Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Reversible posterior leukoencephalopathy syndrome

Terry A Neill, MD
Section Editor
Michael J Aminoff, MD, DSc
Deputy Editor
Janet L Wilterdink, MD


Reversible posterior leukoencephalopathy syndrome (RPLS) is a clinical radiographic syndrome of heterogeneous etiologies that are grouped together because of similar findings on neuroimaging studies. It is also often referred to as:

Posterior reversible encephalopathy syndrome (PRES)

Reversible posterior cerebral edema syndrome

Posterior leukoencephalopathy syndrome

Hyperperfusion encephalopathy

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Oct 2017. | This topic last updated: Apr 29, 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Hinchey J, Chaves C, Appignani B, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996; 334:494.
  2. Covarrubias DJ, Luetmer PH, Campeau NG. Posterior reversible encephalopathy syndrome: prognostic utility of quantitative diffusion-weighted MR images. AJNR Am J Neuroradiol 2002; 23:1038.
  3. Kwon S, Koo J, Lee S. Clinical spectrum of reversible posterior leukoencephalopathy syndrome. Pediatr Neurol 2001; 24:361.
  4. Antunes NL, Small TN, George D, et al. Posterior leukoencephalopathy syndrome may not be reversible. Pediatr Neurol 1999; 20:241.
  5. Alehan F, Erol I, Agildere AM, et al. Posterior leukoencephalopathy syndrome in children and adolescents. J Child Neurol 2007; 22:406.
  6. Chen TH, Lin WC, Tseng YH, et al. Posterior Reversible Encephalopathy Syndrome in Children: Case Series and Systematic Review. J Child Neurol 2013; 28:1378.
  7. Raj S, Overby P, Erdfarb A, Ushay HM. Posterior reversible encephalopathy syndrome: incidence and associated factors in a pediatric critical care population. Pediatr Neurol 2013; 49:335.
  8. Ay H, Buonanno FS, Schaefer PW, et al. Posterior leukoencephalopathy without severe hypertension: utility of diffusion-weighted MRI. Neurology 1998; 51:1369.
  9. Provenzale JM, Petrella JR, Cruz LC Jr, et al. Quantitative assessment of diffusion abnormalities in posterior reversible encephalopathy syndrome. AJNR Am J Neuroradiol 2001; 22:1455.
  10. Stott VL, Hurrell MA, Anderson TJ. Reversible posterior leukoencephalopathy syndrome: a misnomer reviewed. Intern Med J 2005; 35:83.
  11. Strandgaard S, Paulson OB. Cerebral autoregulation. Stroke 1984; 15:413.
  12. Paulson OB, Strandgaard S, Edvinsson L. Cerebral autoregulation. Cerebrovasc Brain Metab Rev 1990; 2:161.
  13. Jones BV, Egelhoff JC, Patterson RJ. Hypertensive encephalopathy in children. AJNR Am J Neuroradiol 1997; 18:101.
  14. Koch S, Rabinstein A, Falcone S, Forteza A. Diffusion-weighted imaging shows cytotoxic and vasogenic edema in eclampsia. AJNR Am J Neuroradiol 2001; 22:1068.
  15. Mukherjee P, McKinstry RC. Reversible posterior leukoencephalopathy syndrome: evaluation with diffusion-tensor MR imaging. Radiology 2001; 219:756.
  16. Lewis LK, Hinshaw DB Jr, Will AD, et al. CT and angiographic correlation of severe neurological disease in toxemia of pregnancy. Neuroradiology 1988; 30:59.
  17. Naidu K, Moodley J, Corr P, Hoffmann M. Single photon emission and cerebral computerised tomographic scan and transcranial Doppler sonographic findings in eclampsia. Br J Obstet Gynaecol 1997; 104:1165.
  18. Tajima Y, Isonishi K, Kashiwaba T, Tashiro K. Two similar cases of encephalopathy, possibly a reversible posterior leukoencephalopathy syndrome: serial findings of magnetic resonance imaging, SPECT and angiography. Intern Med 1999; 38:54.
  19. Lanzino G, Cloft H, Hemstreet MK, et al. Reversible posterior leukoencephalopathy following organ transplantation. Description of two cases. Clin Neurol Neurosurg 1997; 99:222.
