TY - JOUR
T1 - Severe vascular disturbance in a case of familial brain calcinosis
AU - Miklossy, Judit
AU - Mackenzie, Ian R.
AU - Dorovini-Zis, Katerina
AU - Calne, Donald B.
AU - Wszolek, Zbigniew K.
AU - Klegeris, Andis
AU - McGeer, Patrick L.
PY - 2005/6/1
Y1 - 2005/6/1
N2 - 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.
AB - 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.
KW - Capillaries
KW - Dystonia
KW - Fahr's disease
KW - Gallyas staining
KW - Inflammation
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U2 - 10.1007/s00401-005-1007-7
DO - 10.1007/s00401-005-1007-7
M3 - Article
C2 - 15937691
AN - SCOPUS:22144455336
VL - 109
SP - 643
EP - 653
JO - Acta Neuropathologica
JF - Acta Neuropathologica
SN - 0001-6322
IS - 6
ER -