Elsevier

Epilepsy Research

Volume 33, Issue 1, 1 January 1999, Pages 1-9
Epilepsy Research

Hippocampal volumetry in children 6 years or younger: assessment of children with and without complex febrile seizures

https://doi.org/10.1016/S0920-1211(98)00068-0Get rights and content

Abstract

Purpose: To study the relationship of complex febrile seizures (CFS) in the evolution of mesial temporal sclerosis. Methods: We studied five children 22–68 (mean 44) months old with MRI volumetry 2 days–46 months after their first CFS, and compared total hippocampal volumes and right to left hippocampal volume ratios to those of 11 controls, 15–83 (mean 55) months old, who had MRI for complaints which turned out to be neurologically insignificant. Results: In control children, total hippocampal volumes increased linearly with age, while right to left hippocampal volume ratios tended to decrease with age. In children with CFS total hippocampal volumes tended to be smaller than in controls. Right to left ratios were greater than 1 in all five children with CFS compared to seven of 11 controls. Hippocampal asymmetry was noted in only one child, with the right to left volume ratio exceeding two standard deviations from the control mean. The MRI of this child also demonstrated a subarachnoid cyst in the left frontocentral region, ipsilateral to the smaller hippocampus. Visual inspection of the remaining patients revealed no definite structural cortical abnormalities. None of the children developed subsequent afebrile seizures during the brief follow-up period. Conclusions: Hippocampal volumetry in controls revealed a linear increase in total hippocampal volumes and a statistically nonsignificant trend toward reduced right larger than left hippocampal ratios between 17 and 83 months old. The tendency for smaller total hippocampal volumes and larger right to left hippocampal volume ratios in children with CFS compared to controls could suggest a developmental abnormality, injury during CFS, or be age-related. The significant hippocampal asymmetry in a single child with CFS suggests that age may not be a factor in every case. Further studies are needed to collect control data in young children as well as prospectively follow children with CFS with serial imaging to better understand the relationship between CFS and the evolution of hippocampal atrophy.

Introduction

Hippocampal sclerosis (HS), the most common pathological finding underlying medically intractable temporal lobe epilepsy, is frequently associated with a history of complex-focal, prolonged or repetitive-febrile seizures (CFS) in infancy or early childhood. In surgical series, almost one-third of patients with HS have a history of CFS (Falconer and Taylor, 1968, Cendes et al., 1993, French et al., 1993). This finding led several authors to propose a causative role of CFS in the evolution of HS (Aicardi and Chevrie, 1970, Falconer, 1971, Wallace, 1977, Sagar and Oxbury, 1987, Nohria et al., 1994, Van Landingham et al., 1996), while others propose that CFS may be a marker of pre-existent neurological insults (Cendes et al., 1993, Kuks et al., 1993, Nohria et al., 1994, Van Landingham et al., 1996). Magnetic resonance imaging (MRI) has enhanced our ability to recognize hippocampal atrophy and sclerosis. Hippocampal volumetry has been applied to MRI scans with the aim to quantify the degree of atrophy (Cascino et al., 1991, Jack et al., 1990a, Ashtari et al., 1991, Berkovic et al., 1991, Lencz et al., 1992). Hippocampal injury after febrile or afebrile convulsive status have been reported in individual cases: unilateral or bilateral hippocampal edema in the acute stage, followed by hippocampal atrophy and sclerosis within months to years (Nohria et al., 1994, Tien and Felsberg, 1995, Van Landingham et al., 1996). Other retrospective studies showed that hippocampal atrophy is more severe in patients with medically intractable temporal lobe epilepsy and a history of prolonged febrile seizures (Jack et al., 1990a, Cendes et al., 1993, Tenerry et al., 1993). Although it appears that febrile or afebrile status can lead to unilateral hippocampal atrophy, it is still not clear whether less prolonged, repetitive or focal febrile seizures are associated with hippocampal injury. As there is little published data on hippocampal volumes in children at the time of their CFS, or for normal controls in this age range, we performed hippocampal volumetry in children with and without CFS to better define the degree of hippocampal asymmetry in these two groups.

Section snippets

Patients

Recruitment of completely normal infants and young children was attempted for the MRI studies to assess hippocampal volumes. However, due to the parental reluctance to subject their children to sedation, no children could be enrolled. As an alternative approach, we studied MRI hippocampal volumes in children who were referred for MRI by their physicians for evaluation of a clinical complaint which turned out to be neurologically insignificant. This control group included 11 children (seven

Methods

All MRI scans were performed on the Siemens 1.5 Tesla SP63/IMPAC and Vision machines. Two MRI sequences were performed in each case: the MPRAGE (magnetization prepared rapid acquisition gradient echo) protocol, acquiring contiguous 2.0 mm slices through the head (flip angle 10°, a matrix size 130 * 256, TR 10, TE 4, field of vision 250), and contiguous 6 mm coronal T-2 weighted images. The 128 images acquired by the MPRAGE protocol were prepared by an ISG post-processing system. Children with CFS

Controls

In each case hippocampi appeared normal in size and signal intensity. Increases in total hippocampal volume were significantly correlated with age for control children between 15 and 83 months old (P=0.009, r2=0.548) (Table 1, Fig. 1). The estimated slope was 38 mm3/month. The mean hippocampal R/L volume ratio was 1.03 (S.D.±0.06), indicating that right hippocampal volumes were slightly greater than those on the left (Table 1, Fig. 2). There was an insignificant trend of R/L hippocampal volume

Discussion

MRI with hippocampal volumetry has become a well-established tool used by epilepsy surgery centers to define hippocampal sclerosis and atrophy (Kuzniecky et al., 1987, Jack et al., 1990a, Ashtari et al., 1991, Berkovic et al., 1991, Watson et al., 1992, Cendes et al., 1993). Previous surgical series used adult or adolescent controls, so little is known about hippocampal volumetry in normal infant and children. Therefore, it was necessary to obtain pediatric control data before the assessment of

Acknowledgements

Special thanks to The Cleveland Clinic Foundation for granting financial support for this project, and to Chris Skibinski for the statistical analysis of our data.

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