|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 25, No 17 (June 10), 2007: pp. 2484-2486 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.10.9991
Dexamethasone-Induced Posterior Reversible Encephalopathy SyndromeUniversity of North Carolina at Chapel Hill, Chapel Hill, NC A 48-year-old woman presented to the emergency department with complaints of right hip pain, diplopia, and left ptosis. Two months prior, she was diagnosed with metastatic non–small-cell lung carcinoma after presenting with superior vena cava syndrome and diffuse visceral metastatic disease. Despite having been treated with both external-beam radiotherapy and gemcitabine and carboplatin chemotherapy, she demonstrated radiographic evidence of tumor progression. Plain films were performed, which demonstrated pathologic fractures of the right proximal femur. A magnetic resonance imaging (MRI) scan with contrast of the brain showed multiple new subcentimeter brain metastases without mass effect or edema (Fig 1, arrow). A lumbar puncture was performed to evaluate for carcinomatous meningitis. Both cerebral spinal fluid (CSF) studies and CSF cytology returned within normal limits. She was admitted to the hospital for surgical fixation of her fractures and started on 4 mg of oral dexamethasone every 6 hours in preparation for potential external-beam radiation therapy for her brain metastases. On day 3 in the hospital, she underwent surgical fixation of the right femur. On day 5 in the hospital, the patient became progressively disoriented and agitated. She was treated with trazodone and zolpidem, and a single dose of haldol. The following morning she became obtunded with associated autonomic instability. Her vital signs showed a blood pressure of 190/100 mmHg and a pulse rate of 160 beats per minute. On physical exam she was found to have anisocoria and sluggish pupillary reflexes. Her lower extremity reflexes were 2+ and brisk and her Babinski responses were upgoing bilaterally. Laboratory studies demonstrated no evidence of infection or metabolic abnormalities, whereas a computed tomography (CT) scan of the head showed no acute intracranial hemorrhage or mass effect. A second lumbar puncture was performed, and both CSF studies and CSF cytology again returned within normal limits. A repeat MRI/magnetic resonance angiography of the brain showed stable brain metastases, but fluid attenuation inversion recovery images demonstrated diffuse cortical and subcortical white matter signal abnormality in a symmetric bilateral distribution involving predominantly the occipital areas, superior frontal areas, the cerebellum, and some focal areas of the thalami bilaterally (Fig 2A), not evident on T1-weighted images (Fig 2B). These radiographic findings were most consistent with posterior reversible encephalopathy syndrome (PRES).
Although trazodone may cause serotonin syndrome and haldol may cause neuroleptic malignant syndrome, her clinical presentation and studies were most consistent with dexamethasone-induced PRES. Her hypertension was treated aggressively, and the dexamethasone was quickly tapered, resulting in resolution of her delirium within 48 hours. A repeat brain MRI 4 days later showed improving PRES. Hospice was initiated, and she did not receive radiation therapy to the brain. The presenting clinical features of PRES include headaches, seizures, visual disturbances (including cortical blindness and visual hallucinations), and alterations in mental status (confusion, stupor). Hypertension is typically present, though some patients with PRES are normotensive. Clinical exam findings are relatively unimpressive, with the exception of brisk deep tendon reflexes (particularly of the lower extremities) and extensor plantar responses.1-3 On neuroimaging, MRI of the brain demonstrates hyperintense lesions of the white matter and adjacent gray matter on fluid attenuation inversion recovery and T2-weighted images located in the occipital lobes and posterior parietal lobes. Involvement of other areas of the brain are less frequent but reported.1,3 The use of corticosteroids in clinical oncology is widespread. Even though the customary adverse effects of corticosteroid use are widely known, we describe a rare but reversible complication of high-dose dexamethasone therapy: PRES. Corticosteroid use has been associated with PRES in patients being treated for renal diseaes,1,2 hematologic malignancies,2,4-9 as well as bone marrow and solid organ transplantation.1,3,10 However, the patients were uniformly either acutely ill or exposed to other agents implicated in causing PRES (ie, immunosuppressive agents or cytotoxic chemotherapy). Therefore, the lack of concomitant medications in this patient is unique and implicates dexamethasone as playing an