort, Sandra, Brodsky, Nina N., Carpier, Jean-Marie, Ji, Weizhen, Ionita, Cristian, Roy, Bhaskar, Morrow, Jon S., Darbinyan, Armine, Iyer, Krishna, Aul, Ritu B., Chao, Katherine R., Cobbold, Laura, Cohen, Stacey, Custodio, Helena M., Drummond-Borg, Margaret, Finanger, Erika, Hainline, Bryan E., Helbig, Ingo, Hewson, Stacy, Hu, Ying, Jackson, Adam, Konstantino, Monica, Leach, Meganne E., McCormick, David, Nelson, Stanley, Nguyen, Joanne, Nugent, Kimberly, Ortega, Lucy, Goodkin, Howard P., Roeder, Elizabeth, Roy, Sani, Sapp, Katie, Saade, Dimah, Sisodiya, Sanjay M., Stals, Karen, Towner, Shelley, Wilson, William, Khokha, Mustafa K., Bönnemann, Carsten G., Lucas, Carrie L., and Lakhani, Saquib A.

Published
2024
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5. A team science approach to discover novel targets for infantile spasms (IS)

Author

Vezzani, Annamaria, Berg, Anne T, Lowenstein, Daniel H, Klitgaard, Henrik, Goodkin, Howard P, Rho, Jong M, Katsarou, Anna Maria, Pirone, Antonella, Galanopoulou, Aristea S, Dulla, Chris, Nordli, Douglas R, Iacobas, Dumitru A, Sherr, Elliott, Cloyd, James, Veliskova, Jana, Noebels, Jeff L, Millichap, John J, Swann, John W, Koh, Sookyung, Velisek, Libor, Coles, Lisa, Patel, Manisha, Siehr, Meagan S, Jacob, Michele, Seo, Ryan, Heischmann, Svenja, Moshe, Solomon L, Chachua, Tamar, Brima, Tufikameni, Mowrey, Wenzhu B, White, H Steve, Milder, Julie, Lubbers, Laura, and Iyengar, Sloka S

Subjects
Neurosciences, Brain Disorders, Neurodegenerative, Epilepsy, Clinical Research, Neurological, Electroencephalography, Humans, Infant, Interdisciplinary Research, Spasms, Infantile, Translational Research, Biomedical, CURE Infantile Spasms Consortium, CURE Staff, Citizens United for Research in Epilepsy, Hypsarhythmia, West syndrome, infantile spasms, team science
Abstract

Infantile spasms (IS) is a devastating epilepsy syndrome that typically begins in the first year of life. Symptoms consist of stereotypical spasms, developmental delay, and electroencephalogram (EEG) that may demonstrate Hypsarhythmia. Current therapeutic approaches are not always effective, and there is no reliable way to predict which patient will respond to therapy. Given this disorder's complexity and the potential impact of a disease-modifying approach, Citizens United for Research in Epilepsy (CURE) employed a "team science" approach to advance the understanding of IS pathology and explore therapeutic modalities that might lead to the development of new ways to potentially prevent spasms and Hypsarhythmia. This approach was a first-of-its-kind collaborative initiative in epilepsy. The IS initiative funded 8 investigative teams over the course of 1-3 years. Projects included the following: discovery on the basic biology of IS, discovery of novel therapeutic targets, cross-validation of targets, discovery of biomarkers, and prognosis and treatment of IS. The combined efforts of a strong investigative team led to numerous advances in understanding the neural pathways underlying IS, testing of small molecules in preclinical models of IS and generated preliminary data on potential biomarkers. Thus far, the initiative has resulted in over 19 publications and subsequent funding for several investigators. Investigators reported that the IS initiative generally affected their research positively due to its collaborative and iterative nature. It also provided a unique opportunity to mentor junior investigators with an interest in translational research. Learnings included the need for a dedicated project manager and more transparent and real-time communication with investigators. The CURE IS initiative represents a unique approach to fund scientific discoveries on epilepsy. It brought together an interdisciplinary group of investigators-who otherwise would not have collaborated-to find transformative therapies for IS. Learnings from this initiative are being utilized for subsequent initiatives at CURE.

Published
2021

6. Design and implementation of electronic health record common data elements for pediatric epilepsy: Foundations for a learning health care system.

