Neurology®
The most widely read and highly cited peer-reviewed Neurology journal
Quick Search
Advanced Search
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Correspondence:
Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Correspondence are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
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 Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schmidt, R.
Right arrow Articles by Fazekas, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schmidt, R.
Right arrow Articles by Fazekas, F.
Related Collections
Right arrow MRI
Right arrow All Clinical trials
Right arrow Clinical trials Methodology/study design
Right arrow Vascular dementia
NEUROLOGY 2004;63:139-144
© 2004 American Academy of Neurology
Medical Hypothesis

White matter lesion progression

A surrogate endpoint for trials in cerebral small-vessel disease R. Schmidt, MD, Ph. Scheltens, MD, T. Erkinjuntti, MD, L. Pantoni, MD PhD, H. S. Markus, FRCP, A. Wallin, MD, F. Barkhof, MD and F. Fazekas, MD for the European Task Force on Age-Related White Matter Changes

From the Department of Neurology (Drs. Schmidt and Fazekas), Medical University Graz, Austria; Department of Neurology (Dr. Scheltens) and Image Analysis Center (Dr. Barkhof), Vrije Universiteit Medical Center, Amsterdam, the Netherlands; Memory Research Unit (Dr. Erkinjuntti), Department of Clinical Neurosciences, Helsinki University Central Hospital, Finland; Department of Neurological and Psychiatric Sciences (Dr. Pantoni), University of Florence, Italy; Clinical Neuroscience (Dr. Markus), St. George’s Hospital Medical School, London, UK; and Institute of Clinical Neuroscience (Dr. Wallin), Sahlgrenska University Hospital, Mölndahl, Sweden.

Address correspondence and reprint requests to Dr. R. Schmidt, Department of Neurology, Medical University Graz, Auenbruggerplatz 22, A-8036 Graz, Austria; e-mail: reinhold.schmidt{at}meduni-graz.at

There is neuropathologic evidence that confluent MRI white matter lesions in the elderly reflect ischemic brain damage due to microangiopathy. The authors hypothesize that measuring changes in the progression of white matter lesions as shown by MRI may provide a surrogate marker in clinical trials on cerebral small-vessel disease in which the currently used primary outcomes are cognitive impairment and dementia. This hypothesis is based on evidence that confluent white matter lesions progress rapidly as shown in a recent follow-up study in community-dwelling subjects. The mean increase in lesion volume was 5.2 cm3 after 3 years. Based on these data in a clinical trial, 195 subjects with confluent lesions would be required per treatment arm to demonstrate a 20% reduction in the rate of disease progression over a 3-year period. Like any other MRI metric, the change in white matter lesion volume cannot be considered preferable to clinical outcomes unless it has been demonstrated that it matters to the patient in terms of function.

Received November 20, 2003. Accepted in final form February 23, 2004.




This article has been cited by other articles:


Home page
 Ann. Thorac. Surg.Home page
N. Morimoto, K. Okada, K. Uotani, F. Kanda, and Y. Okita
Leukoaraiosis and Hippocampal Atrophy Predict Neurologic Outcome in Patients Who Undergo Total Aortic Arch Replacement
Ann. Thorac. Surg., August 1, 2009; 88(2): 476 - 481.
[Abstract] [Full Text] [PDF]

Home page
 BMJHome page
D. Inzitari, G. Pracucci, A. Poggesi, G. Carlucci, F. Barkhof, H. Chabriat, T. Erkinjuntti, F. Fazekas, J. M Ferro, M. Hennerici, et al.
Changes in white matter as determinant of global functional decline in older independent outpatients: three year follow-up of LADIS (leukoaraiosis and disability) study cohort
BMJ, July 6, 2009; 339(jul06_1): b2477 - b2477.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
B. T. Baune
The Puzzle of Predicting the Impact of Brain Infarcts on Cognitive Impairment in the Aging Brain
Stroke, March 1, 2009; 40(3): 667 - 669.
[Full Text] [PDF]

