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Show Dorsolateral Midbrain MRI Abnormalities and Ocular Motor Deficits Following Cytarabine-Based Chemotherapy for Acute Myelogenous Leukemia Thuy Doan, MD, PhD, Norman Lacayo, MD, Paul G. Fisher,MD, Yaping Joyce Liao, MD, PhD Cytarabine-based chemotherapy is a mainstay in the treatment of hematologic malignancies despite its known neurologic toxicities, including cerebellar ataxia, diplopia, locked-in syndrome, myelopathy, cognitive de-cline, encephalitis, headache, and papilledema (1-8). We report a case of ocular motor deficits with striking midbrain MRI abnormalities. A 12-year-old boy with acute myelogenous leukemia (AML) was treated with induction chemotherapy, which included intrathecal (IT) cytarabine (60 mg) and in-travenous (IV) cytarabine (3,000 mg/m2, 6 times), dau-nomycin (50 mg/m2, 3 times), and etoposide (100 mg/m2, 5 times). Induction continued with 36 mg IT cytarabine, 12 mg methotrexate, and 24 mg hydrocortisone (triple therapy) in addition to IV cytarabine, daunomycin, and etoposide. Following the first round of consolidation therapy, which consisted of IT triple therapy and IV cytarabine and etoposide, the patient developed right-sided appendicular ataxia, instability of gait, and nystagmus. Brain CT was negative, and the ataxia gradually improved. For the second consolidation round, the IT cytarabine was withheld, and the IV cytarabine dose was reduced by 66%. Even so, ataxia, diplopia, and slurred speech occurred. For the third consolidation round, IT and IV cytarabine were withheld, and no further clinical deficits developed. Neuro-ophthalmologic examination 2 months following the third consolidation round, after a cumulative dose of 132 mg of IT cytarabine, revealed visual acuities of 20/20 in both eyes; normal color perception by Hardy-Rand-Rittler pseudochromatic plates; and unremarkable pupils, anterior and posterior segments, and automated visual fields. Ex-traocular movements were full, with an exotropia of 25 prism diopters, right hypertropia of 6 prism diopters, and convergence insufficiency. High-speed binocular infrared oculography demonstrated horizontal pendular nystagmus during fixation, hypometric horizontal and vertical saccades, subtle saccadic dysmetria, and impaired pursuit. He had a wide-based gait and an abnormal Romberg sign. A pure tone audiogram showed high-frequency hearing loss in the left ear, and videonystagmography revealed normal caloric responses bilaterally. Brain MRI performed 2 months following the third consolidation round revealed prominent hyperintensities on FLAIR sequences in the dorsal midbrain, including the periaqueductal gray, superior colliculi, and superficial lateral tegmentum (Fig. 1). There were 2 punctate T2 hyper-intensities in the right cerebrum. There was no pathologic contrast enhancement. Brain MRI performed 7 months later showed that all MRI abnormalities had largely dis-appeared (Fig. 1). The patient's ocular motor deficits, hearing loss, and subtle ataxia never improved. This is the first case to document ocular motor deficits in conjunction with midbrain MRI signal abnormalities as a result of chemotherapy in the treatment of AML. The clinical findings and MRI abnormalities appeared following multiple exposures to cytarabine, consistent with a cumu-lative effect (1). Acute infusion-induced neurotoxicity was preventable by withholding cytarabine. Cytarabine therapy has been associated with cerebellar atrophy and, rarely, signal abnormalities in the spinal cord (5-8) and cerebellum (9-12). Midbrain signal abnormali-ties have not previously been reported. Close surveillance of neuro-ophthalmologic findings, prompt readjustment of medications and treatment routes, and timely serial MRI Departments of Ophthalmology (TD, YJL), Hematology-Oncology (NL), and Neurology (PGF), Stanford University School of Medicine, Stanford, California. Supported by a K08 grant from the National Institute of Neurological Diseases and Stroke and the Career Awards in Biomedical Sciences from the Burroughs Wellcome Foundation to YJL Address correspondence to Yaping Joyce Liao, MD, PhD, Department of Ophthalmology, Stanford University Medical Center, 900 Blake Wilbur Drive, Room W3047 Stanford, CA 94304-5353; E-mail: yhliao@stanford.edu 52 Doan et al: J Neuro-Ophthalmol 2011; 31: 52-53 Clinical Observation Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. studies are essential in reducing central nervous system toxicity while still allowing for lifesaving treatment of he-matologic cancers. REFERENCES 1. Baker WJ, Royer GL Jr, Weiss RB. Cytarabine and neurologic toxicity. J Clin Oncol. 1991;9:679-693. 2. Jabbour E, O'Brien S, Kantarjian H, Garcia-Manero G, Ferrajoli A, Ravandi F, Cabanillas M, Thomas DA. 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Neurology. 2000;55: 1234. FIG. 1. Axial FLAIR MRI performed 2 months after the third consolidation round of cytarabine-based chemotherapy for acute myelogenous leukemia (A, B) discloses focal high-signal areas in the midbrain (arrows). Axial FLAIR MRI per-formed 7 months later (C, D) shows that these signal abnormalities have largely disappeared, although clinical ab-normalities persisted. Doan et al: J Neuro-Ophthalmol 2011; 31: 52-53 53 Clinical Observation Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. |