Author

Grinspan, Zachary, Patel, Anup, Shellhaas, Renée, Berg, Anne, Axeen, Erika, Bolton, Jeffrey, Clarke, David, Coryell, Jason, Gaillard, William, Goodkin, Howard, Koh, Sookyong, Kukla, Alison, Mbwana, Juma, Morgan, Lindsey, Singhal, Nilika, Storey, Margaret, Yozawitz, Elissa, Abend, Nicholas, Fitzgerald, Mark, Fridinger, Sara, Helbig, Ingo, Massey, Shavonne, Prelack, Marisa, and Buchhalter, Jeffrey

Subjects
Common Data Elements, Comparative Effectiveness Research, Electronic Health Records, Epidemiological Monitoring, Epilepsy, Health Services Research, Humans, Implementation Science, Neurology, Outcome and Process Assessment, Health Care, Pediatrics, Quality Improvement
Abstract

OBJECTIVE: Common data elements (CDEs) are standardized questions and answer choices that allow aggregation, analysis, and comparison of observations from multiple sources. Clinical CDEs are foundational for learning health care systems, a data-driven approach to health care focused on continuous improvement of outcomes. We aimed to create clinical CDEs for pediatric epilepsy. METHODS: A multiple stakeholder group (clinicians, researchers, parents, caregivers, advocates, and electronic health record [EHR] vendors) developed clinical CDEs for routine care of children with epilepsy. Initial drafts drew from clinical epilepsy note templates, CDEs created for clinical research, items in existing registries, consensus documents and guidelines, quality metrics, and outcomes needed for demonstration projects. The CDEs were refined through discussion and field testing. We describe the development process, rationale for CDE selection, findings from piloting, and the CDEs themselves. We also describe early implementation, including experience with EHR systems and compatibility with the International League Against Epilepsy classification of seizure types. RESULTS: Common data elements were drafted in August 2017 and finalized in January 2020. Prioritized outcomes included seizure control, seizure freedom, American Academy of Neurology quality measures, presence of common comorbidities, and quality of life. The CDEs were piloted at 224 visits at 10 centers. The final CDEs included 36 questions in nine sections (number of questions): diagnosis (1), seizure frequency (9), quality of life (2), epilepsy history (6), etiology (8), comorbidities (2), treatment (2), process measures (5), and longitudinal history notes (1). Seizures are categorized as generalized tonic-clonic (regardless of onset), motor, nonmotor, and epileptic spasms. Focality is collected as epilepsy type rather than seizure type. Seizure frequency is measured in nine levels (all used during piloting). The CDEs were implemented in three vendor systems. Early clinical adoption included 1294 encounters at one center. SIGNIFICANCE: We created, piloted, refined, finalized, and implemented a novel set of clinical CDEs for pediatric epilepsy.

Published
2021

9. Time to Treatment in Pediatric Convulsive Refractory Status Epilepticus: The Weekend Effect

Author

Barcia Aguilar, Cristina, Amengual-Gual, Marta, Sánchez Fernández, Iván, Abend, Nicholas S., Anderson, Anne, Appavu, Brian, Arya, Ravindra, Brenton, J. Nicholas, Carpenter, Jessica L., Chapman, Kevin E., Clark, Justice, Farias-Moeller, Raquel, Gaillard, William D., Gaínza-Lein, Marina, Glauser, Tracy, Goldstein, Joshua L., Goodkin, Howard P., Guerriero, Rejean M., Huh, Linda, Lai, Yi-Chen, McDonough, Tiffani L., Mikati, Mohamad A., Morgan, Lyndsey A., Novotny, Edward J., Ostendorf, Adam, Payne, Eric T., Peariso, Katrina, Piantino, Juan, Riviello, James, Sannagowdara, Kumar, Sheehan, Theodore, Sands, Tristan T., Tasker, Robert C., Tchapyjnikov, Dmitry, Topjian, Alexis A., Vasquez, Alejandra, Wainwright, Mark S., Wilfong, Angus A., Williams, Korwyn, and Loddenkemper, Tobias

Published
2021
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11. The significance of multimodality approach in the management of non‐lesional drug‐resistant focal parietal lobe epilepsies.

