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Adult-Onset Neurodegeneration With Brain Iron Accumulation and Cortical -Synuclein and Tau Pathology

A Distinct Clinicopathological Entity

George K. Tofaris, PhD, MRCP; Tamas Revesz, MD, FRCPath; Thomas S. Jacques, PhD, MRCP, MRCPath; Savvas Papacostas, MD; Jeremy Chataway, MA, PhD, MRCP

Arch Neurol. 2007;64(2):280-282.

Background  Neurodegeneration with brain iron accumulation is a rare neurodegenerative disorder characterized by iron deposition in the basal ganglia and neuroaxonal dystrophy. Familial cases with mutations in the pantothenate kinase gene are associated with a specific phenotype. In contrast, sporadic cases are heterogeneous in their clinical presentation.

Objective  To describe an atypical case of sporadic late-onset neurodegeneration with brain iron accumulation.

Design, Setting, and Patient  Case report of a patient who presented with psychiatric features at age 22 years followed by progressive gait disturbance, extrapyramidal symptoms, epilepsy, and corticospinal tract involvement.

Results  Magnetic resonance imaging showed iron deposition in the globus pallidus and substantia nigra. Cortical biopsy revealed Lewy bodies with predominant -synuclein and less extensive tau-positive neurites.

Conclusions  Our findings in association with previously reported cases suggest that cortical neuritic and Lewy body pathology is a feature of atypical neurodegeneration with brain iron accumulation, clinically characterized by adult onset and psychiatric symptoms. These observations raise the possibility that these cases of atypical neurodegeneration with brain iron accumulation represent a distinct clinicopathological syndrome and suggest a molecular link between iron deposition and -synuclein accumulation.

Author Affiliations: Department of Clinical Neurology, National Hospital for Neurology and Neurosurgery (Drs Tofaris and Chataway), Division of Neuropathology, Institute of Neurology (Dr Revesz), and Neural Development Unit and Department of Histopathology, Institute of Child Health and Great Ormond Street Hospital (Dr Jacques), London, England; and Institute of Neurology and Genetics, Nicosia, Cyprus (Dr Papacostas).

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