Spectrum of epileptogenicity in different cortical tuber radiological subtypes: A stereoelectroencephalographic study

Tuberous sclerosis complex (TSC) causes focal drug-resistant epilepsy. Prediction of which tubers are epileptogenic remains challenging. We used stereoelectroencephalography (SEEG) to investigate epileptogenic zone (EZ) organization in TSC-related epilepsy, focusing on epileptogenicity of different tuber radiological subtypes.

We retrospectively studied consecutive patients with TSC-related epilepsy explored by SEEG. Presence of "focal EZ" (comprising "focal tuber," "tuber-plus," and "focal nontuber") or "diffuse EZ" was determined. In focal EZ involving tubers, interictal and ictal epileptogenic biomarkers were compared to the radiological appearance of tubers. In addition to four previously described tuber subtypes, we propose a novel subtype: type E (focal cortical depression, hypointense base on T2/fluid-attenuated inversion recovery).

Among 63 patients, 55 (87.3%) patients exhibited focal EZ, including focal tuber (n = 32, 50.8%), tuber-plus (n = 11, 17.5%), and focal nontuber (n = 12, 19.0%, of which 7/12 involved focal cortical dysplasia [FCD]). In the 43 of 63 (68.3%) patients with focal EZ involving at least one tuber, epileptogenicity of 265 explored tubers was analyzed with regard to radiological subtypes. Tuber subtypes A and B were most prevalent (186/265, 70.2%) but among the least epileptogenic on SEEG. The highest ictal epileptogenicity was in subtypes D (77.8%) and E (77.5%) compared to type A/B/C (Fisher exact test; all p < .05). Type D/E tubers exhibited higher interictal biomarkers than type A/B/ C (linear mixed model; p < .05). In patients with focal EZ, following surgical intervention, 36 of 55 (65.5%) achieved Engel class I outcomes, with a higher odds ratio of Engel I in the combined group of focal tuber/focal nontuber compared to tuber-plus EZ (p < .05).

Most TSC-related epilepsy represents focal EZ related to tubers, but focal extratuber EZ can also occur (FCD or hippocampus). Radiologically, calcified tubers (type D) and tubers with focal cortical depression and central hypointensity (type E) exhibit the highest epileptogenicity, similar to FCD type II.