Is there a delayed gastric emptying of patients with early-stage, untreated Parkinson's disease? An analysis using the C-13-acetate breath test

Department of Neurology and Geriatrics, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu City, 501-1194 Gifu Prefecture, Japan.
Journal of Neurology (Impact Factor: 3.38). 10/2010; 258(3):421-6. DOI: 10.1007/s00415-010-5769-z
Source: PubMed


During the pre-symptomatic stage of Parkinson’s disease (PD), the idiopathic PD related abnormal synuclein immunostaining is confined to the medulla oblongata and olfactory bulb, according to Braak. In the study of the enteric nervous system of PD, it has reported that Lewy bodies were found in the Auerbach’s and Meissner’s plexuses. These lesions may cause dysfunction of the gastrointestinal tract (GI) as pre-clinical symptoms of PD. However, because l-dopa therapy itself may worsen the symptoms of the digestive tract function, it is needed to evaluate the gastrointestinal tract function in patients with early-stage, untreated (de novo) PD. In the present study, using the 13C-acetate breath test (13C-ABT), we investigated gastric emptying in 20 untreated, early-stage PD patients and 40 treated, advanced-stage PD patients, and 20 healthy volunteers. Gastric emptying was examined by the 13C-ABT [the half emptying time (HET), the peak time of the 13C% dose-excess curve (T
max)]. The T
max and HET of gastric emptying as assessed using the 13C-ABT was significantly delayed in untreated, early-stage PD patients as compared to the controls (P < 0.001). The T
max and HET of gastric emptying were not significantly delayed in untreated, early-stage PD patients as compared to treated, advanced-stage PD patients. The results demonstrated that delay in gastric emptying did not differ between untreated, early-stage and treated, advanced-stage PD patients. Gastric emptying of untreated, early-stage PD is already delayed. Delayed gastric emptying may be one of markers of the pre-clinical stage of PD.

