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July 1996

Localized Cerebellar Reductions in Benzodiazepine Receptor Density in Human Partial Epilepsy

Author Affiliations

From the Division of Human Brain Research, Department of Neuroscience, Karolinska Institute, and the Department of Neurology, Sodersjukhuset (Dr Savic), and the Karolinska Pharmacy (Dr Thorell), Stockholm, Sweden.

Arch Neurol. 1996;53(7):656-662. doi:10.1001/archneur.1996.00550070094016

Background:  Previous studies suggest that the morphological substrate for cerebellar dysfunction is destruction of Purkinje cells, but disagree on whether this is caused by seizure- or drug-related toxicity. The benzodiazepine (BZ) receptor antagonist flumazenil tagged with carbon 11 is a sensitive marker of Purkinje cells.

Objective:  To investigate whether cerebellar dysfunction in partial epilepsy is related to seizures through cerebrocerebellar connections.

Design:  Positron emission tomography with [11C]flumazenil was conducted in 5 patients with frontal lobe seizures, 12 patients with mesial temporal lobe seizures, and 7 healthy men. Eight patients also had [18F]-fluorodeoxyglucose positron emission tomography. Cerebellar regions of interest were delineated using magnetic resonance imaging and a computerized anatomical brain atlas, and the epileptogenic regions were determined with a multimethod assessment.

Results:  Patients with frontal lobe seizures had a significantly reduced BZ receptor density in the anterior cerebellum contralateral to the seizure onset region (P≤.001, 2-way repeated-measure analysis of variance). Patients with mesial temporal lobe seizures had reductions in the ipsilateral (posterior and anterior) cerebellum (P≤.001 for both). No significant asymmetries were found in regional glucose metabolism.

Conclusions:  The observed distribution of BZ receptor reductions is congruent with animal experiments showing that frontal lobe projections to the cerebellum are crossed, whereas projections from mesial temporal lobe are predominantly ipsilateral. The results thus indicate a functional relation with seizures and may reflect excitotoxic lesions or specific changes in the γ-aminobutyric BZ system.

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