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Yuan XY, Chen YS, Liu Z. Relationship among Parkinson's disease, constipation, microbes, and microbiological therapy. World J Gastroenterol 2024; 30:225-237. [PMID: 38314132 PMCID: PMC10835526 DOI: 10.3748/wjg.v30.i3.225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 11/16/2023] [Accepted: 12/26/2023] [Indexed: 01/18/2024] Open
Abstract
This comprehensive review elucidates the complex interplay between gut microbiota and constipation in Parkinson's disease (PD), a prevalent non-motor symptom contributing significantly to patients' morbidity. A marked alteration in the gut microbiota, predominantly an increase in the abundance of Proteobacteria and Bacteroidetes, is observed in PD-related constipation. Conventional treatments, although safe, have failed to effectively alleviate symptoms, thereby necessitating the development of novel therapeutic strategies. Microbiological interventions such as prebiotics, probiotics, and fecal microbiota transplantation (FMT) hold therapeutic potential. While prebiotics improve bowel movements, probiotics are effective in enhancing stool consistency and alleviating abdominal discomfort. FMT shows potential for significantly alleviating constipation symptoms by restoring gut microbiota balance in patients with PD. Despite promising developments, the causal relationship between changes in gut microbiota and PD-related constipation remains elusive, highlighting the need for further research in this expanding field.
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Affiliation(s)
- Xin-Yang Yuan
- Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, Guangdong Province, China
- Institute of Neurology, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Zhanjiang 524000, Guangdong Province, China
| | - Yu-Sen Chen
- Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, Guangdong Province, China
- Institute of Neurology, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Zhanjiang 524000, Guangdong Province, China
| | - Zhou Liu
- Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, Guangdong Province, China
- Institute of Neurology, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Zhanjiang 524000, Guangdong Province, China
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2
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Quigley EMM. Constipation in Parkinson's Disease. Semin Neurol 2023; 43:562-571. [PMID: 37579786 DOI: 10.1055/s-0043-1771457] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/16/2023]
Abstract
Constipation is one of the most common gastrointestinal features of Parkinson's disease (PD), occurring in over 50% of all PD patients during the course of their disease. Furthermore, constipation is now recognized as an important, prodromal symptom and may predate the onset of the classical motor symptoms by decades. Thereafter, the prevalence and severity of constipation in PD tend to parallel the course of both motor and nonmotor phenomena such as cognitive decline and depression. Difficult defecation (obstructed defecation, dyssynergia) is the primary pathophysiology underlying constipation and likely reflects involvement by the PD process of one or more of the many skeletal muscle groups that are involved in effecting defecation. Management of constipation in PD may be complicated by several patient factors including dysphagia, cognitive impairment, depression, and weak sphincter tone. While the armamentarium available to those who treat constipation, in general, has expanded considerably in recent years, the evidence supporting any therapy in the management of this symptom in PD has remained slim.
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Affiliation(s)
- Eamonn M M Quigley
- Division of Gastroenterology and Hepatology, Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist Hospital, Houston, Texas
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3
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Tan AH, Chuah KH, Beh YY, Schee JP, Mahadeva S, Lim SY. Gastrointestinal Dysfunction in Parkinson's Disease: Neuro-Gastroenterology Perspectives on a Multifaceted Problem. J Mov Disord 2023; 16:138-151. [PMID: 37258277 DOI: 10.14802/jmd.22220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 02/21/2023] [Indexed: 06/02/2023] Open
Abstract
Patients with Parkinson's disease (PD) face a multitude of gastrointestinal (GI) symptoms, including nausea, bloating, reduced bowel movements, and difficulties with defecation. These symptoms are common and may accumulate during the course of PD but are often under-recognized and challenging to manage. Objective testing can be burdensome to patients and does not correlate well with symptoms. Effective treatment options are limited. Evidence is often based on studies in the general population, and specific evidence in PD is scarce. Upper GI dysfunction may also interfere with the pharmacological treatment of PD motor symptoms, which poses significant management challenges. Several new less invasive assessment tools and novel treatment options have emerged in recent years. The current review provides an overview and a practical approach to recognizing and diagnosing common upper and lower GI problems in PD, e.g., dyspepsia, gastroparesis, small bowel dysfunction, chronic constipation, and defecatory dysfunction. Management aspects are discussed based on the latest evidence from the PD and general populations, with insights for future research pertaining to GI dysfunction in PD.
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Affiliation(s)
- Ai Huey Tan
- Division of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
- Mah Pooi Soo & Tan Chin Nam Centre for Parkinson's & Related Disorders, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Kee Huat Chuah
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Yuan Ye Beh
- Department of Medicine, Hospital Pulau Pinang, Penang, Malaysia
| | - Jie Ping Schee
- Division of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
- Mah Pooi Soo & Tan Chin Nam Centre for Parkinson's & Related Disorders, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Sanjiv Mahadeva
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Shen-Yang Lim
- Division of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
- Mah Pooi Soo & Tan Chin Nam Centre for Parkinson's & Related Disorders, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
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Katunina E, Shipilova N, Katunin D. Mechanisms of development of constipation in Parkinson’s disease and therapeutic approaches. Zh Nevrol Psikhiatr Im S S Korsakova 2022; 122:21-26. [DOI: 10.17116/jnevro202212208121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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Fearon C, Lees AJ, McKinley JJ, McCarthy A, Smyth S, Farrell M, Lynch T. On the Emergence of Tremor in Prodromal Parkinson's Disease. JOURNAL OF PARKINSONS DISEASE 2020; 11:261-269. [PMID: 33325397 DOI: 10.3233/jpd-202322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Clinical, neuropathological and neuroimaging research suggests that pathological changes in Parkinson's disease (PD) start many years before the emergence of motor signs. Since disease-modifying treatments are likely to be most effective when initiated early in the disease process, there has been significant interest in characterizing prodromal PD. Some people with PD describe autonomic symptoms at the time of diagnosis suggesting that autonomic dysfunction is a common feature of prodromal PD. Furthermore, subtle motor signs may be present and emerge prior to the time of diagnosis. We present a series of patients who, in the prodromal phase of PD, experienced the emergence of tremor initially only while yawning or straining at stool and discuss how early involvement of autonomic brainstem nuclei could lead to these previously unreported phenomena. The hypothalamic paraventricular nucleus (PVN) plays a central role in autonomic control including bowel/bladder function, cardiovascular homeostasis and yawning and innervates multiple brainstem nuclei involved in autonomic functions (including brainstem reticular formation, locus ceruleus, dorsal raphe nucleus and motor nucleus of the vagus). The PVN is affected in PD and evidence from related phenomena suggest that the PVN could increase tremor either by increasing downstream cholinergic activity on brainstem nuclei such as the reticular formation or by stimulating the locus ceruleus to activate the cerebellothalamocortical network via the ventrolateral nucleus of the thalamus. Aberrant cholinergic/noradrenergic transmission between these brainstem nuclei early in PD couldlead to tremor before the emergence of other parkinsonian signs, representing an early clinical clue to prodromal PD.
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Affiliation(s)
- Conor Fearon
- Centre for Brain Health, Dublin Neurological Institute at the Mater Misericordiae University Hospital, Dublin, Ireland
| | - Andrew J Lees
- Reta Lila Weston Institute of Neurological Studies University College London, London, UK
| | - John J McKinley
- Department of Neurology, Royal Victoria Hospital, Belfast, UK
| | - Allan McCarthy
- Department of Neurology, Tallaght University Hospital, Dublin, Ireland
| | - Shane Smyth
- Centre for Brain Health, Dublin Neurological Institute at the Mater Misericordiae University Hospital, Dublin, Ireland
| | - Michael Farrell
- Department of Neuropathology, Beaumont Hospital, Dublin, Ireland
| | - Timothy Lynch
- Centre for Brain Health, Dublin Neurological Institute at the Mater Misericordiae University Hospital, Dublin, Ireland.,Health Affairs, University College Dublin, Dublin, Ireland
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Abstract
PURPOSE OF REVIEW This article reviews the α-synucleinopathies pure autonomic failure, multiple system atrophy, dementia with Lewy bodies, and Parkinson disease with respect to autonomic failure. RECENT FINDINGS The pattern and severity of autonomic involvement in the synucleinopathies is related to differences in cellular deposition and neuronal populations affected by α-synuclein aggregation, which influences the degree and manifestation of autonomic failure. Clinical and laboratory autonomic features distinguish the different synucleinopathies based on pattern and severity. These features also determine which patients are at risk for evolution from pure autonomic failure to the synucleinopathies with prominent motor involvement, such as multiple system atrophy, dementia with Lewy bodies, or Parkinson disease. SUMMARY Autonomic failure is a key feature of the synucleinopathies, with varying type and degree of dysfunction from predominantly peripheral involvement in the Lewy body disorders to central involvement in multiple system atrophy.
