Magnetic resonance imaging in spinocerebellar ataxias.
ABSTRACT Magnetic resonance (MR) imaging is widely used to visualize atrophic processes that occur during the pathogenesis of spinocerebellar ataxias (SCAs). T1-weighted images are utilized to rate the atrophy of cerebellar vermis, cerebellar hemispheres, pons and midbrain. Signal changes in the basal ganglia and ponto-cerebellar fibers are evaluated by T2-weighted and proton density-weighted images. However, two-dimensional (2D) images do not allow a reliable quantification of the degree of atrophy. The latter is now possible through the application of three-dimensional (3D) true volumetric methods, which should be used for research purposes. Ideally, these methods should allow automated segmentation of contrast-defined boundaries by using region growing algorithms, which can be applied successfully in structures of the posterior fossa and basal ganglia. Thin slice thickness helps to minimize partial volume effects. Whereas volumetric approaches rely on predetermined anatomical boundaries, voxel-based morphometry has been developed to determine group differences between different types of SCA (cross-sectional studies) or within one SCA entity (longitudinal studies). We will review recent results and how these methods are currently used to (i) separate sporadic and dominantly inherited forms of cerebellar ataxias; (ii) identify specific SCA genotypes; (iii) correlate patho-anatomical changes with SCA disease symptoms or severity; and (iv) visualize and estimate the rate of progression in SCA.
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ABSTRACT: During voluntary limb movements, humans exert anticipatory postural adjustments (APAs) to prevent any upcoming equilibrium disturbance that might be provoked by the limb movements. Dysfunction in generation or control of APAs is associated with postural deficits in some human patients with cerebellar damage. To examine the role of the cerebellum in APAs, we investigated a conditional transgenic mouse of spinocerebellar ataxia type 3 (SCA3Tg) that has defective cerebellar Purkinje cells. Kinematic analyses and monitoring of electromyographic activities during quadrupedal standing showed that SCA3Tg mice exhibited greater hindlimb instability than wild-type mice. This instability increased during a reaching task that required postural adjustments associated with voluntary neck movements. Normally, the activities of the hindlimb muscles are synchronized with those in the neck that are the agonists for movement of the head in this reaching task; however, in SCA3Tg mice, activities in the hindlimbs were markedly delayed compared to the neck. These observations cannot simply be explained as a secondary outcome of the muscle atrophy that occurs in SCA3Tg mice. In wild-type mice with muscle atrophy induced by immobilization of the hindlimbs, we did not find impairment of APAs. These findings suggest that the deficits in APAs during the reaching task in SCA3Tg mice were not due to muscle atrophy in the hindlimbs, but were mainly caused by cerebellar degeneration. Therefore, we conclude that the cerebellum is critically involved in APAs.Neuroscience 04/2013; · 3.12 Impact Factor
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ABSTRACT: INTRODUCTION: Spinocerebellar ataxias 1, 2 and 3 (SCA1, SCA2 and SCA3) are CAG repeat disorders. The prevalence of changes in the cortical excitability and central motor conduction time (CMCT) in these disorders is largely unknown, and there are few studies which have compared these findings in the subtypes of SCA. The objectives of this study were to measure the cortical resting motor threshold (RMT) and CMCT using transcranial magnetic stimulation in patients with SCA1, SCA2, and SCA3. METHODS: The subjects of this study were 32 genetically confirmed patients with SCA (SCA1 = 15, SCA2 = 11, SCA3 = 6). Transcranial magnetic stimulation (TMS) was performed using a figure-of-eight coil attached to Magstim 200 stimulator. Motor evoked potentials were recorded from first dorsal interosseous at rest. RMT was determined using standard techniques and the CMCT by 'F' wave method. Comparison was made with data from 32 healthy controls. RESULTS: Compared to controls, the patients with SCA had significantly higher mean RMT as well as CMCT (RMT: 49.9 ± 9.1 vs. 41.5 ± 6.6, p < 0.0001; CMCT: 7.7 ± 2.3 ms vs. 4.8 ± 0.6 ms; p < 0.0001). When compared separately with the controls, while all the three subtypes of SCAs had significantly prolonged CMCT, only SCA1 and SCA3, but not SCA2 had significantly greater RMT. RMT and CMCT between patients with SCA2 and SCA3, and between SCA1 and SCA3 did not differ significantly, while SCA1 had significantly higher RMT and CMCT than SCA2. CONCLUSIONS: Patients with SCA have reduced cortical excitability and prolonged central motor conduction time, which was most evident in SCA1 and least in SCA2.Parkinsonism & Related Disorders 12/2012; · 3.27 Impact Factor
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ABSTRACT: Spinocerebellar ataxia type 7 (SCA7) is an autosomal-dominant neurodegenerative disorder characterized by progressive ataxia and retinal dystrophy. It is caused by a CAG trinucleotide expansion in the ataxin7 gene. Anatomical studies have shown severe cerebellar degeneration and region-specific neocortical atrophy in SCA7 patients. However, the impact of the neurodegeneration on the functional integration of the remaining tissue is still unknown. The aim of this study was to examine functional connectivity abnormalities in areas with significant gray matter atrophy in SCA7 patients and their relationship with number of CAG repeats. Using a combination of voxel-based morphometry and resting-state fMRI, we studied 26 genetically confirmed SCA7 patients and aged-matched healthy controls. In SCA7 patients we found reduced functional interaction between the cerebellum and the middle and superior frontal gyri, disrupted functional connectivity between the visual and motor cortices, and increased functional coordination between atrophied areas of the cerebellum and a range of visual cortical areas compared with healthy controls. The degree of mutation expansion showed a negative effect on both the functional interaction between the right anterior cerebellum and the left superior frontal gyrus and the connectivity between the right anterior cerebellum and left parahippocampal gyrus. We found abnormal functional connectivity patterns, including both hypo- and hyperconnectivity, compared with controls. These abnormal patterns show reasonable association with the severity of gene mutation. Our findings suggest that aberrant changes are prevalent in both motor and visual systems, adding significantly to our understanding of the pathophysiology of SCA7. © 2013 Movement Disorder Society.Movement Disorders 08/2013; · 4.56 Impact Factor