Topography of cerebral monoamine transporter availability in families with SCA2 mutations: a voxel-wise [123I]β-CIT SPECT analysis

The purpose of this study was to investigate the monoamine transporter status of dopamine, serotonin and norepinephrine throughout the brain in spinocerebellar ataxia type 2 (SCA2). To this end, nine patients were studied with [123I]β-CIT SPECT. Data were compared with ten age-matched healthy control subjects and ten patients with young-onset Parkinson's disease (YOPD), matched for age. Parametric SPECT images of the specific-to-non-displaceable equilibrium partition coefficient (V3''), which is proportional to the receptor density (Bmax), were generated. In order to objectively localise focal changes in β-CIT uptake throughout the brain volume without having to make an a priori hypothesis as to their location, statistical parametric mapping (SPM) was applied to SPECT images. Data clusters revealed by SPM, showing significant differences in V3'' values between groups, were transformed onto the individual V3'' image to obtain mean regional uptake values. Both SCA2 and YOPD patients showed significant decreases in striatal [123I]β-CIT SPECT uptake when compared with controls. However, in SCA2 patients, additional reductions in caudate/anterior putamen, midbrain and pons [123I]β-CIT uptake were localised with SPM. Voxel-wise analysis of [123I]β-CIT SPECT revealed more widespread decline of monoamine transporter availability in SCA2 than in YOPD, reflecting differences in the underlying pathology. We suggest that the quantification of midbrain and pons [123I]β-CIT signal is likely to improve the diagnostic accuracy in patients presenting with clinical features of both SCA2 and YOPD at initial investigation. (orig.)