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Gastrointestinal dysfunction in the synucleinopathies. Clin Auton Res 2020; 31:77-99. [PMID: 33247399 DOI: 10.1007/s10286-020-00745-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Accepted: 11/04/2020] [Indexed: 12/15/2022]
Abstract
Interest in gastrointestinal dysfunction in Parkinson's disease has blossomed over the past 30 years and has generated a wealth of investigation into this non-motor aspect of the disorder, research that has encompassed its pathophysiology, its clinical features, and its impact on quality of life. The question of gastrointestinal dysfunction in the other synucleinopathies has not received nearly as much attention, but information and knowledge are growing. In this review, the current knowledge, controversies, and gaps in our understanding of the pathophysiology of gastrointestinal dysfunction in Parkinson's disease and the other synucleinopathies will be addressed, and extended focus will be directed toward the clinical problems involving saliva management, swallowing, gastric emptying, small intestinal function, and bowel function that are so problematic in these disorders.
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Parkinson disease and the gut: new insights into pathogenesis and clinical relevance. Nat Rev Gastroenterol Hepatol 2020; 17:673-685. [PMID: 32737460 DOI: 10.1038/s41575-020-0339-z] [Citation(s) in RCA: 128] [Impact Index Per Article: 25.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/23/2020] [Indexed: 12/12/2022]
Abstract
The classic view portrays Parkinson disease (PD) as a motor disorder resulting from loss of substantia nigra pars compacta dopaminergic neurons. Multiple studies, however, describe prodromal, non-motor dysfunctions that affect the quality of life of patients who subsequently develop PD. These prodromal dysfunctions comprise a wide array of gastrointestinal motility disorders including dysphagia, delayed gastric emptying and chronic constipation. The histological hallmark of PD - misfolded α-synuclein aggregates that form Lewy bodies and neurites - is detected in the enteric nervous system prior to clinical diagnosis, suggesting that the gastrointestinal tract and its neural (vagal) connection to the central nervous system could have a major role in disease aetiology. This Review provides novel insights on the pathogenesis of PD, including gut-to-brain trafficking of α-synuclein as well as the newly discovered nigro-vagal pathway, and highlights how vagal connections from the gut could be the conduit by which ingested environmental pathogens enter the central nervous system and ultimately induce, or accelerate, PD progression. The pathogenic potential of various environmental neurotoxicants and the suitability and translational potential of experimental animal models of PD will be highlighted and appraised. Finally, the clinical manifestations of gastrointestinal involvement in PD and medications will be discussed briefly.
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Chen Z, Li G, Liu J. Autonomic dysfunction in Parkinson's disease: Implications for pathophysiology, diagnosis, and treatment. Neurobiol Dis 2019; 134:104700. [PMID: 31809788 DOI: 10.1016/j.nbd.2019.104700] [Citation(s) in RCA: 165] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2019] [Revised: 11/13/2019] [Accepted: 12/02/2019] [Indexed: 12/17/2022] Open
Abstract
Parkinson's disease (PD) is a neurodegenerative disease with a 200 year-long research history. Our understanding about its clinical phenotype and pathogenesis remains limited, although dopaminergic replacement therapy has significantly improved patient outcomes. Autonomic dysfunction is an essential category of non-motor phenotypes that has recently become a cutting edge field that directs frontier research in PD. In this review, we initially describe the epidemiology of dysautonomic symptoms in PD. Then, we perform a meticulous analysis of the pathophysiology of autonomic dysfunction in PD and propose that the peripheral autonomic nervous system may be a key route for α-synuclein pathology propagation from the periphery to the central nervous system. In addition, we recommend that constipation, orthostatic hypotension, urinary dysfunction, erectile dysfunction, and pure autonomic failure should be viewed as prodromal dysautonomic markers in PD prediction and diagnosis. Finally, we summarize the strategies currently available for the treatment of autonomic dysfunction in PD and suggest that high-quality, better-designed, randomized clinical trials should be conducted in the future.
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Affiliation(s)
- Zhichun Chen
- Department of Neurology, Institute of Neurology, Ruijin Hospital affiliated with the Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Guanglu Li
- Department of Neurology, Institute of Neurology, Ruijin Hospital affiliated with the Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jun Liu
- Department of Neurology, Institute of Neurology, Ruijin Hospital affiliated with the Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Abstract
This article reviews the most common gastrointestinal (GI) problems that occur in patients with Parkinson disease, including weight loss, drooling, dysphagia, delayed gastric emptying, constipation, and defecatory dysfunction. Appropriate workup and treatment options are reviewed in detail in order to provide clinicians with a comprehensive and practical guide to managing these problems in Parkinson disease patients. GI adverse effects of commonly used Parkinson disease motor medications are also reviewed.
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Affiliation(s)
- John Legge
- Department of Neurology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA; VCU NOW Center, 11958 West Broad Street, 4th Floor, Box 980220, Henrico, VA 23298-0220, USA
| | - Nicholas Fleming
- Department of Neurology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA; VCU NOW Center, 11958 West Broad Street, 4th Floor, Box 980220, Henrico, VA 23298-0220, USA
| | - Leslie Jameleh Cloud
- VCU NOW Center, 11958 West Broad Street, 4th Floor, Box 980220, Henrico, VA 23298-0220, USA; Parkinson's and Movement Disorders Center, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
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De Pablo-Fernández E, Passananti V, Zárate-López N, Emmanuel A, Warner T. Colonic transit, high-resolution anorectal manometry and MRI defecography study of constipation in Parkinson's disease. Parkinsonism Relat Disord 2019; 66:195-201. [PMID: 31473084 DOI: 10.1016/j.parkreldis.2019.08.016] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Revised: 08/27/2019] [Accepted: 08/27/2019] [Indexed: 01/28/2023]
Abstract
INTRODUCTION Despite clinical relevance and potential role on the disease pathogenesis, underlying mechanisms of constipation in Parkinson's disease (PD) remain poorly understood. A systematic assessment using complementary physiological investigations was performed to elucidate constipation pathophysiology in order to improve its symptomatic management. METHODS PD patients with constipation were evaluated with clinical questionnaires, colonic transit, high-resolution anorectal manometry and MRI defecography. Results were compared and correlated with clinical features. RESULTS A total of 42 patients (69% male; age 68 ± 8 years; disease duration 10.5 ± 6.1 years) were included, of whom 33 (78.6%) had objective constipation defined by < 3 bowel movements per week or straining. Severity of constipation measured by self-administered questionnaires correlated with disease severity, burden of motor and non-motor symptoms but not with age, disease duration or Parkinson's medications. Colonic transit and anorectal function (high-resolution anorectal manometry and/or MRI defecography) was assessed in 15 patients. A combination of both delayed colonic transit and anorectal dysfunction was the pattern most commonly found (60% of patients) and overall anorectal dysfunction was more prevalent than isolated slow transit constipation. Physiological findings were heterogeneous including reduced colonic motility, rectal hyposensitivity, defecatory dyssynergia and poor motor rectal function. CONCLUSION Subjective constipation in PD is poorly correlated with commonly used definition, assessment questionnaires and physiological results. Multiple complex overlapping pathophysiological mechanisms are responsible including slow transit and anorectal dysfunction. Complementary investigations to assess colonic transit and anorectal function are required in those with refractory symptoms for a systematic assessment and appropriate symptomatic management.
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Affiliation(s)
- Eduardo De Pablo-Fernández
- Reta Lila Weston Institute of Neurological Studies, University College London Queen Square Institute of Neurology, 1 Wakefield Street, London, WC1N 1PJ, United Kingdom; Queen Square Brain Bank for Neurological Disorders, University College London Queen Square Institute of Neurology, 1 Wakefield Street, London, WC1N 1PJ, United Kingdom.
| | - Valentina Passananti
- Gastrointestinal Physiology Unit, University College London Hospital, 235 Euston Road, London, NW1 2BU, United Kingdom.
| | - Natalia Zárate-López
- Gastrointestinal Physiology Unit, University College London Hospital, 235 Euston Road, London, NW1 2BU, United Kingdom.
| | - Anton Emmanuel
- Gastrointestinal Physiology Unit, University College London Hospital, 235 Euston Road, London, NW1 2BU, United Kingdom.
| | - Thomas Warner
- Reta Lila Weston Institute of Neurological Studies, University College London Queen Square Institute of Neurology, 1 Wakefield Street, London, WC1N 1PJ, United Kingdom; Queen Square Brain Bank for Neurological Disorders, University College London Queen Square Institute of Neurology, 1 Wakefield Street, London, WC1N 1PJ, United Kingdom.
