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Epilepsy Surgery Outcome in Children With Tuberous Sclerosis Complex Evaluated With -[11C]Methyl-L-Tryptophan Positron Emission Tomography (PET)

Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI

Diane C. Chugani, PhD

Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, Department of Radiology, Wayne State University School of Medicine, Detroit, MI

Eishi Asano, MD, PhD

Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, Department of Neurology Children's Hospital of Michigan, Detroit Medical Center, Wayne State University School of Medicine, Detroit, MI

Csaba Juhász, MD, PhD

Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, Department of Neurology Children's Hospital of Michigan, Detroit Medical Center, Wayne State University School of Medicine, Detroit, MI

Otto Muzik, PhD

Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, Department of Radiology, Wayne State University School of Medicine, Detroit, MI

Aashit Shah, MD

Department of Neurology Children's Hospital of Michigan, Detroit Medical Center, Wayne State University School of Medicine, Detroit, MI

Jagdish Shah, MD

Department of Neurology Children's Hospital of Michigan, Detroit Medical Center, Wayne State University School of Medicine, Detroit, MI

Sandeep Sood, MD

Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI

William J. Kupsky, MD

Department of Pathology, Wayne State University School of Medicine, Detroit, MI

Thomas J. Mangner, PhD

Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, Department of Radiology, Wayne State University School of Medicine, Detroit, MI

Pulak K. Chakraborty, PhD

Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, Department of Radiology, Wayne State University School of Medicine, Detroit, MI

Harry T. Chugani, MD

Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, Department of Radiology, Wayne State University School of Medicine, Detroit, MI, Department of Neurology Children's Hospital of Michigan, Detroit Medical Center, Wayne State University School of Medicine, Detroit, MI, hchugani{at}pet.wayne.edu

Tuberous sclerosis complex is commonly associated with medically intractable seizures. We previously demonstrated that high uptake of -[¹¹C]methyl-L-tryptophan (AMT) on positron emission tomography (PET) occurs in a subset of epileptogenic tubers consistent with the location of seizure focus. In the present study, we analyzed the surgical outcome of children with tuberous sclerosis complex in relation to AMT PET results. Seventeen children (mean age 4.7 years) underwent epilepsy surgery, guided by long-term videoelectroencephalography (EEG) (including intracranial EEG in 14 cases), magnetic resonance imaging (MRI), and AMT PET. AMT uptake values of cortical tubers were measured using regions of interest delineated on coregistered MRI and were divided by the value for normal-appearing cortex to obtain an AMT uptake ratio. Based on surgical outcome data, tubers showing increased AMT uptake (uptake ratio greater than 1.00) were classified into three categories: (1) epileptogenic (tubers within an EEG-defined epileptic focus whose resection resulted in seizure-free outcome), (2) nonepileptogenic (tubers that were not resected but the patient became seizure free), or (3) uncertain (all other tubers). Increased AMT uptake was found in 30 tubers of 16 children, and 23 of these tubers (77%) were located in an EEG-defined epileptic focus. The tuber with the highest uptake was located in an ictal EEG onset region in each patient. Increased AMT uptake indicated an epileptic region not suspected by scalp EEG in four cases. Twelve children (71%) achieved seizure-free outcome (median follow-up 15 months). Based on outcome criteria, 19 of 30 tubers (63%) with increased AMT uptake were epileptogenic, and these tubers had significantly higher AMT uptake than the nonepileptogenic ones (P = .009). Tubers with at least 10% increase of AMT uptake (in nine patients) were all epileptogenic. Using a cutoff threshold of 1.02 for AMT uptake ratio provided an optimal accuracy of 83% for detecting tubers that needed to be resected to achieve a seizure-free outcome. The findings suggest that resection of tubers with increased AMT uptake is highly desirable to achieve seizure-free surgical outcome in children with tuberous sclerosis complex and intractable epilepsy. AMT PET can provide independent complementary information regarding the localization of epileptogenic regions in tuberous sclerosis complex and enhance the confidence of patient selection for successful epilepsy surgery. (J Child Neurol 2005;20:429—438).

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