Spinocerebellar ataxia type 3, spinocerebellar ataxia type 6 and Friedreich's ataxia
are common hereditary ataxias. Different patterns of atrophy of the cerebellar cortex
are well known. Data on cerebellar nuclei are sparse. Whereas cerebellar nuclei have
long been thought to be preserved in spinocerebellar ataxia type 6, histology shows
marked atrophy of the nuclei in Friedreich's ataxia and spinocerebellar ataxia type
3. In the present study susceptibility weighted imaging was used to assess atrophy
of the cerebellar nuclei in patients with spinocerebellar ataxia type 6 (n = 12, age
range 41-76 years, five female), Friedreich's ataxia (n = 12, age range 21-55 years,
seven female), spinocerebellar ataxia type 3 (n = 10, age range 34-67 years, three
female), and age- and gender-matched controls (total n = 23, age range 22-75 years,
10 female). T1-weighted magnetic resonance images were used to calculate the volume
of the cerebellum. In addition, ultra-high field functional magnetic resonance imaging
was performed with optimized normalization methods to assess function of the cerebellar
cortex and nuclei during simple hand movements. As expected, the volume of the cerebellum
was markedly reduced in spinocerebellar ataxia type 6, preserved in Friedreich's ataxia,
and mildy reduced in spinocerebellar ataxia type 3. The volume of the cerebellar nuclei
was reduced in the three patient groups compared to matched controls (P-values < 0.05;
two-sample t-tests). Atrophy of the cerebellar nuclei was most pronounced in spinocerebellar
ataxia type 6. On a functional level, hand-movement-related cerebellar activation
was altered in all three disorders. Within the cerebellar cortex, functional magnetic
resonance imaging signal was significantly reduced in spinocerebellar ataxia type
6 and Friedreich's ataxia compared to matched controls (P-values < 0.001, bootstrap-corrected
cluster-size threshold; two-sample t-tests). The difference missed significance in
spinocerebellar ataxia type 3. Within the cerebellar nuclei, reductions were significant
when comparing spinocerebellar ataxia type 6 and Friedreich's ataxia to matched controls
(P < 0.01, bootstrap-corrected cluster-size threshold; two-sample t-tests). Susceptibility
weighted imaging allowed depiction of atrophy of the cerebellar nuclei in patients
with Friedreich's ataxia and spinocerebellar ataxia type 3. In spinocerebellar ataxia
type 6, pathology was not restricted to the cerebellar cortex but also involved the
cerebellar nuclei. Functional magnetic resonance imaging data, on the other hand,
revealed that pathology in Friedreich's ataxia and spinocerebellar ataxia type 3 is
not restricted to the cerebellar nuclei. There was functional involvement of the cerebellar
cortex despite no or little structural changes.