Neurodegeneration with Brain Iron Accumulation: Diagnosis and Management

Abstract

Neurodegeneration with brain iron accumulation (NBIA) encompasses a group of inherited disorders that share the clinical features of an extrapyramidal movement disorder accompanied by varying degrees of intellectual disability and abnormal iron deposition in the basal ganglia. The genetic basis of ten forms of NBIA is now known. The clinical features of NBIA range from rapid global neurodevelopmental regression in infancy to mild parkinsonism with minimal cognitive impairment in adulthood, with wide variation seen between and within the specific NBIA sub-type. This review describes the clinical presentations, imaging findings, pathologic features, and treatment considerations for this heterogeneous group of disorders.

What’s in a name? Problems, facts and controversies regarding neurological eponyms

“…In 1922, Hallervorden and Spatz reported the case of a family with five affected sisters with dystonia, cognitive dysfunction and confirmed neuropathological lesions of the globus pallidus and substantia nigra 5,6 . After this kindred-case description, the disease became known around the world as Hallervorden-Spatz syndrome (HSS) 5,6 . But, in spite of their seminal description, a shadowy past would lead to a change in nomenclature for this syndrome: Julius Hallervorden and Hugo Spatz were important German neuropathologists who performed several neuropathological studies on brain specimens of individuals with mental retardation executed during the Third Reich euthanasia program 5,6 .…”

“…Neurodegeneration with brain iron accumulation (NBIA) represents a heterogeneous group of inherited neurodegenerative diseases characterized by excess iron accumulation, particularly in the basal ganglia and to a lesser degree in the substantia nigra and adjacent regions 5 . Common clinical features of NBIA include movement disorders, particularly parkinsonism and dystonia, cognitive dysfunction, pyramidal signs and retinal abnormalities 5 .…”

“…Common clinical features of NBIA include movement disorders, particularly parkinsonism and dystonia, cognitive dysfunction, pyramidal signs and retinal abnormalities 5 . In 1922, Hallervorden and Spatz reported the case of a family with five affected sisters with dystonia, cognitive dysfunction and confirmed neuropathological lesions of the globus pallidus and substantia nigra 5,6 . After this kindred-case description, the disease became known around the world as Hallervorden-Spatz syndrome (HSS) 5,6 .…”

“…After this kindred-case description, the disease became known around the world as Hallervorden-Spatz syndrome (HSS) 5,6 . But, in spite of their seminal description, a shadowy past would lead to a change in nomenclature for this syndrome: Julius Hallervorden and Hugo Spatz were important German neuropathologists who performed several neuropathological studies on brain specimens of individuals with mental retardation executed during the Third Reich euthanasia program 5,6 . After confirmation of Hallervorden's and Spatz's involvement in the euthanasia program operated by the Nazi regime in Germany and recent neuroimaging and genetic discoveries, this syndrome was renamed NBIA 5,6 .…”

“…But, in spite of their seminal description, a shadowy past would lead to a change in nomenclature for this syndrome: Julius Hallervorden and Hugo Spatz were important German neuropathologists who performed several neuropathological studies on brain specimens of individuals with mental retardation executed during the Third Reich euthanasia program 5,6 . After confirmation of Hallervorden's and Spatz's involvement in the euthanasia program operated by the Nazi regime in Germany and recent neuroimaging and genetic discoveries, this syndrome was renamed NBIA 5,6 . To date, ten forms of NBIA have been described, the most common of which are pantothenate kinase-associated neurodegeneration (PKAN), caused by mutations in the PANK2 gene 5 .…”