Incomplete hippocampal inversion and epilepsy: A systematic review and meta‐analysis

Abstract

Objective Incomplete hippocampal inversion (IHI) is a relatively frequent radiological finding at visual inspection in both epilepsy and healthy controls, but its clinical significance is unclear. Here, we systematically retrieve and assess the association between epilepsy and IHI using a meta‐analytic approach. Additionally, we estimate the prevalence of IHI in patients with malformation of cortical development (MCD). Methods We systematically searched two databases (Embase and PubMed) to identify potentially eligible studies from their inception to December 2019. For inclusion, studies were population‐based, case–control, observational studies reporting on epilepsy and IHI. The risk of developing epilepsy in IHI (estimated with odds ratio [ORs]) and the frequency of IHI among patients with MCD are provided. Results We screened 3601 records and assessed eligibility of 2812 full‐text articles. The final material included 13 studies involving 1630 subjects. Seven studies (1329 subjects: 952 epileptic and 377 nonepileptic) were included for the estimation of the risk of developing epilepsy in the presence of IHI. The estimated OR of active epilepsy in IHI was 1.699 (95% confidence interval = 0.880–3.281), with moderate heterogeneity across studies (I2 = 71%). Seven studies (591 patients) provided information about the frequency of IHI in MCD. Up to one third of patients with MCD (27.9%) presented coexistent IHI. Significance The present findings confirm that IHI is commonly observed in patients with MCD especially in periventricular nodular heterotopia or polymicrogyria. However, the estimated OR indicates overall weak increased odds of epilepsy in people with IHI, suggesting that the presence of isolated IHI cannot be considered a strong independent predictor for epilepsy development. Clear‐cut neuroradiological criteria for IHI and advanced postprocessing analyses on structural magnetic resonance imaging scans are recommended to highlight differences between epileptogenic and nonepileptogenic IHI.

Hippocampal Malrotation Could Be Less Significant in Epilepsy Caused by Focal Cortical Dysplasia Type I and Type II

“…Due to the subjectivity, we did not include this in our study. Consistent with us, a 7-T MRI study found that the internal architecture of the hippocampus is actually not blurred in patients with HIMAL (10,40), and should probably not be considered a requirement for HIMAL diagnosis. In consideration of the above issues, criteria for a more scientific diagnostic of HIMAL are urgent.…”

“…Additionally, a previous study ( 22 ) detected no relationship between the laterality of abnormal EEG and the laterality of HIMAL. In respect to the susceptibility of HIMAL persons to develop epilepsy, a systematic review found no significantly increased probability of epilepsy, suggesting that the presence of HIMAL should not be considered a strong independent predictor for epilepsy development ( 10 ). Based on the above, HIMAL seemed to have no tight relationship with epilepsy.…”

“…We evaluated each hippocampus in four aspects ( 10 ): (1) round shape; (2) vertical dominant inferior temporal sulcus (DITS, the most prominent of the collateral or occipitotemporal sulcus); (3) enlarged temporal horn; and (4) a low position of ipsilateral fornix ( Figure 1A ). These four aspects were judged based on the comparison with the opposite side.…”

“…We evaluated each hippocampus in four aspects (10): (1) round shape; (2) vertical dominant inferior temporal sulcus (DITS, the most prominent of the collateral or occipitotemporal sulcus);…”

“…Due to the similar appearance of HIMAL and fetal hippocampus at 14-20 weeks of gestation, some scholars speculate that HIMAL is the consequence of incomplete infolding of medial temporal structures during embryonic brain development, and could be a marker of developmental brain disorders (2,6). It has been reported that patients with periventricular nodular heterotopia, lissencephaly, polymicrogyria, holoprosencephaly, and hemimegalencephaly often have HIMAL (4,(7)(8)(9)(10)(11), and eventually present epilepsy. Although HIMAL has not been directly considered as an epileptogenic lesion, it may be a factor of susceptibility to neuropathological processes which lead to the hippocampal neuronal loss and hippocampal sclerosis (12)(13)(14).…”