Parahippocampal gray matter alterations in Spinocerebellar Ataxia Type 2 identified by voxel based morphometry

Mercadillo, Roberto E.; Gálvez, Víctor; Dı́az, Rosalinda; Hernandez‐Castillo, Carlos R.; Campos‐Romo, Aurelio; Boll, Marie‐Catherine; Pasaye, Erick H.; Fernández-Ruíz, Juan

doi:10.1016/j.jns.2014.09.018

Cited by 31 publications

(39 citation statements)

References 88 publications

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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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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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“…After initially searching, the titles and abstracts with the search strategy, eight VBM studies (Brenneis et al., 2003; D'Agata, Caroppo, Boghi et al., 2011; Goel et al., 2011; Hernandez‐Castillo et al., 2015; Jacobi et al., 2013; Mercadillo et al., 2014; Nave, Ginestroni, Tessa, Cosottini et al., 2008; Nave, Ginestroni, Tessa, Salvatore et al., 2008) were identified as potentially meeting the inclusion criteria. A detailed review of the full text was then performed, and two studies (Hernandez‐Castillo et al., 2015; Jacobi et al., 2013) were excluded due to absence of stereotactic coordinates.…”

Section: Resultsmentioning

confidence: 99%

“…All these findings above indicated that the atrophy of lobule VI/VII and Crus I/II detected in the current meta‐analysis accounted for cognitive impairments in SCA2. However, only one study did report the cognition impairment of SCA2 patients (Mercadillo et al., 2014). …”

Section: Discussionmentioning

confidence: 99%

“…Voxel‐based morphometry (VBM), a processing technique of magnetic resonance imaging (MRI) that can detect regional morphological changes in the whole brain, has been commonly used to evaluate gray matter (GM) and white matter (WM) volume abnormalities in SCA2 patients (Brenneis, Bosch, Schocke, Wenning, & Poewe, 2003; D'Agata, Caroppo, Boghi et al., 2011; Goel et al., 2011; Hernandez‐Castillo et al., 2015; Jacobi et al., 2013; Mercadillo et al., 2014; Nave, Ginestroni, Tessa, Cosottini et al., 2008; Nave, Ginestroni, Tessa, Salvatore et al., 2008; Olivito et al., 2018). However, the findings of these studies are variable and conflicting.…”

Section: Introductionmentioning

confidence: 99%

“…Some studies reported regional cerebral atrophy in frontal, parietal, and temporal lobes (Brenneis et al., 2003; Goel et al., 2011; Hernandez‐Castillo et al., 2015; Mercadillo et al., 2014; Nave, Ginestroni, Tessa, Salvatore et al., 2008), while some studies found brain volume reductions limited in the infratentorial regions such as cerebellum and pons (D'Agata, Caroppo, Boghi et al., 2011; Jacobi et al., 2013; Nave, Ginestroni, Tessa, Cosottini et al., 2008; Olivito et al., 2018). The atrophy of mesencephalon and thalamus was also detected in a few studies (Brenneis et al., 2003; Nave, Ginestroni, Tessa, Salvatore et al., 2008), and significant parahippocampal atrophy was demonstrated in one study (Mercadillo et al., 2014). Although all of these neuroimaging studies reported GM and WM volume reductions in the cerebellum in SCA2, the neurological hallmark for SCAs, the predominant side and regions of cerebellum involved were inconsistent.…”

Section: Introductionmentioning

confidence: 99%

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Voxel‐based meta‐analysis of gray and white matter volume abnormalities in spinocerebellar ataxia type 2

et al. 2018

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ObjectiveTo identify the consistent findings from the whole‐brain voxel‐based morphometry (VBM) studies on spinocerebellar ataxia type 2 (SCA2).MethodsThe whole‐brain VBM studies comparing SCA2 patients and healthy controls (HCs) were systematically searched in PubMed, Embase databases from January 2000 to June 2017. The coordinates with significant differences in gray matter (GM) and white matter (WM) between SCA2 patients and HCs were extracted separately from each cluster. A meta‐analysis was performed using anisotropic effect size‐based signed differential mapping (AES‐SDM) software.ResultsA total of five studies with 65 SCA2 patients and 124 HCs were included in the GM meta‐analysis. Four of the five studies with 50 SCA2 patients and 109 HCs were included in the WM meta‐analysis. Significant and consistent GM volume reductions were detected in bilateral cerebellar hemispheres, cerebellar vermis, the right fusiform gyrus, the right parahippocampal gyrus, and the right lingual gyrus. The WM volume reductions were observed in bilateral cerebellar hemispheres, cerebellar vermis, middle cerebellar peduncles, pons, and bilateral cortico‐spinal projections. The findings of the study remained largely unchanged in jackknife sensitivity analysis.ConclusionsThe consistent findings from our meta‐analysis showed that GM volume reductions in SCA2 patients were not limited in cerebellum while significant WM volume reductions widely existed in cerebellum and pyramidal system. The findings provide morphological basis for further studies on SCA2.

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Modifications of resting state networks in spinocerebellar ataxia type 2

Cocozza

Saccà²,

Cervo

et al. 2015

Movement Disorders

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Parahippocampal gray matter alterations in Spinocerebellar Ataxia Type 2 identified by voxel based morphometry

Cited by 31 publications

References 88 publications

Brain atrophy measures in preclinical and manifest spinocerebellar ataxia type 2

Brain atrophy measures in preclinical and manifest spinocerebellar ataxia type 2

Voxel‐based meta‐analysis of gray and white matter volume abnormalities in spinocerebellar ataxia type 2

Modifications of resting state networks in spinocerebellar ataxia type 2

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