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Relationship of flumazenil and glucose PET abnormalities to neocortical epilepsy surgery outcome

From the Departments of Pediatrics (Drs. Juhász, D.C. Chugani, and H.T. Chugani), Neurology (Drs. Juhász, A. Shah, J. Shah, Watson, and H.T. Chugani), Radiology (Drs. D.C. Chugani, Muzik, and H.T. Chugani), and Neurosurgery (Dr. Canady), Children’s Hospital of Michigan, Detroit Medical Center, Wayne State University School of Medicine, Detroit, MI.

Address correspondence and reprint requests to Dr. Harry T. Chugani, Pediatric Neurology/PET Center, Children’s Hospital of Michigan, 3901 Beaubien Blvd., Detroit, MI 48201; e-mail: hchugani{at}pet.wayne.edu

BACKGROUND: Cortical areas showing abnormal glucose metabolism and [¹¹C]flumazenil (FMZ) binding are commonly seen on PET scans of patients with intractable partial epilepsy, but it is unclear whether these must be totally resected to achieve seizure control.

OBJECTIVE: To analyze whether the extent of cortex showing 2-deoxy-2-[¹⁸F]fluoro-D-glucose (FDG) or FMZ PET abnormalities correlates with the outcome of resective epilepsy surgery.

METHODS: Cortical FDG and FMZ PET abnormalities in 15 young patients (mean age, 12.2 ± 7.0 years) with intractable partial epilepsy of neocortical origin were marked as regions with abnormal asymmetry using an objective semiautomated software package. These marked regions were then projected and measured on the brain surface reconstructed from the coregistered high-resolution MRI. Following cortical resection, the size of nonresected cortex with preoperative PET abnormalities was also measured (calculated separately for marked areas in the lobe of seizure onset as defined by long-term video EEG monitoring, and in remote cortical areas). Extent of preoperative PET abnormalities and postoperative nonresected cortex abnormalities on PET were correlated with outcome scores.

RESULTS: Large preoperative FMZ PET abnormalities were associated with poor outcome (r = 0.57; p = 0.025). Larger areas of nonresected cortex with preoperative FMZ PET abnormalities in the lobe of seizure onset were also associated with worse outcome in the whole group (r = 0.66; p = 0.007) as well as in patients with extratemporal resection (r = 0.73; p = 0.007), and in those with no lesion on MRI (r = 0.60; p = 0.049). Patients with seizure-free outcome had significantly smaller nonresected cortex with preoperative FMZ PET abnormalities than those who continued to have seizures (p = 0.022). No significant correlations between nonresected FDG PET abnormalities and surgical outcome were found.

CONCLUSIONS: Extensive cortical abnormalities on FMZ PET predict poor outcome in neocortical epilepsy surgery. Resection of FMZ abnormalities in the lobe of seizure onset is associated with excellent outcome even in the absence of a structural lesion. In contrast, although FDG PET abnormalities regionalized the epileptogenic area, their size was not related to the extent of epileptogenic tissue to be removed.

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