Methotrexate-induced myelopathy

Last revised by Henry Knipe on 25 Nov 2022

Citation, DOI, disclosures and article data

Citation:

Gaillard F, Knipe H, Sharma R, Methotrexate-induced myelopathy. Reference article, Radiopaedia.org (Accessed on 20 Apr 2024) https://doi.org/10.53347/rID-75485

DOI:

https://doi.org/10.53347/rID-75485

Permalink:

https://radiopaedia.org/articles/75485

rID:

75485

Article created:

30 Mar 2020, Frank Gaillard ◉ ◈

Disclosures:

At the time the article was created Frank Gaillard had no recorded disclosures.

View Frank Gaillard's current disclosures

Last revised:

25 Nov 2022, Henry Knipe ◉ ◈

Disclosures:

At the time the article was last revised Henry Knipe had the following disclosures:

Radiopaedia Events Pty Ltd, Speaker fees (past)
Integral Diagnostics, Shareholder (ongoing)
Micro-X Ltd, Shareholder (ongoing)

These were assessed during peer review and were determined to not be relevant to the changes that were made.

View Henry Knipe's current disclosures

Revisions:

4 times, by 3 contributors - see full revision history and disclosures

Systems:

Central Nervous System, Spine

Tags:

cases, case2

Methotrexate-induced myelopathy is an uncommon toxic manifestation of intrathecal methotrexate administration that closely mimics subacute combined degeneration of the cord but with normal vitamin B₁₂ and copper ^1,2. It is far less common than methotrexate-related leukoencephalopathy.

Methotrexate-induced myelopathy is rare with only case reports and small series reported. As intrathecal methotrexate is most commonly administered for the treatment of hematologic malignancies, especially acute lymphocytic leukemia, the epidemiology of affected individuals largely matches that of the underlying diseases with most being children or young-to-middle-aged adults ^1,2.

Clinical presentation

The clinical presentation of affected individuals relates to dorsal column impairment with bilateral paresthesia, lower-limb weakness and bowel and/or bladder dysfunction ².

CSF levels of myelin basic protein and homocysteine are often elevated ².

Pathology

Although clinically and radiologically methotrexate-induced myelopathy is indistinguishable from subacute combined degeneration of the cord it is not believed to be due to abnormal vitamin B12 or copper metabolism ¹. Rather, it has been postulated that methotrexate results in the disruption of normal methionine synthesis from homocysteine resulting in both the elevated levels of homocysteine detectable in CSF and the reduction of S-adenosylmethionine (synthesized from methionine) that is important in the maintenance of normal myelin sheaths ³. At present, however, it is unclear if this results in demyelination ³, or some form of axonal damage ². Interpretation of postmortem samples has been complicated by concurrent radiation effects ².

Radiographic features

MRI

MRI demonstrates imaging features indistinguishable to subacute combined degeneration of the cord with bilateral long segment dorsal column high T2 signal ^1-3.