Download PDF
Semin Neurol 2017; 37(02): 176-185
DOI: 10.1055/s-0037-1601568
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Management of Autonomic Dysfunction in Parkinson's Disease

Ronald F. Pfeiffer
1   Department of Neurology, Oregon Health and Science University, Portland, Oregon
› Author Affiliations
Further Information

Publication History

Publication Date:
16 May 2017 (online)

    Permissions and Reprints

Abstract

Autonomic dysfunction is a frequent and important nonmotor feature of Parkinson's disease (PD). Autonomic dysfunction in PD spans a broad clinical spectrum. Cardiovascular dysfunction is characterized most prominently by orthostatic hypotension. Gastrointestinal dysfunction can involve virtually all levels of the gastrointestinal tract. Urinary dysfunction can entail either too frequent voiding or difficulty voiding. Sexual dysfunction is frequent and frustrating for both the patient and the partner. Alterations in sweating and body temperature are not widely recognized, but often are present. The presence of effective treatment for at least some aspects of autonomic dysfunction makes it vitally important that the assessment of autonomic dysfunction be a regular component of the neurologic history and examination for individuals with PD.

Keywords

autonomic - gastrointestinal - orthostatic hypotension - urinary - erectile dysfunction - thermoregulatory
 

  • References

  • 1 Siddiqui MF, Rast S, Lynn MJ, Auchus AP, Pfeiffer RF. Autonomic dysfunction in Parkinson's disease: a comprehensive symptom survey. Parkinsonism Relat Disord 2002; 8 (4) 277-284
    CrossrefPubMedGoogle Scholar
  • 2 Khoo TK, Yarnall AJ, Duncan GW , et al. The spectrum of nonmotor symptoms in early Parkinson disease. Neurology 2013; 80 (3) 276-281
    CrossrefPubMedGoogle Scholar
  • 3 Djaldetti R, Lev N, Melamed E. Lesions outside the CNS in Parkinson's disease. Mov Disord 2009; 24 (6) 793-800
    CrossrefPubMedGoogle Scholar
  • 4 Pfeiffer RF. Autonomic dysfunction in Parkinson's disease. Expert Rev Neurother 2012; 12 (6) 697-706
    CrossrefPubMedGoogle Scholar
  • 5 Amino T, Orimo S, Itoh Y, Takahashi A, Uchihara T, Mizusawa H. Profound cardiac sympathetic denervation occurs in Parkinson disease. Brain Pathol 2005; 15 (1) 29-34
    PubMedGoogle Scholar
  • 6 Rascol O, Schelosky L. 123I-metaiodobenzylguanidine scintigraphy in Parkinson's disease and related disorders. Mov Disord 2009; 24 (Suppl. 02) S732-S741
    CrossrefPubMedGoogle Scholar
  • 7 Orimo S, Suzuki M, Inaba A, Mizusawa H. 123I-MIBG myocardial scintigraphy for differentiating Parkinson's disease from other neurodegenerative parkinsonism: a systematic review and meta-analysis. Parkinsonism Relat Disord 2012; 18 (5) 494-500
    CrossrefPubMedGoogle Scholar
  • 8 Haensch CA, Lerch H, Jörg J, Isenmann S. Cardiac denervation occurs independent of orthostatic hypotension and impaired heart rate variability in Parkinson's disease. Parkinsonism Relat Disord 2009; 15 (2) 134-137
    CrossrefPubMedGoogle Scholar
  • 9 Katagiri A, Asahina M, Araki N , et al. Myocardial (123)I-MIBG uptake and cardiovascular autonomic function in Parkinson's disease. Parkinsons Dis 2015; 2015: 805351
    PubMedGoogle Scholar
  • 10 Velseboer DC, de Haan RJ, Wieling W, Goldstein DS, de Bie RM. Prevalence of orthostatic hypotension in Parkinson's disease: a systematic review and meta-analysis. Parkinsonism Relat Disord 2011; 17 (10) 724-729
    CrossrefPubMedGoogle Scholar
  • 11 Senard JM, Raï S, Lapeyre-Mestre M , et al. Prevalence of orthostatic hypotension in Parkinson's disease. J Neurol Neurosurg Psychiatry 1997; 63 (5) 584-589
    CrossrefPubMedGoogle Scholar
  • 12 Merola A, Romagnolo A, Rosso M , et al. Orthostatic hypotension in Parkinson's disease: does it matter if asymptomatic?. Parkinsonism Relat Disord 2016; 33: 65-71
    CrossrefPubMedGoogle Scholar
  • 13 Goldstein DS. Orthostatic hypotension as an early finding in Parkinson's disease. Clin Auton Res 2006; 16 (1) 46-54
