Regression of symptoms after selective iron chelation therapy in a case of neurodegeneration with brain iron accumulation

Forni, Gian Luca; Balocco, Manuela; Cremonesi, Laura; Abbruzzese, Giovanni; Parodi, Roberto; Marchese, Roberta

doi:10.1002/mds.22002

Cited by 73 publications

(51 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4 An individual case report 5 and a separate pilot phase II study by Zorzi et al 6 have suggested that deferiprone is safe, well-tolerated and effective in lowering iron levels in brain as measured by MRI; conclusions also supported by the current study. Clinical benefit, however, is less clear from these combined data.…”

supporting

confidence: 73%

As iron goes, so goes disease?

Hayflick¹,

Hogarth²

2011

Haematologica

View full text Add to dashboard Cite

supporting

confidence: 73%

As iron goes, so goes disease?

Hayflick¹,

Hogarth²

2011

Haematologica

View full text Add to dashboard Cite

“…12 One case of putative NBIA was treated successfully at our center, resulting in the disappearance of choreic dyskinesias and the normalization of gait disturbances. 13 Deferiprone, despite its possible side effects (gastrointestinal disturbances, transient increase of transaminases, and, especial- Inclusion criteria were: patients over 18 years of age with neurological symptoms correlated with iron deposition in the basal ganglia as documented by MRI (T2* and T2 signal decrease in the basal ganglia), performed within six months of enrolment. Exclusion criteria were: inability to undergo MRI; renal insufficiency (creatinine >1.5 mg/dL); neoplasias, systemic cardiovascular, severe renal and hepatic diseases; known hypersensitivity to deferiprone; pregnancy and breastfeeding.…”

Section: Introductionmentioning

confidence: 99%

A pilot trial of deferiprone for neurodegeneration with brain iron accumulation

Abbruzzese¹,

Cossu²,

Balocco³

et al. 2011

Haematologica

121

View full text Add to dashboard Cite

Acknowledgments: this is a not-for-profit study. We thank Jane Tricker and Silvia Caviglia for editorial assistance in the preparation of this article. We are also grateful to Alessandra Rosa for assistance with the statistical analysis. This trial was partially supported by E.O. Ospedali Galliera Scientific Committee and Fondazione CARIGE. Manuscript received on February 24, 2011. Revised version arrived on June 30, 2011. Manuscript accepted on July 4, 2011. Email: gianluca.forni@galliera.it Deferiprone was shown to reverse iron deposition in Friedreich's ataxia. This multi-center, unblinded, single-arm pilot study evaluated safety and efficacy of deferiprone for reducing cerebral iron accumulation in neurodegeneration with brain iron accumulation. Four patients with genetically-confirmed pantothenate kinase-associated neurodegeneration, and 2 with parkinsonism and focal dystonia, but inconclusive genetic tests, received 15 mg/kg deferiprone bid. Magnetic resonance imaging and neurological examinations were conducted at baseline, six and 12 months. Chelation treatment caused no apparent hematologic or neurological side effects. Magnetic resonance imaging revealed decreased iron accumulation in the globus pallidus of 2 patients (one with pantothenate kinase-associated neurodegeneration). Clinical rating scales and blinded video rating evaluations documented mild-to-moderate motor improvement in 3 patients (2 with pantothenate kinaseassociated neurodegeneration). These results underline the safety and tolerability of deferiprone, and suggest that chelating treatment might be effective in improving neurological manifestations associated with iron accumulation. Haematologica 2011;96(11):1708-1711. doi:10.3324/haematol.2011 This is an open-access paper. ABSTRACTly, agranulocytosis), currently represents the only possibility for removing and/or preventing iron accumulation in the brain. This was a multi-center, unblinded, single-arm pilot study, lasting one year, to evaluate the efficacy and safety of chelation therapy with deferiprone on cerebral iron accumulation in patients with a clinical diagnosis of NBIA. 4 Design and Methods PatientsInclusion criteria were: patients over 18 years of age with neurological symptoms correlated with iron deposition in the basal ganglia as documented by MRI (T2* and T2 signal decrease in the basal ganglia), performed within six months of enrolment. Exclusion criteria were: inability to undergo MRI; renal insufficiency (creatinine >1.5 mg/dL); neoplasias, systemic cardiovascular, severe renal and hepatic diseases; known hypersensitivity to deferiprone; pregnancy and breastfeeding. Additional exclusion criteria were average alanine transaminase (ALT) levels over 300, variations in ALT or aspartate transaminase (AST) levels of 300% during the year prior to enrolment, and patients judged potentially unreliable and/or uncooperative with regard to study procedures.The trial was approved by the E.O. Ospedali Galliera Ethics Committee and the local Ethics Committee at the Cagliari cent...

