E032 Low dose methotextrate induced leukoencephalopathy: a case report
Authors: Doddamani Parveen , Kinder Alison 
Published: April 2024

Abstract

Background/Aims
Methotextrate is a widely used disease modifying anti-rheumatic drug (DMARD) used to treat connective tissue disorder and inflammatory arthritis. Methotextrate induced neurological toxicity includes vomiting, headaches, blurred vision, mood alteration, somolescence, brain fog, hyperosmia, leukoencephalopathy and pseudo-stroke like syndrome. Here we report a case of methotextrate induced headache with leptomeningeal enhancement, which reversed after stopping the methotextrate.

Methods
A 66 year old male with known diagnosis of sero-positive rheumatoid arthritis with past medical history of Hodgkins lymphoma in remission. He started on dual DMARD combination of 15 mg methotextrate subcutaneously once a week and 200 mg hydroxychlroquin twice daily. Thereafter he reported history of headaches, which needed hospital admission. He underwent a CT-head scan on admission which did not show any acute concerns. The case was then discussed with the haematology team and later he underwent a PET scan of the whole body which was reviewed in Lymphoma MDT which showed non-specific uptake in hilar nodes, which does not significantly increase the suspicion of lymphoma relapse. On discharge he had MRI head contrast and MRV cerebral veins, which showed a few areas of irregular nodular curvilinear foci of predominantly meningeal enhancement noted in occipital lobes and adjacent T2 /flair hypertense signal noted in relation to these. These changes were discussed in neurology MDT, given the history of lymphomas a possibility, though rare in the absence of systemic relapse. The differential included low dose (oral) methotextrate related neurotoxicity. Patient was advised to stop methotextrate, they repeated MRI scan 3 weeks later which showed disappearance of the curvilinear lesions with leptomeningeal enhancement and patient reported headaches improved.

Results
List of investigations 1. CSF- profile, no protein, no growth 2. CSF PCR panel for Adeno/Paracheo/Entero/Varicella Zoster/HSV type 1&2-negative 3. Histology report of CSF- No evidence of lymphoma 4. Neuronal Ab: Purkinje cell/ Hu Ab/Ri Ab amd Anti-amphiphysin Ab-negative 5. Myeloma screen- no paraprotein detected 6. Virus panel- EBV- IgM-, HIV /Hep B and C, Cytomegalovirus IgM-not detected.

Conclusion
Methotextrate is a potent anti-metabolite preventing the formation of tetrahydrofolate, and used as immunosuppressant and anti-neoplastic medication. Though the exact mechanism of the neurotoxicity is not known, the common hypothesis include; interference with myelin synthesis or maintenance and/or interference with neurotransmitter synthesis. The case reported here reiterates the importance of recognizing the neurological side effects in patients on methotextrate even on low dose of methotextrate. It also emphasizes the fact that the neurological changes are reversible on stopping methotextrate. Headaches can still be a side effect and might mimic stroke like episode in patients treated with low dose of subcutaneous methotextrate and hence stopping the medication should be considered in such cases.

Disclosure
P. Doddamani: None. A. Kinder: None.