Neurodegeneration with brain iron accumulation — Clinical syndromes and neuroimaging

Iron participates in a wide array of cellular functions and is essential for normal neural development and physiology. However, if inappropriately managed, the transition metal is capable of generating neurotoxic reactive oxygen species. A number of hereditary conditions perturb body iron homeostasis and some, collectively referred to as neurodegeneration with brain iron accumulation (NBIA), promote pathological deposition of the metal predominantly or exclusively within the central nervous system (CNS). In this article, we discuss seven NBIA disorders with emphasis on the clinical syndromes and neuroimaging. The latter primarily entails magnetic resonance scanning using iron-sensitive sequences. The conditions considered are Friedreich ataxia (FA), pantothenate kinase 2-associated neurodegeneration (PKAN), PLA2G6-associated neurodegeneration (PLAN), FA2H-associated neurodegeneration (FAHN), Kufor-Rakeb disease (KRD), aceruloplasminemia, and neuroferritinopathy. An approach to differential diagnosis and the status of iron chelation therapy for several of these entities are presented. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

► Iron is vital to life but may generate neurotoxic reactive oxygen species if inappropriately handled. ► A group of heritable disorders are collectively known as neurodegeneration with brain iron accumulation (NBIA). ► Known NBIA conditions include PKAN, PLAN, FAHN, KRD, aceruloplasminemia and neuroferritinopathy. ► Friedreich ataxia (FA), although not classically an NBIA, also features excessive brain iron deposition. ► Diagnosis of NBIA considers inheritance patterns, clinical syndromes, genetic testing and iron-sensitive neuroimaging.