Top

Current Neurology and Neuroscience Reports

Published in:

01-08-2012 | Critical Care (SA Mayer, Section Editor)

Critical Care of the Potential Organ Donor

Authors: Anna J. Dare, Adam S. Bartlett, John F. Fraser

Published in: Current Neurology and Neuroscience Reports | Issue 4/2012

Abstract

Organ transplantation represents one of the great success stories of 20th century medicine. However, its continued success is greatly limited by the shortage of donor organs. This has led to an increased focus within the critical care community on optimal identification and management of the potential organ donor. The multi-organ donor can represent one of the most complex intensive care patients, with numerous competing physiological priorities. However, appropriate management of the donor not only increases the number of organs that can be successfully donated but has long-term implications for the outcomes of multiple recipients. This review outlines current understandings of the physiological derangements seen in the organ donor and evaluates the available evidence for management strategies designed to optimize donation potential and organ recovery. Finally, emerging management strategies for the potential donor are discussed within the current ethical and legal frameworks permitting donation after both brain and circulatory death.

Langone A, Helderman J. Disparity between solid-organ supply and demand. NEJM. 2003;349:704–7.PubMedCrossRef

The Organ Procurement and Transplantation Network; Data. In: Editor (ed)^(eds) Book The Organ Procurement and Transplantation Network; Data. OPTN, City, pp.

Beecher H. A definition of irreversible coma. Report of the Ad Hoc Committee of the Harvard Medical School to examine the definition of brain death. JAMA. 1968;205:337–40.CrossRef

Novitzsky D. Detrimental effects of brain death on the potential organ donor. Transplant Proc. 1997;29:3770–2.CrossRef

Vienenkoetter D, Esmaeilzadeh M, Unterberg A, Ahmadi R. Critical care management of potential organ donors: our current standard. Clin Transplant. 2009;23:2–9.PubMed

Non heart-beating organ transplantation: Practice and Protocols. In: Editor (ed)^(eds) Book Non heart-beating organ transplantation: Practice and Protocols. Institute of Medicine, City, pp. 174

Bernat J, D’Alessandro A, Port F, Bleck T, Heard S, Medina J, et al. Report of a national conference on donation after cardiac death. Am J Transplant. 2006;6:281–91.PubMedCrossRef

Reich D, Mulligan P, Pruett T, Abecassis M, D’Alessandro A, Pomfret E, et al. ASTS recommended practice guidelines for controlled donation after cardiac death organ procurement and transplantation. Am J Transplant. 2009;9:2004–11.PubMedCrossRef

Sanchez-Fructosis A, Prats D, Torrente J, Perez-Contin M, Fernandez C, Alvarez J, et al. Renal transplantation from non-heart beating donors: a promising alternative to enlarge the donor pool. J Am Soc Nephrol. 2000;11:350–8.

10.

Kootstra G, Daemen J, Oomen A. Categories of non-heart-beating donors. Transplant Proc. 1995;27:2893–4.PubMed

11.

Wilhelm M, Pratschke J, Laskowski I, Paz D, Tilney N. Brain death and its impact on the donor heart - lessons from animal models. J Heart Lung Transplant. 2000;19:414–8.PubMedCrossRef

12.

Shivalker B, van Loon J, Wieland W, Tjandra-Maga T, Borgers M, Plets C, et al. Variable effects of explosive or gradual increase of intracranial pressure on myocardial structure and function. Circulation. 1993;87:230–9.CrossRef

13.

Novitzsky D, Horak A, Cooper D, Rose A. Electrocardiographic and histopathologic changes developing during experimental brain death in the baboon. Transplant Proc. 1989;21:2567–9.

14.

Novitzsky D, Wicomb W, Cooper D. Electrocardiographic, haemodynamic and endocrine changes occurring during experimental brain death in the Chacma baboon. J Heart Transplant. 1984;4:63.

15.

Power B, van Heerden P. The physiological changes associated with brain death - current concepts and implications for treatment of the brain dead donor. Anaesth Intensive Care. 1995;23:26–36.PubMed

16.

Wood K, Becker B, McCartney J, D’Alessandro A, Coursin D. Care of the potential organ donor. NEJM. 2004;351:2730–9.PubMedCrossRef

17.

Wheeldon D, Potter C, Oduro A, Wallwork J, Large S. Transforming the “unacceptable” donor: outcomes from adoption of a standardized donor management technique. J Heart Lung Transplant. 1995;14:734–42.PubMed

18.

