Methotrexate leukoencephalopathy mimics acute progressive stroke

Abstract

Stroke mimics are often encountered in emergency departments, and previous studies have demonstrated that 25.3% of patients diagnosed with acute ischemic stroke are actually suffering from a nonacute stroke or a transient ischemic attack [1]. Transient leukoencephalopathy has been reported to mimic cerebrovascular disease in chemotherapy recipients [2, 3]. We report a case of a patient with acute lymphocytic leukemia (ALL) who received various combinations of chemotherapy, including methotrexate (MTX), and presented with progressive focal neurological deficits that mimicked acute progressive stroke. A 16 year-old boy with ALL was admitted to our hospital for chemotherapy. The patient received chemotherapy and intrathecal and intravenous MTX injections before neurological dysfunction was noticed. Ten days after the last intrathecal MTX injection, the patient complained of numbness in his right lower extremity, and left hemiparesis occurred soon. Brain computed tomography showed no evidence of hemorrhagic stroke or early ischemic changes. The patient’s neurological symptoms continued to worsen together with motor paresis involving the right lower extremity and alternate sensory disturbances involving the left side of the face and the right extremities. Because of the patient’s clinical presentation, acute progressive stroke was suspected. Diffusion-weighted images (DWI) showed well-demarcated hyperintense multiple lesions within the bilateral white matter with low apparent diffusion coefficients (ADC) (Fig. 1a, b), whereas fluid-attenuated inversion recovery (FLAIR) images showed lesions with nearly normal intensities (Fig. 1c). Although the patient’s neurological presentation indicated acute progressive stroke, serial magnetic resonance imaging (MRI) suggested MTX leukoencephalopathy [4]; therefore, neither tissue plasminogen activator (t-PA) nor antiplatelet agents were administered. The neurological symptoms fluctuated, and he experienced additional sensory disturbances in his left extremities; nevertheless, these symptoms completely disappeared within 2 weeks. Follow-up MRI performed 24 days after recovery showed the disappearance of hyperintense lesions (DWI or FLAIR) and normal ADC were recorded (Fig. 1d–f). MTX has been indicated as a neurotoxic agent responsible for various neurological complications. Acute encephalopathy is estimated to occur in less than 2% of MTX recipients, mostly observed in children under 18 years of age, and tends to develop 5–14 days after highdose or intrathecal MTX administration [5]. Symptoms usually include headache, nausea, emesis, lethargy, altered mental status, blurred vision, aphasia, hemiparesis, and seizures. Neurological symptoms often fluctuate over a few days and the lesions tend to spread to both hemispheres [2, 5]. Although an immediate diagnosis of acute MTX encephalopathy is often difficult, reported radiological characteristics include hyperintensities on DWI with decreased ADC, which are also indicative of cytotoxic edema. The lesions are well demarcated and typically located in the periventricular white matter, particularly in R. Tanaka (&) K. Sasaki-Ikesawa H. Shimura K. Nishioka S. Tanaka Department of Neurology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan e-mail: r_tanaka@juntendo.ac.jp