{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T16:23:08Z","timestamp":1776270188135,"version":"3.50.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Inflammation may contribute to drug-resistant epilepsy (DRE) in children and immunomodulatory therapies, including intravenous immunoglobulin (IVIG), have been described to reduce seizure burden. This retrospective study assesses the effect of IVIG on seizures in a tertiary epilepsy center.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a retrospective chart review of children with DRE using our Pediatric Epilepsy Outcome-Informatics database, which contains standardized information on 3,650 pediatric epilepsy patients collected at the point of care. Inclusion criteria were refractory seizures, regular follow-up and treatment with IVIG for at least 1\u202fyear. Patients with autoimmune encephalitis were excluded from the analysis. Sex, etiology, epilepsy syndromes, seizure types, antiseizure medications (ASM), adverse effects, and seizure frequency scores prior, 3\u202fmonths post-, and 1-year post-IVIG were collected and statistically compared.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Sixty patients aged 2\u201318\u202fyears (mean \u00b1 SD, 11.8\u202f\u00b1\u202f4.13) were included. Patients exhibited focal (38.3%,\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f23), generalized (36.7% (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f22), or both seizure types (25.0%,\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f15). Overall, 36.7% (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f22) demonstrated at least 50% seizure frequency reduction within 1 year of IVIG use, and 36.4% (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f8) achieved seizure freedom. A significant reduction of seizures in individual patients was only observed in those with generalized seizures (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.019). These findings could not be explained by changes in other ASMs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Long-term use of IVIG in pediatric patients can be an effective treatment for refractory seizures, even if exact mechanisms remain unclear.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1796553","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T15:20:26Z","timestamp":1776266426000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy of intravenous immunoglobulin in children with drug-resistant epilepsy"],"prefix":"10.3389","volume":"17","author":[{"given":"Aya","family":"Ebdalla","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Clinical Neurosciences, University of Calgary","place":["Calgary, AB, Canada"]},{"name":"Alberta Children\u2019s Hospital Research Institute","place":["Calgary, AB, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morris H.","family":"Scantlebury","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Clinical Neurosciences, University of Calgary","place":["Calgary, AB, Canada"]},{"name":"Alberta Children\u2019s Hospital Research Institute","place":["Calgary, AB, Canada"]},{"name":"Hotchkiss Brain Institute","place":["Calgary, AB, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan P.","family":"Appendino","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Department of Pediatrics, University of Saskatchewan","place":["Saskatoon, SK, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Clinical Neurosciences, University of Calgary","place":["Calgary, AB, Canada"]},{"name":"Alberta Children\u2019s Hospital Research Institute","place":["Calgary, AB, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Clinical Neurosciences, University of Calgary","place":["Calgary, AB, Canada"]},{"name":"Alberta Children\u2019s Hospital Research Institute","place":["Calgary, AB, Canada"]},{"name":"Hotchkiss Brain Institute","place":["Calgary, AB, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1111\/j.1528-1167.2011.03033.x","article-title":"Inflammation in epilepsy: clinical observations","volume":"52","author":"Aronica","year":"2011","journal-title":"Epilepsia"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.ejpn.2004.10.005","article-title":"Epilepsy and the immune system: is there a link?","volume":"9","author":"Billiau","year":"2005","journal-title":"European Journal of PASMiatric Neurology"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/s1734-1140(10)70317-0","article-title":"Immunological aspects of epilepsy","volume":"62","author":"Zarczuk","year":"2010","journal-title":"Pharmacol Rep"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1111\/j.1528-1167.2007.01134.x","article-title":"Intravenous immunoglobulins in refractory childhood-onset epilepsy: effects on seizure frequency, EEG activity, and cerebrospinal fluid cytokine profile","volume":"48","author":"Billiau","year":"2007","journal-title":"Epilepsia"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"e18200","DOI":"10.1371\/journal.pone.0018200","article-title":"Efficacy of anti-inflammatory therapy in a model of acute seizures and in a population of pediatric drug resistant epileptics","volume":"6","author":"Marchi","year":"2011","journal-title":"PLoS One"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.spen.2014.08.001","article-title":"Immunomodulatory treatments in epilepsy","volume":"21","author":"Melvin","year":"2014","journal-title":"Semin Pediatr