Kutsogiannis D, Pagliarello G, Doig C, Ross H, Shemie S. Medical management to optimize donor organ potential: review of the literature. Can J Anesth. 2006;53:820–30.PubMedCrossRef

19.

Schnuelle P, Berger S, de Boer J, Persijn G, van der Woude F. Effects of catelcholamine application to brain-dead donors on graft survival in solid organ transplantation. Transplantation. 2001;72:455–63.PubMedCrossRef

20.

Debaveye Y, van de Berghe G. Is there still a place for dopamine in the modern intensive care unit? Anaesth Analg. 2004;98:461–8.CrossRef

21.

Finfer S, Bohn D, Colpitts D, Cox P, Fleming F, Barker G. Intensive care management of paediatric donor organs and its effect on post-transplant organ function. Intensive Care Med. 1996;22:1424–32.PubMedCrossRef

22.

Koning O, Ploeg R, van Bockel J, Groenewegen M, van der Woude F, Persijn G, et al. Risk factors for delayed graft function in cadaveric kidney transplantation: a prospective study of renal function and graft survival after preservation with University of Wisconsin solution in multi-organ donors. Transplantation. 1997;63:1620–8.PubMedCrossRef

23.

•• Franklin G, Santos A, Smith J, Galbraith S, Harbrecht B, Garrison R, (2010) Optimization of Donor Management Goals yields increased organ use. The American Surgeon 76. The first data from a UNOS series prospectively evaluating the use of DMGs as end points for resuscitation in the organ donor. Provides interesting insight into which standard goals may be necessary for optimal organ use, namely PaO ₂ , inotrope use, and glucose control, and which appear to have no effect. The full multiregional results evaluating the development and use of DMGs are awaited.

24.

Katz K, Lawler J, Wax J, O’Connor R, Nadkarni V. Vasopressin pressor effects in critically ill children during evaluation for brain death and organ recovery. Resuscitation. 2000;47:33–40.PubMedCrossRef

25.

Pennefether S, Bullock R, Mantle D, Dark J. Use of low dose arginine vasopressin to support brain-dead organ donors. Transplantation. 1995;59:58–62.CrossRef

26.

Hunt S, Baldwin J, Baumgartner W, Bricker J, Costanzo M, Miller L, et al. Cardiovascular management of a potential heart donor: a statement from the Transplantation Committee of the American College of Cardiology. Crit Care Med. 1996;24:1599–601.PubMedCrossRef

27.

Iwai A, Sakano T, Uenishi M, Sugimoto H, Yoshioko T, Sugimoto T. Effect of vasopressin and catecholamines on the maintenance of stability in brain dead patients. Transplantation. 1989;48:613–7.PubMed

28.

Van Raemdonck D, Neyrinck A, Verleden G, Dupont L, Coosemans W, Decauwe H. Lung donor selection and management. Proc Am Thorac Soc. 2009;6:28–38.PubMedCrossRef

29.

Hornby K, Ross H, Keshavjee S, Rao V, Shemie S. Non-utilisation of hearts and lungs after consent for donation: a Canadian multi-centre study. Can J Anaesth. 2006;53:831–7.PubMedCrossRef

30.

Angel L, Levine D, Restrepo M, Johnson S, Sako E, Carpenter A, et al. Impact of a lung transplantation donor-management protocol on lung donation and recipient outcomes. Am J Respir Crit Care Med. 2006;174:710–6.PubMedCrossRef

31.

• Mascia L, Pasero D, Slutsky A, Arguis M, Grasso S, Munari M, Boifava S, Cornara G, Della Corte F, Vivaldi N, Malacarne P, Del Gaudio P, Livigni S, Zavala E, Filippini C, Martin E, Donadio P, Mastromauro I, Ranieri V, (2010) Effect of a lung protective strategy for organ donors on eligibility and availability of lungs for transplantation. JAMA 304: 2620–2627. Lungs remain one of the most difficult organs to maintain donation potential in after brainstem death. This multicenter RCT demonstrates that institution of a lung-protective ventilatory strategy in potential organ donors significantly increased the number of eligible and transplanted lungs compared to conventional ventilatory strategies. PubMedCrossRef

32.