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    • "To the best of our knowledge, this is the first published investigation of the effect of STN-DBS on gastric emptying in patients with Parkinson's disease. Although it is controversial as to whether or not levodopa treatment can improve gastric emptying in patients with Parkinson's disease (Hardoff et al., 2001; Thomaides et al., 2005; Tanaka et al., 2011), we found that early morning treatment with levodopa/ DCI at typical doses did not alter the T max value, indicating that gastric emptying was resistant to levodopa therapy. In contrast, STN-DBS produced a significant improvement in gastric emptying, "
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    ABSTRACT: It is established that deep brain stimulation of the subthalamic nucleus improves motor function in advanced Parkinson's disease, but its effects on autonomic function remain to be elucidated. The present study was undertaken to investigate the effects of subthalamic deep brain stimulation on gastric emptying. A total of 16 patients with Parkinson's disease who underwent bilateral subthalamic deep brain stimulation were enrolled. Gastric emptying was expressed as the peak time of (13)CO(2) excretion (T(max)) in the (13)C-acetate breath test and was assessed in patients with and without administration of 100-150 mg levodopa/decarboxylase inhibitor before surgery, and with and without subthalamic deep brain stimulation at 3 months post-surgery. The pattern of (13)CO(2) excretion curve was analysed. To evaluate potential factors related to the effect of subthalamic deep brain stimulation on gastric emptying, we also examined the association between gastric emptying, clinical characteristics, the equivalent dose of levodopa and serum ghrelin levels. The peak time of (13)CO(2) excretion (T(max)) values for gastric emptying in patients without and with levodopa/decarboxylase inhibitor treatment were 45.6 ± 22.7 min and 42.5 ± 13.6 min, respectively (P = not significant), thus demonstrating levodopa resistance. The peak time of (13)CO(2) excretion (T(max)) values without and with subthalamic deep brain stimulation after surgery were 44.0 ± 17.5 min and 30.0 ± 12.5 min (P < 0.001), respectively, which showed that subthalamic deep brain stimulation was effective. Simultaneously, the pattern of the (13)CO(2) excretion curve was also significantly improved relative to surgery with no stimulation (P = 0.002), although the difference with and without levodopa/decarboxylase inhibitor was not significant. The difference in peak time of (13)CO(2) excretion (T(max)) values without levodopa/decarboxylase inhibitor before surgery and without levodopa/decarboxylase inhibitor and subthalamic deep brain stimulation after surgery was not significant, although motor dysfunction improved and the levodopa equivalent dose decreased after surgery. There was little association between changes in ghrelin levels (Δghrelin) and changes in T(max) values (ΔT(max)) in the subthalamic deep brain stimulation trial after surgery (r = -0.20), and no association between changes in other characteristics and ΔT(max) post-surgery in the subthalamic deep brain stimulation trial. These results showed that levodopa/decarboxylase inhibitor did not influence gastric emptying and that subthalamic deep brain stimulation can improve the dysfunction in patients with Parkinson's disease possibly by altering the neural system that controls gastrointestinal function after subthalamic deep brain stimulation. This is the first report to show the effectiveness of subthalamic deep brain stimulation on gastrointestinal dysfunction as a non-motor symptom in Parkinson's disease.
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    ABSTRACT: Exciting new features have been described concerning neurogenic bowel dysfunction, including interactions between the central nervous system, the enteric nervous system, axonal injury, neuronal loss, neurotransmission of noxious and non-noxious stimuli, and the fields of gastroenterology and neurology. Patients with spinal cord injury, myelomeningocele, multiple sclerosis and Parkinson's disease present with serious upper and lower bowel dysfunctions characterized by constipation, incontinence, gastrointestinal motor dysfunction and altered visceral sensitivity. Spinal cord injury is associated with severe autonomic dysfunction, and bowel dysfunction is a major physical and psychological burden for these patients. An adult myelomeningocele patient commonly has multiple problems reflecting the multisystemic nature of the disease. Multiple sclerosis is a neurodegenerative disorder in which axonal injury, neuronal loss, and atrophy of the central nervous system can lead to permanent neurological damage and clinical disability. Parkinson's disease is a multisystem disorder involving dopaminergic, noradrenergic, serotoninergic and cholinergic systems, characterized by motor and non-motor symptoms. Parkinson's disease affects several neuronal structures outside the substantia nigra, among which is the enteric nervous system. Recent reports have shown that the lesions in the enteric nervous system occur in very early stages of the disease, even before the involvement of the central nervous system. This has led to the postulation that the enteric nervous system could be critical in the pathophysiology of Parkinson's disease, as it could represent the point of entry for a putative environmental factor to initiate the pathological process. This review covers the data related to the etiology, epidemiology, clinical expression, pathophysiology, genetic aspects, gastrointestinal motor dysfunction, visceral sensitivity, management, prevention and prognosis of neurogenic bowel dysfunction patients with these neurological diseases. Embryological, morphological and experimental studies on animal models and humans are also taken into account.
    Full-text · Article · Dec 2011 · World Journal of Gastroenterology
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    ABSTRACT: Some of the gastrointestinal (GI) symptoms commonly experienced by patients with Parkinson's disease (PD) have been attributed to gastroparesis; however, the precise prevalence and relevance of gastric emptying delay in PD is unclear. The definition of gastroparesis varies; currently the most widely accepted definition (from the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium) is the presence of appropriate symptoms (including nausea, retching, vomiting, stomach fullness, and inability to finish a meal) for ≥ 12 weeks, together with delayed gastric emptying on scintigraphy and the absence of any obstructive lesions on upper GI endoscopy. In PD patients, gastroparesis has the potential to affect nutrition and quality of life, as well as the absorption of PD medications, including L-dopa. This reduced absorption of L-dopa has implications for the control of the PD motor symptoms for which it is administered. We performed a systematic review of the literature on gastroparesis in PD with the aim of developing an evidence-based approach to its management. Based on this review, we conclude that while gastric emptying has been reported to be frequently delayed in PD, the existing data do not permit definitive conclusions concerning its true prevalence, relationship to the underlying disease process, relevance to PD management, or the optimal therapy of related GI symptoms. Further study of these important issues is, therefore, required.
    Full-text · Article · Dec 2011 · Parkinsonism & Related Disorders
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