title: Cerebral disease in a nationwide Dutch pseudoxanthoma elasticum cohort with a systematic review of the literature.
abstract: BACKGROUND
  Pseudoxanthoma elasticum (PXE) is a monogenetic disease with progressive calcification of arteries and potential risk of stroke. To gain insights in the cerebral involvement in PXE, we evaluated prevalence and determinants of cerebral disease in our PXE cohort and performed a systematic review of literature.
  
  
  METHODS
  Systematic history taking concerning cerebral disorders was performed in our PXE cohort. Cardiovascular risk factors were compared between PXE patients with and without cerebral disease. Additionally, Pubmed, Embase, the Cochrane Library and PsycINFO were systematically reviewed for studies published up to August 2016 about cerebral disease in PXE.
  
  
  RESULTS
  Of the 178 PXE patients 31 (17%) had cerebral disease including ischemic stroke (n=15, 8%) or transient ischemic attack (n=13, 7%). The cerebral disease group was older (61±12 vs. 52±15years, adjusted p=0.004) and had less favorable profiles of traditional cardiovascular risk factors regarding the use of lipid lowering medication (61% vs. 31%, adjusted p=0.037) and levels of HDL-cholesterol (1.4±0.3 vs. 1.6±0.4mmol/L, adjusted p=0.005). One prospective cohort study reporting an incidence rate of ischemic stroke of 477/100,000/year and two cross-sectional studies with a reported prevalence of ischemic stroke of 14% and 0% were identified. Furthermore, 53 unique cases of cerebral disease in PXE including ischemic stroke (n=16) and transient ischemic attack (n=7) were reported.
  
  
  CONCLUSIONS
  Physicians and patients should be aware of the prevalent occurrence of cerebrovascular disease in PXE, which further stresses the importance of strict cardiovascular risk management in these patients.
authors.affiliation: Department of Vascular Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: Fransk_92@hotmail.com.
authors.forename: Frans
authors.initials: F
authors.lastname: Kauw
authors.affiliation: Department of Vascular Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: G.kranenburg@umcutrecht.nl.
authors.forename: Guido
authors.initials: G
authors.lastname: Kranenburg
authors.affiliation: Department of Neurology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: L.kappelle@umcutrecht.nl.
authors.forename: L Jaap
authors.initials: LJ
authors.lastname: Kappelle
authors.affiliation: Department of Radiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: J.hendrikse@umcutrecht.nl.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Hendrikse
authors.affiliation: Department of Geriatrics, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: H.L.koek@umcutrecht.nl.
authors.forename: Huiberdina L
authors.initials: HL
authors.lastname: Koek
authors.affiliation: Department of Vascular Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: F.L.J.visseren@umcutrecht.nl.
authors.forename: Frank L J
authors.initials: FLJ
authors.lastname: Visseren
authors.affiliation: Department of Radiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: W.mali@umcutrecht.nl.
authors.forename: Willem P T
authors.initials: WPT
authors.lastname: Mali
authors.affiliation: Department of Radiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: P.dejong-8@umcutrecht.nl.
authors.forename: Pim A
authors.initials: PA
authors.lastname: de Jong
authors.affiliation: Department of Vascular Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: W.spiering@umcutrecht.nl.
authors.forename: Wilko
authors.initials: W
authors.lastname: Spiering
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000453:epidemiology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D015995:Prevalence; D011561:Pseudoxanthoma Elasticum / Q000453:epidemiology* / Q000503:physiopathology; D012189:Retrospective Studies; D012307:Risk Factors
keywords: Arterial calcification; Brain diseases; Pseudoxanthoma elasticum; Stroke; Transient ischemic attack