Bittner H, Kendall S, Chen E, Craig D, Van Trigt P. The effects of brain death on cardiopulmonary hemodynamics and pulmonary bloodflow characteristics. Chest. 1995;108:1358–63.PubMedCrossRef

33.

Novitzsky D, Wicomb W, Rose A, Cooper D, Reichart B. Pathophysiology of pulmonary oedema following experimental brain death in the Chacma baboon. Ann Thorac Surg. 1987;43:288–94.CrossRef

34.

van der Zee H, Malik A, Lee B, Hakim T. Lung fluid and protein exchange during intracranial hypertension and role of sympathetic mechanisms. Ann Thorac Surg. 1987;48:273–80.

35.

Fisher A, Donnelly S, Hirani N, Burdick M, Strieter R, Dark J, et al. Enhanced pulmonary inflammation in organ donors following fatal non-traumatic brain injury. Lancet. 1999;353:1412–3.PubMedCrossRef

36.

Fisher A, Donelly S, Hirani N, Haslett C, Strieter R, Dark J, et al. Elevated levels of interleukin-8 in donor lungs is associated with early graft failure after lung transplantation. Am J Respir Crit Care Med. 2001;163:259–65.PubMed

37.

Neyrinck A, Van de Wauwer C, Geudens N, Rega F, Verleden G, Wouters P, et al. Comparative study of donor lung injury in heart-beating versus non-heart beating donors. Eur J Cardiothorac Surg. 2006;30:628–36.PubMedCrossRef

38.

Kang C, Anraku M, Cypel M, Sato M, Yeung J, Gharib S, et al. Transcriptional signatures in donor lungs from donation after cardiac death vs after brain death: a functional pathway analysis. J Heart Lung Transplant. 2011;30:289–98.PubMedCrossRef

39.

Avlonitis V, Fisher A, Kirby J, Dark J. Pulmonary transplantation: the role of brain death in donor lung injury. Transplantation. 2003;75:1928–33.PubMedCrossRef

40.

Gabbay E, Williams T, Griffiths A, Macfarlane L, Kotsimbos T, Esmore D, et al. Maximising the utilization of donor organs offered for lung transplantation. Am J Resp Crit Care Med. 1999;160:265–71.PubMed

41.

Mascia L, Bosma K, Pasero D, Galli T, Cortese G, Donadio P, et al. Ventilatory and hemodynamic management of potential organ donors: an observational study. Crit Care Med. 2006;34:321–7.PubMedCrossRef

42.

Botha P, Rostron A, Fisher A, Dark J. Current strategies in donor selection and management. Semin Thorac Cardiovasc Surg. 2008;20:143–51.PubMedCrossRef

43.

Noiseux N, Nguyen B, Marsolais P, Dupont J, Simard L, Houde I, et al. Pulmonary recruitment protocol for organ donors: a new strategy to improve rate of lung utilisation. Transplant Proc. 2009;41:3284–9.PubMedCrossRef

44.

Ware L, Fang X, Wang Y, Sakuma T, Hall T, Matthay M. Selected contribution: mechanisms that may stimulate the resolution of alveolar edema in the transplanted human lung. J Appl Physiol. 2002;93:1869–74.PubMed

45.

Neyrinck A, Rega F, Fransen L, De Winter H, Jannis N, Wouters P, et al. b-adrenergic stimulation of alveolar liquid clearance: a novel strategy to resolve pulmonary edema after lung transplantation? (Abstract). Eur J Anaesthesiol. 2004;21:A664.CrossRef

46.

• Ware L, Koyama T, Billheimer D, Landeck M, Johnson E, Brady S, Bernard G, Matthay M, (2011) Advancing donor management research: design and implentation of a large, randomized, placebo-controlled trial. Annals of Intensive Care 1. Evaluates the logistical challenges of conducting RCTs in the setting of organ donor management, based on the group’s personal experiences with instigating one of the few placebo-controlled RCTs in this field. Given the need to improve the quality of evidence pertaining to the management of the potential organ donor this is an important paper both for investigators planning future clinical trials in the brain-dead donor population and for intensivists who are involved in the care of the brain-dead organ donors and in the design and conduct of research in this field.

47.

Folkesson H, Norlin A, Wang Y, Abedinpour P, Matthay M. Dexamethasone and thyroid hormone pre-treatment upregulate alveloar epithelial fluid clearance in adult rats. J Appl Physiol. 2000;88:416–24.PubMedCrossRef

48.