Author

Hartnett, Patrick, Zomorodi, Naseem, Goodkin, Howard P., and Zawar, Ifrah

Subjects
PARIETAL lobe, EPILEPTIFORM discharges, EPILEPSY surgery, PEOPLE with epilepsy, DIAGNOSIS methods
Abstract

Due to extensive connectivity of the parietal lobe, non‐lesional drug‐resistant (DRE) parietal lobe epilepsies (PLEs) are difficult to localize and often imitate other epilepsies. Therefore, patients with PLEs have low rates of seizure freedom following epilepsy surgery. Previous studies have highlighted the need to combine EEG and semiology for more accurate localization of PLEs. As sophisticated tools for localization become more available, the use of multiple different neuroimaging and neurophysiologic diagnostic tests may more readily identify PLE. We hereby report a unique case of a complex localization in a non‐lesional PLE, which was initially falsely localized to frontal lobe. This case underscores the utility of voxel‐based morphometry (VBM) in identifying an epileptogenic lesion on a non‐lesional MRI and the significance of multimodality approach including PET, magnetoencephalopathy (MEG), interictal and ictal EEG, semiology and cortical stimulation for accurate localization of PLEs. Understanding epilepsy through multimodality approach in this fashion can help with accurate localization especially in difficulty to localize and deceptive non‐lesional PLEs. Plain Language Summary: Parietal lobe epilepsies are hard to pinpoint in the brain and can mimic other types of epilepsy, especially when brain MRIs appear normal. As sophisticated tools for locating epilepsies in the brain become more available, using multiple diagnostic tests may help identify parietal lobe epilepsies more easily. We describe a unique case of a parietal lobe epilepsy patient with normal brain MRI whose epilepsy was initially misidentified as being in the frontal lobe. Using various advanced diagnostic tests, we accurately found the epilepsy's true location in the parietal lobe and successfully treated the patient with surgery. [ABSTRACT FROM AUTHOR]

Published
2024
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13. The onset of pediatric refractory status epilepticus is not distributed uniformly during the day

Author

Sánchez Fernández, Iván, Gaínza-Lein, Marina, Abend, Nicholas S., Amengual-Gual, Marta, Anderson, Anne, Arya, Ravindra, Brenton, J. Nicholas, Carpenter, Jessica L., Chapman, Kevin E., Clark, Justice, Farias-Moeller, Raquel, Davis Gaillard, William, Glauser, Tracy A., Goldstein, Joshua, Goodkin, Howard P., Guerriero, Réjean M., Hecox, Kurt, Jackson, Michele, Kapur, Kush, Kelley, Sarah A., Kossoff, Eric H.W., Lai, Yi-Chen, McDonough, Tiffani L., Mikati, Mohamad A., Morgan, Lindsey A., Novotny, Edward J., Ostendorf, Adam P., Payne, Eric T., Peariso, Katrina, Piantino, Juan, Riviello, James J., Jr., Sannagowdara, Kumar, Stafstrom, Carl E., Tasker, Robert C., Tchapyjnikov, Dmitry, Topjian, Alexis A., Vasquez, Alejandra, Wainwright, Mark S., Wilfong, Angus, Williams, Korwyn, and Loddenkemper, Tobias

Published
2019
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15. Super-Refractory Status Epilepticus in Children: A Retrospective Cohort Study

Author

Vasquez, Alejandra, Farias-Moeller, Raquel, Sánchez-Fernández, Iván, Abend, Nicholas S., Amengual-Gual, Marta, Anderson, Anne, Arya, Ravindra, Brenton, James N., Carpenter, Jessica L., Chapman, Kevin, Clark, Justice, Gaillard, William D., Glauser, Tracy, Goldstein, Joshua L., Goodkin, Howard P., Guerriero, Rejean M., Lai, Yi-Chen, McDonough, Tiffani L., Mikati, Mohamad A., Morgan, Lindsey A., Novotny, Edward J., Ostendorf, Adam P., Payne, Eric T., Peariso, Katrina, Piantino, Juan, Riviello, James J., Sands, Tristan T., Sannagowdara, Kumar, Tasker, Robert C., Tchapyjnikov, Dmitry, Topjian, Alexis, Wainwright, Mark S., Wilfong, Angus, Williams, Korwyn, and Loddenkemper, Tobias

Published
2021
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17. Hospital Emergency Treatment of Convulsive Status Epilepticus: Comparison of Pathways From Ten Pediatric Research Centers