    CrossrefPubMedGoogle Scholar
  • 14 Kim JS, Lee SH, Oh YS , et al. Cardiovascular autonomic dysfunction in mild and advanced Parkinson's disease. J Mov Disord 2016; 9 (2) 97-103
    PubMedGoogle Scholar
  • 15 Strano S, Fanciulli A, Rizzo M , et al. Cardiovascular dysfunction in untreated Parkinson's disease: A multi-modality assessment. J Neurol Sci 2016; 370: 251-255
    CrossrefPubMedGoogle Scholar
  • 16 Rascol O, Perez-Lloret S, Damier P , et al. Falls in ambulatory non-demented patients with Parkinson's disease. J Neural Transm (Vienna) 2015; 122 (10) 1447-1455
    CrossrefPubMedGoogle Scholar
  • 17 Gibbons CH, Schmidt P, Biaggioni I , et al. The recommendations of a consensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension. J Neurol 2017
    PubMedGoogle Scholar
  • 18 Espay AJ, LeWitt PA, Hauser RA, Merola A, Masellis M, Lang AE. Neurogenic orthostatic hypotension and supine hypertension in Parkinson's disease and related synucleinopathies: prioritisation of treatment targets. Lancet Neurol 2016; 15 (9) 954-966
    CrossrefPubMedGoogle Scholar
  • 19 Rowell LB, Detry JM, Blackmon JR, Wyss C. Importance of the splanchnic vascular bed in human blood pressure regulation. J Appl Physiol 1972; 32 (2) 213-220
    CrossrefPubMedGoogle Scholar
  • 20 Figueroa JJ, Singer W, Sandroni P , et al. Effects of patient-controlled abdominal compression on standing systolic blood pressure in adults with orthostatic hypotension. Arch Phys Med Rehabil 2015; 96 (3) 505-510
    CrossrefPubMedGoogle Scholar
  • 21 Low PA, Tomalia VA. Orthostatic hypotension: mechanisms, causes, management. J Clin Neurol 2015; 11 (3) 220-226
    CrossrefPubMedGoogle Scholar
  • 22 Hussain RM, McIntosh SJ, Lawson J, Kenny RA. Fludrocortisone in the treatment of hypotensive disorders in the elderly. Heart 1996; 76 (6) 507-509
    CrossrefPubMedGoogle Scholar
  • 23 McClellan KJ, Wiseman LR, Wilde MI. Midodrine. A review of its therapeutic use in the management of orthostatic hypotension. Drugs Aging 1998; 12 (1) 76-86
    PubMedGoogle Scholar
  • 24 Kaufmann H, Norcliffe-Kaufmann L, Hewitt LA, Rowse GJ, White WB. Effects of the novel norepinephrine prodrug, droxidopa, on ambulatory blood pressure in patients with neurogenic orthostatic hypotension. J Am Soc Hypertens 2016; 10 (10) 819-826
    CrossrefPubMedGoogle Scholar
  • 25 Sharabi Y, Goldstein DS. Mechanisms of orthostatic hypotension and supine hypertension in Parkinson disease. J Neurol Sci 2011; 310 (1-2): 123-128
    CrossrefPubMedGoogle Scholar
  • 26 Umehara T, Nakahara A, Matsuno H, Toyoda C, Oka H. Predictors of postprandial hypotension in elderly patients with de novo Parkinson's disease. J Neural Transm (Vienna) 2016; 123 (11) 1331-1339
    CrossrefPubMedGoogle Scholar
  • 27 Cicconetti P, Ciotti V, Monteforte G , et al. Circadian blood pressure pattern and cognitive function in newly diagnosed older hypertensives. Blood Press 2003; 12 (3) 168-174
    CrossrefPubMedGoogle Scholar
  • 28 Routledge F, McFetridge-Durdle J. Nondipping blood pressure patterns among individuals with essential hypertension: a review of the literature. Eur J Cardiovasc Nurs 2007; 6 (1) 9-26
    PubMedGoogle Scholar
  • 29 Sommer S, Aral-Becher B, Jost W. Nondipping in Parkinson's disease. Parkinsons Dis 2011; 2011: 897586
    PubMedGoogle Scholar
  • 30 Fanciulli A, Göbel G, Ndayisaba JP , et al. Supine hypertension in Parkinson's disease and multiple system atrophy. Clin Auton Res 2016; 26 (2) 97-105
    CrossrefPubMedGoogle Scholar
  • 31 Umehara T, Matsuno H, Toyoda C, Oka H. Clinical characteristics of supine hypertension in de novo Parkinson disease. Clin Auton Res 2016; 26 (1) 15-21
    CrossrefPubMedGoogle Scholar
  • 32 Li K, Reichmann H, Ziemssen T. Recognition and treatment of autonomic disturbances in Parkinson's disease. Expert Rev Neurother 2015; 15 (10) 1189-1203
    CrossrefPubMedGoogle Scholar
  • 33 Parkinson J. An Essay on the Shaking Palsy. Whittingham and Rowland. London, 2017
