Localized cerebellar reductions in benzodiazepine receptor density in human partial epilepsy.
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.


METHODS
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 < or = .001), 2-way repeated-measure analysis of variance). Patients with mesial temporal lobe seizures had reductions in the ipsilateral (posterior and anterior) cerebellum (P < or = .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 tht frontal lobe projections to the cerebellum are crossed, whereas projections from mesial temporal loe are predominantly ipsilateral. The results thus indicate a functional relation with seizures and may reflect excitotoxic lesions or specific changes in the gamma-aminobutyric BZ system.
Savic
I
I
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Thorell
J O
JO
D000328:Adult; D002531:Cerebellum / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003847:Deoxyglucose / Q000031:analogs & derivatives; D004828:Epilepsies, Partial / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism; D017034:Epilepsy, Frontal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D004833:Epilepsy, Temporal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D005442:Flumazenil; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011963:Receptors, GABA-A / Q000378:metabolism*; D012016:Reference Values; D014055:Tomography, Emission-Computed
D005462:Fluorine Radioisotopes; D011963:Receptors, GABA-A; D019788:Fluorodeoxyglucose F18; D005442:Flumazenil; D003847:Deoxyglucose