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Abstract
PURPOSE OF REVIEW During the past 25 years, there has been an explosion of information regarding the occurrence of gastrointestinal dysfunction in Parkinson's disease. In this review, the clinical features of gastrointestinal dysfunction in Parkinson's disease will be described and information regarding the potential role of the enteric nervous system and the gut microbiome in the genesis of Parkinson's disease will be addressed. RECENT FINDINGS Recognition is growing regarding the role that gastroparesis and small intestinal dysfunction may play in Parkinson's disease, especially with regard to erratic responses to anti-Parkinson medication. The presence of enteric nervous system involvement in Parkinson's disease is now well established, but whether the enteric nervous system is the starting point for Parkinson's disease pathology remains a source of debate. The potential role of the gut microbiome also is beginning to emerge. Gastrointestinal dysfunction is a prominent nonmotor feature of Parkinson's disease and dysfunction can be found along the entire length of the gastrointestinal tract. The enteric nervous system is clearly involved in Parkinson's disease. Whether it is the initial source of pathology is still a source of controversy. There also is growing recognition of the role that the gut microbiome may play in Parkinson's disease, but much more research is needed to fully assess this aspect of the disorder.
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Affiliation(s)
- Ronald F Pfeiffer
- Department of Neurology, Oregon Health and Science University, Portland, OR, USA.
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13
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Stocchi F, Torti M. Constipation in Parkinson's Disease. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2017; 134:811-826. [PMID: 28805584 DOI: 10.1016/bs.irn.2017.06.003] [Citation(s) in RCA: 76] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Constipation is one of the main and disabling nonmotor symptoms in Parkinson's disease (PD), with a prevalence ranging from 24.6% to 63% according to the different diagnostic criteria used to define chronic constipation. Constipation is currently recognized as a risk factor of PD in relation to the number of evacuation per week and its severity. Moreover, several studies have demonstrated that constipation may precede the occurrence of motor symptoms underlying an earlier involvement of the enteric nervous system and the dorsal motor nucleus of the vagus in the α-synuclein pathology. In PD, constipation is mainly due to slower colonic transit or puborectalis dyssynergia, but the concomitant use of antiparkinsonian, pain, and antidepressant medications may worsen it. An accurate diagnosis and an adequate treatment of constipation it is pivotal to prevent complications such as intestinal occlusion and to ensure an optimal clinical response to levodopa.
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Affiliation(s)
- Fabrizio Stocchi
- University and Institute for Research and Medical Care, IRCCS San Raffaele, Rome, Italy.
| | - Margherita Torti
- University and Institute for Research and Medical Care, IRCCS San Raffaele, Rome, Italy.
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Abstract
Apart from the typical motor symptoms, Parkinson's disease is characterized by a wide range of different non-motor symptoms, which are highly prevalent in all stages of the disease and have an incisive influence on quality of life. Moreover, their treatment continues to be challenging. In this review, we critically summarize the evidence for the impact of dopaminergic therapies on non-motor symptoms in Parkinson's disease. We performed a PubMed search to identify relevant clinical studies that investigated the response of non-motor symptoms to dopaminergic therapy. In the domain of neuropsychiatric disturbances, there is increasing evidence that dopamine agonists can ameliorate depression or anxiety. Other neuropsychiatric symptoms such as psychosis or impulse control disorders can also be worsened or even be induced by dopaminergic agents. For the treatment of sleep disturbances, it is essential to identify different subtypes of sleep pathologies. While there is for example profound evidence for the effectiveness of dopaminergic medication for the treatment of restless legs syndrome and sleep fragmentation, evidence for an improvement of rapid eye movement sleep behavior disorder is lacking. With regard to the broad spectrum of autonomic disturbances, response to dopaminergic treatment seems to differ largely, with on the one hand, some evidence for an improvement of sexual function or sweating with dopaminergic treatment, while on the other hand, constipation can be worsened. Finally, the analysis of sensory deficits reveals that some forms of pain, in particular fluctuation-dependent dystonic pain, can be well addressed by adapting the dopaminergic therapy, while no effect has been seen so far for hyposmia or visual deficits. Moreover, the occurrence of non-motor fluctuations is gaining increased attention, as they can be specifically addressed by a more continuous dopaminergic intake. Taken together, there is evidence of a good response of some (but not all) non-motor symptoms to dopaminergic therapy, which must be individually adapted to the special spectrum of symptoms.
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Affiliation(s)
- Eva Schaeffer
- Department of Neurology, Christians-Albrechts University, Arnold-Heller-Str. 3, Haus 41, Kiel, 24105, Germany.
| | - Daniela Berg
- Department of Neurology, Christians-Albrechts University, Arnold-Heller-Str. 3, Haus 41, Kiel, 24105, Germany
- Department of Neurodegeneration, Hertie-Institute of Clinical Brain Research, Tuebingen, Germany
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Mundt-Petersen U, Odin P. Infusional Therapies, Continuous Dopaminergic Stimulation, and Nonmotor Symptoms. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2017; 134:1019-1044. [DOI: 10.1016/bs.irn.2017.05.036] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/17/2023]
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Gastrointestinal Dysfunctions in Parkinson's Disease: Symptoms and Treatments. PARKINSONS DISEASE 2016; 2016:6762528. [PMID: 28050310 PMCID: PMC5168460 DOI: 10.1155/2016/6762528] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Accepted: 10/16/2016] [Indexed: 12/21/2022]
Abstract
A diagnosis of Parkinson's disease is classically established after the manifestation of motor symptoms such as rigidity, bradykinesia, and tremor. However, a growing body of evidence supports the hypothesis that nonmotor symptoms, especially gastrointestinal dysfunctions, could be considered as early biomarkers since they are ubiquitously found among confirmed patients and occur much earlier than their motor manifestations. According to Braak's hypothesis, the disease is postulated to originate in the intestine and then spread to the brain via the vagus nerve, a phenomenon that would involve other neuronal types than the well-established dopaminergic population. It has therefore been proposed that peripheral nondopaminergic impairments might precede the alteration of dopaminergic neurons in the central nervous system and, ultimately, the emergence of motor symptoms. Considering the growing interest in the gut-brain axis in Parkinson's disease, this review aims at providing a comprehensive picture of the multiple gastrointestinal features of the disease, along with the therapeutic approaches used to reduce their burden. Moreover, we highlight the importance of gastrointestinal symptoms with respect to the patients' responses towards medical treatments and discuss the various possible adverse interactions that can potentially occur, which are still poorly understood.
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The efficacy of apomorphine – A non-motor perspective. Parkinsonism Relat Disord 2016; 33 Suppl 1:S28-S35. [DOI: 10.1016/j.parkreldis.2016.11.020] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Revised: 11/25/2016] [Accepted: 11/30/2016] [Indexed: 01/09/2023]
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Knudsen K, Krogh K, Østergaard K, Borghammer P. Constipation in parkinson's disease: Subjective symptoms, objective markers, and new perspectives. Mov Disord 2016; 32:94-105. [PMID: 27873359 DOI: 10.1002/mds.26866] [Citation(s) in RCA: 121] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2016] [Revised: 09/30/2016] [Accepted: 10/05/2016] [Indexed: 12/16/2022] Open
Abstract
Constipation is among the first nonmotor symptoms to develop in the prodromal phase of PD. Pathological alpha-synuclein deposition is present throughout the gastrointestinal tract up to 20 years preceding diagnosis. Nevertheless, constipation in the context of PD remains ill defined and poorly understood. In this review, we summarize current knowledge of subjective symptoms and objective measures of constipation in PD. More than 10 different definitions of constipation have been used in the PD literature, making generalizations difficult. When pooling results from the most homogeneous studies in PD, a median constipation prevalence of 40% to 50% emerges, but with large variation across individual studies. Also, constipation prevalence tends to increase with disease progression. A similar prevalence is observed among patients with idiopathic rapid eye movement sleep behavior disorder. Interestingly, we detected a correlation between constipation prevalence in PD patients and healthy control groups in individual studies, raising concerns about how various constipation questionnaires are implemented across study populations. More than 80% of PD patients exhibit prolonged colonic transit time, and the same is probably true for de novo PD patients. Thus, the prevalence of objective colonic dysfunction exceeds the prevalence of subjective constipation. Colonic transit time measures are simple, widely available, and hold promise as a useful biomarker in manifest PD. More research is needed to elucidate the role of gastrointestinal dysfunction in disease progression of PD. Moreover, colonic transit measures may have utility as a more accurate risk factor for predicting PD in the prodromal phase. © 2016 International Parkinson and Movement Disorder Society.
