Author(s): Julien Lagarde 1,4, Romain Valabrègue 3,4,5, Jean-Christophe Corvol 1,4,5,6, Fanny Pineau 1,6, Isabelle Le Ber 1,4,5,7, Marie Vidailhet 1,4,5, Bruno Dubois 1,4,5,7, Richard Levy 2,4,5,*
Progressive supranuclear palsy (PSP) and frontotemporal lobar degeneration (FTD) are usually considered two distinct clinicohistological entities. Indeed, on the basis of the clinical syndromes, the topography of brain lesions and their histological/biological characteristics, many features differentiate them: the most frequent clinical form of FTD (called the "behavioral variant") is a behavioral dementia of the frontal type, while the most typical clinical form of PSP (called the Richardson form) is characterized by axial parkinsonism and supranuclear oculomotor palsy. The topography of neurodegeneration is mostly cortical in FTD, affecting the ventromedial prefrontal cortex (PFC) and to some extent the temporal lobes and dorsal PFC , while it is mostly subcortical in PSP, affecting the brainstem, cerebellum and basal ganglia . In terms of the underlying proteinopathies, tau pathology is only found in 20-30% of FTD cases and affects the A, C and E tau isoforms, while PSP is consistently associated with a tauopathy affecting the B, D and F tau isoforms .
Despite these important differences, from a clinical standpoint, it is important to note that PSP and FTD share a prominent frontal cognitive syndrome, which is consistently seen in the "classic" Richardson form of PSP. It is present in more than half the patients from the first year of the clinical disease , and consists mostly of a dysexecutive syndrome with "cognitive inertia", i.e. an increased latency of responses, the impairment of information retrieval and reasoning and a lack of mental flexibility , . This cognitive syndrome is associated with severe frontal behavioral signs such as apathy/abulia/apragmatism, an environmental dependency syndrome and, more rarely than in bvFTD, behavioral disinhibition -. This frontal cognitive syndrome is sometimes so marked that it has served as the prototypical description of the so-called "subcortical dementia" . However, it is also strongly correlated with frontal hypometabolism , more pronounced in the lateral superior and medial PFC . Even though it has been shown to be related to frontal deafferentation due to subcortical lesions (mostly in the basal ganglia) , it is now well established that direct cortical lesions involving the frontal cortex do exist , and could be implicated in the frontal signs observed in PSP. Conversely, the widespread disruption of subcortical structures has been shown in FTD and could account for some of the observed cognitive or behavioral features of the disease , . In addition, frontal dysfunction may appear early in the course of PSP and may present with only one other clinical feature in 20% of patients , . Consequently, it is sometimes difficult, at least in the early stages, to clinically distinguish these atypical forms of PSP from the behavioral variant of FTD (bvFTD) .
Taken as a whole, these findings suggest that, it would be of interest to compare and clarify the clinical and anatomical features characterizing the frontal cognitive syndrome in PSP and...