show abstract

“…This has important clinical implications because clinical trials are currently underway for deferiprone, a chelating agent known to traverse the blood-brain barrier. 15 Deferiprone has been shown to reverse iron deposition in Friedreich ataxia, associated with an appreciable decrease in iron content as measured by MR imaging. 12 It remains to be seen whether this agent will have a similar effect in NBIA and whether decreasing the brain iron burden will affect patients' clinical courses.…”

mentioning

confidence: 99%

Neuroimaging Features of Neurodegeneration with Brain Iron Accumulation

Kruer¹,

Boddaert²,

Schneider³

et al. 2011

AJNR Am J Neuroradiol

187

161

View full text Add to dashboard Cite

SUMMARY: NBIA characterizes a class of neurodegenerative diseases that feature a prominent extrapyramidal movement disorder, intellectual deterioration, and a characteristic deposition of iron in the basal ganglia. The diagnosis of NBIA is made on the basis of the combination of representative clinical features along with MR imaging evidence of iron accumulation. In many cases, confirmatory molecular genetic testing is now available as well. A number of new subtypes of NBIA have recently been described, with distinct neuroradiologic and clinical features. This article outlines the known subtypes of NBIA, delineates their clinical and radiographic features, and suggests an algorithm for evaluation.ABBREVIATIONS: ACP ϭ aceruloplasminemia; CNS ϭ central nervous system; FAHN ϭ fatty acid hydroxylase-associated neurodegeneration; INAD ϭ infantile neuroaxonal dystrophy; KRS ϭ KuforRakeb syndrome; NAD ϭ neuroaxonal dystrophy; NBIA ϭ neurodegeneration with brain iron accumulation; NFT ϭ neuroferritinopathy; PKAN ϭ pantothenate kinase-associated neurodegeneration; PLAN ϭ phospholipase-associated neurodegeneration; SENDA ϭ static encephalopathy of childhood with neurodegeneration in adulthood; WSS ϭ Woodhouse-Sakati syndrome B efore the widespread availability of MR imaging, a diagnosis of NBIA could be made only at the time of autopsy. In contrast, current diagnosis is facilitated by evaluation by using both T1-and T2-weighted sequences. As a paramagnetic substance, Fe 3ϩ catalyzes the nuclear spin relaxation of neighboring water protons. With standard clinical parameters, areas rich in iron appear hypointense on T2-weighted sequences, and isointense on T1 sequences. T2*-weighted acquisitions (gradient-echo sequences) may accentuate this degree of hypointensity ("blooming") and may be helpful in identifying NBIA disorders as may susceptibility-weighted images.1 In biologic iron-oxides, Fe 2ϩ typically has fewer unpaired electrons than Fe 3ϩ and is less effective in quenching T2-weighted signal intensity.2 Calcium may also appear isointense on T1 and hypointense on T2-weighted sequences, mimicking the appearance of iron. The 2 minerals are readily distinguished by CT, however, because Ca 2ϩ characteristically appears hyperintense to the surrounding brain parenchyma, while iron is isointense. In addition, iron typically appears markedly hypointense on both standard clinical diffusionweighted and apparent diffusion coefficient sequences. Other metals that may be deposited in neurodegenerative disorders, such as manganese and copper, have a distinct appearance on T1-and T2-weighted sequences, enabling a heuristic approach to diagnosis based on MR imaging parameters. The characteristics of these metals are summarized in Table 1. Despite the utility of MR imaging in this setting, it does not preclude the need for elemental analysis of neuropathologic specimens; rather, it enables putative diagnosis to be made during life.The radiographic appearance of the lesions themselves is of prime importance. Iron deposition occurs in mul...

show abstract

Regression of symptoms after selective iron chelation therapy in a case of neurodegeneration with brain iron accumulation

Cited by 73 publications

References 11 publications

As iron goes, so goes disease?

As iron goes, so goes disease?

A pilot trial of deferiprone for neurodegeneration with brain iron accumulation

Neuroimaging Features of Neurodegeneration with Brain Iron Accumulation

Contact Info

Product

Resources

About