Agranulocytosis with deferiprone treatment of superficial siderosis

Abstract

SUMMARYSuperficial siderosis of the central nervous system is a rare neurological disorder caused by deposits of haemosiderin on subplial brain matter. Characterised by a thin dark layer surrounding the brain stem, cerebellum and cortical fissures on the T2-weighted MRI, symptoms include sensorineural hearing loss and progressive gait ataxia. A specific aetiology for the blood in the subarachnoid space is identified in less than 50% of cases. While identification of a specific vascular defect allows for vascular repair, treatment options are limited for idiopathic superficial siderosis. Recently, a pilot safety study demonstrated promising results using an iron chelator, deferiprone. While this approach is promising, we present a potential serious complication of this therapy-the first report of agranulocytosis in the treatment of superficial siderosis following deferiprone therapy. BACKGROUND

Iron chelation in the treatment of neurodegenerative diseases

“…In a 65 year-old patient with SupSid from an unknown source, who was followed for more than three years after initiation of deferiprone, a significant reduction of hemosiderin deposits in the cortex and cerebellum was seen, together with a resolution of hearing loss and ataxia [113,114] ( Table 5). Improvement after several months of deferiprone therapy was also documented in two other case reports of SupSid [115,116] while worsening was observed after discontinuation of the chelating drug in another one [107]. A similar beneficial clinical effect was also reported for trientine, which is a copper and iron chelating drug [106].…”

Infratentorial superficial siderosis: Classification, diagnostic criteria, and rational investigation pathway

“…[31][32][33] Although iron chelation has unproven efficacy in iSS, it has been associated with possible clinical or radiological improvement [31][32][33][34][35][36] and decreased ferritin in the CSF. [31][32][33] Although iron chelation has unproven efficacy in iSS, it has been associated with possible clinical or radiological improvement [31][32][33][34][35][36] and decreased ferritin in the CSF.…”

“…[31][32][33] Although iron chelation has unproven efficacy in iSS, it has been associated with possible clinical or radiological improvement [31][32][33][34][35][36] and decreased ferritin in the CSF. 35 Thus, whether iron chelation might lead to clear clinical benefit in iSS remains unproven; randomized controlled trials are needed to test this hypothesis, but will be challenging due to the rarity and slow progression of iSS. 35 Thus, whether iron chelation might lead to clear clinical benefit in iSS remains unproven; randomized controlled trials are needed to test this hypothesis, but will be challenging due to the rarity and slow progression of iSS.…”

Cochlear implantation in the presence of superficial siderosis

“…18 Treatment had to be withdrawn after 4 months in one subject due to sepsis secondary to agranulocytosis, which was attributed to deferiprone use, and however, subjective improvement in symptoms was noted prior to treatment cessation. 19 The third patient was treated for 90 days and had an initial demonstrable improvement in symptoms seen as a reduction in post-treatment Scale for the Assessment and Rating of Ataxia (SARA) score, and however, three months post-treatment was found to have a further deterioration in symptoms. 20 Post-treatment MRI failed to show reduction in haemosiderin deposition in any of the three cases.…”