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Regional brain metabolite abnormalities in inherited prion disease and asymptomatic gene carriers demonstrated in vivo by quantitative proton magnetic resonance spectroscopy

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Abstract

Introduction

Inherited prion diseases are caused by mutations in the gene which codes for prion protein (PrP), leading to proliferation of abnormal PrP isomers in the brain and neurodegeneration; they include Gerstmann–Sträussler–Scheinker disease (GSS), fatal familial insomnia (FFI) and familial Creutzfeldt–Jakob disease (fCJD).

Methods

We studied two patients with symptomatic inherited prion disease (P102L) and two pre-symptomatic P102L gene carriers using quantitative magnetic resonance spectroscopy (MRS). Short echo time spectra were acquired from the thalamus, caudate region and frontal white matter, metabolite levels and ratios were measured and z-scores calculated for individual patients relative to age-matched normal controls. MRS data were compared with structural magnetic resonance imaging.

Results

One fCJD case had generalised atrophy and showed increased levels of myo-inositol (MI) in the thalamus (z=3.7). The other had decreased levels of N-acetylaspartate (z=4) and diffuse signal abnormality in the frontal white matter. Both asymptomatic gene carriers had normal imaging, but increased frontal white matter MI (z=4.3, 4.1), and one also had increased MI in the caudate (z=5.3).

Conclusion

Isolated MI abnormalities in asymptomatic gene carriers are a novel finding and may reflect early glial proliferation, prior to significant neuronal damage. MRS provides potential non-invasive surrogate markers of early disease and progression in inherited prion disease.

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Acknowledgements

The authors would like to acknowledge the financial support of the Medical Research Council (grant G9627315), the assistance of colleagues in the Dementia Research Group, MRC Prion Unit and National Prion Clinic, and statistical advice from Hilary Watt, from the Institute of Neurology.

Conflict of interest statement We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Dementia Research Group, Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London, WC1 3BG, UK

    A. D. Waldman, R. J. Cordery, A. Godbolt & M. N. Rossor

  2. Division of Neuroscience & Psychological Medicine, Faculty of Medicine, Imperial College of Science, Technology & Medicine, London, UK

    A. D. Waldman, R. J. Cordery, A. Godbolt & M. N. Rossor

  3. NMR Research Unit, Department of Clinical Neurology, Institute of Neurology, University College London, London, UK

    D. G. MacManus

  4. MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UK

    J. Collinge

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  1. A. D. Waldman
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  2. R. J. Cordery
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  3. D. G. MacManus
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  4. A. Godbolt
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  5. J. Collinge
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  6. M. N. Rossor
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Correspondence to A. D. Waldman.

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Waldman, A.D., Cordery, R.J., MacManus, D.G. et al. Regional brain metabolite abnormalities in inherited prion disease and asymptomatic gene carriers demonstrated in vivo by quantitative proton magnetic resonance spectroscopy. Neuroradiology 48, 428–433 (2006). https://doi.org/10.1007/s00234-006-0068-1

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  • DOI: https://doi.org/10.1007/s00234-006-0068-1

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