    PubMedGoogle Scholar
  • 34 Eadie MJ, Tyrer JH. Alimentary disorder in parkinsonism. Australas Ann Med 1965; 14: 13-22
    PubMedGoogle Scholar
  • 35 Korczyn AD. Autonomic nervous system disturbances in Parkinson's disease. Adv Neurol 1990; 53: 463-468
    PubMedGoogle Scholar
  • 36 Edwards LL, Pfeiffer RF, Quigley EM, Hofman R, Balluff M. Gastrointestinal symptoms in Parkinson's disease. Mov Disord 1991; 6 (2) 151-156
    CrossrefPubMedGoogle Scholar
  • 37 Jost WH, Schimrigk K. Constipation in Parkinson's disease. Klin Wochenschr 1991; 69: 906-909
    CrossrefPubMedGoogle Scholar
  • 38 Pfeiffer RF. Gastrointestinal dysfunction in Parkinson's disease. Lancet Neurol 2003; 2 (2) 107-116
    CrossrefPubMedGoogle Scholar
  • 39 Qualman SJ, Haupt HM, Yang P, Hamilton SR. Esophageal Lewy bodies associated with ganglion cell loss in achalasia. Similarity to Parkinson's disease. Gastroenterology 1984; 87 (4) 848-856
    PubMedGoogle Scholar
  • 40 Kupsky WJ, Grimes MM, Sweeting J, Bertsch R, Cote LJ. Parkinson's disease and megacolon: concentric hyaline inclusions (Lewy bodies) in enteric ganglion cells. Neurology 1987; 37 (7) 1253-1255
    CrossrefPubMedGoogle Scholar
  • 41 Wakabayashi K, Takahashi H, Ohama E, Ikuta F. Parkinson's disease: an immunohistochemical study of Lewy body-containing neurons in the enteric nervous system. Acta Neuropathol 1990; 79 (6) 581-583
    CrossrefPubMedGoogle Scholar
  • 42 Singaram C, Ashraf W, Gaumnitz EA , et al. Dopaminergic defect of enteric nervous system in Parkinson's disease patients with chronic constipation. Lancet 1995; 346 (8979): 861-864
    CrossrefPubMedGoogle Scholar
  • 43 Del Tredici K, Rüb U, De Vos RA, Bohl JR, Braak H. Where does Parkinson disease pathology begin in the brain?. J Neuropathol Exp Neurol 2002; 61 (5) 413-426
    CrossrefPubMedGoogle Scholar
  • 44 Braak H, de Vos RA, Bohl J, Del Tredici K. Gastric alpha-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology. Neurosci Lett 2006; 396 (1) 67-72
    CrossrefPubMedGoogle Scholar
  • 45 Keshavarzian A, Green SJ, Engen PA , et al. Colonic bacterial composition in Parkinson's disease. Mov Disord 2015; 30 (10) 1351-1360
    CrossrefPubMedGoogle Scholar
  • 46 Scheperjans F, Aho V, Pereira PA , et al. Gut microbiota are related to Parkinson's disease and clinical phenotype. Mov Disord 2015; 30 (3) 350-358
    CrossrefPubMedGoogle Scholar
  • 47 Unger MM, Spiegel J, Dillmann KU , et al. Short chain fatty acids and gut microbiota differ between patients with Parkinson's disease and age-matched controls. Parkinsonism Relat Disord 2016; 32: 66-72
    CrossrefPubMedGoogle Scholar
  • 48 Felice VD, Quigley EM, Sullivan AM, O'Keeffe GW, O'Mahony SM. Microbiota-gut-brain signalling in Parkinson's disease: implications for non-motor symptoms. Parkinsonism Relat Disord 2016; 27: 1-8
    CrossrefPubMedGoogle Scholar
  • 49 Sampson TR, Debelius JW, Thron T , et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease. Cell 2016; 167 (6) 1469-1480.e12
    CrossrefPubMedGoogle Scholar
  • 50 Abbott RA, Cox M, Markus H, Tomkins A. Diet, body size and micronutrient status in Parkinson's disease. Eur J Clin Nutr 1992; 46 (12) 879-884
    PubMedGoogle Scholar
  • 51 Wang G, Wan Y, Cheng Q , et al. Malnutrition and associated factors in Chinese patients with Parkinson's disease: Results from a pilot investigation. Parkinsonism Relat Disord 2010; 16 (2) 119-123
    CrossrefPubMedGoogle Scholar
  • 52 Markaki E, Ellul J, Kefalopoulou Z , et al. The role of ghrelin, neuropeptide Y and leptin peptides in weight gain after deep brain stimulation for Parkinson's disease. Stereotact Funct Neurosurg 2012; 90 (2) 104-112
    CrossrefPubMedGoogle Scholar
  • 53 Novakova L, Haluzik M, Jech R, Urgosik D, Ruzicka F, Ruzicka E. Hormonal regulators of food intake and weight gain in Parkinson's disease after subthalamic nucleus stimulation. Neuroendocrinol Lett 2011; 32 (4) 437-441
    PubMedGoogle Scholar
