Very Late-Onset Neurodegeneration with Brain Iron Accumulation Associated with Mild Chorea: A Clinicopathological Case

Abstract

Background: Neurodegeneration with Brain Iron Accumulation (NBIA) rarely manifests after the age of 50 years. The phenotype in these cases is most often parkinsonism.

Objectives: To present the case with the oldest age of NBIA onset reported so far.

Methods: Clinico-pathological case.

Results: A female patient presented at 84 years of age with wobbling of the head that had started approximately 2 years ago. Choreiform movements of the head and upper body were observed and these abated when she focused on doing something else or lay down but started again when she was talking or moving. There were no cerebellar signs, abnormal reflexes or sensory disturbance. Cognitive screening tests were abnormal but significant cognitive symptoms absent. Magnetic Resonance Imaging (MRI) showed extensive iron accumulation in the basal ganglia and upper pons. Extensive analyses yielded no genetic diagnosis. She died suddenly 19 months after her first appointment. In neuropathological analysis the basal ganglia, especially the lenticular nuclei, were macroscopically darker than normal with notable iron accumulation in the arterial walls in these areas. Prominent axonal ballooning was observed especially in the internal globus pallidus. Globus pallidus displayed iron accumulation, observed to a slightly lesser extent also in the substantia nigra pars reticulata. The neuropathological phenotype resembled classical pantothenate kinase-associated neurodegeneration (PKAN). Concomitant beta-amyloid, hyperphosphorylated tau protein (consistent with primary age-related tauopathy, or PART) and TDP-43 (consistent with LATE-NC) pathologies were also evident.

Conclusions: NBIA may manifest at a very advanced age with a mild phenotype, likely influenced by coexisting neuropathology.

Keywords: chorea; limbic‐predominant age‐related TDP‐43 encephalopathy (LATE); neurodegeneration with brain iron accumulation; neuropathology; primary age‐related tauopathy (PART).