Reduced dopamine transporters without Parkinson syndrome in SCA2/3: PET findings, clinical data and post mortem histopathology

Objectives In spinocerebellar ataxia (SCA) type 2 and 3, presynaptic deficits in the striatum have been described similar to Parkinson disease (PD) while clinical features of PD were absent. We investigated this discrepancy comparing clinical features in SCA2/3 with dopaminergic PET and histopathologic findings (2nd cohort).

Methods 6 pts. with SCA2 and 14 pts. with SCA3 (median age 45y) were investigated with PET and the dopamine transporter (DaT) ligand [11C]d-threo-methylphenidate (dMP) and the D2 receptor ligand [11C]raclopride (RAC). After inj. of up to 700 MBq dMP and RAC, resp., dyn. PET was acquired for 60min. Time activity curves were obtained from putamen and occipital cortex (reference) and analyzed with Logan-GA (dMP) and SRTM (RAC). Comparison samples: 15 healthy controls (HC), 19 pts with PD. Histopathologic analyses were conducted in 4 SCA2 and 9 SCA3 pts (substantia nigra, SNc; ventral anterior nucl.; subthalamic nucl., STN; pedunculopontine nucl., PPN).

Results Parkinson's symptoms (PS) were present in 1 SCA2 and in 3 SCA3 pts of the PET sample and in only 1 pat. of the post mortem sample (SCA3). dMP PET showed reduced DaT in all SCA (BPND 0.37-0.92) without overlap (except 1 pat.) with HC (BPND 0.84-1.82) and without association with the presence of PS. 15 SCA pts. were within the range of PD (BPND < 0.82). RAC-PET showed no differences between SCA2/3 and HC. All post mortem pts. showed a degeneration of the SNc comparable to PD. In addition, all analyzed nuclei were affected, with the exception of one pat. with a normal PPN and one pat. with a normal STN. The latter was the very pat. with PS.

Conclusions We confirmed a striking discrepancy between dopaminergic deficit and a lack of PS in SCA2/3. It might be caused by additional degeneration of the STN, resembling the situation in PD under deep brain stimulation.