HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schmidt, R. Articles by Fazekas, F. Search for Related Content PubMed PubMed Citation Articles by Schmidt, R. Articles by Fazekas, F. Related Collections MRI All Clinical trials Clinical trials Methodology/study design Vascular dementia

White matter lesion progression

A surrogate endpoint for trials in cerebral small-vessel disease

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:

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]