Quantitative Evaluation of Medial Temporal Lobe Morphology in Children with Febrile Status Epilepticus: Results of the FEBSTAT Study

Abstract

Purpose The pathogenesis of febrile status epilepticus is poorly understood, but prior studies suggest an association with temporal lobe abnormalities including hippocampal malrotation. We employ a quantitative morphometric method to assess the association between temporal lobe morphology and febrile status epilepticus. Methods Brain MR imaging was obtained in children presenting with febrile status epilepticus and control subjects as part of the FEBSTAT study. Medial temporal lobe morphologic parameters were measured manually, including distance of the hippocampus from midline, hippocampal height:width ratio, hippocampal angle, collateral sulcus angle, and width of the temporal horn. Results Temporal lobe morphologic parameters are correlated with presence of visual hippocampal malrotation; the strongest association is with left temporal horn width (p < 0.001, Adjusted OR 10.59). Multiple morphologic parameters correlate with febrile status epilepticus, encompassing both right and left sides. This association is statistically strongest in the right temporal lobe, whereas hippocampal malrotation is almost exclusively left-sided in this cohort. The association between temporal lobe measurements and febrile status epilepticus persists when the analysis is restricted to cases with visually normal imaging without hippocampal malrotation or other visually apparent abnormality. Conclusions Several component morphological features of hippocampal malrotation are independently associated with febrile status epilepticus, even when complete hippocampal malrotation is absent. Unexpectedly, this association predominantly involves the right temporal lobe. These findings suggest that a spectrum of bilateral temporal lobe anomalies are associated with febrile status epilepticus in children. Hippocampal malrotation may represent a visually apparent subset of this spectrum.

Review: The past, present and future challenges in epilepsy‐related and sudden deaths and biobanking

“…Hippocampal malrotation is a developmental anatomical variant, identified in 23% of the general population on MRI in one series and more commonly left sided [71]. Malrotation of the hippocampus was found on MRI in 8.8% of patients with febrile status in the FEBSTAT study [72] with predilection for the left side, compared to 2.1% in their control groups [73]. Hippocampal malrotation may represent a substrate to febrile seizure and epilepsy [74] and granule cell dispersion is postulated as a morphological biomarker in SIDS that could indicate impaired connectivity between the hippocampus and brainstem [68] or a manifestation of previous unrecognised ictal activity [75].…”

Hippocampal morphometry in sudden and unexpected death in epilepsy (SUDEP)

“…Evaluation of HMAL is confounded by lack of universally applied diagnostic criteria, both for MRI and neuropathology, to enable reliable comparisons of its incidence across disease groups in published studies 15,26 . Reported incidences of HMAL vary from 8% 27 to 16% 16 in non-HS TLE, 8.8% in febrile status 28 to 88% in SUDC associated with FS 9 . Furthermore, quantitative MRI evaluations of healthy controls report an incidence of HMAL in 23-24%, more commonly involving the left side 15,16 .…”

Genetic Contributions to Acquired Epilepsies

“…32 In some children with prolonged febrile seizures, however, there are preexisting hippocampal abnormalities which may predispose to hippocampal damage. 33 The prospective FEBSTAT (Consequences of Prolonged Febrile Seizures in Childhood) study suggests that both mechanisms may be operative. 32,33 Genetic factors are also implicated.…”

“…33 The prospective FEBSTAT (Consequences of Prolonged Febrile Seizures in Childhood) study suggests that both mechanisms may be operative. 32,33 Genetic factors are also implicated. Children with their first febrile seizure had a 3-fold higher risk of presenting with febrile status epilepticus than a simple febrile seizure if they had a first-degree family history of febrile seizures.…”