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Affiliation(s)
- Karoline Knudsen
- Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark
| | - Klaus Krogh
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Karen Østergaard
- Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
| | - Per Borghammer
- Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark
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Stirpe P, Hoffman M, Badiali D, Colosimo C. Constipation: an emerging risk factor for Parkinson's disease? Eur J Neurol 2016; 23:1606-1613. [PMID: 27444575 DOI: 10.1111/ene.13082] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2016] [Accepted: 06/09/2016] [Indexed: 12/11/2022]
Abstract
Constipation is the most prominent and disabling manifestation of lower gastrointestinal (GI) dysfunction in Parkinson's disease (PD). The prevalence of constipation in PD patients ranges from 24.6% to 63%; this variability is due to the different criteria used to define constipation and to the type of population enrolled in the studies. In addition, constipation may play an active role in the pathophysiological changes that underlie motor fluctuations in advanced PD through its negative effects on absorption of levodopa. Several clinical studies now consistently suggest that constipation may precede the first occurrence of classical motor features in PD. Studies in vivo, using biopsies of the GI tract and more recently functional imaging investigations, showed the presence of α-synuclein (α-SYN) aggregates and neurotransmitter alterations in enteric tissues. All these findings support the Braak proposed model for the pathophysiology of α-SYN aggregates in PD, with early pathological involvement of the enteric nervous system and dorsal motor nucleus of the vagus. Therefore, constipation could have the potential sensitivity to be used as a clinical biomarker of the prodromal phase of the disease. The use of colonic biopsies to look at α-SYN pathology, once confirmed by larger prospective studies, might eventually represent a feasible, albeit partially invasive, new diagnostic biomarker for PD.
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Affiliation(s)
- P Stirpe
- Department of Neurology, Institute for Research and Medical Care (IRCCS) San Raffaele, Rome, Italy
| | - M Hoffman
- Drexel University College of Medicine, Philadelphia, PA, USA
| | - D Badiali
- Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | - C Colosimo
- Department of Neurology, Santa Maria University Hospital, Terni, Italy. ,
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Martínez-Fernández R, Schmitt E, Martinez-Martin P, Krack P. The hidden sister of motor fluctuations in Parkinson's disease: A review on nonmotor fluctuations. Mov Disord 2016; 31:1080-94. [PMID: 27431515 DOI: 10.1002/mds.26731] [Citation(s) in RCA: 117] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2015] [Revised: 06/13/2016] [Accepted: 06/19/2016] [Indexed: 12/29/2022] Open
Abstract
Only a few years after the introduction of levodopa, the first descriptions of motor fluctuations and dyskinesia related to dopaminergic therapy appeared. In PD, attention turned to their management, that had dampened the euphoria of the "levodopa miracle." It soon became clear that neuropsychiatric, autonomic, and sensory features also tend to develop fluctuations after chronic exposure to l-dopa. The diversity of fluctuating nonmotor symptoms, their largely subjective nature, coupled with a frequent lack of insight led to difficulties in identification and quantification. This may explain why, despite the high impact of nonmotor symptoms on patient autonomy and quality of life, evaluation of nonmotor fluctuations is not part of clinical routine. In view of the lack of specific validated assessment tools, detailed anamnesis should ideally be coupled with an evaluation in both ON and OFF drug conditions. The mechanisms of nonmotor fluctuations are not well understood. It is thought that they share dopaminergic presynaptic pharmacokinetic and postsynaptic pharmacodynamic mechanisms with the classical motor complications, but involve different neural pathways. Although symptoms fluctuate with dopaminergic treatment, serotonine and norepinephrine denervation, as well as interactions between neurotransmitter systems, probably contribute to their diversity. The lack of validated tools for assessment of these phenomena explains the almost complete absence of treatment studies. Management, largely resulting from expert opinion, includes psychiatric follow-up, nondopaminergic drugs, and advanced dopaminergic treatment, including drug delivery pumps and DBS. This review aims to provide a starting point for the understanding, diagnosis, and management of nonmotor fluctuations. © 2016 International Parkinson and Movement Disorder Society.
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Affiliation(s)
| | - Emmanuelle Schmitt
- Movement Disorders Unit, Department of Psychiatry and Neurology, CHU de Grenoble, Université de Grenoble Alpes and Grenoble Institut des Neurosciences, INSERM U386, Grenoble, France
| | - Pablo Martinez-Martin
- National Center of Epidemiology, Carlos III Institute of Health and CIBERNED, Madrid, Spain
| | - Paul Krack
- Neurology Division, Department of Clinical Neurosciences, University Hospital of Geneva, Geneva, Switzerland
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Sveinbjornsdottir S. The clinical symptoms of Parkinson's disease. J Neurochem 2016; 139 Suppl 1:318-324. [PMID: 27401947 DOI: 10.1111/jnc.13691] [Citation(s) in RCA: 744] [Impact Index Per Article: 82.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2016] [Revised: 05/21/2016] [Accepted: 05/31/2016] [Indexed: 12/11/2022]
Abstract
In this review, the clinical features of Parkinson's disease, both motor and non-motor, are described in the context of the progression of the disease. Also briefly discussed are the major treatment strategies and their complications. Parkinson's disease is a slowly progressing neurodegenerative disorder, causing impaired motor function with slow movements, tremor and gait and balance disturbances. A variety of non-motor symptoms are common in Parkinson's disease. They include disturbed autonomic function with orthostatic hypotension, constipation and urinary disturbances, a variety of sleep disorders and a spectrum of neuropsychiatric symptoms. This article describes the different clinical symptoms that may occur and the clinical course of the disease. This article is part of a special issue on Parkinson disease.
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Affiliation(s)
- Sigurlaug Sveinbjornsdottir
- Department of Neurology, Broomfield Hospital, Chelmsford, Essex, CM1 7ET, UK. .,Queen Mary School of Medicine and Dentistry, University of London, London, UK.
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Ali SA, Yin N, Rehman A, Justilien V. Parkinson Disease-Mediated Gastrointestinal Disorders and Rational for Combinatorial Therapies. Med Sci (Basel) 2016; 4:medsci4010001. [PMID: 29083365 PMCID: PMC5635767 DOI: 10.3390/medsci4010001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2015] [Revised: 12/24/2015] [Accepted: 01/13/2016] [Indexed: 12/29/2022] Open
Abstract
A gradual loss of dopamine-producing nerve cells gives rise to a common neurodegenerative Parkinson’s disease (PD). This disease causes a neurotransmitter imbalance in the brain and initiates a cascade of complications in the rest of the body that appears as distressing symptoms which include gait problems, tremor, gastrointestinal (GI) disorders and cognitive decline. To aid dopamine deficiency, treatment in PD patients includes oral medications, in addition to other methods such as deep brain stimulation and surgical lesioning. Scientists are extensively studying molecular and signaling mechanisms, particularly those involving phenotypic transcription factors and their co-regulatory proteins that are associated with neuronal stem cell (SC) fate determination, maintenance and disease state, and their role in the pathogenesis of PD. Advancement in scientific research and “personalized medicine” to augment current therapeutic intervention and minimize the side effects of chemotherapy may lead to the development of more effective therapeutic strategies in the near future. This review focuses on PD and associated GI complications and summarizes the current therapeutic modalities that include stem cell studies and combinatorial drug treatment.
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Affiliation(s)
- Syed A Ali
- Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, FL 32224, USA.
| | - Ning Yin
- Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, FL 32224, USA.
| | - Arkam Rehman
- Department of Pain Medicine, Baptist Medical Center, Jacksonville, FL 32258, USA.
| | - Verline Justilien
- Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, FL 32224, USA.
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Essa H, Hamdy S. Evaluating the Scope of Gastrointestinal Symptoms of Parkinson's Disease: A Review of the Evidence. ACTA ACUST UNITED AC 2016. [DOI: 10.4303/ne/235955] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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Unti E, Ceravolo R, Bonuccelli U. Apomorphine hydrochloride for the treatment of Parkinson’s disease. Expert Rev Neurother 2015; 15:723-32. [DOI: 10.1586/14737175.2015.1051468] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Kim JS, Sung HY. Gastrointestinal Autonomic Dysfunction in Patients with Parkinson's Disease. J Mov Disord 2015; 8:76-82. [PMID: 26090079 PMCID: PMC4460543 DOI: 10.14802/jmd.15008] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Revised: 04/03/2015] [Accepted: 04/07/2015] [Indexed: 12/20/2022] Open
Abstract
Currently, gastrointestinal dysfunctions in Parkinson’s disease (PD) are well-recognized problems and are known to be an initial symptom in the pathological process that eventually results in PD. Gastrointestinal symptoms may result from the involvement of either the central or enteric nervous systems, or these symptoms may be side effects of antiparkinsonian medications. Weight loss, excessive salivation, dysphagia, nausea/gastroparesis, constipation, and defecation dysfunction all may occur. Increased identification and early detection of these symptoms can result in a significant improvement in the quality of life for PD patients.
