The bvFTD phenocopy syndrome: a case study supported by repeated MRI, [¹⁸F]FDG-PET and pathological assessment

Abstract

A clinical syndrome with neuropsychiatric features of bvFTD without neuroimaging abnormalities and a lack of decline is a phenocopy of bvFTD (phFTD). Growing evidence suggests that psychological, psychiatric and environmental factors underlie phFTD. We describe a patient diagnosed with bvFTD prior to the revision of the diagnostic guidelines of FTD. Repeated neuroimaging was normal and there was no FTD pathology at autopsy, rejecting the diagnosis. We hypothesize on etiological factors that on hindsight might have played a role. This case report contributes to the understanding of phFTD and adds to the sparse literature of the postmortem assessment of phFTD.

The neurology ‐ psychiatry interface: variations on a diagnostic theme

“…As regards the latter, neuropathological data are exceedingly sparse but changes typical of neurodegenerative disorder have not been reported, merely those consistent with age-related change. 8,9 Pathogenic hexanucleotide repeat expansions in the C9orf72 gene, which of course establish a diagnosis of definite bvFTD (see Box 2), have seldom been found in patients with a clinical diagnosis of phFTD. 10 A number of learning points emerge from the consideration of this case.…”

“…A consequence of a misdiagnosis of functional cognitive disorder as early‐stage neurodegeneration (the converse can certainly occur). An indolent, non‐progressive presentation of bvFTD. As regards the latter, neuropathological data are exceedingly sparse but changes typical of neurodegenerative disorder have not been reported, merely those consistent with age‐related change 8,9 . Pathogenic hexanucleotide repeat expansions in the C9orf72 gene, which of course establish a diagnosis of definite bvFTD (see Box 2), have seldom been found in patients with a clinical diagnosis of phFTD 10 …”

Frontotemporal Dementia and Late-Onset Bipolar Disorder: The Many Directions of a Busy Road

“…The etiology of the bvFTD phenocopy syndrome has been a matter of great interest ( 10 , 30 , 33 , 55 , 65 ). Intriguingly, a few patients coming to autopsy did not have any frontotemporal lobar degeneration (FTLD) pathology ( 12 , 66 ). FTLD-ubiquitin pathology was observed in the post-mortem examination of a patient with a very slowly progressive form of FTD, whose son had a similar history in addition to brain imaging that was stable for over a decade ( 67 ).…”

“…Differential diagnosis of bvFTD with personality or mood disorders is particularly challenging ( 8 ). Indeed, whereas standard neuroimaging methods, such as the fluorodeoxyglucose positron emission (FDG-PET), may show a sensitivity of 97% and specificity of 86% for distinguishing FTD from AD ( 9 ), the main differential of FTD is with primary psychiatric disorders ( 10 ), and some cases will remain unsolved despite neuroimaging and expert evaluation ( 11 , 12 ) ( Figure 1 ). Many neurodegenerative disorders, particularly FTD, are preceded by affective symptoms, such as mania, racing thoughts, catatonia, and apathy, and numerous genetic of typical FTD symptoms and psychosis have been described ( 13 ).…”

Social cognition differentiates phenocopy syndrome of behavioural variant frontotemporal dementia from behavioural variant frontotemporal dementia

“…Nonetheless, the two remaining cases showed some signs of possible ubiquitin-positive inclusions. 4,6,10,11 Caution is also warranted with respect to carriers of the C9ORF72 repeat expansion, that is associated with an extremely slow disease course with preserved neuroimaging. 12,13 The clinical distinction of phFTD and bvFTD at presentation is challenging due to the great overlap in the nature of the behavioural symptoms, symptom duration at first presentation and severity as reported by spouses or family members.…”