Gastrointestinal motility disorders in neurologic disease

Abstract

The extrinsic and autonomic nervous system intricately controls the major functions of the gastrointestinal tract through the enteric nervous system; these include motor, secretory, sensory, storage, and excretory functions. Disorders of the nervous system affecting gastrointestinal tract function manifest primarily as abnormalities in motor (rather than secretory) functions. Common gastrointestinal symptoms in neurologic disorders include sialorrhea, dysphagia, gastroparesis, intestinal pseudo-obstruction, constipation, diarrhea, and fecal incontinence. Diseases of the entire neural axis ranging from the cerebral hemispheres to the peripheral autonomic nerves can result in gastrointestinal motility disorders. The most common neurologic diseases affecting gastrointestinal function are stroke, parkinsonism, multiple sclerosis, and diabetic neuropathy. Diagnosis involves identification of the neurologic disease and its distribution, and documentation of segmental gut dysfunction, typically using noninvasive imaging, transit measurements, or intraluminal measurements of pressure activity and coordination of motility. Apart from treatment of the underlying neurologic disease, management focuses on restoration of normal hydration and nutrition and pharmacologic treatment of the gut neuromuscular disorder.

Figure 1. Control of gut motility: extrinsic autonomic neural control, enteric nervous system, and smooth muscle function.

The left panel shows extrinsic neural control, including the vagus and sacral parasympathetic nerves (blue) and the sympathetic innervation (red) originating from levels thoracic 5 to lumbar 2 in the spinal cord. The right panel shows the organization of the enteric nervous system, which demonstrates plexuses in the submucosal and intermuscular layers called the submucosal plexus and myenteric plexus. In addition, there are pacemakers in the wall of the intestine, including the interstitial cells of Cajal (ICCs) and fibroblast-like cells bearing receptors for PDGFRα, which convey the neural stimulus to the smooth muscle cells. These pacemaker cells and plexuses help to coordinate muscular and secretory functions of the digestive tract.

Figure 2. Components of the peristaltic reflex and relationship to enteric and extrinsic neural control.

In the peristaltic reflex, distension of the intestine by a bolus is sensed by the intrinsic primary afferent neurons, which stimulate interneurons to activate ascending contraction proximal to the bolus through excitatory neurons. Stimulation of muscles occurs through effects of transmitters such as acetyl choline and neurokinins such as substance P and substance K. The intrinsic primary afferent neuron also stimulates descending inhibition in the receiving segment of the intestine distal to the bolus, and this effect is mediated by inhibitory transmitters, such as VIP and nitric oxide (NO).

Figure 3. Neurologic disorders known to affect gastrointestinal motility.

These disease processes involve craniosacral parasympathetic pathways (left), sympathetic pathways (middle), and/or primary enteric nerves or smooth muscle (right). ENS, enteric nervous system.