Is there an Association between Parkinsons Disease and IBD? M. W. Johnson, K. Lithgo, T. Price Gastroenterology Department, Luton & Dunstable University.

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Is there an Association between Parkinsons Disease and IBD? M. W. Johnson, K. Lithgo, T. Price Gastroenterology Department, Luton & Dunstable University Hospital, Luton. LU40DZ. UK. Introduction The BRAAK theory of Parkinsons disease believes that the aetiology may all start in the bowel with a slow virus entering the central nervous system after passing through the intestinal mucosa {Hawkes C.H., 2007}. There is already work confirming an increased frequency of H. pylori infections (requiring treatment) in the 5 years prior to Parkinsons disease being diagnosed {Nielsen H.H. 2012}. Recently a gene associated with the inherited form of Parkinsons disease (leucine-rich repeat kinase 2 - LRRK2), has been shown to regulate the transcription factor NFAT1 (nuclear factor of activated T cells 1), which in turn appears to regulate cells in the immune system, including macrophages, dendritic cells and T cells. Higher quantities of NFAT1 activity are seen in the colonic mucosa of Crohns patients, where the total quantity directly correlates to the severity of the disease {Liu Z., 2011}. Aims To assess whether there was a higher than expected association between inflammatory bowel disease (IBD) and Parkinsons disease (PD). Methods A cross correlation analysis was performed using the IBD and PD databases at the Luton & Dunstable University Hospital. A retrospective analysis was also performed using medical notes and the internal electronic results system to assess the disease severity of these two conditions. Results The prevalence of IBD and PD within the UK population is said to be 225/100,000 (UC 150/100,000 + CrD 75/100,000) and 140/100,000, respectively. The L&D catchment area covers 330,000 and so one would have expected approximately 742 IBD and 462 PD patients, respectively. The databases had 2783 IBD patients (median age = 51) and 350 PD patients (median age = 79) listed. Probability analysis predicted that we would find just 1 patient with both PK and IBD, however, we found 6 subjects with these conditions concomitantly. This translates into 0.2% of IBD patients having PD and 1.72% of PD patients having IBD. Mild-to-moderate PD was noted in 3 patients, and all 3 had mild-tomoderate IBD. Three of the PD patients were scored as having moderate-to-severe disease, and 2 of these also had moderate-to-severe IBD. Conclusions The proportion of PD patients having concomitant IBD is considerably higher than one would have expected by chance. This raises questions abount a possible shared aetiology. There are a variety of aetiological theories in IBD, that consider bacteria (or a change in the balance of mucosal adherent flora) to be a precipitating or aggrevating factor in the subsequent intra-mucosal inflammatory cascade. As the BRAAK theory states; it is possible that the initial insult in Parkinsons disease may come from the translocation of bacteria (or pathogens) across the intestinal mucosal barrier. The breakdown in this barrier mechanism may be related to the two conditions having shared common genetic associations. Interestingly, those patients with more significant IBD also had more severe PD. References Lenardo, M. et al (2011) Autoimmune Diseases; Protein involved in Parkinsons disease also regulates inflammatory bowel disease. Nature immunology (9). Parkinsons disease foundation (2012) Common bacterium related to Parkinsons disease. Parkinsons disease foundation. Pierantozzi, M. et al (2006) Helicobacter pylori eradication and L-dopa absorption in patients PD and motor fluctuation. BMA Neurology: vol – Rees, K et al (2011) Helicobacter pylori eradication for Parkinsons disease. Wiley online library. [assess on: 09/2012] Schnabel, J. (2010) Does Parkinsons disease start outside the brain? Schulz, J. et al (2006) Cycad toxins, helicobacter pylori and Parkinsonism: Cholesterol glucosides as the common denominator. Medline 66 (6) Identifier PD SeverityIBD Severity AModerate to serveModerate to severe BMild to moderate CModerate to serveMild to moderate D E FModerate to serveModerate to severe Table 1. Association between PK and IBD Disease Severity Scores BSG