Posterior reversible encephalopathy syndrome in an oncological normotensive patient: evidence for a pathogenic role of concomitant low magnesium serum levels and chemotherapy treatment

Main Article Content

Federica Zappia
Ignazio Verzicco
Riccardo Simoni
Massimiliano Ferrari
Pietro Coghi
Francesca Bozzetti
Valentina Cannone
Riccardo Volpi
Aderville Cabassi

Keywords

Key words: posterior reversible encephalopathy syndrome, hypomagnesemia, breast cancer, chemotherapy, cerebral thrombosis.

Abstract

Background: Posterior reversible encephalopathy (PRES) is a rare syndrome characterized by headache, confusion, seizures, visual changes and white matter edema at radiological imaging. Its pathophysiology is not clarified and different causes, including uncontrolled hypertension, eclampsia, chemotherapy and hypomagnesemia have been suggested. Case report: A woman affected by stage IV breast cancer with lower extremity deep vein thrombosis treated with low-molecular-weight-heparin, currently in therapy with Palbociclib/Fulvestrant (antiCDK4 and 6/estrogen receptor antagonist) but previously treated with several other chemotherapy lines (including VEGF inhibitor bevacizumab), was admitted to our Internal Medicine department because of ascites and abdominal pain. She was treated with diuretics (and paracentesis). Recently (six-month earlier) a pan-encephalic radiotherapy was done because of brain and skull metastasis. Among blood tests, low serum levels of hypomagnesemia were observed. She developed PRES that rapidly progressed to lethargy, unresponsiveness till coma without changes in blood pressure. Magnetic Resonance Imaging study showed bilateral parieto-occipital edema and a thrombosis of left transverse and sigmoid sinuses. Anti-edema therapy, intravenous supplementation of magnesium and decoagulation were started, with complete and rapid recovery (within 18 hours) of clinical and radiologic changes. Conclusions: PRES diagnosis was based on the rapid clinical recovery after antiedema treatment and magnesium supplementation. Low magnesium level related to both diuretic and Fulvestrant/Palbociclib therapies and recent radiotherapy can represent potential mechanisms favouring PRES development. The previous bevacizumab treatment may also be involved as a PRES predisposing factor. The concomitant occurrence of cerebral thrombosis can have precipitated the clinical situation.

a

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...
Abstract 394 | PDF Downloads 176

