Baram, TZ

Shinnar, S

Neurology

PubMed

Baram, Tallie Z

Shinnar, Shlomo

eScholarship - University of California

UC IrvineUC Irvine Previously Published WorksTitleDo febrile seizures improve memory?Permalinkhttps://escholarship.org/uc/item/6732c5c8JournalNeurology, 57(1)ISSN0028-3878AuthorsBaram, Tallie ZShinnar, ShlomoPublication Date2001-07-10DOI10.1212/wnl.57.1.7Copyright InformationThis work is made available under the terms of a Creative Commons Attribution License, availalbe at https://creativecommons.org/licenses/by/4.0/ Peer reviewedeScholarship.org Powered by the California Digital LibraryUniversity of CaliforniaDo febrile seizures improve memory?Tallie Z. Baram, MD, PhD and Shlomo Shinnar, MD, PhDDepartments of Pediatrics, Anatomy/Neurobiology, and Neurology (Dr. Baram), University ofCalifornia at Irvine; and the Departments of Neurology, Pediatrics, and the ComprehensiveEpilepsy Management Center (Dr. Shinnar), Montefiore Medical Center, Albert Einstein Collegeof Medicine, Bronx, NY.In this issue of Neurology, Chang et al.1 present a population-based study on the effects offebrile seizures on working memory, and find that school-aged children with febrile seizuresperformed significantly better than randomly selected, population-based control subjects.However, children with the onset of febrile seizures before the age of 1 year had deficits inlearning, consolidation, and delayed recognition.This article extends prior work on this cohort,2 which found that these school-aged children,except for those with seizure onset under 1 year of age, performed better than population-based control subjects on measures of intelligence and academic achievement. The newresults published in the current article are of particular interest because they focusspecifically on learning and memory aspects, which require an intact hippocampus. In bothhumans3,4 and immature animal models,5,6 prolonged febrile seizures have been associatedwith acute hippocampal injury. Furthermore, a history of prolonged febrile seizures iscommonly elicited in individuals with a specific pattern of chronic hippocampal injury,mesial temporal sclerosis,3,4,7–9 and mesial temporal lobe epilepsy, which are oftenassociated with impaired memory functions.10–13Prior epidemiologic studies of the outcome of febrile seizures in both United States14 andthe United Kingdom15,16 also have not found differences in global cognitive outcomesbetween children with febrile seizures and either siblings14 or population controls,15,16 butthese studies did not specifically examine memory. Interestingly, seizure onset before 1 yearof age was also a risk factor for poor outcome in the recent British study.16 The currentstudy adds reassuring data that memory tasks, which are a more specific indicator ofhippocampal function, are preserved in the majority if children with febrile seizures, butraises concern regarding those children who experience these seizures during the firstpostnatal year.Why be concerned specifically about memory and related hippocampal functions in childrenwith febrile seizures, and what factors might underlie the deficits noted specifically inindividuals experiencing the seizures during infancy? Both human3 and animal5,6,17 datahave suggested recently that at least transient injury to hippocampus and related limbicstructures can occur in individuals with prolonged febrile seizures. In human studies,prospective data using neuroimaging methods demonstrated acute swelling of hippocampusafter prolonged febrile seizures.3 In an infant rat model of prolonged (20-minute) febrileseizures, cytoskeletal changes in neurons were evident within 24 hours and persisted forseveral weeks, without leading to cell loss.5 However, persistently altered functionalCopyright © 2001 by AAN Enterprises, Inc.Address correspondence and reprint requests to Dr. Tallie Z. Baram, Pediatrics, Anatomy/Neurobiology, and Neurology, University ofCalifornia, Irvine, Medical Science 1, ZOT 4475, Irvine, CA 92697-4475.NIH Public AccessAuthor ManuscriptNeurology. Author manuscript; available in PMC 2011 May 24.Published in final edited form as:Neurology. 2001 July 10; 57(1): 7–8.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscriptproperties of these injured neurons were evident.17,18 Thus, it is conceivable that theexposure of hippocampal neurons to febrile seizures early in life, and particularly duringinfancy, may lead to transient injury and more sustained dysfunction of these cells. Theseeffects may be age dependent, and more pronounced during the first postnatal year. Thestrength of the study by Chang et al.1 is its focus on well-defined, sophisticated measures ofhippocampal-dependent working memory function, allowing relatively subtle deficits to bedetected.An unusual finding of this study is that children with febrile seizures actually performedbetter than the control subjects. The authors offer some interesting theoretical speculationsas to why this might be the case. However, it would be premature to tell parents that thefebrile seizure, far from harming their child, was actually beneficial. In their prior report,2the authors found that these same children also scored higher than population controls ontests of intelligence and academic achievement, which is at odds with a number of