  • 54 Verbaan D, Marinus J, Visser M, van Rooden SM, Stiggelbout AM, van Hilten JJ. Patient-reported autonomic symptoms in Parkinson disease. Neurology 2007; 69 (4) 333-341
    CrossrefPubMedGoogle Scholar
  • 55 Müller B, Larsen JP, Wentzel-Larsen T, Skeie GO, Tysnes OB ; Parkwest Study Group. Autonomic and sensory symptoms and signs in incident, untreated Parkinson's disease: frequent but mild. Mov Disord 2011; 26 (1) 65-72
    CrossrefPubMedGoogle Scholar
  • 56 Karakoc M, Yon MI, Cakmakli GY , et al. Pathophysiology underlying drooling in Parkinson's disease: oropharyngeal bradykinesia. Neurol Sci 2016; 37 (12) 1987-1991
    CrossrefPubMedGoogle Scholar
  • 57 Hyson HC, Johnson AM, Jog MS. Sublingual atropine for sialorrhea secondary to parkinsonism: a pilot study. Mov Disord 2002; 17 (6) 1318-1320
    CrossrefPubMedGoogle Scholar
  • 58 Narayanaswami P, Geisbush T, Tarulli A , et al. Drooling in Parkinson's disease: a randomized controlled trial of incobotulinum toxin A and meta-analysis of botulinum toxins. Parkinsonism Relat Disord 2016; 30: 73-77
    CrossrefPubMedGoogle Scholar
  • 59 Ondo WG, Hunter C, Moore W. A double-blind placebo-controlled trial of botulinum toxin B for sialorrhea in Parkinson's disease. Neurology 2004; 62 (1) 37-40
    CrossrefPubMedGoogle Scholar
  • 60 Clifford TJ, Warsi MJ, Burnett CA, Lamey PJ. Burning mouth in Parkinson's disease sufferers. Gerodontology 1998; 15 (2) 73-78
    CrossrefPubMedGoogle Scholar
  • 61 Bonenfant D, Rompré PH, Rei N , et al. Characterization of burning mouth syndrome in patients with Parkinson's disease. J Oral Facial Pain Headache 2016; 30 (4) 318-322
    PubMedGoogle Scholar
  • 62 Pfeiffer RF. Gastrointestinal dysfunction in Parkinson's disease. In: Pfeiffer RF, Wszolek ZK, Ebadi M, , eds. Parkinson's Disease. 2nd ed. Boca Raton, FL: CRC Press; 2013: 309-326
    CrossrefGoogle Scholar
  • 63 Jones CA, Ciucci MR. Multimodal swallowing evaluation with high-resolution manometry reveals subtle swallowing changes in early and mid-stage Parkinson disease. J Parkinsons Dis 2016; 6 (1) 197-208
    PubMedGoogle Scholar
  • 64 Gross RD, Atwood Jr CW, Ross SB, Eichhorn KA, Olszewski JW, Doyle PJ. The coordination of breathing and swallowing in Parkinson's disease. Dysphagia 2008; 23 (2) 136-145
    CrossrefPubMedGoogle Scholar
  • 65 Byrne KG, Pfeiffer R, Quigley EM. Gastrointestinal dysfunction in Parkinson's disease. A report of clinical experience at a single center. J Clin Gastroenterol 1994; 19 (1) 11-16
    CrossrefPubMedGoogle Scholar
  • 66 Suttrup I, Warnecke T. Dysphagia in Parkinson's disease. Dysphagia 2016; 31 (1) 24-32
    CrossrefPubMedGoogle Scholar
  • 67 Menezes C, Melo A. Does levodopa improve swallowing dysfunction in Parkinson's disease patients?. J Clin Pharm Ther 2009; 34 (6) 673-676
    CrossrefPubMedGoogle Scholar
  • 68 Warnecke T, Suttrup I, Schröder JB , et al. Levodopa responsiveness of dysphagia in advanced Parkinson's disease and reliability testing of the FEES-levodopa-test. Parkinsonism Relat Disord 2016; 28: 100-106
    CrossrefPubMedGoogle Scholar
  • 69 Restivo DA, Palmeri A, Marchese-Ragona R. Botulinum toxin for cricopharyngeal dysfunction in Parkinson's disease. N Engl J Med 2002; 346 (15) 1174-1175
    CrossrefPubMedGoogle Scholar
  • 70 Born LJ, Harned RH, Rikkers LF, Pfeiffer RF, Quigley EM. Cricopharyngeal dysfunction in Parkinson's disease: role in dysphagia and response to myotomy. Mov Disord 1996; 11 (1) 53-58
    CrossrefPubMedGoogle Scholar
  • 71 Troche MS, Okun MS, Rosenbek JC , et al. Aspiration and swallowing in Parkinson disease and rehabilitation with EMST: a randomized trial. Neurology 2010; 75 (21) 1912-1919
    CrossrefPubMedGoogle Scholar
  • 72 Byeon H. Effect of simultaneous application of postural techniques and expiratory muscle strength training on the enhancement of the swallowing function of patients with dysphagia caused by Parkinson's disease. J Phys Ther Sci 2016; 28 (6) 1840-1843
    CrossrefPubMedGoogle Scholar
