MRI derived brain atrophy in PSP and MSA-P
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Progressive supranuclear palsy (PSP) and multiple system (MSA) atrophy are associated with progressive brain atrophy. Serial MRI can be applied in order to measure this change in brain volume and to calculate atrophy rates.
We evaluated MRI derived whole brain and regional atrophy rates as potential markers of progression in PSP and the Parkinsonian variant of multiple system atrophy (MSA-P).
17 patients with PSP, 9 with MSA-P and 18 healthy controls underwent two MRI brain scans. MRI scans were registered, and brain and regional atrophy rates (midbrain, pons, cerebellum, third and lateral ventricles) measured. Sample sizes required to detect the effect of a proposed disease-modifying treatment were estimated. The effect of scan interval on the variance of the atrophy rates and sample size was assessed.
Based on the calculated yearly rates of atrophy, for a drug effect equivalent to a 30% reduction in atrophy, fewer PSP subjects are required in each treatment arm when using midbrain rather than whole brain atrophy rates (183 cf. 499). Fewer MSA-P subjects are required, using pontine/cerebellar, rather than whole brain atrophy rates (164/129 cf. 794). A reduction in the variance of measured atrophy rates was observed with a longer scan interval.
Regional rather than whole brain atrophy rates calculated from volumetric serial MRI brain scans in PSP and MSA-P provide a more practical and powerful means of monitoring disease progression in clinical trials.
- Steele JC, Richardson JC, Olszewski J (1964) Progressive Supranuclear Palsy. Arch Neurol 10:333–359
- Lees AJ (1987) The Steele Richardson Olszewski syndrome. Marsden, C. D and Fahn, S. Movement Disorders 2. 272–287, Butterworths
- Gilman S, Low PA, Quinn N, Albanese A, Ben Shlomo Y, Fowler CJ, Kaufmann H, Klockgether T, Lang AE, Lantos PL, Litvan I, Mathias CJ, Oliver E, Robertson D, Schatz I, Wenning GK(1-2-1999) Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci 163:94–98 CrossRef
- Freeborough PA, Fox NC (1997) The boundary shift integral: an accurate and robust measure of cerebral volume changes from registered repeat MRI. IEEE Trans Med Imaging 16:623–629 CrossRef
- Paviour DC, Schott JM, Stevens JM, Revesz T, Holton JL, Rossor MN, Lees AJ, Fox NC (2004) Pathological substrate for regional distribution of increased atrophy rates in progressive supranuclear palsy. J Neurol Neurosurg Psychiatry 75:1772–1775 CrossRef
- Schott JM, Simon JE, Fox NC, King AP, Khan MN, Cipolotti L, Paviour DC, Stevens JM, Rossor MN (2003) Delineating the sites and progression of in vivo atrophy in multiple system atrophy using fluid-registered MRI. Mov Disord 18:955–958 CrossRef
- Phiel CJ, Klein PS (2001) Molecular targets of lithium action. Annu Rev Pharmacol Toxicol 41:789–813 CrossRef
- Fox NC, Cousens S, Scahill R, Harvey RJ, Rossor MN (2000) Using serial registered brain magnetic resonance imaging to measure disease progression in Alzheimer disease: power calculations and estimates of sample size to detect treatment effects. Arch Neurol 57:339–344 CrossRef
- Bigio EH, Brown DF, White CL, III. (1999) Progressive supranuclear palsy with dementia: cortical pathology. J Neuropathol Exp Neurol 58:359–364
- Verny M, Duyckaerts C, Agid Y, Hauw JJ (1996) The significance of cortical pathology in progressive supranuclear palsy. Clinico-pathological data in 10 cases. Brain 119(Pt 4):1123–1136 CrossRef
- Konagaya M, Sakai M, Matsuoka Y, Konagaya Y, Hashizume Y (1999) Multiple system atrophy with remarkable frontal lobe atrophy. Acta Neuropathol (Berl) 97:423–428 CrossRef
- Josephs KA, Whitwell JL, Boeve BF, Shiung MM, Gunter JL, Parisi JE, Dickson DW, and Jack CR (8-11-2005) Rates of cerebral atrophy in autopsy-confirmed progressive supranuclear palsy. Ann Neurol
- Paviour DC, Price SL, Jahanshahi M, Lees AJ, and Fox NC (2-2-2006) Longitudinal MRI in progressive supranuclear palsy and multiple system atrophy: rates and regions of atrophy. Brain
- Litvan I, Bhatia KP, Burn DJ, Goetz CG, Lang AE, McKeith I, Quinn N, Sethi KD, Shults C, Wenning GK (2003) SIC Task Force appraisal of clinical diagnostic criteria for parkinsonian disorders. Mov Disord 18:467–486 CrossRef
- Kirkwood BR and Sterne JAC (2003) Calculation of required sample size. Medical Statistics. Malden, Massachusetts, Blackwell Science 2:413–428
- MRI derived brain atrophy in PSP and MSA-P
Journal of Neurology
Volume 254, Issue 4 , pp 478-481
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- longitudinal MRI
- power calculations
- Industry Sectors
- Author Affiliations
- 1. The Sara Koe PSP Research Centre, Institute of Neurology, 1 Wakefield Street, London WC1N, UK
- 2. Dementia Research Centre, Institute of Neurology UCL, London, UK
- 3. Reta Lila Weston, Institute of Neurological UCL, London, UK