Redefining the multidimensional clinical phenotypes of frontotemporal lobar degeneration syndromes
Publication: Brain A Journal of Neurology
Alexander G Murley, Ian Coyle-Gilchrist, Matthew A Rouse, P Simon Jones, Win Li, Julie Wiggins, Claire Lansdall, Patricia Vázquez Rodríguez, Alicia Wilcox, Kamen A Tsvetanov, Karalyn Patterson, Matthew A Lambon Ralph, James B Rowe
1 May 2020
The syndromes caused by frontotemporal lobar degeneration have highly heterogeneous and overlapping clinical features. There has been great progress in the refinement of clinical diagnostic criteria in the past decade, but the researchers propose that a better understanding of aetiology, pathophysiology and symptomatic treatments can arise from a transdiagnostic approach to clinical phenotype and brain morphometry. In a cross-sectional epidemiological study, they examined 310 patients with a syndrome likely to be caused by frontotemporal lobar degeneration, including behavioural variant frontotemporal dementia, non-fluent, and semantic variants of primary progressive aphasia (PPA), progressive supranuclear palsy and corticobasal syndrome. They included patients with logopenic PPA and those who met criteria for PPA but not a specific subtype.
The results show that syndromes associated with frontotemporal lobar degeneration do not form discrete mutually exclusive categories from their clinical features or structural brain changes, but instead exist in a multidimensional spectrum. Patients often manifest diagnostic features of multiple disorders while deficits in behaviour, movement and language domains are not confined to specific diagnostic groups.
It is important to recognize individual differences in clinical phenotype, both for clinical management and to understand pathogenic mechanisms. The researchers suggest that a transdiagnostic approach to the spectrum of frontotemporal lobar degeneration syndromes provides a useful framework with which to understand disease aetiology, progression, and heterogeneity and to target future treatments to a higher proportion of patients.