title: Decreased cerebral perfusion in Duchenne muscular dystrophy patients.
abstract: Duchenne muscular dystrophy is caused by dystrophin gene mutations which lead to the absence of the protein dystrophin. A significant proportion of patients suffer from learning and behavioural disabilities, in addition to muscle weakness. We have previously shown that these patients have a smaller total brain and grey matter volume, and altered white matter microstructure compared to healthy controls. Patients with more distal gene mutations, predicted to affect dystrophin isoforms Dp140 and Dp427, showed greater grey matter reduction. Now, we studied if cerebral blood flow in Duchenne muscular dystrophy patients is altered, since cerebral expression of dystrophin also occurs in vascular endothelial cells and astrocytes associated with cerebral vasculature. T1-weighted anatomical and pseudo-continuous arterial spin labeling cerebral blood flow images were obtained from 26 patients and 19 age-matched controls (ages 8-18 years) on a 3 tesla MRI scanner. Group comparisons of cerebral blood flow were made with and without correcting for grey matter volume using partial volume correction. Results showed that patients had a lower cerebral blood flow than controls (40.0 ± 6.4 and 47.8 ± 6.3 mL/100 g/min respectively, p = 0.0002). This reduction was independent of grey matter volume, suggesting that they are two different aspects of the pathophysiology. Cerebral blood flow was lowest in patients lacking Dp140. There was no difference in CBF between ambulant and non-ambulant patients. Only three patients showed a reduced left ventricular ejection fraction. No correlation between cerebral blood flow and age was found. Our results indicate that cerebral perfusion is reduced in Duchenne muscular dystrophy patients independent of the reduced grey matter volume.
authors.affiliation: Department of Radiology, C.J. Gorter Center for High Field MRI, Leiden University Medical Center, Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden, The Netherlands; Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: N.Doorenweerd@lumc.nl.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Doorenweerd
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Eve M
authors.initials: EM
authors.lastname: Dumas
authors.affiliation: Department of Radiology, C.J. Gorter Center for High Field MRI, Leiden University Medical Center, Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
authors.forename: Eidrees
authors.initials: E
authors.lastname: Ghariq
authors.affiliation: Department of Radiology, C.J. Gorter Center for High Field MRI, Leiden University Medical Center, Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
authors.forename: Sophie
authors.initials: S
authors.lastname: Schmid
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Chiara S M
authors.initials: CS
authors.lastname: Straathof
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Arno A W
authors.initials: AA
authors.lastname: Roest
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Beatrijs H
authors.initials: BH
authors.lastname: Wokke
authors.affiliation: Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Erik W
authors.initials: EW
authors.lastname: van Zwet
authors.affiliation: Department of Radiology, C.J. Gorter Center for High Field MRI, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Webb
authors.affiliation: Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands; Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Jos G M
authors.initials: JG
authors.lastname: Hendriksen
authors.affiliation: Department of Radiology, C.J. Gorter Center for High Field MRI, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Mark A
authors.initials: MA
authors.lastname: van Buchem
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jan J G M
authors.initials: JJ
authors.lastname: Verschuuren
authors.affiliation: Department of Biomedical Engineering, Rochester Institute of Technology, Rochester, NY, USA.
authors.forename: Iris
authors.initials: I
authors.lastname: Asllani
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Erik H
authors.initials: EH
authors.lastname: Niks
authors.affiliation: Department of Radiology, C.J. Gorter Center for High Field MRI, Leiden University Medical Center, Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
authors.forename: Matthias J P
authors.initials: MJ
authors.lastname: van Osch
authors.affiliation: Department of Radiology, C.J. Gorter Center for High Field MRI, Leiden University Medical Center, Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
authors.forename: Hermien E
authors.initials: HE
authors.lastname: Kan
mesh_terms: D000293:Adolescent; D002560:Cerebrovascular Circulation / Q000502:physiology*; D002648:Child; D016189:Dystrophin / Q000378:metabolism*; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging* / Q000473:pathology; D006801:Humans; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: C094406:140-kDa dystrophin; D016189:Dystrophin
keywords: Brain; CBF; Duchenne muscular dystrophy; Dystrophin; Imaging