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Affiliation(s)
- Joong-Seok Kim
- Department of Neurology, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hye-Young Sung
- Department of Gastroenterology, The Neighborhood Christian Clinic, AZ, USA
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Aquino CC, Fox SH. Clinical spectrum of levodopa-induced complications. Mov Disord 2014; 30:80-9. [PMID: 25488260 DOI: 10.1002/mds.26125] [Citation(s) in RCA: 185] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2014] [Revised: 10/20/2014] [Accepted: 11/24/2014] [Indexed: 12/20/2022] Open
Abstract
The first years of Parkinson disease (PD) treatment are marked by good and sustained responses to dopaminergic therapy. With disease progression and longer exposure to levodopa (l-dopa), patients develop a range of l-dopa-induced complications that include motor and non-motor symptoms. Motor complications include motor fluctuations, characterized by periods of reduced benefit from the medication, and l-dopa-induced dyskinesia, characterized by emergence of hyperkinetic involuntary movements. Dyskinesia can occur at peak effect of l-dopa, at the beginning and end of dose, or between doses. These motor complications are often associated with fluctuations in non-motor symptoms, particularly fluctuations in neuropsychiatric, autonomic, and sensory symptoms. Recognizing such complications and understanding their relationship with the timing of l-dopa doses is essential for adequate diagnosis and management. Society.
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Affiliation(s)
- Camila Catherine Aquino
- Movement Disorder Centre, Edmond J Safra Program in Parkinson Research, Toronto Western Hospital, University of Toronto, Canada
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Henriksen T. Clinical insights into use of apomorphine in Parkinson's disease: tools for clinicians. Neurodegener Dis Manag 2014; 4:271-82. [DOI: 10.2217/nmt.14.17] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
SUMMARY Apomorphine was introduced before the era of levodopa as a treatment for idiopathic Parkinson's disease (iPD). A number of practical obstacles were to be solved before a wider use of the drug was possible. Today, however, the drug is probably still underutilized. Apomorphine is a strong nonergoline D1 and D2 receptor agonist with a dopaminergic effect comparable with levodopa. In this review motor and non-motor indications for intermittent injections and subcutaneous apomorphine infusions are listed. The reduction of 'off' periods is more than 50% on infusion therapy and if monotherapy is achieved a significant reduction of pre-existing levodopainduced dyskinesias is seen. The aim of this review is to give practical insight into apomorphine treatment, highlighting side effects, and complications and device-related problems are discussed with advice on how to prevent or handle these, should they occur. A number of practical points including the apomorphine test, requirements of the clinical setting, how to increase adherence and troubleshooting are added.
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Krismer F, Jellinger KA, Scholz SW, Seppi K, Stefanova N, Antonini A, Poewe W, Wenning GK. Multiple system atrophy as emerging template for accelerated drug discovery in α-synucleinopathies. Parkinsonism Relat Disord 2014; 20:793-9. [PMID: 24894118 PMCID: PMC4141743 DOI: 10.1016/j.parkreldis.2014.05.005] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2013] [Revised: 04/27/2014] [Accepted: 05/07/2014] [Indexed: 12/21/2022]
Abstract
There is evidence that the α-synucleinopathies Parkinson's disease (PD) and the Parkinson variant of multiple system atrophy (MSA-P) overlap at multiple levels. Both disorders are characterized by deposition of abnormally phosphorylated fibrillar α-synuclein within the central nervous system suggesting shared pathophysiological mechanisms. Despite the considerable clinical overlap in the early disease stages, MSA-P, in contrast to PD, is fatal and rapidly progressive. Moreover recent clinical studies have shown that surrogate markers of disease progression can be quantified easily and may reliably depict the rapid course of MSA. We therefore posit that, MSA-P may be exploited as a filter barrier in the development of disease-modifying therapeutic strategies targeting common pathophysiological mechanisms of α-synucleinopathies. This approach might reduce the number of negative phase III clinical trials, and, in turn, shift the available resources to earlier development stages, thereby increasing the number of candidate compounds validated.
α-synucleinopathies overlap at multiple levels. α-synucleinopathies are characterized by an abnormal deposition of α-synuclein. Validated surrogate markers in MSA reliably monitor disease progression. MSA may serve as a template disease for other α-synucleinopathies.
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Affiliation(s)
- Florian Krismer
- Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
| | | | - Sonja W Scholz
- Department of Neurology, The Johns Hopkins Hospital, Baltimore, MD 21287, USA.
| | - Klaus Seppi
- Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
| | - Nadia Stefanova
- Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
| | - Angelo Antonini
- Department of Parkinson's Disease and Movement Disorders, IRCCS San Camillo, Venice, Italy.
| | - Werner Poewe
- Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
| | - Gregor K Wenning
- Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
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Sung HY, Park JW, Kim JS. The frequency and severity of gastrointestinal symptoms in patients with early Parkinson's disease. J Mov Disord 2014; 7:7-12. [PMID: 24926404 PMCID: PMC4051727 DOI: 10.14802/jmd.14002] [Citation(s) in RCA: 70] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2014] [Revised: 02/20/2014] [Accepted: 02/20/2014] [Indexed: 12/11/2022] Open
Abstract
Objective Although gastrointestinal dysfunctions occur in the majority of patients with Parkinson’s disease (PD), they are often unrecognized because many patients remain relatively asymptomatic in the early stage. We investigated the frequency of gastrointestinal symptoms in patients with PD using newly developed gastrointestinal symptom questionnaires. Methods Early PD patients with a symptom duration not exceeding 3 years were included in this study. All PD patients were evaluated using a questionnaire, which consisted of three relevant domains: oropharyngoesophageal (10 items); gastric (3 items); and intestinal-anorectal (7 items). The frequency of symptoms was calculated as a proportion with an item score ≥ 2. Results Of the 54 patients enrolled, 48 patients (88.9%) responded that bowel symptoms developed before the onset of Parkinsonian motor symptoms, and four patients reported that the onset of two types of symptoms (i.e., bowel and neurological) occurred approximately simultaneously, with only months between them. The frequencies of gastrointestinal symptoms are as follows: speech disturbance (40.7%), drooling (24.1%), sense of getting stuck (31.5%), choking (27.8%), globus pharyngis (16.7%), repetitive deglutition (29.6%), pain during swallowing (5.6%), food regurgitation (3.7%), acid reflux (7.4%), nausea/vomiting (11.1%), early satiety (16.7%), postprandial fullness (14.8%), epigastric soreness (9.3%), abdominal pain (3.7%), constipation (46.3%), excessive strain during defecation (33.3%), fecal incontinence (7.4%), tenesmus (20.4%), loose stool or diarrhea (3.7%), and difficulty in relaxing anal sphincter (11.1%). Two patients were scored at zero. Conclusions Our findings confirm that gastrointestinal dysfunction occurs in early PD in relatively high frequency.
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Affiliation(s)
- Hye-Young Sung
- Division of Gastroenterology, Digestive Disease Research Institute, Department of Internal Medicine, Wonkwang University Sanbon Hospital, Gunpo, Korea
| | - Jeong-Wook Park
- Department of Neurology, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Joong-Seok Kim
- Department of Neurology, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Todorova A, Ray Chaudhuri K. Subcutaneous apomorphine and non-motor symptoms in Parkinson's disease. Parkinsonism Relat Disord 2013; 19:1073-8. [PMID: 24051336 DOI: 10.1016/j.parkreldis.2013.08.012] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2013] [Revised: 08/01/2013] [Accepted: 08/19/2013] [Indexed: 10/26/2022]
Abstract
Non-motor symptoms (NMS) are now recognized to occur across all stages of Parkinson's disease (PD) and as a result there has been an increasing focus on their diagnosis, quantification and effective management. While in some subjects, NMS may be present before diagnosis, in advanced PD, NMS can contribute to hospitalization, severe disability and a shortened life expectancy. Strategies for continuous drug delivery have been reported to have a beneficial effect on NMS in PD and while the efficacy of apomorphine on motor function in PD has been confirmed in a number of studies, in addition to its possible anti-dyskinetic effect, a number of reports have also outlined the possible beneficial effect of apomorphine on NMS. This review sets out to examine the efficacy of apomorphine in non-motor aspects of PD, including its effect on neuropsychiatric and gastrointestinal symptoms, sleep (including restless legs syndrome), urinary dysfunction, pain and impulse control disorders. The analysis takes into consideration case reports, and open-label and comparative case-control studies published to date. Results of this review suggest that although data on the effect of apomorphine on NMS in PD patients are limited there is a strong suggestion of a beneficial effect that warrants further investigation in double-blind studies.
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Affiliation(s)
- Antoniya Todorova
- National Parkinson Foundation Centre of Excellence, Department of Neurology, King's College Hospital, and King's Health Partners, London, UK.
