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Pathological substrate for regional distribution of increased atrophy rates in progressive supranuclear palsy
  1. D C Paviour1,
  2. J M Schott2,
  3. J M Stevens3,
  4. T Revesz4,
  5. J L Holton4,
  6. M N Rossor2,5,
  7. A J Lees1,
  8. N C Fox2
  1. 1The Sara Koe PSP Research Centre, Institute of Neurology UCL, London UK
  2. 2Dementia Research Group (UCL), Institute of Neurology, London, UK
  3. 3Department of Clinical Neuroradiology, National Hospital for Neurology and Neurosurgery, London, UK
  4. 4Department of Molecular Pathogenesis, Queen Square Brain Bank and Division of Neuropathology, Institute of Neurology, UCL, London, UK
  5. 5Division of Neuroscience and Psychological Medicine, Faculty of Medicine, Imperial College of Science, Engineering and Medicine, London, UK
  1. Correspondence to:
 Dr D C Paviour
 The Sara Koe PSP Research Centre, Institute of Neurology, 1 Wakefield Street, London, WC1N 1PJ, UK;


Background: Most magnetic resonance imaging (MRI) studies of progressive supranuclear palsy (PSP) are cross-sectional and lack post mortem confirmation of the diagnosis. MRI features described previously in PSP correspond to regions of pathological involvement demonstrated in separate studies, but serial MRI with pathological follow up has not been undertaken.

Objective: To investigate whether regions of increased atrophy rates demonstrated in PSP during life using fluid registered serial MRI correspond with pathological findings in confirmed PSP.

Methods: A 59 year old male presented with a six month history of balance problems and dysarthria. He had a symmetrical, levodopa unresponsive akinetic-rigid syndrome with a vertical supranuclear gaze palsy. A clinical diagnosis of probable PSP was made. His disease progressed relentlessly and he died five years after onset. Two serial MRI scans undertaken during life were reviewed and fluid (non-linear) registration of the images carried out. Post mortem histopathological analysis of the brain was undertaken to definitively confirm the diagnosis and compare regional pathology with the serial imaging.

Results: Fluid registration demonstrated greatest rates of atrophy in the brainstem and frontal cortex, in keeping with the distribution of pathology seen at autopsy.

Conclusion: Fluid registration of serial MRI allows the topography and rates of regional atrophy in PSP to be delineated in life. Atrophy patterns correlated well with regional pathological load. These observations suggest that serial MRI with registration may help differentiate PSP from clinically similar conditions and supports its use as a surrogate marker of disease progression.

  • AD, Alzheimer’s disease
  • GP, globus pallidus
  • LC, locus ceruleus
  • NFT, neurofibrillary tangle
  • NT, neuropil thread
  • PSP, progressive supranuclear palsy
  • STN, subthalamic nucleus
  • magnetic resonance imaging
  • progressive supranuclear palsy

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  • DCP is supported by a grant from the PSP (Europe) Association; the imaging work is supported by a UK Medical Research Council (MRC) Program grant G9626876.

    NCF holds an MRC Senior Clinical Fellowship.

    JH is partly supported by the Reta Lila Weston Institute of Neurological Sciences.

    JMS is in receipt of an Alzheimer’s Society Research Fellowship.

  • Competing interests: This article was submitted before Professor M N Rossor become Editor of the Journal of Neurology, Neurosurgery, and Psychiatry and he had no involvement in the peer review or decision making process.