Author

Vasquez, Alejandra, Gaínza-Lein, Marina, Sánchez Fernández, Iván, Abend, Nicholas S., Anderson, Anne, Brenton, J Nicholas, Carpenter, Jessica L., Chapman, Kevin, Clark, Justice, Gaillard, William D., Glauser, Tracy, Goldstein, Joshua, Goodkin, Howard P., Lai, Yi-Chen, Loddenkemper, Tobias, McDonough, Tiffani L., Mikati, Mohamad A., Nayak, Anuranjita, Payne, Eric, Riviello, James, Tchapyjnikov, Dmitry, Topjian, Alexis A., Wainwright, Mark S., and Tasker, Robert C.

Published
2018
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19. Loss of CLOCK Results in Dysfunction of Brain Circuits Underlying Focal Epilepsy

Author

Li, Peijun, Fu, Xiaoqin, Smith, Nathan A., Ziobro, Julie, Curiel, Julian, Tenga, Milagros J., Martin, Brandon, Freedman, Samuel, Cea-Del Rio, Christian A., Oboti, Livio, Tsuchida, Tammy N., Oluigbo, Chima, Yaun, Amanda, Magge, Suresh N., O’Neill, Brent, Kao, Amy, Zelleke, Tesfaye G., Depositario-Cabacar, Dewi T., Ghimbovschi, Svetlana, Knoblach, Susan, Ho, Chen-Ying, Corbin, Joshua G., Goodkin, Howard P., Vicini, Stefano, Huntsman, Molly M., Gaillard, William D., Valdez, Gregorio, and Liu, Judy S.

Published
2017
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20. First-line medication dosing in pediatric refractory status epilepticus

Author

Vasquez, Alejandra, Gaínza-Lein, Marina, Abend, Nicholas S., Amengual-Gual, Marta, Anderson, Anne, Arya, Ravindra, Brenton, J. Nicholas, Carpenter, Jessica L., Chapman, Kevin, Clark, Justice, Farias-Moeller, Raquel, Gaillard, William D., Glauser, Tracy, Goldstein, Joshua L., Goodkin, Howard P., Guerriero, Rejean M., Kapur, Kush, Lai, Yi-Chen, McDonough, Tiffani L., Mikati, Mohamad A., Morgan, Lindsey A., Novotny, Edward J., Ostendorf, Adam P., Payne, Eric T., Peariso, Katrina, Piantino, Juan, Riviello, James J., Sannagowdara, Kumar, Tasker, Robert C., Tchapyjnikov, Dmitry, Topjian, Alexis, Wainwright, Mark S., Wilfong, Angus, Williams, Korwyn, Loddenkemper, Tobias, Bansal, Seema, Kelley, Sarah, Stafstrom, Carl, Kossoff, Eric, Habela, Christa, Lewis, Dalila, Stanfield, Tony, Sculier, Claudine, Aguilar, Cristina Barcia, Sansevere, Arnold, Sacco, Melissa, Duncan, Abby, McCoy, Jordan, DaSilva-Chiodo, Kathryn, Faist, Robert, Santel, Daniel, LaFay, Victor, Clark, Peggy, Borror, Sarah, Debs, Andrea, Clohessy, Caitlin, Weber, Amanda, Yuliati, Asri, Luat, Aimee, Singh, Azara, Helseth, Ashley, Turner, David, Fernandes, Cecilia, Tran, Linh, McLean, Melissa, Nayak, Anuranjita, Riviello, James J, Jr, Hecox, Kurt, Nallamothu, Rupa, Rehborg, Rebecca, Goldstein, David, Heinzen Cox, Erin, Malone, Colin, Thornburg, Olivia, Grinspan, Zachary, Basma, Natasha, Appavu, Brian, Burrows, Brian, Dyar, Beata, Mishler, Laura, Lee-Eng, Jacqueline, Streb, Madison, Hahn, Cecil, Lalgudi Ganesan, Saptharishi (Rishi), Huh, Linda, and Martic, Nela

Published
2020
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22. Humanized mouse model of Rasmussen's encephalitis supports the immune-mediated hypothesis

