Assessment of Gastrointestinal Autonomic Dysfunction: Present and Future Perspectives

Abstract

The autonomic nervous system delicately regulates the function of several target organs, including the gastrointestinal tract. Thus, nerve lesions or other nerve pathologies may cause autonomic dysfunction (AD). Some of the most common causes of AD are diabetes mellitus and α-synucleinopathies such as Parkinson’s disease. Widespread dysmotility throughout the gastrointestinal tract is a common finding in AD, but no commercially available method exists for direct verification of enteric dysfunction. Thus, assessing segmental enteric physiological function is recommended to aid diagnostics and guide treatment. Several established assessment methods exist, but disadvantages such as lack of standardization, exposure to radiation, advanced data interpretation, or high cost, limit their utility. Emerging methods, including high-resolution colonic manometry, 3D-transit, advanced imaging methods, analysis of gut biopsies, and microbiota, may all assist in the evaluation of gastroenteropathy related to AD. This review provides an overview of established and emerging assessment methods of physiological function within the gut and assessment methods of autonomic neuropathy outside the gut, especially in regards to clinical performance, strengths, and limitations for each method.

Quantitative gastrointestinal function and corresponding symptom profiles in autonomic neuropathy

“…Patients with idiopathic autonomic neuropathy (AN) also frequently present with symptoms affecting multiple organ systems, ranging from sensory, orthostatic, urinary, secretory, and gastrointestinal (GI) (1,2,5), though the functional patterns of GI dysmotility are poorly understood. GI motility is primarily controlled by the three branches of the autonomic nervous system via shared modulation from the parasympathetic and sympathetic nervous systems in addition to the intrinsic GI tract nervous system, known as the enteric nervous system (ENS) (2)(3)(4)(5)(6). While it is well established that ANS function plays an important role in GI motility and control of secretions (1)(2)(3)(6)(7)(8), there is marked diversity and complexity of symptoms among patients with autonomic disorders, often limiting the yield of conventional diagnostic clinical evaluations (5,7).…”

“…Gastrointestinal (GI) dysmotility is a recognized symptom of peripheral neuropathies with autonomic involvement, including in diabetes, systemic autoimmune disease, and hereditary conditions ( 1 – 4 ). Patients with idiopathic autonomic neuropathy (AN) also frequently present with symptoms affecting multiple organ systems, ranging from sensory, orthostatic, urinary, secretory, and gastrointestinal (GI) ( 1 , 2 , 5 ), though the functional patterns of GI dysmotility are poorly understood. GI motility is primarily controlled by the three branches of the autonomic nervous system via shared modulation from the parasympathetic and sympathetic nervous systems in addition to the intrinsic GI tract nervous system, known as the enteric nervous system (ENS) ( 2 – 6 ).…”

“…GI motility is primarily controlled by the three branches of the autonomic nervous system via shared modulation from the parasympathetic and sympathetic nervous systems in addition to the intrinsic GI tract nervous system, known as the enteric nervous system (ENS) ( 2 – 6 ). While it is well established that ANS function plays an important role in GI motility and control of secretions ( 1 – 3 , 6 – 8 ), there is marked diversity and complexity of symptoms among patients with autonomic disorders, often limiting the yield of conventional diagnostic clinical evaluations ( 5 , 7 ). For example, symptoms of delayed or rapid gastric emptying can be ambiguous and difficult to distinguish clinically based on symptoms alone– therefore requiring objective testing in order to further delineate the underlying physiological pattern ( 5 , 7 , 9 – 12 ).…”

“…While it is well established that ANS function plays an important role in GI motility and control of secretions ( 1 – 3 , 6 – 8 ), there is marked diversity and complexity of symptoms among patients with autonomic disorders, often limiting the yield of conventional diagnostic clinical evaluations ( 5 , 7 ). For example, symptoms of delayed or rapid gastric emptying can be ambiguous and difficult to distinguish clinically based on symptoms alone– therefore requiring objective testing in order to further delineate the underlying physiological pattern ( 5 , 7 , 9 – 12 ). The most common clinically utilized diagnostic assessments of GI motility allow only a limited, regional assessment of the proximal foregut or distal hindgut (e.g., esophageal manometry, gastric emptying, Sitz marker testing, and anorectal manometry), leaving large segments of the foregut and midgut uninterrogated ( 5 ).…”

“…For example, symptoms of delayed or rapid gastric emptying can be ambiguous and difficult to distinguish clinically based on symptoms alone– therefore requiring objective testing in order to further delineate the underlying physiological pattern ( 5 , 7 , 9 – 12 ). The most common clinically utilized diagnostic assessments of GI motility allow only a limited, regional assessment of the proximal foregut or distal hindgut (e.g., esophageal manometry, gastric emptying, Sitz marker testing, and anorectal manometry), leaving large segments of the foregut and midgut uninterrogated ( 5 ). Recent advances in wireless motility capsule (WMC) testing now allow improved sampling of these previously uninterrogated regions, with the potential to improve diagnostic yield and ( 7 , 9 ) provide valuable insight into segment-specific enteric involvement.…”