Experimental superficial siderosis of the central nervous system: biochemical correlates

doi:10.1016/0022-510X(92)90129-9

Journal of the Neurological Sciences

Volume 112, Issues 1–2, October 1992, Pages 38-45

https://doi.org/10.1016/0022-510X(92)90129-9 Get rights and content

Abstract

The pathogenesis of superficial siderosis of the central nervous system (CNS) may be examined by the repeated intracisternal injections of washed autologous red blood cells (RBC). In rabbits, the injections cause the accumulation of iron in the cytoplasm of microglial cells and astrocytes cerebellar and cerebral cortices. Immunocytochemistry for ferritin reveals enhanced reaction product mainly in microglia but hemosiderin occurs only after extending the injections to 6 months. In an effort to determine the biochemical correlates of these morphological changes, iron, ferritin, ferritin subunits and the ferritin repressor protein (FRP) were quatitated. There was no increase of total iron or ferritin in the exposed cortical areas. However, the injections of RBC caused dramatic shifts of the relative contributions by heavy (H-) and light (L-) ferritin subunits. The initial response was a prompt increase of the H/L ratio to over 4.0 from the normal ratio near 1.0. Extended injections caused the ratio to drop to below unity, and the predominance of L-ferritin at 6 months coincided with the appearance of granular hemosiderin. This investigation also confirmed the presence of FRP in rabbit brain cytosols but the induction of experimental superficial siderosis did not change its levels or in vitro affinity for the iron-responsive element in ferrith messenger ribonucleic acid. It is proposed that the incrustation by hemosiderin which characterizes superficial siderosis of the CNS in humans occurs when prolonged exposure to hemoglobin persistent shifts of the H/L-ratios by accumulation of L-ferritin.

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Cited by (54)

Secondary superficial siderosis of the central nervous system: Report of three cases
2009, Neurochirurgie
Superficial siderosis (SS) is an under-recognized entity. It is due to repeated microhemorrhages in the subarachnoid spaces resulting in a deposit of hemosiderin at the surface of the central nervous system and/or the cranial nerves. The origin of microhemorrhages remains unknown in almost one third of cases and therefore no treatment can be recommended. Through a literature review and new observations, our goal is to detail the outcome of patients with a recognized etiology of SS and treated surgically.
Series of three cases and review of the literature.
We present three patients with symptomatic SS for whom the origin of microhemorrhages was found. The first two patients complained of longstanding ataxia and neurosensory deafness while the third patient presented with urinary retention, vertigo, diplopia and facial paresis. Neuroradiological explorations revealed a left temporoparietal cavernoma, a fronto-orbital arterio-venous malformation and a cauda equina myxopapillary ependymoma respectively. Surgical resection of the source of hemorrhage was performed in all cases. All outcomes were good with improvement of their SS-related symptoms. These cases are discussed and the current literature is reviewed.
It is important to recognize SS since the treatment of the bleeding source may prevent further deterioration and may even in some cases improve the clinical condition.
La sidérose superficielle (SS) est une entité méconnue. Elle résulte de microhémorragies répétées dans l’espace sous-arachnoïdien entraînant un dépôt d’hémosidérine à la surface du système nerveux central (SNC) et/ou des nerfs crâniens. La source des microhémorragies demeure inconnue dans près d’un tiers des cas et ne peut donc être traitée. À travers une revue de la littérature et de nouvelles observations notre objectif est de préciser le devenir des patients dont l’étiologie est traitée chirurgicalement.
Série de trois cas et revue de la littérature.
Nous présentons trois patients symptomatiques de SS pour lesquels une source hémorragique a été découverte. Deux d’entre eux présentaient une ataxie, une dysarthrie et une surdité tandis que le troisième souffrait d’une rétention urinaire, de vertige, de diplopie et de parésie faciale. Les bilans d’imagerie ont conclu respectivement en un angiome caverneux temporoparietal, une malformation artérioveineuse intracrânienne et un épendymome myxopapillaire de la queue de cheval. Pour chacun de ces cas, la source des microhémorragies a été traitée chirurgicalement. Tous ont évolué favorablement avec une régression de leur symptomatologie en période postopératoire. Nous confrontons ces observations à celles de la littérature.
Il est important de reconnaître la SS car le traitement de la source potentielle d’hémorragie peut enrayer la progression de ses symptômes, voire même en permettre la régression.
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Citation Excerpt :
Recognition of these secondary mechanisms for lower motor neuron findings in patients with SS is important because SS does not directly involve the peripheral nervous system. This is due to the fact that conversion of heme to ferritin and hemosiderin requires the presence of microglia and astrocytes and this does not occur in the Schwann cells of the peripheral nervous system.39–42 An unrelated condition, Hirayama disease, is characterized by slowly progressive weakness and atrophy in the C8-T1 distribution.
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^☆: Presented, in part, at the XIIIth Meeting of the International Society for Neurochemistry, Sydney, Australia, July 18, 1991.

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Research articleExperimental superficial siderosis of the central nervous system: biochemical correlates☆

Abstract

J. Biol. Chem.

J. Biol. Chem.

FEBS Lett.

J. Biol. Chem.

Biochim. Biophys. Acta

Anal. Biochem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Properties of sufficiency and statistical tests

Elektronenmikroskopische Beobachtungen bei experimentell erzeugter Randzonensiderose des Kaninchengehirus

Acta Neuropathol. (Berl.)

Expression of the genes for the ferritin H and L subunits in rat liver and heart

Biochem. J.

T2 values in the human brain: comparison with quantitative assays of iron and ferritin

Radiology

Iron in the brain: a chemical and histochemical examination

Regulation of ferritin gene expression

Regulation of ferritin and heme oxygenase synthesis in rat fibroblasts by different forms of iron

Ferritin: isolation of aluminum-ferritin complex from brain

Research article
Experimental superficial siderosis of the central nervous system: biochemical correlates☆