The cerebral metabolic topography of spinocerebellar ataxia type 3

Sanne K Meles; Jelmer G Kok; Bauke M De Jong; Remco J Renken; Jeroen J de Vries; Jacoba M Spikman; Aaltje L Ziengs; Antoon T M Willemsen; Harm J van der Horn; Klaus L Leenders; Hubertus P H Kremer

doi:10.1016/j.nicl.2018.03.038

The cerebral metabolic topography of spinocerebellar ataxia type 3

Neuroimage Clin. 2018 Mar 29:19:90-97. doi: 10.1016/j.nicl.2018.03.038. eCollection 2018.

Affiliations

¹ Department of Neurology, University of Groningen, University Medical Center Groningen, The Netherlands. Electronic address: s.k.meles@umcg.nl.
² Department of Neurology, University of Groningen, University Medical Center Groningen, The Netherlands.
³ Neuroimaging Center, Department of Neuroscience, University of Groningen, University Medical Center Groningen, The Netherlands.
⁴ Department of Neuropsychology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
⁵ Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, The Netherlands.

Abstract

Introduction: We aimed to uncover the pattern of network-level changes in neuronal function in Spinocerebellar ataxia type 3 (SCA3).

Methods: 17 genetically-confirmed SCA3 patients and 16 controls underwent structural MRI and static resting-state [¹⁸F]‑Fluoro‑deoxyglucose Positron Emission Tomography (FDG-PET) imaging. A SCA3-related pattern (SCA3-RP) was identified using a multivariate method (scaled subprofile model and principal component analysis (SSM PCA)). Participants were evaluated with the Scale for Assessment and Rating of Ataxia (SARA) and with neuropsychological examination including tests for language, executive dysfunction, memory, and information processing speed. The relationships between SCA3-RP expression and clinical scores were explored. Voxel based morphology (VBM) was applied on MRI-T1 images to assess possible correlations between FDG reduction and grey matter atrophy.

Results: The SCA3-RP disclosed relative hypometabolism of the cerebellum, caudate nucleus and posterior parietal cortex, and relatively increased metabolism in somatosensory areas and the limbic system. This topography, which was not explained by regional atrophy, correlated significantly with ataxia (SARA) scores (ρ = 0.72; P = 0.001). SCA3 patients showed significant deficits in executive function and information processing speed, but only letter fluency correlated with SCA3-RP expression (ρ = 0.51; P = 0.04, uncorrected for multiple comparisons).

Conclusion: The SCA3 metabolic profile reflects network-level alterations which are primarily associated with the motor features of the disease. Striatum decreases additional to cerebellar hypometabolism underscores an intrinsic extrapyramidal involvement in SCA3. Cerebellar-posterior parietal hypometabolism together with anterior parietal (sensory) cortex hypermetabolism may reflect a shift from impaired feedforward to compensatory feedback processing in higher-order motor control. The demonstrated SCA3-RP provides basic insight in cerebral network changes in this disease.

Keywords: Cerebellum; FDG-PET; Networks; Neuroimaging; Spinocerebellar ataxia type 3.

MeSH terms

Adolescent
Adult
Aged
Atrophy / diagnostic imaging*
Cerebellar Ataxia / diagnostic imaging
Cerebellum / pathology*
Cerebral Cortex / pathology
Executive Function / physiology
Female
Humans
Machado-Joseph Disease / diagnostic imaging*
Magnetic Resonance Imaging* / methods
Male
Middle Aged
Young Adult