Anatomical features decide the atypical seizure manifestation of parahypothalamic hamartomas

Chang Liu; Wenhan Hu; Chao Zhang; Zhong Zheng; Xiaoli Yang; Xiu Wang; Jiajie Mo; Zhihao Guo; Xiaoqiu Shao; Kai Zhang

doi:10.3389/fneur.2022.981488

Anatomical features decide the atypical seizure manifestation of parahypothalamic hamartomas

Front Neurol. 2022 Sep 12:13:981488. doi: 10.3389/fneur.2022.981488. eCollection 2022.

Authors

Chang Liu¹, Wenhan Hu^{1

2}, Chao Zhang¹, Zhong Zheng³, Xiaoli Yang³, Xiu Wang¹, Jiajie Mo¹, Zhihao Guo¹, Xiaoqiu Shao⁴, Kai Zhang^{1

2}

Affiliations

¹ Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
² Stereotactic and Functional Neurosurgery Laboratory, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
³ Epilepsy Center, Beijing Fengtai Hospital, Beijing, China.
⁴ Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Abstract

Background: The intrahypothalamic phenotype of hypothalamic hamartomas (HH) is associated with epilepsy, and the parahypothalamic phenotype usually leads to central precocious puberty but not neurological comorbidities or seizures. No study has confirmed the pathological role of parahypothalamic hamartomas in epileptogenesis, and the underlying mechanism is yet to be elucidated.

Objective: We aimed to investigate whether parahypothalamic hamartomas are intrinsically epileptogenic and elucidate the underlying pathway of epileptogenesis.

Methods: We reviewed 92 patients with HH-related epilepsy, categorized them by the classification system of Delalande and Fohlen, and further classified Type I (corresponding to parahypothalamic HH) into the following three groups based on the relationship between the lesion and mammillary bodies (MB): entirely invaded (Group 1), partially connected (Group 2), and not connected at all (Group 3). We examined different anatomical features with their relationship to clinical manifestations. Stereoelectroencephalography (SEEG) was implanted in both HH and extra-HH cortices in different groups to identify the epileptogenic zone. Corticocortical evoked potentials (CCEPs) were also used to determine the pathological correlation among different regions to determine the related epileptogenic network.

Results: A total of 13 patients presented with parahypothalamic HH and 10 (76.9%) presented with non-GS only, with late-onset age and normal cognitive development, which is different from classical clinical features. SEEG showed that HH is intrinsically epileptogenic in MB-involved parahypothalamic groups. No statistical difference was found in onset age (p = 0.213), and lesions horizontally oriented from the tuber cinereum without connection to MB were not involved in seizure genesis. CCEP indicated a pathological connection among HH, middle cingulate cortex, and insular cortex.

Conclusion: The parahypothalamic HH can also cause epilepsy and is different from classic HH-related seizures, by non-GS only with the late-onset age and normal cognitive development. MB is proven to be related to non-GS by the mamillo-cingulate-cortex pathway.

Keywords: hypothalamic hamartoma; network; seizure; semiology; stereo-electroencephalography.