Constipation: an emerging risk factor for Parkinson's disease?

Abstract

Constipation is the most prominent and disabling manifestation of lower gastrointestinal (GI) dysfunction in Parkinson's disease (PD). The prevalence of constipation in PD patients ranges from 24.6% to 63%; this variability is due to the different criteria used to define constipation and to the type of population enrolled in the studies. In addition, constipation may play an active role in the pathophysiological changes that underlie motor fluctuations in advanced PD through its negative effects on absorption of levodopa. Several clinical studies now consistently suggest that constipation may precede the first occurrence of classical motor features in PD. Studies in vivo, using biopsies of the GI tract and more recently functional imaging investigations, showed the presence of α-synuclein (α-SYN) aggregates and neurotransmitter alterations in enteric tissues. All these findings support the Braak proposed model for the pathophysiology of α-SYN aggregates in PD, with early pathological involvement of the enteric nervous system and dorsal motor nucleus of the vagus. Therefore, constipation could have the potential sensitivity to be used as a clinical biomarker of the prodromal phase of the disease. The use of colonic biopsies to look at α-SYN pathology, once confirmed by larger prospective studies, might eventually represent a feasible, albeit partially invasive, new diagnostic biomarker for PD.

A New Perspective on Parkinson’s Disease: Pathology Begins in the Gastrointestinal Tract

“…This non-motor symptom could allow for early diagnosis up to ten years sooner than classical diagnostic measures (Stirpe et al, 2016). However, there is a 15-20% prevalence of constipation in the general population, of which only 30-60% are comorbid for both constipation and PD (Postuma & Berg, 2016).…”

“…Lewy bodies accumulate in vasoactive intestinal peptide (VIP) neurons, which amount to nearly 50% of all myenteric neurons (Annerino et al, 2012;Smeyne & Jackson, 2015;Stirpe et al, 2016). Lewy body-filled VIP interneurons disinhibit motor neurons in the GI tract distal smooth muscles, resulting in reflex relaxation impairment (Stirpe et al, 2016). Constipation appears to be more severe in patients who have had PD for many years (Tan et al, 2016).…”

“…Thus, constipation has relatively low prognostic integrity. Constipation has been found to play a role in negatively affecting the absorption of levodopa (Ogawa et al, 2012;Postuma & Berg, 2016;Stirpe et al, 2016;Tan et al, 2016). L-3,4 dihydroxyphestantia nigral degeneration (Mukherjee et al, 2016).…”

“…Since DA levels are depleted in midbrain regions of PD patients, levodopa is administered for subsequent DA synthesis (Bianchine et al, 1971). However, the effects of constipation disrupt oral levodopa absorption, and thus motor fluctuations have been observed (Stirpe et al, 2016). A 2012 case study showcased a 69-year-old man who had both PD and intractable constipation for nine years, and unexpectedly presented with parkinsonism-hyperpyrexia syndrome (PHS) (Ogawa et al, 2012).…”

Advances and insights into neurological practice 2016−17

“…Parkinson disease (PD) in its early years can be well managed with symptomatic dopaminergic therapy , whilst other movement disorders are less satisfactorily treated . The development of motor complications is a significant limitation to the long term use of levodopa.…”