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Table of Contents
Year : 2019  |  Volume : 2  |  Issue : 2  |  Page : 263-264

Panda eye sign on diffusion weighted-MRI for the diagnosis of methotrexate-induced subacute leukoencephalopathy

1 Department of Medical Oncology, Mazumdar Shaw Medical Center, Bengaluru, Karnataka, India
2 Department of Medical Oncology, Ramaiah Medical College, Bengaluru, Karnataka, India

Date of Web Publication20-Dec-2019

Correspondence Address:
Nidhi Tandon
Mazumdar Shaw Medical Center, Narayana Hrudayalaya, Bommasandra Industrial Area, Bengaluru - 560 099, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/CRST.CRST_80_19

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How to cite this article:
Tandon N, Khanderia M, Devadas SK. Panda eye sign on diffusion weighted-MRI for the diagnosis of methotrexate-induced subacute leukoencephalopathy. Cancer Res Stat Treat 2019;2:263-4

How to cite this URL:
Tandon N, Khanderia M, Devadas SK. Panda eye sign on diffusion weighted-MRI for the diagnosis of methotrexate-induced subacute leukoencephalopathy. Cancer Res Stat Treat [serial online] 2019 [cited 2020 Sep 23];2:263-4. Available from: http://www.crstonline.com/text.asp?2019/2/2/263/273696

In this intriguing original article, Mahajan et al. have performed a retrospective analysis of adult acute lymphoblastic leukemia (ALL) patients who were treated with Berlin–Frankfurt–Munster-90 protocol and found a consistent imaging finding of restricted diffusion in the centrum semiovale resembling 'panda eyes' in diffusion-weighted (DW) magnetic resonance imaging (MRI) of the brain among patients who developed methotrexate (MTX)-induced subacute leukoencephalopathy.[1]

High-dose MTX defined as a dose of 500 mg/m2 or higher is associated with neurotoxicity, likely through the disruption of central nervous system (CNS) folate homeostasis and/or direct neuronal damage. Bhojwani et al. performed MRI of the brain prospectively at four time points for 369 children with ALL who were treated with a regimen that included high-dose MTX and triple intrathecal therapy. They found that 86 (23.3%) of the 369 patients had evidence of leukoencephalopathy on at least one screening MRI. These included 73 (20.6%) of 355 asymptomatic patients and 13 (92.9%) of 14 patients with clinical neurotoxicity.[2] This study included the largest cohort of ALL patients under treatment who underwent serial radiologic screening, but, still, it could not establish any diagnostic criteria for MTX-related leukoencephalopathy. Hence, the article by Mahajan et al. is extremely valuable in formulating diagnostic imaging criteria which will be helpful in the appropriate management of an iatrogenic complication.

Although it is a retrospective analysis, this is a relatively large cohort of adult ALL patients who have been uniformly treated with the same chemotherapy protocol. The authors have ascertained that all the patients included in the analysis did not have clinicopathological evidence of CNS involvement at baseline, presented within 14 days of last MTX dose and underwent a computed tomography scan as well as a DW-MRI scan within 48 hours of presentation. The study not only describes a characteristic, consistent, and easy-to-recognize finding on imaging which will lead to early recognition and timely management of this rare condition, but also reports the self-remitting natural history of the same.

As toxic leukoencephalopathy is contributed by the use of both high-dose intravenous and intrathecal MTX,[3] it will be of great help if the authors can mention the median dose of high-dose MTX and the median number of doses of intrathecal MTX received by the patients who developed the same. It will be interesting to evaluate if the patients with MTX-induced leukoencephalopathy also have raised serum ammonia levels such as 5 fluorouracil (5FU)-associated leukoencephalopathy[4] and if 5FU or fludarabine-induced neurotoxicity also leads to similar findings on DW-MRI scans of the brain.[5] We realize the limitations of a retrospective study and hence, it will be worthwhile to validate the 'panda eye' sign prospectively in patients who present with subacute neurotoxicity on high-dose MTX for ALL, high-grade lymphomas, and osteogenic sarcomas and to explore if they have any residual neurocognitive symptoms on longer follow-up.

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  References Top

Mahajan A, Jain H, Simha V, Vaidya T, Kumar GV, Gupta A, et al. Clinical-radiological features of methotrexate-induced subacute leukoencephalopathy in patients with acute lymphoblastic leukemia: Panda eye sign' on diffusion weighted-magnetic resonance imaging. Cancer Res Stat Treat 2019;2:28-33.  Back to cited text no. 1
  [Full text]  
Bhojwani D, Sabin ND, Pei D, Yang JJ, Khan RB, Panetta JC, et al. Methotrexate-induced neurotoxicity and leukoencephalopathy in childhood acute lymphoblastic leukemia. J Clin Oncol 2014;32:949-59.  Back to cited text no. 2
Reddick WE, Glass JO, Helton KJ, Langston JW, Xiong X, Wu S, et al. Prevalence of leukoencephalopathy in children treated for acute lymphoblastic leukemia with high-dose methotrexate. AJNR Am J Neuroradiol 2005;26:1263-9.  Back to cited text no. 3
Choi SM, Lee SH, Yang YS, Kim BC, Kim MK, Cho KH, et al. 5-fluorouracil-induced leukoencephalopathy in patients with breast cancer. J Korean Med Sci 2001;16:328-34.  Back to cited text no. 4
Khaddar S, Patil VM, Noronha V, Joshi A, Menon N, Prabhash K. Delirium and seizures in a patient with head-and-neck squamous cell carcinoma on docetaxel, cisplatin, and 5-fluorouracil. Cancer Res Stat Treat 2019;2:105-7.  Back to cited text no. 5
  [Full text]  

This article has been cited by
1 Author reply to: Tandon N., et al. and Majumdar S, et al.
Hasmukh Jain,Abhishek Mahajan,Vishakha Phatak
Cancer Research, Statistics, and Treatment. 2019; 2(2): 264
[Pubmed] | [DOI]


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