Kelly G Knupp1, Erin Leister2, Jason Coryell3, Katherine C Nickels4, Nicole Ryan5, Elizabeth Juarez-Colunga2, William D Gaillard6, John R Mytinger7, Anne T Berg8,9, John Millichap8,9, Douglas R Nordli8,9, Sucheta Joshi10, Renée A Shellhaas10, Tobias Loddenkemper11, Dennis Dlugos5, Elaine Wirrell4, Joseph Sullivan12, Adam L Hartman13, Eric H Kossoff13, Zachary M Grinspan14, Lorie Hamikawa15. 1. Department of Pediatrics and Neurology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, U.S.A. 2. Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, U.S.A. 3. Departments of Pediatrics and Neurology, School of Medicine, Oregon Health & Sciences University, Portland, Oregon, U.S.A. 4. Departments of Neurology and Pediatrics, Mayo Clinic, Rochester, Minnesota, U.S.A. 5. Division of Neurology, The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A. 6. Center For Neuroscience, Children's National Health System, Washington, District of Columbia, U.S.A. 7. Division of Pediatric Neurology, Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, U.S.A. 8. Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, U.S.A. 9. Departments of Pediatrics and Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, U.S.A. 10. Department of Pediatrics & Communicable Diseases (Division of Pediatric Neurology), University of Michigan, Ann Arbor, Michigan, U.S.A. 11. Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Boston, Massachusetts, U.S.A. 12. Departments of Pediatrics and Neurology, University of California San Francisco, San Francisco, California, U.S.A. 13. Departments of Neurology and Pediatrics, Johns Hopkins Hospital, Baltimore, Maryland, U.S.A. 14. Departments of Pediatrics and Healthcare Policy & Research, Weill Cornell Medical Center, New York, New York, U.S.A. 15. Department of Neurology, University of Washington, Seattle, Washington, U.S.A.
Abstract
OBJECTIVE: Infantile spasms (IS) represent a severe epileptic encephalopathy presenting in the first 2 years of life. Recommended first-line therapies (hormonal therapy or vigabatrin) often fail. We evaluated response to second treatment for IS in children in whom the initial therapy failed to produce both clinical remission and electrographic resolution of hypsarhythmia and whether time to treatment was related to outcome. METHODS: The National Infantile Spasms Consortium established a multicenter, prospective database enrolling infants with new diagnosis of IS. Children were considered nonresponders to first treatment if there was no clinical remission or persistence of hypsarhythmia. Treatment was evaluated as hormonal therapy (adrenocorticotropic hormone [ACTH] or oral corticosteroids), vigabatrin, or "other." Standard treatments (hormonal and vigabatrin) were compared to all other nonstandard treatments. We compared response rates using chi-square tests and multivariable logistic regression models. RESULTS: One hundred eighteen infants were included from 19 centers. Overall response rate to a second treatment was 37% (n = 44). Children who received standard medications with differing mechanisms for first and second treatment had higher response rates than other sequences (27/49 [55%] vs. 17/69 [25%], p < 0.001). Children receiving first treatment within 4 weeks of IS onset had a higher response rate to second treatment than those initially treated later (36/82 [44%] vs. 8/34 [24%], p = 0.040). SIGNIFICANCE: Greater than one third of children with IS will respond to a second medication. Choosing a standard medication (ACTH, oral corticosteroids, or vigabatrin) that has a different mechanism of action appears to be more effective. Rapid initial treatment increases the likelihood of response to the second treatment. Wiley Periodicals, Inc.
OBJECTIVE:Infantile spasms (IS) represent a severe epilepticencephalopathy presenting in the first 2 years of life. Recommended first-line therapies (hormonal therapy or vigabatrin) often fail. We evaluated response to second treatment for IS in children in whom the initial therapy failed to produce both clinical remission and electrographic resolution of hypsarhythmia and whether time to treatment was related to outcome. METHODS: The National Infantile Spasms Consortium established a multicenter, prospective database enrolling infants with new diagnosis of IS. Children were considered nonresponders to first treatment if there was no clinical remission or persistence of hypsarhythmia. Treatment was evaluated as hormonal therapy (adrenocorticotropic hormone [ACTH] or oral corticosteroids), vigabatrin, or "other." Standard treatments (hormonal and vigabatrin) were compared to all other nonstandard treatments. We compared response rates using chi-square tests and multivariable logistic regression models. RESULTS: One hundred eighteen infants were included from 19 centers. Overall response rate to a second treatment was 37% (n = 44). Children who received standard medications with differing mechanisms for first and second treatment had higher response rates than other sequences (27/49 [55%] vs. 17/69 [25%], p < 0.001). Children receiving first treatment within 4 weeks of IS onset had a higher response rate to second treatment than those initially treated later (36/82 [44%] vs. 8/34 [24%], p = 0.040). SIGNIFICANCE: Greater than one third of children with IS will respond to a second medication. Choosing a standard medication (ACTH, oral corticosteroids, or vigabatrin) that has a different mechanism of action appears to be more effective. Rapid initial treatment increases the likelihood of response to the second treatment. Wiley Periodicals, Inc.
Authors: Jo M Wilmshurst; William D Gaillard; Kollencheri Puthenveettil Vinayan; Tammy N Tsuchida; Perrine Plouin; Patrick Van Bogaert; Jaime Carrizosa; Maurizio Elia; Dana Craiu; Nebojsa J Jovic; Doug Nordli; Deborah Hirtz; Virginia Wong; Tracy Glauser; Eli M Mizrahi; J Helen Cross Journal: Epilepsia Date: 2015-06-30 Impact factor: 5.864
Authors: Scott T Demarest; Renée A Shellhaas; William D Gaillard; Cynthia Keator; Katherine C Nickels; Shaun A Hussain; Tobias Loddenkemper; Anup D Patel; Russell P Saneto; Elaine Wirrell; Iván Sánchez Fernández; Catherine J Chu; Zachary Grinspan; Courtney J Wusthoff; Sucheta Joshi; Ismail S Mohamed; Carl E Stafstrom; Cynthia V Stack; Elissa Yozawitz; Judith S Bluvstein; Rani K Singh; Kelly G Knupp Journal: Epilepsia Date: 2017-11-03 Impact factor: 5.864