MRI evidence of cerebellar and extraocular muscle atrophy differently contributing to eye movement abnormalities in SCA2 and SCA28 diseases

Letterio Salvatore Politi, Stefania Bianchi Marzoli, Claudia Godi, Marta Panzeri, P. Ciasca, Gianluca Brugnara, Anna Castaldo, Daniela Di Bella, Franco Taroni, Lorenzo Nanetti, Caterina Mariotti

Research output: Contribution to journalArticle

Abstract

PURPOSE. Spinocerebellar ataxias type 2 and 28 (SCA2, SCA28) are autosomal dominant disorders characterized by progressive cerebellar and oculomotor abnormalities. We aimed to investigate cerebellar, brainstem, and extraocular muscle involvement in the mitochondrial SCA28 disease compared with SCA2. METHODS. We obtained orbital and brain 1.5 T-magnetic resonance images (MRI) in eight SCA28 subjects, nine SCA2, and nine age-matched healthy subjects. Automated segmentation of cerebellum and frontal lobe was performed using Freesurfer software. Manual segmentations for midbrain, pons, and extraocular muscles were performed using OsiriX. RESULTS. Eye movement abnormalities in SCA2 subjects were characterized by slow horizontal saccades. Subjects with SCA28 variably presented hypometric saccades, saccadic horizontal pursuit, impaired horizontal gaze holding, and superior eyelid ptosis. Quantitative brain MRI demonstrated that cerebellar and pons volumes were significantly reduced in both SCA2 and SCA28 subjects compared with controls (P <0.03), and in SCA2 subjects compared with SCA28 (P <0.01). Midbrain and frontal lobe volumes were also significantly reduced in SCA2 compared to controls (P <0.03), whereas these volumes did not differ between SCA2 and SCA28 and between SCA28 and control subjects. The extraocular muscle areas were 37% to 48% smaller in SCA28 subjects compared with controls (P <0.002), and 14% to 36% smaller compared with SCA2 subjects (P <0.03). Extraocular muscle areas did not differ between SCA2 and controls. CONCLUSIONS. Our MRI findings support the hypothesis of different cerebellar and extraocular myopathic contributions in the eye movement abnormalities in SCA2 and SCA28 diseases. In SCA28, a myopathic defect selectively involving the extraocular muscles supports a specific impairment of mitochondrial energy metabolism.

Original languageEnglish
Pages (from-to)2714-2720
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume57
Issue number6
DOIs
Publication statusPublished - May 1 2016

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Oculomotor Muscles
Eye Abnormalities
Muscular Atrophy
Eye Movements
Magnetic Resonance Spectroscopy
Saccades
Pons
Frontal Lobe
Mesencephalon
Blepharoptosis
Spinocerebellar Ataxias
Mitochondrial Diseases
Brain
Cerebellum
Energy Metabolism
Brain Stem
Healthy Volunteers
Software

Keywords

  • Cerebellum
  • Mitochondrial disorders
  • Ocular motility
  • Spinocerebellar ataxia
  • Volumetric mri

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

MRI evidence of cerebellar and extraocular muscle atrophy differently contributing to eye movement abnormalities in SCA2 and SCA28 diseases. / Politi, Letterio Salvatore; Bianchi Marzoli, Stefania; Godi, Claudia; Panzeri, Marta; Ciasca, P.; Brugnara, Gianluca; Castaldo, Anna; Di Bella, Daniela; Taroni, Franco; Nanetti, Lorenzo; Mariotti, Caterina.

In: Investigative Ophthalmology and Visual Science, Vol. 57, No. 6, 01.05.2016, p. 2714-2720.

Research output: Contribution to journalArticle

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T1 - MRI evidence of cerebellar and extraocular muscle atrophy differently contributing to eye movement abnormalities in SCA2 and SCA28 diseases

AU - Politi, Letterio Salvatore

AU - Bianchi Marzoli, Stefania

AU - Godi, Claudia

AU - Panzeri, Marta

AU - Ciasca, P.