References

1. Hinchey J, Chaves C, Appignani B, et al. A Reversible Posterior Leukoencephalopathy syndrome. N Engl J Med. 1996:494-500.
2. Stott V., Hurrell M., Anderson TJ. Reversible posterior leukoencephalopathy syndrome: a misnomer reviewed. Intern Med J. 2005;35(2):83-90.
3. Siebert E, Bohner G, Liebig T, Endres M, Liman TG. Factors associated with fatal outcome in posterior reversible encephalopathy syndrome: a retrospective analysis of the Berlin PRES study. J Neurol. 2017;264(2):237-242.
4. Ay H, Buonanno F, Schaefer P, et al. Posterior leukoencephalopathy without severe hypertension: utility of diffusion-weighted MRI. Neurology. 1998;51(5):1369-1376.
5. Mar GR. Encefalopatía reversible posterior en una niña con lupus eritematoso sistémico. Presentación de un caso. Arch Argent Pediatr. 2015;113(5):271-274.
6. Gatla N, Annapureddy N, Sequeira W, Jolly M. Posterior reversible encephalopathy syndrome in systemic lupus erythematosus. J Clin Rheumatol. 2013;19(6):334-340.
7. Camara-Lemarroy C, Escobedo-Zúñiga N, Villarreal-Garza E, García-Valadez E, Góngora-Rivera F, Villarreal-Velázquez HJ. Posterior reversible leukoencephalopathy syndrome (PRES) associated with severe eclampsia: Clinical and biochemical features. Pregnancy Hypertens. 2017;7:44-49.
8. Toledano M, Fugate JE. Posterior reversible encephalopathy in the intensive care unit. Handb Clin Neurol. 2017;141:467-483.
9. Thompson R, Sharp B, Pothof J, Hamedani A. Posterior Reversible Encephalopathy Syndrome in the Emergency Department: Case Series and Literature Review. West J Emerg Med. 2015;16(1):5-10.
10. Maur M, Tomasello C, Frassoldati A, Dieci M., Barbieri E, Conte P. Posterior reversible encephalopathy syndrome during ipilimumab therapy for malignant melanoma. J Clin Oncol. 2012;30(6):76-78.
11. Malkan UY, Gunes G, Demiroglu H, Goker H. Immunosuppression-associated posterior reversible encephalopathy syndrome in an acute leukemia case. Hematol Rep. 2018;10(4):96-97.
12. Yafour N, Krim A, Bouhass R, Bekadja MA. Cyclosporine-related brainstem atypical posterior reversible leukoencephalopathy syndrome following hematopoietic stem cell transplant. Hematol Oncol Stem Cell Ther. 2016;9(1):36-38.
13. Nakamura Y, Sugino M, Tsukahara A, Nakazawa H, Yamamoto N, Arawaka S. Posterior reversible encephalopathy syndrome with extensive cytotoxic edema after blood transfusion: a case report and literature review. BMC Neurol. 2018;18(1):190.
14. Chardain A, Mesnage V, Alamowitch S, et al. Posterior reversible encephalopathy syndrome (PRES) and hypomagnesemia: A frequent association? Rev Neurol (Paris). 2016;172:384-388.
15. Schweitzer A, Parikh N, Askin G, et al. Imaging Characteristics Associated with Clinical Outcomes in Posterior Reversible Encephalopathy Syndrome. Neuroradiology. 2017;59(4):379-386.
16. Bartynski WS. Posterior reversible encephalopathy syndrome, Part 2: Controversies surrounding pathophysiology of vasogenic edema. Am J Neuroradiol. 2008;29(6):1043-1049.
17. Fugate J, Rabinstein AA. Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions. Lancet Neurol. 2015;14(9):914-925.
18. Largeau B, Le Tilly O, Sautenet B, Salmon Gandonnière C, Barin-Le Guellec C, Ehrmann S. Arginine Vasopressin and Posterior Reversible Encephalopathy Syndrome Pathophysiology: the Missing Link? Mol Neurobiol. 2019.
19. Seet R., Rabinstein AA. Clinical features and outcomes of posterior reversible encephalopathy syndrome following bevacizumab treatment. Qjm. 2012;105(1):69-75.
20. Katada E, Mitsui A, Sasaki S, Uematsu N, Anan C. Posterior Reversible Encephalopathy Syndrome after a Variety of Combined Chemotherapies Containing Bevacizumab for Metastatic Colon Cancer. Intern Med. 2018;57(16):2403-2407.
21. Eryllmaz MK, Mutlu H, Salim DK, Musri FY, Coşkun HŞ. Fatal posterior revesible leukoencephalopathy syndrome associated coma induced by bevacizumab in metastatic colorectal cancer and review of literature. J Oncol Pharm Pract. 2016;22(6):806-810.
22. El Maalouf G, Mitry E, Lacout A, Lièvre A, Rougier P. Isolated brainstem involvement in posterior reversible leukoencephalopathy induced by bevacizumab. J Neurol. 2008;255(2):295-296.
23. Hamid M, Ghani A, Micaily I, Sarwar U, Lashari B, Malik F. Posterior reversible encephalopathy syndrome (PRES) after bevacizumab therapy for metastatic colorectal cancer. J Community Hosp Intern Med Perspect. 2018;8(3):130-133.