Mukadam M, Harrington D, Wilson I, Mascaro J, Rooney S, Thompson R, et al. Does donor catelcholamine administration effect early lung function after transplantation? J Thorac Cardiovasc Surg. 2005;130:926–7.PubMedCrossRef

49.

Cooper D, Novitzsky D, Wicomb W. The pathophysiological effects of brain death on potential donor organs, with particular reference to the heart. Ann R Coll Surg Engl. 1989;71:261–6.PubMed

50.

Wicomb W, Cooper D, Lanza R, Novitzsky D, Isaacs S. Storage by hypothermic perfusion on donor heart function in the pig. J Thorac Cardiovasc Surg. 1986;91:896–909.PubMed

51.

Dictus C, Vienenkoetter B, Esmaeilzadeh M, Unterberg A, Ahmadi R. Critical care management of potential organ donors: our current standard. Clin Transplant. 2009;23:2–9.PubMedCrossRef

52.

Novitzsky D, Cooper D, Rosendale J, Kauffman H. Hormonal therapy of the brain-dead organ donor: experimental and clinical studies. Transplantation. 2006;82:1396–401.CrossRef

53.

Rosendale J, Kauffman H, McBride M, Chabalewski F, Zaroff J, Garrity E, et al. Hormonal resuscitation yields more transplanted hearts with improved early function. Transplantation. 2003;75:1336–8.PubMedCrossRef

54.

Holmes C, Patel B, Russell J, Walley K. Physiology of vasopressin relevant to management of septic shock. Chest. 2001;120:989–1002.PubMedCrossRef

55.

Figueras J, Busquets J, Grande L, Jaurrieta E, Perez-Ferreiroa J, Mir J, et al. The deleterious effect of donor high plasma sodium and extended preservation in liver transplantation. A multivariate analysis. Transplantation. 1996;61:410–3.PubMedCrossRef

56.

Avolio A, Agnes S, Magalini S, Foco M, Castagneto M. Importance of donor blood chemistry data (AST, serum sodium) in predicting liver transplant outcome. Transplant Proc. 1991;23:2451–2.PubMed

57.

Gonzalez F, Rimmola A, Grande L, Antolin M, Garcia-Valdecasas J, Fuster J, et al. Predictive factors of early postoperative graft function in human liver transplantation. Hepatology. 1994;20:565–73.PubMed

58.

Totsuka E, Dodson F, Urakami A, Moras N, Ishii T, Lee M, et al. Influence of high donor serum sodium levels on early postoperative graft function in human liver transplantation: effect of correction of donor hypernatremia. Liver Transpl Surg. 1999;5:421–8.PubMedCrossRef

59.

Mangus R, Fridell J, Vianna R, Milgrom M, Chestovich P, Vandenboom C, et al. Severe hypernatremia in deceased liver donors does not impact early transplant outcome. Transplantation. 2010;90:438–43.PubMedCrossRef

60.

Tector A, Mangus R, Chestovich P, Vianna R, Fridell J, Milgrom M, et al. Use of extended criteria livers decrease wait time for liver transplantation without adversely impacting posttransplant survival. Ann Surg. 2006;244:439–50.PubMed

61.

Tekin K, Imber C, Atli M, Gunson B, Bramhall S, Mayer D, et al. A simple scoring system to evaluate the effects of cold ischemia on marginal liver donors. Transplantation. 2004;77:411–6.PubMedCrossRef

62.

Renz J, Kin C, Kinkhabwala M, Jan D, Varadarajan R, Goldstein M, et al. Utilization of extended donor criteria liver allografts maximises donor use and patient access to liver transplantation. Ann Surg. 2005;242:556–63.PubMed

63.

Rosendale J, Kauffman H, McBride M, Chabalewski F, Zaroff J, Garrity E, et al. Aggressive pharmacological donor management results in more transplanted organs. Transplantation. 2003;75:482–7.PubMedCrossRef

64.

Masson F, Thicoipe M, Gin H, De Mascarela A, Angibeau R, Favarel-Garrigues J, et al. The endocrine pancreas in brain-dead donors. Transplantation. 1993;56:363–7.PubMedCrossRef

65.

Gores P, Gillingham K, Dunn D, Moudry-Munns K, Najarian J, Sutherland D. Donor hyperglycaemia as a minor risk factor and immunologic variables as major risk factors for pancreas allograft loss in a multivariate analysis of a single institution’s experience. Ann Surg. 1992;215:217–30.PubMedCrossRef

66.

