Cortical thickness, stance control, and arithmetic skill: An exploratory study in premanifest Huntington disease

Lorenzo Nanetti, Valeria Elisa Contarino, Anna Castaldo, Lidia Sarro, Anne Catherine Bachoud-Levi, Maria Giavazzi, Serena Frittoli, Andrea Ciammola, Elena Rizzo, Cinzia Gellera, Maria Grazia Bruzzone, Franco Taroni, Marina Grisoli, Caterina Mariotti

Research output: Contribution to journalArticle

Abstract

Background: Huntington disease (HD) is an inherited neurodegenerative disorder most commonly manifesting in adulthood. Identification of biomarkers tracking neurodegeneration before the onset of motor symptoms is important for future interventional studies. Our study aimed to contribute in the phenotypic characterization of the premanifest HD phase. Methods: 28 premanifest subjects (preHD), 25 age-matched controls, and 12 manifest HD patients were enrolled for the study. The participants underwent a multimodal protocol including cognitive evaluations, arithmetic ability test, posturography, composite cerebellar functional test (CCFS), and brain 3T-MRI. PreHD were divided at the group median for predicted years to expected onset into “far-from-onset” (>15 years, PreHD-far), and “close-to-onset” (≤15 years, preHD-close). Basal ganglia volumes and cortical thickness were computed using FreeSurfer. Results: PreHD-close showed significantly lower scores than controls in Symbol Digit Modalities Test (p = 0.017), Arithmetic subtraction task (p = 0.04), and MMSE (p < 0.006). At posturography, preHD-close showed increased sway velocity (<0.04) and distance (p < 0.02) compared to controls. PreHD-close had reduced striatum and globus pallidus volumes and left occipital cortical thinning compared to controls. Compared to PreHD far-from-onset, PreHD-close showed bilateral cortical thinning in occipital and parahippocampal regions, inversely correlating with burden score and prognostic index for HD. CCFS only differed between controls and manifest HD. PreHD far-from-onset did not show significant differences in comparison with controls. Conclusions: We confirmed that quantitative brain MRI represents a valid biomarker of neurodegeneration in preHD. Posturography and Arithmentic tests seem promising tools for detecting early changes in premanifest HD, but need to be further confirmed in large cohorts.

Original languageEnglish
Pages (from-to)17-23
Number of pages7
JournalParkinsonism and Related Disorders
Volume51
DOIs
Publication statusPublished - Jun 1 2018

Fingerprint

Huntington Disease
Biomarkers
Occipital Lobe
Globus Pallidus
Aptitude
Brain
Basal Ganglia
Neurodegenerative Diseases

Keywords

  • Arithmetic task
  • Burden score
  • Cortical thickness
  • Posturography
  • Premanifest mutation carrier
  • Striatal volume

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

Cortical thickness, stance control, and arithmetic skill : An exploratory study in premanifest Huntington disease. / Nanetti, Lorenzo; Contarino, Valeria Elisa; Castaldo, Anna; Sarro, Lidia; Bachoud-Levi, Anne Catherine; Giavazzi, Maria; Frittoli, Serena; Ciammola, Andrea; Rizzo, Elena; Gellera, Cinzia; Bruzzone, Maria Grazia; Taroni, Franco; Grisoli, Marina; Mariotti, Caterina.

In: Parkinsonism and Related Disorders, Vol. 51, 01.06.2018, p. 17-23.

Research output: Contribution to journalArticle

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abstract = "Background: Huntington disease (HD) is an inherited neurodegenerative disorder most commonly manifesting in adulthood. Identification of biomarkers tracking neurodegeneration before the onset of motor symptoms is important for future interventional studies. Our study aimed to contribute in the phenotypic characterization of the premanifest HD phase. Methods: 28 premanifest subjects (preHD), 25 age-matched controls, and 12 manifest HD patients were enrolled for the study. The participants underwent a multimodal protocol including cognitive evaluations, arithmetic ability test, posturography, composite cerebellar functional test (CCFS), and brain 3T-MRI. PreHD were divided at the group median for predicted years to expected onset into “far-from-onset” (>15 years, PreHD-far), and “close-to-onset” (≤15 years, preHD-close). Basal ganglia volumes and cortical thickness were computed using FreeSurfer. Results: PreHD-close showed significantly lower scores than controls in Symbol Digit Modalities Test (p = 0.017), Arithmetic subtraction task (p = 0.04), and MMSE (p < 0.006). At posturography, preHD-close showed increased sway velocity (<0.04) and distance (p < 0.02) compared to controls. PreHD-close had reduced striatum and globus pallidus volumes and left occipital cortical thinning compared to controls. Compared to PreHD far-from-onset, PreHD-close showed bilateral cortical thinning in occipital and parahippocampal regions, inversely correlating with burden score and prognostic index for HD. CCFS only differed between controls and manifest HD. PreHD far-from-onset did not show significant differences in comparison with controls. Conclusions: We confirmed that quantitative brain MRI represents a valid biomarker of neurodegeneration in preHD. Posturography and Arithmentic tests seem promising tools for detecting early changes in premanifest HD, but need to be further confirmed in large cohorts.",
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T2 - An exploratory study in premanifest Huntington disease

AU - Nanetti, Lorenzo

AU - Contarino, Valeria Elisa

AU - Castaldo, Anna

AU - Sarro, Lidia

AU - Bachoud-Levi, Anne Catherine

AU - Giavazzi, Maria

AU - Frittoli, Serena

AU - Ciammola, Andrea

AU - Rizzo, Elena

AU - Gellera, Cinzia

AU - Bruzzone, Maria Grazia

AU - Taroni, Franco

AU - Grisoli, Marina

AU - Mariotti, Caterina

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