332 ■ The Annals of Pharmacotherapy ■ 2006 February, Volume 40 www.theannals.com I fosfamide is a chemotherapeutic agent used in the treat- ment of various solid tumors, as well as lymphomas, in children and adults. Myelosuppression, hemorrhagic cysti- tis, nausea, and vomiting are the most common acute ad- verse effects. Ifosfamide-related central nervous system (CNS) toxicity is characterized by a metabolic encephalo- pathy of varying severity and usually affects patients re- ceiving high-dose regimens (>1.5 g/m 2 /day). 1,2 This toxici- ty may present with hallucinations, personality changes, confusion, lethargy, somnolence, cranial nerve palsies, cerebellar dysfunction, seizures, mutism, and, rarely, coma. 3 Nonconvulsive status epilepticus (NCSE) is an epileptic disorder in which typical convulsive activity is absent. Mental status changes may be the only presenting signs in NCSE, and its diagnosis may therefore be chal- lenging. We present 2 cases of ifosfamide-related NCSE. Case Reports CASE 1 A 55-year-old woman was diagnosed with mesenteric lymph node diffuse large B-cell lymphoma. She received 6 cycles of combination chemotherapy consisting of cyclophosphamide, doxorubicin (adri- amycin), vincristine, and prednisolone (CHOP) followed by 4 weekly doses of rituximab. Complete remission was achieved, but the patient experienced a relapse 6 months later. A chemotherapy protocol consist- ing of ifosfamide 1000 mg/m 2 (1 h infusion on days 1–5 with mesna uro- protection), idarubicin 10 mg/m 2 (1 h infusion on days 1 and 2), and etoposide 150 mg/m 2 (3 h infusion on days 1–3) was administered. On the third day of chemotherapy, the woman became confused and lethargic. Her speech deteriorated and, after several hours, she became mute. Chemotherapy was discontinued. Blood biochemistry values are summarized in Table 1. Computed cranial tomography did not show any hemorrhage, ischemic lesion, or mass that could account for the clinical findings. Lumbar puncture was negative for both microorganisms and malignant cells, and cerebrospinal fluid biochemistry was within normal limits. She was already receiving omeprazole 20 mg/day and granisetron 3 mg/day, both of which would not significantly increase the risk of CNS toxicity. An electroencephalogram (EEG) showed slow background ac- Nonconvulsive Status Epilepticus Due to Ifosfamide Saadettin Kilickap, Mustafa Cakar, Ibrahim K Onal, Abdurrahman Tufan, Hadim Akoglu, Sercan Aksoy, Mustafa Erman, and Gulten Tekuzman Author information provided at the end of the text. OBJECTIVE: To report 2 cases of nonconvulsive status epilepticus (NCSE) following infusion of ifosfamide. CASE SUMMARIES: Two patients who received ifosfamide-containing chemotherapy developed NCSE. One woman received ifosfamide 1000 mg/m 2 (1 h infusion on days 1–5); confusion, lethargy, and speech deterioration developed on day 3. The second patient developed similar symptoms on day 3 of treatment with 2500 mg/m 2 . Both patients responded to intravenous administration of diazepam 10 mg and were given levetiracetam as maintenance therapy. DISCUSSION: The severity and presentation of central nervous system toxicity due to ifosfamide varies greatly and involves a spectrum ranging from subclinical electroencephalogram changes to coma. NCSE, an epileptic disorder in which typical convulsive activity is absent, has previously been reported in only 4 patients receiving ifosfamide. Levetiracetam may be used for maintenance antiepileptic therapy after diazepam administration. CONCLUSIONS: Among the many presentations of ifosfamide neurotoxicity, clinicians should consider NCSE as a possible explanation for changes in consciousness in a patient receiving this agent. An objective causality assessment by use of the Naranjo probability scale revealed that NCSE due to ifosfamide was probable. KEY WORDS: ifosfamide, levetiracetam, nonconvulsive status epilepticus. Ann Pharmacother 2006;40:332-5. Published Online, 31 Jan 2006, www.theannals.com, DOI 10.1345/aph.1G363 by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from