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J Neuropathol Exp Neurol. 2009 Feb;68(2):136-47. doi: 10.1097/NEN.0b013e318195203.

Hyaline protoplasmic astrocytopathy of neocortex.

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  • 1Charles S. Kubik Laboratory for Neuropathology, Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.


Eosinophilic inclusions in the cytoplasm of protoplasmic astrocytes of the neocortex, usually in the clinical setting of epilepsy and/or psychomotor retardation, were first recognized and illustrated by Alois Alzheimer in 1910. Traditional special stains have failed to elucidate the specific nature of these inclusions. Ultrastructurally, the material was composed predominantly of highly electron-dense, non-membrane-bound, granular material distinct from Rosenthal fibers. Immunohistochemical examination has been informative but also sometimes inconsistent; it has recently been suggested that they may represent a filaminopathy (filamin A). We examined 5 cases with neocortical eosinophilic inclusions (3 autopsies, 2 surgical resections) using a standardized immunohistochemical protocol at a single institution. The specimens were immunostained with 32 antibodies to 30 potentially relevant proteins using several antigen retrieval protocols. We confirmed the presence of filamin A in these inclusions, but several additional proteins, particularly cytoglobin and glutamate transporter 1, were also identified. By electron microscopy in 2 cases, the granular fine structure of the inclusions was confirmed; mitochondria adjacent to, and perhaps within, the inclusions that contained many pleomorphic vesicular and membranous elements were also noted in 1 case. The pathophysiologic relevance of these proteins and the clinical significance of the hyaline inclusions are discussed.

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