Smith M. Physiologic changes during brainstem death: lessons for management of the organ donor. J Heart Lung Transplant. 2004;23:S217–22.PubMedCrossRef

67.

Cipolla J, Stawicki S, Spatz D. Haemodynamic monitoring of organ donors: a novel use of the oesophageal echo-Doppler probe. Am Surg. 2006;72:500–4.PubMed

68.

Uchino S, Bellomo R, Morimatsu H, Sugihara M, French C, Stephens D, et al. Pulmonary artery catheter versus pulse contour analysis: a prospective epidemiological study. Crit Care. 2006;10:R174.PubMedCrossRef

69.

Jenkins D, Reilly P, Schwab C. Improving the approach to organ donation: a review. World J Surg. 1999;23:644–9.PubMedCrossRef

70.

Lopez-Navidad A, Caballero F. For a rational approach to the critical points of the cadaveric donation process. Transplant Proc. 2001;33:795–805.PubMedCrossRef

71.

Grossman M, Reilly P, McMahon D, (1996) Loss of potential organ donors due to medical failure. Crit Care Med 24

72.

Hagan M, McClean D, Falcone C, Arrington J, Matthews D, Summe C. Attaining specific donor management goals increases number of organs transplanted per donor: a quality improvement project. Prog Transplant. 2009;19:227–31.PubMed

73.

Santisea G, D’Anconaa G, Fallettab C, Pironea F, Sciaccaa S, Turrisia M, et al. Donor pharmacological hemodynamic support is associated with primary graft failure in human heart transplantation. Interact Cardiovasc Thorac Surg. 2009;9:476–9.CrossRef

74.

Reilly P, Morgan L, Grossman M, Shapiro M, Anderson H, Hawthorne R, Schwab C, Lung procurement from solid organ donors: role of fluid resuscitation in procurement failures. The Internet Journal of Emergency and Intensive Care Medicine. 1999;3

75.

Kunzendorf U, Hohenstein B, Oberbarnscheid M, Muller E, Renders L, Schott G, et al. Duration of donor brain death and its influence on kidney graft function. Am J Transplant. 2002;2:292–4.PubMedCrossRef

76.

Lopez-Navidad A, Domingo P, Caballero F. Organ shortage: viability of potential organ donors and possible loss depend on health care workers who are responsible for the organ procurement program. Transplant Proc. 1997;29:3614–6.PubMedCrossRef

77.

•• Kootstra G (2009) History of non-heart beating donation. In: Talbot D, D’Alessandro A (eds) Organ donation and transplantation after cardiac death. Oxford University Press, Oxford. Written by a team of international experts, this book provides a detailed and comprehensive overview of both the basic science and the clinical evidence currently available that has underpinned the development of DCD protocols in the UK and Europe. It also provides an outline of the moral, legal, and ethical considerations in the development of DCD programs. It is probably the most considered and authorative overview of DCD to date.

78.

Shemie S, De Vita M. Legal, moral and ethical issues. In: Talbot D, D’Alessandro A, editors. Organ donation and transplantation after cardiac death. Oxford: Oxford University Press; 2009.

79.

Ethics Committee, American College of Critical Care Medicine; Society of Critical Care Medicine. Recommendations for nonheart-beating organ donation. A position paper by the Ethics Committee, American College of Critical Care Medicine, Society of Critical Care Medicine. Crit Care Med. 2001;29:1826–31.CrossRef

80.

United Network of Organ Sharing. Donation after cardiac death; A reference guide. UNOS, Richmond, VA

81.

Rubenstein S, (2008) Caifornia surgeon cleared of hastening organ donor’s death. The Wall Street J

82.

Lewis J, Peltier J, Nelson H, Snyder W, Schneider K, Steinberger D, et al. Development of th University of Wisconsin donation after cardiac death evaluation tool. Prog Transplant. 2003;13:265–73.PubMed

83.

Lee K, Simpkins C, Montgomery R, Locke J, Segev D, Maley W. Factors affecting graft survival after liver transplantation from donation after cardiac death donors. Transplantation. 2006;82:1683–8.PubMedCrossRef

84.

