{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:49:34Z","timestamp":1787014174273,"version":"build-2736575974"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2016,9,12]],"date-time":"2016-09-12T00:00:00Z","timestamp":1473638400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100001454","name":"American Epilepsy Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001454","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007775","name":"Universidade Cat\u00f3lica de Bras\u00edlia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007775","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001720","name":"Nutricia Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001720","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003769","name":"Eisai","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Infantile spasms (\n                      <jats:styled-content style=\"fixed-case\">IS<\/jats:styled-content>\n                      ) represent a severe epileptic encephalopathy presenting in the first 2 years of life. Recommended first\u2010line therapies (hormonal therapy or vigabatrin) often fail. We evaluated response to second treatment for\n                      <jats:styled-content style=\"fixed-case\">IS<\/jats:styled-content>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      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 [\n                      <jats:styled-content style=\"fixed-case\">ACTH<\/jats:styled-content>\n                      ] or oral corticosteroids), vigabatrin, or \u201cother.\u201d Standard treatments (hormonal and vigabatrin) were compared to all other nonstandard treatments. We compared response rates using chi\u2010square tests and multivariable logistic regression models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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 &lt; 0.001). Children receiving first treatment within 4 weeks of\n                      <jats:styled-content style=\"fixed-case\">IS<\/jats:styled-content>\n                      onset had a higher response rate to second treatment than those initially treated later (36\/82 [44%] vs. 8\/34 [24%], p = 0.040).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      Greater than one third of children with\n                      <jats:styled-content style=\"fixed-case\">IS<\/jats:styled-content>\n                      will respond to a second medication. Choosing a standard medication (\n                      <jats:styled-content style=\"fixed-case\">ACTH<\/jats:styled-content>\n                      , 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.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.13557","type":"journal-article","created":{"date-parts":[[2016,9,12]],"date-time":"2016-09-12T02:49:55Z","timestamp":1473648595000},"page":"1834-1842","source":"Crossref","is-referenced-by-count":80,"title":["Response to second treatment after initial failed treatment in a multicenter prospective infantile spasms cohort"],"prefix":"10.1111","volume":"57","author":[{"given":"Kelly G.","family":"Knupp","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Neurology School of Medicine University of Colorado Anschutz Medical Campus Aurora Colorado U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Leister","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Informatics Colorado School of Public Health University of Colorado Anschutz Medical Campus Aurora Colorado U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Coryell","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Neurology School of Medicine Oregon Health &amp; Sciences University Portland Oregon U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine C.","family":"Nickels","sequence":"additional","affiliation":[{"name":"Departments of Neurology and Pediatrics Mayo Clinic Rochester Minnesota U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Ryan","sequence":"additional","affiliation":[{"name":"Division of Neurology The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Juarez\u2010Colunga","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Informatics Colorado School of Public Health University of Colorado Anschutz Medical Campus Aurora Colorado U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D.","family":"Gaillard","sequence":"additional","affiliation":[{"name":"Center For Neuroscience Children's National Health System Washington District of Columbia U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Mytinger","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology Department of Pediatrics Nationwide Children's Hospital The Ohio State University Columbus Ohio U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne T.","family":"Berg","sequence":"additional","affiliation":[{"name":"Ann &amp; Robert H. Lurie Children's Hospital of Chicago Chicago Illinois U.S.A"},{"name":"Departments of Pediatrics and Neurology Northwestern University Feinberg School of Medicine Chicago Illinois U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0798-0131","authenticated-orcid":false,"given":"John","family":"Millichap","sequence":"additional","affiliation":[{"name":"Ann &amp; Robert H. Lurie Children's Hospital of Chicago Chicago Illinois U.S.A"},{"name":"Departments of Pediatrics and Neurology Northwestern University Feinberg School of Medicine Chicago Illinois U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Douglas R.","family":"Nordli","sequence":"additional","affiliation":[{"name":"Ann &amp; Robert H. Lurie Children's Hospital of Chicago Chicago Illinois U.S.A"},{"name":"Departments of Pediatrics and Neurology Northwestern University Feinberg School of Medicine Chicago Illinois U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sucheta","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics &amp; Communicable Diseases (Division of Pediatric Neurology) University of Michigan Ann Arbor Michigan U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9e A.","family":"Shellhaas","sequence":"additional","affiliation":[{"name":"Department of Pediatrics &amp; Communicable Diseases (Division of Pediatric Neurology) University of Michigan Ann Arbor Michigan U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Loddenkemper","sequence":"additional","affiliation":[{"name":"Division of Epilepsy and Clinical Neurophysiology Department of Neurology Boston Children's Hospital Boston Massachusetts U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Dlugos","sequence":"additional","affiliation":[{"name":"Division of Neurology The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Wirrell","sequence":"additional","affiliation":[{"name":"Departments of Neurology and Pediatrics Mayo Clinic Rochester Minnesota U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Neurology University of California San Francisco San Francisco California U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam L.","family":"Hartman","sequence":"additional","affiliation":[{"name":"Departments of Neurology and Pediatrics Johns Hopkins Hospital Baltimore Maryland U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric H.","family":"Kossoff","sequence":"additional","affiliation":[{"name":"Departments of Neurology and Pediatrics Johns Hopkins Hospital Baltimore Maryland U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary M.","family":"Grinspan","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Healthcare Policy &amp; Research Weill Cornell Medical Center New York New York U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorie","family":"Hamikawa","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Washington Seattle Washington U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Pediatric Epilepsy Research Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,9,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.1979.tb01625.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307389100600412"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1994.tb02514.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1995.tb02569.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2011.03127.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2010.01.008"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2013.06.014"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2014.11.012"},{"key":"e_1_2_8_10_1","first-page":"130","article-title":"Findings in 21 cases of Gibbs\u2019 hypsarrhythmia; spectacular effectiveness of ACTH","volume":"58","author":"Sorel L","year":"1958","journal-title":"Acta Neurol Psychiatr Belg"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.22.6.1165"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24594"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17400-X"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1997.tb00063.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1999.tb02049.x"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000127773.72699.C8"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318259e2cf"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073812455692"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307380502000101"},{"key":"e_1_2_8_20_1","first-page":"143","article-title":"Ineffectiveness of topiramate and levetiracetam in infantile spasms non\u2010responsive to steroids. 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