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Advanced Neurology Gastrointestinal symptoms in PD

the dorsal vagal nucleus is first affected by LBs in the CNS. the brain through the vagus nerve, which consequently
However, LBs are not a unique pathological hallmark of causes the degeneration of dopaminergic neurons as well
CNS and have also been found in the GI tract, including as PD-like motor symptoms . The metabolites of the
[34]
the esophagus, stomach, small intestine, colon, and rectum. gut microbiota are short-chain fatty acids (SCFAs), which
Interestingly, LBs occur in the GI tract before the dorsal stimulate microglia activation and promote α-synuclein-
vagal nucleus . The frequency of LB detection decreases dependent motor symptoms. Microbiota from patients
[27]
along the GI tract from the esophagus to the rectum, with PD aggravate motor symptoms in mice . Overall, the
[6]
displaying a distance-dependent distribution. The reason evidence suggests that PD may arise from the GI tract, and
for this LB distribution pattern has not been studied and the gut pathology spreads to the brain through the vagus
may be related to the distance from the brain. Therefore, nerve and gut immune inflammation network.
it has been hypothesized that PD originates from the
intestine. 4. Evaluation and management
The neural network is divided into the CNS and the 4.1. Drooling
peripheral nervous system (PNS). In the mid-19 century, 4.1.1. Assessment of salivation
th
abundant neural networks were found in the intestinal wall
and defined as the ENS, which is an important part of the The excessive salivation in PD may be attributed to the rate
PNS. The ENS shares many similarities with the CNS and of salivary secretion and saliva swallowing. A study used
contains 80–100 million neurons, which are supported technetium-99m scintigraphy to show that the salivary
by glial cells, and various neurotransmitters have been secretion is the same in patients with PD and healthy
[35]
identified [28,29] . The ENS produces the same amount of controls . However, salivary secretion in response to
dopamine as the brain, providing half of the dopamine for discrete stimuli is significantly higher in patients with PD
[35]
the body. Dopamine is an important neurotransmitter in with excessive salivation . Regarding salivary swallowing,
the brain, and its deficiency is the direct cause of PD. In barium swallowing and fluoroscopy evaluation in patients
addition, the ENS provides more than 95% of the serotonin with PD with excessive salivation proved that the severity
in the body, and serotonin deficiency in the brain is of dysphagia is directly related to the severity of excessive
[36]
associated with depression. This line of evidence indicates salivation . A study of the maximum tongue pressure
that the gut and brain share high degrees of similarity in during swallowing showed that animal models and
both structure and function. Therefore, the ENS is also patients with PD have a slow tongue extension speed and
called the “second brain” . significantly longer average tongue pressing time than
[30]
normal controls . Furthermore, the maximum tongue
[37]
The ENS communicates with the CNS through the vagus pressure is lower in patients with advanced PD than in
nerve. The ENS contains a large number and wide variety patients with early or moderate PD, and the oropharyngeal
of complex microbiota. The human intestine contains transport time is negatively correlated with the tongue
about 10 –10 bacteria (i.e., intestinal flora), consisting of movement speed .
13
14
[38]
more than 1000 species with 100 times more genes than
humans . Because the intestinal flora has a heightened 4.1.2. Management
[31]
sensitivity to changes from the outside world, microbiota The main methods used to manage drooling are drug
composition and metabolites tend to fluctuate immediately therapy and non-pharmaceutical therapy.
in response to the changes, leading to activation of the
immune and inflammatory systems, which then feed this Drug therapies include anticholinergic drugs and
information back to the CNS [32,33] . Therefore, the ENS is a botulinum toxin (BoNT). Anticholinergic drugs include
pivotal bridge between the external environment and the sublingual atropine, sublingual bromine ipratropium
brain. Structurally, the ENS and the brain are connected spray, oral pyruvate, and oral tropicamide. The Movement
[34]
through the vagus nerve . Functionally, the gut and Disorder Society has stated that pyruvate is effective, but
brain form a complex neuroendocrine immune network there is no evidence for its long-term effectiveness [39,40] .
with a strong biphasic regulation. The close connection in The mechanism of BoNT is to inhibit the release of
structure and function suggests the critical link between acetylcholine. The two serotypes of BoNT are BoNT-A
the gut and brain [6,34] . However, the relationship between and BoNT-B, which have both been studied in patients
PD and the gut needs further study. An association between with PD with excessive salivation. Local injection of BoNT
complete vagotomy and a lower incidence of PD has been into the salivary gland inhibits the activities of cholinergic
shown in a large epidemiological study in Denmark and parasympathetic nerves and postganglionic sympathetic
in a transgenic PD mouse model. Kim et al. demonstrated nerves, resulting in decreased salivary secretion. BoNT-A
the gradual transfer of α-synuclein from the intestine to and BoNT-B are effective in controlling salivation

Volume 1 Issue 1 (2022) 4 https://doi.org/10.36922/an.v1i1.9