I. Savic et Jo. Thorell, LOCALIZED CEREBELLAR REDUCTIONS IN BENZODIAZEPINE RECEPTOR DENSITY INHUMAN PARTIAL EPILEPSY, Archives of neurology, 53(7), 1996, pp. 656-662
Background: Previous studies suggest that the morphological substrate
for cerebellar dysfunction is destruction of Purkinje cells, but disag
ree on whether this is caused by seizure- or drug-related toxicity. Th
e benzodiazepine (BZ) receptor antagonist flumazenil tagged with carbo
n 11 is a sensitive marker of Purkinje cells. Objective: To investigat
e whether cerebellar dysfunction in partial epilepsy is related to sei
zures through cerebrocerebellar connections. Design: Positron emission
tomography with [C-11]flumazenil conducted in 5 patients with frontal
lobe seizures, 12 patients with mesial temporal lobe seizures, and 7
healthy men. Eight patients also had [F-18]fluorodeoxyglucose positron
emission tomography. Cerebellar regions of interest were delineated u
sing magnetic resonance imaging and a computerized anatomical brain at
las, and the epileptogenic regions were determined with a multimethod
assessment. Results: Patients with frontal lobe seizures had a signifi
cantly reduced BZ receptor density in the anterior cerebellum contrala
teral to the seizure onset region (P less than or equal to.001, 2-way
repeated-measure analysis of variance). Patients with mesial temporal
lobe seizures had reductions in the ipsilateral (posterior and anterio
r) cerebellum (P less than or equal to.001 for both). No significant a
symmetries were found in regional glucose metabolism. Conclusions: The
observed distribution of BZ receptor reductions is congruent with ani
mal experiments showing that frontal lobe projections to the cerebellu
m are crossed, whereas projections from mesial temporal lobe are predo
minantly ipsilateral. The results thus indicate a functional relation
with seizures and may reflect excitotoxic lesions or specific changes
in the gamma-aminobutyric BZ system.