Diffusion-Weighted MRI Correlates of Subacute Methotrexate-Related Neurotoxicity

Haykin, ME; Gorman, Mark; Hoff, Jack van; Fulbright, R.K.; Baehring, J.M.

doi:10.1007/s11060-005-4569-2

Cited by 74 publications

(47 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We can speculate that this might be related to ecstasy-induced cytotoxic edema, as observed in other neurotoxic substances (Heaney et al, 2003;Haykin et al, 2005), although it also could be related to protracted vasoconstriction, since we also observed a decreased rrCBV in the thalamus (Pearson correlation between these findings is 0.65, po0.001). With DTI we also encountered the unexpected finding of increased FA in the centrum semiovale related to the total amount of ecstasy tablets, although this 0.9% increase was very small (Cohen's d ¼ 0.15).…”

Section: Discussionsupporting

confidence: 67%

“…In the brain, the motion is restricted in amplitude and direction by cellular structures such as axons. (Sub)acute processes that involve axonal injury and ischemia can lead to a decreased apparent diffusion coefficient (ADC) of water due to cytotoxic edema (Haykin et al, 2005). However, in chronic stage of axonal damage, ADC can be increased and fractional anisotropy (FA) of water can be decreased due to increased extracellular water content.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Prospective Cohort Study on Sustained Effects of Low-Dose Ecstasy Use on the Brain in New Ecstasy Users

Win

Reneman

Jager

et al. 2006

Neuropsychopharmacol

View full text Add to dashboard Cite

It is debated whether ecstasy use has neurotoxic effects on the human brain and what the effects are of a low dose of ecstasy use. We prospectively studied sustained effects (42 weeks abstinence) of a low dose of ecstasy on the brain in ecstasy-naive volunteers using a combination of advanced MR techniques and self-report questionnaires on psychopathology as part of the NeXT (Netherlands XTC Toxicity) study. Outcomes of proton magnetic resonance spectroscopy ( 1 H-MRS), diffusion tensor imaging (DTI), perfusion-weighted imaging (PWI), and questionnaires on depression, impulsivity, and sensation seeking were compared in 30 subjects (12M, 21.873.1 years) in two sessions before and after first ecstasy use (1.871.3 tablets). Interval between baseline and follow-up was on average 8.176.5 months and time between last ecstasy use and follow-up was 7.774.4 weeks. Using 1 H-MRS, no significant changes were observed in metabolite concentrations of N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), and creatine (Cr), nor in ratios of NAA, Cho, and mI relative to Cr. However, ecstasy use was followed by a sustained 0.9% increase in fractional anisotropy (FA) in frontoparietal white matter, a 3.4% decrease in apparent diffusion (ADC) in the thalamus and a sustained decrease in relative regional cerebral blood volume (rrCBV) in the thalamus (À6.2%), dorsolateral frontal cortex (À4.0%), and superior parietal cortex (À3.0%) (all significant at po0.05, paired t-tests). After correction for multiple comparisons, only the rrCBV decrease in the dorsolateral frontal cortex remained significant. We also observed increased impulsivity ( + 3.7% on the Barratt Impulsiveness Scale) and decreased depression (À28.0% on the Beck Depression Inventory) in novel ecstasy users, although effect sizes were limited and clinical relevance questionable. As no indications were found for structural neuronal damage with the currently used techniques, our data do not support the concern that incidental ecstasy use leads to extensive axonal damage. However, sustained decreases in rrCBV and ADC values may indicate that even low ecstasy doses can induce prolonged vasoconstriction in some brain areas, although it is not known whether this effect is permanent. Additional studies are needed to replicate these findings.

show abstract

Section: Discussionsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

A Prospective Cohort Study on Sustained Effects of Low-Dose Ecstasy Use on the Brain in New Ecstasy Users

Win

Reneman

Jager

et al. 2006

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…Neurotoxicity was confirmed by MRI, which has been shown to reflect subacute neurotoxicity and transient leukoencephalopathy [40,41]. Both patients had low 5-methyl-THF and considerably decreased SAM concentrations shortly after toxicity episodes indicating that these patients exhibited biochemical disorders possibly related to MTX administration.…”

Section: Discussionmentioning

confidence: 90%

Methotrexate‐associated alterations of the folate and methyl‐transfer pathway in the CSF of ALL patients with and without symptoms of neurotoxicity

