PT  - JOURNAL ARTICLE
AU  - Kathrin Brockmann
AU  - Matthias Reimold
AU  - Christoph Globas
AU  - Till Karsten Hauser
AU  - Uwe Walter
AU  - Hans-Jürgen Machulla
AU  - Arndt Rolfs
AU  - Ludger Schöls
TI  - PET and MRI Reveal Early Evidence of Neurodegeneration in Spinocerebellar Ataxia Type 17
AID  - 10.2967/jnumed.111.101543
DP  - 2012 Jul 01
TA  - Journal of Nuclear Medicine
PG  - 1074--1080
VI  - 53
IP  - 7
4099  - http://jnm.snmjournals.org/content/53/7/1074.short
4100  - http://jnm.snmjournals.org/content/53/7/1074.full
SO  - J Nucl Med2012 Jul 01; 53
AB  - Spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominantly inherited neurodegenerative disorder presenting with a variable phenotype including ataxia, dystonia, chorea, and parkinsonism, as well as cognitive impairment. We evaluated morphologic and functional imaging characteristics to elucidate evidence of neurodegeneration in SCA17, even in the presymptomatic stage of the disease. Methods: Nine individuals of 3 large SCA17 pedigrees, including 4 presymptomatic mutation carriers, underwent cranial 3-dimensional MRI volumetry, as well as multitracer PET with 18F-FDG, 11C-d-threo-methylphenidate, and 11C-raclopride. Healthy subjects showing no signs of a neurologic or psychiatric disease served as controls. Results: MRI volumetry revealed atrophy of the cerebellum and caudate nucleus in manifesting patients (P = 0.04 and 0.05, respectively) and in presymptomatic mutation carriers (P = 0.04 and 0.01, respectively). PET demonstrated decreased glucose metabolism in the striatum, as well as in the cuneus, cingulum, and parietal lobe, in all SCA17 patients and presymptomatic mutation carriers. In addition, PET was closely correlated with motor performance as assessed by the Scale for the Assessment and Rating of Ataxia (P = 0.037) and Unified Parkinson Disease Rating Scale (P = 0.05) and with cognitive function as assessed by the Mini-Mental Status Examination (P = 0.037). Furthermore, 11C-raclopride PET showed impairment of the postsynaptic dopaminergic compartment of the putamen and caudate nucleus not only in manifest SCA17 patients (P = 0.04 and 0.008, respectively) but also in yet-unaffected mutation carriers (P = 0.05 and 0.05, respectively). The degree of postsynaptic dopaminergic dysfunction was associated with impairment of motor performance. In contrast, significant presynaptic dopaminergic deficits assessed with 11C-d-threo-methylphenidate PET were not detected. Conclusion: MRI volumetry, as well as 11C-raclopride and 18F-FDG PET, reveal neuronal dysfunction and neurodegeneration even in the presymptomatic stage and may serve as markers for disease activity in upcoming interventional trials on SCA17.