Clinical and radiological characteristics of methotrexate-induced acute encephalopathy in pediatric patients with cancer.
ABSTRACT Little information is available about the diagnosis and management of acute methotrexate (MTX)-induced encephalopathy.
We reviewed clinical and magnetic resonance imaging (MRI) [including diffusion-weighted imaging (DWI)] characteristics of this complication in pediatric cancer patients treated from 2000 to 2006.
Six of 754 (0.8%) patients with leukemia or lymphoma and 2 of 44 (4.5%) with bone sarcoma experienced acute encephalopathy within 2 weeks (median, 7.5 days) after receiving high-dose i.v. and/or intrathecal MTX. The signs and symptoms varied at presentation and during episodes: hemiparesis (eight patients, alternating from side to side in four), dysphasia (six), confusion/emotionality (six), headache (three), choreoathetosis (two), and seizure (two). All patients recovered after 1-7 days (median, 5.5 days). DWI revealed restricted diffusion in anatomic brain regions associated with the symptoms; changes on T2-weighted and fluid-attenuated inversion recovery (FLAIR) imaging were consistently less marked. After recovery, DWI findings were normal but T2 and/or FLAIR imaging usually showed residual abnormalities.
Acute MTX toxicity often manifests as fluctuating neurologic symptoms with alternating hemispheric involvement. Restricted diffusion on DWI is a reliable early sign of acute MTX encephalopathy and resolves as clinical status improves, despite the persistence of subtle abnormalities on MRI.
Article: Central nervous system chemotoxicity during treatment of pediatric acute lymphoblastic leukemia/lymphoma.[show abstract] [hide abstract]
ABSTRACT: In the last decades, increasing success rates are being obtained in the chemotherapy of pediatric leukemia and lymphoma. However, the cornerstone of this treatment is still formed by a reduced number of drugs with a highly toxic profile. In particular, central nervous system complications remain a challenging clinical problem, requiring rapid detection and prompt treatment to limit permanent damage. Furthermore, clinicians are often challenged to discriminate between CNS involvement by the disease, toxicity of drugs or infections. This clinically oriented review will help recognize and handle the main neurologic adverse effects induced by chemotherapy in pediatric patients with lymphoblastic leukemia/lymphoma. Different clinical entities and putative drugs involved are discussed in each chapter, with clinical cases illustrating the most relevant and challenging events. In addition, specific clinical-radiological patterns of some of these neurologic events are detailed. Finally, the role of pharmacogenetics, with special focus on those polymorphisms that could help explain the occurrence of neurotoxicity, is also discussed.Critical reviews in oncology/hematology 05/2012; 84(2):274-86. · 5.27 Impact Factor
Article: Methotrexate-induced subacute neurotoxicity in a child with acute lymphoblastic leukemia carrying genetic polymorphisms related to folate homeostasis.[show abstract] [hide abstract]
ABSTRACT: Subacute methotrexate neurotoxicity (MTX-NT) may occur days to weeks after systemic or intrathecal (IT) MTX administration and is often manifest by stroke-like symptoms. The pathogenesis of MTX-NT has mainly been associated with cerebral folate homeostasis, but the specific mechanism leading to the development of this complication is mostly unknown and is likely to be multifactorial. Most of studies aimed to determine putative genetic determinants of this syndrome have been focused on the methylenetetrahydrofolate reductase (MTHFR) C677T single nucleotide polymorphism (SNP). However, there are other functional polymorphisms that have also been identified in enzymes and transporters related to MTX and folate homeostasis. In this context, we carried out an extensive genetic analysis through the screening of 21 SNPs in 11 relevant genes in a five-year-old girl with acute lymphoblastic leukemia (ALL) who developed MTX-NT. The analysis revealed the presence of numerous genetic variants that may have accounted for the neurotoxicity observed. We discuss the putative role of MTX pharmacogenetics in the pathogenesis of MTX-NT.American Journal of Hematology 09/2010; 86(1):98-101. · 4.67 Impact Factor