Gastrointestinal Dysfunctions in Parkinson’s Disease: Symptoms and Treatments

Table 1

GI physiopathologic manifestations in PD. Summary of clinical studies exploring Lewy bodies expression and/or presence of neurodegeneration in enteric nervous system of parkinsonian patients.

Studies	GI part	Plexi	Disease stage or duration	Symptoms; (number of PD patients)	GI pathological observations; (number of PD patients)
Qualman et al., 1984 [80]	Esophagus and colon	Myenteric	Unknown		Lewy bodies (2/3)
Kupsky et al., 1987 [81]	Colon	Myenteric	Unknown	Megacolon (1/1)	Lewy bodies (1/1)
Wakabayashi et al., 1988 [82]	Upper esophagus to the rectum	Myenteric and submucosal	From less than 1 year to 27 years	⁢	Intraneuritic Lewy bodies in myenteric neurons of the esophagus (7/7), stomach (2/7), duodenum (2/7), jejunum (1/7), colon (1/7), and rectum (1/7); Intraneuritic Lewy bodies in submucosal neurons of the jejunum (1/7), colon (2/7), and rectum (1/7); Intracytoplasmic Lewy bodies in myenteric neurons of the esophagus (1/7)
Wakabayashi et al., 1990 [83]	Upper esophagus to the rectum	Myenteric and submucosal	8 years, 27 years, and unknown	⁢	Almost all neurons containing Lewy bodies were TH^+or VIP^+ (3/3); No apparent loss of TH^+ and VIP^+ neurons cell; bodies and process
Singaram et al., 1995 [99]	Ascending colon	Myenteric and submucosal	Longstanding severe disease; (>20 years for 8 patients)	Megacolon (9/11); Colon cancer (1/11); Needed manual evacuation (7/11)	Decrease in DAergic neurons number (9/11); Lewy bodies in myenteric neurons (11/11); observed in VIP and TH^+ neurons; Decrease in DA concentration; No difference in TH^+, VIP^+, and total neurons number
Braak et al., 2006 [84]	Distal esophagus and stomach	Myenteric and submucosal	Stage 2 to stage 5	⁢	Intraneuronal Lewy bodies (5/5)
Lebouvier et al., 2008 [102]	Ascending colon	Submucosal	>5 years	Constipation	Lewy neurites (4/5); No difference in TH^+ and total neurons number
Beach et al., 2010 [79]	Upper esophagus to the rectum, submandibular gland, liver, pancreas, and gallbladder	Myenteric and submucosal	More than 80% in stage 3 or 4	⁢	Lewy bodies inclusions (11/17); 14/15 patients for only esophagus and submandibular gland
Lebouvier et al., 2010 [89]	Ascending and descending colon	Submucosal	Group 1: ≤6 years (9 patients); Group 2: 7–12 years (10 patients); Group 3: ≥13 years (10 patients)	Chronic constipation; frequent among patients with Lewy neurites	Lewy neurites (21/29); 1 = 7; Group 2 = 5; Group 3 = 9; of patients with Lewy pathology did not correlate with disease progression but positively correlated with age; 60% were found in TH^+ neurons; Decrease in total neurons number
Annerino et al., 2012 [92]	Stomach, duodenum, ileum, transverse colon, and rectum	Myenteric	From 4 to 22 years	⁢	Lewy bodies (12/13); Lewy neurites (13/13); 3% were found in TH^+ neurons; correlation with age or disease progression; No difference in TH^+, VIP^+, NOS^+, and total; neurons number
Pouclet et al., 2012 [90]	Ascending and descending colon and rectum	Submucosal	From 1 to 24 years	⁢	Lewy neurites in ascending colon (17/26), in descending colon (11/26), and in rectum (6/26)
Pouclet et al., 2012 [91]	Descending colon	Submucosal	From 3 to 15 years	⁢	Lewy neurites (4/9)
Shannon et al., 2012 [86]	Sigmoid colon	Submucosal	From 6 months to 8 years	Mild disabilities	α-syn positive staining (9/9)
Gold et al., 2013 [87]	Colon	Myenteric and submucosal	Unknown	⁢	α-syn positive staining (10/10); prevalence and grade of α-syn detectability than controls
Hilton et al., 2014 [85]	Esophagus, stomach, small intestine, colon, and gall bladder	Submucosal	From 8 years prior to the onset of motor symptoms to 15 years after diagnosis	Postural hypotension, constipation, dysphagia, urinary incontinence, impotence, nocturia, and drooling	α-syn positive staining (7/62); 11% in “postdiagnosis” tissues, 7% in “up to 5 years prior to diagnosis” tissues, 17% in “5–10 years prior to diagnosis” tissues, and 0% in “more than 10 years before diagnosis” tissues; of positive biopsies in both the upper and the lower GI tract were similar
Gelpi et al., 2014 [93]	Distal esophagus, stomach, ileum, colon, and rectum	Myenteric	Average of 11.5 years; of 18 years for PD patients with dementia	Dementia (6/10)	Lewy neurites and Lewy bodies inclusions in distal esophagus, stomach, and colon (8/10)
Corbillé et al., 2014 [103]	Ascending and descending colon	Submucosal	From 1 to 24 years	⁢	No difference in TH^+ and total neurons number
Beach et al., 2016 [96]	Sigmoid colon	Myenteric and submucosal	Average of 15.2 years	⁢	α-syn positive staining in the submucosal (5/5) and myenteric (4/5) plexi

: note.