Exploring the phenotypic spectrum of frontotemporal lobar degeneration

Frontotemporal lobar degeneration (FTLD) refers to a spectrum of neuropathology preferentially affecting the frontal and temporal lobes manifesting with progressive behavioral, language, and motor impairment. These clinical symptoms linked to FTLD are collectively referred to as frontotemporal spectrum disorders (FTSD) and include behavioral-variant frontotemporal dementia, nonfluent/agrammatic primary progressive aphasia, semantic variant primary progressive aphasia, right temporal variant frontotemporal dementia, corticobasal syndrome, progressive supranuclear palsy, and amyotrophic lateral sclerosis-frontotemporal spectrum disorders. While some patients with FTLD present with a single, well-defined syndrome, others exhibit features of multiple syndromes, and clinical phenotypes frequently evolve over time. Moreover, there is substantial phenotypic overlap between FTSD and other neurological disorders, contributing to frequent misdiagnosis and diagnostic delays. To address these challenges, we provide a practical, clinically oriented framework for the diagnosis of FTSD. We review common and nuanced clinical features, pertinent diagnostic testing, and the role of genetic testing in the context of current understanding of neuropathological correlates. Despite the absence of disease-modifying therapies, we also outline evidence-informed strategies for the symptomatic management of FTSD.