  • 73 Pasricha PJ, Parkman HP. Gastroparesis: definitions and diagnosis. Gastroenterol Clin North Am 2015; 44 (1) 1-7
    CrossrefPubMedGoogle Scholar
  • 74 Heetun ZS, Quigley EM. Gastroparesis and Parkinson's disease: a systematic review. Parkinsonism Relat Disord 2012; 18 (5) 433-440
    CrossrefPubMedGoogle Scholar
  • 75 Tanaka Y, Kato T, Nishida H , et al. Is there a delayed gastric emptying of patients with early-stage, untreated Parkinson's disease? An analysis using the 13C-acetate breath test. J Neurol 2011; 258 (3) 421-426
    CrossrefPubMedGoogle Scholar
  • 76 Soykan I, Sarosiek I, Shifflett J, Wooten GF, McCallum RW. Effect of chronic oral domperidone therapy on gastrointestinal symptoms and gastric emptying in patients with Parkinson's disease. Mov Disord 1997; 12 (6) 952-957
    CrossrefPubMedGoogle Scholar
  • 77 Leelakanok N, Holcombe A, Schweizer ML. Domperidone and risk of ventricular arrhythmia and cardiac death: a systematic review and meta-analysis. Clin Drug Investig 2016; 36 (2) 97-107
    CrossrefPubMedGoogle Scholar
  • 78 Buffery PJ, Strother RM. Domperidone safety: a mini-review of the science of QT prolongation and clinical implications of recent global regulatory recommendations. N Z Med J 2015; 128 (1416): 66-74
    PubMedGoogle Scholar
  • 79 Gil RA, Hwynn N, Fabian T, Joseph S, Fernandez HH. Botulinum toxin type A for the treatment of gastroparesis in Parkinson's disease patients. Parkinsonism Relat Disord 2011; 17 (4) 285-287
    CrossrefPubMedGoogle Scholar
  • 80 Lembo A, Camilleri M, McCallum R , et al; RM-131-004 Trial Group. Relamorelin reduces vomiting frequency and severity and accelerates gastric emptying in adults with diabetic gastroparesis. Gastroenterology 2016; 151 (1) 87-96.e6
    CrossrefPubMedGoogle Scholar
  • 81 Camilleri M. Novel diet, drugs, and gastric interventions for gastroparesis. Clin Gastroenterol Hepatol 2016; 14 (8) 1072-1080
    CrossrefPubMedGoogle Scholar
  • 82 Fasano A, Bove F, Gabrielli M , et al. The role of small intestinal bacterial overgrowth in Parkinson's disease. Mov Disord 2013; 28 (9) 1241-1249
    CrossrefPubMedGoogle Scholar
  • 83 Tan AH, Mahadeva S, Thalha AM , et al. Small intestinal bacterial overgrowth in Parkinson's disease. Parkinsonism Relat Disord 2014; 20 (5) 535-540
    CrossrefPubMedGoogle Scholar
  • 84 Niu XL, Liu L, Song ZX , et al. Prevalence of small intestinal bacterial overgrowth in Chinese patents with Parkinson's disease. J Neural Transm (Vienna) 2016; 123: 1381-1386
    CrossrefPubMedGoogle Scholar
  • 85 Quigley EM. Small intestinal bacterial overgrowth: what it is and what it is not. Curr Opin Gastroenterol 2014; 30 (2) 141-146
    CrossrefPubMedGoogle Scholar
  • 86 Pfeiffer RF. Gastrointestinal dysfunction in Parkinson's disease. Parkinsonism Relat Disord 2011; 17 (1) 10-15
    CrossrefPubMedGoogle Scholar
  • 87 Knudsen K, Krogh K, Østergaard K, Borghammer P. Constipation in Parkinson's disease: subjective symptoms, objective markers, and new perspectives. Mov Disord 2017; 32 (1) 94-105
    CrossrefPubMedGoogle Scholar
  • 88 Jost WH, Schimrigk K. Constipation in Parkinson's disease. Klin Wochenschr 1991; 69 (20) 906-909
    CrossrefPubMedGoogle Scholar
  • 89 Savica R, Carlin JM, Grossardt BR , et al. Medical records documentation of constipation preceding Parkinson disease: a case-control study. Neurology 2009; 73 (21) 1752-1758
    CrossrefPubMedGoogle Scholar
  • 90 Svensson E, Henderson VW, Borghammer P, Horváth-Puhó E, Sørensen HT. Constipation and risk of Parkinson's disease: a Danish population-based cohort study. Parkinsonism Relat Disord 2016; 28: 18-22
    CrossrefPubMedGoogle Scholar
  • 91 Lin CH, Lin JW, Liu YC, Chang CH, Wu RM. Risk of Parkinson's disease following severe constipation: a nationwide population-based cohort study. Parkinsonism Relat Disord 2014; 20 (12) 1371-1375
    CrossrefPubMedGoogle Scholar
  • 92 Toebosch S, Tudyka V, Masclee A, Koek G. Treatment of recurrent sigmoid volvulus in Parkinson's disease by percutaneous endoscopic colostomy. World J Gastroenterol 2012; 18 (40) 5812-5815
