Progressive volume loss and white matter degeneration in cstb-deficient mice: a diffusion tensor and longitudinal volumetry MRI study

PLoS One. 2014 Mar 6;9(6):e90709. doi: 10.1371/journal.pone.0090709. eCollection 2014.


Unverricht-Lundborg type progressive myoclonus epilepsy (EPM1, OMIM 254800) is an autosomal recessive disorder characterized by onset at the age of 6 to 16 years, incapacitating stimulus-sensitive myoclonus and tonic-clonic epileptic seizures. It is caused by mutations in the gene encoding cystatin B. Previously, widespread white matter changes and atrophy has been detected both in adult EPM1 patients and in 6-month-old cystatin B-deficient mice, a mouse model for the EPM1 disease. In order to elucidate the spatiotemporal dynamics of the brain atrophy and white matter changes in EPM1, we conducted longitudinal in vivo magnetic resonance imaging and ex vivo diffusion tensor imaging accompanied with tract-based spatial statistics analysis to compare volumetric changes and fractional anisotropy in the brains of 1 to 6 months of age cystatin B-deficient and control mice. The results reveal progressive but non-uniform volume loss of the cystatin B-deficient mouse brains, indicating that different neuronal populations possess distinct sensitivity to the damage caused by cystatin B deficiency. The diffusion tensor imaging data reveal early and progressive white matter alterations in cystatin B-deficient mice affecting all major tracts. The results also indicate that the white matter damage in the cystatin B-deficient brain is most likely secondary to glial activation and neurodegenerative events rather than a primary result of CSTB deficiency. The data also show that diffusion tensor imaging combined with TBSS analysis provides a feasible approach not only to follow white matter damage in neurodegenerative mouse models but also to detect fractional anisotropy changes related to normal white matter maturation and reorganisation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebellum / pathology*
  • Cystatin B / deficiency*
  • Diffusion Tensor Imaging
  • Disease Progression
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Mice, Knockout
  • Organ Size
  • Thalamus / pathology*
  • Unverricht-Lundborg Syndrome / pathology*


  • Cstb protein, mouse
  • Cystatin B

Grant support

This study was funded by the Folkhälsan Research Foundation, the Sigrid Jusélius Foundation ( and the Academy of Finland (grant # 137950) (, the Finnish Brain Foundation (, Finnish Foundation for Epilepsy research (, Oskar Öflund Foundation ( and UEF Brain strategic funding from the University of Eastern Finland ( The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.