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Neurostimulation for neurogenic bowel dysfunction. Gastroenterol Res Pract 2013; 2013:563294. [PMID: 23573076 PMCID: PMC3618949 DOI: 10.1155/2013/563294] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2013] [Accepted: 02/20/2013] [Indexed: 12/11/2022] Open
Abstract
Background. Loss of normal bowel function caused by nerve injury, neurological disease or congenital defects of the nervous system is termed neurogenic bowel dysfunction (NBD). It usually includes combinations of fecal incontinence, constipation, abdominal pain and bloating. When standard treatment of NBD fails surgical procedures are often needed. Neurostimulation has also been investigated, but no consensus exists about efficacy or clinical use. Methods. A systematic literature search of NBD treated by sacral anterior root stimulation (SARS), sacral nerve stimulation (SNS), peripheral nerve stimulation, magnetic stimulation, and nerve re-routing was made in Pubmed, Embase, Scopus, and the Cochrane Library. Results. SARS improves bowel function in some patients with complete spinal cord injury (SCI). Nerve re-routing is claimed to facilitate defecation through mechanical stimulation of dermatomes in patients with complete or incomplete SCI or myelomeningocele. SNS can reduce NBD in selected patients with a variety of incomplete neurological lesions. Peripheral stimulation using electrical stimulation or magnetic stimulation may represent non-invasive alternatives. Conclusion. Numerous methods of neurostimulation to treat NBD have been investigated in pilot studies or retrospective studies. Therefore, larger controlled trials with well-defined inclusion criteria and endpoints are recommended before widespread clinical use of neurostimulation against NBD.
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Kaufmann H, Goldstein DS. Autonomic dysfunction in Parkinson disease. HANDBOOK OF CLINICAL NEUROLOGY 2013; 117:259-78. [DOI: 10.1016/b978-0-444-53491-0.00021-3] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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Del Tredici K, Braak H. Spinal cord lesions in sporadic Parkinson's disease. Acta Neuropathol 2012; 124:643-64. [PMID: 22926675 DOI: 10.1007/s00401-012-1028-y] [Citation(s) in RCA: 126] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2012] [Revised: 07/25/2012] [Accepted: 07/25/2012] [Indexed: 12/14/2022]
Abstract
In this autopsy-based study, α-synuclein immunohistochemistry and lipofuscin pigment-Nissl architectonics in serial sections of 100 μm thickness were used to investigate the spinal cords and brains of 46 individuals: 28 patients with clinically and neuropathologically confirmed Parkinson's disease, 6 cases with incidental Lewy body disease, and 12 age-matched controls. α-Synuclein inclusions (particulate aggregations, Lewy neurites/bodies) in the spinal cord were present between neuropathological stages 2-6 in all cases whose brains were staged for Parkinson's disease-related synucleinopathy. The only individuals who did not have Lewy pathology in the spinal cord were a single stage 1 case (incidental Lewy body disease) and all controls. Because the Parkinson's disease-related lesions were observable in the spinal cord only after Lewy pathology was seen in the brain, it could be concluded that, within the central nervous system, sporadic Parkinson's disease does not begin in the spinal cord. In addition: (1) α-Synuclein-immunoreactive axons clearly predominated over Lewy bodies throughout the spinal cord and were visible in medial and anterior portions of the anterolateral funiculus. Their terminal axons formed dense α-synuclein-immunoreactive networks in the gray matter and were most conspicuous in the lateral portions of layers 1, 7, and in the cellular islands of layer 9. (2) Notably, this axonopathy increased remarkably in density from cervicothoracic segments to lumbosacral segments of the cord. (3) Topographically, it is likely that the spinal cord α-synuclein immunoreactive axonal networks represent descending projections from the supraspinal level setting nuclei (locus coeruleus, lower raphe nuclei, magnocellular portions of the reticular formation). (4) Following the appearance of the spinal cord axonal networks, select types of projection neurons in the spinal cord gray matter displayed α-synuclein-immunoreactive inclusions: chiefly, nociceptive neurons of the dorsal horn in layer 1, sympathetic and parasympathetic preganglionic neurons in layer 7, the cellular pools of α-motoneurons in layer 9, and the smaller motoneurons in Onuf's nucleus in layer 9 (ventral horn). The spinal cord lesions may contribute to clinical symptoms (e.g., pain, constipation, poor balance, lower urinary tract complaints, and sexual dysfunction) that occur during the premotor and motor phases of sporadic Parkinson's disease.
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Affiliation(s)
- Kelly Del Tredici
- Clinical Neuroanatomy Section, Department of Neurology, Center for Biomedical Research, University of Ulm, Germany.
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Sung HY, Choi MG, Kim YI, Lee KS, Kim JS. Anorectal manometric dysfunctions in newly diagnosed, early-stage Parkinson's disease. J Clin Neurol 2012; 8:184-9. [PMID: 23091527 PMCID: PMC3469798 DOI: 10.3988/jcn.2012.8.3.184] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2011] [Revised: 02/03/2012] [Accepted: 02/03/2012] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND AND PURPOSE Anorectal dysmotility is common in advanced Parkinson's disease (PD), but there have been few evaluations in newly diagnosed PD patients. METHODS We conducted anorectal manometric evaluations in 19 newly diagnosed, drug-naïve, early-stage PD patients. All of the PD patients were questioned regarding the presence of anorectal symptoms. RESULTS Anorectal manometry was abnormal in 12 of the 19 patients. These abnormalities were more common in patients with more severe anorectal symptoms, as measured using a self-reported scale. However, more than 40% of patients with no or minimal symptoms also exhibited manometric abnormalities. CONCLUSIONS These results suggest that anorectal dysmotility manifests in many early-stage PD patients, which this represent evidence for the involvement of neuronal structures in such nonmotor manifestations in PD.
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Affiliation(s)
- Hye Young Sung
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, Korea
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Abstract
The recognition and treatment of nonmotor symptoms are increasingly emphasized in the care of Parkinson's disease (PD) patients. This manuscript will review signs and symptoms localized, generally, to the cortex, basal ganglia, brainstem, spinal cord, and peripheral nervous system. Cortical manifestations include dementia, mild cognitive impairment, and psychosis. Apathy, restlessness (akathisia), and impulse control disorders will be linked as basal ganglia symptoms. Symptoms attributed to the brainstem comprise depression, anxiety, and sleep disorders. Peripheral nervous system disturbances may lead to orthostatic hypotension, constipation, pain, and sensory disturbances.
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Affiliation(s)
- Mark Stacy
- Department of Neurology, Duke University Medical Center, Durham, North Carolina 27705, USA.
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Gastrointestinale Störungen beim idiopathischen Parkinson-Syndrom. DER NERVENARZT 2012; 83:1282-91. [DOI: 10.1007/s00115-012-3575-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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Abstract
BACKGROUND Although the diagnosis of Parkinson disease (PD) still relies mainly on the appearance of its classical motor features of resting tremor, rigidity, bradykinesia, and postural instability, nonmotor manifestations in PD are now recognized as an integral component of this multisystem disorder. REVIEW SUMMARY Nonmotor complications in PD occur commonly. The current understanding of cognitive dysfunction; neuropsychiatric manifestations including psychosis, impulsive control, and compulsive disorders, depression, anxiety and apathy; autonomic complications such as hypotension, erectile dysfunction, and urinary complications; sleep disorders and other nonmotor manifestations are summarized in this review. CONCLUSION Nonmotor complications often carry a greater impact than motor features in PD. Therefore, heightened awareness and proper recognition of these features are critical in improving a Parkinson patient's quality of life.
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Tateno F, Sakakibara R, Yokoi Y, Kishi M, Ogawa E, Uchiyama T, Yamamoto T, Yamanishi T, Takahashi O. Levodopa ameliorated anorectal constipation in de novo Parkinson's disease: The QL-GAT study. Parkinsonism Relat Disord 2011; 17:662-6. [PMID: 21705259 DOI: 10.1016/j.parkreldis.2011.06.002] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2010] [Revised: 05/26/2011] [Accepted: 06/02/2011] [Indexed: 02/09/2023]
Abstract
BACKGROUND Gastrointestinal tract (GIT) dysfunction is common in Parkinson's disease (PD) patients. However, it remains unclear whether levodopa affects GIT function in PD. OBJECTIVE To perform an open study of levodopa's effects on anorectal constipation in de novo PD patients by the quantitative lower-gastrointestinal autonomic test (QL-GAT). METHODS Nineteen unselected de novo PD patients (10 men, 9 women; mean age, 66 years; mean duration of the disease, 2.2 years) were recruited for the study. Eighteen of the patients reported constipation. These patients were treated with 200/20 mg b.i.d. of levodopa/carbidopa for 3 months. Pre- and post-treatment, objective parameters in the QL-GAT that comprised the colonic transit time (CTT) and rectoanal videomanometry were obtained. RESULTS Levodopa was well tolerated by all patients. There was a trend toward subjective improvements in bowel frequency and difficulty defecating. Levodopa did not significantly change CTT of the total colon or any segment of the colon. During rectal filling, levodopa significantly lessened the first sensation (p < 0.05). It also tended to augment the amplitude of spontaneous phasic rectal contraction (not statistically significant). During defecation, levodopa significantly lessened the amplitude in paradoxical sphincter contraction upon defecation (PSD) (p < 0.01). It also tended to augment the amplitude of rectal contraction and lessen the amplitude of abdominal strain (not statistically significant). Overall, levodopa significantly lessened post-defecation residuals (p < 0.05). CONCLUSIONS The QL-GAT in the present study showed for the first time that levodopa augmented rectal contraction, lessened PSD, and thereby ameliorated anorectal constipation in de novo PD patients.