Author

Kebir, Hania, Carman, Lionel, Fontaine, Francois, Beland, Kathie, Bosoi, Ciprian M., Sanon, Nathalie T., Alvarez, Jorge I., Desgen, Sebastien, Pittet, Camille L., Heber, David, Langlois, Marie- Josee, Rebillard, Rose-Marie, Nguyen, Dang K., Cieuta-Walti, Cecile, Holmes, Gregory L., Goodkin, Howard P., Mytinger, John R., Connolly, Mary B., Pra, Alexandre, and Haddad, Elie

Subjects
Hemispherectomy -- Usage, Encephalitis -- Risk factors -- Genetic aspects -- Care and treatment, Health care industry
Abstract

Rasmussen's encephalitis (RE) is a chronic inflammatory brain disorder that causes frequent seizures and unilateral hemispheric atrophy with progressive neurological deficits. Hemispherectomy remains the only treatment that leads to seizure freedom for this refractory epileptic syndrome. The absence of an animal model of disease has been a major obstacle hampering the development of effective therapies. Here, we describe an experimental mouse model that shares several clinical and pathological features with the human disease. Immunodeficient mice injected with peripheral blood mononuclear cells from RE patients and monitored by video electroencephalography developed severe seizures of cortical origin and showed intense astrogliosis and accumulation of human IFN-[gamma]- and granzyme B-expressing T lymphocytes in the brain compared with mice injected with immune cells from control subjects. We also provide evidence for the efficacy of [alpha]4 integrin blockade, an approved therapy for the treatment of multiple sclerosis and Crohn's disease, in reducing inflammatory markers associated with RE in the CNS. This model holds promise as a valuable tool for understanding the pathology of RE and for developing patient-tailored experimental therapeutics., Introduction Rasmussen's encephalitis (RE) is a severe brain disorder that usually manifests itself during childhood with the onset of frequent focal seizures (1). These seizures often progress to epilepsia partialis [...]

Published
2018
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26. Electroencephalographic Reporting for Refractory Status Epilepticus

Author

Sansevere, Arnold J., Arya, Ravindra, Sánchez Fernández, Iván, Gaillard, William D., Tasker, Robert C., Lai, Yi-Chen, Anderson, Anne E., Tchapyjnikov, Dmitry, Chapman, Kevin E., Brenton, J. Nicholas, Carpenter, Jessica L., Gaínza-Lein, Marina, Goldstein, Joshua L., Goodkin, Howard P., Jackson, Michele C., Kapur, Kush, Mikati, Mohamad A., Peariso, Katrina, Glauser, Tracy A., Topjian, Alexis A., Wainwright, Mark, Wilfong, Angus A., Williams, Korwyn L., Loddenkemper, Tobias, and Abend, Nicholas S.

Published
2019
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28. Pediatric status epilepticus management by Emergency Medical Services (the pSERG cohort)

Author

Amengual-Gual, Marta, Sánchez Fernández, Iván, Vasquez, Alejandra, Abend, Nicholas S., Anderson, Anne, Arya, Ravindra, Barcia Aguilar, Cristina, Brenton, J. Nicholas, Carpenter, Jessica L., Chapman, Kevin E., Clark, Justice, Farias-Moeller, Raquel, Gaillard, William D., Glauser, Tracy A., Goldstein, Joshua L., Goodkin, Howard P., Lai, Yi-Chen, Mikati, Mohamad A., Morgan, Lindsey A., Novotny, Edward J., Ostendorf, Adam P., Payne, Eric T., Peariso, Katrina, Piantino, Juan, Reece, Latania, Riviello, James J., Sannagowdara, Kumar, Sheehan, Theodore, Tasker, Robert C., Tchapyjnikov, Dmitry, Topjian, Alexis A., Wainwright, Mark S., Wilfong, Angus, Williams, Korwyn, and Loddenkemper, Tobias

Published
2023
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29. Gaps and opportunities in refractory status epilepticus research in children: A multi-center approach by the Pediatric Status Epilepticus Research Group (pSERG)

Author

Sánchez Fernández, Iván, Abend, Nicholas S., Agadi, Satish, An, Sookee, Arya, Ravindra, Carpenter, Jessica L., Chapman, Kevin E., Gaillard, William D., Glauser, Tracy A., Goldstein, David B., Goldstein, Joshua L., Goodkin, Howard P., Hahn, Cecil D., Heinzen, Erin L., Mikati, Mohamad A., Peariso, Katrina, Pestian, John P., Ream, Margie, Riviello, James J., Jr., Tasker, Robert C., Williams, Korwyn, and Loddenkemper, Tobias

