A total of 28 children (aged 18 years and younger) with TSC and intractable epilepsy underwent presurgical evaluation from July 2000 to June 2007 (). There were 14 boys, with an average age of 5.5 years (range 0.75–17 years) at the time of evaluation. Two children had prior resection at another institution, 1 had his entire evaluation at UCLA but had surgery at another institution closer to home without invasive studies, and 1 patient had 3 prior nonresective surgeries at UCLA (vagal nerve stimulator implantation, 2-staged corpus callosotomy) before his resective surgery.
The MRI studies were assessed for tuber counts. MRI studies demonstrated 20 or more tubers for all children with TSC, except for patient 10, whose tuber count was 10 to 20, and patient 13, whose tuber count was slightly less than 10. Tubers were bihemispheric in all 28 patients with TSC. All 28 patients with TSC had FDG-PET/MRI coregistration, and 18 had both MSI and FDG-PET/MRI coregistration. Thirteen of the 18 children with TSC who had both tests went on to have resective surgery ().
Of the 28 children with TSC who had presurgical evaluations, 10 did not proceed to resective surgery (). Three (patients 19–21) had temporary cessation of seizures during their surgical evaluation, and surgery was not further pursued even when seizures recurred or changed (conversion of infantile spasms to complex partial seizures in 1 case). Another 6 children were not offered surgery after additional MSI and FDG-PET/MRI coregistration tests because of nonlateralizing results or multiple bilateral independent sites of interictal discharges. One child (patient 28) was offered surgery after additional MSI and FDG-PET/MRI coregistration detected a surgical target, but the family declined the offer because of the size of the proposed resection. All 10 of these children continued to have seizures at their last follow-up visit.
The remaining 18 children were offered and underwent resective surgery using the MSI and FDG-PET MRI coregistration in planning the surgery (), and 12 became seizure free (67%). Their average (± SD) postoperative follow-up was 4.1 ± 1.4 years, with a range of 1.75 to 8.50 years.
Figure An illustrative case (patient 7, )
Of the 12 seizure-free children, their antiepileptic drugs (AEDs) were reduced gradually after surgery. Preoperatively, the average number of AEDs was 2.2 ± 0.7, which was reduced to an average of 0.7 ± 0.6 AEDs postoperatively (paired t test, p < 0.0001) at the last follow-up visit. Five postsurgical TSC children were using no AEDs and were seizure free.
Of the 6 children who did not gain seizure freedom after their first surgery, their seizures all returned within weeks after surgery. All except 1 underwent a second presurgical evaluation. Two of 5 children had seizures that were insufficiently localized for a second resective surgery, and they subsequently had a vagal nerve stimulator implanted. The remaining 3 children had localizable seizures, all originating from different tubers removed in the first surgery and not apparent in the first presurgical evaluation including MSI and FDG-PET/MRI coregistration. All 3 children underwent a second resective surgery (), which removed tubers distant from the first surgical resection in patient 14 (who continued to have seizures after the second resection) and extended and enlarged the previous resection zones in 2 patients (patient 15 continued to have seizures after the second resection, whereas patient 17 is seizure free 11 months after the second resection).
All surgical pathologic specimens from all resections, including first and second operations, found cortical tubers. One child had the additional finding of hemimegalencephaly (patient 1, ), and a second child had additional cortical dysplasia that was normal on MRI and not apparent as tubers or cortical dysplasia (patient 8, ). Both children with the additional pathologic findings achieved seizure freedom postoperatively.
Correlating clinical findings to seizure outcome.
Clinical characteristics were compared between children who were seizure free and not seizure free after surgery (). Age at the time of surgery differed, with a younger age for those who were seizure free (4.1 ± 2.9 years) compared with those whose seizures continued postoperatively (7.9 ± 4.0 years; t test, p = 0.036). Seizure duration, defined as the time from age at seizure onset to age at surgery, also differed, with a shorter seizure duration for those who attained seizure freedom (3.7 ± 2.7 years) compared with those not seizure free after surgery (7.6 ± 4.0 years; t test, p = 0.028).
Table 2 Clinical characteristics comparison
When these comparisons included children who were not offered surgery (), using age at presurgical evaluation rather than age at surgery, those who attained seizure freedom were the youngest (3.6 ± 2.7 years), those who continued to have seizures postoperatively were intermediate in age (6.8 ± 3.8 years), and those who were not offered surgery were the oldest (8.0 ± 3.3 years; analysis of variance [ANOVA], p = 0.023).
Similarly for seizure duration, modified to reflect the time span between age at seizure onset and age at presurgical evaluation, those who were seizure free had the shortest seizure duration (3.2 ± 2.5 years), those who continued with seizures had intermediate seizure duration (6.5 ± 3.8 years), and those who were not offered surgery had the longest seizure duration (7.3 ± 3.4 years; ANOVA, p = 0.024).