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Affiliation(s)
- Fuyuki Tateno
- Neurology Division, Department of Internal Medicine, Sakura Medical Center, Toho University, 564-1 Shimoshizu, Sakura 285-8741, Japan
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Abstract
Gastrointestinal (GI) symptoms are among the most common nonmotor manifestations of Parkinson's disease (PD), and they have many important ramifications for patients. The purpose of this review is to raise awareness of the full spectrum of GI symptoms in PD which include weight loss, sialorrhea, dysphagia, nausea, constipation, and defecatory dysfunction. We will discuss their practical significance, and outline a clear approach to their evaluation and management. A brief discussion about the impacts of commonly used medical and surgical PD therapies on GI symptom manifestation is also included.
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Sakakibara R, Kishi M, Ogawa E, Tateno F, Uchiyama T, Yamamoto T, Yamanishi T. Bladder, bowel, and sexual dysfunction in Parkinson's disease. PARKINSONS DISEASE 2011; 2011:924605. [PMID: 21918729 PMCID: PMC3171780 DOI: 10.4061/2011/924605] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/17/2010] [Revised: 05/06/2011] [Accepted: 05/30/2011] [Indexed: 12/14/2022]
Abstract
Bladder dysfunction (urinary urgency/frequency), bowel dysfunction (constipation), and sexual dysfunction (erectile dysfunction) (also called “pelvic organ” dysfunctions) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, pelvic organ autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, peripheral myenteric pathology causing slowed colonic transit (loss of rectal contractions) and central pathology causing weak strain and paradoxical anal sphincter contraction on defecation (PSD, also called as anismus) are responsible for the bowel dysfunction. In addition, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Dietary fibers, laxatives, and “prokinetic” drugs such as serotonergic agonists are used to treat bowel dysfunction in PD. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life.
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Affiliation(s)
- Ryuji Sakakibara
- Neurology Division, Department of Internal Medicine, Sakura Medical Center, Toho University, 564-1 Shimoshizu, Sakura 285-8741, Japan
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Kim JS, Sung HY, Lee KS, Kim YI, Kim HT. Anorectal dysfunctions in Parkinson's disease. J Neurol Sci 2011; 310:144-51. [PMID: 21696777 DOI: 10.1016/j.jns.2011.05.048] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2011] [Revised: 05/23/2011] [Accepted: 05/31/2011] [Indexed: 12/14/2022]
Abstract
Anorectal symptoms are frequently found in patients with Parkinson's disease (PD), mainly manifested as diffuse lower abdominal discomfort, constipation, and fecal incontinence. Among these symptoms, constipation may precede by years the motor manifestations of PD. Research has focused for decades on selection of a measurement method for detection of abnormalities and support of clinometric instruments for anorectal symptoms. We review those manifestations and their contribution to evaluation of the anorectal symptoms in patients with PD.
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Affiliation(s)
- Joong-Seok Kim
- Department of Neurology, The Catholic University of Korea, Seoul, Republic of Korea.
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Clinical review of treatment options for select nonmotor symptoms of Parkinson's disease. ACTA ACUST UNITED AC 2010; 8:294-315. [PMID: 20869620 DOI: 10.1016/j.amjopharm.2010.08.002] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/12/2010] [Indexed: 10/19/2022]
Abstract
BACKGROUND Parkinson's disease (PD) is associated with a host of nonmotor symptoms, including psychosis, cognitive impairment, depression, sleep disturbance, swallowing disorders, gastrointestinal symptoms, and autonomic dysfunction. The nonmotor symptoms of PD have the potential to be more debilitating than the motor features of the disorder. OBJECTIVE The aim of this article was to review treatment options for the nonmotor manifestations of PD, including pharmacologic and nonpharmacologic interventions. METHODS The PubMed and MEDLINE databases were searched for articles published in English between January 1966 and April 2010, using the terms Parkinson's disease, nonmotor, psychosis, hallucination, antipsychotic, cognitive impairment, dementia, depression, sleep disturbance, sleepiness, REM (rapid eye movement) sleep behavior disorder, dysphagia, swallowing disorder, sialorrhea, gastrointestinal, constipation, autonomic dysfunction, orthostatic hypotension, gastroparesis, erectile dysfunction, sexual dysfunction, and urinary dysfunction. Articles were selected for review if they were randomized controlled trials (RCTs), meta-analyses, or evidence-based reviews of treatment of patients with PD, and/or expert opinion regarding the treatment of nonmotor symptoms of PD. RESULTS A total of 148 articles, including RCTs, meta-analyses, and evidence-based reviews, were included in this review. The treatment of hallucinations or psychosis in PD should include a stepwise reduction in medications for motor symptoms, followed by the use of quetiapine or clozapine. Dementia may be treated with acetylcholinesterase inhibitors. Evidence is lacking concerning the optimal pharmacologic treatment for depression in PD, with expert opinions indicating selective serotonin reuptake inhibitors as the antidepressants of choice. However, the largest study to date found nortriptyline therapy to be efficacious compared with placebo, whereas paroxetine controlled release was not. A variety of sleep disturbances may plague a person with PD, and treatment must be individualized to the patient's specific sleep disturbance pattern and contributing factors. Swallowing disorders may lead to aspiration and pneumonia, and patients with dysphagia should be referred to a speech therapist for further evaluation and treatment. Orthostasis may be treated with nonpharmacologic interventions as well as pharmacologic treatments (eg, fludrocortisone, midodrine, indomethacin). Other autonomic symptoms are managed in a manner similar to that in patients without PD, although careful attention must be aimed at avoiding dopamine-blocking therapies in the treatment of gastrointestinal dysfunction and gastroparesis. CONCLUSIONS Various pharmacologic and nonpharmacologic strategies are available for the management of the nonmotor symptoms of PD. The challenges associated with nonmotor symptoms must not be forgotten in light of the motor symptoms of PD, and treatment of nonmotor symptoms should be encouraged.
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Pfeiffer RF. Gastrointestinal dysfunction in Parkinson's disease. Parkinsonism Relat Disord 2010; 17:10-5. [PMID: 20829091 DOI: 10.1016/j.parkreldis.2010.08.003] [Citation(s) in RCA: 188] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2010] [Accepted: 08/04/2010] [Indexed: 02/06/2023]
Abstract
In recent years, an increasingly detailed picture of gastrointestinal dysfunction in the setting of Parkinson's disease has emerged. Abnormalities of function may occur at virtually all levels of the gastrointestinal tract. Weight loss, dental deterioration, salivary excess, dysphagia, gastroparesis, decreased bowel movement frequency, and anorectal dysfunction all may occur. The pathophysiologic basis for this dysfunction entails both central and enteric nervous system involvement.
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Affiliation(s)
- Ronald F Pfeiffer
- Department of Neurology, University of Tennessee Health Science Center, 855 Monroe Avenue, Memphis, TN 38163, USA.