Vezmar

Schüsseler

Becker

et al. 2008

Pediatric Blood & Cancer

View full text Add to dashboard Cite

BackgroundSevere neurotoxicity has been observed after systemic high‐dose and intrathecal methotrexate (MTX) treatment. The role of biochemical MTX‐induced alterations of the folate and methyl‐transfer pathway in the development of neurotoxic symptoms is not yet fully elucidated.ProcedureMTX, 5‐methyltetrahydrofolate, calcium folinate, S‐adenosylmethionine, and S‐adenosylhomocysteine were measured in the cerebrospinal fluid (CSF) of 29 patients with acute lymphoblastic leukemia (ALL) who were treated with high‐dose MTX (5 g/m2) followed by calcium folinate rescue (3 × 15 mg/m2) and/or intrathecal (8–12 mg) MTX. Two patients developed subacute MTX‐associated neurotoxicity. CSF was obtained by lumbal puncture 1–3 weeks after administration of MTX and shortly after the occurrence of neurotoxicity. The analytes were measured using HPLC assays with UV and/or fluorescence detection.ResultsIn non‐toxic patients, CSF concentrations of 5‐methyltetrahydrofolate and S‐adenosylmethionine were in the normal range 2 weeks after administration of high‐dose and intrathecal MTX followed by rescue. In contrast, when these patients received intrathecal MTX without rescue, 5‐methyltetrahydrofolate concentrations were significantly decreased 12 days after the first MTX administration. S‐adenosylmethionine concentrations were significantly decreased up to 45 days. The two patients suffering from neurotoxicity had decreased levels of 5‐methyltetrahydrofolate and S‐adenosylmethionine during or following toxicity. S‐adenosylhomocysteine was determined in all samples of neurotoxic patients but was below the limit of quantification in most samples of non‐toxic patients. Calcium folinate was not detected; MTX was present only in samples obtained during its infusion.ConclusionIntrathecal MTX without folinate rescue as well as MTX‐associated neurotoxicity are likely to be associated with specific alterations of the folate and methyl‐transfer pathway. Pediatr Blood Cancer 2009;52:26–32. © 2008 Wiley‐Liss, Inc.

show abstract

“…T2-weighted and Fluid attenuated inversion recovery (FLAIR) imaging show abnormalities but these take time to appear. Moreover, these images may continue to show residual abnormalities long after the resolution of neurological deficits [4,12,13]. Residual lesions detected on MRI do not preclude clinical recovery as in our case and the long term implications of these persistent imaging abnormalities lesions are not known.…”

Section: Discussionmentioning

confidence: 57%

Methotrexate Induced Acute Encephalopathy-Occurrence on Re-challenge and Response to Aminophylline

Ganesan

Bajpai

Shah

et al. 2013

Indian J Hematol Blood Transfus

View full text Add to dashboard Cite

Methotrexate-induced acute encephalopathy is a serious complication of a common chemotherapy agent used in lymphoblastic leukemia. As this drug is considered vital for therapeutic success of leukemia therapy it is often rechallenged in these patients. A patient of acute lymphoblastic leukemia developed mild, transient hemiparesis after the 2nd dose of high dose methotrexate (5 g/m 2 ) during the consolidation phase of the BFM-95 protocol. When we repeated the drug in the 3rd cycle he developed severe life threatening quadriparesis and cranial nerve palsies. The toxicity was reversed after treatment with Aminophylline. The relevant literature is reviewed.

show abstract

Diffusion-Weighted MRI Correlates of Subacute Methotrexate-Related Neurotoxicity

Abstract: DWI findings in this cohort seem to reflect cytotoxic edema within cerebral white matter suggesting a reversible metabolic derangement, rather than ischemia, as the basis for this syndrome.

Cited by 74 publications

References 19 publications

A Prospective Cohort Study on Sustained Effects of Low-Dose Ecstasy Use on the Brain in New Ecstasy Users

A Prospective Cohort Study on Sustained Effects of Low-Dose Ecstasy Use on the Brain in New Ecstasy Users

Methotrexate‐associated alterations of the folate and methyl‐transfer pathway in the CSF of ALL patients with and without symptoms of neurotoxicity

Methotrexate Induced Acute Encephalopathy-Occurrence on Re-challenge and Response to Aminophylline

Contact Info

Product

Resources

About