  20. Schwartz RB, Jones KM, Kalina P, et al. Hypertensive encephalopathy: findings on CT, MR imaging, and SPECT imaging in 14 cases. AJR Am J Roentgenol 1992; 159:379.
  21. Ito Y, Arahata Y, Goto Y, et al. Cisplatin neurotoxicity presenting as reversible posterior leukoencephalopathy syndrome. AJNR Am J Neuroradiol 1998; 19:415.
  22. Schwartz RB, Feske SK, Polak JF, et al. Preeclampsia-eclampsia: clinical and neuroradiographic correlates and insights into the pathogenesis of hypertensive encephalopathy. Radiology 2000; 217:371.
  23. Savvidou MD, Hingorani AD, Tsikas D, et al. Endothelial dysfunction and raised plasma concentrations of asymmetric dimethylarginine in pregnant women who subsequently develop pre-eclampsia. Lancet 2003; 361:1511.
  24. Easton JD. Severe preeclampsia/eclampsia: hypertensive encephalopathy of pregnancy? Cerebrovasc Dis 1998; 8:53.
  25. Lindenbaum J. An approach to the anemias. In: Cecil's Textbook of Medicine, Bennett JC, Plum F (Eds), Philadelphia 1996. p.823.
  26. Rodgers GM, Taylor RN, Roberts JM. Preeclampsia is associated with a serum factor cytotoxic to human endothelial cells. Am J Obstet Gynecol 1988; 159:908.
  27. Blann AD, Taberner DA. A reliable marker of endothelial cell dysfunction: does it exist? Br J Haematol 1995; 90:244.
  28. Roberts JM, Redman CW. Pre-eclampsia: more than pregnancy-induced hypertension. Lancet 1993; 341:1447.
  29. Burrus TM, Mandrekar J, Wijdicks EF, Rabinstein AA. Renal failure and posterior reversible encephalopathy syndrome in patients with thrombotic thrombocytopenic purpura. Arch Neurol 2010; 67:831.
  30. Hawley JS, Ney JP, Swanberg MM. Thrombotic thrombocytopenic purpura-induced posterior leukoencephalopathy in a patient without significant renal or hypertensive complications. J Postgrad Med 2004; 50:197.
  31. Brightman MW, Klatzo I, Olsson Y, Reese TS. The blood-brain barrier to proteins under normal and pathological conditions. J Neurol Sci 1970; 10:215.
  32. Kalimo H, Fredriksson K, Nordborg C, et al. The spread of brain oedema in hypertensive brain injury. Med Biol 1986; 64:133.
  33. Beausang-Linder M, Bill A. Cerebral circulation in acute arterial hypertension--protective effects of sympathetic nervous activity. Acta Physiol Scand 1981; 111:193.
  34. Edvinsson L, Owman C, Sjöberg NO. Autonomic nerves, mast cells, and amine receptors in human brain vessels. A histochemical and pharmacological study. Brain Res 1976; 115:377.
  35. Lamy C, Oppenheim C, Méder JF, Mas JL. Neuroimaging in posterior reversible encephalopathy syndrome. J Neuroimaging 2004; 14:89.
  36. Fugate JE, Claassen DO, Cloft HJ, et al. Posterior reversible encephalopathy syndrome: associated clinical and radiologic findings. Mayo Clin Proc 2010; 85:427.
  37. Staykov D, Schwab S. Posterior reversible encephalopathy syndrome. J Intensive Care Med 2012; 27:11.
  38. Magaña SM, Matiello M, Pittock SJ, et al. Posterior reversible encephalopathy syndrome in neuromyelitis optica spectrum disorders. Neurology 2009; 72:712.
  39. Barton JR, Sibai BM. Cerebral pathology in eclampsia. Clin Perinatol 1991; 18:891.
  40. Schaefer PW, Buonanno FS, Gonzalez RG, Schwamm LH. Diffusion-weighted imaging discriminates between cytotoxic and vasogenic edema in a patient with eclampsia. Stroke 1997; 28:1082.
  41. Schwartz RB, Mulkern RV, Gudbjartsson H, Jolesz F. Diffusion-weighted MR imaging in hypertensive encephalopathy: clues to pathogenesis. AJNR Am J Neuroradiol 1998; 19:859.
