MRI abnormalities following febrile status epilepticus in children
The FEBSTAT study
Abstract
Objective:
The FEBSTAT study is a prospective study that seeks to determine the acute and long-term consequences of febrile status epilepticus (FSE) in childhood.
Methods:
From 2003 to 2010, 199 children age 1 month to 5 years presenting with FSE (>30 minutes) were enrolled in FEBSTAT within 72 hours of the FSE episode. Of these, 191 had imaging with emphasis on the hippocampus. All MRIs were reviewed by 2 neuroradiologists blinded to clinical details. A group of 96 children with first simple FS who were imaged using a similar protocol served as controls.
Results:
A total of 22 (11.5%) children had definitely abnormal (n = 17) or equivocal (n = 5) increased T2 signal in the hippocampus following FSE compared with none in the control group (p < 0.0001). Developmental abnormalities of the hippocampus were more common in the FSE group (n = 20, 10.5%) than in controls (n = 2, 2.1%) (p = 0.0097) with hippocampal malrotation being the most common (15 cases and 2 controls). Extrahippocampal imaging abnormalities were present in 15.7% of the FSE group and 15.6% of the controls. However, extrahippocampal imaging abnormalities of the temporal lobe were more common in the FSE group (7.9%) than in controls (1.0%) (p = 0.015).
Conclusions:
This prospective study demonstrates that children with FSE are at risk for acute hippocampal injury and that a substantial number also have abnormalities in hippocampal development. Follow-up studies are in progress to determine the long-term outcomes in these children.
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Supplementary Material
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Information & Authors
Information
Published In
Presented at
Presented in part at the American Epilepsy Society meetings, Washington, DC, December 2 to 6, 2005, and San Diego, CA, December 1 to 5, 2006.
Copyright
Copyright © 2012 by AAN Enterprises, Inc.
Publication History
Received: February 4, 2012
Accepted: April 19, 2012
Published online: July 25, 2012
Published in issue: August 28, 2012
Disclosure
S. Shinnar is funded by NIH grants NS 43209, NS 045911, NS 053998, NS 066929, 1U10NS077308, and UL1 RR025759; serves on a DSMB for King Pharmaceuticals; has received personal compensation for serving on Scientific Advisory Boards for Questcor and Sunovion, for consulting for Eisai, Questcor, and Neuronex, and speaker honoraria from Eisai, Questcor, and UCB. He has also given expert testimony in medico-legal cases. J. Bello is funded by NIH grant NS 43209. S. Chan is funded by NIH grant NS 43209. D. Hesdorffer is funded by NIH grants NS043209, NS31146, NS078419, 5U01NS04911, HD042823, CDC grants DP002209, MM1002, AUCD grant RT01, Maternal and Child Health Bureau grant MC00007, and grants from the Epilepsy Study Consortium and Epilepsy Foundation of America. She is a consultant to Mt Sinai Medical Center, New York, and has a received a travel grant award from Glaxo Smith Kline. D. Lewis is funded by NIH grant NS 43209. J. MacFall is funded by NIH grants NS43209, MH077745, and CA096821 and a grant from Duke Coulter Translational Research Fund. J. Pellock is funded by NIH grants NS043209 and NS045911 and a grant from the CDC. He has also received research support from Eisai, Marinus, Lundbeck, Pfizer, Questcor, and UCB. He has received compensation for serving on Scientific Advisory Boards for Eisai, Lundbeck, Questcor, Sepracor, and UCB and as a consultant to Catalyst, Eisai, GlaxoSmithKline, King, KV Pharmaceuticals, Lundbeck, Marinus, Neuropace, Pfizer, Questcor, Sepracor, Sunovion, UCB, Upsher Smith, and Valeant. All grants, research support, consultant fees, and honoraria are paid to Virginia Commonwealth University or the physician practice plan (MCV Physicians). D. Nordli is funded by NIH grant NS 43209. L.M. Frank is funded by NIH grants NS043209 and NS045911 and has received grant support from Schwarz-UCB, Ovation-Lundbeck, Eisai, Supernus, and AVI BioPharma. He serves on the Board of Directors at Chesapeake Bay Academy, a school for special needs children. He holds or has held stock in AVI Biopharma, Oncothyreon, Neurologix, Peregrine, Positiveid, and Nanoviricides. He has received personal compensation for work in medico legal cases. S. Moshé is funded by grants from NIH NS43209, NS20253, NS45911, and from the Heffer Family Foundation. He received a consultant fee from Eisai and a speaker's fee and travel expenses from GSK. W. Gomes reports no disclosures. R.C. Shinnar is funded by NIH grants NS043209 and NS045911. She has received compensation for serving on advisory panels for Questcor Pharmaceuticals, Eisai, and Lundbeck and speaker honoraria from Cyberonics and Questcor. She also serves as an expert consultant for the US Department of Justice and has received compensation for work as an expert on medico-legal cases. S. Sun is funded by NIH research 1R01HD060913, 7R01DK071485, 1U01HL101064, 1UL1RR031990, R01HD038356, 2R01HL040619, and R01NS043209. She also serves as a consultant for Nestle. Go to Neurology.org for full disclosures.
Authors
Author Contributions
All authors participated in the design and execution of the overall FEBSTAT project. Drs. Shinnar, Bello, Chan, Hesdorffer, Lewis, and MacFall designed the specific imaging project reported in this manuscript. All authors participated in the execution of the work reported in this manuscript. The data analysis and statistics were performed by Drs. Hesdorffer and Sun. All authors participated in writing and editing the manuscript.
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We read with interest the article by the FEBSTAT team [1] and accompanying editorial.[2] The concern regarding febrile status epilepticus (FSE) is whether the ictal phenomenon itself is deleterious to the cortex, specifically the hippocampus. The answer is vital as this will determine how aggressively febrile seizures should be treated. Signal abnormalities following within hours or days of FSE does not prove that ictal activity itself can produce neurologic injury. The results of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) map in those patients with T2 high signals are not mentioned in this article. It would be interesting to know if cytotoxic edema appeared in these children. The account of febrile seizures leading to neuronal injury comes from the observation that many adult patients with mesiotemporal epilepsy, including those with hippocampal sclerosis, reported FSE during the first years of life.[3] Later, with the results of the large population-based studies, this notion has changed. [4] Seizures leading to neuronal loss and gliosis cannot be ruled out as a hypothesis. However, it seems that these and many other authors are biased in believing that this does occur. In the Introduction, Shinnar et al. even refer to FEBSTAT as the "Consequences of Prolonged Febrile Seizures in Childhood (FEBSTAT)" study. As Berg and Abou-Khalil state in their editorial [2], signal abnormalities could be a cause and not a consequence of FSE.
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2. Berg MJ, Abou-Khalil B. Childhood febrile status epilepticus: Chicken or egg? Does it matter? Neurology 2012;79:840-841.
3. Epstein L, Shinnar S, Hesdorffer DC, et al. Human herpesvirus 6 and 7 in febrile status epilepticus: The FEBSTAT study. Epilepsia 2012:1-8.
4. Taylor DC, Ounsted C. Biological mechanisms influencing the outcome of seizures in response to fever. Epilepsia 1971;12:33-45.
5. Verity CM, Golding J. Risk of epilepsy after febrile convulsions: a national cohort study. BMJ 1991;303:1373-1376.
For disclosures, contact the editorial office.