Parkinson’s Disease

Abstract

Parkinson’s Disease (PD) is generally considered a movement disorder characterized by loss of dopaminergic neurons in the central nervous system (CNS), most notably in the substantia nigra. The pathogenesis of the neuronal degeneration is not completely understood but is characterized by abnormal protein deposits forming characteristic neuronal inclusions, which are visible by light microscopy of autopsy samples, and termed Lewy bodies. α-Synuclein is one of the proteins found in these inclusions and has attracted interest because mutations of the gene encoding for this protein are found in familiar cases of PD. Most of the disability associated with PD is indeed the result of this CNS defect, and the treatment is aimed at increasing dopamine levels in the CNS, while avoiding as much as possible an increase in the periphery. Less widely recognized is the fact that orthostatic hypotension can occur in PD patients and can become symptomatic and disabling in a significant proportion of patients. The incidence of documented orthostatic hypotension in PD, in community-based studies, ranges from 10% to 40%. Orthostatic hypotension in PD is commonly attributed to the known adverse effects of dopaminergic drugs. However, over the last decade there is growing evidence that peripheral nerves, particularly autonomic neurons, are also involved in PD. Lewy body inclusions, containing α-synuclein, have been found in peripheral autonomic neurons in autopsy cases of otherwise classic PD.1 Microscopically, eosinophilic ubiquitin- and α-synuclein–positive Lewy Bodies and Lewy neurites are not only found in the substantia nigra and locus ceruleus but also are widespread in ganglions cells …