  42. Lamy C, Mas JL. Hypertensive encephalopathy. In: Stroke: Pathophysiology, Diagnosis, and Management, 4th, Mohr JP, Choi D, Grotta J, et al (Eds), Churchill Livingstone, New York 2004. Vol 2004.
  43. Bartynski WS. Posterior reversible encephalopathy syndrome, part 1: fundamental imaging and clinical features. AJNR Am J Neuroradiol 2008; 29:1036.
  44. Leroux G, Sellam J, Costedoat-Chalumeau N, et al. Posterior reversible encephalopathy syndrome during systemic lupus erythematosus: four new cases and review of the literature. Lupus 2008; 17:139.
  45. Mak A, Chan BP, Yeh IB, et al. Neuropsychiatric lupus and reversible posterior leucoencephalopathy syndrome: a challenging clinical dilemma. Rheumatology (Oxford) 2008; 47:256.
  46. Hodson AK, Doughty RA, Norman ME. Acute encephalopathy, streptococcal infection, and cryoglobulinemia. Arch Neurol 1978; 35:43.
  47. Port JD, Beauchamp NJ Jr. Reversible intracerebral pathologic entities mediated by vascular autoregulatory dysfunction. Radiographics 1998; 18:353.
  48. Magnano MD, Bush TM, Herrera I, Altman RD. Reversible posterior leukoencephalopathy in patients with systemic lupus erythematosus. Semin Arthritis Rheum 2006; 35:396.
  49. Schwartz RB, Bravo SM, Klufas RA, et al. Cyclosporine neurotoxicity and its relationship to hypertensive encephalopathy: CT and MR findings in 16 cases. AJR Am J Roentgenol 1995; 165:627.
  50. Dinsdale HB. Hypertensive encephalopathy. Neurol Clin 1983; 1:3.
  51. Garg RK. Posterior leukoencephalopathy syndrome. Postgrad Med J 2001; 77:24.
  52. Raps EC, Galetta SL, Broderick M, Atlas SW. Delayed peripartum vasculopathy: cerebral eclampsia revisited. Ann Neurol 1993; 33:222.
  53. Ille O, Woimant F, Pruna A, et al. Hypertensive encephalopathy after bilateral carotid endarterectomy. Stroke 1995; 26:488.
  54. Serkova NJ, Christians U, Benet LZ. Biochemical mechanisms of cyclosporine neurotoxicity. Mol Interv 2004; 4:97.
  55. Kou R, Greif D, Michel T. Dephosphorylation of endothelial nitric-oxide synthase by vascular endothelial growth factor. Implications for the vascular responses to cyclosporin A. J Biol Chem 2002; 277:29669.
  56. Beal MF. Mitochondrial dysfunction in neurodegenerative diseases. Biochim Biophys Acta 1998; 1366:211.
  57. Glusker P, Recht L, Lane B. Reversible posterior leukoencephalopathy syndrome and bevacizumab. N Engl J Med 2006; 354:980.
  58. Ozcan C, Wong SJ, Hari P. Reversible posterior leukoencephalopathy syndrome and bevacizumab. N Engl J Med 2006; 354:980.
  59. Allen JA, Adlakha A, Bergethon PR. Reversible posterior leukoencephalopathy syndrome after bevacizumab/FOLFIRI regimen for metastatic colon cancer. Arch Neurol 2006; 63:1475.
  60. Bodkin CL, Eidelman BH. Sirolimus-induced posterior reversible encephalopathy. Neurology 2007; 68:2039.
  61. Rajasekhar A, George TJ Jr. Gemcitabine-induced reversible posterior leukoencephalopathy syndrome: a case report and review of the literature. Oncologist 2007; 12:1332.
  62. Junna MR, Rabinstein AA. Tacrolimus induced leukoencephalopathy presenting with status epilepticus and prolonged coma. J Neurol Neurosurg Psychiatry 2007; 78:1410.
  63. Kozak OS, Wijdicks EF, Manno EM, et al. Status epilepticus as initial manifestation of posterior reversible encephalopathy syndrome. Neurology 2007; 69:894.
  64. Seet RC, Rabinstein AA. Clinical features and outcomes of posterior reversible encephalopathy syndrome following bevacizumab treatment. QJM 2012; 105:69.
