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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parkinson's disease is a common progressive bradykinetic disorder that can be accurately diagnosed. It is characterised by the presence of severe pars-compacta nigral-cell loss, and accumulation of aggregated alpha-synuclein in specific brain stem, spinal cord, and cortical regions. The main known risk factor is age. Susceptibility genes including alpha-synuclein, leucine rich repeat kinase 2 (LRRK-2), and glucocerebrosidase (GBA) have shown that genetic predisposition is another important causal factor. Dopamine replacement therapy considerably reduces motor handicap, and effective treatment of associated depression, pain, constipation, and nocturnal difficulties can improve quality of life. Embryonic stem cells and gene therapy are promising research therapeutic approaches.
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PMID:Parkinson's disease. 1952 82

Gastrointestinal disorders, particularly severe constipation and delayed gastric emptying, are core symptoms of Parkinson's disease that affect most patients. However, the neuropathological substrate and physiological basis for this dysfunction are poorly defined. To begin to explore these phenomena in laboratory models of PD, rats were treated with either vehicle or rotenone (2.0 mg/kg, i.p.; 5 days/week) for 6-weeks. Myenteric plexus alpha-synuclein aggregate pathology and neuron loss were assessed 3-days and 6-months after the last rotenone injection. Gastrointestinal motility was assessed at 3-days, 1-month and 6-months after the last rotenone injection. Rotenone treatment caused an acute reduction in alpha-synuclein-immunoreactivity, but this was followed 6 months later by a robust increase in aggregate pathology and cytoplasmic inclusions that were similar in appearance to enteric Lewy-bodies in idiopathic PD. Rotenone-treated rats also had a moderate but permanent loss of small intestine myenteric neurons and an associated modest slowing of gastrointestinal motility 6-months after treatment. Our results suggest that a circumscribed exposure to an environmental toxicant can cause the delayed appearance of parkinsonian alpha-synuclein pathology in the enteric nervous system and an associated functional deficit in gastrointestinal motility. The rotenone model may therefore, provide a means to investigate pathogenic mechanisms and to test new therapeutic interventions into gastrointestinal dysfunction in PD.
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PMID:Chronic rotenone exposure reproduces Parkinson's disease gastrointestinal neuropathology. 1959 68

Constipation and faecal incontinence are common symptoms among patients with spinal cord injury (SCI), myelomeningocoele (MMC), multiple sclerosis (MS), Parkinson's disease (PD) and stroke. Faecal incontinence in SCI, MMC and MS is mainly due to abnormal rectosigmoid compliance and rectoanal reflexes, loss of rectoanal sensibility and loss of voluntary control of the external anal sphincter. Constipation in SCI, MMC and MS is probably due to immobilisation, abnormal colonic contractility, tone and rectoanal reflexes or side effects from medication. In PD, dystonia of the external anal sphincter causes difficult rectal evacuation and the loss of dopaminergic neurons in the enteric nervous system probably causes slow-transit constipation. Changes after stroke remain to be studied. Though dietary adjustments, oral laxatives, suppositories and other conservative treatment modalities are commonly used, evidence for their use in patients with central neurological disorders is scarce. For patients with severe symptoms trans-anal irrigation, the Malone appendicostomy or a colostomy can be recommended.
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PMID:Neurogenic colorectal and pelvic floor dysfunction. 1964 88

