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‘Stroke-like syndrome’ caused by intrathecal methotrexate in patients treated during the UKALL 2003 trial

Leukemia volume 27, pages 954–956 (2013)Cite this article

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Successful treatment of acute lymphoblastic leukaemia (ALL) depends on effective eradication of presymptomatic disease from the central nervous system (CNS). All patients treated for ALL as part of the Medical Research Council UKALL 2003 trial receive CNS prophylaxis with intrathecal (IT) methotrexate (MTX). MTX is associated with an encephalopathy, which typically develops between 2 and 14 days of administration.1 A diverse range of symptoms is reported, with seizures and headache being the most common.2 A ‘stroke-like syndrome’ (SLS; also known as subacute MTX-related neurotoxicity) is well described; the clinical features typically include focal weakness or hemiparesis, often accompanied by disturbances in speech and/or affect, which may wax and wane over the course of hours to days.3

The pathogenesis of toxicity remains poorly understood and may relate to neuroexcitatory properties of adenosine (the release of which is stimulated by MTX)4 or metabolites of folate metabolism such as homocysteine.5 Magnetic resonance imaging (MRI) has revealed consistent cerebral white matter changes, best seen in diffusion-weighted and T2-weighted images.1, 6 The encephalopathy appears to be completely reversible in almost all cases. Although evidence from large-scale series is lacking, it appears that IT MTX can usually be readministered to patients, without recurrence of previous symptoms.2

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Acknowledgements

Sue Richards and Rachel Clack of the Clinical Trial Service Unit (Oxford) coordinated questionnaire return and provided patient data. We would like to thank all the UK Children’s Cancer and Leukaemia Group centres for their participation in this study.

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Authors and Affiliations

  1. Medical Research Council Clinical Sciences Centre, Imperial College London, London, UK

    J Bond

  2. Department of Paediatric Haematology and Stem Cell Transplantation, St Mary’s Hospital, London, UK

    J Bond

  3. Department of Haematology, University College London Hospitals, London, UK

    R Hough

  4. Department of Paediatric Haematology and Oncology, Bristol Royal Hospital for Children, London, UK

    J Moppett

  5. Department of Haematology, Sheffield Children’s Hospital, London, UK

    A Vora

  6. John Radcliffe Hospital, Oxford, London, UK

    C Mitchell

  7. Department of Haematology, Great Ormond Street Hospital for Children, London, UK

    N Goulden

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Correspondence to N Goulden.

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Bond, J., Hough, R., Moppett, J. et al. ‘Stroke-like syndrome’ caused by intrathecal methotrexate in patients treated during the UKALL 2003 trial. Leukemia 27, 954–956 (2013). https://doi.org/10.1038/leu.2012.328

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