Corticobasal degeneration

75 Introduction and history While historical review suggests earlier reports of the entity now known as corticobasal degeneration (CBD), the disease was fi rst clearly described in a series of three cases in 1968, when it was termed corticodentatonigral degeneration with neuronal achromasia [ 1 ]. Subsequent terminology has included corticonigral degeneration with neuronal achromasia [ 2 ], corticobasal ganglionic degeneration [ 3 ], cortical-basal ganglionic degeneration [ 4 ], and corticobasal degeneration [ 5 ]. While the more precise terminology of corticalbasal ganglionic degeneration (CBGD) may be favored, the most commonly used descriptor today is CBD. As understanding of this complex disease process has grown over the forty years since the original clinicopathological series, it has become clear that the corticobasal spectrum involves a clinical syndrome and a pathological entity that only sometimes overlap ( Figure 5.1 ). Because of this, the clinical diagnosis is now labeled the corticobasal syndrome (CBS) while the term CBD is reserved for pathologically confi rmed diagnoses [ 6 ]. As will be discussed further, the pathological entity of CBD is associated with varying clinical presentations that can change even in a single individual over time, while CBS is associated with a variety of fi ndings on pathological examination. It is only in this context that the current understanding of CBD can be discussed. Th e overlap of CBS, CBD, and related disorders is considerable, making accurate clinical diagnosis challenging and emphasizing the need for continued research. Because CBD is a pathological diagnosis, discussion of this entity must begin with neuropathological fi ndings. CBD is a sporadic neurodegenerative process related to abnormal aggregation of hyperphosphorylated tau. Tau is a microtubule-associated protein the role of which in the neuron is to promote microtubule assembly and stabilization. Other tauopathies include frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), progressive supranuclear palsy (PSP), and Pick’s disease (PiD). In particular, CBD is associated with abnormal insoluble tau isoforms with four conserved repeat sequences (4R tau), discussed further in the following sections. Th e Offi ce of Rare Diseases published criteria for CBD in 2002 ( Table 5.1 ). Th e crit eria emphasize the presence of tau-immunoreactive lesions in addition to the presence of ballooned neurons, cortical atrophy, and nigral degeneration [ 7 ]. Diagnosis is based on histopathological fi ndings, although gross fi ndings can provide supportive information. Confi rmation of the diagnosis requires identifi cation of the pathological features of CBD Corticobasal degeneration