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[¹¹C]Flumazenil binding in the medial temporal lobe in patients with temporal lobe epilepsy

Correlation with hippocampal MR volumetry, T2 relaxometry, and neuropathology

From the Department of Neurology (Drs. Lamusuo, Ruottinen, and Rinne), University of Turku; A.I. Virtanen Institute (Dr. Pitkänen) and Departments of Neuroscience and Neurology (Dr. Ylinen) and Neurosurgery (Dr. Vapalahti), University of Kuopio; Departments of Neurology (Drs. Pitkänen, Jutila, Ylinen, and Kälviäinen) and Radiology, MRI Unit (Drs. Partanen and Vainio), Kuopio University Hospital; and PET Unit (Drs. Oikonen and Rinne) and Radiopharmaceutical Chemistry Laboratory (Drs. Någren and Lehikoinen), Turku PET Centre, Finland.

Address correspondence and reprint requests to Dr. Juha Rinne, Department of Neurology, University of Turku, P.O. Box 52, FIN-20521 Turku; e-mail: juha.rinne{at}pet.tyks.fi

OBJECTIVE: To detect reduced [¹¹C]flumazenil in patients with temporal lobe epilepsy (TLE) and to relate binding to histopathology.

METHODS: The authors studied 16 patients who underwent epilepsy surgery because of drug-resistant TLE using [¹¹C]flumazenil PET and quantitative MRI. In 12 patients, resected hippocampus was available for histologic analysis. [¹¹C]Flumazenil binding potential (fitted BP) was assessed with the simplified reference tissue model.

RESULTS: [¹¹C]Flumazenil fitted BP in the medial temporal lobe was reduced in all patients with abnormal hippocampal volumetry or T2 relaxometry on MRI. Fitted BP was also reduced in 46% of the patients with hippocampal volume within the normal range and in 38% of patients with less than 2 SD T2 prolongation. In all MRI-negative/PET-positive patients, the histologic analysis verified hippocampal damage. Also, [¹¹C]flumazenil fitted BP correlated with the severity of reduced hippocampal volume, T2 prolongation, and histologically assessed neuronal loss and astrogliosis.

CONCLUSION: [¹¹C]Flumazenil PET provides a useful tool for investigating the hippocampal damage in vivo even in patients with no remarkable hippocampal abnormalities on quantitative MRI.

Key words: Epilepsy—Flumazenil—MR volumetry—Neuropathology—T2 relaxometry.

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