Frontotemporal lobar degeneration with ubiquitin pathology: an autopsy case presenting with semantic dementia and upper motor neuron signs with a clinical course of 19 years

We report a case of a right-handed 74-year-old man who showed semantic dementia with a disease duration of 19 years. He initially presented with excessive use of pronouns and semantic paraphasia at the age of 55 years. Impairment of object recognition developed 5 years after the onset. Face recognition impairment and stereotypic behaviors developed 11 years after onset, and pyramidal signs 2 years before death. Pathological examination disclosed circumscribed severe atrophy in not only the bilateral temporal tips but also in the left precentral gyrus and pars opercularis in a motor speech field. Pyramidal tract involvement and loss of Betz cells were also evident. On the other hand, neurons in the anterior horns and hypoglossal nuclei were spared in number, although astrocytes were mildly proliferated. Ubiquitin-positive lesions were observed in the hippocampus, and frontal and temporal cortices. Neither Bunina bodies nor Pick bodies were present. These features clinically fit the international diagnostic criteria of semantic dementia and, histopathologically, frontotemporal lobar degeneration with motor neuron disease (FTLD-MND). This case suggests that (1) the distribution of cortical lesions associated with language disturbance is not uniform in FTLD-MND. It may be that only some cases of FTLD with ubiquitin pathology develop semantic dementia despite the high incidence of language disturbance, and (2) the precentral gyrus can be severely affected in FTLD-MND. After reviewing previous cases of FTLD-MND with a clinical course of more than 10 years, we also noticed that (3) FTLD-MND cases with a long disease duration often show upper motor neuron-predominant involvement.