24. Munoz J, Kumar V, Hamilton J. Posterior Reversible Encephalopathy Syndrome: More Than Meets the Eye. J Clin Oncol. 2013;31(20):360-363.
25. Ozcan C, Wong S., Hari P. Reversible posterior leukoencephalopathy syndrome and bevacizumab. N Engl J Med. 2006;354(9):980-982.
26. Wu S, Kim C, Baer L, Zhu X. Bevacizumab increases risk for severe proteinuria in cancer patients. J Am Soc Nephrol. 2010;21(8):1381-1389.
27. Lafayette RA, McCall B, Li N, et al. Incidence and Relevance of Proteinuria in Bevacizumab-Treated Patients: Pooled Analysis from Randomized Controlled Trials. Am J Nephrol. 2014;40:75-83.
28. Lazarus M, Amundson S, Belani R. An Association between Bevacizumab and Recurrent Posterior Reversible Encephalopathy Syndrome in a Patient Presenting with Deep Vein Thrombosis: A Case Report and Review of the Literature. Case Rep Oncol Med. 2012;2012:1-4.
29. Lio CF, Lee YH, Chan HY, Yu CC, Peng NJ, Chan HP. Posterior reversible encephalopathy syndrome in a postpartum hemorrhagic woman without hypertension. Med (United States). 2017;96(16).
30. Dabla S, Juneja H, Garg A, Bansal R, Kumar S. Cerebral Venous Sinus Thrombosis and Posterior Reversible Encephalopathy Syndrome Coexisting in a Woman: A Rare Coincidence. J assoc Physicians India. 2017;65(4):90-92.
31. Saran S, Bansal P, Singhal S, Malik A. Coexisting cerebral venous sinus thrombosis and posterior reversible encephalopathy syndrome in a preeclamptic female. Ann Afr Med. 2018;17(2):94-95.
32. Almoussa M, Goertzen A, Brauckmann S, Fauser B, Zimmermann CW. Posterior Reversible Encephalopathy Syndrome due to Hypomagnesemia: A Case Report and Literature Review. Case Rep Med. 2018;2018:1-6.
33. Santos AF, Sousa F, Rodrigues M, Ferreira C, Soares-Fernandes J, Maré R. Reversible cerebellar syndrome induced by hypomagnesemia. Neurol Clin Neurosci. 2015;3(5):190-191.
34. Blasco LM. Cerebellar Syndrome in Chronic Cyclic Magnesium Depletion. The Cerebellum. 2013;12(4):587-588.
35. Laurant P, Touyz RM. Physiological and pathophysiological role of magnesium in the cardiovascular system: implications in hypertension. J Hypertens. 2000;18(9):1177-1191.
36. Grubbs RD, Maguire ME. Magnesium as a regulatory cation: criteria and evaluation. Magnesium 1987;6(3):113-27. 1987;6(3):113-127.
37. Ebel H, Günther T. Magnesium metabolism: a review. J Clin Chem Clin Biochem. 1980;18(5):257-270.
38. Bara M, Guiet-Bara A. Potassium, magnesium and membranes. Review of present status and new findings. Magnesium 1984;3(4-6):215-25. 1984;3(4-6):215-225.
39. Altura B, Gebrewold A, Zhang A, Altura B. Low extracellular magnesium ions induce lipid peroxidation and activation of nuclear factor-kappa B in canine cerebral vascular smooth muscle: possible relation to traumatic brain injury and strokes. Neurosci Lett. 2003;341(3):189-192.
40. Billard JM. Ageing, hippocampal synaptic activity and magnesium. Magnes Res. 2006;19(3):199-215.
41. Rayssiguier Y, Libako P, Nowacki W, Rock E. Magnesium deficiency and metabolic syndrome: stress and inflammation may reflect calcium activation. Magnes Res. 2010;23(2):73-80.
42. Amiry-Moghaddam M, Otsuka T, Hurn P, et al. An alfa-syntrophin-dependent pool of AQP4 in astroglial end-feet confers bidirectional water flow between blood and brain. Proc Natl Acad Sci. 2003;100(4):2106-2111.
43. Zador Z, Stiver S, Wang V, Manley GT. Role of aquaporin-4 in cerebral edema and stroke. Handb Exp Pharmacol. 2009;190: 159-170.
44. Ghabriel M, Thomas A, Vink R. Magnesium restores altered aquaporin-4 immunoreactivity following traumatic brain injury to a pre-injury state. Acta Neurochir Suppl. 2006; 96:402-406.
45. Okiyama K, Smith D., Gennarelli T., Simon R., Leach M, McIntosh TK. The sodium channel blocker and glutamate release inhibitor BW1003C87 and magnesium attenuate regional cerebral edema following experimental brain injury in the rat. J Neurochem. 1995;2: 802-809.
46. Palbociclib (PD-0332991), Investigator’s Brochure February 2015.
47. Regolisti G, Cabassi A, Parenti E, Maggiore U, Fiaccadori E. Severe Hypomagnesemia During Long-term Treatment With a Proton Pump Inhibitor. Am J Kidney Dis. 2010;56(1):168-174.
48. Roongpiboonsopit D, Kuijf HJ, Charidimou A, et al. Evolution of cerebral microbleeds after cranial irradiation in medulloblastoma patients. Neurology. 2017;88(8):789-796.

Most read articles by the same author(s)