Hippocampal volumetry in children 6 years or younger: assessment of children with and without complex febrile seizures
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.
References (27)
- et al.
Quantitative MRI hippocampal volumes, association with onset and duration of epilepsy, and febrile convulsions in temporal lobectomy patients
Epilepsy Res.
(1993) - et al.
Convulsive status epilepticus in infants and children: a study of 239 cases
Epilepsia
(1970) - et al.
Three-dimensional fast low-angle shot imaging and computerized volume measurement of the hippocampus in patients with chronic epilepsy of the temporal lobe
Am. J. Neuroradiol.
(1991) - et al.
Myelination of a key relay zone in the hippocampal formation occurs in the human brain during childhood, adolescence and adulthood
Arch. Gen. Psych.
(1994) - et al.
Hippocampal sclerosis in temporal lobe epilepsy demonstrated by magnetic resonance imaging
Ann. Neurol.
(1991) - Best, C.T., 1988. Emergence of cerebral asymmetries in early human development: a literature review and a...
- et al.
Magnetic resonance-based volume studies in temporal lobe epilepsy: pathological correlations
Ann. Neurol.
(1991) - et al.
Early childhood prolonged febrile convulsions, atrophy and sclerosis of mesial structures, and temporal lobe epilepsy
Neurology
(1993) - et al.
MRI volumetrics and memory function in patients with intractable temporal lobe epilepsy
Epilepsia
(1995) - Diamond, M.C., 1985. Rat brain morphology: Right–left: Male–female: Young–old: Enriched–impoverished. In: Glick, S.D....
Genetic and related aetiological factors in temporal lobe epilepsy
Epilepsia
Surgical treatment of drug-resistant epilepsy due to mesial temporal sclerosis: etiology and significance
Arch. Neurol.
Characteristics of medial temporal lobe epilepsy: I. Results of history and physical examination
D. Ann. Neurol.
Cited by (40)
Relations between neural structures and children's self-derivation of new knowledge through memory integration
2019, Developmental Cognitive NeuroscienceCitation Excerpt :Although we did not predict this pattern, it is not without precedent in the literature. Hippocampal hemispheric asymmetry, with greater volume in the right than left, is well established; the effect is observed across development (e.g., Pfluger et al., 1999; Utsunomiya et al., 1999), though it tends to decrease with age (Gogtay et al., 2006; Szabó et al., 1999 perhaps contributing to the observation that among adults, the asymmetry may be limited to the hippocampal head: Woolard and Heckers, 2012). Among adults, right hippocampal volume is correlated with performance on tests of general cognitive function, including immediate and delayed tests of verbal learning.
Anatomical and functional correlates of human hippocampal volume asymmetry
2012, Psychiatry Research - NeuroimagingCitation Excerpt :We interpret our finding of right anterior > left anterior hippocampal volume as a result of this growth vector. The right > left hippocampal volume ratio tends to decrease during development (Giedd et al., 1996; Szabo et al., 1999; Gogtay et al., 2006). Abnormal increases of right > left hippocampal asymmetry have been linked to the emergence of complex febrile seizures in children (Szabo et al., 1999) and psychopathy in adults (Raine et al., 2004).
Serial changes of prefrontal lobe growth in the patients with benign childhood epilepsy with centrotemporal spikes presenting with cognitive impairments/behavioral problems
2011, Brain and DevelopmentCitation Excerpt :Magnetic resonance imaging (MRI)-based volumetry has become established as a versatile, reliable method for investigating the biology of the human brain [9]. Such volumetric analysis has contributed to the search for structural correlates of developmental disorders such as autism [10] and seizure disorders such as temporal lobe epilepsy [11]. We have reported development of the prefrontal lobe using by three-dimensional (3D) MRI [12,13].
The Neurobiology of Psychopathy
2008, Psychiatric Clinics of North AmericaCitation Excerpt :Atypical brain asymmetries are thought in part to reflect disrupted neurodevelopmental processes [54]. Brain asymmetries first appear during fetal development, but tend to decrease somewhat with age in healthy children [55]. Structural asymmetries in psychopaths may reflect an interruption to the normal developmental process.
Hippocampal volume in childhood complex partial seizures
2006, Epilepsy Research