Adult-onset neurodegeneration with brain iron accumulation and cortical alpha-synuclein and tau pathology: a distinct clinicopathological entity.

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 alpha-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 alpha-synuclein accumulation.