Gastrointestinal involvement in Parkinson's disease: pathophysiology, diagnosis, and management

Abstract

Growing evidence suggests an increasing significance for the extent of gastrointestinal tract (GIT) dysfunction in Parkinson's disease (PD). Most patients suffer from GIT symptoms, including dysphagia, sialorrhea, bloating, nausea, vomiting, gastroparesis, and constipation during the disease course. The underlying pathomechanisms of this α-synucleinopathy play an important role in disease development and progression, i.e., early accumulation of Lewy pathology in the enteric and central nervous systems is implicated in pharyngeal discoordination, esophageal and gastric motility/peristalsis impairment, chronic pain, altered intestinal permeability and autonomic dysfunction of the colon, with subsequent constipation. Severe complications, including malnutrition, dehydration, insufficient drug effects, aspiration pneumonia, intestinal obstruction, and megacolon, frequently result in hospitalization. Sophisticated diagnostic tools are now available that permit more detailed examination of specific GIT impairment patterns. Furthermore, novel treatment approaches have been evaluated, although high-level evidence trials are often missing. Finally, the burgeoning literature devoted to the GIT microbiome reveals its importance for neurologists. We review current knowledge about GIT pathoanatomy, pathophysiology, diagnosis, and treatment in PD and provide recommendations for management in daily practice.

Fig. 1. Diagram showing possible bidirectional (white arrows) parasympathetic (blue background) and sympathetic (pink background) pathways along which pathological α-synuclein propagation in ILBD and PD could occur between the periphery, including the ENS, and the CNS.

Retrograde: parasympathetic (distal esophagus/stomach → pN. X → dorsal motor nucleus of the vagus nerve, dmX); parasympathetic (appendix vermiformis → RIM → pN. X → dmX); parasympathetic (descending colon and further distal → ganglion pelvicum → SPS preganglionic neurons → lower brainstem level-setting nuclei); sympathetic (distal esophagus/stomach → prevertebral celiac ganglion postganglionic neurons → IML preganglionic neurons → lower brainstem level-setting nuclei). Alternatively, anterograde: parasympathetic (dmX → pN. X → distal esophagus/stomach); parasympathetic (lower brainsteim level-setting nuclei → SPS preganglionic neurons → prevertebral postganglionic ganglion pelvicum → descending colon and portions further distal); sympathetic (appendix vermiformis → RIM → prevertebral SMG postganglionic neurons → Nn. splachnici → IML preganglionic neurons → lower brainstem level-setting nuclei).Abbreviations: pN. X peripheral vagus nerve, dmX dorsal motor nucleus of the vagus nerve, IML intermediate mediolateral nucleus, SPS sacral parasympathetic nucleus, RIM root of the small intestine mesentery, sup. mes. ggl. superior mesenteric ganglion. The level-setting nuclei consist of the lower raphe nuclei, magnocellular nucleus of the reticular formation, and locus coeruleus. The RIM contains parasympathetic and sympathetic fibers innervating the upper GIT extending from the proximal jejunum to the distal ileum, thereby making it another potentially useful structure for neuropathological diagnosis of the existence of LP in the small intestine^,. Illustrations showing LP in a–m are not to scale: a great raphe nucleus. b dmx and intramedullary N. X. c pN. X at level of the carotid bifurcation. d SPS. e Gastric cardia, Auerbach plexus, tangential section. f Jejunum, Meissner (submucous) plexus, transversal section. g Locus coeruleus. h IML. i Splanchnic nerve at the level of the celiac ganglion. k Celiac ganglion. l Distal esophagus, Auerbach plexus, tangential section. m Gastric cardia, Meissner (submucous) plexus, tangential section. LP within the lamina propria reach the mucosa near gastric glands. Syn-1 immunohistochemistry (BD Biosciences, Eysins, Switzerland) in 100–150 µm sections.

Fig. 2. Dual Task examination algorithm via Flexible Endoscopic Evaluation of Swallowing (FEES) (adapted from ref. ).

FEES examination protocol including cognitive and motor dual-task for evaluation of swallowing function in PD patients.

Fig. 3. Examples for pharyngeal residue via FEES.

a Mild residue for solid food located in the valleculae. b Moderate to severe residue for solid food located in the valleculae and piriform sinus with penetration into the laryngeal vestibule. c Tablet residue located in the valleculae. d Tablet penetration.

Fig. 4. Colonic transit time in a 72-year-old male PD patient.

White spots in the entire colon are radiopaque markers (erect, anterior-posterior).