Hippocampal sclerosis and temporal lobe epilepsy following febrile status epilepticus: The FEBSTAT study

Author:

Lewis Darrell V.1ORCID,Voyvodic James2,Shinnar Shlomo3,Chan Stephen4,Bello Jacqueline A.5,Moshé Solomon L.6ORCID,Nordli Douglas R.7,Frank L. Matthew8,Pellock John M.9,Hesdorffer Dale C.10ORCID,Xu Yuan1,Shinnar Ruth C.3,Seinfeld Syndi11,Epstein Leon G.12,Masur David13,Gallentine William14,Weiss Erica13ORCID,Deng Xiaoyan15,Sun Shumei15,

Affiliation:

1. Department of Pediatrics (Neurology) Duke University Medical Center Durham North Carolina USA

2. Department of Radiology Duke University Medical Center Durham North Carolina USA

3. Isabelle Rapin Division of Child Neurology, Saul R. Korey Department of Neurology and Department of Pediatrics, Montefiore Medical Center Albert Einstein College of Medicine Bronx New York USA

4. Department of Radiology, Harlem Hospital Center Columbia University New York New York USA

5. Department of Radiology, Montefiore Medical Center Albert Einstein College of Medicine Bronx New York USA

6. Isabelle Rapin Division of Child Neurology, Saul R. Korey Department of Neurology and Departments of Neuroscience and Pediatrics Albert Einstein College of Medicine, and Montefiore Medical Center Bronx New York USA

7. Department of Pediatrics, Section of Child Neurology University of Chicago Chicago Illinois USA

8. Department of Neurology Children's Hospital of the King's Daughters and Eastern Virginia Medical School Norfolk Virginia USA

9. Department of Neurology Medical College of Virginia, Virginia Commonwealth University Richmond Virginia USA

10. Department of Epidemiology, G. H. Sergievsky Center Columbia University New York New York USA

11. Pediatric Epilepsy Program Joe DiMaggio Children's Hospital Hollywood Florida USA

12. Department of Pediatrics Northwestern University Feinberg School of Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago Chicago Illinois USA

13. Department of Neurology, Montefiore Medical Center Albert Einstein College of Medicine Bronx New York USA

14. Stanford University Lucile Packard Children's Hospital Palo Alto California USA

15. Biostatistics and International Epilepsy Consortium, Virginia Commonwealth University Richmond Virginia USA

Abstract

AbstractObjectiveThis study was undertaken to determine whether hippocampal T2 hyperintensity predicts sequelae of febrile status epilepticus, including hippocampal atrophy, sclerosis, and mesial temporal lobe epilepsy.MethodsAcute magnetic resonance imaging (MRI) was obtained within a mean of 4.4 (SD = 5.5, median = 2.0) days after febrile status on >200 infants with follow‐up MRI at approximately 1, 5, and 10 years. Hippocampal size, morphology, and T2 signal intensity were scored visually by neuroradiologists blinded to clinical details. Hippocampal volumetry provided quantitative measurement. Upon the occurrence of two or more unprovoked seizures, subjects were reassessed for epilepsy. Hippocampal volumes were normalized using total brain volumes.ResultsFourteen of 22 subjects with acute hippocampal T2 hyperintensity returned for follow‐up MRI, and 10 developed definite hippocampal sclerosis, which persisted through the 10‐year follow‐up. Hippocampi appearing normal initially remained normal on visual inspection. However, in subjects with normal‐appearing hippocampi, volumetrics indicated that male, but not female, hippocampi were smaller than controls, but increasing hippocampal asymmetry was not seen following febrile status. Forty‐four subjects developed epilepsy; six developed mesial temporal lobe epilepsy and, of the six, two had definite, two had equivocal, and two had no hippocampal sclerosis. Only one subject developed mesial temporal epilepsy without initial hyperintensity, and that subject had hippocampal malrotation. Ten‐year cumulative incidence of all types of epilepsy, including mesial temporal epilepsy, was highest in subjects with initial T2 hyperintensity and lowest in those with normal signal and no other brain abnormalities.SignificanceHippocampal T2 hyperintensity following febrile status epilepticus predicted hippocampal sclerosis and significant likelihood of mesial temporal lobe epilepsy. Normal hippocampal appearance in the acute postictal MRI was followed by maintained normal appearance, symmetric growth, and lower risk of epilepsy. Volumetric measurement detected mildly decreased hippocampal volume in males with febrile status.

Funder

Dana Foundation

Eunice Kennedy Shriver National Institute of Child Health and Human Development

National Institute of Neurological Disorders and Stroke

Publisher

Wiley

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