    CrossrefPubMedGoogle Scholar
  • 93 Blackley S, Maguire C, Daniels T. Seven cases of sigmoid volvulus in Parkinson's disease. J R Coll Physicians Edinb 2016; 46 (3) 157-159
    PubMedGoogle Scholar
  • 94 Ondo WG, Kenney C, Sullivan K , et al. Placebo-controlled trial of lubiprostone for constipation associated with Parkinson disease. Neurology 2012; 78 (21) 1650-1654
    CrossrefPubMedGoogle Scholar
  • 95 Sadjadpour K. Pyridostigmine bromide and constipation in Parkinson's disease. JAMA 1983; 249 (9) 1148
    PubMedGoogle Scholar
  • 96 Sakakibara R, Doi H, Sato M , et al. Nizatidine ameliorates slow transit constipation in Parkinson's disease. J Am Geriatr Soc 2015; 63 (2) 399-401
    CrossrefPubMedGoogle Scholar
  • 97 Pagano G, Tan EE, Haider JM, Bautista A, Tagliati M. Constipation is reduced by beta-blockers and increased by dopaminergic medications in Parkinson's disease. Parkinsonism Relat Disord 2015; 21 (2) 120-125
    CrossrefPubMedGoogle Scholar
  • 98 Chiu CM, Wang CP, Sung WH, Huang SF, Chiang SC, Tsai PY. Functional magnetic stimulation in constipation associated with Parkinson's disease. J Rehabil Med 2009; 41 (13) 1085-1089
    CrossrefPubMedGoogle Scholar
  • 99 McClurg D, Walker K, Aitchison P , et al. Abdominal massage for the relief of constipation in people with Parkinson's: a qualitative study. Parkinsons Dis 2016; 2016: 4842090
    PubMedGoogle Scholar
  • 100 Barichella M, Pacchetti C, Bolliri C , et al. Probiotics and prebiotic fiber for constipation associated with Parkinson disease: an RCT. Neurology 2016; 87 (12) 1274-1280
    CrossrefPubMedGoogle Scholar
  • 101 Bassotti G, Maggio D, Battaglia E , et al. Manometric investigation of anorectal function in early and late stage Parkinson's disease. J Neurol Neurosurg Psychiatry 2000; 68 (6) 768-770
    CrossrefPubMedGoogle Scholar
  • 102 Cersosimo MG, Raina GB, Pecci C , et al. Gastrointestinal manifestations in Parkinson's disease: prevalence and occurrence before motor symptoms. J Neurol 2013; 260 (5) 1332-1338
    CrossrefPubMedGoogle Scholar
  • 103 Tateno F, Sakakibara R, Yokoi Y , et al. Levodopa ameliorated anorectal constipation in de novo Parkinson's disease: the QL-GAT study. Parkinsonism Relat Disord 2011; 17 (9) 662-666
    CrossrefPubMedGoogle Scholar
  • 104 Edwards LL, Quigley EM, Harned RK, Hofman R, Pfeiffer RF. Defecatory function in Parkinson's disease: response to apomorphine. Ann Neurol 1993; 33 (5) 490-493
    CrossrefPubMedGoogle Scholar
  • 105 Albanese A, Brisinda G, Bentivoglio AR, Maria G. Treatment of outlet obstruction constipation in Parkinson's disease with botulinum neurotoxin A. Am J Gastroenterol 2003; 98 (6) 1439-1440
    CrossrefPubMedGoogle Scholar
  • 106 McDonald C, Winge K, Burn DJ. Lower urinary tract symptoms in Parkinson's disease: prevalence, aetiology and management. Parkinsonism Relat Disord 2017; 35: 8-16
    CrossrefPubMedGoogle Scholar
  • 107 Martinez-Martin P, Schapira AH, Stocchi F , et al. Prevalence of nonmotor symptoms in Parkinson's disease in an international setting; study using nonmotor symptoms questionnaire in 545 patients. Mov Disord 2007; 22 (11) 1623-1629
    CrossrefPubMedGoogle Scholar
  • 108 O'Sullivan SS, Williams DR, Gallagher DA, Massey LA, Silveira-Moriyama L, Lees AJ. Nonmotor symptoms as presenting complaints in Parkinson's disease: a clinicopathological study. Mov Disord 2008; 23 (1) 101-106
    CrossrefPubMedGoogle Scholar
  • 109 Winge K, Fowler CJ. Bladder dysfunction in Parkinsonism: mechanisms, prevalence, symptoms, and management. Mov Disord 2006; 21 (6) 737-745
    CrossrefPubMedGoogle Scholar
  • 110 Singer C, Moore H. Urological dysfunction. In: Pfeiffer RF, Wszolek ZK, Ebadi M, eds. Parkinson's Disease. 2nd ed. Boca Raton, FL: CRC Press; 2013: 327-341
    Google Scholar
  • 111 Ragab MM, Mohammed ES. Idiopathic Parkinson's disease patients at the urologic clinic. Neurourol Urodyn 2011; 30 (7) 1258-1261
