UCSF

In 2009, inclusions containing the fused in sarcoma (FUS) protein were identified as a third major molecular class of pathology underlying the behavioral variant frontotemporal dementia (bvFTD) syndrome. Due to the low prevalence of FUS pathology, few clinical descriptions have been published and none provides information about specific social-emotional deficits despite evidence for severe behavioral manifestations in this disorder. We evaluated a patient with bvFTD due to FUS pathology using a comprehensive battery of cognitive and social- emotional tests. A structural MRI scan and genetic tests for tau, progranulin, and FUS mutations were also performed. The patient showed preserved general cognitive functioning and superior working memory, but severe deficits in emotion attribution, sensitivity to punishment, and diminished capacity for interpersonal warmth and empathy. The gray matter atrophy pattern corresponded to this focal deficit profile, with preservation of dorsolateral fronto-parietal regions associated with executive functioning but severe damage to right worse than left frontoinsula, temporal pole, subgenual anterior cingulate, medial orbitofrontal cortex, amygdala, and caudate. This patient demonstrates the striking focality associated with FUS neuropathology in patients with bvFTD.