Published
2014
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34. Refractory status epilepticus in children with and without prior epilepsy or status epilepticus

Author

Sánchez Fernández, Iván, Jackson, Michele C., Abend, Nicholas S., Arya, Ravindra, Brenton, James N., Carpenter, Jessica L., Chapman, Kevin E., Gaillard, William D., Gaínza-Lein, Marina, Glauser, Tracy A., Goldstein, Joshua L., Goodkin, Howard P., Helseth, Ashley, Kapur, Kush, McDonough, Tiffani L., Mikati, Mohamad A., Peariso, Katrina, Riviello, James, Jr, Tasker, Robert C., Topjian, Alexis A., Wainwright, Mark S., Wilfong, Angus, Williams, Korwyn, and Loddenkemper, Tobias

Published
2017
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36. Preclinical pharmacokinetics and tolerability of a novel meglumine‐based parenteral solution of topiramate and topiramate combinations for treatment of status epilepticus.

Author

Rundfeldt, Chris, Klein, Pavel, Boison, Detlev, Rotenberg, Alexander, D'Ambrosio, Raimondo, Eastman, Cliff, Purnell, Benton, Murugan, Madhuvika, Goodkin, Howard P., and Löscher, Wolfgang

Subjects
PARENTERAL solutions, STATUS epilepticus, TOPIRAMATE, PHARMACOKINETICS, NASOENTERAL tubes
Abstract

Objective: For an antiseizure medication (ASM) to be effective in status epilepticus (SE), the drug should be administered intravenously (i.v.) to provide quick access to the brain. However, poor aqueous solubility is a major problem in the development of parenteral drug solutions. Given its multiple mechanisms of action, topiramate (TPM) is a promising candidate for the treatment of established or refractory SE, as supported by clinical studies using nasogastric tube TPM administration. However, TPM is not clinically available as a solution for i.v. administration, which hampers its use in the treatment of SE. Here, we describe a novel easy‐to‐use and easy‐to‐prepare i.v. TPM formulation using the U.S. Food and Drug Administration (FDA)–approved excipient meglumine. Methods: During formulation development, we compared the solubility of TPM in bi‐distilled water with vs without a range of meglumine concentrations. Furthermore, the solubility of combinations of TPM and levetiracetam and TPM, levetiracetam, and atorvastatin in aqueous meglumine concentrations was determined. Subsequently, the pharmacokinetics and tolerability of meglumine‐based solutions of TPM and TPM combinations were evaluated in rats, including animals following fluid percussion injury or pilocarpine‐induced SE. Results: The amino sugar meglumine markedly enhances the aqueous solubility of TPM. A comparison with data on dissolving TPM using sulfobutylether‐β‐cyclodextrin (Captisol) demonstrates that meglumine is much more effective for dissolving TPM. Furthermore, meglumine can be used to prepare drug cocktails where TPM is co‐administered with another ASM for SE treatment. The tolerability studies of the meglumine‐based TPM solution and meglumine‐based TPM combinations in normal rats and the rat fluid percussion injury and pilocarpine‐induced SE models demonstrate excellent tolerability of the novel drug solutions. Preclinical studies on antiseizure efficacy in the SE model are underway. Significance: In conclusion, the novel meglumine‐based solution of TPM presented here may be well suited for clinical development. [ABSTRACT FROM AUTHOR]

Published
2023
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45. Altered closed state inactivation gating in Kv4.2 channels results in developmental and epileptic encephalopathies in human patients.

Author

Bavan, Selvan, Goodkin, Howard P., and Papazian, Diane M.