  65. Lee VH, Wijdicks EF, Manno EM, Rabinstein AA. Clinical spectrum of reversible posterior leukoencephalopathy syndrome. Arch Neurol 2008; 65:205.
  66. Kastrup O, Gerwig M, Frings M, Diener HC. Posterior reversible encephalopathy syndrome (PRES): electroencephalographic findings and seizure patterns. J Neurol 2012; 259:1383.
  67. Bakshi R, Bates VE, Mechtler LL, et al. Occipital lobe seizures as the major clinical manifestation of reversible posterior leukoencephalopathy syndrome: magnetic resonance imaging findings. Epilepsia 1998; 39:295.
  68. Lysandropoulos AP, Rossetti AO. Postictal cortical visual impairment: a symptom of posterior reversible encephalopathy. Epilepsy Behav 2010; 17:276.
  69. Keswani SC, Wityk R. Don't throw in the towel! A case of reversible coma. J Neurol Neurosurg Psychiatry 2002; 73:83.
  70. de Havenon A, Joos Z, Longenecker L, et al. Posterior reversible encephalopathy syndrome with spinal cord involvement. Neurology 2014; 83:2002.
  71. McKinney AM, Jagadeesan BD, Truwit CL. Central-variant posterior reversible encephalopathy syndrome: brainstem or basal ganglia involvement lacking cortical or subcortical cerebral edema. AJR Am J Roentgenol 2013; 201:631.
  72. Wang MC, Escott EJ, Breeze RE. Posterior fossa swelling and hydrocephalus resulting from hypertensive encephalopathy: case report and review of the literature. Neurosurgery 1999; 44:1325.
  73. de Seze J, Mastain B, Stojkovic T, et al. Unusual MR findings of the brain stem in arterial hypertension. AJNR Am J Neuroradiol 2000; 21:391.
  74. Oliverio PJ, Restrepo L, Mitchell SA, et al. Reversible tacrolimus-induced neurotoxicity isolated to the brain stem. AJNR Am J Neuroradiol 2000; 21:1251.
  75. Kitaguchi H, Tomimoto H, Miki Y, et al. A brainstem variant of reversible posterior leukoencephalopathy syndrome. Neuroradiology 2005; 47:652.
  76. Meylaerts L, Ooms V, Lyra S, et al. Hypertensive brain stem encephalopathy in a patient with chronic renal failure. Clin Nephrol 2006; 65:138.
  77. Friese S, Fetter M, Küker W. Extensive brainstem edema in eclampsia: diffusion-weighted MRI may indicate a favorable prognosis. J Neurol 2000; 247:465.
  78. Lapuyade B, Sibon I, Jeanin S, Dousset V. Neurological picture. Spinal cord involvement in posterior reversible encephalopathy syndrome. J Neurol Neurosurg Psychiatry 2009; 80:35.
  79. Briganti C, Caulo M, Notturno F, et al. Asymptomatic spinal cord involvement in posterior reversible encephalopathy syndrome. Neurology 2009; 73:1507.
  80. Digre KB, Varner MW, Osborn AG, Crawford S. Cranial magnetic resonance imaging in severe preeclampsia vs eclampsia. Arch Neurol 1993; 50:399.
  81. Weingarten K, Barbut D, Filippi CG, Zimmerman RD. Acute hypertensive encephalopathy: findings on spin-echo and gradient-echo MR imaging. AJR Am J Roentgenol 1994; 162:665.
  82. Oppenheim C, Logak M, Dormont D, et al. Diagnosis of acute ischaemic stroke with fluid-attenuated inversion recovery and diffusion-weighted sequences. Neuroradiology 2000; 42:602.
  83. Oppenheim C, Galanaud D, Samson Y, et al. Can diffusion weighted magnetic resonance imaging help differentiate stroke from stroke-like events in MELAS? J Neurol Neurosurg Psychiatry 2000; 69:248.
  84. Trommer BL, Homer D, Mikhael MA. Cerebral vasospasm and eclampsia. Stroke 1988; 19:326.
  85. Heo K, Park S, Lee JY, et al. Post-transfusion posterior leukoencephalopathy with cytotoxic and vasogenic edema precipitated by vasospasm. Cerebrovasc Dis 2003; 15:230.