As with other neurodegenerative diseases, neurologic and nutritional elements may interact affecting each other in Parkinson's disease (PD). However, the long-term effects of such interactions on prognosis and outcome have not been given much attention and are poorly addressed by current research. Factors contributing to the clinical conditions of patients with PD are not only the basic features of PD, progression of disease, and the therapeutic approach but also fiber and nutrient intakes (in terms of both energy and protein content), fluid and micronutrient balance, and pharmaconutrient interactions (protein and levodopa). During the course of PD nutritional requirements frequently change. Accordingly, both body weight gain and loss may occur and, despite controversy, it seems that both changes in energy expenditure and food intake contribute. Nonmotor symptoms play a significant role and dysphagia may be responsible for the impairment of nutritional status and fluid balance. Constipation, gastroparesis, and gastro-oesophageal reflux significantly affect quality of life. Finally, any micronutrient deficiencies should be taken into account. Nutritional assessments should be performed routinely. Optimization of pharmacologic treatment for both motor and nonmotor symptoms is essential, but nutritional interventions and counseling could and should also be planned with regard to nutritional balance designed to prevent weight loss or gain; optimization of levodopa pharmacokinetics and avoidance of interaction with proteins; improvement in gastrointestinal dysfunction (e.g., dysphagia and constipation); prevention and treatment of nutritional deficiencies (micronutrients or vitamins). A balanced Mediterranean-like dietary regimen should be recommended before the introduction of levodopa; afterward, patients with advanced disease may benefit considerably from protein redistribution and low-protein regimens.
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PMID:Major nutritional issues in the management of Parkinson's disease. 1969 Nov 25

Gastrointestinal (GI) motility is very frequently disturbed in Parkinson's disease (PD), manifesting chiefly as dysphagia, impaired gastric emptying and constipation. All these symptoms - constipation in particular - may precede the clinical diagnosis of PD for years. In the future, these symptoms might serve as useful early indicators in the premotor stage. Disturbed gastric emptying is an important factor in unpredictable fluctuations. The most likely causes are degenerations of the dorsal vagal nucleus and the intramural plexus of the whole intestine. These degenerations are likely to develop prior to the degeneration of dopaminergic neurons of the substantia nigra. Diagnosis includes history, clinical examination, barium meal, breath test, scintiscan of stomach, and colonic transit time. Therapeutic efforts are limited when it comes to disturbed motility of the upper GI-tract. Hypersalivation can be reduced by anticholinergics or botulinum toxin injections; motility of the upper gastrointestinal tract is only moderately impacted on by domperidone. In constipation, the conservative therapeutic option is administration of macrogol (polyethylene glycol), which leads to marked improvement.
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PMID:Gastrointestinal dysfunction in Parkinson's Disease. 1971 68

Patients with Parkinson's disease develop motor disturbances often accompanied by peripheral autonomic dysfunctions, including gastrointestinal disorders, such as dysphagia, gastric stasis and constipation. While the mechanisms subserving enteric autonomic dysfunctions are not clearly understood, they may involve the enteric dopaminergic and/or nitrergic systems. In the present study, we demonstrate that rats with unilateral 6-hydroxydopamine lesion of nigrostriatal dopaminergic neurons develop a marked inhibition of propulsive activity compared to sham-operated controls, as indicated by a 60% reduction of daily fecal output at the 4th week of observation. Immunohistochemical data revealed that 6-hydroxydopamine treatment did not affect the total number of HuC/D-positive myenteric neurons in both the proximal and distal segments of ileum and colon. Conversely, in the distal ileum and proximal colon the number of nitrergic neurons was significantly reduced. These results suggest that a disturbed distal gut transit, reminiscent of constipation in the clinical setting, may occur as a consequence of a reduced propulsive motility, likely due to an impairment of a nitric oxide-mediated descending inhibition during peristalsis.
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PMID:Functional and neurochemical changes of the gastrointestinal tract in a rodent model of Parkinson's disease. 1983 30

