Iron in the Hallervorden-Spatz syndrome

The dark discoloration of globus pallidus and substantia nigra pars reticul aris in the Hallervorden-Spatz syndrome is due to the accumulation of iron. Routine iron stains detect the metal mostly in microglia and macrophages, but scattered neurons are also reactive. Axonal spheroids are characteristi c of the disease, and many of these expansions give a positive iron reactio n. Globus pallidus and substantia nigra are normally rich in iron, and addi tional "storage" of the metal has often been considered the essential facto r in the pathogenesis of Hallervorden-Spatz syndrome. However, other equall y iron-rich structures, such as the red nucleus and the dentate nucleus, re main unaffected. In normal globus pallidus and substantia nigra pars reticu laris, double-label immunofluorescence microscopy of ferritin, as an indire ct marker of cellular iron localization, and phosphorylated neurofilament p rotein reveal close proximity of ferritin-reactive microglial and oligodend roglial processes to tightly packed axons. It is proposed that a primary ax onal disorder allows the seepage of iron into the axoplasm. Iron may contri bute to the axonal disease, but accumulation of the metal probably should b e viewed as an epiphenomenon. Pallidal and nigral iron excess is not unique to Hallervorden-Spatz; syndrome, and some previously reported postmortem e xaminations may actually represent pallidonigroluysian atrophy. (C) 2001 by Elsevier Science Inc. All rights reserved.