Methotrexate (MTX) is an anti‐metabolite medication that inhibits deoxyribonucleic acid synthesis. Due to poor drug penetration through the blood–brain barrier, it is often administered intrathecally to attain higher cerebrospinal fluid (CSF) concentration. However, intrathecal (IT) administration of MTX is generally concomitant with higher neurotoxicity. MTX myelopathy is defined as the development of isolated spinal cord dysfunction following the IT administration of MTX. Documented manifestations vary from vacuolar degeneration of the lateral and posterior funiculi to complete transverse necrosis of the spinal cord. 1 Here, we present the clinical presentations and image findings of a women with bilateral paresthesia after IT administration of MTX.
A 31‐year‐old woman presented with bilateral lower limb numbness. The numbness was symmetric without shooting pain. In the following 2 weeks, weakness of the lower extremities developed from the distal and gradually progressed upwards. She also experienced urinary incontinence and severe low back pain. On admission, physical examination revealed decreased pain and proprioception below L4 level and absence below S3. Deep tendon reflexes were hyperactive over bilateral lower extremities, accompanied with bilateral ankle clonus. Muscle power of bilateral proximal and distal legs was 2 and 1 on a scale of 1 to 5, respectively.
She had been diagnosed with acute myeloid leukemia 10 months before the onset of weakness. Two days after the diagnosis, induction chemotherapy with idarubicin and cytarabine (I3A7) was initiated. Subsequent bone marrow and CSF studies showed positive central nervous system involvement. Therefore, IT MTX was given for therapeutic purposes, and the total accumulative dose of IT MTX during the following 10 months since the initial diagnosis of acute myeloid leukemia was 120 mg (12 mg × 10 sessions). After the eradication of blast cells in CSF, she received haploidentical bone marrow transplantation, followed by haploidentical peripheral blood stem cell transplantation. She had complete remission and achieved successful trilineage engraftment. Six weeks after the last dose of IT MTX administration, ascending weakness developed. Magnetic resonance imaging disclosed bilateral symmetrical signal change in spinal cord, predominately in the posterior and lateral columns (Figure 1). MTX‐induced myelopathy was diagnosed. Leucovorin, prednisone and vitamins B12 were administered for rescue treatment. Physical therapy was also arranged. Before discharge, she was able to walk over 100 m without device assistance.
FIGURE 1.
Sagittal (A) and axial (B) views of T2 weighted magnetic resonance image disclosed symmetrical bilateral increased signal change in the spinal cord, predominately at the posterior and lateral columns (white arrow)
Myelopathy is an uncommon complication after IT administration of MTX. The reported incidence was around 3%. 2 An observation study showed that median number of weeks from the first day of IT MTX to the first neurotoxicity event was 51 weeks (ranging from 4 to 127 weeks). As a dihydrofolate reductase inhibitor that inhibits the conversion of folate to tetrahydrofolate, MTX blocks myelin synthesis and myelopathy ensues. 3 Diagnosing MTX‐related myelopathy might be challenging since it might be mistaken as subacute combined degeneration of the spinal cord. 4 Previous case series revealed that patients with ascending motor weakness after IT MTX had symmetrically increased signal density within the posterior column of the spinal cord on T2‐weighted magnetic resonance images. 5 The image of our patient matched aforementioned findings. Eventually, decreased proprioception, sensory ataxia, and reduced muscle power over bilateral lower legs would become clinically evident resulting from the involvement of posterior and lateral columns of spinal cord.
In conclusion, we reported a case of ascending myelopathy following IT administration of MTX. Our case highlights the importance of taking myelopathy into account when ascending lower leg weakness and numbness occurs following IT administration of MTX.
CONFLICT OF INTEREST
The authors declare no conflicts of interest.
ACKNOWLEDGMENTS
The authors thank the patient and her family for allowing us to share her details.
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