Pathological and neuroimaging studies have shown that in Parkinson's disease (PD) there is a "subclinical" or "premotor" period during which dopaminergic neurons in the substantia nigra (SN) degenerate but typical motor symptoms have not yet developed. Post-mortem studies based on nigral cell counts and evaluating dopamine levels in the striata, and imaging studies assessing the nigrostriatal pathway in vivo, have estimated that this time period could last 3 to 6 years. In addition, emerging evidence indicates that the neuropathological process of PD does not start in the SN but more likely elsewhere in the nervous system: in the lower brainstem and the olfactory bulb, or even more distant from the SN, such as in the peripheral autonomic nervous system. Patients with PD frequently can present non-motor symptoms, such as hyposmia or constipation, years before the development of classical motor signs. The physiopathology of these "premotor" symptoms, though still unclear, is currently thought to be related to early involvement by the pathological process underlying PD of non-dopaminergic lower brainstem structures or autonomic plexuses. However, the answer to the question "when does PD start" remains uncertain. Here, we review clinical, pathological, and neuroimaging data related to the onset of the pathological process of PD, and propose that its onset is non-motor and that non-motor symptoms could begin in many instances 10 and 20 years before onset of motor symptoms. The variable course of the disorder once the motor symptoms develop, suggests that the start and progression of premotor PD is also highly variable and given the heterogeneous nature of PD, may differ depending on the cause/s of the syndrome. When and where the neuropathological process develops in PD remains uncertain.
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PMID:When does Parkinson's disease begin? 1987 43

Parkinson's disease (PD) is most frequently associated with characteristic motor symptoms that are known to arise with degeneration of dopaminergic neurons. However, patients with this disease also experience a multitude of non-motor symptoms, such as sleep disturbances, fatigue, apathy, anxiety, depression, cognitive impairment, dementia, olfactory dysfunction, pain, sweating and constipation, some of which can be at least as debilitating as the movement disorders and have a major impact on patients' quality of life. Many of these non-motor symptoms may be evident prior to the onset of motor dysfunction. The neuropathology of PD has shown that complex, interconnected neuronal systems, regulated by a number of different neurotransmitters in addition to dopamine, are involved in the aetiology of motor and non-motor symptoms. This review focuses on the non-dopaminergic neurotransmission systems associated with PD with particular reference to the effect that their modulation and interaction with dopamine has on the non-motor symptoms of the disease. PD treatments that focus on the dopaminergic system alone are unable to alleviate both motor and non-motor symptoms, particularly those that develop at early stages of the disease. The development of agents that interact with several of the affected neurotransmission systems could prove invaluable for the treatment of this disease.
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PMID:Neurotransmission in Parkinson's disease: beyond dopamine. 2005 Aug 85

Non-motor symptoms are increasingly recognized to adversely impact on the quality of life of patients with in Parkinson's disease (PD), particularly as the disease progresses. Autonomic symptom severity in patients with PD seems to correlate with older age, greater disease severity, psychiatric complications, sleep disorders, and higher doses of dopaminergic medication. The following therapeutic strategies are frequently used in the treatment of PD-related dysautonomia: 1. Orthostatic hypotension: fludrocortisone, midodrine, and droxidopa; 2. Sialorrhea: glycopyrrolate and botulinun toxin injections; 3. Constipation: symbiotic yogurt and bulking agents, macrogol, lubiprostone, mosapride citrate and tegaserod, pyridostigmine bromide, botulinum toxin injections and sacral nerve stimulation; 4. Urinary frequency: oxybutynin, tolterodine, solifenacin, darifenacin, botulinum toxin injections; 5. Erectile dysfunction: sildenafil and other phosphodiesterase type 5 inhibitors. More effective symptomatic and pathogenesis-targeted therapies are needed to ameliorate the non-motor symptoms of PD that usually do not respond well to dopaminergic medications.
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PMID:Treatment of dysautonomia associated with Parkinson's disease. 2008 97

Parkinson's disease (PD) is the second most common neurodegenerative disease and primarily considered as a movement disorder defined by the presence of motor symptoms, such as bradykinesia, tremor and rigidity. However, it is nowadays widely recognized that in addition there is impairment of cognitive function, mood and the autonomic nervous system in a high percentage of PD patients, which is sometimes even more harming quality of life. These symptoms not only occur during the course of the disease but may even precede the onset of motor symptoms. Typical examples of non-motor features of PD are depression, constipation, REM sleep behaviour disorder, and hyposmia.
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PMID:Non-motor features of Parkinson's disease: depression and dementia. 2008 17


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