title: The brain in late-onset glycogenosis II: a structural and functional MRI study.
abstract: BACKGROUND
  Late-onset glycogenosis type II (GSD II) is a rare, multisystem disorder mainly affecting limb and respiratory muscles due to acid alpha glucosidase deficiency. Despite evidence at autopsy of glycogen accumulation in the brain, no study exploring brain functions is yet available.
  
  
  OBJECTIVE
  Our objective in this study was to assess brain changes in late-onset GSD II.
  
  
  METHODS
  Each patient underwent a standardized neuropsychological assessment, regional grey-matter (GM) atrophy, and resting-state functional magnetic resonance imaging (RS-fMRI). Functional connectivity maps of the salience (SN) and default-mode (DMN) networks were considered. A group of age- and gender-matched healthy controls was enrolled for MRI comparisons. P values family-wise error (FWE) cluster level corrected inferior to 0.05 were considered.
  
  
  RESULTS
  Nine GSD II patients (age 46.6 ± 8.0; 55% male) were recruited. No significant GM atrophy was found in patients compared with controls (n = 18; age 48.0 ± 9.8,;40% male). Functional connectivity within the SN was selectively reduced in patients, and cingulate gyrus and medial frontal cortex were mainly involved. Accordingly, patients had significant impairment of executive functions (as measured by Wisconsin Card Sorting test), whereas other cognitive domains were within mean normal ranges.
  
  
  CONCLUSIONS
  Our findings extend the clinical spectrum of GSD II by indicating that brain changes occur in this muscular disorder. Above all, these results should lead to better examinations of therapeutic approaches and perspectives for the affected patients. Further studies evaluating in depth these issues are warranted.
authors.affiliation: Neurology Unit, University of Brescia, Piazza Spedali Civili 1, 25125, Brescia, Italy, bborroni@inwind.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Borroni
authors.forename: M S
authors.initials: MS
authors.lastname: Cotelli
authors.forename: E
authors.initials: E
authors.lastname: Premi
authors.forename: S
authors.initials: S
authors.lastname: Gazzina
authors.forename: M
authors.initials: M
authors.lastname: Cosseddu
authors.forename: A
authors.initials: A
authors.lastname: Formenti
authors.forename: R
authors.initials: R
authors.lastname: Gasparotti
authors.forename: M
authors.initials: M
authors.lastname: Filosto
authors.forename: A
authors.initials: A
authors.lastname: Padovani
mesh_terms: D000328:Adult; D017668:Age of Onset; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D016022:Case-Control Studies; D005260:Female; D059907:Functional Neuroimaging / Q000379:methods; D006009:Glycogen Storage Disease Type II / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests