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Leukoencephalopathy due to oral methotrexate

I González-Suárez1, M J Aguilar-Amat, M Trigueros

  • 1Department of Neurology, IdiPAZHealth Research Institute, La Paz University Hospital, School of Medicine, Universidad Autónoma de Madrid, Paseo de la Castellana 261, 28046, Madrid, Spain, igonsua@gmail.com.

Cerebellum (London, England)
|September 27, 2013
PubMed

Insights

Methotrexate (MTX) can cause rare, severe neurotoxicity like leukoencephalopathy, even at low oral doses for rheumatoid arthritis. Early drug withdrawal is crucial for patient recovery and improved prognosis.

Area of Science:

  • Neurology
  • Rheumatology
  • Pharmacology

Background:

  • Methotrexate (MTX) is a primary treatment for rheumatoid arthritis (RA).
  • While generally safe, MTX can cause neurotoxicity, ranging from mild to severe encephalopathy, particularly with parenteral administration.
  • Severe neurotoxicity, such as leukoencephalopathy, is rarely reported with long-term, low-dose oral MTX.

Observation:

  • A 68-year-old male with RA on long-term oral MTX (25 mg weekly) developed progressive dysarthria, ataxia, and cognitive dysfunction.
  • MRI revealed cerebellar white matter lesions with diffusion restriction and mild enhancement, consistent with a demyelinating pattern.
  • Pharmacogenetic testing showed heterozygous MTHFR and ABCB1 genotypes.

Findings:

  • The patient's symptoms improved after MTX discontinuation, indicating MTX-induced leukoencephalopathy.
  • Cerebellar involvement in MTX-induced leukoencephalopathy is uncommon, with occipital lobe predilection typically observed.
  • The pathogenesis may involve cumulative toxicity to the blood-brain barrier, potentially influenced by genetic factors.

Implications:

  • MTX-induced leukoencephalopathy can occur with low-dose oral administration, necessitating vigilance in RA patients.
  • Early diagnosis and cessation of MTX are critical for favorable outcomes.
  • Further research is needed to elucidate the precise pathogenic mechanisms and the role of genetic polymorphisms in MTX neurotoxicity.

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