Subacute Encephalopathy with Transhemispheric Transition of a Focal Lesion Following Intrathecal Methotrexate Injection in Pre-B-Cell Acute Lymphoblastic Leukemia: A Case Report

Case Report

A Case Report. Ann Hematol Oncol. 2016; 3(9): 1112.

Subacute Encephalopathy with Transhemispheric Transition of a Focal Lesion Following Intrathecal Methotrexate Injection in Pre-B-Cell Acute Lymphoblastic Leukemia: A Case Report

Ando Y¹, Sato Y¹*, Kuwashima S², Fukushima K¹, Okuya M¹, Imataka G¹, Kurosawa H¹ and Arisaka O¹

¹Department of Pediatrics, Dokkyo Medical University, Japan

²Department of Radiology, Dokkyo Medical University, Japan

*Corresponding author: Yuya Sato, Department of Pediatrics, Dokkyo Medical University School of Medicine 880 Kita-Kobayashi, Mibu, Tochigi 321-0207, Japan

Received: August 27, 2016; Accepted: October 03, 2016; Published: October 04, 2016

Abstract

Intrathecal injection of methotrexate (MTX) is important in the treatment of meningeal leukemia to prevent relapse in the central nerve system in patients with acute lymphoblastic leukemia (ALL). However, intrathecal injection of MTX sometime induces subacute encephalopathy.

A female patient with pre-B cell ALL developed relapsing-remitting encephalopathy associated with the intrathecal injection of methotrexate. The Japan Pediatric Leukemia Study Group ALL B-12 protocol had been followed. Right-sided paralysis developed 2 days after the fourth intrathecal injection of MTX. Diffusion-weighted images (DWI) during magnetic resonance imaging revealed a high-signal area in the left centrum semiovale. The right-sided paralysis resolved, only to be followed by left-sided paralysis and dysarthria. Simultaneously with these symptoms, the left-sided DWI signal was decreased and a new abnormal signal intensity lesion appeared on the right. The patient recovered from the paralysis and dysarthria 4 days after the onset of the neurological symptoms. The phenomena with which our patient presented were similar to those of multiple sclerosis, but no myelin basic protein or oligoclonal band was detected in the cerebrospinal fluid.

The mechanism that causes subacute encephalopathy after intrathecal injection of MTX is similar to that in the development of multiple sclerosis, but with no induction of myelin basic protein or oligoclonal band.

Keywords: Subacute encephalopathy; Methotrexate; Acute lymphoblastic leukemia; Intrathecal injection

Introduction

Methotrexate (MTX) is key drug in patients with acute lymphoblastic leukemia (ALL) for the treatment of meningeal leukemia or to prevent relapse in the central nervous system. MTX is administered by intravenous or intrathecal injection. However, it has also neurotoxic effects [1]. Cases of subacute MTX-induced encephalopathy reported previously showed strong signal changes on diffusion-weighted images (DWIs) obtained with magnetic resonance imaging (MRI) [1-11]. Although the intravenous or intrathecal injection of MTX is assumed to be neurotoxic because it induces metabolic changes in the central nervous system, the mechanism underlying the development of subacute encephalopathy is unclear [1,7,10-12].

We report a patient in whom subacute encephalopathy was induced by the intrathecal injection of MTX. Subacute encephalopathy was observed as chronological and spatial changes on DWI, with the simultaneous development of central nervous system disorders, which was similar to pathogenesis of multiple sclerosis. We propose a mechanism underlying subacute MTX-induced encephalopathy.

Case Presentation

A 10-year-old female child was admitted to our hospital with pre-B-cell ALL, which was positive forCD10, CD19, CD22, CD20, CD24, and HLA-DR. The leukemic blasts had not infiltrated the central nervous system. There was not neurological symptom. Induction therapy was administered for 5 weeks according to the Japan Pediatric Leukemia Study Group (JPLSG) ALL B-12 protocol, with two intrathecal injections of three drugs: 12 mg of MTX, 30 mg of cytarabine, and 10 mg of prednisolone. Complete remission was achieved with this induction therapy. Consolidation therapy, which consisted of cytarabine, cyclophosphamide, mercaptopurine, l-asparaginase, and two intrathecal injections of MTX, cytarabine, and prednisolone, was commenced on day 36 after the induction therapy was completed. The fourth intrathecal injection of MTX, cytarabine, and prednisolone was given on day 45. Paralysis of the right side developed on day 57, and DWI revealed a high-signal lesion in the left centrum semiovale (Figure 1A). Magnetic resonance angiography (MRA) revealed no obstructions or malformations of the cerebral arteries (Figure 1B). The patient’s platelet count was 1.5×1010/L. The prothrombin time international normalization ratio was 1.00. The activated partial thromboplastin time was 31.3s. Fibrinogen was 448 mg/dL. No bacteria or viruses were cultured from the cerebrospinal fluid (CSF). No myelin basic protein or oligoclonal band was detected in the CSF. Anticoagulant and antiplatelet therapies were performed. The physical symptoms resolved by day 58, but paralysis of the left side and dysarthria developed suddenly on day 59. The signal of the left-sided cerebral lesion was decreased, and a new lesion was detected on the right side (Figure 1C). No defect was detected with singlephoton emission computed tomography (SPECT) (Figure1D). All the phenomena had disappeared by day 60. There were not abnormalities of laboratory analysis during paralysis developing. Remaining JPLSG ALL-12 protocol which included that nine time of MTX intrathecal injections and four rounds of high-dose MTX therapy were done for our patient, but paralysis was never developed again.

Citation: Ando Y, Sato Y, Kuwashima S, Fukushima K, Okuya M, Imataka G, et al. Subacute Encephalopathy with Transhemispheric Transition of a Focal Lesion Following Intrathecal Methotrexate Injection in Pre-B-Cell Acute Lymphoblastic Leukemia: A Case Report. Ann Hematol Oncol. 2016; 3(9): 1112. ISSN : 2375-7965