Extended use dexamethasone-associated posterior reversible encephalopathy syndrome with cisplatin-based chemotherapy MyChau T. Nguyen a , Irim Y. Virk b , Lita Chew a , J. Lee Villano b, * a Department of Pharmacy, The University of Illinois at Chicago, Chicago, Illinois, USA b Department of Medicine, Section of Hematology and Oncology, Room 3133 (M/C 734), University of Illinois at Chicago, 909 South Wolcott Avenue, Chicago, Illinois 60612, USA article info Article history: Received 20 May 2009 Accepted 23 May 2009 Keywords: Cisplatin Dexamethasone Encephalopathy Posterior reversible encephalopathy syndrome (PRES) abstract We describe a normotensive patient who developed posterior reversible encephalopathy syndrome fol- lowing prolonged use of dexamethasone for nausea control with cisplatin and pemetrexed chemother- apy. A 32-year-old woman with advanced intraperitoneal mesothelioma developed new-onset seizures and cognitive impairment. MRI of the brain demonstrated several areas of increased signal on T2- weighted and fluid-attenuated inversion recovery sequences within the subcortical white matter of both hemispheres. Chemotherapy was discontinued and dexamethasone tapered-off. She returned to her baseline with resolution of MRI abnormalities. We hypothesize that extended use of dexamethasone potentiated the relatively uncommon complication of leukotoxicity associated with cisplatin, and we elaborate on dexamethasone’s contribution. Ó 2009 Elsevier Ltd. All rights reserved. 1. Introduction Dexamethasone is a potent long-acting, synthetic glucocorti- coid commonly prescribed in cancer for cytotoxic activity in hema- tologic malignancies and to manage and ameliorate many central nervous system (CNS) symptoms including nausea and vomiting, pain, lack of appetite, and mass effect induced edema. Although the exact mechanism is not well understood, dexamethasone is of- ten the preferred glucocorticoid for CNS symptoms due to favor- able pharmacokinetics; with twice the ratio of plasma to cerebrospinal fluid (CSF) concentration and a longer CNS half-life than prednisone. 1 Corticosteroids can have significant adverse effects including euphoria, insomnia, personality changes, depression, mania, hallu- cinations, and psychosis. Recently, Irvin et al. described a patient with posterior reversible encephalopathy syndrome (PRES) in a woman with lung cancer after 5 days of high-dose dexamethasone with concomitant hypertensive crises. 2 PRES is a clinicoradiological diagnosis characterized by head- ache, confusion, visual disturbances, seizures, and transient neuro- imaging changes in the posterior circulation distribution. A myriad of CNS toxic insults are associated including hypertensive crises, infections, eclampsia, hypercalcemia, and neurotoxic drugs. Here we describe a normotensive patient with PRES induced by ex- tended use of dexamethasone on cisplatin-based chemotherapy. 2. Case report A 32-year-old female with advanced intraperitoneal mesotheli- oma was hospitalized for new-onset seizures. She originally pre- sented at age 21 with ascites that resolved upon therapeutic drainage, and underwent an unrevealing exploratory laparotomy. Two years prior to presentation, she underwent incisional hernia repair and was noted to have peritoneal lymphadenopathy that demonstrated well-differentiated peritoneal mesothelioma. After cytoreductive surgery she received intraperitoneal melphalan che- motherapy at an outside institution. One year prior to presenta- tion, she underwent re-exploration for recurrent disease and received cytoreductive surgery and intraperitoneal melphalan. She received two more cycles of intraperitoneal paclitaxel, but developed grade II nausea (Common Terminology Criteria for Ad- verse Events [CTCAE]) and discontinued therapy. Six months prior to presentation, she was referred to our insti- tution and initiated on systemic chemotherapy with pemetrexed and cisplatin. 3 Due to her history of nausea and vomiting, she was started on a regimen of aprepitant, palonosetron, lorazepam, oral dexamethasone four mg twice daily starting the day before chemotherapy for 5 days, and rescue prochlorperazine if needed. One week after the first cycle, she reported persistent nausea despite rescue antiemetics. Nausea was well-controlled only on dexamethasone, and scheduled therapy of ondansetron, prochlor- perazine, and diphenhydramine was started. Five additional days of dexamethasone was also prescribed. Over the next few chemo- therapy cycles, she continued to experience significant nausea while off dexamethasone. To avoid adverse effects of long-term steroid use, a trial of dronabinol was initiated, but failed. She was then placed on a total of 8 mg of dexamethasone daily for 8 days. This regimen was repeated every 21 days in-line with her chemotherapy cycle. She also had as needed dexamethasone, which she could take for rescue, and she slowly expanded the days she was on dexamethasone to 14 out of 21 days. On day 11 of her 7th cycle, she was admitted for new-onset sei- zures. She also had complaints of dizziness and forgetfulness. She had her fourth seizure in the emergency department and was given intravenous diazepam and fosphenytoin. She remained seizure- free, based on electroencephalogram (EEG) and clinical findings. Her vital signs were unremarkable: blood pressure (BP) 112/ 85 mmHg and heart rate 105 beats/minute. Serum electrolytes were significant for mild abnormalities: sodium 132 mmol/L, potassium 3.1 mmol/L, and magnesium 1.5 mg/dL. Her neurological examination demonstrated slow, but deliber- ate speech, and global neurocognitive slowing. Repeat EEG demon- strated generalized cerebral slowing without evidence of epileptiform or paroxysmal discharges. The CT scan of the head was unremarkable; however, the MRI demonstrated several scat- tered areas of increased non-enhancing T2-weighted /fluid-attenu- ated inversion recovery (FLAIR) signal within the subcortical white matter of both hemispheres (Fig. 1A,B,C). Throughout her hospitalization she remained normotensive (systolic BP < 140 mmHg and diastolic BP < 86 mmHg). One week following admission she returned to baseline cognitive status and * Corresponding author. Tel.: +1 312 996 6768; fax: +1 312 413 4205. E-mail address: jvillano@uic.edu (J.L. Villano) 1688 Case Reports / Journal of Clinical Neuroscience 16 (2009) 1688–1690