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Indian Pediatr 2017;54: 159 |
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Repeated Episodes of Leukoencephalopathy
after High-dose Methotrexate in a Child with Acute Lymphoblastic
Leukemia
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Teng-Fu Tsao and
*Yu-Hua Chao
From Departments of Medical Imaging and *Pediatrics,
Chung Shan Medical University Hospital; School of Medical Imaging and
Radiological Sciences and School of Medicine, Chung Shan Medical
University, Taichung, Taiwan.
Email: [email protected]
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A 13-year-old girl with acute lymphoblastic leukemia (ALL) achieved
complete remission after induction according to the TPOG ALL 2002-HR
protocol [1]. On the 9th day after the 2nd high-dose methotrexate
(HDMTX), progressive right hemiparesis with headache, dysphagia,
dysarthria, and emotional disturbances were noted. Magnetic resonance
imaging (MRI) of brain showed high intensity in bilateral centrum
semiovales on diffusion-weighted image (DWI) and low intensity on
apparent diffusion coefficient (ADC) maps (Web Fig. 1a – 1d).
Findings on fluid attenuated inversion recovery (FLAIR) images were much
less prominent. Dexamethasone and aminophylline were administered;
symptoms resolved soon. A recurrent episode of similar symptoms but with
more intense severity and left hemiparesis occurred after the 3rd HDMTX.
MRI (Web Fig.1d - 1f) illustrated extension
of hyperintense on DWI and hypointense on ADC maps with new lesions in
the right side. Increased intensity on FLAIR images was now evident.
Administration of leucovorin with dexamethasone and aminophylline
improved the condition gradually. Considering the risk of her ALL, HDMTX
with intrathecal chemotherapy was resumed as the schedule despite the
residual leg weakness. To prevent recurrence, four doses of
dexamethasone were administered before HDMTX and an additional dose of
leucovorin was given six hours before the schedule. No related
side-effects occurred after the 4th course. She is now in complete
remission without neurological sequelae. Follow-up MRI (Web
Fig. 1g - 1r) showed resolution of hyperintensity on DWI
and hypointensity on ADC maps. The high intensity on FLAIR images was
most prominent 3 months after the second episode. As resolved slowly
thereafter, it remained evident in the absence of a clinical correlate.
HDMTX is the mainstay during consolidation for
children with ALL [2], and leukoencephalopathy is rare in these patients
who receive MTX at a dose of 1-5 g/m 2
[3]. From 2002 to 2013, we treated 1,620 children with ALL with the TPOG
ALL 2002 protocol, which included four courses HDMTX (2.5 g/m2
or 5 g/m2) during
consolidation phase. Only two patients without delayed MTX clearance had
leukoencephalopathy, and only the present patient experienced two
episodes.
Contributors: TFT: Radiographic evaluation and
diagnosis; YHC: Patient management and writing the manuscript.
Funding: None; Competing interests:
None stated
References
1. Yen HJ, Chang WH, Liu HC, Yeh TC, Hung GY, Wu KH,
et al. Outcomes following discontinuation of E. coli l-asparaginase
upon severe allergic reactions in children with acute lymphoblastic
leukemia. Pediatr Blood Cancer. 2016;63:665-70.
2. Pui CH, Yang JJ, Hunger SP, Pieters R, Schrappe M,
Biondi A, et al. Childhood acute lymphoblastic leukemia: progress
through collaboration. J Clin Oncol. 2015;33:2938-48.
3. Inaba H, Khan RB, Laningham FH, Crews KR, Pui CH,
Daw NC. Clinical and radiological characteristics of methotrexate-induced
acute encephalopathy in pediatric patients with cancer. Ann Oncol.
2008;19:178-84.
4. Schaefer PW, Grant PE, Gonzalez RG.
Diffusion-weighted MR imaging of the brain. Radiology. 2000;217:331-45.
5. Haykin M, Gorman M, van Hoff J, Fulbright RK,
Baehring JM. Diffusion-weighted MRI correlates of subacute methotrexate-related
neurotoxicity. J Neurooncol. 2006;76:153-7.
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