Reactions of vessel walls and brain parenchyma to the accumulation of Gaucher cells in the Norrbottnian type (type III) of Gaucher disease

Summary

Splenectomy in children with the Norrbottnian type of Gaucher disease is followed by increased blood levels of glucosylceramide and imparied neurological and mental status. High blood levels are associated with an increased accumulation of glucosylceramide in perivascular Gaucher cells in the brain compared to non-splenectomised cases. Surrounding the Gaucher cell infiltrates there is loss of neurons and slight demyelinaton in the brain parenchyma. The brains of four cases with the Norrbottnian type of Gaucher disease were examined by immunohistochemical stains in an attempt to further characterize the perivascular Gaucher cells and to examine the reactions of the vessel walls and brain parenchyma to the accumulation of Gaucher cells. The perivascular storage cells showed granular staining with antibodies to muramidase and α₁-antichymotrypsin confirming that they are blood-derived macrophages belonging to the monocyte-macrophage system. The Gaucher cells contained material positive for antisera to plasma proteins strongly suggesting that large molecules (including glucosylceramide) can escape from the blood and be taken up by the macrophages in Gaucher disease. The storage cells were surrounded by a reticulin network stained by antisera to collagen type III, type IV and laminin. The infiltrates were bounded from the brain parenchyma by a membrane strongly positive with antiserum for the basal lamina protein collagen type IV and laminin. The formation of a basal lamina around the Gaucher cell cuffs probably constitutes a protective phenomenon governing the brain parenchyma against the foreign cells. A focal loss of neurons but only minor loss of axons could be demonstrated with the antiserum to neurofilament. The brain parenchyma surrounding the Gaucher cell infiltrates showed marked astrogliosis in the anti-glial fibrillary acidic protein stain.

In the two cases previously shown to have higher blood levels of glucosylceramide there were astrocytes positive for plasma proteins indicating passage of plasma proteins into the brain, this was not seen in the non-splenectomised cases. The additive effect of low-grade tissue damage in the vicinity of the Gaucher cell infiltrates is probably enough to explain the increased neurological symptoms and mental retardation following splenectomy in the Norrbottnian type of Gaucher disease.