title: Brain and spine MRI features of Hunter disease: frequency, natural evolution and response to therapy.
abstract: BACKGROUND
  Hunter disease is a rare X-linked mucopolysaccharidosis. Despite frequent neurological involvement, characterizing the severe phenotype, neuroimaging studies are scarce.
  
  
  OBJECTIVE
  To determine frequency and severity of neuroradiological mucopolysaccharidosis-related features; to correlate them with clinical phenotype; to evaluate their natural evolution and the impact of intravenous enzymatic replacement therapy (ERT).
  
  
  METHODS
  Sixty nine brain MRI examinations of 36 Italian patients (mean-age 10.4 years; age-range 2.2-30.8; severe phenotype in 22 patients) were evaluated. Twenty patients had multiple MRIs (median follow-up 3.1 years, range 1-16.9): among them 15 had MRIs before and after ERT, six had repeated MRIs without being on ERT and five while on ERT. Perivascular, subarachnoid and ventricle space enlargement, white matter abnormality (WMA) burden, pituitary sella/skull/posterior fossa abnormalities, periodontoid thickening, spinal stenosis, dens hypoplasia, myelopathy, vertebral and intervertebral disc abnormalities were graded by means of dedicated scales.
  
  
  RESULTS
  Perivascular spaces enlargement (89%), WMAs (97%), subarachnoid space enlargement (83%), IIIrd-ventricle dilatation (100%), pituitary sella abnormalities (80%), cranial hyperostosis (19%), craniosynostosis (19%), enlarged cisterna magna (39%), dens hypoplasia (66%), periodontoid thickening (94%), spinal stenosis (46%), platyspondylia (84%) and disc abnormalities (79%) were frequently detected. WMAs, IIIrd-ventricle dilatation and hyperostosis correlated with the severe phenotype (p < 0.05). Subarachnoid spaces and ventricle enlargement, WMAs and spinal stenosis progressed despite ERT, while other MR features showed minimal or no changes.
  
  
  CONCLUSIONS
  The spectrum of brain and spine MRI abnormalities in Hunter disease is extremely wide and requires a thorough evaluation. WMAs, atrophy/communicating hydrocephalus and spinal stenosis progress over time and might represent possible disease severity markers for new treatment efficacy assessment.
authors.affiliation: Neuroradiologic Unit, University Hospital of Padua, via Giustiniani 2, 35128 Padova, Italy. renzo.manara@sanita.padova.it
authors.forename: Renzo
authors.initials: R
authors.lastname: Manara
authors.forename: Elena
authors.initials: E
authors.lastname: Priante
authors.forename: Marco
authors.initials: M
authors.lastname: Grimaldi
authors.forename: Lucia
authors.initials: L
authors.lastname: Santoro
authors.forename: Luca
authors.initials: L
authors.lastname: Astarita
authors.forename: Rita
authors.initials: R
authors.lastname: Barone
authors.forename: Daniela
authors.initials: D
authors.lastname: Concolino
authors.forename: Maja
authors.initials: M
authors.lastname: Di Rocco
authors.forename: Maria Alice
authors.initials: MA
authors.lastname: Donati
authors.forename: Simona
authors.initials: S
authors.lastname: Fecarotta
authors.forename: Anna
authors.initials: A
authors.lastname: Ficcadenti
authors.forename: Agata
authors.initials: A
authors.lastname: Fiumara
authors.forename: Francesca
authors.initials: F
authors.lastname: Furlan
authors.forename: Irene
authors.initials: I
authors.lastname: Giovannini
authors.forename: Franco
authors.initials: F
authors.lastname: Lilliu
authors.forename: Rodica
authors.initials: R
authors.lastname: Mardari
authors.forename: Gabriele
authors.initials: G
authors.lastname: Polonara
authors.forename: Elena
authors.initials: E
authors.lastname: Procopio
authors.forename: Angelica
authors.initials: A
authors.lastname: Rampazzo
authors.forename: Andrea
authors.initials: A
authors.lastname: Rossi
authors.forename: Graziolina
authors.initials: G
authors.lastname: Sanna
authors.forename: Rossella
authors.initials: R
authors.lastname: Parini
authors.forename: Maurizio
authors.initials: M
authors.lastname: Scarpa
mesh_terms: D000293:Adolescent; D000328:Adult; D001848:Bone Diseases, Developmental / Q000000981:diagnostic imaging* / Q000453:epidemiology* / Q000209:etiology / Q000628:therapy; D001921:Brain / Q000000981:diagnostic imaging*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D006801:Humans; D015994:Incidence; D008279:Magnetic Resonance Imaging; D008297:Male; D016532:Mucopolysaccharidosis II / Q000150:complications / Q000000981:diagnostic imaging* / Q000628:therapy*; D010641:Phenotype; D011859:Radiography; D013115:Spinal Canal / Q000000981:diagnostic imaging*; D016896:Treatment Outcome; D055815:Young Adult