THE PATHOGENESIS OF SUPERFICIAL SIDEROSIS OF THE CENTRAL-NERVOUS-SYSTEM

In advanced cases of superficial siderosis of the human central nervou s system, the clinical triad of hearing loss, cerebellar ataxia, and m yelopathy permits the diagnosis at the bedside, and magnetic resonance imaging readily confirms the hemosiderin deposits in brainstem, cereb ellum, and spinal cord. To study the pathogenesis of this condition an d explain the selective vulnerability of the cerebellum, experimental siderosis was induced in rabbits by the repeated intracisternal inject ion of autologous red blood cells. The earliest cellular response in t he cerebellar molecular layer was hyperplasia and hypertrophy of micro glia as displayed by immunocytochemistry for ferritin. Microglia also contained iron, but ferritin biosynthesis appeared to proceed without commensurate iron accumulation. This early apoferritin response probab ly occurred due to the presence of heme, rather than iron, in the cere brospinal fluid and subpial tissue. Ferritin biosynthesis is accelerat ed when the ferritin repressor protein is dissociated from ferritin me ssenger ribonucleic acid. A specific antiserum localized ferritin repr essor protein predominantly to astrocytes including Bergmann glia. It is proposed that abundance and proximity of ferritin repressor protein -immunoreactive Bergmann glia and ferritin-containing microglia in the cerebellar molecular layer permit prompt cellular interaction in the conversion of heme to ferritin and ultimately hemosiderin.