To expand the knowledge of presentation, imaging and potential therapies of Methotrexate induced leukoencephalopathy (MTX-LE).
A 20-year-old female with recently diagnosed ALL developed lower limb weakness and numbness seven days after receiving the fourth dose of intrathecal MTX. Her exam showed diffuse weakness, worse in the lower limbs along with decreased sensation and absence of patellar and Achilles reflexes. Brain MRI revealed ovoid restricted diffusion in the bilateral centrum semiovale with FLAIR hyperintensities suggesting a MTX-induced leukoencephalopathy. Administration of dextromethorphan 75mg twice daily resulted in symptom resolution in three days.
A week later, she was brought to the emergency department due to an alternation in her mental status and slow speech. Her neurological exam initially fluctuated but a repeat MRI revealed new areas of restricted diffusion with increased FLAIR signals in the centrum semiovale, along with a slight improvement in the previous lesions. She was restarted on dextromethorphan with significant improvement.
Chemotherapy, mainly MTX, can cause acute neurotoxicity leading to a condition called MTX-induced leukoencephalopathy. It can manifest with focal symptoms, stroke-like events, seizures, or encephalopathy. Diagnosis is supported by brain MRI showing areas of restricted diffusion in the centrum semiovale.
MTX is believed to directly affect axons, increase adenosine and cause homocysteine elevation affecting NMDA receptors. Thus, drugs like leucovorin, aminophylline, and dextromethorphan have been used to successfully treat MTX-LE and reverse its effect.
Our case demonstrated a challenging presentation; while most reported cases had a single-phase-attack, our case had recurrent and fluctuating symptoms with worsening MRI findings despite treatment. We suggest that this presentation could be explained by the potentially fluctuating nature of MTX-LE or the progression of her condition. Further research is needed to understand MTX-LE, characteristic MRI findings and its treatments.