Anatomical features decide the atypical seizure manifestation of parahypothalamic hamartomas

Abstract

BackgroundThe 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.ObjectiveWe aimed to investigate whether parahypothalamic hamartomas are intrinsically epileptogenic and elucidate the underlying pathway of epileptogenesis.MethodsWe 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.ResultsA 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.ConclusionThe 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.

Epilepsy in hypothalamic hamartomas: semiology spectrum and predictor analyses of 78 patients

“…Stereotactic depth recordings of seizure onset and direct HH stimulation have additionally provided direct evidence for GS ictogenesis, 11–13 while electrical 14 and ictal SPECT 15 studies of HH patients have shown that the interface between the HH and the hypothalamus, rather than the entirety of the HH, was associated with seizure incidence 15 . This is consistent with the finding that intrahypothalamic HH lesions are related to GS onset more often than are parahypothalamic HH cases, as was observed in this study and other past reports 4,6,16 . As such, efforts to ablate primarily this interface region and to establish a disconnect via endoscopic surgery, stereotactic radiofrequency thermocoagulation, 12 or laser interstitial thermotherapy 17,18 is clinically viable.…”

“… 15 This is consistent with the finding that intrahypothalamic HH lesions are related to GS onset more often than are parahypothalamic HH cases, as was observed in this study and other past reports. 4 , 6 , 16 As such, efforts to ablate primarily this interface region and to establish a disconnect via endoscopic surgery, stereotactic radiofrequency thermocoagulation, 12 or laser interstitial thermotherapy 17 , 18 is clinically viable. The present results also confirmed that the intraventricular portion of HH lesions was primarily associated with epilepsy disease evolution.…”