Clin Mol Hepatol > Volume 29(4); 2023 > Article
Ryu, Baek, and Kim: Correspondence on Letter regarding “Evidence-based hyponatremia management in liver disease”
Dear Editor,
We appreciate Theodorou and coauthors [1] for introducing clinical manifestation of osmotic demyelination syndrome (ODS) including reversible and irreversible sequelae and emphasizing that magnetic resonance (MR) imaging is needed for early detection and proper diagnosis of ODS in hyponatremic patients with liver disease. Furthermore, MR imaging might have prognostic value due to the regenerative potential of neuroglial cells in patients with liver disease and resolving ODS [1,2]. Generally, ODS is diagnosed clinically and by MR image [3,4].
Our review focused on pathophysiology, diagnosis, and treatment of hyponatremia in patients with liver diseases [5]. We were unable to discuss ODS itself thoroughly. ODS is symmetric, non-inflammatory demyelination of neurons, which can be classified into two types based on location: central pontine myelinolysis and extrapontine myelinolysis [6-8]. It occurs as a result of apoptosis of oligodendrocytes and infiltration of myelin degrading macrophages [8,9]. Hyponatremia and overly rapid correction of hyponatremia have been well-known as potent causative factors of ODS [4,10-12]. The only recommendation of ODS till date is conservative treatment. The best approach is focused on prevention strategies with two aspects: identifying patients at risk and implementing proper correction, especially with a strict maximum of 8 mmol/L per day for individuals at risk of ODS [10-12]. However, it should be noted that ODS can occur even in the absence of hyponatremia or overcorrection of hyponatremia in patients with high risk of ODS. Patients with chronic alcohol consumption (the most common) or liver cirrhosis/liver transplantation (third largest group) are more susceptible to ODS because of reduced ability of astrocytes to synthesize new intracellular osmolytes in response to osmotic changes [4,7,10-15]. In a recent study involving 547,544 adult inpatients with cirrhosis, ODS was found to be developed in only 0.02% of patients. It was associated with alcohol-related cirrhosis, young age, and female gender. ODS was not associated with liver disease severity (decompensated cirrhosis) or specific complications including ascites or hepatic encephalopathy [13]. Patients undergoing liver transplant are also at risk for rapid correction of serum sodium due to intraoperative administration of intravenous crystalloids, blood products, and sodium bicarbonate during operation, in addition to preexisting conditions [4]. The incidence of ODS is 0.8% to 1,4% [3,4]. Symptom onset is known to be within 1 to 2 weeks after liver transplantation [3]. Additionally, although relatively less prevalent, ODS can occur in patients with burns, malnutrition, chemotherapy, diabetes mellitus, adrenal insufficiency, acquired immune deficiency syndrome, severe illness/sepsis, hypoglycemia/hypokalemia/hypophosphatemia, and renal disease with or without liver disease [4].
In summary, individuals with advanced liver disease are more susceptible to ODS. For patients with liver diseases accompanied by aforementioned predisposing disease or circumstances or those undergoing liver transplantation, greater attention should be paid to ODS.


Authors’ contribution
JYR: drafting of the manuscript. SHB, SK: critical review and final approval of the manuscript.
Conflicts of Interest
The authors have no conflicts to disclose.


osmotic demyelination syndrome
magnetic resonance


1. Theodorou DJ, Theodorou SJ, Mitselos IV. Letter regarding “Evidence-based hyponatremia management in liver disease”. Clin Mol Hepatol 2023 Jul 5. doi: 10.3350/cmh.2023.0204.
crossref pmid
2. Neely SA, Williamson JM, Klingseisen A, Zoupi L, Early JJ, Williams A, et al. New oligodendrocytes exhibit more abundant and accurate myelin regeneration than those that survive demyelination. Nat Neurosci 2022;25:415-420.
crossref pmid pmc pdf
3. Rondon-Berrios H, Velez JCQ. Hyponatremia in cirrhosis. Clin Liver Dis 2022;26:149-164.
crossref pmid pmc
4. Verbeek TA, Saner FH, Bezinover D. Hyponatremia and liver transplantation: A narrative review. J Cardiothorac Vasc Anesth 2022;36:1458-1466.
crossref pmid
5. Ryu JY, Baek SH, Kim S. Evidence-based hyponatremia management in liver disease. Clin Mol Hepatol 2023 Jun 5. doi: 10.3350/cmh.2023.0090.
crossref pmid
6. Huq S, Wong M, Chan H, Crimmins D. Osmotic demyelination syndromes: central and extrapontine myelinolysis. J Clin Neurosci 2007;14:684-688.
crossref pmid
7. Dahal A, Bhattarai AM, Bhattarai AM, Pathak BD, Karki A, Aryal E. Central pontine myelinolysis in a chronic alcoholic patient with mild hyponatremia: A case report. Ann Med Surg (Lond) 2022;78:103736.
crossref pmid pmc
8. DeLuca GC, Nagy Z, Esiri MM, Davey P. Evidence for a role for apoptosis in central pontine myelinolysis. Acta Neuropathol 2002;103:590-598.
crossref pmid pdf
9. Nicaise C, Marneffe C, Bouchat J, Gilloteaux J. Osmotic demyelination: From an oligodendrocyte to an astrocyte perspective. Int J Mol Sci 2019;20:1124.
crossref pmid pmc
10. Spasovski G, Vanholder R, Allolio B, Annane D, Ball S, Bichet D, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol 2014;170:G1-47.
crossref pmid
11. Verbalis JG, Goldsmith SR, Greenberg A, Korzelius C, Schrier RW, Sterns RH, et al. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med 2013;126(10 Suppl 1):S1-42.
crossref pmid
12. Lee Y, Yoo KD, Baek SH, Kim YG, Kim HJ, Ryu JY, et al. Korean Society of Nephrology 2022 Recommendations on controversial issues in diagnosis and management of hyponatremia. Kidney Res Clin Pract 2022;41:393-411.
crossref pmid pmc pdf
13. Berry K, Rubin JB, Lai JC. Osmotic demyelination syndrome in hospitalized patients with cirrhosis: Analysis of the national inpatient sample (NIS). J Clin Gastroenterol 2022;56:280-283.
pmid pmc
14. Lee EM, Kang JK, Yun SC, Kim KH, Kim SJ, Hwang KS, et al. Risk factors for central pontine and extrapontine myelinolysis following orthotopic liver transplantation. Eur Neurol 2009;62:362-368.
crossref pmid pdf
15. Bronster DJ, Emre S, Boccagni P, Sheiner PA, Schwartz ME, Miller CM. Central nervous system complications in liver transplant recipients--incidence, timing, and long-term follow-up. Clin Transplant 2000;14:1-7.
crossref pmid pdf

Editorial Office
The Korean Association for the Study of the Liver
Room A1210, 53 Mapo-daero(MapoTrapalace, Dowha-dong), Mapo-gu, Seoul, 04158, Korea
TEL: +82-2-703-0051   FAX: +82-2-703-0071    E-mail:
Copyright © The Korean Association for the Study of the Liver.         
TODAY : 292
TOTAL : 1854805
Close layer