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Sakakibara R, Tsunoyama K, Hosoi H, Takahashi O, Sugiyama M, Kishi M, Ogawa E, Terada H, Uchiyama T, Yamanishi T. Influence of Body Position on Defecation in Humans. Low Urin Tract Symptoms 2010; 2:16-21. [PMID: 26676214 DOI: 10.1111/j.1757-5672.2009.00057.x] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
OBJECTIVES To compare three positions for defecation by measuring abdominal pressure and the anorectal angle simultaneously. METHODS We recruited six healthy volunteers. The videomanometric measures included simultaneous fluoroscopic images, abdominal pressures, subtracted rectal pressures and anal sphincter pressures. Three positions were used: sitting, sitting with the hip flexing at 60 ° with respect to the rest of the body, and squatting with the hip flexing at 22.5 ° with respect to the rest of the body. RESULTS Basal abdominal pressure before defecation on hip-flex sitting was lower than that with normal sitting, although the difference did not reach statistical significance. Basal abdominal pressure before defecation on squatting (26 cmH2 O) was lower than that with normal sitting (P < 0.01). Abdominal pressure increase (strain) on hip-flex sitting was lower than that with normal sitting, although this difference did not reach statistical significance. Similarly, the abdominal pressure increase on squatting was smaller than that with normal sitting, and yet the difference did not reach statistical significance. The rectoanal angle on defecation on hip-flex sitting did not differ from that with normal sitting. The rectoanal angle on defecation on squatting (126 °) was larger than that with normal sitting (100 °) (P < 0.05), and was also larger than that with hip-flex sitting (99 °) (P < 0.01). CONCLUSION The results of the present study suggest that the greater the hip flexion achieved by squatting, the straighter the rectoanal canal will be, and accordingly, less strain will be required for defecation.
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Affiliation(s)
- Ryuji Sakakibara
- Department of Internal Medicine, Division of Neurology, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Urology, Tokyo Women's Medical University, Tokyo, JapanAishin Seiki Inc., Tokyo, JapanClinical Physiology Unit, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Radiology, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Neurology, Chiba University, Chiba, JapanDepartment of Urology, Dokkyo Medical College, Tochigi, Japan
| | - Kuniko Tsunoyama
- Department of Internal Medicine, Division of Neurology, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Urology, Tokyo Women's Medical University, Tokyo, JapanAishin Seiki Inc., Tokyo, JapanClinical Physiology Unit, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Radiology, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Neurology, Chiba University, Chiba, JapanDepartment of Urology, Dokkyo Medical College, Tochigi, Japan
| | - Hiroyasu Hosoi
- Department of Internal Medicine, Division of Neurology, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Urology, Tokyo Women's Medical University, Tokyo, JapanAishin Seiki Inc., Tokyo, JapanClinical Physiology Unit, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Radiology, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Neurology, Chiba University, Chiba, JapanDepartment of Urology, Dokkyo Medical College, Tochigi, Japan
| | - Osamu Takahashi
- Department of Internal Medicine, Division of Neurology, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Urology, Tokyo Women's Medical University, Tokyo, JapanAishin Seiki Inc., Tokyo, JapanClinical Physiology Unit, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Radiology, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Neurology, Chiba University, Chiba, JapanDepartment of Urology, Dokkyo Medical College, Tochigi, Japan
| | - Megumi Sugiyama
- Department of Internal Medicine, Division of Neurology, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Urology, Tokyo Women's Medical University, Tokyo, JapanAishin Seiki Inc., Tokyo, JapanClinical Physiology Unit, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Radiology, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Neurology, Chiba University, Chiba, JapanDepartment of Urology, Dokkyo Medical College, Tochigi, Japan
| | - Masahiko Kishi
- Department of Internal Medicine, Division of Neurology, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Urology, Tokyo Women's Medical University, Tokyo, JapanAishin Seiki Inc., Tokyo, JapanClinical Physiology Unit, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Radiology, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Neurology, Chiba University, Chiba, JapanDepartment of Urology, Dokkyo Medical College, Tochigi, Japan
| | - Emina Ogawa
- Department of Internal Medicine, Division of Neurology, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Urology, Tokyo Women's Medical University, Tokyo, JapanAishin Seiki Inc., Tokyo, JapanClinical Physiology Unit, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Radiology, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Neurology, Chiba University, Chiba, JapanDepartment of Urology, Dokkyo Medical College, Tochigi, Japan
| | - Hitoshi Terada
- Department of Internal Medicine, Division of Neurology, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Urology, Tokyo Women's Medical University, Tokyo, JapanAishin Seiki Inc., Tokyo, JapanClinical Physiology Unit, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Radiology, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Neurology, Chiba University, Chiba, JapanDepartment of Urology, Dokkyo Medical College, Tochigi, Japan
| | - Tomoyuki Uchiyama
- Department of Internal Medicine, Division of Neurology, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Urology, Tokyo Women's Medical University, Tokyo, JapanAishin Seiki Inc., Tokyo, JapanClinical Physiology Unit, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Radiology, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Neurology, Chiba University, Chiba, JapanDepartment of Urology, Dokkyo Medical College, Tochigi, Japan
| | - Tomonori Yamanishi
- Department of Internal Medicine, Division of Neurology, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Urology, Tokyo Women's Medical University, Tokyo, JapanAishin Seiki Inc., Tokyo, JapanClinical Physiology Unit, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Radiology, Sakura Medical Center, Toho University, Sakura, JapanDepartment of Neurology, Chiba University, Chiba, JapanDepartment of Urology, Dokkyo Medical College, Tochigi, Japan
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Abstract
The cardinal characteristics of Parkinson disease (PD) include resting tremor, rigidity, and bradykinesia. Patients may also develop autonomic dysfunction, cognitive changes, psychiatric symptoms, sensory complaints, and sleep disturbances. The treatment of motor and non-motor symptoms of Parkinson disease is addressed in this article.
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Affiliation(s)
- Mark Stacy
- Division of Neurology, Department of Medicine, Duke University Medical Center, Durham, NC 27705, USA.
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Bayulkem K, Lopez G. Nonmotor fluctuations in Parkinson's disease: clinical spectrum and classification. J Neurol Sci 2009; 289:89-92. [PMID: 19747695 DOI: 10.1016/j.jns.2009.08.022] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
UNLABELLED The majority of patients with Parkinson's disease (PD) on levodopa (LD) treatment usually experience motor fluctuations (MFs) within several years of initiation of treatment. Besides the classic MFs, many nonmotor fluctuations (NMFs) may occur in PD. NMFs appear both in the "on" state and "off" state. However, the clinical spectrum and the frequency of these symptoms are not well recognized. NMFs are usually mild and less disabling than MFs but sometimes can lead to unnecessary tests and therapies. NMFs occurring in association with the "on" state are better known and therefore more frequently diagnosed than those occurring in the "off" state. NMFs can be classified into three groups: autonomic, cognitive/psychiatric, and sensory. They include gastrointestinal and urinary symptoms, drenching sweats, temperature and blood-pressure changes, depression, anxiety, hallucinations, hypomania, moaning/screaming, confusion, cognitive dysfunction, sexual deviations and dopamine dysregulation syndrome (DDS), pain, akathisia, internal tremor, numbness/parasthesia, and dyspnea. CONCLUSION Recognition of NMFs may prevent unnecessary diagnostic tests and may lead to treatment modifications aimed to minimize their occurrence.
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Affiliation(s)
- Kemal Bayulkem
- Cerrahpsa Faculty of Medicine, University of Istanbul, Department of Neurology, Istanbul, Turkey.
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Abstract
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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Affiliation(s)
- Wolfgang H Jost
- Dept. of Neurology, Deutsche Klinik für Diagnostik, Wiesbaden, Germany.
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49
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Abstract
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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Affiliation(s)
- Klaus Krogh
- Neurogastroenterology Unit, Department of Hepatology and Gastroenterology V, Aarhus University Hospital, Norrebrogade 2, 8000 Aarhus C, Denmark.
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Petrovitch H, Abbott RD, Ross GW, Nelson J, Masaki KH, Tanner CM, Launer LJ, White LR. Bowel movement frequency in late-life and substantia nigra neuron density at death. Mov Disord 2009; 24:371-6. [PMID: 19006191 PMCID: PMC3272050 DOI: 10.1002/mds.22360] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Constipation is associated with future risk of Parkinson's disease (PD) and with incidental Lewy bodies (LB) in the locus ceruleus or substantia nigra (SN). Our purpose is to examine the independent association between bowel movement frequency in late-life and postmortem SN neuron density. Bowel movement frequency was assessed in the Honolulu-Asia Aging Study from 1991 to 1993 in 414 men aged 71 to 93 years with later postmortem evaluations. Brains were examined for LB in the SN and locus ceruleus and neurons were counted in four quadrants from a transverse section of SN. In nonsmokers, neuron densities (counts/mm(2)) for men with >1, 1, and <1 bowel movement daily were 18.5, 18.8, 10.1 (P < 0.001) for dorsomedial; 15.3, 16.4, 10.2 (P < 0.03) for ventromedial; and 18.6, 18.3, 10.9 (P = 0.011) for ventrolateral quadrants. Relationships were not significant in the dorsolateral quadrant or in any quadrant among smokers. After adjustment for age, time to death, coffee drinking, tricep skinfold thickness, excessive daytime sleepiness, cognitive function, PD, and incidental LB, density ratios in nonsmokers with 1 or more bowel movement(s) daily were significantly higher compared to those with <1 daily. Constipation is associated with low SN neuron density independent of the presence of LB.
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