Hippocampal malrotation and temporal lobe epilepsy: what is the relationship?

The importance of the hippocampus, in epileptic networks, which underpin temporal lobe epilepsy, have long been appreciated. Advances in MR imaging has facilitated the identification of structural lesions in the hippocampus. In the past few years, hippocampal malrotation or incomplete inversion of the hippocampus is increasingly reported in patients with and without epilepsy and the clinical significance of this imaging finding is unclear and controversial. During fetal development the hippocampus undergoes folding, transforming it from a smooth structure to a complex folded one1. The process of folding to the adult horizontal orientation is usually completed after 18 weeks gestation. In hippocampal malrotation, the folding is incomplete and the hippocampus has a vertically oriented, rounded appearance. This signifies a disruption of brain development and has been correlated with other markers of abnormal cortical development, such as increased cortical folding complexity and temporal lobe epilepsy2. Hippocampal malrotation is often seen in association with malformations of cortical development such as focal cortical dysplasia and polymicrogyria3 and nodular heterotopias4. Early pathological processes which affect hippocampal development may affect development of areas of the brain, either directly through hippocampal projections or through another common underlying pathological process. Hippocampal malrotation is thought to be a macroscopic marker of altered hippocampal development. In a study of 527 patients suspected to have epilepsy who had MR studies, 32 had hippocampal malrotation and in 7 of 32 there were additional developmental brain abnormalities5. Bernasconi and colleagues, observed hippocampal malrotation in 49% of 76 patients with malformations of cortical development, and 43% of 30 patients with temporal lobe epilepsy and 10% of 50 healthy control patients3. In 497 patients without epilepsy who underwent MRI, no patients had all diagnostic features of hippocampal malrotation but six patients had two or more features6. In this issue of the journal, Andrade and colleagues reported hippocampal malrotation using 3 Tesla MRI in 9 of 14 adults with 22q11.2 deletion syndrome, a population with a 7 fold increased risk of developing epilepsy compared to the general population7. However, hippocampal malrotation was seen in six patients who did not have epilepsy. Three of four patients with epilepsy had hippocampal malrotation but also had polymicrogyria and periventricular nodular heterotopia. Thus, while this study adds to the literature on the subject, it raises further questions about the clinical significance of hippocampal malrotation as it was more common in those without epilepsy in the study. However, the prevalence of hippocampal malrotation in patients without epilepsy in Dr. Andrade’s study suggests that other genetic or environmental factors may be important in Hippocampal Malrotation and Temporal Lobe Epilepsy: What is the Relationship?