  86. Will AD, Lewis KL, Hinshaw DB Jr, et al. Cerebral vasoconstriction in toxemia. Neurology 1987; 37:1555.
  87. Kaplan PW. Reversible hypercalcemic cerebral vasoconstriction with seizures and blindness: a paradigm for eclampsia? Clin Electroencephalogr 1998; 29:120.
  88. Voltz R, Rosen FV, Yousry T, et al. Reversible encephalopathy with cerebral vasospasm in a Guillain-Barré syndrome patient treated with intravenous immunoglobulin. Neurology 1996; 46:250.
  89. Henderson RD, Rajah T, Nicol AJ, Read SJ. Posterior leukoencephalopathy following intrathecal chemotherapy with MRA-documented vasospasm. Neurology 2003; 60:326.
  90. Ito Y, Niwa H, Iida T, et al. Post-transfusion reversible posterior leukoencephalopathy syndrome with cerebral vasoconstriction. Neurology 1997; 49:1174.
  91. Boughammoura A, Touzé E, Oppenheim C, et al. Reversible angiopathy and encephalopathy after blood transfusion. J Neurol 2003; 250:116.
  92. Eichler FS, Wang P, Wityk RJ, et al. Diffuse metabolic abnormalities in reversible posterior leukoencephalopathy syndrome. AJNR Am J Neuroradiol 2002; 23:833.
  93. Delanty N, Vaughan C, Frucht S, Stubgen P. Erythropoietin-associated hypertensive posterior leukoencephalopathy. Neurology 1997; 49:686.
  94. Casey SO, Sampaio RC, Michel E, Truwit CL. Posterior reversible encephalopathy syndrome: utility of fluid-attenuated inversion recovery MR imaging in the detection of cortical and subcortical lesions. AJNR Am J Neuroradiol 2000; 21:1199.
  95. Kupferschmidt H, Bont A, Schnorf H, et al. Transient cortical blindness and bioccipital brain lesions in two patients with acute intermittent porphyria. Ann Intern Med 1995; 123:598.
  96. Kaplan, NM. Hypertensive crises. In: Clinical Hypertension, 7th, Kaplan NM (Ed), Williams & Wilkins, Baltimore 1998. p.265.
  97. Vaughan CJ, Delanty N. Hypertensive emergencies. Lancet 2000; 356:411.
  98. Ledingham JG, Rajagopalan B. Cerebral complications in the treatment of accelerated hypertension. Q J Med 1979; 48:25.
  99. Neutel JM, Smith DH, Wallin D, et al. A comparison of intravenous nicardipine and sodium nitroprusside in the immediate treatment of severe hypertension. Am J Hypertens 1994; 7:623.
  100. Arnoldus EP, Van Laar T. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996; 334:1745; author reply 1746.
  101. Eberly AL, Anderson GD, Bubalo JS, McCune JS. Optimal prevention of seizures induced by high-dose busulfan. Pharmacotherapy 2008; 28:1502.
  102. Datar S, Singh T, Rabinstein AA, et al. Long-term risk of seizures and epilepsy in patients with posterior reversible encephalopathy syndrome. Epilepsia 2015; 56:564.
  103. Baldini M, Bartolini E, Gori S, et al. Epilepsy after neuroimaging normalization in a woman with tacrolimus-related posterior reversible encephalopathy syndrome. Epilepsy Behav 2010; 17:558.
  104. Gijtenbeek JM, van den Bent MJ, Vecht CJ. Cyclosporine neurotoxicity: a review. J Neurol 1999; 246:339.
  105. Hauben M. Cyclosporine neurotoxicity. Pharmacotherapy 1996; 16:576.
  106. Hayes D Jr, Adler B, Turner TL, Mansour HM. Alternative tacrolimus and sirolimus regimen associated with rapid resolution of posterior reversible encephalopathy syndrome after lung transplantation. Pediatr Neurol 2014; 50:272.
  107. Tam CS, Galanos J, Seymour JF, et al. Reversible posterior leukoencephalopathy syndrome complicating cytotoxic chemotherapy for hematologic malignancies. Am J Hematol 2004; 77:72.
  108. Eaton JM. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996; 334:1744.
  109. Roth C, Ferbert A. Posterior reversible encephalopathy syndrome: long-term follow-up. J Neurol Neurosurg Psychiatry 2010; 81:773.