Lesions outside the CNS in Parkinson's disease

Abstract

Parkinson's disease (PD) is not a simple movement disorder induced just by loss of dopaminergic neurons in the substantia nigra pars compacta. Apparently, the substantia nigra is not the only or the first brain region damaged in PD. Moreover, older and recent studies have shown that the degenerative process in PD is much more extensive and affects not only the central nervous system (CNS) but also the peripheral autonomic nervous system and the organs outside the brain that the latter innervates. These include mainly the gastrointestinal tract, the heart, kidneys, urogenital system, and skin. Additional extra-CNS organs that are involved in PD include the eye and the adrenal gland. This article reviews the anatomical, physiological, and clinical features of extracerebral manifestations of PD, and describes their relevance to the etiology and pathogenesis of the disease. It establishes this illness as a systemic CNS and peripheral disorder that warrants new hypotheses regarding its causation and progression.

The pathology roadmap in Parkinson disease

“…In PD patients, Lewy pathology has been seen in both in the submandibular gland and the superior cervical ganglion. 11 Djaldetti and colleagues have reported a marked denervation of all autonomic neurites in skin, 13 work supported by analyses of skin biopsies from PD patients. 5,14 Lewy pathology and dopaminergic neuron loss also has been found in the enteric nervous system of many PD patients, particularly the lower gastrointestinal tract, which might be responsible for decreased gastric motility and constipation.…”

Synuclein deposition and non-motor symptoms in Parkinson disease

“…Altered intraretinal dopaminergic synaptic activity, in addtion to disorders of higher (cortical) visual processing contribute to visual symptoms experienced by PD patients [70,71].…”

α‐Synuclein inclusions in the skin of Parkinson's disease and parkinsonism

“…Dopamine transporter (DAT) scans and magnetic resonance imaging (MRI) are helpful but cannot differentiate among PD, MSA, and PSP since all of them exhibit a similar dopamine deficit and characteristic signs are not always pathognomonic (the “hot cross bun” for MSA and the “hummingbird sign” for PSP) 17–20. There is not a strong biomarker to help differentiate between these diseases yet, but the presence of α -synuclein has been confirmed in PD21 in a number of different tissues, including skin tissue 22,23. While studies suggest that the sebaceous glands can express protein aggregates during neurodegenerative diseases,22 there is little information available regarding the in vivo accumulation of α -synuclein,24 since a low positive rate is reported in postmortem studies 8,9.…”