Imaging epileptogenic tubers in children with tuberous sclerosis complex usingα‐[¹¹C]Methyl‐L‐tryptophan positron emission tomography

Abstract

Several reports have indicated that cortical resection is effective in alleviating intractable epilepsy in children with tuberous sclerosis complex (TSC). Because of the multitude of cortical lesions, however, identifying the epileptogenic tuber(s) is difficult and often requires invasive intracranial electroencephalographic (EEG) monitoring. As increased concentrations of serotonin and serotonin-immunoreactive processes have been reported in resected human epileptic cortex, we used alpha-[11C]methyl-L-tryptophan ([11C]AMT) positron emission tomography (PET) to test the hypothesis that serotonin synthesis is increased interictally in epileptogenic tubers in patients with TSC. Nine children with TSC and epilepsy, aged 1 to 9 years (mean, 4 years 1 month), were studied. All children underwent scalp video-EEG monitoring, PET scans of glucose metabolism and serotonin synthesis, and EEG monitoring during both PET studies. [11C]AMT scans were coregistered with magnetic resonance imaging and with glucose metabolism scans. Whereas glucose metabolism PET showed multifocal cortical hypometabolism corresponding to the locations of tubers in all 9 children, [11C]AMT uptake was increased in one tuber (n=3), two tubers (n=3), three tubers (n=1), and four tubers (n=1) in 8 of the 9 children. All other tubers showed decreased [11C]AMT uptake. Ictal EEG data available in 8 children showed seizure onset corresponding to foci of increased [11C]AMT uptake in 4 children (including 2 with intracranial EEG recordings). In 2 children, ictal EEG was nonlocalizing, and in 1 child there was discordance between the region of increased [11C]AMT uptake and the region of ictal onset on EEG. The only child whose [11C]AMT scan showed no regions of increased uptake had a left frontal seizure focus on EEG; however, at the time of his [11C]AMT PET scan, his seizures had come under control. [11C]AMT PET may be a powerful tool in differentiating between epileptogenic and nonepileptogenic tubers in patients with TSC.

Epilepsy surgery in tuberous sclerosis: a review

“…Epileptogenic tubers have been found to have increased AMT uptake compared with surrounding cortex and nonepileptogenic tubers. 2,10 In an analysis of 17 patients selected for resection, AMT-PET studies were included in the preoperative evaluation, and 77% of the cortical tubers with increased AMT uptake were within the EEG-defined region. Of those patients with a single tuber that exhibited AMT uptake, the tuber was always within the electroencephalographic region of interest.…”

In Vivo Uptake and Metabolism of α-[11C]Methyl-l-Tryptophan in Human Brain Tumors

“…Subsequent studies using AMT PET in children with tuberous sclerosis and epilepsy have shown focal accumulation of AMT in epileptogenic (but not in nonepileptogenic) tubers (Chugani et al, 1998a;Asano et al, 2000;Fedi et al, 2003); this accumulation is likely the result of epileptogenic tubers containing increased levels of quinolinic acid, which is a convulsant and neurotoxic metabolite of the kynurenine pathway (Chugani et al, 1998b;Chugani and Muzik, 2000). Subsequent studies in patients with intractable seizures of various etiologies, including malformations of cortical development, found that increased AMT was highly specific for epileptogenic cortical regions and is a useful method for presurgical evaluation of some patients with intractable epilepsy (Asano et al, 2000;Fedi et al, 2001;Juhász et al, 2003).…”

α-[ 11 C]-Methyl- l -tryptophan–PET in 191 patients with tuberous sclerosis complex

“…11 We previously reported, in a relatively small number of patients with TSC, that a-[ 11 C]-methyl-Ltryptophan (AMT)-PET scanning may differentiate between epileptogenic tubers (high AMT uptake) and nonepileptogenic tubers (low AMT uptake) and that the location of high AMT uptake corresponds to the seizure focus on EEG. 6,12,13 …”

“…Our results are consistent with previous smaller studies demonstrating that epileptogenic tubers frequently show increased AMT uptake. 6,12,13,21 The incremental value of AMT-PET over standard investigations is illustrated by i) 10 of 17 patients (58%) with nonlateralizing ictal scalp EEG but lateralized increased AMT-PET uptake, and ii) 28 of 68 patients (41%) whose ictal EEG was lateralizing but nonlocalizing in whom AMT-PET provided localizing information to guide placement of intracranial electrodes. Our findings suggest that AMT-PET could provide additional lateralization/localization data to the standard modalities in the pre-epilepsy surgical evaluation of patients with TSC.…”

“…11 We previously reported, in a relatively small number of patients with TSC, that a-[ 11 C]-methyl-Ltryptophan (AMT)-PET scanning may differentiate between epileptogenic tubers (high AMT uptake) and nonepileptogenic tubers (low AMT uptake) and that the location of high AMT uptake corresponds to the seizure focus on EEG. 6,12,13 The present study was performed in 191 patients with TSC and intractable epilepsy who underwent AMT-PET during epilepsy surgery evaluation to address whether i) presence of increased AMT uptake is related to duration of seizure intractability, ii) increased AMT uptake in epileptogenic tubers is related to specific TSC gene mutations, and iii) there is concordance between areas of increased AMT uptake and seizure lateralization/localization on scalp EEG.…”