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

Darrell V Lewis; James Voyvodic; Shlomo Shinnar; Stephen Chan; Jacqueline A Bello; Solomon L Moshé; Douglas R Nordli Jr; L Matthew Frank; John M Pellock; Dale C Hesdorffer; Yuan Xu; Ruth C Shinnar; Syndi Seinfeld; Leon G Epstein; David Masur; William Gallentine; Erica Weiss; Xiaoyan Deng; Shumei Sun; FEBSTAT Study Team

doi:10.1111/epi.17979

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

Epilepsia. 2024 Apr 12. doi: 10.1111/epi.17979. Online ahead of print.

Authors

Darrell V Lewis¹, James Voyvodic², Shlomo Shinnar³, Stephen Chan⁴, Jacqueline A Bello⁵, Solomon L Moshé⁶, Douglas R Nordli Jr⁷, L Matthew Frank⁸, John M Pellock⁹, Dale C Hesdorffer¹⁰, Yuan Xu¹, Ruth C Shinnar³, Syndi Seinfeld¹¹, Leon G Epstein¹², David Masur¹³, William Gallentine¹⁴, Erica Weiss¹³, Xiaoyan Deng¹⁵, Shumei Sun¹⁵; FEBSTAT Study Team

Affiliations

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.

PMID: 38606600
DOI: 10.1111/epi.17979

Abstract

Objective: This study was undertaken to determine whether hippocampal T2 hyperintensity predicts sequelae of febrile status epilepticus, including hippocampal atrophy, sclerosis, and mesial temporal lobe epilepsy.

Methods: Acute 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.

Results: Fourteen 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.

Significance: Hippocampal 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.

Keywords: MRI volumetry; T2 signal intensity; febrile seizures; hippocampal malrotation.

Grants and funding

43209/NS/NINDS NIH HHS/United States