Home page
 J Gerontol A Biol Sci Med SciHome page
B. T. Baune, A. Roesler, S. Knecht, and K. Berger
Single and Combined Effects of Cerebral White Matter Lesions and Lacunar Infarctions on Cognitive Function in an Elderly Population
J Gerontol A Biol Sci Med Sci, January 27, 2009; (2009) gln004v2.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
V. Srikanth, R. Beare, L. Blizzard, T. Phan, J. Stapleton, J. Chen, M. Callisaya, K. Martin, and D. Reutens
Cerebral White Matter Lesions, Gait, and the Risk of Incident Falls: A Prospective Population-Based Study
Stroke, January 1, 2009; 40(1): 175 - 180.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurol. Neurosurg. PsychiatryHome page
R Schmidt, S Ropele, B Pendl, P Ofner, C Enzinger, H Schmidt, A Berghold, M Windisch, H Kolassa, and F Fazekas
Longitudinal multimodal imaging in mild to moderate Alzheimer disease: a pilot study with memantine
J. Neurol. Neurosurg. Psychiatry, December 1, 2008; 79(12): 1312 - 1317.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
E. J. van Dijk, N. D. Prins, H. A. Vrooman, A. Hofman, P. J. Koudstaal, and M. M.B. Breteler
Progression of Cerebral Small Vessel Disease in Relation to Risk Factors and Cognitive Consequences: Rotterdam Scan Study
Stroke, October 1, 2008; 39(10): 2712 - 2719.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
A. Nitkunan, T. R. Barrick, R. A. Charlton, C. A. Clark, and H. S. Markus
Multimodal MRI in Cerebral Small Vessel Disease: Its Relationship With Cognition and Sensitivity to Change Over Time
Stroke, July 1, 2008; 39(7): 1999 - 2005.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
L. Pantoni
Leukoaraiosis: From an Ancient Term to an Actual Marker of Poor Prognosis
Stroke, May 1, 2008; 39(5): 1401 - 1403.
[Full Text] [PDF]

Home page
 StrokeHome page
R. Schmidt, K. Petrovic, S. Ropele, C. Enzinger, and F. Fazekas
Progression of Leukoaraiosis and Cognition
Stroke, September 1, 2007; 38(9): 2619 - 2625.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
P. Sachdev, W. Wen, X. Chen, and H. Brodaty
Progression of white matter hyperintensities in elderly individuals over 3 years
Neurology, January 16, 2007; 68(3): 214 - 222.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
F.-E. de Leeuw, E. Korf, F. Barkhof, and P. Scheltens
White Matter Lesions Are Associated With Progression of Medial Temporal Lobe Atrophy in Alzheimer Disease
Stroke, September 1, 2006; 37(9): 2248 - 2252.
[Abstract] [Full Text] [PDF]

Home page
 Cereb CortexHome page
D. M. Kronhaus and D. J. Willshaw
The Cingulate as a Catalyst Region for Global Dysfunction: a Dynamical Modelling Paradigm
Cereb Cortex, August 1, 2006; 16(8): 1212 - 1224.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
F. Fazekas, S. Ropele, C. Enzinger, F. Gorani, A. Seewann, K. Petrovic, and R. Schmidt
MTI of white matter hyperintensities
Brain, December 1, 2005; 128(12): 2926 - 2932.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
M. Holtmannspotter, N. Peters, C. Opherk, D. Martin, J. Herzog, H. Bruckmann, P. Samann, A. Gschwendtner, and M. Dichgans
Diffusion Magnetic Resonance Histograms as a Surrogate Marker and Predictor of Disease Progression in CADASIL: A Two-Year Follow-Up Study
Stroke, December 1, 2005; 36(12): 2559 - 2565.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurol. Neurosurg. PsychiatryHome page
F-E de Leeuw, F Barkhof, and P Scheltens
Progression of cerebral white matter lesions in Alzheimer's disease: a new window for therapy?
J. Neurol. Neurosurg. Psychiatry, September 1, 2005; 76(9): 1286 - 1288.
[Abstract] [Full Text] [PDF]