Neurol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/s0920-1211(00)00140-6","article-title":"Interleukin-6 and interleukin-1 receptor antagonist in cerebrospinal fluid from patients with recent tonic\u2013clonic seizures","volume":"41","author":"Peltola","year":"2000","journal-title":"Epilepsy Res"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/j.bbi.2008.03.009","article-title":"The role of cytokines in the pathophysiology of epilepsy","volume":"22","author":"Vezzani","year":"2008","journal-title":"Brain Behav Immun"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1724","DOI":"10.1111\/j.1528-1167.2005.00298.x","article-title":"Brain inflammation in epilepsy: experimental and clinical evidence","volume":"46","author":"Vezzani","year":"2005","journal-title":"Epilepsia"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e174753","DOI":"10.1172\/jci.insight.174753","article-title":"The immune system and metabolic products in epilepsy and glioma-associated epilepsy: emerging therapeutic directions","volume":"9","author":"Tripathi","year":"2024","journal-title":"JCI Insight"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1517\/17425255.4.10.1245","article-title":"A critical overview of the influence of inflammation and infection on P-glycoprotein expression and activity in the brain","volume":"4","author":"Roberts","year":"2008","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.pedneo.2018.10.006","article-title":"Immunotherapy for anti-NMDA receptor encephalitis: experience from a single center in Taiwan","volume":"60","author":"Kong","year":"2019","journal-title":"Pediatr Neonatol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1176\/appi.neuropsych.11070151","article-title":"A multidisciplinary approach to the treatment of anti-NMDA-receptor antibody encephalitis: a case and review of the literature","volume":"24","author":"Mann","year":"2012","journal-title":"J Neuropsychiatry Clin Neurosci"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1111\/j.1600-0404.1993.tb04217.x","article-title":"Intravenous high-dose gammaglobulins for intractable childhood epilepsy","volume":"88","author":"Gross-Tsur","year":"1993","journal-title":"Acta Neurol Scand"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1007\/bf02592447","article-title":"Treatment of refractory epilepsy with intravenous immunoglobulins","volume":"24","author":"van Rijckevorsel-Harmant","year":"1994","journal-title":"Int J Clin Lab Res"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.yebeh.2009.10.020","article-title":"Intravenous immunoglobulin therapy in intractable childhood epilepsy: open-label study and review of the literature","volume":"17","author":"Mikati","year":"2010","journal-title":"Epilepsy Behav"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.pediatrneurol.2012.03.015","article-title":"Immunoglobulin treatment for severe childhood epilepsy","volume":"46","author":"Geva-Dayan","year":"2012","journal-title":"Pediatr Neurol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/j.pediatrneurol.2014.11.011","article-title":"Efficacy of intravenous immunoglobulin in a cohort of children with drug-resistant epilepsy","volume":"52","author":"Bello-Espinosa","year":"2015","journal-title":"Pediatr Neurol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.pediatrneurol.2017.07.009","article-title":"Intravenous immunoglobulin as a treatment for intractable epilepsy secondary to focal cortical dysplasia: a meta-analysis","volume":"76","author":"Al Amrani","year":"2017","journal-title":"Pediatr Neurol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/j.nrleng.2019.05.009","article-title":"Intravenous immunoglobulin G as adjuvant treatment in drug-resistant childhood epilepsy","volume":"35","author":"Gonz\u00e1lez-Castillo","year":"2020","journal-title":"Neurolog\u00eda (English Edition)"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.seizure.2017.03.004","article-title":"Breaking the cycle: a comparison between intravenous immunoglobulins and high dosage prednisone in the treatment of medically intractable epilepsy in children","volume":"47","author":"Tang-Wai","year":"2017","journal-title":"Seizure"},{"key":"ref22","first-page":"495","article-title":"High-dose intravenous immunoglobulin treatment in intractable childhood epilepsy","volume":"30","author":"Uran","year":"2000","journal-title":"Turk J Med Sci"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1212\/WNL.44.6.1030","article-title":"Medical treatment of Rasmussen's syndrome (chronic encephalitis and epilepsy): effect of high-dose steroids or immunoglobulins in 19 patients","volume":"44","author":"Hart","year":"1994","journal-title":"Neurology"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1212\/WNL.52.4.738","article-title":"Improvement in adult-onset Rasmussen\u2019s encephalitis with long-term immunomodulatory therapy","volume":"52","author":"Leach","year":"1999","journal-title":"Neurology"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"S33","DOI":"10.1046\/j.1528-1157.2002.00034.x","article-title":"The use of immunoglobulins in the treatment of human epilepsy","volume":"23","author":"Villani","year":"2002","journal-title":"Neurol Sci"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1212\/wnl.56.2.248","article-title":"Positive response to immunomodulatory therapy in an adult patient with Rasmussen\u2019s