Neuropathology and staging of parkinson’s disease

In the present discussion, Parkinson’s disease (PD) is considered to be a term for an extrapyramidal motor syndrome characterized by bradykinesia, rigidity, postural instability, and tremor, while Lewy body disease (LBD) is a pathologic term for a disorder characterized by neuronal lesions [i.e., Lewy bodies (LBs)] composed of a-synuclein (SNCA). Autopsy studies have shown that LBD is the most common substrate for PD, but other disorders, most notably progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), can produce a similar extrapyramidal syndrome. Complicating this discussion is the fact that nonmotor manifestations are common in PD, and it is possible that the earliest clinical features of PD may not be those of an extrapyramidal motor dysfunction, but rather a syndrome characterized by autonomic dysfunction, anosmia, or a sleep disturbance. Clinical features of advanced PD may be overwhelmingly cognitive or psychiatric in nature, rather than motor. Moreover, LBD is also the pathologic substrate of non-PD clinical syndromes, including focal dystonias, pure autonomic failure, rapid eye movement behavior disorder (RBD) and some cases of essential tremor as well as dementia, with fluctuations and psychotic features referred to as dementia with Lewy bodies (DLB).