title: MRI Evidence of Cerebellar and Extraocular Muscle Atrophy Differently Contributing to Eye Movement Abnormalities in SCA2 and SCA28 Diseases.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Neuroradiology Department and Neuroradiology Research Unit San Raffaele Scientific Institute, Milan.
authors.forename: Letterio Salvatore
authors.initials: LS
authors.lastname: Politi
authors.affiliation: Neuro-Ophthalmology Service, Department of Ophthalmology, Fondazione IRCCS Istituto Auxologico Italiano, Milan.
authors.forename: Stefania
authors.initials: S
authors.lastname: Bianchi Marzoli
authors.affiliation: Neuroradiology Department and Neuroradiology Research Unit San Raffaele Scientific Institute, Milan.
authors.forename: Claudia
authors.initials: C
authors.lastname: Godi
authors.affiliation: Unit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS-Istituto Neurologico Carlo Besta, Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Panzeri
authors.affiliation: Neuro-Ophthalmology Service, Department of Ophthalmology, Fondazione IRCCS Istituto Auxologico Italiano, Milan.
authors.forename: Paola
authors.initials: P
authors.lastname: Ciasca
authors.affiliation: Neuroradiology Department and Neuroradiology Research Unit San Raffaele Scientific Institute, Milan.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Brugnara
authors.affiliation: Unit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS-Istituto Neurologico Carlo Besta, Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Castaldo
authors.affiliation: Unit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS-Istituto Neurologico Carlo Besta, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Di Bella
authors.affiliation: Unit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS-Istituto Neurologico Carlo Besta, Milan, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Taroni
authors.affiliation: Unit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS-Istituto Neurologico Carlo Besta, Milan, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Nanetti
authors.affiliation: Unit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS-Istituto Neurologico Carlo Besta, Milan, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Mariotti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001284:Atrophy / Q000175:diagnosis; D002531:Cerebellum / Q000473:pathology*; D005133:Eye Movements / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015835:Ocular Motility Disorders / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D009801:Oculomotor Muscles / Q000473:pathology* / Q000503:physiopathology; D015203:Reproducibility of Results; D020754:Spinocerebellar Ataxias / Q000150:complications / Q000151:congenital* / Q000175:diagnosis* / Q000503:physiopathology; D055815:Young Adult