encephalitis","volume":"56","author":"Villani","year":"2001","journal-title":"Neurology"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1111\/epi.12142","article-title":"Autoimmune epilepsy in children: case series and proposed guidelines for identification","volume":"54","author":"Suleiman","year":"","journal-title":"Epilepsia"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1111\/j.1528-1157.1985.tb05194.x","article-title":"Effects of \u03b3-globulin therapy in severely epileptic children","volume":"26","author":"Bedini","year":"1985","journal-title":"Epilepsia"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1111\/j.1528-1167.2009.02397.x","article-title":"Definition of drug resistant epilepsy: consensus proposal by the ad hoc task force of the ILAE commission on therapeutic strategies","volume":"51","author":"Kwan","year":"2010","journal-title":"Epilepsia"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1002\/epi4.12480","article-title":"Creation and implementation of an electronic health record note for quality improvement in pediatric epilepsy: practical considerations and lessons learned","volume":"6","author":"Buchhalter","year":"2021","journal-title":"Epilepsia open"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"e45","DOI":"10.1111\/epi.14038","article-title":"Altered vaccine-induced immunity in children with Dravet syndrome","volume":"59","author":"Auvin","year":"2018","journal-title":"Epilepsia"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1111\/j.1365-3083.1995.tb03555.x","article-title":"A dysbalanced immune system in cryptogenic Lennox-Gastaut syndrome","volume":"41","author":"van Engelen","year":"1995","journal-title":"Scand J Immunol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"30","DOI":"10.3928\/00904481-20150203-09","article-title":"Common pediatric epilepsy syndromes","volume":"44","author":"Park","year":"2015","journal-title":"Pediatr Ann"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/s0387-7604(87)80117-1","article-title":"Immunoglobulin therapy in the west syndrome","volume":"9","author":"Ariizumi","year":"1987","journal-title":"Brain Dev"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1177\/08830738030180061001","article-title":"Intravenous immunoglobulin as adjunctive therapy for juvenile spasms","volume":"18","author":"Bingel","year":"2003","journal-title":"J Child Neurol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1007\/BF01954498","article-title":"High-dose intravenous immunoglobulin treatment in cryptogenic west and Lennox-Gastaut syndrome; an add-on study","volume":"153","author":"van Engelen","year":"1994","journal-title":"Eur J Pediatr"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1111\/dmcn.12748","article-title":"The recognition and treatment of autoimmune epilepsy in children","volume":"57","author":"Suleiman","year":"2015","journal-title":"Dev Med Child Neurol"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"2091","DOI":"10.1111\/epi.12405","article-title":"Autoantibodies to neuronal antigens in children with new-onset seizures classified according to the revised ILAE organization of seizures and epilepsies","volume":"54","author":"Suleiman","year":"","journal-title":"Epilepsia"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"CD008557","DOI":"10.1002\/14651858.CD008557.pub3","article-title":"Intravenous immunoglobulins for epilepsy","volume":"12","author":"Geng","year":"2019","journal-title":"Cochrane Database Syst Rev"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1111\/cei.1996.104.s1.71","article-title":"Intravenous immune globulin in the treatment of intractable childhood epilepsy","volume":"104","author":"Duse","year":"1996","journal-title":"Clin Expl Immunol"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1016\/j.neurol.2015.06.004","article-title":"Predictors factors of refractory epilepsy in childhood","volume":"171","author":"Fray","year":"2015","journal-title":"Rev Neurol"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/j.jpsychores.2006.07.018","article-title":"Clinical predictors of intractable childhood epilepsy","volume":"61","author":"Gururaj","year":"2006","journal-title":"J Psychosom Res"},{"key":"ref43","first-page":"158","article-title":"Predictors of intractable childhood epilepsy","volume":"18","author":"Malik","year":"2008","journal-title":"J Coll Physicians Surg Pak"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/S0887-8994(99)00031-4","article-title":"Epilepsy syndromes in patients with childhood-onset seizures in Finland","volume":"21","author":"Sillanp\u00e4\u00e4","year":"1999","journal-title":"Pediatr Neurol"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.pediatrneurol.2012.09.008","article-title":"Predictors of intractable childhood epilepsy","volume":"48","author":"Yilmaz","year":"2013","journal-title":"Pediatr Neurol"},{"key":"ref46","first-page":"198","article-title":"Gamma-globulin therapy in infantile spasms","volume":"6","author":"Shiihara","year":"1984","journal-title":"Brain Dev"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1796553\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T15:20:27Z","timestamp":1776266427000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1796553\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,13]]},"references-count":46,"alternative-id":["10.3389\/fneur.2026.1796553"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2026.1796553","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,13]]},"article-number":"1796553"}}