well-designed larger studies that—while finding no adverse effect of febrile seizures—did notfind an improvement.14–16 Therefore, the “take home” message from these new data shouldbe that most febrile seizures do not adversely affect global measures of intelligence, nor dothey harm more specific hippocampal functions such as memory, in children older than 1year of age.Although this report is a valuable contribution, many questions remain unanswered. Theauthors did not find significant differences in memory between children with complex andsimple febrile seizures. Some studies have found adverse outcomes on intelligence inchildren with prolonged febrile seizures,19 though others have not.14–16 Because Chang etal.1 had 87 children with febrile seizures, the number with prolonged febrile seizures wasrelatively small. Approximately 10% of all febrile seizures last more than 15 minutes, and5% last 30 minutes or longer.20 Because simple febrile seizures have not been associatedwith hippocampal injury in either human or animal data, future research should focus onmemory and other hippocampal-dependent functions in children who experience prolongedfebrile seizures. Chang et al.1 demonstrate the feasibility of such studies. We now needlarge-scale investigations analyzing the contribution of seizure duration and the age of thechild at seizure onset to specific outcome measures of learning and memory.References1. Chang YC, Guo NW, Wang ST, Huang CC, Tsai JJ. Working memory of school-aged children witha history of febrile convulsions: a population study. Neurology. 2001; 57:37–42. [PubMed:11445625]2. Chang Y-C, Guo N-W, Huang C-C, Wang ST, Tsai JJ. Neurocognitive attention and behavioroutcome of school-age children with a history of febrile convulsions: a population study. Epilepsia.2000; 41:412–420. [PubMed: 10756406]3. Vanlandingham KE, Heinz ER, Cavazos JE, Lewis DV. MRI evidence of hippocampal injury afterprolonged, focal febrile convulsions. Ann Neurol. 1998; 43:413–426. [PubMed: 9546321]4. Shinnar S. Prolonged febrile seizures and mesial temporal sclerosis. Ann Neurol. 1998; 43:411–412.[PubMed: 9546320]5. Toth Z, Yan XX, Haftoglou S, Ribak CE, Baram TZ. Seizure-induced neuronal injury: vulnerabilityto febrile seizures in immature rat model. J Neurosci. 1998; 18:4285–4294. [PubMed: 9592105]6. Jiang W, Duong TM, de Lanerolle NC. The neuropathology of hyperthermic seizures in the rat.Epilepsia. 1999; 40:5–19. [PubMed: 9924896]7. Abou–Khalil B, Andermann E, Andermann F, Olivier A, Quesney LF. Temporal lobe epilepsy afterprolonged febrile convulsions: excellent outcome after surgical treatment. Epilepsia. 1993; 34:878–883. [PubMed: 8404740]Baram and Shinnar Page 2Neurology. Author manuscript; available in PMC 2011 May 24.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript8. Cendes F, Andermann F, Dubeau F, et al. Early childhood prolonged febrile convulsions, atrophyand sclerosis of mesial structures, and temporal lobe epilepsy: an MRI volumetric study. Neurology.1993; 43:1083–1087. [PubMed: 8170546]9. French JA, Williamson PD, Thadani M, et al. Characteristics of medial temporal lobe epilepsy. I.Results of history and physical examination. Ann Neurol. 1993; 34:774–780. [PubMed: 8250525]10. Squire LR. Memory and the hippocampus: a synthesis of findings with rats, monkeys, and humans.Psychol Rev. 1992; 99:195–231. [PubMed: 1594723]11. Sass K, Spencer M, Kim J, Westerveld M, Novelly R, Lencz T. Verbal memory impairmentcorrelates with hippocampal cell density. Neurology. 1990; 40:1694–1697. [PubMed: 2234424]12. Sass K, Sass A, Westerveld M, et al. Specificity in the correlation of verbal memory andhippocampal neuron loss: dissociation of memory, language, and verbal intellectual ability. J ClinExp Neuropsychol. 1992; 14:662–672. [PubMed: 1474137]13. Rausch R, Babb T. Hippocampal neuron loss and memory scores before and after temporal lobesurgery for epilepsy. Arch Neurol. 1993; 50:812–817. [PubMed: 8352666]14. Ellenberg JH, Nelson KB. Febrile seizures and later intellectual performance. Arch Neurol. 1978;35:17–21. [PubMed: 619868]15. Ross EM, Peckham CS, West PB, Butler NR. Epilepsy in childhood: findings from the nationalchild development study. BMJ. 1980; 280:207–210. [PubMed: 7427082]16. Verity CM, Greenwood R, Golding J. Long-term intellectual and behavioral outcomes of childrenwith febrile convulsions. N Engl J Med. 1998; 338:1723–1728. [PubMed: 9624192]17. Dube C, Chen K, Eghbal–Ahmadi M, Brunson K, Soltesz I, Baram TZ. Prolonged febrile seizuresin the immature rat model enhance hippocampal excitability long term. Ann Neurol. 2000;47:336–344. [PubMed: 10716253]18. Chen K, Baram TZ, Soltesz I. Febrile seizures in the developing brain result in persistentmodification of neuronal excitability in limbic circuits. Nat Med. 1999; 5:888–894. [PubMed:10426311]19. Kölfen W, Pehle K, König S. Is the long-term outcome of children following febrile convulsionsfavorable? Dev Med Child Neurol. 1998; 40:667–671. [PubMed: 9851235]20. Berg AT, Shinnar S. Complex febrile seizures. Epilepsia. 1996; 37:126–133. [PubMed: 8635422]Baram and Shinnar Page 3Neurology. Author manuscript; available in PMC 2011 May 24.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript

Do febrile seizures improve memory?

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