Skip Navigation



Brain Advance Access published online on June 30, 2004
Brain, doi:10.1093/brain/awh223
© 2004 by Guarantors of Brain
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
127/9/2031    most recent
awh223v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Singhal, S.
Right arrow Articles by Markus, H. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Singhal, S.
Right arrow Articles by Markus, H. S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received February 17, 2004
Revised April 28, 2004
Accepted April 28, 2004

Article

The influence of genetic and cardiovascular risk factors on the CADASIL phenotype

Sumeet Singhal 1, Steve Bevan 1, Tom Barrick 1, Philip Rich 2, Hugh S. Markus 1*

1 Clinical Neuroscience, St George's Hospital Medical School, London, UK
2 Neuroradiology, Atkinson Morley Neuroscience Centre, St George's Hospital, London, UK

* To whom correspondence should be addressed. E-mail: h.markus{at}sghms.ac.uk.


  Abstract

Summary The clinical phenotype in cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL), an autosomal dominant cerebral arteriopathy, is variable, but the reasons for this remain uncertain. Possible factors include the mutation site and the influence of additional modulating factors, which could include both epistatic interactions and interactions with cardiovascular risk factors known to cause sporadic small vessel disease. In a large prospectively recruited cohort of CADASIL subjects we determined relationships between phenotype and mutation site, the apoE genotype and cardiovascular risk factors. In addition to clinical features, disease severity was assessed by MRI lesion volume, measured both semiquantitatively (Scheltens scale) and quantitatively. One hundred and twenty-seven CADASIL cases from 65 families with 17 different mutations were studied. Site of mutation was not associated with the presence or age of onset of stroke, migraine, dementia, dependency or MRI lesion load. There was no evidence of intrafamilial clustering of particular phenotypes. Amongst subjects with stroke/transient ischaemic attack, smoking at the time of the event was independently associated with earlier age of onset (P = 0.01). There were no associations between age of onset or presence of stroke and other cardiovascular risk factors, including homocysteine. Homocysteine levels were higher in migraineurs [mean (SD) 12.8 (5.6) versus 9.8 (3.4) µmol/l, P = 0.02)] and elevated homocysteine was independently associated with an earlier age of onset of migraine (P = 0.01). No relationship was found between MRI lesion volume and risk factors, or between apoE genotype and phenotype. Our results show no notch 3 genotype-phenotype correlations. This implies that modulating factors influence phenotype. Smoking appears to increase the risk of stroke, while high homocysteine levels are associated with an increased risk of migraine.

Keywords: CADASIL; genotype-phenotype; homocysteine; risk factors; apolipoprotein E.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 BrainHome page
M. Monet-Lepretre, B. Bardot, B. Lemaire, V. Domenga, O. Godin, M. Dichgans, E. Tournier-Lasserve, M. Cohen-Tannoudji, H. Chabriat, and A. Joutel
Distinct phenotypic and functional features of CADASIL mutations in the Notch3 ligand binding domain
Brain, June 1, 2009; 132(6): 1601 - 1612.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
K. Mykkanen, M. Junna, K. Amberla, L. Bronge, H. Kaariainen, M. Poyhonen, H. Kalimo, and M. Viitanen
Different Clinical Phenotypes in Monozygotic CADASIL Twins With a Novel NOTCH3 Mutation
Stroke, June 1, 2009; 40(6): 2215 - 2218.
[Abstract] [Full Text] [PDF]

Home page
 Adv. Psychiatr. Treat.Home page
M. H. Taylor and G. A. Doody
CADASIL: a guide to a comparatively unrecognised condition in psychiatry
Adv. Psychiatr. Treat., September 1, 2008; 14(5): 350 - 357.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
P.A. Kempster and J.E. Alty
John Ruskin's relapsing encephalopathy
Brain, September 1, 2008; 131(9): 2520 - 2525.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
A. Stenborg, H. Kalimo, M. Viitanen, A. Terent, and L. Lind
Impaired Endothelial Function of Forearm Resistance Arteries in CADASIL Patients
Stroke, October 1, 2007; 38(10): 2692 - 2697.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
M. K. Liem, J. van der Grond, J. Haan, R. van den Boom, M. D. Ferrari, Y. M. Knaap, M. H. Breuning, M. A. van Buchem, H. A.M. Middelkoop, and S. A.J. Lesnik Oberstein
Lacunar Infarcts Are the Main Correlate With Cognitive Dysfunction in CADASIL
Stroke, March 1, 2007; 38(3): 923 - 928.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
A. Rufa, F. Guideri, M. Acampa, G. Cevenini, S. Bianchi, N. De Stefano, M. L. Stromillo, A. Federico, and M. T. Dotti
Cardiac Autonomic Nervous System and Risk of Arrhythmias in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL)
Stroke, February 1, 2007; 38(2): 276 - 280.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
J. C. Choi, S.-Y. Kang, J.-H. Kang, and J.-K. Park
Intracerebral hemorrhages in CADASIL
Neurology, December 12, 2006; 67(11): 2042 - 2044.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
C. Opherk, N. Peters, M. Holtmannspotter, A. Gschwendtner, B. Muller-Myhsok, and M. Dichgans
Heritability of MRI Lesion Volume in CADASIL: Evidence for Genetic Modifiers
Stroke, November 1, 2006; 37(11): 2684 - 2689.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
A. Viswanathan, J.-P. Guichard, A. Gschwendtner, F. Buffon, R. Cumurcuic, C. Boutron, E. Vicaut, M. Holtmannspotter, C. Pachai, M.-G. Bousser, et al.
Blood pressure and haemoglobin A1c are associated with microhaemorrhage in CADASIL: a two-centre cohort study
Brain, September 1, 2006; 129(9): 2375 - 2383.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
R. Cumurciuc, P. Henry, C. Gobron, E. Vicaut, M.-G. Bousser, H. Chabriat, and K. Vahedi
Electrocardiogram in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Patients Without Any Clinical Evidence of Coronary Artery Disease: A Case-Control Study
Stroke, April 1, 2006; 37(4): 1100 - 1102.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Neuroradiol.Home page
R. van den Boom, S.A.J. Lesnick Oberstein, A.A. van den Berg-Huysmans, M.D. Ferrari, M.A. van Buchem, and J. Haan
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy: Structural MR Imaging Changes and Apolipoprotein E Genotype.
AJNR Am. J. Neuroradiol., February 1, 2006; 27(2): 359 - 362.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
H. S. Markus and M. J. Alberts
Update on Genetics of Stroke and Cerebrovascular Disease 2005
Stroke, February 1, 2006; 37(2): 288 - 290.
[Full Text] [PDF]

Home page
 StrokeHome page
G. G. Leblanc, J. F. Meschia, D. T. Stuss, and V. Hachinski
Genetics of Vascular Cognitive Impairment: The Opportunity and the Challenges
Stroke, January 1, 2006; 37(1): 248 - 255.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
A. Rufa, M. T. Dotti, M. Franchi, M. L. Stromillo, G. Cevenini, S. Bianchi, N. De Stefano, and A. Federico
Systemic Blood Pressure Profile in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy
Stroke, December 1, 2005; 36(12): 2554 - 2558.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.