Fernandez L, Di Carlo A, Odorico J, Leverson G, Shames B, Becker Y, et al. Simultaneous pancreas-kidney transplantation from donation after cardiac death: successful long term outcomes. Ann Surg. 2005;242:732–8.CrossRef

85.

DeVita M, Brooks M, Zawistowski C, Rudich S, Daly B, Chaitin E. Donors after Cardiac Death: Validation of identification Criteria (DVIC) study for predictors of rapid death. Am J Transp. 2008;8:432–41.CrossRef

86.

Herdman R, Beauchamp T, Potts J. The Institute of Medicine’s report on non-heart beating organ transplantation. Kennedy Inst Ethics. 1998;8:83–90.CrossRef

87.

Casavilla A, Ramirez CS R, Nghiem D, Miracle J, Fung J, Starzl T. Experience with liver and kidney allografts from non heart beating donors. Transplant Proc. 1995;27:2898.PubMed

88.

Veatch R. Transplantation Ethics. Washington: Georgetown University Press; 2000.

89.

Koffman G, Gambaro G. Renal transplantation from non-heart beating donors: a review of the European experience. J Nephrol. 2003;16:334–41.PubMed

90.

Shemie S, Baker A, Knoll G, Wall W, Rocker G, Howes D. Donation after cardiocirculatory death in Canada. CMAJ. 2006;175:S1–S24.PubMedCrossRef

91.

Organ donation: opportunities for action. In: Editor (ed)^(eds) Book Organ donation: opportunities for action. Institution of Medicine, City, pp. 358

92.

Punch J (2009) Extracorporeal circulatory-assisted non heart beating organ donation. In: Talbot D, D'Alessandro A (eds) Organ donation and transplantation after cardiac death. Oxford University Press

93.

Magliocca J, Magee J, Rowe S, Gravel M, Chenault R, Merion R, et al. Extracorporeal support for organ donation after cardiac death effectively expands the donor pool. J Trauma. 2005;58:1095–102.PubMedCrossRef

94.

Ko W, Chen Y, Tsai P, Lee P. Extracorporeal membrane oxygenation support of donor abdominal organs in non-heart beating donors. Clin Transplant. 2000;14:152–6.PubMedCrossRef

95.

Gravel M, Arenas J, Chenault R, Magee J, Rudich S, Maraschio M, et al. Kidney transplantation from organ donors following cardiopulmonary death using extracorporeal membrane oxygenation support. Am J Transplant. 2004;9:57–8.

96.

Fondevila C, Hessheimer A, Ruiz A, Calatayud D, Ferrer J, Charco R, et al. Liver transplant using donors after unexpected cardiac death: Novel preservation protocol and acceptance criteria. Am J Transplant. 2007;7:1849–55.PubMedCrossRef

97.

• Bernat J, Capron A, Bleck T, Blosser S, Bratton S, Childress J, DeVita M, Fulda G, Gries C, Mathur M, Nakagawa T, Rushton C, Shemie S, White D, (2010) The circulatory-respiratory determination of death in organ donation. Crit Care Med 38: 963–970. This paper represents the report of an interdisciplinary panel convened by the Health Resources and Services Administration, Division of Transplantation in the US, on the role and means of death determination using circulatory-repsiratory tests, with particular reference to the use of postmortem ECMO to support donor organs and the transplantation of hearts. This report outlines many of the key ethical and technical issues and controversies associated with advancing management of the DCD donor. PubMedCrossRef

Title: Critical Care of the Potential Organ Donor
Authors: Anna J. Dare
Adam S. Bartlett
John F. Fraser
Publication date: 01-08-2012
Publisher: Current Science Inc.
Published in: Current Neurology and Neuroscience Reports / Issue 4/2012
Print ISSN: 1528-4042
Electronic ISSN: 1534-6293
DOI: https://doi.org/10.1007/s11910-012-0272-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Critical Care of the Potential Organ Donor

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2012

Neuroinflammation and Non-motor Symptoms: The Dark Passenger of Parkinson’s Disease?

Urate in Parkinson’s Disease: More Than a Biomarker?

Recent Developments in Our Understanding of the Semiology and Treatment of Psychogenic Nonepileptic Seizures

Sodium and Fluid Management in Acute Brain Injury

Botulinum Toxin for the Treatment of Movement Disorders

Mammalian Target of Rapamycin (mTOR) Inhibition: Potential for Antiseizure, Antiepileptogenic, and Epileptostatic Therapy