Abstract

Kv4.2 subunits, encoded by KCND2, serve as the pore‐forming components of voltage‐gated, inactivating ISA K+ channels expressed in the brain. ISA channels inactivate without opening in response to subthreshold excitatory input, temporarily increasing neuronal excitability, the back propagation of action potentials, and Ca2+ influx into dendrites, thereby regulating mechanisms of spike timing‐dependent synaptic plasticity. As previously described, a de novo variant in Kv4.2, p.Val404Met, is associated with an infant‐onset developmental and epileptic encephalopathy in monozygotic twin boys. The p.Val404Met variant enhances inactivation directly from closed states, but dramatically impairs inactivation after channel opening. We now report the identification of a closely related, novel, de novo variant in Kv4.2, p.Val402Leu, in a boy with an early‐onset pharmacoresistant epilepsy that evolved to an epileptic aphasia syndrome (Continuous Spike Wave during Sleep Syndrome). Like p.Val404Met, the p.Val402Leu variant increases the rate of inactivation from closed states, but significantly slows inactivation after the pore opens. Although quantitatively the p.Val402Leu mutation alters channel kinetics less dramatically than p.Val404Met, our results strongly support the conclusion that p.Val402Leu and p.Val404Met cause the clinical features seen in the affected individuals and underscore the importance of closed state inactivation in ISA channels in normal brain development and function. [ABSTRACT FROM AUTHOR]

Published
2022
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47. Intracerebral abscess in children: historical trends at Children's Hospital Boston

Author

Goodkin, Howard P., Harper, Marvin B., and Pomeroy, Scott L.

Subjects
Brain -- Abscess, Brain -- Research, Children -- Health aspects
Abstract

Objectives. A previous study performed at Children's Hospital Boston describing the natural history of intracerebral abscess between 1945 and 1980 demonstrated a decline in mortality after 1970. This current study examines the occurrence of intracerebral abscess at Children's Hospital Boston between 1981 and 2000, inclusive, and compares the results with the previous study. Our objectives were to determine whether there had been a change in the predisposing factors, whether there were changes in the microbiology of intracerebral abscesses, and whether mortality rate had continued to decline. Methods. To ensure that all occurrences of intracerebral abscess treated at Children's Hospital Boston between 1981 and 2000 were identified, we searched 4 separately maintained databases for the keywords "brain" or "abscess" or the International Classification of Diseases, Ninth Revision code 324.x. This search yielded the names of 386 patients. Of these 386 patients, a solitary intracerebral abscess or multiple noncontiguous intracerebral abscesses could be confirmed in 54 patients on the basis of cranial imaging (computed tomography or magnetic resonance imaging) or autopsy reports. The complete retrospective review of the medical records of these 54 patients constitutes the basis for this study. Results. Congenital heart disease was the most common predisposing factor during both eras. Compared with the previous era, important historical trends identified include a reduction in the number of abscesses that occurred in the settings of sinus or otitic infection (11% during 1981-2000 vs 26% during 1945-1980), an increase in number of intracranial abscesses in infants (18% vs 7%) and in the setting of immunosuppression (16% vs 1%), an increase in the number of children who were treated with antibiotics alone (22% vs 1%), a stable over-all mortality rate (24% vs 27%), and the identification of Citrobacter and fungus as causes of intracranial abscess not observed during the previous era of 1945-1980. Citrobacter was observed only during the neonatal period. Fungi were the causative organisms predominantly in the setting of immunosuppression. Conclusions. Intracerebral abscess in children continues to be associated with high rates of neurologic impairment and death. Because earlier detection may reduce morbidity and mortality, intracranial abscess should be considered when evaluating children with new-onset neurologic signs or symptoms, especially in children who have acute immunosuppression and disseminated fungal disease or fungemia, abscess, brain, children., ABBREVIATIONS. VP, ventriculoperitoneal; CT, computed tomography; MRI, magnetic resonance imaging; CI, confidence interval. Intracerebral abscesses result from the invasion of infectious organisms into the parenchyma of the brain as a [...]

Published
2004

48. Intravenous ketamine for the treatment of refractory status epilepticus: A retrospective multicenter study

Author

Gaspard, Nicolas, Foreman, Brandon, Judd, Lilith M., Brenton, James N., Nathan, Barnett R., McCoy, Blathnaid M., Al-Otaibi, Ali, Kilbride, Ronan, Fernández, Ivan Sánchez, Mendoza, Lucy, Samuel, Sophie, Zakaria, Asma, Kalamangalam, Giridhar P., Legros, Benjamin, Szaflarski, Jerzy P., Loddenkemper, Tobias, Hahn, Cecil D., Goodkin, Howard P., Claassen, Jan, Hirsch, Lawrence J., and LaRoche, Suzette M.

Published
2013
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