Abstract
BackgroundThe presence of Lewy bodies and Lewy neurites (LN) has been demonstrated in the enteric nervous system (ENS) of Parkinson's disease (PD) patients. The aims of the present research were to use routine colonoscopy biopsies (1) to analyze, in depth, enteric pathology throughout the colonic submucosal plexus (SMP), and (2) to correlate the pathological burden with neurological and gastrointestinal (GI) symptoms.Methodology/Principal FindingsA total of 10 control and 29 PD patients divided into 3 groups according to disease duration were included. PD and GI symptoms were assessed using the Unified Parkinson's Disease Rating Scale part III and the Rome III questionnaire, respectively. Four biopsies were taken from the ascending and descending colon during the course of a total colonoscopy. Immunohistochemical analysis was performed using antibodies against phosphorylated alpha-synuclein, neurofilaments NF 220 kDa (NF) and tyrosine hydroxylase (TH). The density of LN, labeled by anti-phosphorylated alpha-synuclein antibodies, was evaluated using a quantitative rating score. Lewy pathology was apparent in the colonic biopsies from 21 patients and in none of the controls. A decreased number of NF-immunoreactive neurons per ganglion was observed in the SMP of PD patients compared to controls. The amount of LN in the ENS was inversely correlated with neuronal count and positively correlated with levodopa-unresponsive features and constipation.Conclusion/SignificanceAnalysis of the ENS by routine colonoscopy biopsies is a useful tool for pre-mortem neuropathological diagnosis of PD, and also provides insight into the progression of motor and non-motor symptoms.
Highlights
Normal function of the gastrointestinal (GI) tract relies both on intrinsic reflexes and extrinsic control
The four main outcomes of the present survey are (1) the demonstration of Lewy neurites (LN) in the submucosal plexus (SMP) of 72% of Parkinson’s disease (PD) patients, but in none of the controls, (2) a higher frequency of constipation in LNpositive patients, (3) a strong correlation between LN burden and disease severity, (4) the possibility to readily and reproducibly analyze the enteric nervous system (ENS) in living patients, thereby providing an opportunity to develop an original biomarker for PD
Lewy pathology in the SMP was composed of LN only
Summary
Normal function of the gastrointestinal (GI) tract relies both on intrinsic reflexes and extrinsic control. The intrinsic innervation relies on the enteric nervous system (ENS), an integrative neuronal network organized in two main plexuses, myenteric and submucosal, that control bowel motility and transmucosal fluid exchange, respectively [1]. A wide range of GI diseases associated with motility dysfunction can be considered, in part, as extrinsic and/or enteric neuropathies [2]. Parkinson’s disease (PD) is likely to be a prime example because alterations of the ENS and GI dysfunction have been described in the course of the disease [6]. Whether these alterations mirror brain pathology, and how they relate to clinical symptoms, remain open questions. The aims of the present research were to use routine colonoscopy biopsies (1) to analyze, in depth, enteric pathology throughout the colonic submucosal plexus (SMP), and (2) to correlate the pathological burden with neurological and gastrointestinal (GI) symptoms
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