Role of manganese in the pathophysiology of hepatic encephalopathy: scoping review protocol


  • Iván Pérez-Neri Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez
  • Hugo Sandoval National Institute of Rehabilitation Luis Guillermo Ibarra Ibarra
  • Antonio Malvaso
  • Neluwa-Liyanage R. Indika
  • Christoper A. Alarcon-Ruiz
  • Manoochehr Ebrahimian
  • Camilo Ríos



Manganese, Ammonia, Oxidative stress, Neurotransmitter, Neuronal death


Introduction: Hepatic encephalopathy (HE) is a neuropsychiatric complication of liver disease and/or portosystemic blood shunting, characterized by alterations of alertness, personality, cognition, and motor functions. Its severity is defined from mild symptoms to coma according to four grades. This disease may affect several brain regions including the cingulate gyrus, the insular cortex, and the globus pallidus. The pathophysiology of HE is thought to be multifactorial and involves manganese accumulation in the brain, damaging effect of ammonia on glial cells, etc. Previous studies describe the pathophysiology of HE or the effect of manganese in the central nervous system but there is no review addressing both topics from an integrative perspective and using a systematic methodology. This scoping review aims to evaluate the role of manganese in HE. Methods: Published studies (all publication types) will be retrieved from Web of Science, MEDLINE, Scopus, EBSCOhost, Ovid, and Google Scholar. Inclusion criteria are: studies reporting manganese levels in any biological sample or tissue of patients with HE, any experimental model reporting the effect of manganese administration on measures of neuroprotection in models of liver damage, or showing an effect on manganese levels in the liver and/or the brain. Exclusion criteria are: studies reporting subjects exposed occupationally or environmentally to manganese, or written in languages different than Spanish or English that could not be appropriately translated, or whose full-text files could not be retrieved. Either clinical or preclinical studies will be analyzed separately but might be discussed together. Data summaries will be presented in graphs, figures, and tables. A narrative synthesis will be presented. This protocol complies with PRISMA-P.


