Argyrophilic grain disease with delusions and hallucinations: a pathological study

No clear clinical syndrome for argyrophilic grain disease (AGD) has yet been identified. Previous studies have documented its clinical features, namely, personality changes characterized by emotional disorder involving aggression or ill temper and relatively well-preserved cognitive function, but the clinical manifestations of delusions and hallucinations as they appear in AGD have not been thoroughly described. Here, we report on a 72-year-old Japanese AGD patient who showed psychiatric symptoms, memory impairment and emotional change. He perceived and described a person who was not present and tried to grasp things on the floor though nothing was there. He also insisted that somebody was watching him and consequently always kept his curtains closed. These psychiatric symptoms were observed at an early stage in the patient's disease course. Serial neuroradiological examination showed progressive atrophy of the bilateral temporal lobes. The patient died at 79 years-of-age. Microscopic neuropathological examination showed transactivation responsive region (TAR)-DNA-binding protein of 43 kDa (TDP-43) positive structures in addition to widespread argyrophilic grains and coiled bodies. According to recent recommendations for pathological diagnosis, this case corresponds to AGD with limbic TDP-43 pathology. This case shows that patients with AGD that is eventually confirmed through autopsy can present with delusions and hallucinations early in the course of their disease. The clinical significance of TDP-43 pathology in the brains of patients with AGD remains uncertain.