AU - Brugnara, Gianluca

AU - Castaldo, Anna

AU - Di Bella, Daniela

AU - Taroni, Franco

AU - Nanetti, Lorenzo

AU - Mariotti, Caterina

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N2 - PURPOSE. Spinocerebellar ataxias type 2 and 28 (SCA2, SCA28) are autosomal dominant disorders characterized by progressive cerebellar and oculomotor abnormalities. We aimed to investigate cerebellar, brainstem, and extraocular muscle involvement in the mitochondrial SCA28 disease compared with SCA2. METHODS. We obtained orbital and brain 1.5 T-magnetic resonance images (MRI) in eight SCA28 subjects, nine SCA2, and nine age-matched healthy subjects. Automated segmentation of cerebellum and frontal lobe was performed using Freesurfer software. Manual segmentations for midbrain, pons, and extraocular muscles were performed using OsiriX. RESULTS. Eye movement abnormalities in SCA2 subjects were characterized by slow horizontal saccades. Subjects with SCA28 variably presented hypometric saccades, saccadic horizontal pursuit, impaired horizontal gaze holding, and superior eyelid ptosis. Quantitative brain MRI demonstrated that cerebellar and pons volumes were significantly reduced in both SCA2 and SCA28 subjects compared with controls (P <0.03), and in SCA2 subjects compared with SCA28 (P <0.01). Midbrain and frontal lobe volumes were also significantly reduced in SCA2 compared to controls (P <0.03), whereas these volumes did not differ between SCA2 and SCA28 and between SCA28 and control subjects. The extraocular muscle areas were 37% to 48% smaller in SCA28 subjects compared with controls (P <0.002), and 14% to 36% smaller compared with SCA2 subjects (P <0.03). Extraocular muscle areas did not differ between SCA2 and controls. CONCLUSIONS. Our MRI findings support the hypothesis of different cerebellar and extraocular myopathic contributions in the eye movement abnormalities in SCA2 and SCA28 diseases. In SCA28, a myopathic defect selectively involving the extraocular muscles supports a specific impairment of mitochondrial energy metabolism.

AB - PURPOSE. Spinocerebellar ataxias type 2 and 28 (SCA2, SCA28) are autosomal dominant disorders characterized by progressive cerebellar and oculomotor abnormalities. We aimed to investigate cerebellar, brainstem, and extraocular muscle involvement in the mitochondrial SCA28 disease compared with SCA2. METHODS. We obtained orbital and brain 1.5 T-magnetic resonance images (MRI) in eight SCA28 subjects, nine SCA2, and nine age-matched healthy subjects. Automated segmentation of cerebellum and frontal lobe was performed using Freesurfer software. Manual segmentations for midbrain, pons, and extraocular muscles were performed using OsiriX. RESULTS. Eye movement abnormalities in SCA2 subjects were characterized by slow horizontal saccades. Subjects with SCA28 variably presented hypometric saccades, saccadic horizontal pursuit, impaired horizontal gaze holding, and superior eyelid ptosis. Quantitative brain MRI demonstrated that cerebellar and pons volumes were significantly reduced in both SCA2 and SCA28 subjects compared with controls (P <0.03), and in SCA2 subjects compared with SCA28 (P <0.01). Midbrain and frontal lobe volumes were also significantly reduced in SCA2 compared to controls (P <0.03), whereas these volumes did not differ between SCA2 and SCA28 and between SCA28 and control subjects. The extraocular muscle areas were 37% to 48% smaller in SCA28 subjects compared with controls (P <0.002), and 14% to 36% smaller compared with SCA2 subjects (P <0.03). Extraocular muscle areas did not differ between SCA2 and controls. CONCLUSIONS. Our MRI findings support the hypothesis of different cerebellar and extraocular myopathic contributions in the eye movement abnormalities in SCA2 and SCA28 diseases. In SCA28, a myopathic defect selectively involving the extraocular muscles supports a specific impairment of mitochondrial energy metabolism.

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KW - Mitochondrial disorders

KW - Ocular motility

KW - Spinocerebellar ataxia

KW - Volumetric mri

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