Our understanding of dysfunction of the gastrointestinal system in patients with Parkinson's disease has increased substantially in the past decade. The entire gastrointestinal tract is affected in these patients, causing complications that range from oral issues, including drooling and swallowing problems, to delays in gastric emptying and constipation. Additionally, small intestinal bacterial overgrowth and Helicobacter pylori infection affect motor fluctuations by interfering with the absorption of antiparkinsonian drugs. The multifaceted role of the gastrointestinal system in Parkinson's disease necessitates a specific and detailed assessment and treatment plan. The presence of pervasive α-synuclein deposition in the gastrointestinal tract strongly implicates this system in the pathogenesis of Parkinson's disease. Future studies elucidating the role of the gastrointestinal tract in the pathological progression of Parkinson's disease might hold potential for early disease detection and development of neuroprotective approaches.
Objective: To determine the utility of detecting a-synuclein (aSyn) in colonic mucosal biopsy tissue as a potential diagnostic biomarker for Parkinson disease (PD). Methods:We used the paraffin-embedded tissue (PET) blot, which degrades physiologic nonaggregated aSyn using proteinase K and enhances antigen retrieval allowing sensitive and selective detection of remaining protein aggregates, to detect aSyn in colonic mucosal biopsies from 15 patients with early PD (,3 years), 7 patients with later PD (.5 years), and 11 individuals without PD. aSyn and serine 129-phosphorylated aSyn (Ser129p-aSyn) were assessed by PET blot and conventional immunohistochemistry.Results: PET blot-resistant aggregated aSyn and Ser129p-aSyn was present in 12 of 15 individuals with early PD, 7 of 7 individuals with later PD, and 11 of 11 control subjects. The number of biopsies positive by PET blot relative to conventional immunohistochemistry was significantly lower in both PD groups compared with the control group for both aSyn and Ser129p-aSyn, whereas routine immunohistochemistry was positive more often in PD, but was positive in as many as 9 of 11 control individuals.Conclusion: Strong evidence of the presence of aggregated hyperphosphorylated aSyn in individuals with and without PD, using such a sensitive and specific method as the PET blot, suggests that colonic deposition of aSyn is not a useful diagnostic test for PD. The utility of detecting aSyn in the colon as a biomarker in combination with other assessments remains to be determined. An accurate diagnostic test for early or prodromal Parkinson disease (PD) is a significant unmet need. Studies suggesting that abnormal deposition of a-synuclein (aSyn) may originate in the peripheral autonomic nervous system, 1,2 coupled with evidence of a prion-like spread of synucleinopathy, 3 have generated much interest in evaluating enteric nervous system (ENS) aSyn to assess early PD neuropathology before disease spread and long before markers reliant on advanced disease are affected. 4 Several recent studies of aSyn staining in colonic tissue from living patients with PD report sensitivities ranging from 72% to a remarkable 100%. [5][6][7] However, the description of some degree of aSyn labeling in controls in these studies and reports of aSyn in colonic tissue from individuals without PD have raised concerns regarding specificity. 8,9 The aim of the present study was to optimize the immunohistochemical detection of aSyn in colonic biopsies by adapting the paraffin-embedded tissue (PET) blot, a method developed to increase sensitivity and specificity of detecting aggregated proteins in a related proteinopathy, Creutzfeldt-Jakob disease. The PET blot degrades nonaggregated proteins allowing the selective detection of remaining, presumably pathologic, protein aggregates.
An accurate early diagnostic test for Parkinson's disease (PD) is a critical unmet need. Recently, independent groups using different histological techniques have reported that the presence of alpha-synuclein (α-syn) in colonic biopsy tissue is able to distinguish living patients with PD from those without the disease. In addition, a further study has suggested that the presence of α-syn in colonic biopsy tissue may be evident in early or even prodromal PD. However, several questions remain regarding the translation of these findings into using the assessment of α-syn deposition in the enteric nervous system as a diagnostic biomarker for prodromal PD. Here we address critical issues related to the location and quantification of enteric α-syn, detection of α-syn with currently available histological techniques, timing of detection of α-syn deposition, and, most crucially, whether enteric α-syn can distinguish those with PD from both healthy individuals and individuals with other related diseases. We conclude that, although enteric α-syn is a very exciting prospect, further studies will be vital to determine whether enteric α-syn deposition has the potential to be the biomarker for prodromal PD that the field so desperately seeks.
Patients undergoing radiotherapy for head and neck cancer (HNC) often experience malnutrition and dehydration during treatment. As a result, some centres place PEG tubes prophylactically (pPEG) to prevent these negative consequences. However, recent research has suggested that pPEG use may negatively affect swallowing physiology, function and/or quality of life, especially in the long term. The purpose of this study was to systematically review the literature on pPEG use in HNC patients undergoing radiotherapy and to determine its impact on swallowing-related outcomes. The following electronic databases were searched for all relevant primary research published through February 24, 2014: AMED, CINAHL, the Cochrane Library, Embase, Healthstar, Medline, and PsycINFO. Main search terms included HNC, radiotherapy, deglutition disorders, feeding tube(s), and prophylactic or elective. References for all accepted papers were hand searched to identify additional relevant research. Methodological quality was assessed using Cochrane's Risk of Bias. At all levels, two blinded raters provided judgments. Discrepancies were resolved by consensus. The search retrieved 181 unique citations. Twenty studies met our inclusion criteria. Quality assessment revealed that all studies were at risk for bias due to non-randomized sampling and unreported or inadequate blinding. Ten studies demonstrated selection bias with significant baseline differences between pPEG patients and controls. Results regarding the frequency and severity of dysphagia and swallowing-related outcomes were varied and inconclusive. The impact of pPEG use on swallowing and swallowing-related outcomes remains unclear. Well-controlled, randomized trials are needed to determine if pPEG places patients at greater risk for developing long-term dysphagia.
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