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Severe vascular disturbance in a case of familial brain calcinosis

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Abstract

Here we present the first neuropathological study of a case of autosomal dominant brain calcinosis in a family followed through five generations. The 71-year-old female who came to autopsy had unusually severe and extensive bilateral brain calcifications. The process appeared to start with deposition of minute calcium-positive spheroids of less than 1 μm in diameter in capillaries that otherwise appeared normal. These could be observed extending to areas distant from the main pathology. In more advanced stages, larger spheroids completely covered some capillaries while sparing others. In heavily affected regions, ghost capillaries were observed where only calcium spheroids remained after endothelial cells and basement membranes had disappeared. Vessels of all sizes were affected, and large accretions were observed in the basal ganglia, thalamus and cerebellum. Combined scanning electron microscopy and X-ray spectrometry of these large deposits revealed a dominant presence of calcium and phosphorous, plus carbon and oxygen indicative of organic material, and small amounts of sodium, potassium, sulfur, and magnesium. Reactive astrocytes and reactive microglia accumulated around the calcified deposits, indicating a mild ongoing inflammatory process. The results suggest that severe vascular impairment and mild inflammation contribute to the slow but inexorable progression of hereditary brain calcinosis.

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Acknowledgements

We thank Susan Calne, RN for assistance in obtaining the autopsy material. We are grateful to Sheng Yu for help with histology and to Mary Mager for her assistance in the SEM-EDX analysis. This work was supported by grants from the Pacific Parkinson’s Research Institute, the Jack Brown and family AD Research Fund as well as donations from individual British Columbians.

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Authors and Affiliations

  1. Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, British Columbia, V6T1Z3, Canada

    Judit Miklossy, Andis Klegeris & Patrick L. McGeer

  2. Department of Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada

    Ian R. Mackenzie & Katerina Dorovini-Zis

  3. Department of Neurology, University of British Columbia, Vancouver, British Columbia, Canada

    Donald B. Calne

  4. Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA

    Zbigniew K. Wszolek

Authors
  1. Judit Miklossy
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  2. Ian R. Mackenzie
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  3. Katerina Dorovini-Zis
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  4. Donald B. Calne
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  5. Zbigniew K. Wszolek
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  6. Andis Klegeris
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  7. Patrick L. McGeer
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Correspondence to Patrick L. McGeer.

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Miklossy, J., Mackenzie, I.R., Dorovini-Zis, K. et al. Severe vascular disturbance in a case of familial brain calcinosis. Acta Neuropathol 109, 643–653 (2005). https://doi.org/10.1007/s00401-005-1007-7

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  • DOI: https://doi.org/10.1007/s00401-005-1007-7

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