Response: Temporal encephalocele and epileptogenesis—Reflections of MRI metrics of brain parenchymal tethering

We thank the correspondents for their thoughtful appraisal. The letter raises several important points that merit further discussion: Our primary objective was to establish proof-of-concept that frontotemporal aperture (FTA) and opercular angle (OA) metrics capture systematic alterations in Sylvian fissure geometry in a cohort with epileptogenic, surgically-confirmed temporal encephalocele, rather than propose immediate per-patient thresholds for routine decision-making.1 Aggregate analyses were emphasized to demonstrate robust group-level effects and control for multiple comparisons within a modest sample. We agree that defining normative ranges and embedding values within multivariate models incorporating volume, location, and other covariates are critical next steps toward future clinical translation. Nevertheless, we hope to have contributed candidate imaging biomarkers supporting such efforts in subsequent investigations. The suggestion to correlate maximal FTA/OA values with stereo-electroencephalography (SEEG)–defined epileptogenic networks is aligned with our broader goals. Understandably, in our cohort spanning 8 years, SEEG implantations were not optimized prospectively to sample the gradient of geometric changes observed. To avoid overinterpretation of limited sampling, we did not present voxel-based structure–function correlations. A prospective design integrating SEEG targeting with regions defined by maximal FTA/OA values is better suited to test the tethering hypothesis. With respect to “hippocampal-sparing,” this denotes preservation of the hippocampal formation proper, with tailored removal of the parahippocampal/entorhinal cortex. Moreover, correlations between encephalocele site and Sylvian fissure widening are conceptually aligned with our proposed tethering framework. In this series, sample size and lesion heterogeneity limited the feasibility of robust correlation analyses; the apparent “outliers” highlighted by the correspondents likely reflect local anatomic variability rather than a systematic dissociation between the two. Our colleagues highlighted that contralateral encephalocele volumes appeared larger yet were associated with narrower FTA/OA metrics, challenging the tethering concept. It is important to distinguish apparent volumetric differences from clinically-dominant pathology, and we appreciate the opportunity to clarify this point. Among six patients with bilateral encephaloceles, the side identified as epileptogenic and thus surgically-targeted—with subsequent seizure freedom—showed greater FTA/OA widening, with five patients having larger-volume contralateral encephaloceles than the ipsilateral/surgical side. These findings therefore imply that epileptogenicity arises from the more tethered side (with largest FTA/OA metrics on the ipsilateral/surgical side), rather than the side harboring the largest encephalocele—further supporting the tethering mechanism postulated in our study. The observation of T2 signal changes in the encephalocele neck as a potential marker of chronic tethering is intriguing. In our cohort, these abnormalities were not sufficiently robust for formal quantitative analysis, but represent another complementary target for future studies. We concur that etiologic stratification, and explicit comparison among encephaloceles with or without overt tethering, will refine mechanistic understanding of this pathology. We also suggest that detailed pathological tissue analysis of these lesions (incorporating histopathology, immunohistochemistry, molecular/genetic techniques, etc.) may offer additional opportunities for high-yield research. We thank the correspondents for supporting this framework for novel, quantitative imaging biomarkers in temporal encephalocele–related epilepsy.1 This work aims to provide a road map motivating future investigations into the epileptogenicity of this interesting pathology. None. Imad Najm is on the Speakers' bureau of SK Life Science. The remaining authors have no competing interests to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.