Age at seizure onset did not differ among these groups, and neither did seizure frequency on the video-EEG, seizure type, active infantile spasms, history of infantile spasms, use of vigabatrin, gender, type of surgical resection, side of resection, or tuber count (). There also was no difference in the postoperative follow-up period between the 2 postoperative groups (ANOVA, p = 0.75). Similarly, there did not seem to be referral or patient selection bias, e.g., no difference in age at the time of presurgical evaluation between the 2 halves of the 7-year inclusion period (ANOVA, p = 0.77).
Magnetic source imaging.
Eighteen children with TSC had MSI. All AEDs were maintained at their usual doses for the MSI study. Eight of the MSI studies were performed at Scripps, and 10 were performed at UCSF. MSI findings did not differ between the 2 facilities when dipole yield, correlation with video-EEG localization, correlation with FDG-PET hypometabolic locations, and correlation with seizure freedom were individually compared.
Four MSI studies were not localizing for presurgical evaluation, either because no dipoles were detected (2 studies) or because dipoles were multifocal (2 studies). In the remaining 14 MSI studies, interictal dipoles clustered over a single tuber or a single group of closely located tubers (6 at Scripps and 8 at UCSF). For this study, dipole clusters were defined as 5 or more epileptiform dipoles in 1 or contiguous sublobar regions of the brain.12
By chance, patients 5 and 16 had seizures during their magnetoencephalography (MEG) studies (), and the ictal onset zone closely matched the region localized by the interictal dipoles in the same study.
Whereas 1 patient who had MSI elected not to undergo surgery, the other 13 children underwent surgery, with the final resection based on all noninvasive tests, and the intraoperative electrocorticography. Seven patients had complete removal of the dipole clusters and all became seizure free postoperatively, 5 children had partial removal of the dipole clusters (limited resection for 1 because of eloquent cortex [patient 16 with the ictal MEG study]) and 2 achieved postoperative seizure freedom, and 1 child had no removal of the dipole cluster and continued with seizures postoperatively (). Thus, complete removal of MSI dipole clusters correlated with postoperative seizure freedom (χ2, p = 0.025).
For the 8 children whose video-EEG ictal onset was localized to a quadrant and had MSI, MSI confirmed that localization in 6 (75%) and was nonlocalizing in 2 (). For the 7 children with MSI whose video-EEG ictal onset was lateralized to 1 hemisphere but not further localized within that hemisphere, MSI provided localization in 6 and was nonlocalizing in 1. For the 3 children whose video-EEG ictal onset was nonlateralized, MSI provided localization in 2 and was nonlocalizing in 1. Thus, for these 2 groups of children with hemispheric or generalized ictal onset, MSI was able to provide further localization over ictal EEG in 8 of 10 children (80%).
All 28 children with TSC had coregistration of their FDG-PET and their structural MRI. Sixteen of these coregistrations were nonlocalizing because no single tuber or group of tubers had the larger volume of hypometabolism relative to the actual tuber volume on MRI. The remaining 12 studies found the largest volume of hypometabolism, relative to the actual tuber volume on MRI, over a single tuber or group of tubers. Of these 12 patients, 8 had complete removal of the hypometabolic volume and 6 became seizure free postoperatively. Two children had partial removal of the hypometabolism and 1 achieved postoperative seizure freedom, and 2 children had no removal of the hypometabolic volume and 1 was seizure free postoperatively (). Complete removal of hypometabolism on the FDG-PET/MRI coregistration did not correlate with postoperative seizure freedom (χ2, p = 0.69).
For the 11 children whose video-EEG ictal onset was localized to a quadrant, FDG-PET/MRI coregistration confirmed that localization in 5 and was nonlocalizing in 6 (45%). For the 10 children whose video-EEG ictal onset was lateralized to 1 hemisphere but not further localized within that hemisphere, FDG-PET/MRI coregistration provided further localization in 4 and was nonlocalizing in 6. For the 7 children whose video-EEG ictal onset was nonlateralized, FDG-PET/MRI coregistration provided localization in 2 and was nonlocalizing in 5. Thus, for these 2 groups of children with hemispheric or generalized ictal onset, FDG-PET/MRI coregistration was able to provide further localization over ictal EEG in 6 of the 17 children (35%).
Seven patients had combined MSI and FDG-PET/MRI coregistration findings that colocalized over a single area of the cerebral cortex. Six (86%) were seizure free after resection ().
There were no surgical mortalities, and there were no known surgical complications, including no CSF shunts, no transient or permanent motor or sensory deficit, no language deficits, and no infections.