MRI Shows a Region-Specific Pattern of Atrophy in Spinocerebellar Ataxia Type 2

Jung, Brian C.; Choi, Soo In; Du, Annie; Cuzzocreo, Jennifer L.; Ying, Howard S.; Landman, Bennett A.; Perlman, Susan; Baloh, Robert W.; Zee, David S.; Toga, Arthur W.; Prince, Jerry L.; Ying, Sarah H.

doi:10.1007/s12311-011-0308-8

Cited by 47 publications

(50 citation statements)

References 29 publications

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“…SCA2 showed significant atrophy of the CM, middle lobe, and superior vermis with relative sparing of the posterior-inferior regions of the cerebellum. The above results were consistent with the observations reported in [24, 25]. For SCA3, significant atrophy was found in the CM region and near significant atrophy was found in the anterior lobes.…”

Section: Methodssupporting

confidence: 93%

Automated cerebellar lobule segmentation with application to cerebellar structural analysis in cerebellar disease

Yang

Bogovic

et al. 2016

NeuroImage

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The cerebellum plays an important role in both motor control and cognitive function. Cerebellar function is topographically organized and diseases that affect specific parts of the cerebellum are associated with specific patterns of symptoms. Accordingly, delineation and quantification of cerebellar sub-regions from magnetic resonance images are important in the study of cerebellar atrophy and associated functional losses. This paper describes an automated cerebellar lobule segmentation method based on a graph cut segmentation framework. Results from multi-atlas labeling and tissue classification contribute to the region terms in the graph cut energy function and boundary classification contributes to the boundary term in the energy function. A cerebellar parcellation is achieved by minimizing the energy function using the α-expansion technique. The proposed method was evaluated using a leave-one-out cross-validation on 15 subjects including both healthy controls and patients with cerebellar diseases. Based on reported Dice coefficients, the proposed method outperforms two state-of-the-art methods. The proposed method was then applied to 77 subjects to study the region-specific cerebellar structural differences in three spinocerebellar ataxia (SCA) genetic subtypes. Quantitative analysis of the lobule volumes show distinct patterns of volume changes associated with different SCA subtypes consistent with known patterns of atrophy in these genetic subtypes.

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Section: Methodssupporting

confidence: 93%

Automated cerebellar lobule segmentation with application to cerebellar structural analysis in cerebellar disease

Yang

Bogovic

et al. 2016

NeuroImage

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“…Magnetic resonance imaging (MRI) data are sparse and often comprise only small sample sizes in this orphan disease. The available structural MRI data have so far confirmed the neuropathological findings showing atrophy of the brainstem and cerebellum,6, 7, 8 but there is also some evidence for cortical brain atrophy and microstructural abnormalities in SCA2 patients 9, 10, 11, 12, 13. For preclinical SCA2 mutation carriers, only two structural MRI studies exist.…”

Section: Introductionmentioning

confidence: 68%

Brain atrophy measures in preclinical and manifest spinocerebellar ataxia type 2

Reetz

Rodríguez‐Labrada²,

Dogan

et al. 2018

Ann Clin Transl Neurol

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ObjectiveSpinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited neurodegenerative disease mainly affecting the cerebellum and brainstem. In this Cuban‐German research collaboration, we aimed to characterize atrophy patterns and associations with clinical measures in preclinical and manifest SCA2.MethodsIn this study, 16 nonmanifest SCA2 mutation carriers, 26 manifest patients with SCA2, and 18 healthy control subjects underwent magnetic resonance imaging, as well as genetic and clinical characterization including assessment of ataxia (Scale for the Assessment and Rating of Ataxia) and saccade velocity in Cuba were enrolled. Semiautomated quantitative volumetry of the cerebellum and brainstem, subdivided into the medulla oblongata, the pontine brainstem, and mesencephalon was performed. Additionally, the anteroposterior diameter of the pontine brainstem was measured.ResultsAnalysis of volumetric data revealed degeneration of the cerebellum and brainstem, in particular of pontine volumes and the anteroposterior diameter of the pons, in both manifest SCA2 patients and individuals at risk for SCA2 compared to controls. Comparing patients with nonataxic preclinical SCA2 mutation carriers, we found more pronounced reductions of the pontine brainstem and cerebellum in manifest SCA2. Volumetric data further showed associations with CAG repeat length and predicted age of onset in preclinical SCA2 individuals, and by trend with ataxia signs in patients. Although saccade velocity was associated with reduction in the pontine brainstem in preclinical and manifest SCA2, reduced ability to suppress interfering stimuli measured by the Stroop task was related to cerebellar volume loss in patients.InterpretationPreclinical SCA2 mutation carriers exhibit brain abnormalities, which could be targeted as surrogate parameters for disease progression and in future preventive trials.

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“…25 In contrast, extrapolation of cross-sectional data from symptomatic SCA2 patients in another study suggested atrophy of both cerebellum and pons occurring as early as 7 years before onset of symptoms. 26 This pattern of degeneration seemed to be lobule-specific, affecting certain cerebellar subregions and sparing others. This finding of region specificity was supported by Jacobi and coworkers, 12 who demonstrated selective loss of gray matter in lobules V and VI and, additionally, reduced brainstem volumes in preclinical SCA2 carriers.…”

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confidence: 97%

The preclinical stage of spinocerebellar ataxias

et al. 2015

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The autosomal dominant spinocerebellar ataxias (SCAs) are a heterogeneous group of degenerative diseases of the cerebellum and connected regions. The discovery of various SCA genes and the subsequent possibility of predictive testing currently allow a genetic diagnosis to be established years or even decades before the actual appearance of ataxia symptoms. A growing body of evidence, however, indicates that this preclinical stage is subject to the earliest pathophysiologic changes. This review article comprehensively summarizes the studies conducted in preclinical carriers of a mutation in one of the SCA genes. From these data, it can indeed be concluded that the preclinical phase in SCA is already characterized by detectable central and peripheral nervous system changes, which are reflected by subtle abnormalities during a careful clinical examination, changes in structural and functional brain imaging, abnormal neurophysiologic measurements, and/or altered motor learning paradigms. As these may be compensated for a long time, ataxia symptoms probably only appear after a certain threshold of dysfunction or degeneration has been exceeded. Detailed knowledge of this disease stage is of particular relevance for a better understanding of the pathogenesis of SCAs, will allow us to determine the optimal point in time for interventions in future therapeutic trials, and points to objective, valid biomarkers to assess disease progression. Further studies will benefit from a consensus-based definition of the preclinical stage, from using one and the same validated ataxia rating scale with one fixed cutoff value, and from applying similar mathematical models to calculate time to predicted disease onset.

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MRI Shows a Region-Specific Pattern of Atrophy in Spinocerebellar Ataxia Type 2

Cited by 47 publications

References 29 publications

Automated cerebellar lobule segmentation with application to cerebellar structural analysis in cerebellar disease

Automated cerebellar lobule segmentation with application to cerebellar structural analysis in cerebellar disease

Brain atrophy measures in preclinical and manifest spinocerebellar ataxia type 2

The preclinical stage of spinocerebellar ataxias

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