1. Butterworth RF. Hepatic encephalopathy in alcoholic cirrhosis. Handbook of clinical neurology. 2014;125:589-602. doi: 10.1016/B978-0-444-62619-6.00034-3
2. Feltracco P, Cagnin A, Carollo C, Barbieri S, Ori C. Neurological disorders in liver transplant candidates: Pathophysiology and clinical assessment. Transplantation Reviews. 2017;31(3):193-206. doi: 10.1016/j.trre.2017.02.006
3. Gow AG. Hepatic Encephalopathy. Veterinary Clinics of North America: Small Animal Practice. 2017;47(3):585-599. doi: 10.1016/j.cvsm.2016.11.008
4. Sureka B, Bansal K, Patidar Y, Rajesh S, Mukund A, Arora A. Neurologic Manifestations of Chronic Liver Disease and Liver Cirrhosis. Curr Probl Diagn Radiol. 2015;44(5):449-461. doi: 10.1067/j.cpradiol.2015.03.004
5. Elwir S, Rahimi RS. Hepatic Encephalopathy: An Update on the Pathophysiology and Therapeutic Options. Journal of Clinical and Translational Hepatology. 2017;XX:1-10. doi: 10.14218/JCTH.2016.00069
6. Pérez-Neri I, Ríos-Castañeda C. Glutamine-mediated nitric oxide synthase inhibition might explain the ‘arginine paradox’. Archivos de Neurociencias. 2021;26(2):7-9. doi: 10.31157/archneurosciencesmex.v26i2.277
7. Hardy G. Manganese in Parenteral Nutrition: Who, When, and Why Should We Supplement. Gastroenterology. 2009;137(5):S29-S35. doi: 10.1053/j.gastro.2009.08.011
8. Rivera-Mancía S, Ríos C, Montes S. Manganese accumulation in the CNS and associated pathologies. BioMetals. 2011;24(5):811-825. doi: 10.1007/s10534-011-9454-1
9. Pérez-Neri I, Diéguez-Campaa CE, Sandoval H, Chávez VA, Castro-Martínez E, Ríos C. Therapeutic potential of dehydroepiandrosterone for Parkinson’s disease: scoping review protocol. Arch Neurocien. 2022; in press
10. Rosca EC, Tudor R, Cornea A, Simu M. Parkinson’s Disease in Romania: A Scoping Review Protocol. Brain Sci. 2021;11(2):251. doi: 10.3390/brainsci11020251
11. Polhemus AM, Bergquist R, Bosch de Basea M, Brittain G, Buttery SC, Chynkiamis N et al. Walking-related digital mobility outcomes as clinical trial endpoint measures: protocol for a scoping review. BMJ Open. 2020;10(7):e038704. doi: 10.1136/bmjopen-2020-038704
12. Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021;372:n160. doi: 10.1136/bmj.n160
13. Beller EM, Glasziou PP, Altman DG, Hopewell S, Bastian H, Chalmers I et al. PRISMA for Abstracts: reporting systematic reviews in journal and conference abstracts. PLoS Med. 2013;10(4):e1001419. doi: 10.1371/journal.pmed.1001419
14. Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015;350:g7647. doi: 10.1136/bmj.g7647
15. Tricco AC, Lillie E, Zarin W, O’Brien KK, Colquhoun H, Levac D et al. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann Intern Med. 2018;169(7):467-473. doi: 10.7326/M18-0850
16. Aromataris E, Munn Z, editors. JBI Manual for Evidence Synthesis. JBI; 2020
17. Tanila T, Tenhunen H, Hirvonen P. Value Mechanisms in the Implementation of Intelligent Patient Flow Management System - A Multiple Case Study. Stud Health Technol Inform. 2020;270:708-712. doi: 10.3233/SHTI200252
18. Strech D, Synofzik M, Marckmann G. Systematic reviews of empirical bioethics. J Med Ethics. 2008;34(6):472-477. doi: 10.1136/jme.2007.021709
19. Rethlefsen ML, Kirtley S, Waffenschmidt S, Ayala AP, Moher D, Page MJ et al. PRISMA-S: an extension to the PRISMA Statement for Reporting Literature Searches in Systematic Reviews. Syst Rev. 2021;10(1):39. doi: 10.5195/jmla.2021.962
20. McGowan J, Sampson M, Salzwedel DM, Cogo E, Foerster V, Lefebvre C. PRESS Peer Review of Electronic Search Strategies: 2015 Guideline Statement. J Clin Epidemiol. 2016;75:40-46. doi: 10.1016/j.jclinepi.2016.01.021
21. Bramer, W. M., & de Jonge, G. B. Improving efficiency and confidence in systematic literature searching. EAHIL+ ICAHIS+ ICLC. 2015
22. Willcox MDP, Walsh K, Nichols JJ, Morgan PB, Jones LW. The ocular surface, coronaviruses and COVID ‐19. Clin Exp Optom. 2020;103(4):418-424. doi: 10.1111/cxo.13088
23. Pérez-Neri I, González-Aguilar A, Sandoval H, Pineda C, Ríos C. Therapeutic Potential of Ultrasound Neuromodulation in Decreasing Neuropathic Pain: Clinical and Experimental Evidence. Curr Neuropharmacol. 2021;19(3):334-348. doi: 10.2174/1570159X18666200720175253
24. McKeown S, Mir ZM. Considerations for conducting systematic reviews: evaluating the performance of different methods for de-duplicating references. Syst Rev. 2021;10(1):38. doi: 10.1186/s13643-021-01583-y
25. Bozada T, Borden J, Workman J, Del Cid M, Malinowski J, Luechtefeld T. Sysrev: A FAIR Platform for Data Curation and Systematic Evidence Review. Front Artif Intell. 2021;4:685298. doi: 10.3389/frai.2021.685298. eCollection 2021
26. Garritty C, Gartlehner G, Nussbaumer-Streit B, King VJ, Hamel C, Kamel C et al. Cochrane Rapid Reviews Methods Group offers evidence-informed guidance to conduct rapid reviews. J Clin Epidemiol. 2021;130:13-22. doi: 10.1016/j.jclinepi.2020.10.007
27. Haddaway NR, McGuinness LA. PRISMA 2020: R package and ShinyApp for producing PRISMA 2020 compliant flow diagrams (Version 0.0.2). medRxiv. 2021
28. Usher R, Stapleton T. Approaches for assessing decision-making capacity in older adults: a scoping review protocol. JBI Evidence Synthesis. 2020;18(4):832-840. doi: 10.11124/JBISRIR-D-19-00068



How to Cite

Pérez-Neri, I., Sandoval, H., Malvaso, A. ., Indika, N.-L. R. ., Alarcon-Ruiz, C. A. ., Ebrahimian, M. ., & Ríos, C. (2022). Role of manganese in the pathophysiology of hepatic encephalopathy: scoping review protocol. Archivos De Neurociencias, 1(Inpress).



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