Cortical thickness, stance control, and arithmetic skill: An exploratory study in premanifest Huntington disease. (June 2018)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Parkinsonism & related disorders. Volume 51(2018)
• Page Start: 17
• Page End: 23
• Publication Date: 2018-06
• Subjects: Premanifest mutation carrier -- Cortical thickness -- Striatal volume -- Posturography -- Arithmetic task -- Burden score; Parkinson's disease -- Periodicals; Movement disorders -- Periodicals; Movement Disorders -- Periodicals; Nerve Degeneration -- Periodicals; Nervous System Diseases -- Periodicals; Parkinson Disease -- Periodicals; Tremor -- Periodicals; Parkinson, Maladie de -- Périodiques; Parkinson's disease; 616.833
• DOI: 10.1016/j.parkreldis.2018.02.033
• Languages: English
• ISSNs: 1353-8020

Abstract

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. Highlights: Neurodegeneration in Huntington disease may be traced before symptom manifestation. A multimodal protocol for phenotypic study of premanifest carriers is proposed. Striatal atrophy and occipital thinning is confirmed in close-to-onset carriers. Posturography shows stance control deficits in close-to-onset carriers. Calculation subtraction test shows defective combinatorial rule application.