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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


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Literature review current through: Apr 2015. | This topic last updated: Apr 29, 2015.
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  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. Oliviero, PJ, Restrepo, L, Mitchell, SA, et al. Reversible tacrolimus-induced neurotoxicity isolated to the brainstem. 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 C, 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.