    PubMedGoogle Scholar
  • 112 Kay GG, Ebinger U. Preserving cognitive function for patients with overactive bladder: evidence for a differential effect with darifenacin. Int J Clin Pract 2008; 62 (11) 1792-1800
    CrossrefPubMedGoogle Scholar
  • 113 Zesiewicz TA, Evatt M, Vaughan CP , et al; Non-Motor Working Group of the Parkinson Study Group (PSG). Randomized, controlled pilot trial of solifenacin succinate for overactive bladder in Parkinson's disease. Parkinsonism Relat Disord 2015; 21 (5) 514-520
    CrossrefPubMedGoogle Scholar
  • 114 Kulaksizoglu H, Parman Y. Use of botulinim toxin-A for the treatment of overactive bladder symptoms in patients with Parkinsons's disease. Parkinsonism Relat Disord 2010; 16 (8) 531-534
    CrossrefPubMedGoogle Scholar
  • 115 Giannantoni A, Conte A, Proietti S , et al. Botulinum toxin type A in patients with Parkinson's disease and refractory overactive bladder. J Urol 2011; 186 (3) 960-964
    CrossrefPubMedGoogle Scholar
  • 116 Mock S, Osborn DJ, Brown ET , et al. The impact of pallidal and subthalamic deep brain stimulation on urologic function in Parkinson's disease. Neuromodulation 2016; 19 (7) 717-723
    CrossrefPubMedGoogle Scholar
  • 117 Moore H, Singer C. Urological dysfunction. In: Pfeiffer RF, Bodis-Wollner I, , eds. Parkinson's Disease and Nonmotor Dysfunction. 2nd ed. New York, NY: Humana Press; 2013: 187-200
    CrossrefGoogle Scholar
  • 118 Pavlakis AJ, Siroky MB, Goldstein I, Krane RJ. Neurourologic findings in Parkinson's disease. J Urol 1983; 129 (1) 80-83
    CrossrefPubMedGoogle Scholar
  • 119 Galloway NT. Urethral sphincter abnormalities in Parkinsonism. Br J Urol 1983; 55 (6) 691-693
    CrossrefPubMedGoogle Scholar
  • 120 Stocchi F, Carbone A, Inghilleri M , et al. Urodynamic and neurophysiological evaluation in Parkinson's disease and multiple system atrophy. J Neurol Neurosurg Psychiatry 1997; 62 (5) 507-511
    CrossrefPubMedGoogle Scholar
  • 121 van Hees PJ, van der Plas AA, van Ek GF , et al. Discussing sexuality with patients with Parkinson's disease: a survey among Dutch neurologists. J Neural Transm (Vienna) 2017; 124 (3) 361-368
    CrossrefPubMedGoogle Scholar
  • 122 Bronner G. Sexual problems in Parkinson's disease: the multidimensional nature of the problem and of the intervention. J Neurol Sci 2011; 310 (1-2): 139-143
    CrossrefPubMedGoogle Scholar
  • 123 Jitkritsadakul O, Jagota P, Bhidayasiri R. Postural instability, the absence of sexual intercourse in the past month, and loss of libido are predictors of sexual dysfunction in Parkinson's disease. Parkinsonism Relat Disord 2015; 21 (1) 61-67
    CrossrefPubMedGoogle Scholar
  • 124 Koller WC, Vetere-Overfield B, Williamson A, Busenbark K, Nash J, Parrish D. Sexual dysfunction in Parkinson's disease. Clin Neuropharmacol 1990; 13 (5) 461-463
    CrossrefPubMedGoogle Scholar
  • 125 Sakakibara R, Kishi M, Ogawa E , et al. Bladder, bowel, and sexual dysfunction in Parkinson's disease. Parkinsons Dis 2011; 2011: 924605
    PubMedGoogle Scholar
  • 126 Deng X, Xiao B, Li HH , et al. Sexual dysfunction is associated with postural instability gait difficulty subtype of Parkinson's disease. J Neurol 2015; 262 (11) 2433-2439
    CrossrefPubMedGoogle Scholar
  • 127 Ferrucci R, Panzeri M, Ronconi L , et al. Abnormal sexuality in Parkinson's disease: fact or fancy?. J Neurol Sci 2016; 369: 5-10
    CrossrefPubMedGoogle Scholar
  • 128 Zesiewicz TA, Helal M, Hauser RA. Sildenafil citrate (Viagra) for the treatment of erectile dysfunction in men with Parkinson's disease. Mov Disord 2000; 15 (2) 305-308
    CrossrefPubMedGoogle Scholar
  • 129 Hussain IF, Brady CM, Swinn MJ, Mathias CJ, Fowler CJ. Treatment of erectile dysfunction with sildenafil citrate (Viagra) in parkinsonism due to Parkinson's disease or multiple system atrophy with observations on orthostatic hypotension. J Neurol Neurosurg Psychiatry 2001; 71 (3) 371-374
    CrossrefPubMedGoogle Scholar