active role in provoking PRES. A variety of other drugs used in clinical oncology have been implicated in causing PRES: immunosuppressive therapy,1-3 erythropoietin,11 interferon alfa,3,11 antithymocyte globulin,12 cytotoxic chemotherapy,1-3,13 and most recently molecular-targeted agents such as sorafenib14 and bevacizumab.15 Hypertension is believed to be the unifying precipitant in many cases of PRES, but it does occur in the absence of hypertension,2,3 and thus the mechanism whereby such diverse diagnoses and compounds provoke PRES remains unclear. Two theories have been put forth: the cytotoxic theory and the vasogenic theory. Whereas the former postulates that a direct toxic effect on the endothelial cells of the cerebral vasculature results in cell autonomous endothelial dysfunction, the latter proposes that an acute increase in blood pressure overrides the autoregulation of cerebral mean arterial pressure, leading to vasodilatation and a noncell autonomous endothelial insult.2,3 In both cases, the end result is the diffusion of plasma proteins and cells into the extracellular space and subsequent cerebral edema. Hypertension is a well-known adverse effect of high-dose corticosteroid therapy primarily mediated by its effects on the mineralocorticoid receptor, and we hypothesize that this is the etiology of PRES in this patient. Whereas the underlying mechanism of corticosteroid-induced PRES is likely to be secondary to rare idiosyncratic acute rises in blood pressure, a direct effect of the medication cannot be ruled out. Given the widespread and multifaceted use of dexamethasone within the field of oncology, it is important to recognize PRES as a rare and serious but reversible complication of high-dose corticosteroid use. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
REFERENCES
1. Hinchey J, Chaves C, Appignani B, et al: A reversible posterior leukoencephalopathy syndrome. N Engl J Med 334:494-500, 1996 2. Kwon S, Koo J, Lee S: Clinical spectrum of reversible posterior leukoencephalopathy syndrome. Pediatr Neurol 24:361-364, 2001[Medline] 3. Stott VL, Hurrell MA, Anderson TJ: Reversible posterior leukoencephalopathy syndrome: A misnomer reviewed. Intern Med J 35:83-90, 2005[CrossRef][Medline] 4. Edwards MJ, Walker R, Vinnicombe S, et al: Reversible posterior leukoencephalopathy syndrome following CHOP chemotherapy for diffuse large B-cell lymphoma. Ann Oncol 12:1327-1329, 2001 5. Shin RK, Stern JW, Janss AJ, et al: Reversible posterior leukoencephalopathy during the treatment of acute lymphoblastic leukemia. Neurology 56:388-391, 2001 6. D'Angelo P, Farruggia P, Lo Bello A, et al: Reversible posterior leukoencephalopathy syndrome: Report of 2 simultaneous cases in children. J Pediatr Hematol Oncol 28:177-181, 2006[CrossRef][Medline] 7. Greenwood MJ, Dodds AJ, Garricik R, et al: Posterior leukoencephalopathy in association with the tumour lysis syndrome in acute lymphoblastic leukaemia: A case with clinicopathological correlation. Leuk Lymphoma 44:719-721, 2003[CrossRef][Medline] 8. Pandey R, Patel A, Shah S, et al: A rare complication in a case of multiple myeloma on therapy with thalidomide and dexamethasone: Reversible posterior lobe leukoencephalopathy. Leuk Lymphoma 47:1431-1434, 2006[Medline] 9. Tam CS, Galanos J, Seymour JF, et al: Reversible posterior leukoencephalopathy syndrome complicating cytotoxic chemotherapy for hematologic malignancies. Am J Hematol 77:72-76, 2004[CrossRef][Medline] 10. Lanzino G, Cloft H, Hemstreet MK, et al: Reversible posterior leukoencephalopathy following organ transplantation: Description of two cases. Clin Neurol Neurosurg 99:222-226, 1997[CrossRef][Medline] 11. Kamar N, Kany M, Bories P, et al: Reversible posterior leukoencephalopathy syndrome in hepatitis C virus-positive long-term hemodialysis patients. Am J Kidney Dis 37:E29, 2001[Medline] 12. Greaves P, Oakervee H, Kon SS, et al: Posterior reversible encephalopathy syndrome following anti-lymphocyte globulin treatment for severe aplastic anaemia. Br J Haematol 134:251, 2006[CrossRef][Medline] 13. Saito B, Nakamaki T, Nakashima H, et al: Reversible posterior leukoencephalopathy syndrome after repeat intermediate-dose cytarabine chemotherapy in a patient with acute myeloid leukemia. Am J Hematol 82:304-306, 2007[CrossRef][Medline] 14. Govindarajan R, Adusumilli J, Baxter DL, et al: Reversible posterior leukoencephalopathy syndrome induced by RAF kinase inhibitor BAY 43-9006. J Clin Oncol 24:E48, 2006[CrossRef][Medline] 15. Allen JA, Adlakha A, Bergethon PR: Reversible posterior leukoencephalopathy syndrome after bevacizumab/FOLFIRI regimen for metastatic colon cancer. Arch Neurol 63:1475-1478, 2006 This article has been cited by other articles:
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
