Localized cerebellar reductions in benzodiazepine receptor density in human partial epilepsy
I. Savic and J. O. Thorell
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
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
< 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.