  • 130 Okun MS, McDonald WM, DeLong MR. Refractory nonmotor symptoms in male patients with Parkinson disease due to testosterone deficiency: a common unrecognized comorbidity. Arch Neurol 2002; 59 (5) 807-811
    CrossrefPubMedGoogle Scholar
  • 131 Simonsen U, Comerma-Steffensen S, Andersson KE. Modulation of dopaminergic pathways to treat erectile dysfunction. Basic Clin Pharmacol Toxicol 2016; 119 (Suppl. 03) 63-74
    CrossrefPubMedGoogle Scholar
  • 132 Bronner G, Aharon-Peretz J, Hassin-Baer S. Sexuality in patients with Parkinson's disease, Alzheimer's disease, and other dementias. Handb Clin Neurol 2015; 130: 297-323
    PubMedGoogle Scholar
  • 133 Langston JW, Forno LS. The hypothalamus in Parkinson disease. Ann Neurol 1978; 3 (2) 129-133
    CrossrefPubMedGoogle Scholar
  • 134 Beach TG, Adler CH, Sue LI , et al; Arizona Parkinson's Disease Consortium. Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders. Acta Neuropathol 2010; 119 (6) 689-702
    CrossrefPubMedGoogle Scholar
  • 135 Kataoka H, Ueno S. Severe cold lower limbs in patients with Parkinson's disease during the summer. Neurol Int 2016; 8 (4) 6676
    PubMedGoogle Scholar
  • 136 Shindo K, Kobayashi F, Miwa M, Nagasaka T, Takiyama Y, Shiozawa Z. Temporal prolongation of decreased skin blood flow causes cold limbs in Parkinson's disease. J Neural Transm (Vienna) 2013; 120 (3) 445-451
    CrossrefPubMedGoogle Scholar
  • 137 Snider SR, Fahn S, Isgreen WP, Cote LJ. Primary sensory symptoms in parkinsonism. Neurology 1976; 26 (5) 423-429
    CrossrefPubMedGoogle Scholar
  • 138 Turkka JT, Myllylä VV. Sweating dysfunction in Parkinson's disease. Eur Neurol 1987; 26 (1) 1-7
    PubMedGoogle Scholar
  • 139 De Marinis M, Stocchi F, Testa SR, De Pandis F, Agnoli A. Alterations of thermoregulation in Parkinson's disease. Funct Neurol 1991; 6 (3) 279-283
    PubMedGoogle Scholar
  • 140 Lipp A, Sandroni P, Ahlskog JE , et al. Prospective differentiation of multiple system atrophy from Parkinson disease, with and without autonomic failure. Arch Neurol 2009; 66 (6) 742-750
    CrossrefPubMedGoogle Scholar
  • 141 Pursiainen V, Haapaniemi TH, Korpelainen JT, Sotaniemi KA, Myllylä VV. Sweating in Parkinsonian patients with wearing-off. Mov Disord 2007; 22 (6) 828-832
    CrossrefPubMedGoogle Scholar
  • 142 Sage JI, Mark MH. Drenching sweats as an off phenomenon in Parkinson's disease: treatment and relation to plasma levodopa profile. Ann Neurol 1995; 37 (1) 120-122
    CrossrefPubMedGoogle Scholar
  • 143 van Hilten BJ, Roos RA. The continuum of hyperthermic syndromes with impaired dopaminergic activity. Arch Intern Med 1992; 152 (8) 1727-1730 , 1730
    CrossrefPubMedGoogle Scholar
  • 144 Reutens DC, Harrison WB, Goldswain PR. Neuroleptic malignant syndrome complicating levodopa withdrawal. Med J Aust 1991; 155 (1) 53-54
    PubMedGoogle Scholar
  • 145 Bonnici A, Ruiner CE, St-Laurent L, Hornstein D. An interaction between levodopa and enteral nutrition resulting in neuroleptic malignant-like syndrome and prolonged ICU stay. Ann Pharmacother 2010; 44 (9) 1504-1507
    CrossrefPubMedGoogle Scholar
  • 146 Whitman CB, Ablordeppey E, Taylor B. Levodopa withdrawal presenting as fever in a critically ill patient receiving concomitant enteral nutrition. J Pharm Pract 2016; 29 (6) 574-578
    CrossrefPubMedGoogle Scholar
  • 147 Pfeiffer RF, Sucha EL. “On-off”-induced lethal hyperthermia. Mov Disord 1989; 4 (4) 338-341
    CrossrefPubMedGoogle Scholar
  • 148 Trachani E, Constantoyannis C, Sirrou V, Kefalopoulou Z, Markaki E, Chroni E. Effects of subthalamic nucleus deep brain stimulation on sweating function in Parkinson's disease. Clin Neurol Neurosurg 2010; 112 (3) 213-217
    CrossrefPubMedGoogle Scholar
  • 149 Sanghera MK, Ward C, Stewart RM, Mewes K, Simpson RK, Lai EC. Alleviation of drenching sweats following subthalamic deep brain stimulation in a patient with Parkinson's disease--a case report. J Neurol Sci 2009; 285 (1-2): 246-249
    CrossrefPubMedGoogle Scholar