Consistency of Ictal Epileptogenic Foci in Children With Tuberous Sclerosis Complex and Its Clinical Predictors

PURPOSE: The course of epilepsy in patients with tuberous sclerosis complex (TSC) is highly variable. Consistency of the epileptogenic zone is considered important in presurgical evaluation. The authors aimed to (1) assess consistency of ictal epileptogenic foci over time in patients with TSC, (2) evaluate concordance between interictal epileptiform abnormalities and ictal epileptogenic foci, and (3) identify determinants of ictal consistency. METHODS: This single-center retrospective, observational study included children with definite TSC and epilepsy with ≥2 ictal presurgical EEGs with an interval ≥1 year. In all EEGs, the regional localization of interictal and ictal epileptiform abnormalities was scored based on the EEG reports. All ictal epileptogenic foci were classified with an "ictal focus consistency score," according to one of the following subcategories: "single focus, consistent," "from unclear localization/diffuse or generalized to unifocal," "≥2 or more foci, each consistent," "≥2 foci of which at least one is consistent," "starting multifocal but at last EEG unifocal," and "multifocal changing otherwise." The primary end point was unifocal or multifocal consistency of ictal foci. The secondary end point was concordance between ictal epileptogenic foci and localization of interictal epileptiform abnormalities. The third end point involved an exploratory assessment of potential determinants of ictal consistency, including TSC variant, age at epilepsy onset, epileptic spasms, multiple seizure types, interictal multifocality, and tuber load. RESULTS: The authors included 45 patients with TSC with a median of 3 (interquartile range 2-4) ictal and 8 (interquartile range 5-10) interictal EEGs per patient. Median time between first and last ictal EEG was 28.4 months (19.0-60.3). Ictal foci were consistent over time in 11 patients (24.4%), of whom 9 had 1 consistent ictal focus. Nine other patients had a single consistent ictal focus on the first EEGs, but developed a second focus at the median age of 67.7 months. Of the 13 patients who later underwent surgery, 3 had a single focus, and only 2 of 13 had consistent ictal EEGs. The same three patients with a single focus over time were part of the seven postoperative seizure-free patients. All six nonseizure-free children had ictal multifocality. Interictal and ictal epileptogenic foci were discordant in 42 of 45 patients (93.3%). Exploratory analyses of potential determinants of ictal consistency suggested a negative association with interictal multifocality (risk ratio 0.32, 95% confidence interval 0.06-0.97, p = 0.04), which was not significant after adjustment for monitoring duration. CONCLUSIONS: Ictal epileptogenic foci are consistent in only 25% of the patients with TSC. Interictal epileptogenic foci are often discordant with ictal foci. This instability in the ictal epileptogenic focus might be explained by the presence of larger epileptogenic networks in TSC that undergo evolution over time. SIGNIFICANCE: The findings in this study could have important implications for presurgical evaluation in patients with TSC and might help to understand the cause of (late) surgical failure.