UC San Diego

Introduction

Superficial siderosis is a rare, neurodegenerative disease caused by toxic accumulation of hemosiderin on the surface of the brain and the spinal cord, most commonly from chronic subarachnoid hemorrhage.

Aims

The aim of this study was to assess the clinical and radiological outcomes of superficial siderosis patients using deferiprone, a cell permeant iron chelator. Subjects obtained pre- and post-treatment brain MRIs and weekly laboratory tests. Osirix software was used to develop a method of quantifying hemosiderin deposition. Three-dimensional whole brain images of gradient echo images were rendered and compared by dividing the mean T2 hyperintensity to the maximal cerebrospinal fluid signal.

Results

A total of 38 subjects completed the study, of which clinical and radiological data were available for 30. The average age was 64 years (range 37-86), 53% were male, 94% were white. Nineteen subjects (63%) reported either no progression of disease or an improvement in at least one neurological domain, with 40% of patients reporting a stabilization in hearing function and 30% reporting stable or improved coordination and walking. By MRI, there was an overall mean increase in T2 hyperintensity of the whole brain of 1%-13% over the 2-year time period in half of patients, indicating a reduction hemosiderosis. There were no cases of agranulocytosis, and declines of white blood cells counts and neutrophils averaged <10%. Fatigue was the most common side effect.

Conclusion

This is the first long-term prospective study of superficial siderosis on the iron chelator, deferiprone. MRI quantification of hemosiderin appears to demonstrate a measurable reduction in half of patients and this correlated with a stabilized or improving disease course. A future placebo-controlled trial is necessary to determine whether deferiprone is an effective therapy for superficial siderosis.